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Applications of Additional Techniques to Melanocytic Pathology

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Pathology of Challenging Melanocytic Neoplasms

Abstract

Within the last 10 years, it has become evident that the traditional histologic classification of melanoma based upon cellular and architectural phenotypes (e.g., acral, superficial spreading, lentigo maligna) correlates with distinct, recurring genetic alterations. Thus, lentigo maligna, typically located in areas of chronic sun exposure, shows genetic abnormalities distinct from those seen in superficial spreading melanomas, which commonly occur on the trunk, and thus have a lesser degree of sun exposure. Molecular techniques such as fluorescent in situ hybridization (FISH), comparative genomic hybridization (CGH), and DNA sequencing methodologies can detect such differences. As an example, CGH indicates that more than 95 % of melanomas show chromosomal copy number aberrations and as many as 80 % of cutaneous melanomas have mutations in BRAF, NRAS, or KIT. This chapter will review the common mutations and the role of these techniques in the diagnosis, prognosis, and treatment of cutaneous melanoma.

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References

  1. Prickett TD, Wei X, Cardenas-Navia I, et al. Exon capture analysis of G protein-coupled receptors identifies activating mutations in GRM3 in melanoma. Nat Genet. 2011;43(11):1119–26.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  2. Davies H, Bignell GR, Cox C, et al. Mutations of the BRAF gene in human cancer. Nature. 2002;417(6892):949–54.

    Article  CAS  PubMed  Google Scholar 

  3. Pollock PM, Harper UL, Hansen KS, et al. High frequency of BRAF mutations in nevi. Nat Genet. 2003;33(1):19–20.

    Article  CAS  PubMed  Google Scholar 

  4. Hocker T, Tsao H. Ultraviolet radiation and melanoma: a systematic review and analysis of reported sequence variants. Hum Mutat. 2007;28(6):578–88.

    Article  CAS  PubMed  Google Scholar 

  5. Beadling C, Jacobson-Dunlop E, Hodi FS, et al. KIT gene mutations and copy number in melanoma subtypes. Clin Cancer Res. 2008;14(21):6821–8.

    Article  CAS  PubMed  Google Scholar 

  6. Curtin JA, Fridlyand J, Kageshita T, et al. Distinct sets of genetic alterations in melanoma. N Engl J Med. 2005;353(20):2135–47.

    Article  CAS  PubMed  Google Scholar 

  7. Lee JH, Choi JW, Kim YS. Frequencies of BRAF and NRAS mutations are different in histological types and sites of origin of cutaneous melanoma: a meta-analysis. Br J Dermatol. 2011;164(4):776–84.

    Article  CAS  PubMed  Google Scholar 

  8. Goel VK, Lazar AJ, Warneke CL, Redston MS, Haluska FG. Examination of mutations in BRAF, NRAS, and PTEN in primary cutaneous melanoma. J Invest Dermatol. 2006;126(1):154–60.

    Article  CAS  PubMed  Google Scholar 

  9. 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(3):967–72.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Da Forno PD, Pringle JH, Fletcher A, et al. BRAF, NRAS and HRAS mutations in spitzoid tumours and their possible pathogenetic significance. Br J Dermatol. 2009;161(2):364–72.

    Article  PubMed  Google Scholar 

  11. van Dijk MC, Bernsen MR, Ruiter DJ. Analysis of mutations in B-RAF, N-RAS, and H-RAS genes in the differential diagnosis of Spitz nevus and spitzoid melanoma. Am J Surg Pathol. 2005;29(9):1145–51.

    Article  PubMed  Google Scholar 

  12. Ellerhorst JA, Greene VR, Ekmekcioglu S, et al. Clinical correlates of NRAS and BRAF mutations in primary human melanoma. Clin Cancer Res. 2011;17(2):229–35.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Jakob JA, Bassett RL, Ng CS, Lazar AF, Joseph RW, Alvarado GC, Rohlfs ML, Richard J, Curry JL, Gershenwald JE, Hwu P, Kim KB, Davies MA. NRAS mutation status is an independent prognostic factor in metastatic melanoma. Cancer. 2012;118(16):4014–23.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Curtin JA, Busam K, Pinkel D, Bastian BC. Somatic activation of KIT in distinct subtypes of melanoma. J Clin Oncol. 2006;24(26):4340–6.

    Article  CAS  PubMed  Google Scholar 

  15. Torres-Cabala CA, Wang WL, Trent J, et al. Correlation between KIT expression and KIT mutation in melanoma: a study of 173 cases with emphasis on the acral-lentiginous/mucosal type. Mod Pathol. 2009;22(11):1446–56.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Hornick JL, Fletcher CD. The role of KIT in the management of patients with gastrointestinal stromal tumors. Hum Pathol. 2007;38(5):679–87.

    Article  CAS  PubMed  Google Scholar 

  17. Corless CL, Heinrich MC. Molecular pathobiology of gastrointestinal stromal sarcomas. Annu Rev Pathol. 2008;3:557–86.

    Article  CAS  PubMed  Google Scholar 

  18. Van Raamsdonk CD, Bezrookove V, Green G, et al. Frequent somatic mutations of GNAQ in uveal melanoma and blue naevi. Nature. 2009;457(7229):599–602.

    Article  PubMed Central  PubMed  Google Scholar 

  19. Haluska FG, Housman DE. Recent advances in the molecular genetics of malignant melanoma. Cancer Surv. 1995;25:277–92.

    CAS  PubMed  Google Scholar 

  20. Czajkowski R, Placek W, Drewa G, Czajkowska A, Uchanska G. FAMMM syndrome: pathogenesis and management. Dermatol Surg. 2004;30(2 Pt 2):291–6.

    PubMed  Google Scholar 

  21. Piepkorn M. Melanoma genetics: an update with focus on the CDKN2A(p16)/ARF tumor suppressors. J Am Acad Dermatol. 2000;42(5 Pt 1):705–22. quiz 723–706.

    Article  CAS  PubMed  Google Scholar 

  22. Ranade K, Hussussian CJ, Sikorski RS, et al. Mutations associated with familial melanoma impair p16INK4 function. Nat Genet. 1995;10(1):114–6.

    Article  CAS  PubMed  Google Scholar 

  23. Bastian BC, LeBoit PE, Hamm H, Brocker EB, Pinkel D. Chromosomal gains and losses in primary cutaneous melanomas detected by comparative genomic hybridization. Cancer Res. 1998;58(10):2170–5.

    CAS  PubMed  Google Scholar 

  24. Bastian BC, Olshen AB, LeBoit PE, Pinkel D. Classifying melanocytic tumors based on DNA copy number changes. Am J Pathol. 2003;163(5):1765–70.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Gerami P, Jewell SS, Morrison LE, et al. Fluorescence in situ hybridization (FISH) as an ancillary diagnostic tool in the diagnosis of melanoma. Am J Surg Pathol. 2009;33(8):1146–56.

    Article  PubMed  Google Scholar 

  26. Gaiser T, Kutzner H, Palmedo G, et al. Classifying ambiguous melanocytic lesions with FISH and correlation with clinical long-term follow up. Mod Pathol. 2010;23(3):413–9.

    Article  CAS  PubMed  Google Scholar 

  27. Vergier B, Prochazkova-Carlotti M, de la Fouchardiere A, et al. Fluorescence in situ hybridization, a diagnostic aid in ambiguous melanocytic tumors: European study of 113 cases. Mod Pathol. 2011;24(5):613–23.

    Article  CAS  PubMed  Google Scholar 

  28. Tetzlaff MT, Wang WL, Milless TL, et al. Ambiguous melanocytic tumors in a tertiary referral center: the contribution of fluorescence in situ hybridization (FISH) to conventional histopathologic and immunophenotypic analyses. Am J Surg Pathol. 2013;37(12):1783–96.

    Article  PubMed  Google Scholar 

  29. Isaac AK, Lertsburapa T, Pathria Mundi J, Martini M, Guitart J, Gerami P. Polyploidy in spitz nevi: a not uncommon karyotypic abnormality identifiable by fluorescence in situ hybridization. Am J Dermatopathol. 2010;32(2):144–8.

    Article  PubMed  Google Scholar 

  30. Gerami P, Cooper C, Bajaj S, et al. Outcomes of atypical spitz tumors with chromosomal copy number aberrations and conventional melanomas in children. Am J Surg Pathol. 2013;37(9):1387–94.

    Article  PubMed  Google Scholar 

  31. Pouryazdanparast P, Brenner A, Haghighat Z, Guitart J, Rademaker A, Gerami P. The role of 8q24 copy number gains and c-MYC expression in amelanotic cutaneous melanoma. Mod Pathol. 2012;25(9):1221–6.

    Article  CAS  PubMed  Google Scholar 

  32. Lazova R, Seeley EH, Keenan M, Gueorguieva R, Caprioli RM. Imaging mass spectrometry—a new and promising method to differentiate Spitz nevi from Spitzoid malignant melanomas. Am J Dermatopathol. 2012;34(1):82–90.

    Article  PubMed Central  PubMed  Google Scholar 

  33. Daniels AB, Lee JE, MacConaill LE, et al. High throughput mass spectrometry-based mutation profiling of primary uveal melanoma. Invest Ophthalmol Vis Sci. 2012;53(11):6991–6.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  34. Devitt B, Liu W, Salemi R, et al. Clinical outcome and pathological features associated with NRAS mutation in cutaneous melanoma. Pigment Cell Melanoma Res. 2011;24(4):666–72.

    Article  CAS  PubMed  Google Scholar 

  35. Long GV, Menzies AM, Nagrial AM, et al. Prognostic and clinicopathologic associations of oncogenic BRAF in metastatic melanoma. J Clin Oncol. 2011;29(10):1239–46.

    Article  PubMed  Google Scholar 

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Correspondence to Victor G. Prieto M.D., Ph.D. .

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Prieto, V.G., Shea, C.R., Reed, J.A. (2015). Applications of Additional Techniques to Melanocytic Pathology. In: Shea, C., Reed, J., Prieto, V. (eds) Pathology of Challenging Melanocytic Neoplasms. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1444-9_5

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  • DOI: https://doi.org/10.1007/978-1-4939-1444-9_5

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