Tumors of the Skin

  • Yong-Hang Zhu
  • Gui-Xiu Zhang
  • Li Tang
  • Xiao-Jie Li
  • Wen-Yuan Zhu
  • Ru-Zhi Zhang
  • Ming-Yu Xia
  • Lei Wang
  • Ying Ren
  • Hui-Pu Zhou
  • De-Hai Pan
  • Li-Jian Xiang
  • Jin-Fa Su
  • Hui Zhang
  • Juan Du
  • Mai-Hua Hou
  • Dong-Lai Ma
  • Shu-Qin Lv
  • Xi-Chuan Yang
  • Jie Gao
  • Ting Lin
  • Shao-Wen Peng
  • Zhi-Ping Sun
  • Li Yang
  • Cheng TanEmail author
  • Ji-Ling Zhang
  • Yan Wu
  • Hong Zhang
  • Gang Liu
  • Bao-Chun Li
  • Shun-Fan Li
  • Lan Yang
  • Jie Yan
  • Yang Guan
  • Yin Xiao
  • Yan Yan
  • Zhi-Fang Zhai
  • Shan Tang
  • Zhong Xie
  • Feng Wu
  • Xiao-Mei Zhang
  • Jian-Fang Sun
  • Wen-Hai Li
  • Mei Cai
  • Chun-Mei Zhang
  • Xian Zhang
  • Gang Wang
  • Hong-Hao Jiang
  • Jiang Jin
  • Xiong-Ming Pu
  • Jian-Min Chang
  • Yan Lu
  • Xiao-Jun Zhu
  • Cun-Cai Zhou
  • Shu-Fang Qiao
  • Jian-Ping Liang
  • Zhi-Xin Song
  • Yi-Ming Xu
  • Jun Peng
  • Hong-Zhong Jin
  • Chun-Xing Xu
  • Jing Fang
  • Chuan-Ping Xing
  • Xiao-Bing Pi
  • Dian-Ying Zhuang
  • Jia-Bi Wang
  • Jian-Ying Zeng
  • Min Huang
  • Chun-Yang Li
  • Bing-Nan Cui
  • Xiao-Yan Guo
  • Tong Lin
  • Bing-Sen Qiu
  • Bin Su
  • Xue-Jun Zhu
  • Pei-Hua Song
  • Guang-Cai Xiang
  • Guang-Ren Liu
  • Sheng-Shun Tan
  • Yi-Qun Jiang
  • Min Zheng
  • Jin Hu
  • Guang-He Yang
  • Zheng Ge
  • Jing Chen
  • Lin Cai
  • Sheng Wang
  • An Liu
  • Xian Jiang


Skin tumor is the most intriguing topic for the clinicians. This chapter covers a wide range of issues and provides with informative clues and tips associated with clinical features and pathological presentations and keeps pace with the latest development in molecular biology and immunohistochemistry to assist the readers in the establishment of accurate diagnosis. These following disorders are elaborately selected and arranged from a histopathological perspective.

(1) Tumors of the epidermis include epidermal nevus, unilateral epidermal nevus, epidermal nevus syndrome, seborrheic keratosis, seborrheic keratosis and pityrosporum ovale, large cell acanthoma, giant cutaneous horn, multiple Bowen’s disease, extramammary Paget’s disease, eruptive keratoacanthoma, superficial basal cell carcinoma, fibroepithelioma of Pinkus, Marjolin’s ulcer of squamous cell carcinoma secondary to radiation, cutaneous clear cell squamous cell carcinoma, and milia en plaque.

(2) The list of cutaneous appendage proliferations and tumors present cases with eruptive vellus hair cysts, nevus comedonicus, dilated pore, inverted follicular keratosis, infundibulocystic basal cell carcinoma, trichofolliculoma, trichoepithelioma, bullous pilomatricoma, areolar sebaceous hyperplasia, nevus sebaceous with apocrine cystadenoma, linear nevus sebaceous syndrome, apocrine hidrocystoma, eccrine angiomatous hamartoma, syringocystadenoma papilliferum, eruptive milium-like syringoma, segmental multiple eccrine spiradenomas, clear cell hidradenoma, malignant eccrine poroma, or microcystic adnexal carcinoma.

(3) The category of cutaneous soft tissue proliferations and neoplasms introduces acquired digital fibrokeratoma, epithelioid cell histiocytoma, multiple eruptive dermatofibromas, intradermal nodular fasciitis, dermatofibrosarcoma protuberan, epithelioid sarcoma, superficial angiomyxoma, multicentric reticulohistiocytosis, Letterer-Siwe disease, cutaneous Rosai-Dorfman disease, phakomatosis pigmentovascularis, angiokeratoma corporis diffusum, angiokeratoma of Fordyce, angioma serpiginosum, reactive angioendotheliomatosis, epithelioid hemangioma, tufted angioma, verrucous hemangioma, targetoid hemosiderotic hemangioma, microvenular hemangioma, glomus tumor, spindle cell hemangioma, Kaposiform hemangioendothelioma, classic Kaposi’s sarcoma, cutaneous angiosarcoma, acquired progressive lymphangioma, lymphangioma, nevus lipomatosus superficialis, encephalocraniocutaneous lipomatosis, madelung disease, multiple leiomyoma, cutaneous leiomyosarcoma, subungual exostosis, and cutaneous endometriosis.

(4) Palisaded encapsulated neuroma, schwannoma, and cutaneous Merkel cell carcinoma belong to neural tumors.

(5) Melanocytic nevi and neoplasms include agminated Spitz nevus, subungual melanoma, fatal leptomeningeal melanoma in neurocutaneous melanosis, as well as rare forms of cutaneous melanoma.

(6) Cutaneous lymphoid proliferations and leukemic infiltration consist of cutaneous pseudolymphoma, Jessner’s lymphocytic infiltration of the skin Jessner, Ketron-Goodman disease, mycosis fungoides, erythrodermic cutaneous T-cell lymphoma, subcutaneous panniculitis-like T-cell lymphoma, hydroa vacciniforme-like lymphoma, extranodal NK-/T-cell lymphoma, primary cutaneous B-cell lymphoma, maculopapular cutaneous mastocytosis, diffuse cutaneous mastocytosis, mastocytoma, cutaneous plasmacytoma, polycythemia vera, leukemia cutis, and so on.

(7) Cutaneous metastases include cutaneous metastasis for lung cancer, cutaneous metastasis of gastrointestinal malignancy, Sister Mary Joseph’s nodule, and carcinoma en cuirasse.

27.1 Epidermal Nevus [1, 2, 3]

  • The clinical features of epidermal nevus (DE) are quite variable from forms of the localized, the generalized, and the inflammatory.

  • Hyperkeratosis, hypergranulosis, and papillomatosis with elongation of the rete ridges are common pathological traits found in DE. Uncommonly it may display epidermal changes such as acrokeratosis-like, seborrheic keratosis-like, psoriasiform, verrucoid, porokeratosis-like, acantholytic dyskeratotic type (Darier-like), acanthosis nigricans-like, and nevus comedonicus.

  • Acantholytic dyskeratotic epidermal nevus (ADEN) used to describe a rare variant of the DE presenting as a linear keratotic lesion with additional acantholytic and dyskeratotic signs.

  • ADEN should be differentiated from other dermatoses with similar acantholytic and dyskeratotic changes including Darier’s disease, warty dyskeratoma, transient acantholytic dermatosis, and Hailey-Hailey disease.

  • Both ADEN and linear Darier’s disease similarly have a linear configuration and acantholytic dyskeratotic changes under the microscope; however, the former lacks of ATP2A2 gene mutation.

Fig. 27-1-1

Brown papillomatous papules arrangement in sheets and helixes on the axilla and trunk

Fig. 27-1-2

Hyperkeratosis, papillomatosis, and acanthosis with elongation of the rete ridges (HE stain, ×400)

27.2 Unilateral Epidermal Nevus [4, 5]

  • Epidermal nevus (EN) is thought to represent a form of cutaneous mosaicism and is called verrucous epidermal nevus, inflammatory linear verrucous epidermal nevus, or linear epidermal nevus.

  • EN arises as brown, warty papules or plaques that are typically distributed in a linear or whorled fashion.

  • EN may aggregate to be localized, unilateral, or generalized to spread across the whole skin.

  • EN is a congenital, benign form of mosaicism of keratinocytes, hair follicles, sebaceous glands, smooth muscle cells, apocrine glands, and eccrine glands.

Fig. 27-2-1

Verrucous and hyperkeratotic plaques arranged linearly on the left neck, shoulder, trunk, and upper limb

27.3 Epidermal Nevus Syndrome [6, 7, 8]

  • Epidermal nevus syndrome (ENS) presents with epidermal nevus with concomitant skeletal defects and ocular anomalies, including lipodermoid of the conjunctiva or coloboma and neurologic defects, such as hemimegalencephaly with contralateral motor disease.

  • ENS is delineated into nine different syndromes. These are Proteus syndrome, CHILD syndrome, Schimmelpenning syndrome, angora hair nevus syndrome, phakomatosis pigmentokeratotica, FGFR3 epidermal nevus syndrome, Becker’s nevus, type 2 segmental Cowden disease, and nevus comedonicus syndromes.

  • In addition to epidermal nevus, cerebriform connective tissue nevi on the soles are pathognomonic for Proteus syndrome. Additional anomalies include asymmetrical macrodactyly, facial dysmorphism, disproportionate skull, cystic pulmonary lesions, lipomas, mental deficiency, brain malformations, lymphangiomas, telangiectasis, and ovarian cystadenoma.

  • Epidermal nevus in Proteus syndrome tends to be soft, velvety, and rather flat compared to the classical type.

  • ENS is also associated with other disorders, including SCALP syndrome, Bafverstedt syndrome, nevus trichilemmocysticus syndrome, Gobello syndrome, NEVADA syndrome, didymosis aplasticosebacea, and CLOVE syndrome.

Fig. 27-3-1

Verrucous plaques on the right axilla, chest, periareola, and abdomen

Fig. 27-3-2

Toe skin was thickened, with the third toe macrodactyly and the fourth and fifth toes shortened

Fig. 27-3-3

Multiple osteochondroma on the right feet, with the third toe macrodactyly

Fig. 27-3-4

Hyperkeratosis, acanthosis, hyperpigmentation of the basal layer, and infiltration by perivascular lymphocytes in the upper dermis (HE stain, ×100)

27.4 Seborrheic Keratosis [9, 10, 11]

  • The clinical manifestations of seborrheic keratosis (SK) are quite variable.

  • Although SK is mainly distributed over sun-exposed regions, small, popular SK has a predilection for the trunk, presenting with numerous small lesions.

  • SK is configured as linear, dermatomal, or Blaschkoid.

  • The lesions in SK may also run along the Langer’s lines or may cross these lines (defined as raindrop SK).

  • All these mentioned variants are believed to have no relation to internal malignancy.

Fig. 27-4a-1

Numerous small brown papules on the chest and abdomen

Fig. 27-4a-2

Moderate acanthosis and horn cysts in the epidermis (HE stain, ×l00)

Fig. 27-4b-1

Brownish, spindle, and slightly raised papules tended to follow skin cleavage lines on lower back

Fig. 27-4b-2

Hyperkeratosis, acanthosis, horn cysts, and proliferation of basal cells in the epidermis (HE stain, ×100)

Fig. 27-4c-1

Multiple linear, spindle- or leaf-shaped eruptions distributed linearly or radially along the direction of skin cleavage lines

Fig. 27-4c-2

Hyperkeratosis, acanthosis, and horn cysts in the epidermis and chronic inflammatory reaction in the dermis. The stratum malpighii showed moderate acanthosis caused by proliferation of squamous and basal cells (HE stain, ×100)

27.5 Seborrheic Keratosis and Pityrosporum Ovale [12]

  • Our study showed that a large number of variously sized spores without fungal hyphae are present in the skin scrapings of 20 (95%) cases with large seborrheic keratosis (SK).

  • A cohort of 21 cases consists of 15 men and 6 women were investigated. Results showed that the average age at the time of diagnosis is 65 years old, and the mean duration was 5 years (0.5–11 years). The most involved site was the head and face (11 cases), followed by the trunk (9 cases) and extremities (1 case).

  • There were multiple PAS-positive organisms in the stratum corneum in 18 (85%) cases. Scanning electron microscopic (SCM) observation of warty lesions found that numerous pityrosporum ovale were present on the keratinized cells. They were round to ovoid in shape and ranged from 3 to 5 μm in diameter. The surfaces of the spores were smooth without hyphae.

  • Pityrosporum ovale is oval and Pityrosporum orbiculare is round in morphology, and both are distributed on the trunk and scalp, since Pityrosporum orbiculare is known to produce hyphae, which were absent in the skin lesions of SK. The results suggested the presence of pityrosporum ovale.

  • Borenstein et al. reported that the Pityrosporum organisms in the stratum corneum were present in 61% of SK on routine histopathologic sections.

Fig. 27-5-1

A large black keratotic plaque on the head

Fig. 27-5-2

Scanning electronic microscopy showed that lots of round and oval spores on the upper horny layer

27.6 Large Cell Acanthoma [13, 14]

  • Large cell acanthoma (LCA) has a predilection for sun-exposed areas.

  • LCA is clinically indistinguishable from solar lentigo or actinic keratosis.

  • Skin biopsy shows a circumscribed proliferation of keratinocytes whose sizes are no less than twice the normal size.

  • Pinkus suggests that LCA is instead a sign of cutaneous mosaicism, while most investigators consider it to be a histopathologic form of solar lentigo.

Fig. 27-6-1

Brown and slightly raised plaque on the outer side of the calf

Fig. 27-6-2

Epidermal hyperplasia, acanthosis, and inflammatory cell infiltration (HE stain, ×100)

Fig. 27-6-3

Enlarged keratinocytes and acanthosis (HE stain, ×400)

27.7 Giant Cutaneous Horn [15, 16]

  • Cutaneous horn (CH) is a kind of keratotic projection reminiscent of animal horns. CH is a clinical description rather than a pathologic diagnosis.

  • The lesion can be straight, curved, conical, cylindrical, or spiral, with its length ranging from several millimeters to 38 cm.

  • CH often has underlying benign or malignant skin disease, and therefore, ruling out this malignancy is of the utmost importance.

  • It can be categorized into five groups: I CH originated from an epidermoid cyst, II CH developed from the mucosa, III verrucous CH arising from warts, IV papillomatous CH from keratotic epithelial cells, and V filiform variant resulting from normal or hyperkeratotic skin.

  • Squamous cell carcinoma, seborrheic keratosis, Bowen’s disease, actinic keratosis, basal cell carcinoma, melanoma, trichilemma, pilomatricoma, verrucous dyskeratoma, and juvenile xanthogranuloma are classified as the tumorous causes of CH. Other possible causes include molluscum contagiosum, verruca vulgaris, cutaneous leishmaniasis, pyogenic granuloma, epidermal nevus, and tuberculosis.

Fig. 27-7-1

Ox hornlike dark-purple lesion with coarse surface

27.8 Multiple Bowen’s Disease [17, 18]

  • Bowen’s disease (BD) is considered to be a noninvasive, early stage of squamous cell carcinoma.

  • BD presents as well-defined reddish plaques that crust and enlarge gradually. Pathologically, it presents with full-thickness epidermal atypia with adnexal involvement.

  • Only 10–20% of BD has multiple lesions, and this form is defined as multiple BD. Other forms consist of pigmented BD, palmar BD, subungual/periungual BD, and verrucous BD.

  • Vulval intraepithelial neoplasia (VIN), erythroplasia of Queyrat, and Bowenoid papulosis are associated with BD in the genital region, and they have a strong association with human papillomavirus infection.

  • The disease shows a favorable response to currently available treatments, and 3–5% of BD risk the development of an invasive carcinoma.

  • Photodynamic therapy, topical imiquimod, and topical diclofenac are newer options for BD treatment.

Fig. 27-8-1

Brownish papules and plaques with superficial erosions and crusts on the upper arm, chest, and abdomen

Fig. 27-8-2

The cells of the stratum malpighii in different sizes were arranged in chaos, which showed some physaliferous cells and atypia mitoses (HE stain, ×400)

27.9 Extramammary Paget’s Disease (EMPD) [19, 20]

  • Paget’s disease (PD) is an intraepidermal adenocarcinoma with neoplastic mucin-producing Paget’s cells.

  • Primary EMPD only involves the epidermis and cutaneous adnexa.

  • PD shows a predilection for apocrine gland-rich regions, comprising the mammary area and extramammary region.

  • Secondary EMPD is associated with an underlying visceral malignancy.

  • EMPD manifests as a red macule or plaque with characteristic “cake-icing scaling,” and the diagnosis is always complicated by its ulcerated, crusted, or papillomatous surface.

  • It is likely for EMPD patients to have a second primary cancer, particularly the first year after diagnosis.

  • The diagnosis is established with the presentation of Paget’s cells in the epidermis. Paget’s cells are characterized by large nuclei and vacuolated cytoplasm. These cells are highlighted by PAS stain, and they express CK7, CEA, and EMA. However, EMPD with an elevated expression of fatty acid synthase and p53 is likely to have a higher invasive potential.

  • Type I EMPD (keratin 7+, keratin 20+, and GCDFP-15−) is related to distant tumors, and Paget’s cells in type II (keratin 7+, keratin 20−, and GCDFP15 +) are of primary cutaneous origin.

Fig. 27-9-1

Infiltrated well-circumscribed erythemas and plaques with central erosion and superficial ulcers on the scrotum, penis, and perineum

Fig. 27-9-2

Scattered PAS-positive Paget’s cells in the epidermis (PAS stain, ×200)

Fig. 27-9-3

Epithelial membrane antigen (EMA)-positive cells were scattered or grouped in the epidermis (APC stain, ×200)

27.10 Eruptive Keratoacanthoma [21, 22, 23]

  • Keratoacanthoma (KA) typically shows a solitary, rapidly enlarging, and well-differentiated squamous cell epithelium in the epidermis with a central, keratin-filled crater.

  • After 6 months’ induration period, the neoplasm decreases until it completely resolves.

  • In comparison with the classical solitary type, multiple KA tends to arise abruptly, develop quickly, regress slowly, and recur periodically.

  • The number of eruptive KA ranges from a few to several hundred, and they mostly resolve with residual scarring.

  • Although multiple KAs mostly appear in Muir-Torre syndrome, Ferguson-Smith syndrome, xeroderma pigmentosum, and other syndromes, it can be induced by medication with leflunomide, BRAF kinase inhibitors (vemurafenib or sorafenib), or photodynamic therapy. Topical application of 5% imiquimod can be effective in the treatment of multiple KAs.

Fig. 27-10-1

Thirteen firm, dome-shaped nodules of 0.5–1.0 cm in diameter with crateriform centers on the face and wrist

Fig. 27-10-2

A large, irregularly shaped crater was filled with keratin (HE stain, ×40)

Fig. 27-10-3

The proliferative epidermal cells at the base of crater showed nuclear atypia and atypical mitoses (HE stain, ×100)

27.11 Superficial Basal Cell Carcinoma [2425]

  • We can classify basal cell carcinoma (BCC) into nodular, infiltrative, superficial, and mixed subtypes based on their morphological descriptions.

  • Superficial BCC, or multicentric BCC, shows a scaly, pink to red-brown demarcated macule. It predominantly affects the trunk, in contrast to nodular BCC on UV-exposed areas.

  • It can easily be mistaken as psoriasis, lichen planus-like keratosis, or Bowen’s disease.

  • Dermoscopic findings of maple leaflike areas, spoke wheel areas, blue-gray globules and ovoid nest, and arborizing telangiectasis can be helpful in its early diagnosis.

  • Imiquimod 5% is recommended as a treatment in superficial BCC, in addition to its wide application in the management of genital warts and solar keratoses. However, vitiligo-like depigmentation is likely to be a rare complication following its application.

Fig. 27-11-1

A purplish red patch surrounded by dark-brown papules on the back

Fig. 27-11-2

The buds of tumor cells attached to the undersurface of the epidermis. The peripheral cells of the tumor show palisade arrangement (HE stain, ×200)

27.12 Fibroepithelioma of Pinkus [26, 27]

  • Fibroepithelioma of Pinkus (FEP) is a rare cutaneous tumor. Multiple tumors of FEP are rather rare. FEP develops in persons aged between 40 and 60 years. FEP presents as a skin-colored, pink, red, or brown nodule or plaque, with occasional ulceration. But large pedunculated, polypoid, or ulcerated cases have also been reported.

  • They usually are most frequently located on the trunk or extremities. However, lesions occurring on the head, abdomen, anus, penis, scrotum, and breasts have been reported.

  • Only ten cases with multiple FEP have been described. Nine of them were associated with basal cell carcinoma (BCC). The presentation as a multiple BCC is rather rare. Prior radiotherapy is a predisposing factor in the onset of disease.

  • There are very few reports of fibroepithelioma of Pinkus in continuity with a nodular BCC. The classification of fibroepithelioma of Pinkus is controversial and is considered as a variant of either BCC or trichoblastoma.

Figs. 27-12-1, 27-12-2

Four brown or erythematous maculae or patches with a brown-colored, elevated borderline in different sizes on two sides of the waist. Some dilated follicular orifices were seen in the fringe. The central parts of the patches were erythematous and slight atrophied without erosion and infiltration

Fig. 27-12-3

Mild hyperkeratosis and acanthosis in the epidermis (HE stain, ×40)

Fig. 27-12-4

Reticulated strands of basaloid cells extended into the dermis. The macronuclei of basal cells were deeply basophilic. There were more melanin granules in basal layers and the basement membrane was integrated. Hemangiectasia and numerous lymphocyte infiltrated in the mid-dermis (HE stain, ×200)

27.13 Marjolin’s Ulcer of Squamous Cell Carcinoma Secondary to Radiation [28, 29]

  • Marjolin’s ulcer (MU) is the presentation of cutaneous malignant tumor over previous chronic inflammatory skin disorder.

  • MU has a predilection for the scalp, trunk, and extremities.

  • MU is usually induced by burns, snake bites, vaccination, radiation, venous stasis, osteomyelitis, and pilonidal abscesses. Commonly, it takes approximately 35 years for this kind of malignant transformation.

  • Squamous cell carcinoma (SCC) is the chief pathological form of MU, followed by melanoma, basal cell carcinoma, and mesenchymal malignancy.

  • It is more aggressive and usually shows a higher rate of regional metastasis than other skin cancers.

  • Localized toxins, immunological depression, carcinogens, and poor lymphatic drainage are its potential etiological factors.

Fig. 27-13-1

Dryness, keratosis, peeling, hyperpigmentation, and slight atrophy on dorsa of the hands, several marked thickened brownish-yellow nails, an ulcer on the extensor of the first and second knuckles of the index finger

Fig. 27-13-2

Irregular hyperplasia epidermis, many tumor cell masses with marked atypical cells, mitotic figures, and atypical mitosis in the whole dermis (HE stain, ×100)

27.14 Cutaneous Clear Cell Squamous Cell Carcinoma [30, 31]

  • Clear cell squamous cell carcinoma (SCC) typically shows lobular neoplastic cells separated by thin strands of fibrous stroma. These cells have an obviously clear cytoplasm with rounded, ovoid, or wrinkled nuclei.

  • Tumor cells in type I resemble mature adipose cells, which have clear cytoplasm and peripheral nuclei. However, there are foci of pronounced keratinization and fibrotic stroma.

  • Tumor cells in type II are disconnected from the overlying epidermis. These cells have reticulated clear cytoplasm without obvious keratinization or ductal or glandular differentiation.

  • Type III is depicted as an extensive ulceration that is unrelated to the overlying epidermis. Nuclear pleomorphism is discernible with foci of squamous differentiation. There are distinctive dyskeratotic cells and pseudoglandular changes.

  • Clear cell occurs in a variety of conditions, including clear cell hidradenoma, clear cell acanthoma, clear cell Bowen’s disease, tricholemmoma, pagetoid squamous cell carcinoma in situ, Paget’s disease, hidradenocarcinoma, sebaceous carcinoma, balloon cell nevus, and balloon cell melanoma.

Fig. 27-14-1

A 2 × 2 cm nodular and ulcer on the left vizard

Figs. 27-14-2, 27-14-3

The tumor masses were consisted of normal squamous cells and of atypical squamous cells with clear cytoplasm and atypical nuclei (HE stain, (2) ×100; (3) ×400)

27.15 Milia En Plaque [32, 33, 34]

  • Milia en plaque (MEP) is characterized by numerous grouped tiny milia circumscribing an erythematous plaque.

  • MEP is most commonly located in the retroauricular region. Occasionally, the eyelids, the paranasal region, submandibular area, supraclavicular area, and mental crease have also been described.

  • Histopathology is characterized by the presence of keratin-filled epidermal cysts surrounded by a variably mild to dense mononuclear infiltrate.

  • MEP is associated with other diseases, such as pseudoxanthoma elasticum and discoid lupus erythematosus.

Fig. 27-15-1

White-yellow, cystic lesions scattered within slightly erythematous plaques symmetrically localized on the posterior aspects of both his ears

Fig. 27-15-2

Close view of the left ear. Multiple milia and a few open comedones overlaid the erythematous plaques

27.16 Eruptive Vellus Hair Cysts [35, 36, 37]

  • Eruptive vellus hair cysts (EVHC) presents as multiple, small, dome-shaped, comedo-like papules with a smooth surface.

  • EVHC preferentially affects the chest and face. Such a distribution seems to grossly overlap with that of pilosebaceous and apocrine units.

  • The pathological hallmark of EVHC is the existence of multiple vellus hair shafts within the stratified squamous epithelial-lined cysts.

  • EVHC and steatocystoma multiplex belong to two different entities. The nonexistence of attachment of sebaceous glands to the cyst wall, together with negative keratin 10 staining, facilitates this differentiation for EVHC.

  • Other associations, such as keratosis pilaris, trichostasis spinulosa, acneiform eruptions, pilomatricoma, folliculitis, epidermoid cysts, molluscum contagiosum, and perforating dermatosis, have rarely been reported.

Fig. 27-16-1

Numerous blue hair follicle papules on the forehead, a few papules having umbilicated surface

Fig. 27-16-2

Cysts in the upper and mid-dermis were lined by squamous epithelium, and the cysts contained numerous transversely or obliquely cut vellus hairs (HE stain ×40)

27.17 Nevus Comedonicus [38, 39]

  • Nevus comedonicus (NC) presents clusters of follicular horny plugs that are predominantly located on the face and neck.

  • Its lesions may be distributed in a unilateral, bilateral, linear, interrupted, segmental, or blaschkoid way.

  • The first subtype of NC has only comedo-like eruptions, while the second has large cysts, papules, fistulas, abscesses, and scarring in different stages of development.

  • Nevus comedonicus syndrome is defined if NC coexists with additional findings in ocular, skeletal, or neurologic abnormalities. Cataracts, fused vertebrae, scoliosis, delayed mental development, and spina bifida are the most common symptoms in NC.

  • The skin tumors associated with NC syndrome are trichoepithelioma, dilated pore of Winer, syringocystadenoma papilliferum, keratoacanthoma, basal cell carcinoma, hidradenoma papilliferum, or squamous cell carcinoma.

Fig. 27-17-1

Numerous “blackheads” distributed in band and on the left chest

Fig. 27-17-2

There were three keratotic plugs located in dilated follicular orifice (HE stain, ×20)

27.18 Dilated Pore [40, 41]

  • Winer’s dilated pore (DP) is a rare specific neoplasm. The lesion of DP occurs on the face or upper trunk of an elderly individual.

  • The typical lesion of DP presents as an enlarged pore and open comedo. Patients with DP usually have a single lesion. A few patients have two.

  • Histological trait includes infundibular cyst lined by outer root sheath epithelium.

Fig. 27-18-1

A solitary papule with four open comedos on the trunk

Fig. 27-18-2

A dilated pore was filled with lots of keratin (HE stain, ×100)

27.19 Inverted Follicular Keratosis [42, 43]

  • Inverted follicular keratosis (IFK) results from an exoendophytic expansion of the infundibular portion of the hair follicle.

  • The clinical features of IFK are quite variable, from pink papules to keratoacanthoma-like or papillomatous nodules. Its diagnostic confusion includes irritate seborrheic keratosis, warts, keratoacanthoma, adnexal tumor, basal cell carcinoma, and squamous cell carcinoma.

  • Microscopy examination of IFK is a diagnostic step characterized by an endophytic tumor that has peripheral basaloid cells and central larger keratinizing cells with several circumscribed squamous eddies. The absence of atypia, mitotic activity, necrosis, or stromal invasion in IFK helps its differentiation with other dermatoses.

  • The most typical dermoscopic presentation is central keratin encircled by hairpin vessels with a white halo.

Fig. 27-19-1

A millet-sized, well-circumscribed, dust-colored papule with central erosions and black crust on the base of the nose bridge

Fig. 27-19-2

Keratin-filled invaginations were covered with squamous epidermis, surrounded by basaloid cells, which formed squamous eddies, and there were follicular structures in hyperplastic tissue (HE stain, ×20)

27.20 Infundibulocystic Basal Cell Carcinoma [44, 45]

  • Infundibulocystic BCC is a well-differentiated form of BCC that histopathologically shows circumscribed lobular and anastomosing cords of bland basaloid cells with multiple tiny infundibulocystic structures.

  • Infundibulocystic BCC arises as a solitary papule on the face of elder people. Multiple lesions are commonly found in multiple hereditary infundibulocystic BCC syndrome (autosomal dominant inheritance without jaw cysts, palmar pits, or other signs of nevoid basal cell carcinoma syndrome).

  • There is still debate whether infundibulocystic BCC is the same as trichoepithelioma and basaloid follicular hamartoma.

  • It has been noted that infundibulocystic BCC may be established with a paucity of fibrocytes, in contrast to the abundant and highly fibrocystic stroma in trichoepithelioma.

  • Infundibulocystic BCC and basaloid follicular hamartoma might be different names for the same entity, considering their identical morphology and equivalent diffuse distribution of CK20+ cells.

Fig. 27-20-1

A well-circumscribed, intradermal tumor was composed of many anastomosing cords and strands of epithelial cells with a reticulated pattern. There were multiple infundibular cystic structures scattered throughout the neoplasm (HE stain, ×40)

Fig. 27-20-2

Squamoid cells were present in the central of the tumor with oval pale nuclei, while peripheral cell layer was composed of basaloid cells with hyperchromatic, elongated nuclei in a palisade arrangement; the cysts containing corneocytes or wholly hair were lined by follicular infundibular epithelium; follicular bulbs and papillae were seen without mucin deposition (HE stain, ×200)

27.21 Trichofolliculoma [46]

  • Trichofolliculoma typically appears as a central dilated pore with tufted hairs.

  • Histologically, it has a central dilated infundibulum of a primary follicle and several secondary vellus hair follicles derived from it.

Fig. 27-21-1

Slightly reddish nodules on the left nasolabial folds with vellus hairs in a central pore

Fig. 27-21-2

Numerous keratinous cysts in the dermal, hair shaft with double refraction in the cysts (HE stain, ×50)

27.22 Trichoepithelioma [47, 48, 49]

  • Trichoepithelioma (TE) is a benign trichogenic tumor derived from the hair follicle, and solitary, multiple, and dermoplastic TE are three distinctive variants.

  • Microscopic observation of TE reveals basaloid epithelial cell islands, keratinous cysts, and abortive hair follicle structures characterized by follicular differentiation.

  • Dermoplastic TE originates from the outer root sheath of the hair follicle. It usually manifests as a skin-colored, indurated papule or plaque with a peripheral annular ring and a depressed center. Islands of basaloid cells, dense fibrous stroma, and horn cysts serve as a dermatopathological triad for dermoplastic TE.

  • CK20 and androgen receptor are the most reliable immunohistochemical biomarkers to distinguish dermoplastic TE from morpheaform basal cell carcinoma, which is considered potentially more aggressive than the benign nature of dermoplastic TE.

  • Multiple TE may be cosmetically disfiguring, and it may rarely present in a linear configuration following Blaschko’s lines.

  • Trichoepitheliomas are part of a constellation of syndromes, including Brooke-Spiegler syndrome, Bazex syndrome, and Rombo syndrome.

  • While solitary TE results from deletions at 9q22.3, multiple TE is associated with germline mutations in the CYLD gene mapped to chromosome 16q12–q13.

  • Topical sirolimus, imiquimod, and tretinoin are proven to be beneficial in the management of multiple familial trichoepitheliomas.

Fig. 27-22a-1

A mung bean-sized, half ball, light brown papule on the left nose wing

Fig. 27-22a-2

Numerous basaloid cell masses and cell cords containing horn cysts arranged in network in the dermis (HE stain, ×40)

Fig. 27-22b-1

Multiple, varying-sized, rounded, shiny, slightly translucent, flesh-colored nodules on the face, especially on the central face

Fig. 27-22b-2

Numerous masses of basaloid cells in the dermis, keratinous cysts, and infantile follicle also observed (HE stain ×100)

Fig. 27-22c-1

Damask, annular plaque with raised border and damask papules in the center of the scalp

Fig. 27-22c-2

Horn cysts with various sizes, a strand of basaloid tumor cells in the upper dermis, and considerable amounts of collagen fibers (HE stain,×40)

Fig. 27-22c-3

Numerous small horn cysts in the dermis, narrow strands of basaloid cells, and epidermoid cysts infiltrated a fibrotic stroma (HE stain, ×100)

27.23 Bullous Pilomatricoma [50, 51]

  • Pilomatricoma is most seen as a solid, well-demarcated, and slow-growing dermal nodule with an overlying smooth surface. Many subtypes, including familial, bullous, perforating, multinodular, exophytic, anetodermic, and giant clinical types, have been previously reported.

  • Bullous pilomatricoma typically arises as wrinkled, heavily folded, atrophic skin appearance with a predilection for the upper arm and shoulder.

  • Skin biopsy of pilomatricoma exhibits basaloid hair matrix cells, transitional cells, and eosinophilic amorphous ghost cells. The bullous variant additionally features a marked reduction of elastic fiber and prominent dermal edema between the solid tumor and the covering epidermis.

  • The bullous appearance is accredited to the hindrance of lymphatic fluid circulation by the hard central tissue.

Fig. 27-23-1

A wrinkled, purplish, thick-walled, translucent, bulla 2.0 × 2.5 cm in diameter on the left upper arm

Fig. 27-23-2

The marked edema between the epidermis and tumor, markedly dilated thin-walled lymph vessels filled with fluid (HE stain, ×100)

Fig. 27-23-3

The cell islands consisting of basophilic cells, transitional cells, and “shadow” cells with small calcifying areas (HE stain, ×400)

27.24 Areolar Sebaceous Hyperplasia [52, 53, 54]

  • Sebaceous hyperplasia (SH) is a proliferation of the sebaceous gland.

  • The most frequently affected area for SH is the face; the areola, nipples, penis, neck, and chest are atypical locations for it.

  • Areolar SH presents as yellowish papules/plaque or diffuse thickening of the areola, either bilaterally or unilaterally.

  • SH may lead to confusion with milia en plaque, nipple papilloma with sebaceous metaplasia, and Paget’s disease.

  • Giant, linear variants of SH have been documented.

Fig. 27-24-1

Numerous skin-colored nodules around the right nipple

Fig. 27-24-2

Several enlarged sebaceous lobules in the upper dermis (HE stain, ×100)

27.25 Nevus Sebaceous with Apocrine Cystadenoma [55, 56, 57]

  • Nevus sebaceous (NS) is a demarcated, yellowish, hairless patch that commonly involves the scalp.

  • NS and verrucous epidermal nevus may be the same entity, but they differ in locations. NS is designated to patches on the head and neck.

  • NS is an innate hamartoma associated with epidermal, folliculosebaceous, and apocrine structures.

  • The structures previously confirmed as BCC in NS may essentially be the benign tumor of trichoblastoma. Total excision is appropriate for those with a secondary tumor in NS.

  • NS has a higher frequency of oncogenic HPV16 coinfection (39%).

  • Apocrine cystadenoma (AC) is an adenomatous cystic proliferation rather than a simple retention cyst.

  • This cystic tumor consists of layers of cuboidal cells showing decapitation secretion and underlying myoepithelial cells.

  • A complete excision is recommended for AC, which is a real form of proliferation of the apocrine glands.

Fig. 27-25-1

A flaxen plaque with erosions on the scalp

Fig. 27-25-2

Numerous mature sebaceous glands in the upper dermis (HE stain,×100)

Fig. 27-25-3

Papillomatosis in the epidermis, a cystic invagination lined by two rows of cells, decapitation of the nearest luminal cells (HE stain, ×100)

27.26 Linear Nevus Sebaceous Syndrome [58, 59]

  • Linear nevus sebaceous syndrome (LNSS) is within the spectrum of epidermal nevus syndrome or overlaps with neurocutaneous syndrome.

  • Sebaceous nevus is the hallmark of LNSS, and it presents as linear, yellowish plaque, mainly on the midline facial skin. Seizures and mental retardation are its common extracutaneous defects, and they are sometimes difficult to control.

  • The ophthalmologic defects of LNSS are composed of coloboma of the iris, lipodermoid, cataract, ptosis, degenerated retina, detachment of retina, and so on.

  • In addition, there is also a diverse group of abnormalities in the structures of the pulmonary, cardiovascular, skeletal, renal, and gastrointestinal systems.

  • Malignant transformation is likely to occur in LNSS.

Fig. 27-26-1

Lesions of nevus sebaceous located in the midline of the scalp and on both sides of the face, pterygium of bilateral conjunctivae with high myopic retina (Reproduced with the permission from [58, 59])

Fig. 27-26-2

A large number of sebaceous glands and papillomatous hyperplasia of the epidermis with hyperkeratosis (HE stain, ×100)

27.27 Apocrine Hidrocystoma [60, 61]

  • Apocrine hidrocystoma (AH) is a translucent nodular lesion that affects the face, head, and neck.

  • The color of AH varies from flesh-colored to blue, brownish, or even black.

  • AH and apocrine cystadenoma (AC) are both described as a cystic proliferation of apocrine glands.

  • AC is not a simple retention of cyst apocrine; it has papillomatous hyperplasia of the apocrine, which projects into the cystic lumen. Apocrine papillary cystadenoma is regarded as a variant of AC with enormous papillary projections.

  • There is prevailing belief that cystic apocrine neoplasm without papillary projections into the cystic cavity should be diagnosed as apocrine hidrocystoma.

Fig. 27-27-1

A rufous translucent nodule of cystic consistency on the right of the nose bridge

Fig. 27-27-2

The dermis contained several large cystic spaces into which papillary projections often extended; the inner surface of the wall and the papillary projections were lined by a row of secretory cells of variable height showing “decapitation” secretion indicative of apocrine secretion (HE stain, ×100)

27.28 Eccrine Angiomatous Hamartoma [62, 63]

  • Eccrine angiomatous hamartoma (EAH) is abnormal proliferation of the skin eccrine and blood vessels, and it usually has a predilection for the extremities.

  • Approximately half of the patients develop EAH at birth, and 3/4 of the remaining patients develop EAH in adolescence.

  • Lesions in EAH are quite variable, including red, yellow, brown, skin-colored papules or plaque. Hyperkeratotic, verrucous variants are also seen.

  • Some patients may complain about obvious hyperhidrosis, pain, or hypertrichosis.

  • Histological observation reveals a tubular and glandular structure within an enriched vascular structure.

Fig. 27-28-1

Bluish multi-annular macules with elevated edges and numerous follicular papules in the lesions

Fig. 27-28-2

Dilated blood vessels in the lower dermis, nearby numerous dilated ducts of eccrine glands (HE stain, ×400)

27.29 Syringocystadenoma Papilliferum [64, 65, 66]

  • Syringocystadenoma papilliferum (SCAP), in the majority of cases, appears on the scalp, neck, or face in females.

  • SCAP clinically arises as a solitary papule, nodule, or plaque. These lesions are verrucous or exudative. Rarely, it may be present in a linear configuration.

  • A unifying pathological feature of SCAP is the presence of a cystic and papillary projection of scaly epithelium and rich infiltration of plasma cells in the stroma. There are two types of tumor cells. In the outer layer, there are cuboidal cells characterized by round nuclei and scarce cytoplasm. The inner layer is comprised of decapitated columnar cells.

  • SCAP is most contiguous with an organoid nevus comprised of basal cell carcinoma, nevus sebaceous, and trichilemmoma.

Fig. 27-29-1

A solitary red tumor on the flexor aspect of the left leg

Fig. 27-29-2

Numerous papillary projections into the lumina of the invaginations (HE stain, ×100)

Fig. 27-29-3

The invaginations were lined by glandular epithelium consisting of two rows of cells (HE stain, ×400)

27.30 Eruptive Milium-Like Syringoma [6768]

  • Syringoma appears as multiple, firm, flesh-colored, or brownish papules, 1–3 mm in diameter.

  • Friedman et al. proposed that syringoma can be classified into four clinical subtypes: localized, familial, Down syndrome-related, and generalized variants.

  • Skin biopsy of syringoma reveals aggregations of nests, cords, or tubules, lined by single- to double-layered cuboidal epithelium, giving them a tadpole shape. Some ducts are dilated and contain eosinophilic materials.

  • In localized syringoma, the periorbital, vulva, penis, scalp, and axillae are predominantly involved.

  • Generalized syringomas tend to have multiple systemic associations, as shown in Brooke-Spiegler syndrome, Nicolau-Balus syndrome, and Costello syndrome.

  • Eruptive milium-like syringoma occurs in successive crops of small papules with superimposed variable milia that are distributed extensively over the chest, axillae, neck, abdomen, and extremities.

  • Lichen planus-like syringoma has lichenoid plaques caused by repetitive scratching.

  • In comparison to classical syringoma, the onset of the eruptive type mostly occurs before or during puberty.

  • Unilateral syringoma, urticarial pigmentosa-like syringoma, clear cell syringoma, and chondroid syringoma are its other demonstrations.

  • The dermoscopic features of eruptive syringoma are comprised of a rosette structure and a nonspecific structure of the pigment network with a reddish tinge.

Fig. 27-30-1

Dense millet to mung bean-sized skin-colored papules on both of the labia majora

Fig. 27-30-2

Hyperkeratosis, keratin cysts in superficial dermis, cystic ductal lumina filled with acidophil, and many cell cords (HE stain, ×40)

27.31 Segmental Multiple Eccrine Spiradenomas [69, 70, 71]

  • Eccrine spiradenoma (ES) usually occurs as subcutaneous papule or nodule ranging from 1 to 2 cm in diameter. An overlying pink or blue hue is highly suggestive of its diagnosis.

  • ES is in the spectrum of painful skin disorders, including neuroma, leiomyoma, angiolipoma, dermatofibroma, endometrioma, neurilemmoma, granular cell tumor, and glomus tumor.

  • Clinically, ES is classified as solitary and multiple variants. Histological classification of ES includes common, vascular, and cystic variants.

  • ES is comprised of multiple, well-circumscribed, basophilic subcutaneous nodules surrounded by eosinophilic fibrous strands. Two types of distinct cells are clues for its diagnosis: larger, pale staining clustered cells at the center and smaller cells characterized with peripheral hyperchromatic nuclei. Duct-like structures may exist at the center.

  • S-100, pancytokeratin, and CK7 are expressed on tumor cells in ES.

  • Vascular eccrine spiradenoma, a rare variant of ES, contains abundant vascular stroma.

  • In Brooke-Spiegler syndrome, spiradenomas commonly occur jointly with cylindromas and trichoepitheliomas.

Figs. 27-31-1, 27-31-2, 27-31-3

Zosteriform distribution of purple macules on the right chest, flexor side of upper limb, waist, and abdomen along the intercostal nerve or long axis of limb

Figs. 27-31-4

A large and well-circumscribed, dermal nodule comprised of tumors was surrounded by fibrous membrane (HE stain, ×100)

Fig. 27-31-5

Tumors were composed of cells with large, lightly stained nuclei located in the center of the tumor and some cells with small, darkly stained nuclei around the tumor. Some tumor cells were arranged in rose pattern with a few small lumina (HE stain, ×100)

27.32 Clear Cell Hidradenoma [72, 73, 74]

  • Clear cell hidradenoma (CCH) is a benign neoplasm from a skin appendage. It usually presents as a solitary unencapsulated dermal nodule.

  • Microscopic observation in CCH shows a grenz zone between the epidermis and tumor masses. CCH are composed of polyhedral cells with basophilic cytoplasm and oval cells with vacuolated cytoplasm.

  • The oval cells have rich glycogen without lipid, and they stain positively with periodic acid-Schiff and diastase-resistant material.

  • Metastatic renal cell carcinoma and other clear cell neoplasms should be cautiously excluded before the final diagnosis of CCH.

  • Immunohistochemical studies are valuable in distinguishing CCH (CK5+, CK6+, CK7+) from renal cell carcinoma (vimentin+, CD10+).

Fig. 27-32-1

A well-circumscribed, rosiness nodule with crust on the forehead

Fig. 27-32-2

The tumor consisting of polyhedral cells and clear cell, with transitional cells between these two varieties and cystic and lumina spaces also observed (HE stain, ×100)

27.33 Malignant Eccrine Poroma [75, 76, 77]

  • Malignant eccrine poroma (MEP) often appears as nodular, ulcerated, or polypoid, and it occurs on the intraepidermal eccrine duct.

  • MEP arises spontaneously or from an eccrine poroma that has existed for a long time.

  • The neoplasm consists of squamous cells, spindle cells, and differentiated clear cells. Pagetoid spreading of melanocytes is reported in MEP.

  • The vacuolated cytoplasm, duct-like structures, and eosinophilic cuticles in MEP are signs of eccrine differentiation.

  • The nuclei of these tumor cells are large. The cells have a higher mitotic rate (compared to normal cells) and clear cytoplasm, and they show EMA+, S-100 -, and CEA−.

  • Histopathological findings of lymphovascular invasion, mitosis >14 per high-power field, depth of invasion >7 mm, and lymph node involvement are predictive of a fatal prognosis.

Fig. 27-33-1

A well-circumscribed, walnut-sized, brownish-red nodule with erosions and wet base on the scalp

Fig. 27-33-2

Tumor located in the epidermis, composed most of basaloid cells and some atypically eosinophilic squamous cells scattered as masses (HE stain, ×200)

27.34 Microcystic Adnexal Carcinoma [78, 79, 80]

  • Microcystic adnexal carcinoma (MAC) is a locally invasive neoplasm with pilar and eccrine gland differentiation that rarely metastasizes.

  • MAC appears as a firm subcutaneous papule, nodule, plaque, or cystic lesion. It has a predilection for the central face or T zone.

  • The report of numbness, paresthesia, burning, or pruritus at the tumor site indicates perineural invasion.

  • The histological features in MAC are comprised of horn cysts and epithelial cells arranged in a nest strand or a cord pattern in the superficial dermis. Ductal structures are embedded in a desmoplastic matrix in the deep dermis.

  • The lack of circumscription, deep dermal involvement, and perineural invasion are helpful diagnostic features.

  • As radiation promotes MAC development, it should be discouraged in its management.

Fig. 27-34-1

An indurated and unmovable plaque with a black crust on its surface on the right chest

Fig. 27-34-2

Hyperkeratosis and tumor cell were arranged in funicular pattern, cord, and adenoid structures (HE stain, ×100)

Fig. 27-34-3

Sparse solid islands of squamous cells surrounded by basaloid cells (HE stain, ×400)

Fig. 27-34-4

Tumor cells AE1/AE3 positive (En Vision method, ×400)

Fig. 27-34-5

Part tumor cells CEA positive (En Vision method, ×400)

27.35 Acquired Digital Fibrokeratoma [81, 82]

  • Acquired digital fibrokeratoma (ADF) is a hyperkeratotic, fibrous periungual neoplasm.

  • ADF clinically presents as a solitary, smooth, dome-shaped or fingerlike, flesh-colored papule of the extremities.

  • Histologically, it features connective tissue proliferation with an overlying epidermal orthokeratosis or hyperkeratosis, papillomatosis, and acanthosis.

  • Differentiation of ADF with the periungual tumors includes Koenen tumors of tuberous sclerosis, rudimentary supernumerary digits, endochondromas, and neurofibromas.

  • APF is mainly different from acquired digital fibrokeratoma in the aspects of location, microscopic production of a pseudo-nail plate, and a requirement for meticulous surgery to preserve the germinal matrix.

Fig. 27-35-1

A damask, digital neoplasm on the second toe tip of the right foot

Fig. 27-35-2

The epidermis showed marked hyperkeratosis and acanthosis with thickened, branching rete ridges (HE stain, ×40)

Fig. 27-35-3

Considerable amount of collagen fibers and fibroblasts in the dermis (HE stain, ×100)

27.36 Epithelioid Cell Histiocytoma [83, 84, 85]

  • Fibrous histiocytoma has a densely cellular form (histiocytoma) or a dominant collagenous form (fibromas).

  • Histiocytoma can be classified into following subtypes: classic, storiform, xanthomatized, monster cell, hemosiderotic, giant cell, and epithelioid cell histiocytoma (ECH).

  • Several variants of fibroma have been proposed. They are classic, sclerotic, and hyalinized fibroma, as well as angiofibromas.

  • Epithelioid cell histiocytoma can be single, multiple, or eruptive. It is made up of different proportions of proliferated histiocytes, fibroblasts, and collagen.

  • ECH is dominantly an exophytic nodular lesion with a silhouette of pyogenic granuloma.

  • The histological features of ECH include angulated epithelia embedded in massive vascular stroma. The cytoplasm is filled with eosinophilic materials. Spindle-shaped cells with ovoid or tapering nuclei are located underneath the deep dermis.

  • Immunohistochemical stainings are XIIIa+, vimentin+, and al-antitrypsin+. The absence of S-100 and HMB-45 rules out melanocytic disorders.

  • The granular cell variant of ECH has also been documented.

Fig. 27-36-1

A well-circumscribed protuberant violaceous nodule on the forehead

Fig. 27-36-2

Marked hyperplasia and dilated vessels in the tumor tissue and slight collagen fiber hyperplasia (HE stain, ×100)

Fig. 27-36-3

The tumor was mainly composed of epithelioid cells and prominent plasma cells with nuclei mitoses (HE stain, ×400)

27.37 Multiple Eruptive Dermatofibromas [86, 87, 88]

  • Multiple eruptive dermatofibromas are a rare clinical form of dermatofibroma, which is defined as the occurrence of no less than eight dermatofibromas within a 4-month period.

  • There is a spontaneous regression of these lesions over several months.

  • Histiocytosis X, juvenile xanthogranuloma, papular xanthoma, sinus histiocytosis with massive lymphadenopathy, urticaria pigmentosa, and benign cephalic histiocytosis should be excluded before MEDF is diagnosed.

  • The relationship between the immunosuppressive level of the patient and the occurrence of MEDF has led to the speculation that MEDF is an additional sign of immunosuppression.

Fig. 27-37-1

Numerous flesh-colored to red papules on the trunk

Fig. 27-37-2

Infiltrate composed of various types of histiocytes in the dermis (HE stain, ×400)

27.38 Intradermal Nodular Fasciitis [89, 90]

  • Nodular fasciitis (NF) is a benign myofibroblastic proliferation that commonly occurs in young adults.

  • NS has a distinct predilection for subcutaneous (particularly the volar aspect of the forearms), intramuscular, fascial, or periosteal areas. Intradermal nodular fasciitis is extremely rare.

  • It characteristically manifests as a rapidly growing, circumscribed tender nodule within a few weeks.

  • Microscopic observation of NF reveals a loose myxoid stroma and numerous spindle cells with eosinophilic cytoplasm. It can be categorized into myxoid, cellular, and fibrous pathological variants, and the immunoprofile is SMA+, vimentin+, CD34−, and desmin−. In intradermal NF, fibroblast-like spindle cells deeply infiltrate into the subcutaneous skin.

  • NF can be easily misdiagnosed as sarcoma owing to its rapid growth, abundant cellularity, mitotic activity, and contiguous tissue infiltration.

  • Local excision or strict follow-up is appropriate management for the confirmed NF patient.

Fig. 27-38-1

A subcutaneous nodule without pain and ulcer on the left leg

Fig. 27-38-2

Lots of fusiform cells in the dermis and hypodermis (HE stain, ×50)

Fig. 27-38-3

Some fusiform cells had hyperchromatic and irregularly shaped nucleus (HE stain, ×250)

27.39 Dermatofibrosarcoma Protuberans [91, 92, 93]

  • Dermatofibrosarcoma protuberans (DFSP) is a rare fibrohistiocytic tumor with a low-grade malignancy.

  • Although DFSP can occur in children, a congenital case is considered a hamartoma, which is exceedingly rare.

  • Classically, DFSP begins as a solitary, violaceous nodule or plaque on the trunk. It progresses to be multilobulated after years or decades. Atrophic DFSP most commonly appears as an atrophic, morphea-like plaque.

  • Classical DFSP usually exhibits proliferated spindle cells with fingerlike projections deep in the dermis, forming a storiform as a pathological change.

  • XIIIa, S100, and CD56 negativities will assist in making a differential diagnosis with XIIIa-positive dermatofibroma, melanoma, and neurogenic neoplasms.

  • Congenital atrophic DFSP usually masquerades as medallion-like dermal dendrocyte hamartoma (ML-DDH), in which spindle cells express CD34, factor XIIIa, and fascin (dendritic cell markers). DFSP can easily be distinguished from ML-DDH considering its negative stain for factor XIIIa and the formation of the COL1A1-PDGFB fusion protein.

  • Metastasis of DFSP is likely in patients whose skin specimen shows more than eight mitoses per high-power field.

  • Excision with a 2 cm margin is the standard of treatment.

Fig. 27-39a-1

A large brown atrophic patch with six raised, reddish firm smooth nodules on the back

Fig. 27-39a-2

A. Dense, monotonous spindle cells were arranged in a storiform pattern (HE stain, ×100)

Fig. 27-39a-3

CD34 positive in the cytoplasm of tumor cell (SP stain, ×100)

Fig. 27-39b-1

A 3 × 2.5 cm irregular dark erythema with atrophic surface on the right lower back

Fig. 27-39b-2, 27-39b-3

Monotonous spindle cells in the dermis and subcutaneous tissue, penetrating into the subcutaneous fat; some cells were arranged in cartwheel pattern; a few cells with larger and darker nuclei (HE stain, (2) ×40; (3) ×200)

27.40 Epithelioid Sarcoma [94, 95, 96]

  • Epithelioid sarcoma (ES) is a malignant tumor with a high incidence of local recurrence and metastasis, and it arises in deep mesenchymal tissues.

  • ES grows as solitary or multiple subcutaneous nodules with a woody, hard consistency, and it distributes along the fibrous sheaths of tendons or other fibrous structures over the extremities of the young people.

  • ES is basically lethal, although it may easily be mistreated as a benign disease, both clinically and pathologically.

  • Metastasis of ES has a propensity for the regional lymph node, lungs, and scalp, usually in a 5- to 10-year period. Locally recurrent ES appears as annular plaques.

  • Microscopic observation reveals circumferential nodules, usually with central necrosis, that can easily be mistaken as a necrotizing granuloma. The tumor cells are mostly ovoid to polygonal and have rich cytoplasm.

  • ES often expresses cytokeratin and epithelial membrane antigen, which help to differentiate it from other sarcomas, malignant fibrous histiocytoma, and melanoma. Meanwhile, it uniformly lacks common leukocyte antigens, myoglobin, and factor VIII-related antigen.

  • Lesions in ES that are over 3 centimeters in diameter, deep infiltration of tumor cells, and focal necrosis are factors associated with a poor prognosis. The young female ES might have a better outcome than others.

  • The extent of surgery does not show a substantial influence on the survival rate or local recurrence in ES populations.

Fig. 27-40-1

Brownish nodules partly with ulcers on the upper limbs

Fig. 27-40-2

Nodular atypical epithelioid cells with eosinophilic cytoplasm and atypical nuclear (↑) (HE stain, ×400)

Fig. 27-40-3

Positive staining for cytokeratin (CK) in the tumor cells (LSAB, ×400)

Fig. 27-40-4

Positive staining for epithelial membrane antigen (EMA) in the tumor cells (LSAB, ×400)

27.41 Superficial Angiomyxoma [97, 98]

  • Myxoma consists of stellate cells in a loose mucoid matrix.

  • Superficial angiomyxoma (SA) is a cutaneous myxoma that arises in the pronounced vascular component.

  • Pathognomonic signs for the Carney complex consist of multiple cutaneous myxomas and SA, particularly on the external ear.

  • SA displays a well-circumscribed, nodular lesion, which is usually bigger than 5 cm in diameter.

  • Histological observation of SA reveals well-circumscribed multilobulated lesions consisting of numerous stellate fibroblasts, capillary-like vessels, and neutrophils in the dermal matrix.

  • Both keratin cysts and thin strands of squamous cells in the epidermis are suggestive of a higher rate of local recurrence after surgery.

  • The differential diagnosis in SA is very wide, including superficial acral fibromyxoma, intramuscular myxoma, aggressive angiomyxoma, nerve sheath myxoma, juxta-articular myxoma, angiomyofibroblastoma, focal mucinosis, myxoid neurofibroma, angiomyxolipoma, malignant myxomatous, and ganglion cysts.

Fig. 27-41-1

A red nodule measuring 0.5 × 0.5 cm on the scalp

Fig. 27-41-2

The tumor located in the dermis and defined by thick collagen bundles (HE stain, ×40)

Fig. 27-41-3

Myxoid stroma filled the whole tumor, and starlike and spindle-shaped stromal cells were scattered throughout the tumor (HE stain, ×200)

Fig. 27-41-4

Small, thin-walled blood vessels scattered in the tumor and fiber bundles (HE stain, ×400)

27.42 Multicentric Reticulohistiocytosis [99, 100, 101, 102]

  • Multicentric reticulohistiocytosis (MRH) is an uncommon histiocytosis that has extensive papulonodular lesions and severe arthropathy.

  • Most MRH patients seek management of joint problems before their skin lesions manifest. Fatigue, weight loss, and fevers are concomitant symptoms with MRH.

  • The musculoskeletal findings of MRH present as erosive arthritis, which is prone for the development of joint structural deformities. The younger the patient at the time of diagnosis, the higher the likelihood that the development of arthritis mutilans may appear.

  • The skin lesions can be brown-reddish to flesh-colored papules and nodules, usually with residual atrophic scars or disfigurement. Coalesced lesions tend to have a cobblestone appearance. “Coral beads” is the pathogenic sign when the periungual area is involved.

  • Approximately 25% of MRH has underlying malignant disorders, and treatment of these malignancies can only ameliorate its symptoms.

  • Cardiopulmonary features include pleural effusions, pulmonary fibrosis, pericardial effusion, and congestive heart failure, and these features confer a grave prognosis.

  • The gastrointestinal, urogenital, and hepatic systems are occasionally affected.

  • Although spontaneous healing occurs in MRH within approximately 10 years, many individuals have already suffered from irreversible deforming arthritis by then.

  • The pathological hallmarks of MRH diagnosis are comprised of abundant histiocytes with multinucleated giant cells and ground-glass-like cytoplasm. Immunohistochemical profiles are positive for vimentin, CD68, MAC387, HAM-56, CD3, and CD45, while they are negative for S100, CD1a, CD34, XIIIa factor, and CD19. Langerhans granules are not identified under electron microscopy.

  • Bisphosphonates have shown promising results to inhibit osteoclast formation in MRH, and they are regarded as a promising effective modality for its treatment.

Figs. 27-42-1, 27-42-2, 27-42-3, 27-42-4, 27-42-5

There were papules and nodules on the face (1), ears (2), dorsa of the hands (3), elbows (4), and erythematous plaques on the buttocks (5)

Fig. 27-42-6

Numerous nodules in the bronchus

Fig. 27-42-7

A mass 1.5 × 2.0 cm in size on the left aryepiglottic fold

Fig. 27-42-8

Histiocytes and multinucleated giant cells with eosinophilic “ground-glass” cytoplasm in the dermis (HE stain, ×200)

Fig. 27-42-9

Brown-yellow cytoplasm, CD68 positive (SP stain, ×200)

27.43 Letterer-Siwe Disease [103, 104]

  • Histiocyte refers to a category of cells consisting of macrophages and other dendritic cells (antigen-presenting cells: dermal dendrocytes, Langerhans cells, and undetermined cells).

  • Histiocytoses are a spectrum of histiocytic proliferations categorized into Langerhans cell histiocytoses (LCH), non-Langerhans cell histiocytoses, and malignant histiocytoses.

  • Four well-defined variants of LCH have been recognized, namely, Hand-Schüller-Christian disease, Letterer-Siwe disease (LSD), Hashimoto-Pritzker disease, and eosinophilic granuloma.

  • The incidence of dermal infiltrations of lymphomonocytic cells with reniform nucleus is highly suggestive of LCH. The diagnosis is established if the expressions of CD1a, S100, CD 207, CD68, and factor XIIIa are confirmed. Birbeck granules are pathognomonic of LC under electronic microscope.

  • The mortality rate for LCH in children less than 2 years of age with multiorgan involvement tends to have a bad prognosis.

  • Painful intertriginous cutaneous LCH lesions respond well to thalidomide.

  • Crusted or scaly papules and papulovesicles are the most common lesions in skin folds in LSD.

  • Rarely, nodular, vesicular, purpuric, erosion, granuloma, and pustular lesions are likely to display in crops in LSD.

  • Poor prognostic features include younger age; involvement of the nail, gastrointestinal tract, lung, and liver; infections; and anemia.

  • Emperipolesis and positive immunological staining for S100, CD68, and CD1a are the main features in Rosai-Dorfman disease (RDD).

Fig. 27-43-1

The petechiae and brownish papules covered with crusts or scales on the chest and the abdomen

Fig. 27-43-2

There was a superficial dermal infiltration of mononuclear cells; some of them had invaded the epidermis (HE stain, ×200)

27.44 Cutaneous Rosai-Dorfman Disease [105, 106]

  • Rosai-Dorfman disease (RDD), also known as sinus histiocytosis with massive lymphadenopathy, is a self-limited, multiorgan, non-Langerhans cell histiocytosis. It usually has systemic complications of fever, weight loss, night sweating, etc.

  • Cutaneous Rosai-Dorfman disease (C-RDD) is a type of extranodal RDD that involves the skin.

  • The clinical manifestations of C-RDD are quite variable, ranging from papules, nodules, and plaques to rare pustular or acneiform eruptions. However, the most typical lesion is a central noduloplaque with surrounding satellite papules. The colors of the lesions are diverse, ranging from erythematous, brownish, gray-blue, violaceous, or yellowish in appearance.

  • C-RDD is commonly seen in Asia and is divided into the papulonodular type, indurated plaque type, and tumor type.

  • Histopathological features of C-RDD are comprised of the infiltration of lymphocytes, histiocytes, and plasma cells. Histiocytic morphology is highly characterized by vesicular nucleus and pale cytoplasm. The immunoprofile of these histiocytes is CD68+, S100+, CD1a−, Langerin−, Factor XIIIa−, and CD34−. Emperipolesis is the diagnostic pathognomonic finding in its differentiation from other histiocytoses.

  • The engulfed cells seen in emperipolesis are intact and survive in the histiocytes, which differs from phagocytosis.

  • C-RDD is the least responsive to corticosteroids, but surgical excision can be curative. However, commitment with widespread visceral damage usually has a fatal outcome.

Fig. 27-44-1

A brown-red plaque 4.5–7.1 cm in size on the left cheek

Fig. 27-44-2

Epidermal atrophy and many histiocytes, lymphocytes, and plasma cells associated with lymph follicular structure were present in the dermis (HE stain, ×100)

Fig. 27-44-3

The lymphocyte, plasma cell, and nuclear debris were phagocytosed in a big histiocyte around many plasma cells (HE stain, ×400)

Fig. 27-44-4

S100 positive in histiocyte (Envision method, ×400)

Fig. 27-44-5

CD68 positive in histiocyte (Envision method, ×400)

27.45 Phakomatosis Pigmentovascularis [107, 108]

  • Phakomatosis pigmentovascularis syndrome (PPS) is the co-occurrence of cutaneous pigmentary abnormalities and vascular lesions.

  • PPS can be classified into several types (shown in Table 27.27-1).

Table 27.27-1

Classification of phakomatosis pigmentovascularis


Vascular nevus

Pigmentary changes

I a, b

Nevus flammeus

Nevus pigmentosus and verrucosus

I1 a, b

Nevus flammeus ± nevus anemicus

Mongolian spot

111 a, b

Nevus flammeus ± nevus anemicus

Nevus spilus

IV a, b

Nevus flammeus ± nevus anemicus

Mongolian spot, nevus spilus


Cutis marmorata telangiectatica congenita

Mongolian spot

Fig. 27-45-1

A gray-blue spot about 40 × 25 cm on the back and a nevus flammeus about 16 × 10 cm on the left waist

27.46 Angiokeratoma Corporis Diffusum [109, 110]

  • Angiokeratoma is characterized by vascular ectasia in the superficial dermis with acanthosis, hyperkeratosis, and other epidermal changes.

  • Angiokeratoma corporis diffusum (ACD) belongs to a variant of angiokeratoma highlighted by numerous dark-red papules or plaques on the lower part of the trunk, buttocks, and legs.

  • ACD is considered the cutaneous hallmark of Fabry’s disease, fucosidosis type II, Kanzaki disease, mannosidosis, sialidosis, galactosialidosis, and aspartylglycosaminuria, which are caused by a defect of a certain lysosomal enzyme.

  • Fabry’s disease occurs as a result of a dysfunctional lysosomal enzyme named galactosidase A.

Fig. 27-46-1

Numerous clusters of tiny red papules on the left leg

Fig. 27-46-2

Numerous tiny red papules on the lower abdomen

Fig. 27-46-3

Ectasia of blood vessels in the papillary dermis with overlying hyperkeratosis (HE stain, ×100)

Fig. 27-46-4

Lamellar bodies in the lysosome of the epithelium of renal glomeruli

27.47 Angiokeratoma of Fordyce [111, 112]

  • Angiokeratomas display demarcated, verrucous papules with a red, blue, or black color.

  • Histology of the lesion shows hyperkeratosis in the epidermis. In the reticular dermis, blood-filled vessels are notably dilated.

  • Angiokeratoma of Fordyce is a localized variant, which is characterized by the involvement of the penis or vulva.

  • Although angiokeratomas of the scrotum are common, unilateral distribution of the lesions is extremely rare.

Fig. 27-47-1

Clusters of mauve papules on the right scrotum

Fig. 27-47-2

A few small vascular papules on the vulva

27.48 Angioma Serpiginosum [113, 114]

  • Angioma serpiginosum (AS) is a congenital capillary malformation characterized by capillary ectasias in the papillary dermis.

  • Clinically, AS presents multiple, punctate, nonblanchable, and red macules arranged in a serpiginous pattern.

  • Skin biopsy shows ectatic, congested, and tortuous capillaries without inflammation in the superficial dermis.

Fig. 27-48-1

Netlike pattern deeply red maculae and numerous violaceous spots on the buttock

Fig. 27-48-2

Dilated capillaries in the papillae and reticular dermis (HE stain, ×100)

27.49 Reactive Angioendotheliomatosis [115, 116]

  • Reactive angioendotheliomatosis (RAE) is a self-limiting disease. It is regarded as a benign proliferation of endothelial cells in the skin.

  • Observation of the lesions reveals erythematous to violaceous patches, papules, or plaques that occasionally become ulcerated or blistered.

  • Clinically, RAE resembles eruptive disseminated lobular capillary hemangioma, Kaposi’s sarcoma, morphea/scleroderma, pyoderma gangrenosum, calciphylaxis, and angiosarcoma.

  • It is usually associated with a wide spectrum of diseases, such as infections, cryoproteinemias, monoclonal gammopathies, and allergic disorders. Peripheral vascular atherosclerotic disease, pregnancy, and iatrogenic arteriovenous fistulas also correlate to RAE.

  • Malignant angioendotheliomatosis is a counterpart of RAE, which is a fatal, B-cell intravascular lymphoma.

Fig. 27-49-1

There were six to eight patches of erythemas, papules, or plaques presented on the antecubital area, the biggest diameter of which was 4 cm. There were variable pin-sized hemacelinosis inside

27.50 Epithelioid Hemangioma [117, 118]

  • Epithelioid hemangioma (EH) is a neoplasm of blood vessels involving the skin on the head and neck.

  • EH is characterized by a solitary, round, erythematous papule, nodule, or plaque. Multiple lesions or zosteriform figurations are quite rare.

  • Histologically, EH is characterized by an unclear lobular proliferation of epithelioid endothelial cells of various sizes. Variable lymphocytes and eosinophils can be seen around these vessels. Immunohistochemistry is positive for the endothelial biomarkers CD31 and CD34, and it is negative for epithelial markers (cytokeratins).

  • The plump endothelial cells, stromal fibrosis, and distinctive clinical manifestations all differentiate Kimura’s disease from EH.

Fig. 27-50-1

Multiple brownish-red nodules with smooth surfaces on the left scalp

Fig. 27-50-2

Exuberant proliferation of vessels lined by cuboidal to endothelioid cells with inflammatory infiltration (HE stain, ×200)

27.51 Tufted Angioma [119, 120, 121]

  • Tufted angioma (TA) is regarded as a benign vascular neoplasm commonly observed among children under 5.

  • The clinical manifestation of TA is quite variable. It characteristically shows red-brownish, indurated nodules or plaques. TA in linear or annular arrangements has been reported. Rarely, there is hyperhidrosis and hypertrichosis overlying the lesion.

  • Multiple lobular vascular proliferation occupying stroma in the dermis and subcutis (cannonball pattern) is highly suggestive of TA. The endothelial cells are plump with spindle-shaped pericytes.

  • Oral mucosa and vermilion border are preferentially affected in adult TA.

  • TA is occasionally related to systemic diseases, such as chronic coagulopathy, Kasabach-Merritt syndrome, and thrombocytopenia, and it usually has a poor cosmetic outcome.

  • Juvenile capillary hemangioma lacks cannonball nests and glomeruloid structures, which differentiates it from TA.

Fig. 27-51-1

Red-brown plaques with thick indurated border and a central depression similar to a doughnut

Fig. 27-51-2

Well-circumscribed capillary lobules in the dermis (HE stain, ×100)

27.52 Verrucous Hemangioma [122, 123]

  • Verrucous hemangioma (VH) represents a rare congenital vascular anomaly commonly found on the leg unilaterally.

  • VH originally appears as a bluish-purple macule that progresses to a warty plaque or nodule. Its size varies from approximately 0.5 to 8 cm in diameter. These lesions can be solitary or multiple and are distributed in a linear or serpiginous pattern.

  • Histopathologically, VH displays marked verruciform epidermal changes (papillomatosis, hyperkeratosis, and acanthosis) overlying delicate, ectatic thin-walled vessels. Meanwhile, thick-walled, small blood vessels extend deeply into the reticular dermis and subcutaneous tissue, which is a reliable feature for distinguishing VH from angiokeratoma.

  • VH persists after excision, mainly due to deep subcutaneous involvement.

Fig. 27-52-1

A group of several well-circumscribed, hyperkeratotic, dark-red plaques were arranged linearly along the inside aspect of left lower extremity

Fig. 27-52-2

Hyperkeratosis of the epidermis and multiple dilated vessels filled with red blood cells in the superficial dermis (HE stain, ×100)

27.53 Targetoid Hemosiderotic Hemangioma [124, 125]

  • Targetoid hemosiderotic hemangioma (THH), or hobnail hemangioma, is a type of vascular proliferation occurring mostly in adult persons.

  • THH classically presents as a solitary, brown to violaceous papule or plaque enclosed by a thin pale area and an outlying ecchymotic ring, giving a targetoid manifestation. However, this ecchymotic ring is not always present.

  • A histopathological change of THH is a biphasic vascular proliferation pattern. Vascular channels in the papillary dermis are ectatic and lined by the hobnail-like endothelial cells. In the mid-dermis, collagen bundles are dissected by the slit-like or angulated vascular spaces. Abundant hemosiderin deposition, together with extravasated erythrocytes, is noteworthy.

  • A low Ki-67 proliferation index and/or negative immunostaining for Wilms tumor-1 gene indicate a vascular malformation in THH rather than a proliferative nature.

  • Mounting evidence shows that THH is of lymphatic origin: CD31+, CD34−, VEGFR-3+, and D2-40+.

  • Occasionally, THH relapses after spontaneous resolution.

Fig. 27-53-1

A 1.7-cm-sized, targetoid violaceous papule with an annular violaceous and outmost yellowish ring was noted on the upper part of the left shoulder

Fig. 27-53-2

Histologic evaluation revealed dilated and proliferated capillaries in the superficial dermis. Some highly dilated lumina were congested with eosinophilic, homogenous materials. Blood vessels or lymphatic vessels ran parallel to the surface of the skin. Slit-like vessels were located in the mid-dermis and dissected between collagen bundles (HE stain, ×100)

Fig. 27-53-3

Vessels were lined with plump, hobnail-like endothelial cells protruding into the lumen. Extravasated erythrocytes were obvious (HE stain, ×400)

Fig. 27-53-4

Prussian blue stain for iron highlights, abundant hemosiderin deposition between collagen bundles (Prussian blue stain, ×400)

27.54 Microvenular Hemangioma [126, 127]

  • Microvenular hemangioma (MH) is a benign proliferation of the blood vessels with a predilection for adults.

  • It commonly occurs as a solitary papule or plaque with variable size and violaceous-to-red color.

  • The development of MH may be associated with hormonal disturbances after the administration of contraceptive drugs or during pregnancy.

  • Histopathologic findings include irregularly branching small-caliber venules with narrow lumina, which are distributed between the sclerotic collagen bundles. The endothelial cells are walled by pericytes. Cellular atypia, pleomorphism, or mitotic figures are absent.

  • MH is CD31+, CD34+, factor VIII+, and SMA+ for the lesional pericytes but stains negatively for podoplanin.

  • Angiosarcoma and Kaposi’s sarcoma (KS) are distinguished from MH by the nonexistence of pericytes of the vessels and other characteristics.

Fig. 27-54-1

A 7 × 18 cm erythema with irregular border on the chest

Fig. 27-54-2

Slit-like vascular channels in slightly collagenous stroma (HE stain, ×400)

27.55 Glomus Tumor [128, 129]

  • Glomus tumor (GT) is recognized as a benign, vascular hamartoma that originated from the neuromyoarterial glomus unit. The tumor is made up of varying proportions of glomus cells, vascular tissue, and smooth muscle cells.

  • Pinpoint pain, rigorous pain, plus cold hypersensitivity are the triad symptoms of GT. The presence of cold hypersensitivity may be useful to differentiate it from neuroma.

  • Solitary GT presents as a painful purple nodule situated on the extremities, particularly in the nail bed. Histologically, the encapsulated mass consists of dilated capillary vessels encircled by numerous round glomus tissue that fills the spaces. Subungual GT is associated with previous localized trauma or neurofibromatosis.

  • Multiple GTs are usually painless, and they distribute in any site. Microscopical observation reveals noncapsulated cavernous vascular spaces. The vessels are lined by flat endothelium and are peripherally encircled with glomus cells.

Fig. 27-55a-1

A soybean-sized purplish nodule with damask halation on the back of the left thigh

Fig. 27-55a-2

Circumscribed glomus tumors with a few vascular spaces in the dermis (HE stain, ×100)

Fig. 27-55a-3

The glomus cells had a faintly eosinophilic cytoplasm and round to oval nuclei in the center. The glomus tumors were surrounded by a fibrous capsule and a few vascular spaces (HE stain, ×100)

Fig. 27-55b-1

More than 30 purplish red papules or nodules with tenderness on the right ankle

Fig. 27-55b-4

Vimentin positive in glomus cells (immunohistologic technique, ×400)

Fig. 27-55b-3

The vascular lumen lined by a single or many layers of glomus cells (HE stain, ×400)

Fig. 27-55b-2

There were several narrow vascular lumina in masses of tumor cells (HE stain, ×40)

27.56 Spindle Cell Hemangioma [130, 131]

  • Spindle cell hemangioma (SCH) is an uncommon reactive form of vascular malformation that usually develops during childhood or early adulthood. Patients with SCH tend to complain about pain and disfigurement.

  • SCH arises in the skin, spinal cord, cervix, oral cavity, pancreas, spleen, and other viscera, presenting as a solitary, smooth, and firm nodule (spindle cell hemangioma) and as multiple lesions (spindle cell hemangiomatosis).

  • Microscopically, SCH shows proliferations of thin-walled blood vessels within abundant spindle cell areas. There are thrombi or phleboliths in their lumina. No mitosis can be found.

  • Although local wide local excision is the standard treatment, the reoccurrence rate is greater than 50%.

  • Multiple SCH is related to Maffucci’s syndrome, congenital lymphedema, Ollier disease, Klippel-Trenaunay syndrome, and early-onset varicose veins.

Fig. 27-56-1

Several skin-colored or reddish nodules on the fibular margin, external malleolus, and sole of the left foot

Fig. 27-56-2

The tumor composed of spindle tumor cells and cavernous blood vessels with irregular dilated thin-walled sinusoids lined with flattened endothelial cells in the middle and lower dermis (HE stain, ×100)

27.57 Kaposiform Hemangioendothelioma [132, 133]

  • Kaposiform hemangioendothelioma (KHE) is an aggressive vascular neoplasm almost exclusively seen in infancy and childhood.

  • KHE typically shows red to violaceous macules, nodules, and plaques. The appearance of telangiectatic papules is also likely to present. KHE usually occurs with Kasabach-Merritt syndrome, leading to intense thrombocytopenia and coagulopathy.

  • Histologically, KHE has interconnecting sheets or nodules with slit-like or crescent-shaped vessels lined by spindled endothelial cells. In the focal vessel lumina, there are trapped RBCs, platelet thrombi, hyaline eosinophilic globules, and hemosiderin.

  • KHE and tufted angioma reflect different stages in the evolution of the same entity, and they can be discriminated by positive stains with D2-40, Prox1, and lymphatic vessel endothelial hyaluronan receptor-1.

  • Although KHE is histologically benign, it is considered to be a type of intermediate malignancy due to its invasion of local tissue and aggressive growth.

  • The site and size of the lesion, invasive depth, and coagulopathy abnormality are associated with significant morbidity in some cases.

Fig. 27-57-1

Brown-red plaques on the right lower abdomen and groin area

Fig. 27-57-2

Nodular aggregates of spindled cells and ovoid cells associated with vascular spaces, blood red cell, and hemosiderin in the dermis (HE stain, ×400)

Fig. 27-57-3

Tumor was surrounded by dark reticular fibers in the dermis (Reticular fiber stain, ×400)

Fig. 27-57-4

CD31 positive (Vision, ×400)

Fig. 27-57-5

CD34 positive (Vision, ×400)

27.58 Classic Kaposi’s Sarcoma [134, 135]

  • Kaposi’s sarcoma is a mesenchymal tumor that is pathologically classified into four types: classic, African, iatrogenic, and AIDS-related.

  • Most patients are Ashkenazi Jews or elder populations from Eastern European and Mediterranean countries.

  • Classic Kaposi’s sarcoma (CKS) presents as bluish-red macules or firm nodules on the lower extremities.

  • Histology of the lesion typically shows the dermal proliferation of spindle cells. In addition, slit-like vascular spaces, hemorrhage, and extravasated red blood cells have also been reported.

Figs. 27-58-1, 27-58-2, 27-58-3

Three main lesions of KS including nodules, plaques, and patches distributed on the extremities: (1) on the dorsa of the hands, (2) on the palms, and (3) on the feet

Fig. 27-58-4

Chronic nonspecific inflammation appeared in patch lesion (HE stain, ×100)

Fig. 27-58-5

RBC extravasation and abundant deposition of hemosiderin in the tissue (HE stain, ×200)

27.59 Cutaneous Angiosarcoma [118, 136]

  • Cutaneous angiosarcoma (CA) is a highly malignant vascular neoplasm with a very poor prognosis.

  • There are three subtypes of CA: radiation-induced angiosarcomas, head-and-neck-type angiosarcoma, and lymphedema-associated angiosarcoma.

  • The initial presentation of head-and-neck-type CA is a purplish macule, nodule, or plaque that may ultimately become ulcerated and hemorrhagic.

  • Well-differentiated CA shows “lightning-like” vascular slits that are often lined by flattened endothelial cells. For poorly differentiated angiosarcomas, the vascular channels are lined by multiple layers of epithelioid, spindled, or pleomorphic endothelial cells.

  • CA typically expresses endothelial markers, including CD34, CD31, agglutinin 1, and VEGF.

  • Tumors with a diameter larger than 5 cm tend to have a significantly worse prognosis.

  • There are sporadic reports that pemphigus herpetiformis occurs with visceral malignancies, including lung cancer, esophageal carcinoma, prostate cancer, and herein cutaneous angiosarcoma.

Fig. 27-59a-1

A big, purple-red, diffuse infiltrating mass covered with necrosis and crusts on the scalp

Fig. 27-59a-2

In the dermis, there were numerous lumens with variable sizes and configurations,and were lined by plump endothelial cells (HE stain, ×100)

Fig. 27-59a-3

The vascular lumina was lined by atypical endothelial cells that were irregular in shape (HE stain, ×200)

Fig. 27-59b-1

Purpuric papulonodular lesions with dotted ulceration and bleeding on the forehead (Reproduced with the permission from [137])

Fig. 27-59b-2

Numerous erythematous and edematous skin lesions in an annular arrangement, associated with small- to medium-sized blisters on the trunk and extensor aspects of the extremities, Nikolsky sign (−) (Reproduced with the permission from [137])

Fig. 27-59b-3

Vascular hyperplasia and sporadic atypical endothelial cells and moderate dense mononuclear infiltrated with irregular vascular channel formation and extravasation of erythrocytes (HE stain, ×200) (Reproduced with the permission from [137])

Fig. 27-59b-4

Intraepidermal acantholysis and blisters located in the mid- to lower epidermis with mixed infiltration of eosinophils and neutrophils (HE stain, ×200) (Reproduced with the permission from [137])

Fig. 27-59b-5

Direct immunofluorescence study showed intraepidermal deposition of immunoglobulin G localized to the lower upper epidermis (DIF, ×100) (Reproduced with the permission from [137])

27.60 Acquired Progressive Lymphangioma [138, 139]

  • Acquired progressive lymphangioma (APL) is a rare disorder that occurs in childhood or adult time. APL is characterized by bruise-like lesions, red patches, or erythematous macules. APL occurs anywhere and grows slowly.

  • Histopathology of the lesions shows numerous lumina that are dilated and randomly arranged. These lumina are lined by a single layer of endothelial cells with erythrocytes in them.

Fig. 27-60-1

Hyperpigmented, slightly indurated, irregular patches on the right calf (Reproduced with the permission from [140])

Fig. 27-60-2

Interlacing channels in the dermis, lined by vascular endothelium, that tended to coat collagen bundles (HE stain, ×200) (Reproduced with the permission from [140])

27.61 Lymphangioma [138, 141]

  • Lymphangioma is an uncommon malformation of microcystic lymphatic vasculature involving the skin and subcutaneous tissues.

  • Lymphangioma is divided into three types: circumscriptum lymphangioma, cavernous lymphangioma, and cystic lymphangioma. Circumscriptum lymphangioma is superficial, whereas the latter two are much deeper.

  • The pathological features are comprised of dilated lymphatic vessels that are lined by endothelium and filled with clear fluid. These vessels express CD31 and D2-40, while they are negative for SMA.

  • Lymphangioma circumscriptum (LM) occurs as clustered “frog spawn”-like vesicles that contain clear fluid. It begins congenitally or follows radiotherapy for cancers, treatment for cellulitis, and pelvic surgeries.

  • Cavernous lymphangioma mostly presents on the trunk and occurs with Turner’s syndrome or other malformative diseases.

Fig. 27-61a-1

A great soft tumor with ulcers and bleeding on the frontal plane

Fig. 27-61a-2

Dilated lymph tubes with endothelial cell swelling and a few lymphocytes infiltrated in the dermis (HE stain, ×400)

Fig. 27-61b-1

Varying-sized brown papules and verrucous and thick-walled vesicles in diffuse distribution on the left chest and abdomen

Fig. 27-61b-2

Hyperkeratosis and large irregular dilated lymph vessels lined by single-layer endothelial cells associated with hyperplastic capillaries and lymphocyte infiltrating in the dermis (HE stain, ×100)

27.62 Nevus Lipomatosus Superficialis [142, 143]

  • Nevus lipomatosus superficialis (NLS) is a unique developmental anomaly or nevoid form of lipoma.

  • Histopathology of NSL demonstrates isolated adipocytes or an ectopic deposit of mature adipocytes in the dermis.

  • The classic variant presents as clustered, soft, cerebriform, pedunculated papules or nodules. They merge to form a plaque in a zonal pattern. The solitary form manifests as an isolated pedunculated papule. NLS with a scleroderma-like appearance is quite rare.

  • Pigmentary anomalies, retractile testis, and folliculosebaceous cystic hamartoma are common associations with NLS.

Fig. 27-62-1

Irregular hyperpigmentation on both aspects of the umbilicus

Fig. 27-62-2

Hyperkeratosis and acanthosis, numerous fat tissues, and collagen fiber in the upper dermis, similar to homogeneous change (HE stain, ×100)

27.63 Encephalocraniocutaneous Lipomatosis [144, 145]

  • Encephalocraniocutaneous lipomatosis (ECCL) is an unusual syndrome with variable skin, ocular, and neurologic lesions.

  • Dermatological presentations include alopecia, nevus psiloliparus, focal dermal hypoplasia, and lipoma over the frontotemporal area.

  • Brain abnormalities in ECCL are comprised of agenesis of corpus callosum, hydrocephalus, calcification, lipoma, and cyst.

  • Ocular lesions arise as microphthalmia, conjunctival tumors, iris dysplasia, ocular calcifications, and optic nerve pallor.

Fig. 27-63-1

Innate frontoparietal subcutaneous fat oncoma

Fig. 27-63-2

A fat oncoma of cerebral flax

Fig. 27-63-3

Callosal dysplasia

Fig. 27-63-4

Brown fat cell with good differentiation (HE stain, ×200)

27.64 Madelung Disease [146, 147]

  • Madelung disease (MD) represents an uncommon metabolic disease characterized by the accumulation and enlargement of nonencapsulated adipose tissue. The face and neck are predilection sites of involvement.

  • The contour of fat deposits in MD changes to different locations, and it may resemble a horse collar (the neck and nape), hamster’s cheek (parotid regions), and pseudo-athletic appearance (the shoulder, back, and chest).

  • Mounting evidence shows alcohol abuse in MD impairs adrenergic lipolysis and induces unusual fat accumulation. However, abstinence from alcohol shows no promising outcomes.

  • MD is categorized into two types. Fat tissue in type I accumulates on the neck, nape, upper arms, and upper back. In type II, there is a diffuse deposit of fat over the entire body, giving the appearance of generalized obesity.

Fig. 27-64-1

Multiple massive lipomas were around the neck

Fig. 27-64-2

Multiple massive lipomas were symmetrical in the groin

Fig. 27-64-3

Lipoma was composed of cells which did not differ from normal fat cells (HE stain, ×400)

27.65 Multiple Leiomyoma [148, 149]

  • Cutaneous leiomyoma is the most common smooth muscle tumor, and it can be divided into three derivations: piloleiomyoma, genital leiomyoma, and angioleiomyoma.

  • Paroxysmal or spontaneous pain is the most common complication in leiomyoma, followed by regional itching or burning sensations.

  • Both genital leiomyoma and angioleiomyoma show a solitary nodule.

  • Piloleiomyoma may be solitary or multiple. It usually consists of smooth, indurated, and red-brown papulonodules or plaques.

  • Familial multiple leiomyomas have been reported with Reed syndrome, Gardner syndrome, dermatitis herpetiformis, and multiple endocrine neoplasia type I.

  • Histological observation of leiomyoma reveals spindle cells distributed in an interlaced fascicular pattern. These nuclei are oval or cigar-shaped with blunt tips.

Fig. 27-65-1

Numerous amaranth papules and nodules on the left neck, chest, shoulder, and upper of arm; some of them were confluent

Fig. 27-65-2

Tumor was composed of smooth muscle fibers without encapsulation in the dermis (HE stain, ×40)

Fig. 27-65-3

Tumor was composed of massive yellow smooth muscle fibers and a few red collagen in the midst of them (van Gieson stain, ×100)

27.66 Cutaneous Leiomyosarcoma [150, 151, 152]

  • Leiomyosarcoma is a kind of malignancy that arises from the smooth muscles of the extremities.

  • Leiomyosarcoma is comprised of multiple or solitary nodules with a color range from normal to pink or brownish.

  • Skin biopsy of CLS features fascicular proliferation of spindle-shaped cells in the dermis. The tumor cells have elongated, blunt-tipped, and anaplastic nuclei.

  • Immunohistochemical stains for CLS are positive for vimentin, desmin, and actin.

  • Tumor depth has a significant impact on its prognosis. Compared to the subcutaneous type, dermal leiomyosarcoma is more likely to recur with a much lower potential for distant metastasis.

Fig. 27-66-1

Numerous turkey-red nodules on the outside of the left thigh

Fig. 27-66-2

Numerous pleomorphic elongated cells with atypical nuclei mitotic figures in the dermis (HE stain, ×40). The tumor cells were vimentin strong positive (unshown)

27.67 Subungual Exostosis [153, 154]

  • Subungual exostosis (SE) is a relatively rare osteocartilaginous tumor that arises on the distal phalanges.

  • SE is known as a painful, pink or flesh-colored, solid nodule involving the free edge of the nail. The overlying nail is usually deformed and elevated.

  • A radiography should be performed prior to surgical excision, and it will tend to show bony excrescence from the distal phalangeal bone.

  • Histopathologic evaluation typically reveals normal trabecular bone and a fibrocartilaginous cap.

  • The cartilaginous cap should be completely excised to avoid recurrence.

Fig. 27-67-1

A nodule on the nail edge of the left third toe

Fig. 27-67-2

X-rays exhibited a bone mass protruding from the third distal phalanx

27.68 Cutaneous Endometriosis [155, 156]

  • Cutaneous endometriosis (CE) is an iatrogenic growth of endometrial tissue in the skin.

  • Primary CE appears preferentially in the umbilicus area. In contrast, secondary CE generally develops by direct implantation of endometrial tissue on the scar following surgery to the abdomen.

  • The typical clinical presentation of CE is a palpable mass with variable colors due to different underlying hemorrhage states. There may be a history of cyclic pain, swelling, or discharge in menstruation.

  • Biopsy specimen of CE shows an endometrial gland-like lumen embedded in the highly vascular stroma in the dermis. The glandular tissue constitutes a single layer of columnar cells that typically shows decapitation secretion and is occasionally intermingled with clear cells.

  • Immunoprofiles of CE are positive for CD10, estrogen, and progesterone receptors, which facilitates the diagnosis in atypical cases.

Fig. 27-68-1

A brown tumor on the lower part of umbilical

Fig. 27-68-2

Varying-sized glandular lumen around cellular and vascular stroma in the dermis (HE stain, ×40)

Fig. 27-68-3

Decapitation secretion at their luminal surfaces (HE stain, ×400)

27.69 Palisaded Encapsulated Neuroma [157, 158]

  • Palisaded encapsulated neuroma (PEN) is characterized by proliferated Schwann cells and axons within a capsule.

  • PEN typically presents as small, asymptomatic, dome-shaped papules that occur preferentially on the neck and oral mucosa.

  • Microscopically, PEN shows intersecting fascicles separated by artifactual clefts and wavy hyperchromatic nuclei. Although Verocay bodies present in PEN, they are not seen as frequently as they are in schwannoma.

  • Schwann cells can be shown after an S-100 stain. Axons are highlighted with neurofilament protein. The perineurial cells of the capsule can be distinguished by EMA.

  • The absence of glial fibrillary acidic protein helps to differentiate it from schwannoma.

Fig. 27-69-1

Multiple creamy white, corn-sized papules diffused on the lower lip

Fig. 27-69-2

The epidermis was normal. Some irregular cell masses with well-defined margin appeared in the dermis (HE stain, ×200)

Fig. 27-69-3

The nucleus of Schwann cells was arranged in an irregular palisading and whirling pattern (HE stain, ×400)

27.70 Schwannoma [159, 160]

  • Schwannoma, also referred to as neurilemoma, is a well-capsulated benign tumor of the Schwann cells of the peripheral nerve sheath.

  • Cutaneous schwannoma (CS) is usually described as a solitary, glistening, and tender nodule deeply seated in the subcutaneous skin.

  • Multiple schwannomas occur with neurofibromatosis in von Recklinghausen’s disease.

  • CS can be classified into the following clinicopathological patterns: classical, cellular, cranial nerve, plexiform, melanotic, ancient, granular cell, and palisaded encapsulated form.

  • The tumors are well encapsulated and have a biphasic growth pattern of Antoni A regions and Antoni B regions. The Antoni A regions are highlighted with hyalinized acellular material sandwiched between two opposing rows of parallel nuclei, whereas the Antoni B areas consist of a loose meshwork of scattered spindled cells in a loose myxoid stroma.

  • CS expresses S100 protein and collagen type IV. S-100 is much stronger in CS than other S-100 protein-positive neoplasms, such as melanoma.

Fig. 27-70-1

A pink-gray and soft nodule on the dorsum of the right foot

Fig. 27-70-2

A well-circumscribed and nonencapsulated tumor was situated in the dermis with fissures around them (HE stain, ×100)

Fig. 27-70-3

The cells were spindle shaped with poorly defined cytoplasm and elongated basophilic nuclei, which were arranged in bands, which stream and interweave, the nuclei display palisading and were arranged in parallel rows with intervening eosinophilic cytoplasm in a typical appearance known as Verocay bodies (HE stain, ×400)

27.71 Cutaneous Merkel Cell Carcinoma [161, 162]

  • Merkel cell carcinoma (MCC) is rare neuroectodermal neoplasm.

  • Cutaneous MCC often occurs on UV-exposed regions, including the head and neck.

  • At the time of presentation, 34% of MCC has nodal involvement or distant metastases.

  • The lesions of MCC are not pathognomonic, and diagnosis can be confirmed by histopathology.

  • Merkel cells are described as basophilic cells of small to medium size. They have round nuclei, scant cytoplasm, and granular or stippled chromatin. Nodular, infiltrative, and trabecular MCC are its three major histopathologic patterns.

  • Paranuclear dot-like stains of cytokeratin 20 is a hallmark of MCC. In addition, CAM5.2 and neurofilaments are very sensitive and specific to MCC.

  • Small cell lung carcinoma can be excluded immunohistologically without expressions of thyroid transcription factor 1 and cytokeratin 7.

  • The detection of Merkel cell polyomavirus is highly suggestive of the diagnosis of MCC.

Fig. 27-71-1

Red-violet nodules with smooth surface on the left thigh

Fig. 27-71-2

The carcinoma cells with large nuclear in corium with the manner of mass (HE stain, ×200)

Fig. 27-71-3

Chromogranin A positive in cytoplasm of the carcinoma cells (SP method, ×400)

Fig. 27-71-4

Nerve secretion granules in cytoplasm of the carcinoma cells (TEM, ×20,000)

27.72 Agminated Spitz Nevus [163, 164]

  • Spitz nevus (SN) appears as a shiny red or skin-colored papule at a young age.

  • SN may present as disseminated or agminated multiple papules on a hyperpigmented, hypopigmented, or normal background skin color.

  • Due to the likelihood of misdiagnosis between melanoma and SN, excision is often recommended for solitary SN.

  • No case of conversion of multiple Spitz nevi to malignant melanoma has been reported.

Fig. 27-72-1

Multiple pink, small papules confluenting to plaques on the left auricle; part papillary

Fig. 27-72-2

Large amount of epithelioid cells were arranged in nests or funicular in the dermis (HE stain, ×100)

Fig. 27-72-3

Epithelioid tumor cells partly confluenting, artifactual clefts between the nests of nevus cells and the epidermis (HE stain, ×400)

Fig. 27-72-4

S-100 strong positive in the membrane of tumor cells and nuclei (PV double stain,×100)

27.73 Subungual Melanoma [165, 166]

  • Subungual melanoma (SM) has a higher morbidity among Asians than in other populations.

  • SM affects the fingers more often than the toes.

  • Nail plate loss, lifting off of the nail, Hutchinson’s sign, a non-healing ulcer, a tumor nodule, or longitudinal melanonychia should lead to consideration of SM.

  • SM can be amelanotic, and therefore any inexplicable dystrophy raises suspicion of SM.

  • Dermatoscopic signs of longitudinal pigmented lines varying in width, interval, and color make biopsy appropriate.

Fig. 27-73-1

Striated jet black spot on the left middle finger nail; irregular, varying color depth dark-brown macula around it

Fig. 27-73-2

Nest melanocytes in the epidermis (HE stain)

Fig. 27-73-3

Melanoma cells in the upper dermis, moderate perivascular lymphocyte infiltration (HE stain, ×100)

Fig. 27-73-4

Tumor cell S-100 positive in the dermis (S-100 stain, ×100)

27.74 Fatal Leptomeningeal Melanoma in Neurocutaneous Melanosis [167, 168, 169]

  • Fox proposed a diagnostic criterion for neurocutaneous melanosis (NCM). It consists of the presence congenital melanocytic nevi (at least one is larger than 20 cm in diameter, and nevus of Ota is included), benign melanosis, or primary leptomeningeal melanoma (PLM).

  • PLM normally occurs in the arachnoid and pia mater region, and its incidence peaks in the fourth decade of life.

  • Initially, NCM presents with seizure, psychiatric disorder, and elevated intracranial pressure.

  • To exclude malignant degeneration of the lesions in the central nervous system, MRI surveillance should be performed regularly.

Figs. 27-74-1, 27-74-2

Large black patches with black hair on the left chest, neck, shoulder, upper arm, and left nape

Fig. 27-74-3

Large black, irregular plaques on the pia mater encephali

Fig. 27-74-4

Large numbers of atypical tumor cells with multiple melanin granules in the subarachnoid space (HE stain, ×100)

Fig. 27-74-5

HMB45 positive in tumor cells, brown granules in cytoplast (SP stain, ×400)

Fig. 27-74-6

S-100 positive in tumor cells, brown granules in cytoplast (SP stain, ×100)

27.75 Rare Forms of Cutaneous Melanoma [165, 170, 171, 172]

  • Acral lentiginous melanoma (ALM) has a poorer prognosis than other subtypes of melanoma.

  • ALM has a propensity for acral regions and shows radial lentiginous proliferation of large melanocytes along the dermoepidermal junction.

  • According to Kuchelmeister’s research, melanomas arise from the palmoplantar or subungual areas of the ALM type, and by comparison, melanomas located at the dorsum hands and feet were of the superficial spreading melanoma type.

  • Balloon cell melanoma (BCM) is the rarest pathological variant of primary cutaneous melanoma in which more than 50% of the tumors cells are foamy cells.

  • BCM may in fact have a dermal origin and is actually a vertical growth phase of melanoma.

  • Ballooning change in BCM is due to progressive vacuolization of the melanosomes.

  • Head and neck mucosal melanoma (HNMM) behaves aggressively and involves mucosa of the vermilion, nasal cavity, paranasal sinuses, oral cavity, laryngeal pharynx, and even esophagus.

  • Amelanotic acral melanoma (AAM) is rare subtype of melanoma with little or no pigment.

  • AAM can be easily mistaken as a non-melanocytic neoplasm, and therefore it poses a diagnostic challenge.

  • The positive immunostaining for S-100 and HMB-45, the presence of pigment after Fontana-Masson stain, and electron microscopy observation confirm the diagnosis in certain AAM cases.

Fig. 27-75a-1

A black nodule on the periungual region of the right first toe

Fig. 27-75a-2

Many atypical nevus cells in the epidermis (HE stain, ×200)

Fig. 27-75a-3

S-100 positive of atypical nevus cells in the epidermis (DAB stain, ×200)

Fig. 27-75b-1

A jitney-sized brownish-red plaque on the back

Fig. 27-75b-2

Balloon cells constituted the tumor (HE stain, ×200)

Fig. 27-75c-1, 27-75c-2, 27-75c-3

Extensive, black-pigmented, and irregularly bordered macules on the upper lip (1), gingival (2), and the palate (3); an amaranth mass 0.6 cm in diameter with blood crust on the right upper lip

Fig. 27-75c-4

Rounded collections or nests of melanocytes filled the connective tissue. Tumor cells showed cellular pleomorphism and smudged nuclei (HE stain, ×400)

Fig. 27-75d-1

An infiltrating plaque with superficial erosion at the dorsal side of the second toe of the right foot

Fig. 27-75d-2

A mass of infiltrating tumor cells with large irregularly shaped and hyperchromatic nuclei in the reticular dermis (HE stain, ×100)

Fig. 27-75d-3

S-100 positive in the cytoplasm of tumor cells (SP stain, ×100)

27.76 Cutaneous Pseudolymphoma [173, 174, 175]

  • Cutaneous pseudolymphoma (CPL) includes reactive lymphoproliferative disorders with T-cell and/or B-cell phenotypes, which simulates cutaneous lymphomas clinically and pathologically.

  • CPL often presents a smooth flesh-colored to plum-red papule or nodule that predominantly locates on the face and neck.

  • CPL develops in response to stimuli, such as arthropod bites, vaccinations, anemia, allergic reactions, medications, infections, or foreign agents.

  • Biopsy specimen shows a polymorphous infiltration comprised of mixed T cells, B cells, eosinophilic cells, and histiocytes.

  • T-cell CPL can be categorized pathologically into three forms: bandlike, nodular, and perivascular/periadnexal type. The absence of clonal T-cell rearrangements, normal T-cell phenotypes, epidermotrophism, and atypical lymphocytes in CPL warrants differentiation from most MF patients.

  • Nodular infiltration is most commonly seen in B-cell CPL, followed by diffused and acral pseudolymphomatous angiokeratoma in children and a pseudolymphomatous-folliculitis-like pattern. A germinal center is commonly seen in the heavy multinodular CPL.

  • Determination of its monoclonality is helpful for the final diagnosis of possible CPL patients.

Fig. 27-76-1

A brownish-red nodule on the nose

Fig. 27-76-2

There was a narrow free zone between infiltration of lymphocytes and the epidermis in the superficial dermis (HE stain, ×400)

Fig. 27-76-3

CD45RO positive (SP, ×400)

Fig. 27-76-4

CD20 positive (SP, ×400)

27.77 Jessner’s Lymphocytic Infiltration of the Skin [176, 177, 178]

  • Lymphocytic infiltration of the skin (LIS) presents in middle-aged adults. Although LIS predominantly affects the cheeks and earlobe, involvement of the upper trunk, neck, and proximal extremities has already been reported. The LIS is a persistent popular and indurated plaque which is photosensitive on the face.

  • Investigation on LIS indicates that it is a benign cutaneous disorder predominantly of T-cell origin, although B-cell origin has uncommonly reported.

  • Pathology of LIS is characterized by a heavy lymphocytic infiltration around the blood vessels or the adnexal structures.

Fig. 27-77-1

A persistent plaque-like erythema on the left cheek

Fig. 27-77-2

Dense perivascular and diffuse lymphocytic infiltrated in the upper dermis

27.78 Ketron-Goodman Disease [179, 180]

  • Localized pagetoid reticulosis (LPR) is considered to be a solitary indolent form of mycosis fungoides (MF) without extracutaneous spread or lethal outcome.

  • LPR typically displays psoriasiform, erythematous, or verrucous plaques, which are predominantly located on the extremities.

  • Ketron-Goodman (KG) disease is an aggressive disseminated form of LPR in contrast to the classical type.

  • Histologically, it manifests acanthosis with striking pagetoid epidermotropism of atypical medium-sized lymphocytes, which are highlighted by the hyperchromatic nuclei and are surrounded by vacuolated cytoplasm.

  • In addition, epidermotropism may similarly present in lymphomatoid papulosis, lymphomatoid drug reactions, melanoma, or epithelial neoplasia with pagetoid appearance.

  • CD30 positivity is found in approximately 50% of cases with LPR, and 50–60% of cases have a presence of Ki-67 expression.

  • Immunoprofiles of these atypical cells express all T-cell markers of CD3+, CD4+, and CD8+, or, rarely, they are double negative for CD4 and CD8. Clonal a/β TCR gene rearrangement is frequently identified on keratinocytes in ES. However, these ES immunoprofiles do not alter its prognosis.

Fig. 27-78-1

Numerous dark-red plaques with scales and crusts on the face

Fig. 27-78-2

Numerous brown plaques associated with ulcers on the back

Fig. 27-78-3

Infiltration of atypical lymphocytes like pagetoid cells in the epidermis (HE stain, ×400)

Fig. 27-78-4

Infiltration of numerous atypical lymphocytes in the upper and middle dermis (HE stain, ×40)

Fig. 27-78-5

CD45 RO is positive (ABC method, ×400)

Fig. 27-78-6

T-cell receptor γ is positive

27.79 Mycosis Fungoides [181, 182, 183, 184, 185, 186]

  • Mycosis fungoides (MF) is a type of primary cutaneous T-cell lymphoma that can be categorized into three classical forms: patch stage, plaque stage, and tumor stage.

  • MF has several distinct clinicopathologic subtypes, including folliculotropic, hypopigmented, hypopigmented, granulomatous, bullous and poikilodermatous, syringotropic, palmaris and plantaris, solitary, verrucous anetodermic, ichthyosiform, papular, pustular, interstitial, invisible, and CD8+CD56+ MF.

  • The constellation of histological features in classical MF consist of atypical CD4+ cells that have haloed, cerebriform nuclei with typical alignment along the epidermal basal layer. Focal epidermotropism and formation of Pautrier microabscesses are considered hallmarks of MF.

  • Ichthyosiform MF is a distinct variant of MF characterized by widespread ichthyosiform lesions and an indolent course.

  • Rupioid lesions in MF may present in a large spectrum of skin diseases, including reactive arthritis, rupioid psoriasis, crusted scabies, histoplasmosis, and syphilis.

  • Hyperpigmented MF manifests as diffuse hyperpigmented macules.

  • MF has the phenotype of a T-helper memory cell (CD3+, CD4+, CD45RO+, CD8−, CD30−, CD56−). It rarely shows CD8− or CD4−CD8−. Transformation of MF into CD30+ large T-cell lymphoma is defined when less than 25% of the tumor cells are large, pleomorphic, anaplastic lymphocytes in an MF individual. CD2, CD5, and CD7 are known to be T-cell markers, and those molecules may be partially lost in some patients.

  • The detection of thymocyte selection-associated high mobility group box gene in early MF distinguishes it from certain benign inflammatory dermatosis.

Fig. 27-79a-1

Erythematous, scaling patches and rupioid eruptions on the trunk

Fig. 27-79a-2

MF cell infiltrated within the epidermis and dermis, Pautrier microabscesses presented in the epidermis (HE stain, ×40)

Fig. 27-79a-3

Diffuse tumor cells in the dermis (HE stain, ×400)

Fig. 27-79b-1

Dark-brown patches on dorsa of hands and feet, border of the lesions was unclear

Fig. 27-79b-2

Pautrier microabscesses within the epidermis, a bandlike lymphocyte infiltrated in the dermis (HE stain, ×100)

Fig. 27-79b-3

LCA positive in the lymphocytes of the epidermis and dermis (ABC stain, ×200)

Fig. 27-79c-1

Lichenoid plaques on the buttocks

Fig. 27-79c-2

Brownish-red nodules on the extensor of the left calf

Fig. 27-79c-3

Diffuse tumor cell infiltrated in the dermis (HE stain, ×100)

Fig. 27-79c-4

Tumor cell and multinucleated tumor giant cells (HE stain ×1000)

Fig. 27-79c-5

CD45RO-positive tumor cells (ABC method ×400)

Fig. 27-79c-6

CD30-positive tumor cells (ABC method ×400)

Fig. 27-79d-1

Dry skin over the whole body, covered with multiple coarse, whitish, large scales and crusts

Fig. 27-79d-2

Marked swelling with an ulcer 6 cm in diameter in the center on the right forearm

Fig. 27-79d-3

Numerous bean-sized, translucent, white papules and nodules on the axilla

Fig. 27-79d-4

Strip and sheet bald plaques on the occiput, several hair follicle papules on the plaques, covered with a few adherent scales

Fig. 27-79d-5

Epidermal atrophy had mononuclear cell infiltration presenting atypical Pautrier microabscess (HE stain, ×400)

Fig. 27-79d-6

Multiple multinucleated giant cells in the dermis (HE stain, ×400)

Fig. 27-79d-7

CD45RO positive (ABC stain, ×400)

27.80 Erythrodermic Cutaneous T-Cell Lymphoma [187, 188, 189]

  • Erythrodermic cutaneous T-cell lymphoma (e-CTCL) mainly underlies the aggressive subtypes of cutaneous lymphomas, including erythrodermic mycosis fungoides and Sezary syndrome.

  • e-CTCL, lymphadenopathy, and circulating cerebriform T cells are the triad of Sezary syndrome.

  • Pruritus, a sensation of burning or chills, may precede the onset of skin lesions.

  • The algorithm suggested by Dr. Russell-Jones provides valuable guidance in the management of e-CTCL.

Fig. 27-80-1

Diffuse erythema all over the body

Fig. 27-80-2

A few masses of lymphocyte infiltrated with large nuclei in the epidermis (HE stain, ×150)

27.81 Subcutaneous Panniculitis-Like T-Cell Lymphoma [190, 191]

  • Subcutaneous panniculitis-like T-cell lymphoma (SPTL) is a distinct subset of cutaneous T-cell lymphomas that preferentially involves subcutaneous fat of the leg.

  • SPTL is usually mistreated as benign panniculitis for years before confirmation of the diagnosis.

  • SPTL manifests as solitary or multiple deep-seated nodules or plaques. Localized lipoatrophy is likely to be seen after regression of the lesion.

  • Fever, fatigue, weight loss, hemophagocytic syndrome, and autoimmune diseases are common systemic comorbidities with SPTL.

  • Pleomorphic atypical T cells are scattered at the periphery of adipose lobules in SPTL. It is defined as CD8+ cytotoxic T-cell lymphoma and expresses α-/βT-cell receptors.

Fig. 27-81-1

Nodules on the face

Fig. 27-81-2

The infiltration of small- or medium-sized lymphocytes in subcutaneous panniculus adiposus (HE stain, ×125)

Fig. 27-81-3

CD45RO positive (SP stain, ×125)

27.82 Hydroa Vacciniforme-Like Lymphoma [192, 193]

  • Hydroa vacciniforme-like lymphoma (HVLL) designates a rare Epstein-Barr virus-positive cutaneous T-cell lymphoma that clinically mimics hydroa vacciniforme.

  • HVLL appears prone to development in children of Asia and Central America.

  • Most patients complain of edematous face, vesiculopapules, hemorrhagic bullae, ulcerations, and pitted scars, which are mainly located on sun-exposed areas. Systemic complications of intermittent fever, hepatosplenomegaly, and lymphadenopathy have also been reported.

  • Skin biopsy of the lesion reveals pleomorphic small- to medium-sized lymphocytes that infiltrate around blood vessels or the adnexal tissues with notable vasculitis, angiocentricity, or necrosis.

  • Neoplastic cells usually show a CD8 cytotoxic T-cell phenotype, as well as positive expression of TIA-1, perforin, and granzyme B.

  • For the HVLL patient who has high titers of antibodies to Epstein-Barr virus or a strong increase in CD30 expression, the ultimate progression of hemophagocytic syndrome or NK-/T-cell lymphoma is highly probable.

Fig. 27-82-1

Diffuse flushing edema, with some scattered blisters, crusts, and variola like atrophic scars, resembling hydroa vacciniforme on the face

Fig. 27-82-2

Dermal lymphoid cell infiltration; atypical cells with irregular nuclei (HE stain, ×100)

Fig. 27-82-3

Dermal infiltrating lymphoid cells showed positive for CD45RO

Fig. 27-82-4

Dermal infiltrating lymphoid cells showed positive for CD8

Fig. 27-82-5

By in situ hybridization, the majority of dermal lymphoid cells were positive for Epstein-Barr virus

Fig. 27-82-6

Monoclonally rearranged TCR-γ gene (250 bp band) in the DNA from the specimens

27.83 Extranodal NK-/T-Cell Lymphoma [194, 195, 196]

  • The spectrum of NK-cell lymphoma consists of extranodal NK-/T-cell lymphoma (ENTL, including nasal and extranasal types), intravascular NK-/T-cell lymphoma, NK-cell lymphoma, and NK-cell leukemia.

  • ENTL has a facial predominance, often with midline facial destruction. The upper aerodigestive tract, testicles, and skin are similarly affected.

  • Clinically, it occurs as nodules, cellulitis-like swelling, and erythematous to purpuric patches. However, cellulitis with persistent ulceration is highly suspicious for ENTL.

  • Neoplastic cells infiltrate whole layers of the skin, with an angiocentric and angiodestructive growth pattern. The nuclei are ovate or irregular with pale cytoplasm. Angiocentricity and angiodestruction are often present with extensive necrosis.

  • The typical immunophenotype for ENTL is CD2+, CD3ε+, CD56+, and cytotoxic proteins (TIA1+, GramB+, and perforin+), while it is negative for CD4, CD5, and CD8.

  • Although ENTL is consistently associated with CD56 and Epstein-Barr virus, a CD56-negative variant has also been diagnosed with the prerequisite of detection of EBV and expression of cytotoxic proteins.

  • The nasal type of ENTL has less skin involvement and a better survival rate.

  • Intravascular lymphoma is defined as intravascular proliferations of large neoplastic cells. These tumor cells exhibit the phenotype of large B cell, CD30-positive anaplastic large T cell, and NK-/T-cell lymphoma (commonly cutaneous intravascular NK-/T-cell lymphoma).

Fig. 27-83-1

Well-circumscribed plaques and nodules on the sides and bridge of the nose

Fig. 27-83-2

Lymphoid cells with part atypical infiltrating in the dermis (HE stain, ×100)

Fig. 27-83-3

Positive CD56 (ABC stain, ×100)

Fig. 27-83-4

Positive CD45RO (ABC stain, ×100)

27.84 Primary Cutaneous B-Cell Lymphoma [197, 198]

  • Primary cutaneous B-cell lymphoma (PCBCL) represents a variety of lymphomas that originate from skin B lymphocytes in different stages. No extracutaneous manifestations can be found at the time of diagnosis.

  • PCBCL typically manifests with solitary or multiple plum-colored papules, nodules, or plaques. The lesions have a predilection for the scalp, forehead, trunk, and foot.

  • In PCBCL, the clinical characteristics are quite different between its subtypes. Unlike PCDLBCL-LT (primary cutaneous diffuse large B-cell lymphoma, leg type), PCMZL (primary cutaneous marginal zone lymphoma) and PCFCL (primary cutaneous follicle center lymphoma) are rather indolent, and there are quite a lot individuals with PCFCL who undergo spontaneous resolution.

  • CD20 and CD79a immunophenotypes are characteristic of B-cell lymphoma. In addition, PCDLBCL-LT expresses BCL-2 and MUM-1, while diffuse large B-cell lymphoma (DLBCL) shows a positive stain for BCL-2 -and BCL-6. Systemic chemotherapy is likely to have a favorable prognosis in DLBCL patients with CD40 expression.

Fig. 27-84-1

Pigeon egg-sized, half ball, brownish-red tumor on the face

Fig. 27-84-2

Diffuse erythema and infiltrate plaques on the axilla

Fig. 27-84-3

Numerous atypical tumor cells

Fig. 27-84-4

Numerous CD20-positive cells

Fig. 27-84-5

A few CD68-positive cells

27.85 Maculopapular Cutaneous Mastocytosis [199, 200]

  • Maculopapular cutaneous mastocytosis (MCM) consists of classical urticaria pigmentosa (UP), plaque UP, nodular UP, and telangiectasia macularis eruptiva perstans.

  • Pediatric MCM presents with less numerous and more polymorphic maculopapules that are yellowish in color. The adult type presents with more numerous monomorphic reddish lesions.

  • The onset of urticaria pigmentosa (UP) is a variable number of brown macules or papules that urticate with friction.

Fig. 27-85-1

Multiple brown papules on the trunk

Fig. 27-85-2

Mast cell infiltrated in the upper dermis (Giemsa stain, ×200)

27.86 Diffuse Cutaneous Mastocytosis [200, 201]

  • Most diffuse CM cases arise at birth or in early infancy, and they tend to be distributed over the trunk and the scalp. The lesions are quite variable from papules and blisters to hemorrhagic bullae.

  • Diffuse CM is an anaphylactic disease with a potentially life-threatening outcome, and it particularly occurs at a young age due to the heavy load of mast cells in the skin.

  • Diffuse CM mostly appears within 6 months postpartum. Hemorrhagic bullae and small vesicles are regarded as the typical features of diffuse CM.

  • There is evidence showing that diffuse CM is prone to progress to systemic mastocytosis.

Fig. 27-86-1

Generalized red papules on the trunk and extremities

Fig. 27-86-2

Part bleeding lesions

Fig. 27-86-3

Moderate infiltration of mast cells in the upper dermis, some of which showed an abnormal morphology (HE stain, ×200)

Fig. 27-86-4

Violaceous, metachromatic granules were found (Giemsa stain, ×200)

27.87 Mastocytoma [202, 203, 204]

  • Cutaneous mastocytosis (CM) displays an increase and accumulation of mast cells in the dermis, which is distinctive to systemic mastocytosis.

  • Urticaria pigmentosa (UP) is also called maculopapular CM. CM can be categorized into three types: UP, diffuse CM, and solitary mastocytoma.

  • Mast cells can be stained immunohistochemically with azure A, CD25, Giemsa, kit (CD117), toluidine blue, and tryptase.

  • Most mastocytoma develops in infants and children, and the majority resolve completely within 4–10 years.

  • The clinical appearance of the mastocytoma is described as a reddish-brown papule, nodule, or plaque. Blistering, pruritus, and tenderness may also be noted. The diameter of the lesion ranges from several millimeters to 12 cm.

  • Approximately 79% of mastocytomas demonstrate positive Darier’s sign, which is evoked by rubbing the lesion.

Fig. 27-87-1

A large skin-colored nodule with brown-red ring on the dorsum of the right hand

Figs. 27-87-2, 27-87-3

Lots of mast cells contained purple granules in the cytoplasm in the dermis ((2):HE stain, ×100; (3):Giemsa stain, ×400)

27.88 Cutaneous Plasmacytoma [205, 206, 207]

  • Neoplasms of plasma cells are classified into four groups: classic plasma cell myeloma, extramedullary plasmacytoma, isolated plasmacytoma of bone, and plasma cell leukemia.

  • Cutaneous plasmacytoma (CP) is a malignant transformation of plasma cells in the skin.

  • CP arises on the scalp and neck, especially in the nasal cavity and nasopharynx.

  • CP often masquerades as B-cell lymphoma, which displays solitary or multiple, smooth, dome-shaped plaques or nodules with a reddish, violaceous, or normal color.

  • Biopsy specimens show a monomorphic population of atypical plasma cells distributed in a nodular or diffused pattern.

  • The immunoprofiles for CP are CD38+, CD43+, CD56+, CD79a+, CD138+, and EMA+, and monoclonal cytoplasmic light chain expression favors the diagnosis of plasmacytoma.

  • Primary CP is associated with organ transplantation, Epstein-Barr virus activation, and recurrent herpes simplex virus infection.

  • Many CP patients develop local recurrence or visceral metastasis. Unique cases of transformations into multiple myeloma or CD30+ large B-cell lymphoma have also been described.

Fig. 27-88a-1

A solitary red nodule with ulcers in the center of the palate

Fig. 27-88a-2

Numerous violaceous, skin-colored nodules on the internal aspect of both thighs

Fig. 27-88a-3

Diffuse infiltrates of plasma cells in the dermis and subcutaneous tissue (HE stain, ×40)

Fig. 27-88a-4

The plasmacytes varied from sizes and shapes due to clumping of chromatin associated with atypical mitotic figures (HE stain, ×400)

Fig. 27-88b-1

A big dark-red mass and many nodules on the left arm

Fig. 27-88b-2

Lots of tumor cell in the dermis (HE stain, ×100)

Fig. 27-88b-3

Tumor cells had hyperchromatic, irregularly shaped nuclei and atypical mitotic figures (HE stain, ×400)

Fig. 27-88b-4

The bone marrow smear showed many plasmablasts, proplasmacytes, and binucleated plasmacytes (Wright’s stain, ×1000)

27.89 Polycythemia Vera [208, 209]

  • Polycythemia vera (PV) is a myeloproliferative disease characterized by a larger number of red blood cells.

  • The most common cutaneous manifestations of PV include aquagenic pruritus, erythromelalgia, cyanosis, and purple coloration of the skin.

  • These cutaneous manifestations are secondary to the microcirculatory disturbances that are common features of PV.

Fig. 27-89-1

Well-circumscribed violet maculae on the right buttocks, lower limbs, and scrotum

Fig. 27-89-2

Slight atrophy of epidermis, edema with many erythrocytes effusion, and perivascular inflammatory infiltration in the dermis (HE stain, ×40)

27.90 Leukemia Cutis [210, 211, 212]

  • Leukemia cutis (LC) often arises from acute monocytic leukemia, acute myelomonocytic leukemia, chronic lymphocytic leukemia, and chronic myeloid leukemia.

  • LC often presents with papules, nodules, or plaques of varying sizes. These lesions are brown, red, purplish, or hemorrhagic.

  • LC may exist prior to demonstration in the bone marrow or peripheral blood.

  • Clinical characteristics and critical investigation of the bone marrow and circulating blood are of equal importance in the diagnosis of LC.

  • The pleomorphic leukemic cells infiltrate the dermis in a nodular, interstitial, or perivascular pattern. However, the upper papillary dermis is spared. The nuclei of these atypical cells are kidney-shaped, monomorphous, or cytologically bland.

  • To determine the infiltrated cell type of LC, immunophenotypic staining and cytologic analysis should be performed.

  • Detection of specific immunohistochemical markers and molecular genetic data is conducive to a correct diagnosis of LC.

Fig. 27-90-1

Erythematous-to-violaceous nodules and plaques on the chest

Fig. 27-90-2

Large naive monocytes in the bone marrow (Wright stain, ×1000)

Fig. 27-90-3

Lots of small- to medium-sized histiocytes with hyperchromatic nuclei infiltrated in the perivascular area (HE stain, ×40)

Fig. 27-90-4

CD68 positive in tumor cells (SP stain, ×40)

27.91 Cutaneous Metastasis for Lung Cancer [213]

  • While the eyes are the window to the soul, the skin is the window to internal malignancies.

  • The incidence of skin metastasis in lung cancer is approximately 0.2–3.1%, with the majority spreading to the scalp. Those in the upper lobes of the lung tend to metastasize more frequently to the skin. For oat-cell carcinoma, the back is the most common site of involvement.

  • Lung cancer can be classified pathologically as squamous cell carcinoma, adenocarcinoma, small cell carcinoma, large cell carcinoma, and undifferentiated carcinoma.

  • Skin manifestations from lung malignancies are not characteristic. The most common are nodules, papules, and plaques with variable red to pink to violaceous color. Less frequently, these lesions resemble ulcers, herpes zoster, morphea, hemangioma, dermatofibroma, epidermal cysts, pyogenic granuloma, cellulitis, erysipelas, and bullae.

  • Among male patients with lung cancer, skin metastases have a predilection for the chest, abdomen, upper lip, and back. The traumatic area after thoracotomy, needle aspiration, or burning may also be involved.

  • The immunological phenotype of the metastatic cells is TTF-1+, CAM5.2+, CK7−, and CK20−.

Fig. 27-91-1

Lesions on the left axilla, chest, back, and hypochondrium

Fig. 27-91-2

A 4.5 × 4.0 cm tumor in left lower lung

Fig. 27-91-3

Tumor embolism in the dermis (HE stain, ×160)

27.92 Cutaneous Metastasis of Gastrointestinal Malignancy [214, 215]

  • The upper abdominal wall is the predilection site for skin invasion in gastrointestinal malignancies. A Sister Joseph nodule on the umbilicus is the underlying sign, especially for gastric adenocarcinoma.

  • The cutaneous manifestations of gastrointestinal malignancy occur as dome-shaped, skin-colored, pink, whitish, or reddish nonspecific nodules.

  • Skin metastases from colorectal neoplasms are associated with better outcomes compared to other gastrointestinal tumors.

  • According to a survey in male patients, nearly 6% of all cutaneous metastases are from gastric adenocarcinoma.

  • Tumor cells aggregate in the dermis to form clusters or strands of glands, embedded in a rich fibrous stroma. Signet-ring neoplastic cells may also present.

  • Alcian blue and PAS stains are positive for the tumor cells. Meanwhile, expressions for CDX2, CK7, CK20, CEA, and EMA have already been demonstrated. Recently, HIK1083 was applied as a sensitive marker to label signet-ring cells of adenocarcinoma.

Fig. 27-92-1

A 2 × 2 × 1 cm tumor with depressed center on the back of the neck

Fig. 27-92-2

Numerous tumor cells nest in the dermis (HE stain, ×100)

Fig. 27-92-3

Numerous signet-ring cells with variable sizes and shapes (HE stain, ×400)

27.93 Sister Mary Joseph’s Nodule [216, 217, 218]

  • Sister Mary Joseph’s nodule (SMJN) is the umbilicus metastasis of abdominopelvic malignancy.

  • SMJN often presents as an ill-defined, firm mass with overlying ulceration or necrosis. There is blood or purulent discharge in some lesions.

  • The vast majority are metastatic adenocarcinomas that originate from the gastrointestinal tract, ovarian tissue, and bladder.

  • The most common pathological type of SMJN is adenocarcinoma, which is then followed by squamous cell carcinoma, carcinoids, and undifferentiated tumors.

  • The ovarian malignancy expresses CK-7 and Wilms’ tumor gene products. Mucinous tumor of Müllerian origin is positive for estrogen and progesterone receptor stains. In primary peritoneal serous carcinomas, there is high expression of PAX-8. CDX-2 and CK-20 are diagnostic markers for urachal carcinoma.

  • The overall survival of SMJN is 2–11 months in untreated patients.

Fig. 27-93-1

An oval, well-circumscribed plaque 9–10 cm in diameter with hyperpigmentation and papules with papillomatous surface

Fig. 27-93-2

Low-differentiated adenocarcinoma from umbilical-urethral canal remnant (HE stain, ×88)

27.94 Carcinoma en Cuirasse [219, 220, 221]

  • Carcinoma en cuirasse (CC) refers to the armor-like induration resulting from tumor cell infiltration and reactive fibrosis.

  • CC exhibits scattered, firm papulonodules that progress to be brawny hard and eventually merge into a sclerodermoid plaque, reminiscent of the encasement in armor of a cuirassier.

  • The anterior chest is the most common site of involvement. The back, neck, abdomen, vulva, scrotum, and supraclavicular region can also be affected.

  • The pathological changes of CC include extensive dermal fibrosis with interstitial infiltration of atypical epithelial cells in a nodular pattern or in a linear arrangement of dissecting collagen bundles (Indian filing).

  • It is proposed that pleiotrophin, a multifunctional tumor promoter, leads to rapid tumor growth and progression to the scirrhous subtype of invasive carcinoma.

  • Any treatment for CC is now palliative, and because the tumor cells cause extensive reactive fibrosis and decreased vascularity, chemotherapeutic agents may be unable to obtain tumoricidal concentrations locally.

Fig. 27-94-1

Indurated plaque was found on the right side of the upper chest wall measuring 20 × 15 cm in size, and it extended upward to the right part of the neck over an area of 20 × 10 cm, which was grossly distorted and convolutional in shape. The underlying skin was woody hard and unpinchable (Reproduced with the permission from [221])

Fig. 27-94-2

Monomorphous tumor cells with a rich cytoplasm in vacuoles, presented singly or in small clusters between dense collagen bundles in the dermis (HE stain, (1) ×40; (2) ×100; (3) ×400) (Reproduced with the permission from [221])


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Copyright information

© Springer Nature Singapore Pte Ltd. and People's Military Medical Press 2018

Authors and Affiliations

  • Yong-Hang Zhu
    • 1
  • Gui-Xiu Zhang
    • 2
  • Li Tang
    • 3
  • Xiao-Jie Li
    • 4
  • Wen-Yuan Zhu
    • 4
  • Ru-Zhi Zhang
    • 5
  • Ming-Yu Xia
    • 6
  • Lei Wang
    • 7
  • Ying Ren
    • 8
  • Hui-Pu Zhou
    • 9
  • De-Hai Pan
    • 10
  • Li-Jian Xiang
    • 11
  • Jin-Fa Su
    • 12
  • Hui Zhang
    • 13
  • Juan Du
    • 14
  • Mai-Hua Hou
    • 4
  • Dong-Lai Ma
    • 15
  • Shu-Qin Lv
    • 16
  • Xi-Chuan Yang
    • 17
  • Jie Gao
    • 18
  • Ting Lin
    • 19
  • Shao-Wen Peng
    • 17
  • Zhi-Ping Sun
    • 20
  • Li Yang
    • 21
  • Cheng Tan
    • 22
    Email author
  • Ji-Ling Zhang
    • 23
  • Yan Wu
    • 24
  • Hong Zhang
    • 25
  • Gang Liu
    • 26
  • Bao-Chun Li
    • 27
  • Shun-Fan Li
    • 28
  • Lan Yang
    • 15
  • Jie Yan
    • 15
  • Yang Guan
    • 29
  • Yin Xiao
    • 30
  • Yan Yan
    • 15
  • Zhi-Fang Zhai
    • 17
  • Shan Tang
    • 31
  • Zhong Xie
    • 32
  • Feng Wu
    • 33
  • Xiao-Mei Zhang
    • 34
  • Jian-Fang Sun
    • 35
  • Wen-Hai Li
    • 36
  • Mei Cai
    • 37
  • Chun-Mei Zhang
    • 38
  • Xian Zhang
    • 39
  • Gang Wang
    • 7
  • Hong-Hao Jiang
    • 33
  • Jiang Jin
    • 14
  • Xiong-Ming Pu
    • 40
  • Jian-Min Chang
    • 36
  • Yan Lu
    • 4
  • Xiao-Jun Zhu
    • 41
  • Cun-Cai Zhou
    • 42
  • Shu-Fang Qiao
    • 29
  • Jian-Ping Liang
    • 43
  • Zhi-Xin Song
    • 44
  • Yi-Ming Xu
    • 40
  • Jun Peng
    • 45
  • Hong-Zhong Jin
    • 15
  • Chun-Xing Xu
    • 46
  • Jing Fang
    • 4
  • Chuan-Ping Xing
    • 47
  • Xiao-Bing Pi
    • 14
  • Dian-Ying Zhuang
    • 48
  • Jia-Bi Wang
    • 15
  • Jian-Ying Zeng
    • 15
  • Min Huang
    • 49
  • Chun-Yang Li
    • 50
  • Bing-Nan Cui
    • 51
  • Xiao-Yan Guo
    • 52
  • Tong Lin
    • 53
  • Bing-Sen Qiu
    • 54
  • Bin Su
    • 15
  • Xue-Jun Zhu
    • 32
  • Pei-Hua Song
    • 10
  • Guang-Cai Xiang
    • 10
  • Guang-Ren Liu
    • 14
  • Sheng-Shun Tan
    • 55
  • Yi-Qun Jiang
    • 56
  • Min Zheng
    • 57
  • Jin Hu
    • 58
  • Guang-He Yang
    • 59
  • Zheng Ge
    • 60
  • Jing Chen
    • 61
  • Lin Cai
    • 62
  • Sheng Wang
    • 63
  • An Liu
    • 59
  • Xian Jiang
    • 64
  1. 1.Department of DermatologyLiaoning General Hospital of Nuclear IndustryXingchengChina
  2. 2.Department of DermatologyThe First People’s Hospital of YunnanKunmingChina
  3. 3.Department of DermatologyTianjin Academy of Traditional Chinese Medicine Affiliated HospitalTianjinChina
  4. 4.Department of DermatologyThe First Affiliated Hospital of Nanjing Medical UniversityNanjingChina
  5. 5.Department of DermatologyThe Third Affiliated Hospital of Suzhou UniversityChangzhouChina
  6. 6.Nanjing Medical UniversityNanjingChina
  7. 7.Institute of Dermatology of Chinese PLA, Xijing HospitalThe Fourth Military Medical UniversityXi’anChina
  8. 8.Department of DermatologyAffiliated Hospital of Chengde Medical CollegeChengdeChina
  9. 9.Department of DermatologyThe People’s Hospital of ShanweiShanweiChina
  10. 10.Department of DermatologyChina-Japan Friendship HospitalBeijingChina
  11. 11.Department of DermatologyThe First Hospital of HangzhouHangzhouChina
  12. 12.Department of DermatologySkin Disease Prevention CenterJingmenChina
  13. 13.Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina
  14. 14.Department of DermatologyPeking University People’s HospitalBeijingChina
  15. 15.Department of Dermatology, Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
  16. 16.Department of DermatologyFujian Dongshan County HospitalFujianChina
  17. 17.Department of Dermatology and Venereology, Southwest HospitalThird Military Medical UniversityChongqingChina
  18. 18.Department of Dermatology and VenereologyThe First Affiliated Hospital of Nanjing Medical UniversityNanjingChina
  19. 19.Department of DermatologyGeneral Hospital of Guangzhou Military Command of PLAGuangzhouChina
  20. 20.Department of DermatologyDongguan Donghua HospitalGuangzhouChina
  21. 21.Department of Dermatology, Xijing Hospital, Institute of PLA DermatologyThe Fourth Military Medical UniversityXi’anChina
  22. 22.Department of DermatologyAffiliated Hospital of Nanjing University of Chinese MedicineNanjingChina
  23. 23.Department of DermatologyThe Affiliated Hospital of Zunyi Medical CollegeZunyiChina
  24. 24.Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
  25. 25.Department of DermatologyAir Force General Hospital, PLABeijingChina
  26. 26.Department of Plastic SurgeryTianjin Changzheng HospitalTianjinChina
  27. 27.Department of DermatologyXian Yang Central HospitalXian YangChina
  28. 28.Department of DermatologyAffiliated Hospital of Guangzhou Medical UniversityGuangzhouChina
  29. 29.Department of DermatologyTianjin Changzheng HospitalTianjinChina
  30. 30.Department of PathologyTianjin Changzheng HospitalTianjinChina
  31. 31.Institute of Dermatology and STD of Fujian ProvinceFuzhouChina
  32. 32.Department of DermatologyPeking University First HospitalBeijingChina
  33. 33.Department of Dermatology, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
  34. 34.Panyu Chronic Disease HospitalGuangzhouChina
  35. 35.Institute of DermatologyChinese Academy of Medical SciencesNanjingChina
  36. 36.Department of DermatologyBeijing HospitalBeijingChina
  37. 37.Department of Dermatology, The Second Affiliated HospitalKunming Medical CollegeKunmingChina
  38. 38.Department of Dermatology, The Second HospitalShandong UniversityJinanChina
  39. 39.Department of Dermatology, Nantong Rich HospitalFourth Clinical College of Yangzhou UniversityNantongChina
  40. 40.Department of DermatologyThe People’s Hospital of Xinjiang Uygur Autonomous RegionUrumqiChina
  41. 41.Department of DermatologySecond Affiliated Hospital of Sun Yat-Sen UniversityGuangZhouChina
  42. 42.Department of Medical Cosmetology, Heping HospitalThe Changzhi Medical CollegeChangzhiChina
  43. 43.Department of DermatologyDatong Fifth HospitalDatongChina
  44. 44.Department of SurgeryQianan People’s HospitalQiananChina
  45. 45.Department of DermatologyCangzhou People’s HospitalCangzhouChina
  46. 46.Department of DermatologyThe Third Affiliated Hospital of Souzhou UniversityChangzhouChina
  47. 47.Department of PathologyLanzhou General Hospital of Lanzhou Military CommandLanzhouChina
  48. 48.Department of DermatologyChaoyang Dafeng Hospital of ShantouShantouChina
  49. 49.Department of DermatologyShenzhen Center for Chronic Disease ControlShenzhenChina
  50. 50.Department of Dermatology, Qilu HospitalShandong UniversityJinanChina
  51. 51.Department of Dermatology, Guang’anmen HospitalChina Academy of Traditional Chinese MedicineBeijingChina
  52. 52.Department of DermatologyTangshan Union HospitalTangshanChina
  53. 53.Department of Dermatology, Institute of Dermatology and Hospital for Skin DiseasesChinese Academy of Medical Sciences & Peking Union Medical CollageNanjingChina
  54. 54.Department of DermatologyHuashan Hospital of Fudan UniversityShanghaiChina
  55. 55.Department of DermatologySecond Hospital of Xi’an Jiaotong UniversityXi’anChina
  56. 56.Institute of Dermatology, Peking Union Medical CollegeChinese Academy of Medical ScienceNanjingChina
  57. 57.Department of DermatologyThe Second Affiliated Hospital of Zhejiang Medical UniversityHangzhouChina
  58. 58.Department of DermatologyAffiliated Hospital of Children Capital Institute of PediatricsBeijingChina
  59. 59.Department of DermatologyHubei Jianghan Oilfield Central HospitalQianjiangChina
  60. 60.Department of HematologyThe First Affiliated Hospital of Nanjing Medical UniversityNanjingChina
  61. 61.Department of DermatologyTianjin Gong’an HospitalTianjinChina
  62. 62.Department of DermatologyPeople’s Hospital of Beijing UniversityBeijingChina
  63. 63.Department of Dermatology, West China HospitalSichuan UniversityChengduChina
  64. 64.Department of Dermatology and VenereologyWest China Hospital of Sichuan UniversityChengduChina

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