• Rare primary malignant melanocytic neoplasm of the anal mucosa

• ICD-10
  • C21.0 - malignant neoplasm of anus, unspecified
  • C21.1 - malignant neoplasm of anal canal
  • C21.8 - malignant neoplasm of overlapping sites of rectum, anus and anal canal

• Melanocytes are normally found at the anal transition zone and squamous zone (Clin Colon Rectal Surg 2011;24:171)
• Mucosal melanomas, including anal melanoma, are not associated with ultraviolet (UV) radiation exposure, unlike cutaneous melanomas (Nature 2017;545:175)
• Otherwise, the etiology of anal melanoma is not well established

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• 5 year survival is based on stage at diagnosis but is generally poor with 32% for local disease, 17% for regional spread and 0% for distant spread (Surg Clin North Am 2020;100:629)
• Gross and histologic features associated with poor prognosis include tumor size and thickness, regional lymph node involvement, perineural invasion and amelanotic subtype (Surg Clin North Am 2020;100:629, Surg Oncol Clin N Am 2017;26:143)

• 63 year old woman with bleeding per rectum and painful defecation (Cureus 2021;13:e15474)
• 66 year old woman with anal bleeding, pain and tenesmus (World J Clin Cases 2021;9:11369)
• 81 year old woman with hematochezia and perianal pain (Am J Case Rep 2021;22:e933032)
• 84 year old woman with anal mass (Middle East J Dig Dis 2019;11:166)
• 85 year old woman with recurrent anal mass (BMC Surg 2020;20:68)

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• Lesions can be varied in their presentation, including size, shape and color
• Usually present as large, expansive, nodular masses
• Majority of lesions are pigmented but can be nonpigmented
• Ulceration is common
• Reference: Surg Clin North Am 2020;100:629

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• Histomorphology can vary greatly but solid sheets of atypical epithelioid cells originating from the epithelium is the most common presentation; however, the cytomorphology may be composed of spindled, pleomorphic or small round blue cells while the architectural patterns may be nested, pseudopapillary or pseudoalveolar (Hum Pathol 2018;79:77)
• Pigmentation is variable and can be absent in up to 40% of cases, which is much more common than in cutaneous melanoma (< 5% amelanotic) (Hum Pathol 2018;79:77, Surg Oncol Clin N Am 2017;26:143)
• Ulceration can be present
• Identification of a junctional component adjacent to the invasive tumor can support the diagnosis of primary anal melanoma (Surg Oncol Clin N Am 2017;26:143)
• Melanoma, including anorectal examples, may undergo dedifferentiation which is defined as a tumor that has lost evidence of melanocytic differentiation (morphologic and immunophenotypic) (Int J Surg Pathol 2019;27:923)
  • These dedifferentiated examples may aberrantly express various nonmelanocytic markers
  • Dedifferentiation is rare but is seen more commonly in metastases of cutaneous origin

Contributed by Aaron R. Huber, D.O. and @RaulSGonzalezMD on Twitter

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• S100, SOX10, MITF, HMB45, MelanA, PRAME (Surg Pathol Clin 2021;14:165, Mol Diagn Ther 2023;27:49)

• Keratin, CD45, CDX2 and SATB2
• It is important to note that melanoma can aberrantly express many antigens and demonstrate divergent differentiation, which can be a potential diagnostic pitfall (Histopathology 2008;52:119, Int J Surg Pathol 2015;23:329)

• Secondary involvement by rectal adenocarcinoma:
  • More common than anal adenocarcinoma
  • Usually well or moderately differentiated gland forming carcinoma with marked desmoplasia
  • CK20, CDX2 and SATB2 positive
• Anal adenocarcinoma:
  • Haphazardly dispersed small glands with scant mucin production
  • May contain melanin pigment
  • CK7 and MUC5AC positive
• Squamous cell carcinoma:
  • Most common carcinoma of the anal tract
  • Resembles squamous cell carcinoma as seen elsewhere in body
  • Positive for pankeratins and squamous markers (i.e., p40)
• Metastatic melanoma:
  • History of melanoma or image findings consistent with a metastatic lesion
  • Lack of intraepidermal component does not confirm metastasis
• Lymphoma:
  • Atypical population of lymphocytes
  • CD45 positive
• Neuroendocrine carcinoma:
  • Small and large cell subtypes resemble morphology seen in other locations
  • Solid nests of poorly differentiated cells
  • Positive for keratin, p16, p63, HPV ISH and neuroendocrine markers (synaptophysin, chromogranin, INSM1)
  • Usually high Ki67
• Hemorrhoids:
  • Dilated thin walled vascular plexus within stroma
  • Can display metaplastic changes in the surface epithelium
• Gastrointestinal stromal tumor (GIST):
  • May be spindled or epithelioid but usually lacks the overt cytologic atypia seen in melanoma
  • DOG1+
• Malignant peripheral nerve sheath tumor (MPNST):
  • Usually has spindle cells with cytologic atypia and classically occurs in patients with neurofibromatosis type 1 (NF1)
  • May be focally S100 positive but characteristically lacks expression of H3K27me3

A 66 year old White woman presents with anal pain and is found to have a pigmented anal mass. The mass is biopsied and the histology is depicted in the H&E image shown above. Which immunohistochemical stain would best support the correct diagnosis?

1. CD45
2. CDX2
3. HMB45
4. Pancytokeratin

C. HMB45. The H&E image demonstrates anal melanoma. HMB45 is a melanocytic marker that would confirm the diagnosis of melanoma, along with the malignant features seen on H&E. Answer A is incorrect because CD45 is a lymphocytic marker. CD45 should be ordered to rule out lymphoma but a negative result would not confirm the diagnosis in this case. Answer D is incorrect because melanoma is typically pancytokeratin negative. This would be a good confirmatory stain but would not be diagnostic of melanoma by itself. Answer B is incorrect because CDX2 is a common marker for colonic adenocarcinomas. CDX2 should be used to rule out a primary rectal adenocarcinoma that involves the anus but will be negative for any anal malignancies, including melanoma.

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Reference: Anal melanoma

Which of the following characteristics is similar for both cutaneous and anal melanoma?

1. Pathologic staging
2. Presentation
3. Prognosis
4. Staining / IHC

D. Staining / IHC. Cutaneous and anal melanoma will stain with similar melanocytic markers (SOX10, S100, HMB45, MelanA, etc.). Answer C is incorrect because anal melanoma has a worse prognosis when compared to cutaneous melanoma, especially because patients with anal melanoma often have advanced disease on presentation due to the vague clinical symptoms and difficulty in diagnosis. Answer B is incorrect because anal melanoma typically presents with vague symptoms and not the typical ABCDE (asymmetry, border, color, diameter, evolving) criteria for cutaneous melanoma. Answer A is incorrect because anal melanoma does not have a standardized pathologic staging system. Anal melanomas can be staged similarly to cutaneous melanoma but this is not universal.

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Reference: Anal melanoma