Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-5b777bbd6c-cp4x8 Total loading time: 0 Render date: 2025-06-18T20:54:24.784Z Has data issue: false hasContentIssue false

Chapter 7 - Melanocytic Neoplasms

Published online by Cambridge University Press:  17 June 2025

By
Mai P. Hoang
Edited by
Mai P. Hoang
Mai P. Hoang
Affiliation:
Harvard Medical School, Boston
Get access

Summary

In recent years there have been several new immunohistochemical markers made available for diagnosing melanocytic lesions. Immunostains can be helpful in the distinction of benign from atypical melanocytic proliferation and of melanocytic versus non-melanocytic lesions in the appropriate clinical context. The role of immunostains in the following diagnostic settings will be discussed in this chapter: melanoma in situ/ lentigo maligna versus pigmented actinic keratosis/ solar lentigo, nevoid melanoma versus melanocytic nevus, severely atypical compound melanocytic nevus versus invasive melanoma, benign versus atypical proliferative nodule arising in a congenital nevus, atypical Spitz tumor versus Spitzoid melanoma, nodal nevus versus metastatic melanoma, desmoplastic melanoma versus mimics, melanoma versus clear cell sarcoma, melanocytic versus histiocytic, sarcoma, or Merkel cell carcinoma.

Keywords

Melanocytic nevusmelanomaSpitz nevusatypical Spitz tumordesmoplastic melanoma
Type
Chapter
Information
Immunohistochemistry and Ancillary Studies in Diagnostic Dermatopathology , pp. 198 - 234
Publisher: Cambridge University Press
Print publication year: 2025

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Book purchase

Temporarily unavailable

References

Timar, J, Udvarhelyi, N, Banfalvi, T, Gilde, K, Orosz, Z. Accuracy of the determination of S100B protein expression in malignant melanoma using polyclonal or monoclonal antibodies. Histopathology 2004; 44: 180–4.CrossRefGoogle ScholarPubMed
Anstey, A, Cerio, R, Ramnarain, N, Orchard, G, Smith, N, Jones, EW. Desmoplastic malignant melanoma. an immunocytochemical study of 25 cases. Am J Dermatopathol 1994; 16: 14–22.CrossRefGoogle ScholarPubMed
Aung, PP, Sarlomo-Rikala, M, Lasota, J, Lai, JP, Wang, ZF, Miettinen, M. KBA62 and PNL2: 2 new melanoma markers-immunohistochemical analysis of 1563 tumors including metastatic, desmoplastic, and mucosal melanomas and their mimics. Am J Surg Pathol 2012; 36: 265–72.CrossRefGoogle ScholarPubMed
Busam, KJ, Iversen, K, Coplan, KC, Jungbluth, AA. Analysis of microphthalmia transcription factor expression in normal tissues and tumors, and comparison of its expression with S-100 protein, gp100, and tyrosinase in desmoplastic melanoma. Am J Surg Pathol 2001; 25: 197–204.CrossRefGoogle Scholar
Cohen-Knafo, E, al Saati, T, Aziza, J, et al. Production and characterization of an antimelanoma monoclonal antibody KBA.62 using a new melanoma cell line reactive on paraffin wax embedded sections. J Clin Pathol 1995; 48: 826–31.CrossRefGoogle ScholarPubMed
Ferenczi, K, Lastra, RR, Farkas, T, et al. MUM-1 expression differentiates tumors in the PEComa family from clear cell sarcoma and melanoma. Int J Surg Pathol 2012; 20: 29–36.CrossRefGoogle ScholarPubMed
Koch, MB, Shih, IM, Weiss, SW, Folpe, AL. Microphthalmia transcription factor and melnoma cell adhesion molecule expression distinguish desmoplastic/spindle cell melanoma from morphologic mimics. Am J Surg Pathol 2001; 25: 58–64.CrossRefGoogle Scholar
Mangini, J, Li, N, Bhawan, J. Immunohistochemical markers of melanocytic lesions: a review of their diagnostic usefulness. Am J Dermatopathol 2002; 24: 270–81.CrossRefGoogle ScholarPubMed
Miettinen, M, Fernandez, M, Franssila, K, Gatalica, Z, Lasota, J, Sarlomo-Rikala, M. Microphthalmia transcription factor in the immunohistochemical diagnosis of metastatic melanoma: comparison with four other melanoma markers. Am J Surg Pathol 2001; 25: 205–11.CrossRefGoogle ScholarPubMed
Nonaka, D, Chiriboga, L, Rubin, BP. Differential expression of S100 protein subtypes in malignant melanoma, and benign and malignant peripheral nerve sheath tumors. J Cutan Pathol 2008; 35: 1014–19.CrossRefGoogle ScholarPubMed
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 and malignant melanoma. Histochem J 2000; 32: 475–81.CrossRefGoogle Scholar
Pages, C, Rochaix, P, al Saati, T, et al. KBA.62: a useful marker for primary and metastatic melanomas. Hum Pathol 2008; 39: 1136–42.CrossRefGoogle ScholarPubMed
Plaza, JA, Suster, D, 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 2007; 15: 421–5.CrossRefGoogle ScholarPubMed
Rochaix, P, Lacroiz-Triki, M, Lamant, L, et al. PNL2, a new monoclonal antibody directed against a fixative-resistant melanocyte antigen. Mod Pathol 2003; 16: 481–90.CrossRefGoogle ScholarPubMed
Sundram, U, Harvell, JD, Rouse, RV, Natkunam, Y. Expression of the B-cell proliferation marker MUM1 by melanocytic lesions and comparison with S100, gp100 (HMB45), and MelanA. Mod Pathol 2003; 16: 802–10.CrossRefGoogle ScholarPubMed
Shih, IM, Nesbit, M, Herlyn, M, Kurman, RJ. A new Mel-CAM (CD146)-specific monoclonal antibody, MN-4, on paraffin-embedded tissue. Mod Pathol 1998; 11: 1098–106.Google ScholarPubMed
Shin, J, Vincent, JG, Cuda, JD, et al. Sox10 is expressed in primary melanocytic neoplasms of various histologies but not in fibrohistiocytic proliferations and histiocytoses. J Am Acad Dermatol 2012; 67: 717–26.CrossRefGoogle Scholar
Wick, MR, Swanson, PE, Rocamora, A. Recognition of malignant melanoma by monoclonal antibody HMB-45: an immunohistochemical study of 200 paraffin-embedded cutaneous tumors. J Cutan Pathol 1988; 15: 201–7.CrossRefGoogle ScholarPubMed
Zubovits, J, Buzney, E, Yu, L, Duncan, LM. HMB-45, S-100, NK1/C3, and MART-1 in metastatic melanoma. Hum Pathol 2004; 35: 217–23.CrossRefGoogle ScholarPubMed
Skelton 3rd, HG, Smith, KJ, Barrett, TL, Lupton, GP, Graham, JH. HMB-45 staining in benign and malignant melanocytic lesions: a reflection of cellular activation. Am J Dermatopathol 1991; 13: 543–50.Google ScholarPubMed
Romano, RC, Carter, JM, Folpe, AL. Aberrant intermediate filament and synaptophysin expression is a frequent event in malignant melanoma: an immunohistochemical study of 73 cases. Mod Pathol 2015; 28: 1033–42.CrossRefGoogle ScholarPubMed
Ben-Izhak, O, Stark, P, Levy, R, et al. Epithelial markers in malignant melanoma: a study of primary lesions and their metastases. Am J Dermatopathol 1994; 16: 241–6.CrossRefGoogle ScholarPubMed
Sanders, DS, Evans, AT, Allen, CA, et al. Classification of CEA-related positivity in primary and metastatic malignant melanoma. J Pathol 1994; 172: 343–8.CrossRefGoogle ScholarPubMed
Carlson, JA, Dickersin, GR, Sober, AJ, Barnhill, RL. Desmoplastic neurotrophic melanoma. Cancer 1995; 75: 478–94.Google Scholar
Bishop, PW, Menasce, LP, Yates, AJ, Win, NA, Banerjee, SS. An immunophenotypic survey of malignant melanomas. Histopathology 1993; 23: 159–66.CrossRefGoogle ScholarPubMed
Shah, IA, Gani, OS, Wheler, L. Comparative immunoreactivity of CD68 and HMB-45 in malignant melanoma, neural tumors and nevi. Pathol Res Pract 1997; 193: 497–502.CrossRefGoogle ScholarPubMed
Donato, R, Sorci, G, Riuzzi, F, et al. S100B’s double life: intracellular regulator and extracellular signal. Biochim Biophys Acta 2009; 1793: 1008–22.Google ScholarPubMed
Ohsie, SJ, Sarantopoulos, GP, Cochran, AJ, et al. Immunohistochemical characteristics of melanoma. J Cutan Pathol 2008; 35: 433–44.CrossRefGoogle ScholarPubMed
Thum, C, Hollowood, K, Birch, J, Goodlad, JR, Brenn, T. Aberrant Melan-A expression in atypical fibroxanthoma and undifferentiated pleomorphic sarcoma of the skin. J Cutan Pathol 2011; 38: 954–60.CrossRefGoogle ScholarPubMed
Miettinen, M, McCue, PA, Sariomo-Rikala, M, et al. Sox-10 – a marker for not only schwannian and melanocytic neoplasms but also myoepithelial cell tumors of soft tissue: a systematic analysis of 5134 tumors. Am J Surg Pathol 2015; 39: 826–35.CrossRefGoogle Scholar
Lee, ZH, Hou, L, Moellmann, G, et al. Characterization and subcellular localization of human Pmel 17/silver, a 110-kDa (pre)melanosomal membrane protein associated with 5,6-dihydroxyindole-2-carboxylic acid (DHICA) converting activity. J Invest Dermatol 1996; 106: 605–10.CrossRefGoogle ScholarPubMed
Nonaka, D, Chiriboga, L, Rubin, BP. Sox10: a pan-schwannian and melanocytic marker. Am J Surg Pathol 2008; 32: 1291–8.CrossRefGoogle ScholarPubMed
Busam, KJ, Kucukgol, D, Sato, E, Frosina, D, Teruya-Feldstein, J, Jungbluth, AA. Immunohistochemical analysis of novel monoclonal antibody PNL2 and comparison with other melanocyte differentiation markers. Am J Surg Pathol 2005; 29: 400–6.CrossRefGoogle ScholarPubMed
Banerjee, SS, Harris, M. Morphological and immunophenotypic variations in malignant melanoma. Histopathology 2000; 36: 387–402.CrossRefGoogle ScholarPubMed
Petitt, M, Allison, A, Shimoni, T, Uchida, T, Raimer, S, Kelly, B. Lymphatic invasion detected by D2-40/S100 dual immunohistochemistry does not predict sentinel lymph node status in melanoma. J Am Acad Dermatol 2009; 61: 819–28.CrossRefGoogle Scholar
Gerdes, J, Lemke, H, Baisch, H, Wacker, HH, Schwab, U, Stein, H. Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. J Immunol 1984; 133: 1710–15.CrossRefGoogle ScholarPubMed
Ikenberg, K, Pfaltz, M, Rakozy, C, Kempf, W. Immunohistochemical dual staining as an adjunct in assessment of mitotic activity in melanoma. J Cutan Pathol 2012; 39: 324–30.CrossRefGoogle Scholar
Saleem, A, Narala, S, Raghavan, SS. Immunohistochemistry in melanocytic lesions: updates with a practical review for pathologists. Semin Diagn Pathol 2022; 39: 239–247.CrossRefGoogle ScholarPubMed
Karamchandani, JR, Nielsen, TO, van de Rijn, M, West, RB. Sox10 and S100 in the diagnosis of soft-tissue neoplasms. Appl Immunohistochem Mol Morphol 2012; 20: 445–50.CrossRefGoogle ScholarPubMed
Siarov, J, Neittaanmäki, N, Mölne, J, Gillstedt, M, Paoli, J. Digital quantification of melanocytic density in resection margins of lentigo maligna using SOX10 versus hematoxylin-eosin staining. Am J Dermatopathol 2021; 43: 273–7.CrossRefGoogle ScholarPubMed
Behrens, EL, Boothe, W, D’Silva, N, Walterscheid, B, Watkins, P, Tarbox, M. SOX-10 staining in dermal scars. J Cutan Pathol 2019; 46: 579–85.CrossRefGoogle ScholarPubMed
Lezcano, C, Jungbluth, AA, Nehal, KS, Hollmann, TJ, Busam, KJ. PRAME expression in melanocytic tumors. Am J Surg Pathol 2018; 42: 1456–65.CrossRefGoogle ScholarPubMed
Chen, YP, Zhang, WW, Qiu, YT, Ke, LF, Chen, H, Chen, G. PRAME is a useful marker for the differential diagnosis of melanocytic tumours and histological mimics. Histopathology 2023; 82: 285–95.CrossRefGoogle ScholarPubMed
Kunc, M, Żemierowska, N, Skowronek, F, Biernat, W. Diagnostic test accuracy meta-analysis of PRAME in distinguishing primary cutaneous melanomas from benign melanocytic lesions. Histopathology 2023; 83: 3–14.CrossRefGoogle ScholarPubMed
Rothrock, AT, Torres-Cabala, CA, Milton, DR, et al. Diagnostic utility of PRAME expression by immunohistochemistry in subungual and non-subungual acral melanocytic lesions. J Cutan Pathol 2022; 49: 859–67.CrossRefGoogle ScholarPubMed
Hrycaj, SM, Szczepanski, JM, Zhao, L, et al. PRAME expression in spindle cell melanoma, malignant peripheral nerve sheath tumour, and other cutaneous sarcomatoid neoplasms: a comparative analysis. Histopathology 2022; 81: 818–25.CrossRefGoogle ScholarPubMed
Koh, SS, Lau, SK, Scapa, JV, Cassarino, DS. PRAME immunohistochemistry of spitzoid neoplasms. J Cutan Pathol 2022; 49: 709–16.CrossRefGoogle ScholarPubMed
Kline, N, Menge, TD, Hrycaj, SM, et al. PRAME expression in challenging dermal melanocytic neoplasms and soft tissue tumors with melanocytic differentiation. Am J Dermatopathol 2022; 44: 404–10.CrossRefGoogle ScholarPubMed
Scheurleer, WFJ, Braunius, WW, Tijink, BM, et al. PRAME staining in sinonasal mucosal melanoma: a single-center experience. Head Neck Pathol 2023; 17: 401–8.Google ScholarPubMed
Schmitt, TA, Lee, JC, Martinka, M, Ko, KYC. PRAME immunohistochemistry is useful in differentiating oral melanomas from nevi and melanotic macules. J Cutan Pathol 2023; 50: 275–8.CrossRefGoogle ScholarPubMed
Šekoranja, D, Hawlina, G, Pižem, J. PRAME expression in melanocytic lesions of the conjunctiva. Histopathology 2021; 79: 989–96.CrossRefGoogle ScholarPubMed
Hornick, JL, Plaza, JA, Mentzel, T, Gru, AA, Brenn, T. PRAME expression is a useful tool in the diagnosis of primary and metastatic dedifferentiated and undifferentiated melanoma. Am J Surg Pathol 2023; 47: 1390–7.CrossRefGoogle ScholarPubMed
Santandrea, G, Valli, R, Zanetti, E, Ragazzi, M, et al. Comparative analysis of PRAME expression in 127 acral and nail melanocytic lesions. Am J Surg Pathol 2022; 46: 579–90.CrossRefGoogle ScholarPubMed
Cammareri, C, Beltzung, F, Michal, M, et al. PRAME immunohistochemistry in soft tissue tumors and mimics: a study of 350 cases highlighting its imperfect specificity but potentially useful diagnostic applications. Virchows Arch 2023; 483: 145–56.CrossRefGoogle ScholarPubMed
Elsensohn, A, Hanson, J, Ferringer, T. Preferentially expressed antigen in melanoma expression in nonmelanoma skin cancers and melanocytes in surrounding skin. J Cutan Pathol 2021; 48: 1150–5.CrossRefGoogle ScholarPubMed
Kaczorowski, M, Chłopek, M, Kruczak, A, Ryś, J, Lasota, J, Miettinen, M. PRAME expression in cancer. A systematic immunohistochemical study of >5800 epithelial and nonepithelial tumors. Am J Surg Pathol 2022; 46: 1467–76.CrossRefGoogle Scholar
Cesinaro, AM, Piana, S, Paganelli, A, Pedroni, G, Santandrea, G, Maiorana, A. PRAME expression in cellular neurothekeoma: a study of 11 cases. J Cutan Pathol 2022; 49: 338–42.CrossRefGoogle ScholarPubMed
Hendi, A, Wada, DA, Jacobs, MA, et al. Melanocytes in nonlesional sun-exposed skin: a multicenter comparative study. J Am Acad Dermatol 2011; 65: 1186–93.CrossRefGoogle ScholarPubMed
Beltraminelli, H, Shabrawi-Caelen, LE, Kerl, H, Cerroni, L. Melan-a-positive “pseudomelanocytic nests”: a pitfall in the histopathologic and immunohistochemical diagnosis of pigmented lesions on sun-damages skin. Am J Dermatopathol 2009; 31: 305–8.CrossRefGoogle Scholar
Yan, S, Brennick, JB. False-positive rate of the immunoperoxidase stains for MART1/MelanA in lymph nodes. Am J Surg Pathol 2004; 28: 596–600.CrossRefGoogle ScholarPubMed
Buonaccorsi, JN, Prieto, VG, Torres-Cabala, C, Suster, S, Plaza, JA. Diagnostic utility and comparative immunohistochemical analysis of MiTF and Sox10 to distinguish melanoma in situ and actinic keratosis: a clinicopathological and immunohistochemical study of 70 cases. Am J Dermatopathol 2014; 36: 124–30.CrossRefGoogle ScholarPubMed
Gradecki, SE, Valdes-Rodriguez, R, Wick, MR, Gru, AA. PRAME immunohistochemistry as an adjunct for diagnosis and histological margin assessment in lentigo maligna. Histopathology 2021; 78: 1000–8.CrossRefGoogle Scholar
Roy, SF, Panse, G, McNiff, JM. PRAME immunohistochemistry can distinguish melanocytic pseudonests of lichenoid reactions from melanoma in situ. J Cutan Pathol 2023; 50: 450–4.CrossRefGoogle ScholarPubMed
Ramos-Herberth, FI, Karamchandani, J, Kim, J, Dadras, SS. Sox10 immunostaining distinguishes desmoplastic melanoma from excision scar. J Cutan Pathol 2010; 37: 944–52.CrossRefGoogle ScholarPubMed
Harvell, JD, Bastian, BC, LeBoit, PE. Persistent (recurrent) Spitz nevi: a histopathologic, immunohistochemical, and molecular pathologic study of 22 cases. Am J Surg Pathol 2002; 26: 654–61.CrossRefGoogle Scholar
Wood, WS, Tron, VA. Analysis of HMB-45 immunoreactivity in common and cellular blue nevi. J Cutan Pathol 1991; 18: 261–3.CrossRefGoogle ScholarPubMed
Prieto, VG, Shea, CR. Use of immunohistochemistry in melanocytic lesions. J Cutan Pathol 2008; 35: 1–10.CrossRefGoogle ScholarPubMed
Cosgarea, I, Griewank, KG, Ungureanu, L, Tamayo, A, Siepmann, T. Deep penetrating nevus and borderline-deep penetrating nevus: a literature review. Front Oncol 2020; 10: 837. doi: 10.3389/fonc.2020.00837.CrossRefGoogle ScholarPubMed
World Health Organization. Elder, DE, Massi, D, Scoyler, RA, Williemze, R, eds. WHO Classification of Skin Tumors. 4th ed. Lyon, France: IARC, 2018.Google Scholar
Yeh, I, Lang, UE, Durieux, E, et al. Combined activation of MAP kinase pathway and β-catenin signaling cause deep penetrating nevi. Nat Commun 2017; 8: 644. doi: 10.1038/s41467-017-00758-3.CrossRefGoogle ScholarPubMed
Vanderbeck, K, Rothrock, AT, Cho, WC, et al. PRAME and LEF1 in combined deep penetrating nevus and combined blue nevus: utility and pitfalls. Am J Dermatopathol 2023; 45: 549–56.CrossRefGoogle ScholarPubMed
Magro, CM, Abraham, RM, Guo, R, et al. Deep penetrating nevus-like borderline tumors: a unique subset of ambiguous melanocytic tumors with malignant potential and normal cytogenetics. Eur J Dermatol 2014; 24: 594–602.Google ScholarPubMed
Ebbelaar, CF, Schrader, AMR, van Dijk, M, et al. MOLecular Evaluation of Melanocytic Ambiguous Tumors (MOLEMAT) investigators: towards diagnostic criteria for malignant deep penetrating melanocytic tumors using single nucleotide polymorphism array and next-generation sequencing. Mod Pathol 2022; 35: 1110–20.CrossRefGoogle ScholarPubMed
Raghavan, SS, Saleem, A, Wang, JY, Rieger, KE, Brown, RA, Novoa, RA. Diagnostic utility of LEF1 immunohistochemistry in differentiating deep penetrating nevi from histologic mimics. Am J Surg Pathol 2020; 44: 1413–18.CrossRefGoogle ScholarPubMed
de la Fouchardière, A, Caillot, C, Jacquemus, J, et al. β-Catenin nuclear expression discriminates deep penetrating nevi from other cutaneous melanocytic tumors. Virchows Arch 2019; 474: 539–50.CrossRefGoogle ScholarPubMed
Zembowicz, A, Carney, JA, 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 2004; 28: 31–40.CrossRefGoogle ScholarPubMed
Cohen, JN, Joseph, NM, North, JP, Onodera, C, Zembowicz, A, LeBoit, PE. Genomic analysis of pigmented epithelioid melanocytomas reveals recurrent alterations in PRKAR1A, and PRKCA genes. Am J Surg Pathol 2017; 41: 1333–46.CrossRefGoogle ScholarPubMed
de la Fouchardiere, A, Tirode, F, Castillo, C, et al. Attempting to solve the pigmented epithelioid melanocytoma (PEM) conundrum: PRKAR1A inactivation can occur in different genetic backgrounds (common, blue, and Spitz subgroups) with variation in their clinicopathologic characteristics. Am J Surg Pathol 2022; 46: 1106–15.CrossRefGoogle ScholarPubMed
Isales, MC, Mohan, LS, Quan, VL, et al. Distinct genomic patterns in pigmented epithelioid melanocytoma: a molecular and histologic analysis of 16 cases. Am J Surg Pathol 2019; 43: 480–8.CrossRefGoogle ScholarPubMed
Zembowicz, A, Knoepp, SM, Bei, T, et al. Loss of expression of protein kinase a regulatory subunit 1alpha in pigmented epithelioid melanocytoma but not in melanoma or other melanocytic lesions. Am J Surg Pathol 2007; 31: 1764–75.CrossRefGoogle ScholarPubMed
Goto, K, Pissaloux, D, Paindavoine, S, Tirode, F, de la Fouchardière, A. CYSLTR2-mutant cutaneous melanocytic neoplasms frequently simulate “pigmented epithelioid melanocytoma,” expanding the morphologic spectrum of blue tumors: a clinicopathologic study of 7 cases. Am J Surg Pathol 2019; 43: 1368–76.CrossRefGoogle ScholarPubMed
Williams, EA, Shah, N, Danziger, N, et al. Clinical, histopathologic, and molecular profiles of PRKAR1A-inactivated melanocytic neoplasms. J Am Acad Dermatol 2021; 84: 1069–71.CrossRefGoogle ScholarPubMed
Wiesner, T, Obenauf, AC, Murali, R, et al. Germline mutations in BAP1 predispose to melanocytic tumors. Nat Genet 2011; 43: 1018–21.CrossRefGoogle ScholarPubMed
Aung, PP, Nagarajan, P, Tetzlaff, MT, et al. Melanoma with loss of BAP1 expression in patients with no family history of BAP1-associated cancer susceptibility syndrome: a case series. Am J Dermatopathol 2019; 41: 167–79.CrossRefGoogle ScholarPubMed
Piris, A, Mihm, MC Jr, Hoang, MP. BAP1 and BRAFV600E expression in benign and malignant melanocytic proliferations. Hum Pathol 2015; 46: 239–45.CrossRefGoogle ScholarPubMed
Donati, M, Martinek, P, Steiner, P, et al. Novel insights into the BAP1-inactivated melanocytic tumor. Mod Pathol 2022; 35: 664–75.CrossRefGoogle ScholarPubMed
Garfield, EM, Walton, KE, Quan, VL, et al. Histomorphologic spectrum of germline-related and sporadic BAP1-inactivated melanocytic tumors. J Am Acad Dermatol 2018; 79: 525–34.CrossRefGoogle ScholarPubMed
Gammon, B, Traczyk, TN, Gerami, P. Clumped perinuclear BAP1 expression is a frequent finding in sporadic epithelioid Spitz tumors. J Cutan Pathol 2013; 40: 538–42.CrossRefGoogle ScholarPubMed
de la Fourchardière, A, Pissaloux, D, Tirode, F, Hanna, J. Clear cell tumor with melanocytic differentiation and MITF-CREM translocation: a novel entity similar to clear cell sarcoma. Virchows Arch 2021; 479: 841–6.Google Scholar
Zucman, J, Delattre, O, Desmaze, C, et al. EWS and ATF-1 gene fusion induced by t(12;22) translocation in malignant melanoma of soft parts. Nat Genet 1993; 4: 341–5.CrossRefGoogle Scholar
Hanna, J, Ko, JS, Billings, SD, Boivin, F, et al. Cutaneous melanocytic tumor with CRTC1::TRIM11 translocation: an emerging entity analyzed in a series of 41 Cases. Am J Surg Pathol 2022; 46: 1457–66.CrossRefGoogle Scholar
Argani, P, Aulmann, S, Illei, PB, et al. A distinctive subset of PEComas harbors TFE3 gene fusions. Am J Surg Pathol 2010; 34: 1395–406.CrossRefGoogle ScholarPubMed
Yang, L, Yin, Z, Wei, J, et al. Cutaneous melanocytic tumour with CRTC1::TRIM11 fusion in a case with recurrent local lymph node and distant pulmonary metastases at early stage: aggressive rather than indolent? Histopathology 2023; 82: 368–71.CrossRefGoogle Scholar
Kapur, P, Selim, MA, Roy, LC, Yegappan, M, Weinberg, AG, Hoang, MP. Spitz nevi and atypical Spitz nevi/tumors: a histologic and immunohistochemical analysis. Mod Pathol 2005; 18: 197–204.CrossRefGoogle ScholarPubMed
Nasr, MR, El-Zammar, O. Comparison of PHH3, Ki-67, and survivin immunoreactivity in benign and malignant melanocytic lesions. Am J Dermatopathol 2008; 30: 117–22.CrossRefGoogle ScholarPubMed
Phadke, PA, Rakheja, D, Le, LP, et al. Proliferative nodules arising within congenital melanocytic nevi: a histologic, immunohistochemical, and molecular analyses of 43 cases. Am J Surg Pathol 2011; 35: 656–69.CrossRefGoogle ScholarPubMed
Herron, MD, Vanderhooft, SL, Smock, K, Zhou, H, Leachman, SA, Coffin, C. Proliferative nodules in congenital melanocytic nevi: a clinicopathologic and immunohistochemical analysis. Am J Surg Pathol 2004; 28: 1017–25.CrossRefGoogle ScholarPubMed
Hung, T, Piris, A, Lobo, A, et al. Sentinel lymph node metastasis is not predictive of poor outcome in patients with problematic spitzoid melanocytic tumors. Hum Pathol 2013; 44: 87–94.CrossRefGoogle Scholar
Quan, VL, Zhang, B, Zhang, Y, et al. Integrating next generation sequencing with morphology improves prognostic and biologic classification of Spitz neoplasms. J Invest Dermatol 2020; 140: 1599–608.CrossRefGoogle ScholarPubMed
Bastian, BC, LeBoit, PE, Pinkel, D. Mutations and copy number increase of HRAS in Spitz nevi with distinctive histopathological features. Am J Pathol 2000; 157: 967–72.CrossRefGoogle ScholarPubMed
Wiesner, T, Kutzner, H, Cerroni, L, Mihm, MC Jr, Busam, KJ, Murali, R. Genomic aberrations in Spitzoid melanocytic tumors and their implications for diagnosis, prognosis and therapy. Pathology 2016; 48: 113–31.CrossRefGoogle ScholarPubMed
Amin, SM, Haugh, AM, Lee, CY, et al. A comparison of morphologic and molecular features of BRAF, ALK, and NTRK1 fusion Spitzoid neoplasms. Am J Surg Pathol 2017; 41: 491–8.CrossRefGoogle ScholarPubMed
Hagstrom, M, Fumero-Velázquez, M, Dhillon, S, Olivares, S, Gerami, P. An update on genomic aberrations in Spitz naevi and tumours. Pathology 2023; 55: 196–205.CrossRefGoogle ScholarPubMed
Gerami, P, Kim, D, Compres, EV, et al. Clinical, morphologic, and genomic findings in ROS1 fusion Spitz neoplasms. Mod Pathol 2021; 34: 348–57.CrossRefGoogle ScholarPubMed
Yeh, I, Busam, KJ, McCalmont, TH, et al. Filigree-like rete ridges, lobulated nests, rosette-like structures, and exaggerated maturation characterize Spitz tumors with NTRK1 fusion. Am J Surg Pathol 2019; 43: 737–46.CrossRefGoogle ScholarPubMed
Mansour, B, Vanecek, T, Kastnerova, L, Nosek, D, Kazakov, DV, Donati, M. Spitz tumor With SQSTM1::NTRK2 fusion: a clinicopathological study of 5 cases. Am J Dermatopathol 2023; 45: 306–10.CrossRefGoogle Scholar
de la Fouchardière, A, Tee, MK, Peternel, S, et al. Fusion partners of NTRK3 affect subcellular localization of the fusion kinase and cytomorphology of melanocytes. Mod Pathol 2021; 34: 735–47.CrossRefGoogle ScholarPubMed
Hechtman, JF, Benayed, R, Hyman, DM, et al. Pan-Trk immunohistochemistry Is an efficient and reliable screen for the detection of NTRK fusions. Am J Surg Pathol 2017; 41: 1547–51.CrossRefGoogle Scholar
Roy, SF, Milante, R, Pissaloux, D, et al. Spectrum of melanocytic tumors harboring BRAF gene fusions: 58 cases with histomorphologic and genetic correlations. Mod Pathol 2023; 36: 100149. doi: 10.1016/j.modpat.2023.100149.CrossRefGoogle ScholarPubMed
Houlier, A, Pissaloux, D, Masse, I, et al. Melanocytic tumors with MAP3K8 fusions: report of 33 cases with morphological-genetic correlations. Mod Pathol 2020; 33: 846–57.CrossRefGoogle ScholarPubMed
Yeh, I, Botton, T, Talevich, E, et al. Activating MET kinase rearrangements in melanoma and Spitz tumours. Nat Commun 2015; 6: 7174. https://doi.org/10.1038/ncomms8174CrossRefGoogle ScholarPubMed
Williams, EA, Shah, N, Montesion, M, et al. Melanomas with activating RAF1 fusions: clinical, histopathologic, and molecular profiles. Mod Pathol 2020; 33: 1466–74.CrossRefGoogle ScholarPubMed
Donati, M, Nosek, D, Olivares, S, et al. Spitz tumor with RAF1 fusion: A report of 3 cases. Ann Diagn Pathol 2023; 67: 152215. doi: 10.1016/j.anndiagpath.2023.152215.CrossRefGoogle ScholarPubMed
Kim, D, Compres, EV, Zhang, B, et al. A series of RET fusion Spitz neoplasms with plaque-like silhouette and dyscohesive nesting of epithelioid melanocytes. Am J Dermatopathol 2021; 43: 243–51.CrossRefGoogle ScholarPubMed
Sunshine, JC, Kim, D, Zhang, B, et al. Melanocytic neoplasms with MAP2K1 in frame deletions and Spitz morphology. Am J Dermatopathol 2020; 42: 923–31.CrossRefGoogle ScholarPubMed
Ludgate, MW, Fullen, DR, Lee, J, et al. The atypical Spitz tumor of uncertain biologic potential: a series of 67 patients from a single institution. Cancer 2009; 115: 631–41.CrossRefGoogle ScholarPubMed
Massi, D, Tomasini, C, Senetta, R, et al. Atypical Spitz tumors in patients younger than 18 years. J Am Acad Dermatol 2015; 72: 37–46.CrossRefGoogle ScholarPubMed
Vollmer, RT. Use of Bayes rule and MIB-1 proliferation index to discriminate Spitz nevus from malignant melanoma. Am J Clin Pathol 2004; 122: 499–505.CrossRefGoogle ScholarPubMed
George, E, Polissar, NL, Wick, M. Immunohistochemical evaluation of p16INK4A, E-cadherin, and cyclin D1 expression in melanoma and Spitz tumors. Am J Clin Pathol 2010; 133: 370–9.CrossRefGoogle ScholarPubMed
Gerami, P, Scolyer, RA, Xu, X, et al. Risk assessment for atypical spitzoid melanocytic neoplasms using FISH to identify chromosomal copy number aberrations. Am J Surg Pathol 2013; 37: 676–84.CrossRefGoogle Scholar
Yazdan, P, Cooper, C, Sholl, LM, et al. Comparative analysis of atypical Spitz tumors with heterozygous versus homozygous 9p21 deletions for clinical outcomes, histomorphology, BRAF mutation, and p16 expression. Am J Surg Pathol 2014; 38: 638–45.CrossRefGoogle ScholarPubMed
Shen, L, Cooper, C, Bajaj, S, et al. Atypical spitz tumors with 6q23 deletions: a clinical, histological, and molecular study. Am J Dermatopathol 2013; 35: 804–12.CrossRefGoogle ScholarPubMed
Cooper, C, Arva, NC, Lee, C, et al. A clinical, histopathologic, and outcome study of melanonychia striata in childhood. J Am Acad Dermatol 2015; 72: 773–9.CrossRefGoogle ScholarPubMed
Tan, KB, Moncrieff, M, Thompson, JF, et al. Subungual melanoma: a study of 124 cases highlighting features of early lesions, potential pitfalls in diagnosis, and guidelines for histologic reporting. Am J Surg Pathol 2007; 31: 1902–12.CrossRefGoogle ScholarPubMed
Theunis, A, Richert, B, Sass, U, Lateur, N, Sales, F, Andre, J. Immunohistochemical study of 40 cases of longitudinal melanonychia. Am J Dermatopathol 2011; 33: 27–34.CrossRefGoogle ScholarPubMed
Ridolfi, RL, Rosen, PP, Thaler, H. Nevus cell aggregates associated with lymph nodes: estimated frequency and clinical significance. Cancer 1977; 39: 164–71.3.0.CO;2-T>CrossRefGoogle ScholarPubMed
Carson, KF, Wen, DR, Li, PX, et al. Nodal nevi and cutaneous melanoma. Am J Surg Pathol 1996; 20: 834–40.CrossRefGoogle Scholar
Biddle, DA, Evans, HL, Kemp, BL, et al. Intraparenchymal nevus cell aggregates in lymph nodes: a possible diagnostic pitfall with malignant melanoma and carcinoma. Am J Surg Pathol 2003; 27: 673–81.CrossRefGoogle ScholarPubMed
Holt, JB, Sangueza, OP, Levine, EA, et al. Nodal melanocytic nevi in sentinel lymph nodes: correlation with melanoma-associated cutaneous nevi. Am J Clin Pathol 2004; 121: 58–63.CrossRefGoogle ScholarPubMed
Mihic-Probst, D, Saremaslani, P, Komminoth, P, Heitz, PU. Immunostaining for the tumour suppressor gene p16 product is a useful marker to differentiate melanoma metastasis from lymph-node nevus. Virchows Arch 2003; 443: 745–51.CrossRefGoogle ScholarPubMed
See, SHC, Finkelman, BS, Yeldandi, AV. The diagnostic utility of PRAME and p16 in distinguishing nodal nevi from nodal metastatic melanoma. Pathol Res Pract 2020; 216: 153105. doi: 10.1016/j.prp.2020.153105.CrossRefGoogle ScholarPubMed
Mentrikoshi, MJ, Ma, L, Pryor, JG, et al. Diagnostic utility of IMP3 in segregating metastatic melanoma from benign nevi in lymph nodes. Mod Pathol 2009; 22: 1582–7.Google Scholar
Lee, JJ, Granter, SR, Laga, AC, et al. 5-hydroxymethylcytosine expression in metastatic melanoma versus nodal nevus in sentinel lymph node biopsies. Mod Pathol 2015; 28: 218–29.CrossRefGoogle ScholarPubMed
Kucher, C, Zhang, PJ, Pasha, T, et al. Expression of Melan-A and Ki-67 in desmoplastic melanoma and desmoplastic nevi. Am J Dermatopathol 2004; 26: 452–7.CrossRefGoogle ScholarPubMed
Lazova, R, Tantcheva-Poor, I, Sigal, AC. P75 nerve growth factor receptor staining is superior to S100 in identifying spingle cell and desmoplastic melanoma. J Am Acad Dermatol 2010; 63: 852–8.CrossRefGoogle Scholar
Chorny, JA, Barr, RJ. S100-positive spindle cells in scars: a diagnostic pitfall in the re-excision of desmoplastic melanoma. Am J Dermatopathol 2002; 24: 309–12.CrossRefGoogle ScholarPubMed
Bianchi, G, Charoenlap, C, Cocchi, S, et al. Clear cell sarcoma of soft tissue: a retrospective review and analysis of 31 cases treated at Istituto Ortopedico Rizzoli. Eur J Surg Oncol 2014; 40: 505–10.CrossRefGoogle ScholarPubMed
Hisaoka, M, Ishida, T, Kuo, TT, et al. Clear cell sarcoma of soft tissue: a clinicopathologic, immunohistochemical, and molecular analysis of 33 cases. Am J Surg Pathol 2008; 32: 452–60.CrossRefGoogle ScholarPubMed
Granter, SR, Weilbaecher, KN, Quigley, C, Fletcher, CD, Fisher, DE. Clear cell sarcoma shows immunoreactivity for microphthalmia transcription factor: further evidence for melanocytic differentiation. Mod Pathol 2001; 14: 6–9.CrossRefGoogle ScholarPubMed
Aung, PP, Sarlomo-Rikala, M, Lasota, J, Lai, JP, Wang, ZF, Miettinen, M. KBA62 and PNL2: 2 new melanoma markers- immunohistochemical analysis of 1563 tumors including metastatic, desmoplastic, and mucosal melanomas and their mimics. Am J Surg Pathol 2012; 36: 265–72.CrossRefGoogle ScholarPubMed
Karamchandani, JR, Nielsen, TO, van de Rijn, M, West, RB. Sox10 and S100 in the diagnosis of soft-tissue neoplasms. Appl Immunohistochem Mol Morphol 2012; 20: 445–50.CrossRefGoogle ScholarPubMed
Wang, WL, Mayordomo, E, Zhang, W, et al. Detection and characterization of EWSR1/ATF1 and EWSR1/CREB1 chimeric transcripts in clear cell sarcoma (melanoma of soft parts). Mod Pathol 2009; 22: 1201–9.CrossRefGoogle ScholarPubMed
Yang, L, Chen, Y, Cui, T, et al. Identification of biomarkers to distinguish clear cell sarcoma from malignant melanoma. Hum Pathol 2012; 43: 1463–70.CrossRefGoogle ScholarPubMed
Charli-Joseph, Y, Saggini, A, Vemula, S, Weier, J, Mirza, S, LeBoit, PE. Primary cutaneous perivascular epithelioid cell tumor: a clinicopathological and molecular reappraisal. J Am Acad Dermatol 2014; 71: 1127–36.CrossRefGoogle ScholarPubMed
Llamas-Velasco, M, Mentzel, T, Requena, L, Palmedo, G, Kasten, R, Kutzner, H. Cutaneous PEComa does not harbour TFE3 gene fusions: immunohistochemical and molecular study of 17 cases. Histopathology 2013; 63: 122–9.CrossRefGoogle Scholar
Mentzel, T, Reisshauer, S, Rutten, A, Hantschke, M, Soares de Almeida, LM, Kutzner, H. Cutaneous clear cell myomelanocytic tumour: a new member of the growing family of perivascular peithelioid cell tumours (PEComas). Clinicopathological and immunohistochemical analysis of seven cases. Histopathology 2005; 46: 498–504.CrossRefGoogle ScholarPubMed
Greveling, K, Winnepennickx, VJ, Nagtzaam, IF, et al. Malignant perivascular epithelioid tumor: a case report of a cutaneous tumor on the cheek of a male patient. J Am Acad Dermatol 2013; 69: e262-4.CrossRefGoogle ScholarPubMed
Calder, KB, Schlauder, S, Morgan, MB. Malignant perivascular epithelioid cell tumor (“PEComa”): a case report and literature review of cutaneous/subcutaneous presentations. J Cutan Pathol 2008; 35: 499–503.CrossRefGoogle ScholarPubMed
Martignoni, G, Gobbo, S, Camparo, P, et al. Differential expression of cathepsin K in neoplasms harboring TFE3 gene fusions. Mod Pathol 2011; 24: 1313–19.CrossRefGoogle ScholarPubMed
Fernandez-Flores, A, Nguyen, CM, Cassarino, DS. Cutaneous PEComas express CD10: implications for the classification of PEComas and the differential diagnosis with metastatic renal cell carcinoma. Am J Dermatopathol 2016; 38: 645–52.CrossRefGoogle ScholarPubMed
Tallon, B, Beer, TW. MiTF positivity in atypical fibroxanthoma: a diagnostic pitfall. Am J Dermatopathol 2014; 36: 888–91.CrossRefGoogle ScholarPubMed
Suarez-Vilela, D, Izquierdo, FM, Escobar-Stein, J, Mendez-Alvarez, JR. Atypical fibroxanthoma with T-cytotoxic inflammatory infiltrate and aberrant expression of cytokeratin. J Cutan Pathol 2011; 38: 930–2.CrossRefGoogle ScholarPubMed
Uquen, A, Sassolas, B, Mondine, P, et al. NRASQ61 R and BRAFV600E mutation-specific immunohistochemistry is a helpful tool to diagnose metastatic undifferentiated/dedifferentiated melanomas. Am J Surg Pathol 2016; 40: 1004–5.Google Scholar
Saleh, JS, Whittington, CP, Bresler, SC, Patel, RM. Mesenchymal tumours with melanocytic expression: a potential pitfall in the differential diagnosis of malignant melanoma. Pathology 2023; 55: 258–68.CrossRefGoogle ScholarPubMed
Henderson, SA, Torres-Cabala, CA, Curry, JL, et al. p40 is more specific than p63 for the distinction of atypical fibroxanthoma from other cutaneous spindle cell malignancies. Am J Surg Pathol 2014; 38: 1102–10.CrossRefGoogle ScholarPubMed
Kao, GF, Helwig, EB, Graham, JH. Balloon cell malignant melanoma of the skin. A clinicopathologic study of 34 cases with histochemical, immunohistochemical, and ultrastructural observations. Cancer 1992; 69: 2942–52.3.0.CO;2-0>CrossRefGoogle ScholarPubMed
Plaza, JA, Torres-Cabala, C Evans, H, Diwan, HA, Suster, S, Prieto, VG. Cutaneous metastases of malignant melanoma: a clinicopathologic study of 192 cases with emphasis on the morphologic spectrum. Am J Dermatopathol 2010; 32: 129–36.CrossRefGoogle ScholarPubMed

Save book to Kindle

To save this book to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

  • Melanocytic Neoplasms
  • Edited by Mai P. Hoang, Harvard Medical School, Boston
  • Book: Immunohistochemistry and Ancillary Studies in Diagnostic Dermatopathology
  • Online publication: 17 June 2025
  • Chapter DOI: https://doi.org/10.1017/9781009549240.008
Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

  • Melanocytic Neoplasms
  • Edited by Mai P. Hoang, Harvard Medical School, Boston
  • Book: Immunohistochemistry and Ancillary Studies in Diagnostic Dermatopathology
  • Online publication: 17 June 2025
  • Chapter DOI: https://doi.org/10.1017/9781009549240.008
Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

  • Melanocytic Neoplasms
  • Edited by Mai P. Hoang, Harvard Medical School, Boston
  • Book: Immunohistochemistry and Ancillary Studies in Diagnostic Dermatopathology
  • Online publication: 17 June 2025
  • Chapter DOI: https://doi.org/10.1017/9781009549240.008
Available formats
×