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This chapter provides a review of different types of congenital lesions of the skin including their natural history, diagnosis, classification, and treatment options. Most lesions can be approached surgically through a variety of techniques. This chapter aims to provide a familiarity with the diagnosis and help the reader develop a management strategy which satisfies both a functional and aesthetic outcome for these patients.
KeywordsCongenital nevi Blue nevi Café au lait spots Malignancy
Pigmented lesions are a common diagnosis encountered by the pediatric surgeon. Congenital nevi represent a group of skin lesions which occur at birth or within the first several years of life and are characterized by ectopic nests of dermal elements. Although most commonly melanocytic in nature (such as the congenital melanocytic nevus, Nevi of Ota, Nevi of Ito, nevus spilus, café au lait spots and Mongolian spots), nevi can also originate from epidermal (Nevus sebaceous of Jadassohn) and neural elements. Lesion characteristics vary according to the type of cell involved, location within the skin, and level of cell differentiation. Knowledge of the differential diagnosis and natural history of these lesions can help balance the plan of care, so as to address the potential risk of malignant degeneration while accounting for functional and aesthetic concerns encountered during excision and reconstruction.
Congenital Melanocytic Nevi
When evaluating a lesion in a baby, body surface area changes between infancy and adulthood can be used to predict if a lesion falls into the large category. As a general rule, a 12 cm lesion on the head or neck or 7 cm lesion on the body of an infant will grow to meet the large nevi classification (Marghoob et al. 1996). Incidence of CMN decreases with increasing size of the lesion with the relatively common small lesions occurring in 1:100 births, intermediate lesions in 1:1000, large lesions in 1:20,000, and giant lesions in 1:500,000 births (Quaba and Wallace 1986; Alper and Holmes 1983; Illig et al. 1985).
Embryologically, melanocytes originate from neural crest cells as melanoblasts. During early gestation, these melanoblasts migrate to the basal layer of the epidermis at which time they differentiate into dendritic melanocytes and associate into melanosomes that produce pigment for transfer to keratinocytes. Congenital melanocytic nevi result from a disturbance in this migration and differentiation process resulting in ectopic nests of immature cells along their course of migration. Because of this, nevus cells often extend deep into the subcutaneous tissues and can even involve fascia, muscle, periosteum, or the leptomeninges. Congenital melanocytic nevi (CMN) overwhelmingly occur in a sporadic pattern with rare reports of familial cases. There have been several studies seeking to identify genetic hits underlying CMN pathogenesis, and the results of these studies suggest NRAS mutations and, to a lesser extent BRAF mutations, contribute to the development of CMN (Roh et al. 2015). BRAF or NRAS mutations are typically found in small CMN, but the prevalence of NRAS mutations is greater among medium to giant CMN (Charbel et al. 2014).
Although it is difficult to know the true incidence of NCM in association with large CMN because screening of asymptomatic patients is not universally performed, a study of an internet registry found NCM on MRI in approximately 5% of cases of large or giant CMN of which only 5–6% became symptomatic (Agero et al. 2005). Bett reported an incidence of 7.5% in a large cohort of at-risk nevus patients with a mortality rate of 34% in symptomatic patients (Bett 2006).
Symptoms are produced by either malignant degeneration or the benign proliferation of nevus cells within the central nervous system which can block the circulation of cerebral spinal fluid leading to hydrocephalus and increased intracranial pressure. If NCM is to become symptomatic, the vast majority of cases will do so before age 5 years (Bett 2006).
Nevus cells differ from melanocytes histologically as they group together in clusters rather than arrange as individual melanosomes. In addition, nevus cells assume a rounded rather than dendritic shape and keep their pigment within their cytoplasm instead of transferring it to the surrounding keratinocytes (Elder and Elenitsas 1997).
CMN can differ greatly in their size and appearance. Often obvious at birth, some lesions can be quite faint and seem to appear with time over the 1st year of life as they increase in pigmentation. Coloration varies from pale tan to a deep bluish black and may be uniform or extremely variegated. The lesions are often thickened in texture with increased skin markings compared to surrounding normal skin. They often have hair which can range from fine light fuzz to coarse thick follicles. When large lesions are present, they may be accompanied by smaller peripheral satellite lesions of different sizes and numbers which can appear over the course of a lifetime, but predominantly before age three.
Over time, the surface of CMN may change to become verrucous and irregular with darkening of pigmentation. Lightening of color can also be seen in as many as a third of patients with large and giant nevi. Erosion or breakdown is not uncommon in the neonatal period, but may also occur later. This does not necessarily indicate malignant change but warrants further investigation.
The management strategy of CMN can be stratified based on size of the lesion and potential risk of malignant change.
Small and Intermediate Congenital Melanocytic Nevi
Large Congenital Melanocytic Nevi
Management of large CMN is a more complex involved process that again strikes a balance between addressing the risk of malignancy with functional and aesthetic concerns of the lesion and its reconstruction.
At this time, large CMN are not able to be diagnosed prenatally. The appearance of dark, extensive, hairy lesions of the face, trunk, or extremities is by nature devastating for parents who have been anxiously awaiting the birth of their child. Because of this, the infant with large congenital melanocytic nevi should be referred early to a dermatologist and surgeon familiar with the management of these lesions to allow parents to be counseled about the nature of these lesions, risks of malignancy, and potential for excision and reconstructive options. If presented in a compassionate manner, even the news of a multiple-stage reconstruction over many years can be well accepted by families. In over 30 years of experience, the senior author has developed treatment plans for the management of these lesions with the tenet that aesthetic and functional outcome are as important as removal of the nevus itself.
An immediate concern of the family and doctors involved with the care of these patients is the potential risk of malignancy (Lim et al. 2019; Mosa et al. 2019). Historical review of the literature reports a range anywhere from 2% to 31% for the rate of melanoma occurring in patients with large CMN (Kopf et al. 1979; Marghoob et al. 1999; Quaba and Wallace 1986; Alper and Holmes 1983; Sandsmark et al. 1993; Bittencourt et al. 2000). This variance is explained in part by differences in study design and patients (with an increasing number undergoing surgical interventions) and can lead to confusion in how to counsel patient families. In a large systematic review of 14 studies observing over 6500 patients, Krengel and co-workers identified a 2.5% risk of melanoma in LCMN (>20 cm) and 3.1% risk in GCMN (>40 cm) (Krengel et al. 2006). This projected a lower than expected lifetime risk; however, this also was a culmination of many heterogeneic studies. However, current thinking is that the risk is lower than originally predicted, with risk of malignant transformation increasing with the increasing nevus size and distribution. The timing of melanoma diagnosis in patients with large CMN has also been studied with a trend toward development of malignancy early in life. It has been reported that 50% of large CMN that develop malignancy do so in the first 3 years of life, with 60% by childhood and 70% by puberty (Marghoob et al. 1996). Although the true incidence of malignant melanoma arising in untreated large CMN is unlikely to be clearly defined, these numbers encourage early removal.
History and Physical Examination
In the case of large nevi in an axial location especially of the posterior midline scalp or back or when numerous satellite lesions (>20) are present, MRI is recommended to document the presence of NCM. Asymptomatic patients can be identified specifically by T1 shortening on the MRI scan. For increased sensitivity, the MRI should be obtained prior to age 4 months, because as the patient grows increasing myelinization of the CNS can potentially obscure visualization of nevus cells (Barkovich et al. 1994).
It is important to convey that the finding of NCM on MRI does not necessarily imply the future development of neurologic symptoms. It does, however, indicate a risk for later development of benign or malignant melanotic tumors within the CNS. In the cases of symptomatic NCM, the associated poor prognosis should deter the surgeon from aggressive management of the cutaneous lesion. At this point, the low incidence of symptom development reported in asymptomatic patients with a positive screen for NCM would certainly caution against applying that same philosophy to this patient population. Further study will help to fully ascertain the true predicted course of disease in asymptomatic, scan-positive patients and help guide both surgical planning and the role of serial scanning. At this time, if the initial MRI is positive, we proceed with reconstruction as planned and feel that further scans are unnecessary unless neurologic symptoms develop.
Other Congenital Nevi
Nevus of Ota/Nevus of Ito
The nevus of Ito is a blue-gray macular lesion similar to nevus of Ota that affects the shoulder (scapula, deltoid, supraclavicular) area and is sometimes associated with sensory changes (Fig. 8b). It is rarer than nevus of Ota, and more common in Asians.
Both these lesions represent field defects of dermal melanocytosis, histologically characterized by elongated dendritic melanocytes scattered within the collagen bundles mostly in the upper third of reticular dermis. They may contain raised areas within the lesion which are indistinguishable from blue nevus.
Although considered benign, there have been a few reported cases of malignant change, especially in areas similar to cellular blue nevus, and may require biopsy to distinguish from melanoma (Carpo et al. 1999). Historically, cryotherapy and nonselective destruction with CO2 laser was used with mixed esthetic results. Current laser technology allows the surgeon to take advantage of selective photothermolysis to direct laser energy to destroy the melanocytes without damaging the surrounding tissues with excellent cosmetic results. Multiple treatments with a Q-switched ruby laser, Q-switched alexandrite laser, or Q-switched Nd:YAG laser are effective to fade the lesion (Carpo et al. 1999). For Nevus of Ota, an ophthalmologist should be consulted due to the risk of ocular pathology.
Café au Lait Spots
Extensive linear nevi are often seen in the head and neck and present some unique challenges to the reconstructive surgeon. For the larger lesions involving scalp and face, tissue expansion can be applied in a similar fashion which will be described for large CMN. Narrow linear lesions can be excised in stages, often timed so a partial excision is performed at the same time a tissue expander is placed elsewhere and further excision done when the expander is removed for distant flap reconstruction. It is not uncommon to see linear nevi involving the lower lip, chin, and adjacent neck. Given the linear orientation, it is important to design the reconstruction to minimize tension on the repair while breaking up the scar line to avoid scar hypertrophy and contracture. The senior author’s surgical approach has been described in detail in a previous publication (Margulis et al. 2003).
Management of Small and Intermediate Lesions
As stated earlier, many small lesions can be removed at a time during adolescence when the patient can tolerate a local anesthesia. Most of these can be directly excised and the skin closed in layers. For some small lesions and intermediate lesions, excision should be approached in a staged fashion. Goals of serial excision should be complete excision of the lesion in two to three surgeries without distortion of surrounding features or restrictive scar bands. If either of the aforementioned is not possible, or is questionable, tissue expansion should be considered. By staging an excision, the scar will typically be shorter than a single stage excision just by nature of reducing the size of the dog-ears. In the author’s experience, a staged excision can be used to reorient a scar that may not be as feasible in a single stage. This is especially true for nevi of the face that are adjacent to the eyelids, nasal ala, or lips or moderate sized nevi of the trunk near the breast or the genitalia. Time between stages should be calculated based on expected scar maturation and not be performed during the proliferative phase of wound healing. This occurs around 3–4 months postexcision, but may be longer depending on the individual patient, location, wound complications, and scar management.
Management of Large and Giant Congenital Melanocytic Nevi and Other Large Lesions
Treatment for large and giant CMN remains controversial to some, as they feel the risk of malignant degeneration within these lesions is too low to warrant the extensive number of surgeries and potential scar burden associated with removal. Others feel the potential for noncutaneous melanoma to develop in extra-cutaneous nevus cells not amenable to surgical removal (such as in NCM) represents a remaining risk that negates the effectiveness of cutaneous excision for reduction of melanoma risk (Kadonaga and Frieden 1991). However, the significant deformity and associated psychological impact caused by these lesions often tip the scales toward intervention. Management plans should always strive to balance removal of the nevus with a functional and aesthetic reconstruction, and lesions that cannot be effectively addressed in this manner should be considered for conservative management using serial observation by an experienced dermatologist.
Treatment options are most often surgical with excision and reconstruction using adjacent or expanded skin or skin grafts/substitutes, but partial excision techniques can also be used.
Dermabrasion, Curettage, and Laser Therapy
Partial thickness excisions for CMN including dermabrasion, curettage, Versa Jet, and laser therapy have been reported as effective methods of reducing the cell burden to improve appearance of the nevus without completely excising it. The original theory behind these techniques relied on the belief that in infancy nevus cells lay in a superficial location within the upper reticular dermis and epidermis and gradually descended to deeper layers within the 1st weeks of life. However, this theory has not been substantiated (Marghoob 2013). Dermabrasion works to abrade away the surface cells, whereas curettage separates the cells at the natural cleavage plane between the superficial and deep dermis. These methods do nothing to address deeper nevus cells within the deeper dermis or subcutaneous tissues. Therefore, the number of nevus cells within a lesion is reduced but not eliminated. Initially, lesions may be lighter, but may darken with time as described in long term study (Magalon et al. 1998). In addition, any associated hypertrichosis is not affected, as hair follicles are found much deeper extending into the subcutaneous fat. Subsequent problems arise in these patients relating to pruritus and scarring secondary to the disrupted hair follicles with trapped and ingrown hair. Finally, malignant potential remains for the leftover nevus cells and scarring from these interventions may make follow up examination difficult. At least one case has been reported of melanoma arising within a large trunk nevus following dermabrasion (Dragieva et al. 2006). Due to these downsides, many practitioners have largely abandoned split thickness excision as a method of treatment.
Laser offers another potential treatment strategy attractive to both the patient and doctor as a simplified method to reduce the pigmentation of a lesion without scarring. Laser therapy is well suited for the treatment of lesions characterized by superficial dermal pigmentation such as the Nevi of Ota and Ito, persistent Mongolian spots, café au lait macules, and some elements of nevus spilus due to its minimal thickness, location of pigment within the dermis, and low potential for malignancy. Effective treatment relies on proper wavelength and pulse-width selection to allow penetration of the skin and photoselective destruction of melanin while preserving the remaining elements to avoid scarring (Carpo et al. 1999; Alster 1995). Serial treatments are required. Scarring can occur with aggressive treatment or improper setting selection. Hypo- and hyperpigmentation have also been reported which may be temporary or permanent. Exposure to sunlight in the perioperative period can cause significant burning, scarring, and hyperpigmentation.
Unfortunately, because CMN display nevus cells within all layers of the skin as well as within the deeper structures, it is unrealistic to think that a laser could effectively penetrate to the depths necessary to eliminate all pigment-producing cells without significant secondary damage and scarring. In addition, laser treatment vaporizes the specimen, therefore eliminating histologic evaluation of the lesion to determine its nature. Finally, the impact of the exposure of nevus cells to the radiant energy associated with laser therapy is unknown and may not be apparent for many years into the future.
Although dermabrasion, curettage, and laser offer a relatively simple approach to improving the appearance of CMN, they present many drawbacks. In addition, scarring from these therapies may complicate ultimate excisional treatment options in the future. Finally, the delay of more definitive reconstruction may have its own psychological effects on a child. Although limited use of these therapies may be useful in certain areas of reconstruction (such as lightening of a thin lesion in the cosmetic and functionally sensitive eyelid area), thoughtful consideration is warranted prior to widespread implementation of these modalities in a treatment algorithm for large CMN.
Surgical Excision and Reconstruction
The benefits of surgical excision of large and giant CMN include complete removal of involved skin and subcutaneous tissue. Although some have focused on skin grafts, skin substitutes, or cultured epithelium for reconstruction, when possible, use of tissue expansion allows the most functional and aesthetic result by allowing replacement with full thickness normal tissue. Goals of treatment include complete excision at an early age, minimization of scarring, and functional impact with a low requirement for future procedures. Early excision is emphasized for four reasons. First, the greatest risk for malignancy is reported in childhood, most notably in the first 3 years of life. Second, the elasticity and healing capacity of the skin is better the younger the patient. Third, patients operated on in infancy tolerate surgery better both physically and emotionally than their older counterparts. Finally, by completing reconstruction early, the psychological impact of the lesions and surgical interventions can be reduced.
In 1988, the senior author presented a coordinated approach to the management of these lesions in 78 patients (Bauer and Vicari 1988). This report outlined the spectrum of treatment options from skin graft to tissue expansion and assessed the effectiveness of excision and reconstruction with each technique in each body region. Since then, further experience with over 300 patients has allowed further development and refinement of approach (Bauer and Margulis 2004; Margulis et al. 2004, 2009; Unlu et al. 2002; Kryger and Bauer 2008; Alkureishi et al. 2018). Although a full discussion of the nuances of management of each of large CMN is beyond the scope of this chapter, the following is a summary of the author’s current approach.
Several types of tissue expanders exist. The more commonly used include the round and rectangular types; crescent-shaped (and croissant) prostheses, originally developed to minimize dog-ears at the donor site, have fallen out of favor as it has been recognized that the added tissue gained with rectangular expanders may increase the choices possible for flap design (i.e., use of transposition flaps). This author prefers using rectangular expanders in almost all cases. Expander volumes have a wide range and vary according to the anatomic site. Rectangular expanders of 70–1000 cc are standard, but smaller and larger custom expanders are available. Saline is delivered via a remote valve port connected to the device by silicone tubing placed in a separate subcutaneous pocket. Remote, internal ports are preferred in the author’s practice to allow safer home expansion and avoid the risk of perforation by a misplaced needle accessing an integrated port. Risks of the remote port include migration of the port, flipping of the port, tube obstruction, kinking, or separation. To avoid these, meticulous attention is paid to the tubing length and course and ensuring a reliable port connection. As well, dissection of the port pocket is kept to a minimum and the port placed over firm supporting tissue. If needed, the port can be secured with suture. On the extremities larger ports are used to help avoid migration and turnover. The expander is typically positioned directly adjacent to or partially below the nevus itself. Donor skin needs to be free of infection, trauma, or previous scars (or have mature, stable scars) to prevent flap breakdown or extrusion. In the majority of cases, the expander can be placed through an incision within the boarder of the nevus.
Design of the flap is not a frivolous undertaking. Historically, expansion was used to generate advancement flaps only. Experience has demonstrated that expanded transposition and rotation flaps are frequently preferable, allowing greater versatility in flap design and more effective use of the expanded tissue. The capsule of the expanded flap also provides an improved blood supply to the tissue allowing for greater advancement and range of motion on a smaller pedicle than would be allowed in a nonexpanded flap. In applying this principle, it is important to avoid scoring of the capsule so that the added vascularity provided by the capsule is not compromised. In the same vein, when using back cuts to help transpose the tissue, it is important to maintain as much capsule on the free margin of advancing tissue as possible. This will improve the blood flow to this segment of the flap. Inset of the expanded flap is done in layered fashion ensuring that sutures capture a portion of the capsule. By preventing capsular recoil both the arterial inflow and the venous outflow of the flap are preserved.
Scalp reconstruction is complicated by its relatively inflexible quality and the unique aesthetics of maintaining hair quality and direction. Because of this, tissue expansion remains the workhorse for scalp reconstruction during excision of large CMN. Scalp lesions are best reconstructed in stages, with placement of one or more tissue expanders in a subgaleal plane beneath the normal scalp skin. Flaps are designed with consideration of the major blood supply to the scalp (superficial temporal, postauricular, occipital, and contributions from the supraorbital vessels). Following adequate expansion (generally from 10 to 12 weeks), the expanders are removed, lesions excised, and the defect closed using both advancement and transposition flaps designed to preserve hair direction and hairline (Bauer and Margulis 2004). Flaps should be carried out and checked for viability before excision of the nevus. The senior author has found that by planning transposition flaps, the number of expansions needed is reduced. Serial expansion of the scalp typically leads to scarring of the galea to the periosteum. If this occurs, expander placement below the periosteum can be performed in the subsequent stages. In these cases it is often difficult to provide significant prefill of the expander at the time of surgery. Therefore, the expansion process may take slightly longer than the first or second round of expansion. Defects in the temporal hairline are often best treated with a large transposition flap from the occipital scalp. This provides favorable hair direction for both the scars and the hair along the sideburn.
Face and Neck
Large CMN of the face present some of the greatest reconstructive challenges. By dividing the face into aesthetic units, tissue expansion of available adjacent areas of normal skin in the neck and forehead can provide skin of excellent quality match while allowing scars to lie at the junction of aesthetic units and render them less obvious. When advancing tissue from the neck into the cheek area, a transposition design can help improve flap movement while aligning the scars optimally. Whether transposed with the flap based laterally or medially, the transposition minimizes the risk of downward drift of the flap and ectropion of the lower eyelid (Bauer and Margulis 2004). Lesions of the nose are best resurfaced by an expanded forehead flap carried on a supratrochlear, superior orbital, or superficial temporal artery pedicle. In children, the typical wider scar left in adult paramedian donor sites can be quite disfiguring. This can be minimized by pre-expanding the flap. If forehead is not available, an expanded supraclavicular full thickness skin graft provides a suitable option. The periorbital area is also best addressed with expanded full-thickness skin grafts to allow preservation of the thin nature of the tissue while decreasing incidence of ectropion (Margulis et al. 2009). For large facial nevi involving the eyelids, the reconstruction of the lids is the final phase after the rest of the nevus has been excised and the surrounding subunits reconstructed. This allows placement of grafts along stable scar margins. Any ectropion or lid distortion that has been caused by the nevus or prior reconstruction can be addressed at this point as well with either medial or lateral canthoplasty.
With experience, expansion of the extremity skin is feasible. One must assess the lesion and understand the limitations in the basic geometry of the limb (flap movement is easier around the circumference than in an axial direction). Careful planning, choice of expander size and placement, and a slower expansion schedule leads to lower risk of extrusion and flap failure. Placement of expanders is easier above the knee than below. When possible, more than one expander should be used. For large extremity lesions, using expansion as an adjunct to reduce the overall size of the defect to then be covered by a free flap is another useful approach.
Expanded free flaps offer another alternative for larger lesions of the extremities with improved functional and aesthetic outcomes. These prove especially useful for coverage of the knee, lower leg, and ankle. Pre-expansion of the flap or the tissue adjacent to the donor site reduces the donor site morbidity in pediatric patients, often times avoiding the need for a skin graft.
Complications of surgical excision of large CMN with expanded flap reconstruction are uncommon despite the complex nature of these procedures. During the expansion process, the primary risks include expander infection, expander exposure or extrusion, flap compromise, and incisional dehiscence. The incidence of expander infection has been reported at 5%, which can be due to inoculation during expander insertion or repeated expansions, after exposure of the expander or by hematogenous seeding from a distant infection (Adler et al. 2009b). These infections can usually be managed conservatively by antibiotic administration allowing completion of expansion and successful reconstruction. A low threshold for placing the patient on oral antibiotics during healing problems or illness occurring during expansion may help minimize risk. It is also vital to maintain a close communication with the patient caregivers to ensure there is a free flow of information and prompt reporting of any signs of the aforementioned complications. Well-trained ancillary staff, nursing, and on-call personnel can have a dramatic influence on the success of tissue expansion.
Technical considerations for the use of expanded flap reconstruction rely on the understanding of the unique characteristics provided by expansion. Vascularity of a flap through the delay phenomenon makes flap ischemia rare. Preservation of the capsule with judicious capsulotomy and avoidance of excessive tension during closure can prevent this potentially devastating complication. Venous congestion and wound dehiscence can be improved by ensuring the capsule is advanced along with the flap and secured using deeper sutures thereby preventing its recoil during the final closure. Finally, meticulous closure and postoperative scar management help achieve optimal results. It is important to discuss scarring with patient families. While scars can be quite extensive for large and giant CMN, if they run in favorable directions to avoid tension, even long or wide scars can fade very nicely.
Conclusion and Future Directions
The treatment of congenital large and giant nevi presents a continuing challenge to all individuals involved with these patients. The ability to present an organized discussion of current views on risk of malignant change to parents, patients, referring physicians, and other allied health care workers is critical. Treatment strategies should take into consideration the varied opinions regarding malignant risk, emphasize the benefits of early excision on lowering that risk, and most importantly, provide a means of dealing with these often devastating lesions in a manner that optimizes the functional and aesthetic outcome and minimizes the need for major reconstruction in later life.
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