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Pathologic Diagnosis

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Lentigo Maligna Melanoma

Abstract

Lentigo maligna melanoma (LMM) is one of the four traditional subtypes of melanoma along with superficial spreading, nodular, and acral lentiginous melanoma. The non-invasive intraepidermal counterpart is called lentigo maligna (LM) or melanoma in situ, lentigo maligna type. Histologically, LM is characterized by an increased density of predominantly solitary units of melanocytes along the dermal-epidermal junction and above it, typically in association with marked solar elastosis. Neoplastic melanocytes commonly extend into adnexal epithelium. Some lesions also feature junctional nests or pagetoid spread. The differential diagnosis between early or histopathologically subtle LM and benign melanocyte hyperplasia of sun-damaged skin can be challenging. Other entities that may be confused with LM include solar lentigo, pigmented actinic keratosis, junctional melanocytic nevus, or lichen planus-like keratosis. Immunohistochemical stains, such as the nuclear marker MITF or SOX10, may be a helpful ancillary diagnostic test in evaluating the density and growth pattern of melanocytes. Immunohistochemical stains may also help to identify associated invasive melanoma, especially if the invasive component is amelanotic. The traditional clinicopathologic classification of melanoma is being replaced by molecular classification that guides targeted therapy. Melanomas occurring on chronically sun-exposed skin, such as LM/LMM, show a high mutational burden and characteristic genomic signature different from melanomas of intermittently sun-exposed skin.

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References

  1. Clark Jr WH, Mihm Jr MC. Lentigo maligna and lentigo-maligna melanoma. Am J Pathol. 1969;55(1):39–67.

    PubMed  PubMed Central  Google Scholar 

  2. Clark Jr WH, From L, Bernardino EA, Mihm MC. The histogenesis and biologic behavior of primary human malignant melanomas of the skin. Cancer Res. 1969;29(3):705–27.

    PubMed  Google Scholar 

  3. Arrington 3rd JH, Reed RJ, Ichinose H, Krementz ET. Plantar lentiginous melanoma: a distinctive variant of human cutaneous malignant melanoma. Am J Surg Pathol. 1977;1(2):131–43.

    Article  PubMed  Google Scholar 

  4. Massi G, LeBoit PE. Lentigo maligna. In: Massi G, LeBoit PE, editors. Histological diagnosis of nevi and melanoma. 2nd ed. Berlin, Heidelberg: Springer; 2014. p. 437–44.

    Chapter  Google Scholar 

  5. Kallini JR, Jain SK, Khachemoune A. Lentigo maligna: review of salient characteristics and management. Am J Clin Dermatol. 2013;14(6):473–80.

    Article  PubMed  Google Scholar 

  6. Flotte TJ, Mihm Jr MC. Lentigo maligna and malignant melanoma in situ, lentigo maligna type. Hum Pathol. 1999;30(5):533–6.

    Article  CAS  PubMed  Google Scholar 

  7. Hutchinson J. On tissue dotage. Arch Surg. 1892;3:315–22.

    Google Scholar 

  8. Hutchinson J. On cancer. Arch Surg. 1892;4:61–5.

    Google Scholar 

  9. Lentigo-melanosis HJ. A further report. Arch Surg. 1894;5:253–6.

    Google Scholar 

  10. Dubreuilh W. De la melanose circonscrite precancereuse. Ann Derm Syph (Paris). 1912;3(5):129–51.

    Google Scholar 

  11. Mishima Y. Melanosis circumscripta praecancerosa (Dubreuilh), a non-nevoid premelanoma distinct from junction nevus. J Invest Dermatol. 1960;34:361–75.

    Article  CAS  PubMed  Google Scholar 

  12. Cohen LM. Lentigo maligna and lentigo maligna melanoma. J Am Acad Dermatol. 1995;33(6):923–36. quiz 37–40.

    Article  CAS  PubMed  Google Scholar 

  13. Becker SW. Critical evaluation of the so-called junction nevus. J Invest Dermatol. 1954;22(3):217–23.

    Article  CAS  PubMed  Google Scholar 

  14. Network NCC. NCCN clinical practice guidelines in oncology (NCCN Guidelines®) - Melanoma. 2015. Available from: nccn.org.

    Google Scholar 

  15. McGuire LK, Disa JJ, Lee EH, Busam KJ, Nehal KS. Melanoma of the lentigo maligna subtype: diagnostic challenges and current treatment paradigms. Plast Reconstr Surg. 2012;129(2):288e–99.

    Article  CAS  PubMed  Google Scholar 

  16. Mendese G, Maloney M, Bordeaux J. To scoop or not to scoop: the diagnostic and therapeutic utility of the scoop-shave biopsy for pigmented lesions. Dermatol Surg. 2014;40(10):1077–83.

    Article  CAS  PubMed  Google Scholar 

  17. Green A, Little JH, Weedon D. The diagnosis of Hutchinson’s melanotic freckle (lentigo maligna) in Queensland. Pathology. 1983;15(1):33–5.

    Article  CAS  PubMed  Google Scholar 

  18. Cohen LM. The starburst giant cell is useful for distinguishing lentigo maligna from photodamaged skin. J Am Acad Dermatol. 1996;35(6):962–8.

    Article  CAS  PubMed  Google Scholar 

  19. Katz SK, Guitart J. Starburst giant cells in benign nevomelanocytic lesions. J Am Acad Dermatol. 1998;38(2 Pt 1):283.

    Article  CAS  PubMed  Google Scholar 

  20. Smoller BR. Histologic criteria for diagnosing primary cutaneous malignant melanoma. Mod Pathol. 2006;19 Suppl 2:S34–40.

    Article  PubMed  Google Scholar 

  21. Chen LL, Jaimes N, Barker CA, Busam KJ, Marghoob AA. Desmoplastic melanoma: a review. J Am Acad Dermatol. 2013;68(5):825–33.

    Article  PubMed  Google Scholar 

  22. Magro CM, Crowson AN, Mihm MC. Unusual variants of malignant melanoma. Mod Pathol. 2006;19 Suppl 2:S41–70.

    Article  PubMed  Google Scholar 

  23. Carlson JA, Dickersin GR, Sober AJ, Barnhill RL. Desmoplastic neurotropic melanoma. A clinicopathologic analysis of 28 cases. Cancer. 1995;75(2):478–94.

    Article  CAS  PubMed  Google Scholar 

  24. Reed JA, Shea CR. Lentigo maligna: melanoma in situ on chronically sun-damaged skin. Arch Pathol Lab Med. 2011;135(7):838–41.

    PubMed  Google Scholar 

  25. Farrahi F, Egbert BM, Swetter SM. Histologic similarities between lentigo maligna and dysplastic nevus: importance of clinicopathologic distinction. J Cutan Pathol. 2005;32(6):405–12.

    Article  PubMed  Google Scholar 

  26. King R, Page RN, Googe PB, Mihm Jr MC. Lentiginous melanoma: a histologic pattern of melanoma to be distinguished from lentiginous nevus. Mod Pathol. 2005;18(10):1397–401.

    Article  PubMed  Google Scholar 

  27. Suchak R, Hameed OA, Robson A. Evaluation of the role of routine melan-A immunohistochemistry for exclusion of microinvasion in 120 cases of lentigo maligna. Am J Dermatopathol. 2014;36(5):387–91.

    Article  PubMed  Google Scholar 

  28. Prieto VG, Shea CR. Immunohistochemistry of melanocytic proliferations. Arch Pathol Lab Med. 2011;135(7):853–9.

    PubMed  Google Scholar 

  29. Plaza JA, Bonneau P, Prieto V, Sangueza M, Mackinnon A, Suster D, et al. Desmoplastic melanoma: an updated immunohistochemical analysis of 40 cases with a proposal for an additional panel of stains for diagnosis. J Cutan Pathol. 2015.

    Google Scholar 

  30. 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-damaged skin. Am J Dermatopathol. 2009;31(3):305–8.

    Article  PubMed  Google Scholar 

  31. El Shabrawi-Caelen L, Kerl H, Cerroni L. Melan-A: not a helpful marker in distinction between melanoma in situ on sun-damaged skin and pigmented actinic keratosis. Am J Dermatopathol. 2004;26(5):364–6.

    Article  PubMed  Google Scholar 

  32. Blessing K, Sanders DS, Grant JJ. Comparison of immunohistochemical staining of the novel antibody melan-A with S100 protein and HMB-45 in malignant melanoma and melanoma variants. Histopathology. 1998;32(2):139–46.

    Article  CAS  PubMed  Google Scholar 

  33. Kim J, Taube JM, McCalmont TH, Glusac EJ. Quantitative comparison of MiTF, Melan-A, HMB-45 and Mel-5 in solar lentigines and melanoma in situ. J Cutan Pathol. 2011;38(10):775–9.

    PubMed  Google Scholar 

  34. Magro CM, Crowson AN, Desman G, Zippin JH. Soluble adenylyl cyclase antibody profile as a diagnostic adjunct in the assessment of pigmented lesions. Arch Dermatol. 2012;148(3):335–44.

    Article  PubMed  Google Scholar 

  35. Curtin JA, Fridlyand J, Kageshita T, Patel HN, Busam KJ, Kutzner H, et al. Distinct sets of genetic alterations in melanoma. N Engl J Med. 2005;353(20):2135–47.

    Article  CAS  PubMed  Google Scholar 

  36. Liu W, Kelly JW, Trivett M, Murray WK, Dowling JP, Wolfe R, et al. Distinct clinical and pathological features are associated with the BRAF(T1799A(V600E)) mutation in primary melanoma. J Invest Dermatol. 2007;127(4):900–5.

    Article  CAS  PubMed  Google Scholar 

  37. Hosler GAM, Murphy KM. Melanoma. Part I. Risk assessment, diagnosis, and prognosis: using molecular tools to diagnose melanoma, predict its behavior, and evaluate for inheritable forms. In: Hosler GAM, KM, editors. Molecular diagnostic for dermatology. New York: Springer. 2014; p. 63–96.

    Google Scholar 

  38. Gerami P, Cook RW, Russell MC, Wilkinson J, Amaria RN, Gonzalez R, et al. Gene expression profiling for molecular staging of cutaneous melanoma in patients undergoing sentinel lymph node biopsy. J Am Acad Dermatol. 2015;72(5):780–5. e3.

    Article  CAS  PubMed  Google Scholar 

  39. Gerami P, Cook RW, Wilkinson J, Russell MC, Dhillon N, Amaria RN, et al. Development of a prognostic genetic signature to predict the metastatic risk associated with cutaneous melanoma. Clin Cancer Res. 2015;21(1):175–83.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  41. Hosler GAM, Murphy KM. Melanoma. Part II. Personalized medicine: using molecular tools to guide targeted therapy. In: Hosler GAM, KM, editor. Molecular diagnostics for dermatology. Springer Berlin Heidelberg; 2014. p. 97–131.

    Google Scholar 

  42. Bichakjian CK, Halpern AC, Johnson TM, Foote Hood A, Grichnik JM, Swetter SM, Tsao H, Barbosa VH, Chuang TY, Duvic M, Ho VC, Sober AJ, Beutner KR, Bhushan R, Smith Begolka W, American Academy of Dermatology. Guidelines of care for the management of primary cutaneous melanoma. American Academy of Dermatology. J Am Acad Dermatol. 2011;65(5):1032–47.

    Article  PubMed  Google Scholar 

  43. Mitchell RE. The effect of prolonged solar radiation on melanocytes of the human epidermis. J Invest Dermatol. 1963;41:199–212.

    Article  CAS  PubMed  Google Scholar 

  44. Hendi A, Brodland DG, Zitelli JA. Melanocytes in long-standing sun-exposed skin: quantitative analysis using the MART-1 immunostain. Arch Dermatol. 2006;142(7):871–6.

    Article  PubMed  Google Scholar 

  45. Hendi A, Wada DA, Jacobs MA, Crook JE, Kortuem KR, Weed BR, et al. Melanocytes in nonlesional sun-exposed skin: a multicenter comparative study. J Am Acad Dermatol. 2011;65(6):1186–93.

    Article  PubMed  Google Scholar 

  46. Barlow JO, Maize Sr J, Lang PG. The density and distribution of melanocytes adjacent to melanoma and nonmelanoma skin cancers. Dermatol Surg. 2007;33(2):199–207.

    CAS  PubMed  Google Scholar 

  47. Weyers W, Bonczkowitz M, Weyers I, Bittinger A, Schill WB. Melanoma in situ versus melanocytic hyperplasia in sun-damaged skin. Assessment of the significance of histopathologic criteria for differential diagnosis. Am J Dermatopathol. 1996;18(6):560–6.

    Article  CAS  PubMed  Google Scholar 

  48. Busam KJ. Melanocytic proliferations. In: Busam KJ, editor. Dermatopathology foundations of diagnostic pathology. Philadelphia: Saunders Elsevier; 2010. p. 437–98.

    Chapter  Google Scholar 

  49. Chung HJ, Simkin AD, Bhawan J, Wolpowitz D. “Melanocytic nests arising in lichenoid inflammation”: reappraisal of the terminology “melanocytic pseudonests”. Am J Dermatopathol. 2015;37(12):940–3.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Wong SQ, Behren A, Mar VJ, Woods K, Li J, Martin C, et al. Whole exome sequencing identifies a recurrent RQCD1 P131L mutation in cutaneous melanoma. Oncotarget. 2015;6(2):1115–27.

    Article  PubMed  Google Scholar 

  51. Shain AH, Garrido M, Botton T, Talevich E, Yeh I, Sanborn JZ, et al. Exome sequencing of desmoplastic melanoma identifies recurrent NFKBIE promoter mutations and diverse activating mutations in the MAPK pathway. Nat Genet. 2015;47(10):1194–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Wiesner T, Kiuru M, Scott SN, Arcila M, Halpern AC, Hollmann T, et al. NF1 mutations are common in desmoplastic melanoma. Am J Surg Pathol. 2015;39(10):1357–62.

    Article  PubMed  PubMed Central  Google Scholar 

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Correspondence to Klaus J. Busam MD .

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Kiuru, M., Busam, K.J. (2017). Pathologic Diagnosis. In: Nehal, K., Busam, K. (eds) Lentigo Maligna Melanoma. Springer, Cham. https://doi.org/10.1007/978-3-319-43787-3_5

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  • DOI: https://doi.org/10.1007/978-3-319-43787-3_5

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