[en] In recent years, the screening accuracy of clinical dermoscopy has increased in the early detection of evolving atypical melanocytic neoplasms. However, the most dramatic cases of human malignant melanomas (MM), i.e. the fast-growing neoplasms, usually escape the classical clinical criteria of MM. As a result, a number of puzzling cases exhibit uncertain clues for MM. Thus, the risk of microscopic misdiagnosis is likely on the rise if the histological criteria are not fine-tuned. This review summarizes a conceptual classification of atypical melanocytic neoplasms grouped under the heading of melanocytomas. Some immunohistochemical markers are tentatively used as discriminators between fast-growing MM and melanocytomas. However, some differences seem to be more statistically significant than clinically useful due to extensive overlap in immunoreactivity from any case to case. A multipronged immunohistological screening is therefore welcome.
Disciplines :
Dermatology
Author, co-author :
Quatresooz, Pascale ; Centre Hospitalier Universitaire de Liège - CHU > Dermatopathologie
Jemal A, Devesa SS, Hartge P and Tucker MA: Recent trends in cutaneous melanoma incidence among whites in the United States. J Natl Cancer Inst 93: 678-683, 2001.
Quatresooz P, Uhoda I, Fumal I, Piérard-Franchimont C and Piérard GE: Revisiting the gender-linked melanoma burden. Dermatology 209: 197-201, 2004.
Thompson JF, Scolyer RA and Kefford RF: Cutaneous melanoma. Lancet 365: 687-701, 2005.
Uhoda I, Quatresooz P, Fumal I, Nikkels AF, Piérard-Franchimont C and Piérard GE: Updating trends in cutaneous cancers in south-east Belgium. Oncol Rep 12: 111-114, 2004.
Lipsker D: Growth rate, early detection and prevention of melanoma: melanoma epidemiology revisited and future challenges. Arch Dermatol 142: 1638-1640, 2006.
Liu W, Dowling JP, Murray WK, McArthur GA, Thompson JF, Wolfe R and Kelly JW: Rate of growth in melanomas: characteristics and associations of rapidly growing melanoma. Arch Dermatol 142: 1551-1558, 2006.
Liu W, Kelly JW, Trivett M, Murray WK, Dowling JP, Wolfe R, Mason G, Magee J, Angel C, Dobrovic A and McArthur GA: Distinct clinical and pathological features are associated with braf mutation in primary melanoma. J Invest Dermatol 127: 900-905, 2007.
Quatresooz P, Piérard-Franchimont C and Piérard GE: Space-time clustering and seasonality in diagnosing skin cancers in wallonia (south east Belgium). Dermatology 217: 48-51, 2008.
Ohsie SJ, Sarantopoulos GP, Cochran AJ and Binder SW: Immunohistochemical characteristics of melanoma. J Cutan Pathol 35: 433-444, 2008.
Quatresooz P, Piérard-Franchimont C and Piérard GE: Highlighting the immunohistochemical profile of melanocytomas. Oncol Rep 19: 1367-1372, 2008.
Banerjee SS and Harris M: Morphological and immunophenotypic variations in malignant melanoma. Histopathology 36: 387-402, 2000.
Smoller BR: Histologic criteria for diagnosing primary cutaneous malignant melanoma. Mod Pathol 19: S34-S40, 2006.
Chin L: The genetics of malignant melanoma: lessons from mouse and man. Nat Rev Cancer 3: 559-570, 2003.
Ainsworth AM, Folberg R, Reed RJ and Clark WH: Melanocytic nevi, melanocytomas, melanocytic dysplasias, and uncommon forms of melanoma. In: Human Malignant Melanoma, Clinical Oncology Monographs. Clark WH, Goldman KI and Mastrangelo MJ (eds). Grune & Straaton, New York, pp167-208, 1979.
Piérard GE, Piérard-Franchimont C, Nikkels AF, Nikkels-Tassoudji N, Arrese JE and Bourguignon JP: Naevocyte triggering by recombinant human growth hormone. J Pathol 180: 74-79, 1996.
Gurbuz Y, Apaydin R, Muezzinoglu B and Buyukbabani N: A case report and a current dilemma in histopathology, atypical spitz nevus or spitzoid melanoma. Pediatr Dermatol 19: 99-102, 2002.
Quatresooz P, Arrese JE, Piérard-Franchimont C and Piérard GE: Immunohistochemical aid at risk stratification of melanocytic neoplasms. Int J Oncol 24: 211-216, 2004.
Barnhill RL: The spitzoid lesion, rethinking spitz tumors, atypical variants, 'spitzoid melanoma' and risk assessment. Mod Pathol 19: S21-S33, 2006.
Lee JB: Spitz nevus versus melanoma, limitation of the diagnostic methodology exposed. Eur J Dermatol 16: 223-224, 2006.
Zembowicz A, Carney JA and Mihm MC: Pigmented epithelioid melanocytoma: a low-grade melanocytic tumor with metastatic potential indistinguishable from animal-type melanoma and epithelioid blue nevus. Am J Surg Pathol 28: 31-40, 2004.
Fraitag S and Vignon-Pennamen MD: Spitz tumor and pigmented epithelioid melanocytoma: new nosological frameworks for commonly ill-defined tumors. Ann Dermatol Venereol 136: 133-144, 2009.
Sabroe RA, Vaingankar NV, Rigby HS and Peachey RD: Agminate spitz naevi occurring in an adult after the excision of a solitary spitz naevus, report of a case and review of the literature. Clin Exp Dermatol 21: 197-200, 1996.
Turhan T, Oner K, Yurtseven T, Akalin T and Ovul I: Spinal meningeal melanocytoma: report of two cases and review of the literature. J Neurosurg 100: 287-290, 2004.
O'Brien DF, Crooks D, Mallucci C, Javadpour M, Williams D, du Plessis D, Broome J, Foy P and Pizer B: Meningeal melanocytoma. Childs Nerv Syst 22: 556-561, 2006.
Mangni J, Li N and Bhawan J: Immunohistochemical markers of melanocytic lesions: a review of their diagnostic usefulness. Am J Dermatopathol 24: 270-281, 2002.
Alonso SR, Ortiz P, Pollan M, Pérez-Gomez B, Sanchez L, Acuna MJ, Pajares R, Martinez-Tello FJ, Hortelano CM, Piris MA and Rodriguez-Peralto JL: Progression in cutaneous malignant melanoma is associated with distinct expression profiles: a tissue microarray-based study. Am J Pathol 164: 193-203, 2004.
Quatresooz P and Piérard GE: Immunohistochemical investigation of α1 (IV) and α5 (IV) collagen chains in a broad spectrum of melanocytic tumours. Melanoma Res 15: 161-168, 2005.
Fecher LA, Cummings SD, Keefe MJ and Alani RM: Toward a molecular classification of melanoma. J Clin Oncol 25: 1606-1620, 2007.
Plaza JA, Suster D and Perez-Montiel D: Expression of immunohistochemical markers in primary and metastatic malignant melanoma, a comparative study in 70 patients using a tissue microarray technique. Appl Immunohistochem Mol Morphol 15: 421-425, 2007.
Webber A, Lawson D and Cohen C: Maspin and mutant p53 expression in malignant melanoma and carcinoma, use of tissue microarray. Appl Immunohistochem Mol Morphol 16: 19-23, 2008.
Quatresooz P, Piérard-Franchimont C and Piérard GE: Diagnostic challenge of desmoplastic melanoma. Trends Cancer Res 3: 27-34, 2007.
Piérard GE and Al Rustom K: Dysplastic nevi and the concept of triggered melanocytic system. Emerg Med J 7: 3-6, 1989.
Aktürk AS, Bilen N, Bayrämgürler D, Demirsoy EO, Erdogan S and Kiran R: dermoscopy is a suitable method for the observation of the pregnancy-related changes in melanocytic nevi. J Eur Acad Dermatol Venereol 21: 1086-1090, 2007.
Tronnier M and Wolff H: UV-irradiated melanocytic nevi simulating melanoma in situ. Am J Dermatopathol 17: 1-6, 1995.
Brozyna A, Zbytek B, Granese J, Carlson JA, Ross J and Slominski A: Mechanism of UV-related carcinogenesis and its contribution to nevi/ melanoma. Exp Rev Dermatol 2: 451-469, 2007.
Beyeler M, Hafner J, Beinder E, Fauchêre JC, Stoeckli SJ, Fehr M and Dummer R: Special considerations for stage IV melanoma during pregnancy. Arch Dermatol 141: 1077-1079, 2005.
Brochez L, Verhaeghe E, Grosshans E, Haneke E, Piérard G, Ruiter D and Naeyaert JM: Inter-observer variation in the histopathological diagnosis of clinically suspicious pigmented skin lesions. J Pathol 196: 459-466, 2002.
Orchard GE: Comparison of immunohistochemical labelling of melanocyte differentiation antibodies melan-A, tyrosinase and HMB45 with NKIC3 and S100 protein in the evaluation of benign naevi and malignant melanoma. Histochem J 32: 475-481, 2000.
Claessens N, Piérard GE, Piérard-Franchimont C, Arrese JE and Quatresooz P: Immunohistochemical detection of incipient melanoma micrometastases: relationship with sentinel lymph node involvement. Melanoma Res 15: 107-110, 2005.
Shaikh L, Sagebiel RW, Ferreira CM, Nosrati M, Miller JR III and Kashani-Sabet M: The role of microsatellites as a prognostic factor in primary malignant melanoma. Arch Dermatol 141: 739-742, 2005.
Piérard GE, Piérard-Franchimont C, Henry C and Lapière M: The proliferative activity of cells of malignant melanomas. Am J Dermatopathol 6: S317-S324, 1984.
Soyer HP: Ki67 immunostaining in melanocytic skin tumors. correlation with histologic parameters. J Cutan Pathol 18: 264-272, 1991.
Piérard-Franchimont C, Arrese JE, Nikkels AF, Al-Saleh W, Delvenne P and Piérard GE: Factor XIIa-positive dermal dendrocytes and proliferative activity of cutaneous cancers. Virchows Arch 429: 43-48, 1996.
Li LX, Crotty KA, Mccarthy SW, Palmer AA and Kril JJ: A zonal comparison of MIB1-Ki67 immunoreactivity in benign and malignant melanocytic lesions. Am J Dermatopathol 22: 489-495, 2000.
Bergman R, Malkin L, Sabo E and Kerner H: MIB-1 monoclonal antibody to determine proliferative activity of Ki67 antigen as an adjunct to histopathologic differential diagnosis of Spitz nevi. J Am Acad Dermatol 44: 500-504, 2001.
Vollmer RT: Use of bayes rule and MIB-1 proliferation index to discriminate spitz nevus from malignant melanoma. Am J Clin Pathol 122: 499-505, 2004.
Kapur P, Selim MA, Roy LC, Yegappan M, Weinberg AG and Hoang MP: Spitz nevi and atypical spitz nevi/tumors, a histologic and immunohistochemical analysis. Mod Pathol 18: 197-204, 2005.
Schattton T and Frank MH: Cancer stem cells and human malignant melanoma. Pigment Cell Melanoma Res 21: 39-55, 2008.
Bennett DC: How to make a melanoma: what do we know of the primary clonal events? Pigment Cell Melanoma Res 21: 27-38, 2008.
Quatresooz P, Piérard GE, Piérard-Franchimont C and the Mosan Study Group of Pigmented Tumors: Molecular pathways supporting the proliferation staging of malignant melanoma (Review). Int J Mol Med 24: 295-301, 2009.
Hussein MR, Haemel AK and Wood GS: Apoptosis and melanoma: molecular mechanisms. J Pathol 199: 275-288, 2003.
Piérard GE and Piérard-Franchimont C: Stochastic relationship between the growth fraction and vascularity of thin malignant melanomas. Eur J Cancer 33: 1888-1892, 1997.
Piérard-Franchimont C, Henry F, Heymans O and Piérard GE: Vascular retardation in dormant growth-stunted malignant melanomas. Int J Mol Med 4: 403-406, 1999.
Marcoval J, Moreno A, Graells J, et al: Angiogenesis and malignant melanoma: angiogenesis is related to the development of vertical (tumorigenic) growth phase. J Cutan Pathol 24: 212-218, 1997.
Heymans O, Blacher S, Brouers F and Piérard GE: Fractal quantification of the microvasculature heterogeneity in cutaneous melanoma. Dermatology 198: 212-217, 1999.
Diaz-Cascajo C, Borghi S and Weyers W: Angiomatoid spitz nevus, a distinct variant of desmoplastic spitz nevus with prominent vasculature. Am J Dermatopathol 22: 135-139, 2000.
Lorigan P, Eisen T and Hauschild A: Systemic therapy for metastatic malignant melanoma: from deeply disappointing to bright future? Exp Dermatol 17: 383-394, 2008.
Klein WM, Wu BP, Zhao S, Wu H, Klein-Szanto AJ and Tahan SR: Increased expression of stem cell markers in malignant melanoma. Mod Pathol 20: 102-107, 2007.
Schatton T, Murphy GF, Frank NY, Yamaura K, Waaga-Gasser AM, Gasser M, Zhan Q, Jordan S, Duncan LM, Weishaupt C, Fuhlbrigge RC, Kupper TS, Sayegh MH and Frank MH: Identification of cells initiating human melanomas. Nature 451: 345-349, 2008.