Skin melanocytic tumor

• Regression in melanoma can occur spontaneously or in response to treatment (Lab Invest 2017;97:657)
• Histopathological examination reveals a dermal infiltrate comprised of melanophages, chronic inflammation, fibrosis and telangiectasias
• Conflicting data have been reported on the prognosis of regressed melanoma; although it has been proposed that partial regression in < 50 - 75% of tumor cells has no effect on prognosis, whereas extensive regression > 75% of tumor tissue may be associated with metastatic disease (An Bras Dermatol 2021;96:797, Arch Dermatol 2002;138:603, World J Surg 1992;16:196, Arch Dermatol 1987;123:1326)

• Melanoma cells express proteins with strong immunogenic effects such that melanomas with increased expression of MelanA (MART1), gp100 or HLA-A-0201 show increased rates of spontaneous regression (EJC Suppl 2013;11:97)
• Regression is a phenomenon in which the host's cytotoxic T lymphocytes attack the primary melanocytic tumor cells and leave behind a fibrotic scar (J Clin Aesthet Dermatol 2016;9:42)
• Regression of melanoma clinically can demonstrate subtle hyperpigmentation, followed by depigmentation of parts of or the entirety of the lesion yielding blue, pink, white or gray areas (Lab Invest 2017;97:657)
• Some authors postulate 3 levels of regression (Lab Invest 2017;97:657)
  • Early stage: characterized by mononuclear inflammatory cell infiltrate with mature lymphocytes and keratinocytes and dermal layer disruption
  • Intermediate stage: characterized by lack of melanocytes, the presence of macrophages, lymphohistiocytic infiltrate, fibroblastic proliferation, mild collagen deposition and increased vascular pattern in the superficial dermal layer
  • Late stage: lesion with complete absence of melanocytes, fibrosis in the superficial / papillary dermis, ectatic capillaries, variable numbers of melanophages and a small number of inflammatory cells (Exp Ther Med 2020;20:87)

• ~10 - 35% of cutaneous melanoma cases may completely or partially spontaneously regress (Histopathology 1992;20:315)
• Histologic regression may not necessarily correlate with clinical regression (i.e., clinically looks like melanoma)
• Management of regressed melanoma still determined by stage (dependent on Breslow depth and presence or lack of ulceration)

• According to a recent cohort study of 17,721 Dutch and 4,980 Australian patients with stage 1 or 2 melanoma, regression was significantly associated with improved overall survival (especially tumors with Breslow thickness ≤ 4.0 mm) (JAMA Dermatol 2021;157:166)
• However, it is also known that the majority of regressive melanomas are discovered after the occurrence of metastasis, making it a potential negative prognostic factor in melanoma (Exp Ther Med 2020;20:87)

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Contributed by Aadil Ahmed, M.D.
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• Epidermal nevi:
  • Typically present as a linear tan patch or plaque along Blaschko lines that often evolve to become thicker, darker and more verrucous during puberty (Dermatol Clin 2022;40:61)
• Pigmented actinic keratosis:
  • A variant of actinic keratosis in which melanin may be present in keratinocytes of the lower epidermis, in melanocytes or in dermal melanophages (Am J Dermatopathol 2022;44:784)
  • May show mild keratinocyte dysplasia involving only the basal epidermal layers which can be misdiagnosed as melanoma in situ
• Pigmented basal cell carcinoma:
  • A variant of basal cell carcinoma with pigmented nests of basaloid tumor cells
  • Peripheral palisading and retraction clefting can commonly be seen on microscopy (J Clin Diagn Res 2013;7:3010)
• Pigmented squamous cell carcinoma:
  • A variant of squamous cell carcinoma with abundant pigmentation among intraepidermal / dermal aberrant keratinocytes
  • Tumor cells may express both melanin positivity (e.g., MelanA) and cytokeratin (e.g., AE1 / AE3) (An Bras Dermatol 2018;93:96)
• Macular seborrheic keratosis:
  • Acanthosis, hyperkeratosis and pseudohorn cysts may be present (Open Access Maced J Med Sci 2018;6:2270)
• Regressed lichenoid keratosis:
  • More frequently have necrotic keratinocytes in the epidermis
  • Less often have dense infiltrates of melanophages in papillary dermis

A 60 year old man presents with an 11 mm x 9 mm asymmetric, variegated pigmented lesion with gray and pink discoloration on his right leg diagnosed as regressed melanoma. Which of the following would be revealed by histopathology?

1. Dense, dermal melanophage infiltrate but no atypical melanocytes
2. Large basaloid lobules with peripheral nuclear palisade within fibromyxoid stroma
3. Lobules of capillary sized vascular channels, lined by single layer of flattened endothelial cells
4. Lymphocytes surrounding the entire melanocytic proliferation in a band-like pattern
5. Spindled banal appearing melanocytes in the dermis with pigment in the cytoplasm

A. Dense, dermal melanophage infiltrate but no atypical melanocytes. Regressed melanoma can present clinically by initially subtle hyperpigmentation, followed by depigmentation of parts of or the entirety of the lesion yielding blue, pink, white or gray areas. Histopathology is characterized by dense, dermal melanophage infiltrate but no atypical melanocytes. Answer B is incorrect because it describes basal cell carcinoma. Answer C is incorrect because it describes lobular capillary hemangioma. Answer D is incorrect because it describes features of a halo nevus. Answer E is incorrect because it describes blue nevus.

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Reference: Regressed melanoma (tumoral melanosis)

Which immunohistochemical stain is positive in completely regressed melanomas?

1. Fontana-Masson
2. HMB45
3. MelanA
4. S100
5. SOX10

A. Fontana-Masson. Fontana-Masson stains the melanin pigment in melanophages. Answers B - E are incorrect because regressed melanoma is characterized by negative staining for MelanA, SOX10, S100 and HMB45.

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Reference: Regressed melanoma (tumoral melanosis)