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Der Hautarzt

, Volume 70, Issue 9, pp 670–676 | Cite as

Extramammärer Morbus Paget

  • I. Cosgarea
  • A. Zaremba
  • U. HillenEmail author
Leitthema
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Zusammenfassung

Der extramammäre Morbus Paget (EMP) ist ein seltenes, langsam wachsendes, kutanes Adenokarzinom mit einer Inzidenz von 0,1–2,4/1.000.000 Einwohner. Histologisch ist der EMP – ähnlich wie der mammäre Morbus Paget – durch epidermale Paget-Zellen gekennzeichnet. Der EMP wird in einen primären EMP (Typ I) und sekundären EMP (Typ II – assoziiert mit einem kolorektalen Karzinom – und Typ III – assoziiert mit einem urogenitalen Karzinom) unterteilt. Das klinische Bild ist nicht charakteristisch und imitiert chronisch entzündliche Dermatosen. Dies kann eine frühe Diagnosestellung erschweren und hinauszögern. Die mikrographisch kontrollierte Exzision ist die Therapie der Wahl. Bei geplantem Einsatz von topischen Therapien wie Imiquimod bzw. oberflächlichen ablativen Therapien sollte das Ausmaß einer Adnexinfiltration histologisch untersucht werden. Die komplette Exzision des Tumors stellt aufgrund der pathologischen Charakteristika bei schlecht definierbaren Wundrändern eine Herausforderung dar. Im metastasierten Stadium hat der EMP eine schlechte Prognose. Kontrollierte klinische Studien zur Systemtherapie liegen bisher nicht vor.

Schlüsselwörter

Paget-Karzinom Adnexinfiltration Mikroskopisch kontrollierte Chirurgie Kutanes Adenokarzinom Exzision 

Extramammary Paget’s disease

Abstract

Extramammary Paget’s disease (EPD) is a rare, slowly growing, cutaneous adenocarcinoma with an incidence of 0.1–2.4 per 1,000,000 inhabitants. Histologically, EPD is characterized by the presence of epidermal Paget’s cells, similarly to mammary Paget’s disease. The EPD is typically divided into primary EPD (type I) and secondary EPD (type II associated with colorectal carcinoma and type III associated with urogenital carcinoma). From a clinical point of view, EPD is unspecific commonly mimicking chronic inflammatory skin disorders. This unspecific clinical picture can impede and delay the diagnosis of EPD. The treatment of choice for local EPD is the micrographically controlled excision. The extent of the infiltration of adnexal structures should be histologically determined prior to topical therapies, such as imiquimod and superficial ablative therapy. The complete excision of the tumor can be challenging due to ill-defined borders. In the metastatic stage the EPD has a poor prognosis. Controlled clinical trials for systemic treatment are still lacking.

Keywords

Paget’s carcinoma Adnexal infiltration Microscopically controlled surgery Cutaneous adenocarcinoma Excision 

Notes

Einhaltung ethischer Richtlinien

Interessenkonflikt

I. Cosgarea, A. Zaremba und U. Hillen geben an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.

Literatur

  1. 1.
    Barth P, Dulaimi Al-Saleem E, Edwards KW et al (2015) Metastatic extramammary Paget’s disease of scrotum responds completely to single agent trastuzumab in a hemodialysis patient: Case report, molecular profiling and brief review of the literature. Case Rep Oncol Med 2015:895151Google Scholar
  2. 2.
    Chanda JJ (1985) Extramammary Paget’s disease: Prognosis and relationship to internal malignancy. J Am Acad Dermatol 13:1009–1014CrossRefGoogle Scholar
  3. 3.
    Chang K, Li GX, Kong YY et al (2017) Chemokine receptors CXCR4 and CXCR7 are associated with tumor aggressiveness and prognosis in extramammary Paget disease. J Cancer 8:2471–2477CrossRefGoogle Scholar
  4. 4.
    Cheng PS, Lu CL, Cheng CL et al (2014) Significant male predisposition in extramammary Paget disease: A nationwide population-based study in Taiwan. Br J Dermatol 171:191–193CrossRefGoogle Scholar
  5. 5.
    Cho Z, Konishi E, Kanemaru M et al (2017) Podoplanin expression in peritumoral keratinocytes predicts aggressive behavior in extramammary Paget’s disease. J Dermatol Sci 87:29–35CrossRefGoogle Scholar
  6. 6.
    Diaz De Leon E, Carcangiu ML, Prieto VG et al (2000) Extramammary Paget disease is characterized by the consistent lack of estrogen and progesterone receptors but frequently expresses androgen receptor. Am J Clin Pathol 113:572–575CrossRefGoogle Scholar
  7. 7.
    Egashira S, Kajihara I, Kanemaru H et al (2017) Achieved good response of S‑1 and docetaxel combination chemotherapy in two patients with metastatic extramammary Paget’s disease. J Dermatol 44:e103–e104CrossRefGoogle Scholar
  8. 8.
    Fligiel Z, Kaneko M (1975) Extramammary Paget’s disease of the external ear canal in association with ceruminous gland carcinoma. A case report. Cancer 36:1072–1076CrossRefGoogle Scholar
  9. 9.
    Fujisawa Y, Yoshino K, Kiyohara Y et al (2015) The role of sentinel lymph node biopsy in the management of invasive extramammary Paget’s disease: Multi-center, retrospective study of 151 patients. J Dermatol Sci 79:38–42CrossRefGoogle Scholar
  10. 10.
    Fukuda K, Funakoshi T (2018) Metastatic extramammary Paget’s disease: Pathogenesis and novel therapeutic approach. Front Oncol 8:38CrossRefGoogle Scholar
  11. 11.
    Hanawa F, Inozume T, Harada K et al (2011) A case of metastatic extramammary Paget’s disease responding to trastuzumab plus paclitaxel combination therapy. Case Rep Dermatol 3:223–227CrossRefGoogle Scholar
  12. 12.
    Hendi A, Brodland DG, Zitelli JA (2004) Extramammary Paget’s disease: surgical treatment with Mohs micrographic surgery. J Am Acad Dermatol 51:767–773CrossRefGoogle Scholar
  13. 13.
    Herrel LA, Weiss AD, Goodman M et al (2015) Extramammary Paget’s disease in males: Survival outcomes in 495 patients. Ann Surg Oncol 22:1625–1630CrossRefGoogle Scholar
  14. 14.
    Hirai I, Funakoshi T (2017) Modified weekly regimen of cisplatin, epirubicin and paclitaxel induced a durable response in two cases of metastatic extramammary Paget’s disease. J Dermatol 44:1148–1151CrossRefGoogle Scholar
  15. 15.
    Ichiyama T, Gomi D, Fukushima T et al (2017) Successful and long-term response to trastuzumab plus paclitaxel combination therapy in human epidermal growth factor receptor 2‑positive extramammary Paget’s disease: A case report and review of the literature. Mol Clin Oncol 7:763–766CrossRefGoogle Scholar
  16. 16.
    Ito T, Kaku Y, Nagae K et al (2015) Tumor thickness as a prognostic factor in extramammary Paget’s disease. J Dermatol 42:269–275CrossRefGoogle Scholar
  17. 17.
    Jones RE Jr., Austin C, Ackerman AB (1979) Extramammary Paget’s disease. A critical reexamination. Am J Dermatopathol 1:101–132CrossRefGoogle Scholar
  18. 18.
    Kang Z, Xu F, Zhang QA et al (2013) Oncogenic mutations in extramammary Paget’s disease and their clinical relevance. Int J Cancer 132:824–831CrossRefGoogle Scholar
  19. 19.
    Kanitakis J (2007) Mammary and extramammary Paget’s disease. J Eur Acad Dermatol Venereol 21:581–590CrossRefGoogle Scholar
  20. 20.
    Karam A, Berek JS, Stenson A et al (2008) HER-2/neu targeting for recurrent vulvar Paget’s disease: A case report and literature review. Gynecol Oncol 111:568–571CrossRefGoogle Scholar
  21. 21.
    Karam A, Dorigo O (2014) Increased risk and pattern of secondary malignancies in patients with invasive extramammary Paget disease. Br J Dermatol 170:661–671CrossRefGoogle Scholar
  22. 22.
    Kato J, Hida T, Yamashita T et al (2018) Successful TS-1 monotherapy as the second-line treatment for advanced extramammary Paget’s disease: A report of two cases. J Dermatol 45:80–82CrossRefGoogle Scholar
  23. 23.
    Kim SJ, Thompson AK, Zubair AS et al (2017) Surgical treatment and outcomes of patients with extramammary Paget disease: A cohort study. Dermatol Surg 43:708–714CrossRefGoogle Scholar
  24. 24.
    Kiniwa Y, Yasuda J, Saito S et al (2019) Identification of genetic alterations in extramammary Paget disease using whole exome analysis. J Dermatol Sci 94:229–235CrossRefGoogle Scholar
  25. 25.
    Konstantinova AM, Shelekhova KV, Stewart CJ et al (2016) Depth and patterns of adnexal involvement in primary extramammary (anogenital) Paget disease: A study of 178 lesions from 146 patients. Am J Dermatopathol 38:802–808CrossRefGoogle Scholar
  26. 26.
    Liegl B, Horn LC, Moinfar F (2005) Androgen receptors are frequently expressed in mammary and extramammary Paget’s disease. Mod Pathol 18:1283–1288CrossRefGoogle Scholar
  27. 27.
    Lloyd J, Flanagan AM (2000) Mammary and extramammary Paget’s disease. J Clin Pathol 53:742–749CrossRefGoogle Scholar
  28. 28.
    Machida H, Moeini A, Roman LD et al (2015) Effects of imiquimod on vulvar Paget’s disease: A systematic review of literature. Gynecol Oncol 139:165–171CrossRefGoogle Scholar
  29. 29.
    Mauzo SH, Tetzlaff MT, Milton DR et al (2019) Expression of PD-1 and PD-L1 in extramammary Paget disease: Implications for immune-targeted therapy. Cancers (Basel) 11:754CrossRefGoogle Scholar
  30. 30.
    Molina GE, Khalifian S, Mull JL et al (2019) Topical combination of fluorouracil and calcipotriene as a palliative therapy for refractory extramammary Paget disease. JAMA Dermatol 155:599–603CrossRefGoogle Scholar
  31. 31.
    Oashi K, Tsutsumida A, Namikawa K et al (2014) Combination chemotherapy for metastatic extramammary Paget disease. Br J Dermatol 170:1354–1357CrossRefGoogle Scholar
  32. 32.
    Ohara K, Fujisawa Y, Yoshino K et al (2016) A proposal for a TNM staging system for extramammary Paget disease: Retrospective analysis of 301 patients with invasive primary tumors. J Dermatol Sci 83:234–239CrossRefGoogle Scholar
  33. 33.
    Peng X, Qian W, Hou J (2017) 5‑aminolevulinic acid (5-ALA) fluorescence-guided Mohs surgery resection of penile-scrotal extramammary Paget’s disease. Biosci Trends 11:595–599CrossRefGoogle Scholar
  34. 34.
    Richter CE, Hui P, Buza N et al (2010) HER-2/NEU overexpression in vulvar Paget disease: The Yale experience. J Clin Pathol 63:544–547CrossRefGoogle Scholar
  35. 35.
    Siesling S, Elferink MA, Van Dijck JA et al (2007) Epidemiology and treatment of extramammary Paget disease in the Netherlands. Eur J Surg Oncol 33:951–955CrossRefGoogle Scholar
  36. 36.
    St Claire K, Hoover A, Ashack K et al (2019) Extramammary Paget disease. Dermatol Online J 25(4)Google Scholar
  37. 37.
    Tagliaferri L, Casa C, Macchia G et al (2018) The role of radiotherapy in extramammary Paget disease: A systematic review. Int J Gynecol Cancer 28:829–839CrossRefGoogle Scholar
  38. 38.
    Takahagi S, Noda H, Kamegashira A et al (2009) Metastatic extramammary Paget’s disease treated with paclitaxel and trastuzumab combination chemotherapy. J Dermatol 36:457–461CrossRefGoogle Scholar
  39. 39.
    Tanaka R, Sasajima Y, Tsuda H et al (2013) Human epidermal growth factor receptor 2 protein overexpression and gene amplification in extramammary Paget disease. Br J Dermatol 168:1259–1266CrossRefGoogle Scholar
  40. 40.
    Theaker JM (1988) Extramammary Paget’s disease of the oral mucosa with in situ carcinoma of minor salivary gland ducts. Am J Surg Pathol 12:890–895CrossRefGoogle Scholar
  41. 41.
    Tokuda Y, Arakura F, Uhara H (2015) Combination chemotherapy of low-dose 5‑fluorouracil and cisplatin for advanced extramammary Paget’s disease. Int J Clin Oncol 20:194–197CrossRefGoogle Scholar
  42. 42.
    Trofymenko O, Garcia V, Zeitouni NC (2018) Primary extramammary Paget’s disease of the skin: Treatment and survival. Int J Dermatol 57:e76–e78CrossRefGoogle Scholar
  43. 43.
    Van Der Linden M, Meeuwis KA, Bulten J et al (2016) Paget disease of the vulva. Crit Rev Oncol Hematol 101:60–74CrossRefGoogle Scholar
  44. 44.
    Van Der Linden M, Oonk MHM, Van Doorn HC et al (2018) Vulvar Paget disease: A national retrospective cohort study. J Am Acad Dermatol.  https://doi.org/10.1016/j.jaad.2018.11.016 Google Scholar
  45. 45.
    Wagner G, Sachse MM (2011) Extramammary Paget disease—clinical appearance, pathogenesis, management. J Dtsch Dermatol Ges 9:448–454Google Scholar
  46. 46.
    Wakabayashi S, Togawa Y, Yoneyama K et al (2012) Dramatic clinical response of relapsed metastatic extramammary Paget’s disease to trastuzumab monotherapy. Case Rep Dermatol Med 2012:401362Google Scholar
  47. 47.
    Wan M, Ma H, Zhao Y et al (2018) Clinical benefits of preoperative conventional fluorescence diagnosis in surgical treatment of extramammary Paget disease. Dermatol Surg 44:375–382Google Scholar
  48. 48.
    Wang HW, Lv T, Zhang LL et al (2013) A prospective pilot study to evaluate combined topical photodynamic therapy and surgery for extramammary paget’s disease. Lasers Surg Med 45:296–301CrossRefGoogle Scholar
  49. 49.
    Whorton CM, Patterson JB (1955) Carcinoma of Moll’s glands with extramammary Paget’s disease of the eyelid. Cancer 8:1009–1015CrossRefGoogle Scholar
  50. 50.
    Yamada-Kanazawa S, Tasaki Y, Kajihara I et al (2019) The expression of EpCAM in extramammary Paget’s disease. Intractable Rare Dis Res 8:20–23CrossRefGoogle Scholar
  51. 51.
    Yao H, Xie M, Fu S et al (2018) Survival analysis of patients with invasive extramammary Paget disease: Implications of anatomic sites. BMC Cancer 18:403CrossRefGoogle Scholar
  52. 52.
    Yoneyama K, Kamada N, Kinoshita K et al (2005) Androgen-deprivation regimen for multiple bone metastases of extramammary Paget disease. Br J Dermatol 153:853–855CrossRefGoogle Scholar
  53. 53.
    Yoshino K, Fujisawa Y, Kiyohara Y et al (2016) Usefulness of docetaxel as first-line chemotherapy for metastatic extramammary Paget’s disease. J Dermatol 43:633–637CrossRefGoogle Scholar
  54. 54.
    Zampogna JC, Flowers FP, Roth WI et al (2002) Treatment of primary limited cutaneous extramammary Paget’s disease with topical imiquimod monotherapy: Two case reports. J Am Acad Dermatol 47:S229–S235CrossRefGoogle Scholar

Copyright information

© Springer Medizin Verlag GmbH, ein Teil von Springer Nature 2019

Authors and Affiliations

  1. 1.Dermatological Sciences, Institute of Cellular MedicineNewcastle UniversityNewcastle upon TyneGroßbritannien
  2. 2.Klinik für DermatologieUniversitätsklinikum EssenEssenDeutschland
  3. 3.Klinik für Dermatologie und Venerologie, Vivantes Netzwerk für Gesundheit GmbHVivantes Klinikum NeuköllnBerlinDeutschland

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