Skin melanocytic tumor

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Contributed by Alison Potter, M.B.B.S.

Contributed by Alison Potter, M.B.B.S.

Images hosted on other servers:

Contributed by Alison Potter, M.B.B.S.

• Skin, left proximal thigh, excision:
  • Dermal melanoma, favor cutaneous / in transit metastasis (see comment)
  • Comment: Sections of the left proximal thigh lesion show a dermal nodule of malignant epithelioid and spindled cells in keeping with melanoma. The tumor is located within the papillary dermis and attenuates an overlying epidermis, without evidence of a junctional melanocytic component. No significant surrounding inflammation or fibrosis is seen. Adjacent lymphatic spaces contain small tumor nests, in keeping with lymphovascular space invasion. Central tumor necrosis is present as well as numerous mitoses (6 per mm²). No background nevus component is appreciated. Margins are clear of tumor by 4 mm (both peripheral and deep). BRAF V600E immunohistochemistry is negative and tissue has been sent for formal molecular testing for melanoma associated targetable mutations; a separate molecular report will be issued.

• Small bowel, excision:
  • Metastatic melanoma (see comment)
  • Comment: Sections show multiple deposits of metastatic melanoma, between 10 and 150 mm in size. Several deposits involve the mucosal surface with extension into lamina propria and secondary erosion of the overlying epithelium. There is evidence of patchy tumor necrosis and a sparse infiltrate of lymphocytes. Most tumor appears viable and is highlighted on immunohistochemistry for S100, SOX10, MelanA, HMB45 and BRAF V600E. 22 lymph nodes are identified, none of which show metastatic melanoma (0/22). The melanoma deposits appear completely excised. The closest margin is 2 mm (gastric margin).

• Right axilla lymph node / mass, excision:
  • Metastatic poorly differentiated / dedifferentiated melanoma (see comment)
  • Comment: Sections of the left axillary mass show a poorly differentiated epithelioid malignancy with cohesive sheet-like growth and large areas of necrosis. There is no evidence of glandular or squamoid differentiation and no melanin pigment is seen. A large range of immunostains (performed on block A8) show the tumor is negative for a large range of melanocytic, epithelial and lymphoid markers. Due to the poorly differentiated morphology, additional stains were performed (on block A1) and these demonstrate a small focus of viable tumor with positivity for SOX10, S100, HMB45, MelanA, tyrosinase, MITF and PRAME. The tumor cells are also positive for BRAF V600E. Repeated staining for SMA, desmin, MNF116, p40, myogenin and MyoD1 are negative. Overall, despite being focal in nature, the expression of a panel of melanocytic markers would favor this nodal disease to represent poorly differentiated / dedifferentiated metastatic melanoma.

• Primary cutaneous melanoma (versus satellite melanoma metastasis):
  • Multiple step sections are required to exclude contiguous soft tissue or periadnexal / perineural tracking from the primary tumor
• Primary dermal melanoma (versus in transit melanoma metastasis):
  • Presence of an inflammatory infiltrate, surrounding fibrosis, junctional activity or adjacent benign nevus are all features which favor a primary (dermal) nodular melanoma, over a metastatic deposit (Histopathology 2018;72:472)
• Capsular nevus (versus lymph node metastatic melanoma):
  • Seen in lymph nodes draining the skin, capsular nevi are commonly present within the fibrous capsule and trabeculae (rather than sinus and parenchyma)
  • Nevus cells lack cytological atypia, pleomorphism and mitotic activity
  • Immunohistochemistry for S100 and SOX10 are strongly positive but HMB45 shows negative to weak expression, compared to the strong diffuse expression of most melanomas
  • Lack of PRAME expression may also support a benign nevus if a culprit primary melanoma is known to be PRAME positive
• Primary tumor of the visceral site of disease (versus visceral metastatic melanoma):
  • Melanoma can mimic tumors from a range of organs and cell lineages.
  • Clinicopathological correlation and knowledge of primary tumors within the particular visceral site is required to aid in distinction
  • Alterations and premalignant change in the adjacent organ may provide diagnostic clues
  • Judicious use of a panel of immunohistochemical stains and molecular studies may assist in the correct diagnosis
• Undifferentiated pleomorphic sarcoma (versus undifferentiated / dedifferentiated melanoma):
  • Identification of transition between conventional and dedifferentiated / undifferentiated components can aid in the diagnosis of melanoma
  • Factors favoring a dedifferentiated / undifferentiated melanoma include (Am J Surg Pathol 2021;45:240)
    • Previous history of melanoma
    • Metastatic disease in a regional nodal basin or site uncommon for sarcomas (including neck, axilla, inguinal, viscera)
    • Multifocal disease
    • Identification of a melanoma associated mutation or molecular signature concordant with that of a culprit primary tumor
    • Absence of a bona fide primary tumor at another site with alternative histogenesis
• Clear cell sarcoma (versus dermal or soft tissue melanoma metastasis):
  • These tumors show overlap in architecture, cytology, immunohistochemistry (S100, HMB45 and MelanA) and ultrastructure
  • Presence of wreath-like multinucleated tumor cells would favor clear cell sarcoma, with definitive diagnosis by FISH or PCR to detect EWSR1 rearrangement, with common fusion partners ATF1 or CREB1
  • Intraepidermal involvement can be seen in both melanoma metastasis and cutaneous clear cell sarcoma (Am J Surg Pathol 2020;44:21, Pathology 2022;54:369)
• PEComa (versus soft tissue metastatic melanoma):
  • Overlapping immunohistochemical profile (HMB45 and MelanA positive) but lack expression of S100
  • Evidence of smooth muscle differentiation may also be seen (desmin, caldesmon, calponin, SMA)
• Cellular blue nevus / malignant blue nevus (versus dermal metastasis):
  • These tumors have distinct morphological features and demonstrate aberrations in GNAQ or GNA11
• Cutaneous tumor with CRTC1::TRIM11 rearrangement (versus dermal melanoma metastasis)
  • These tumors frequently show intersecting bundles and nests of tumor cells with cytological uniformity and expression of melanocytic markers (S100, HMB45)
  • Definitive distinction can be made on molecular studies (Am J Surg Pathol 2022;46:1457)

This undifferentiated epithelioid malignancy is identified within the right groin of a 76 year old man. The patient was diagnosed with a 1.2 mm Breslow thickness superficial spreading melanoma on the right lateral ankle 3 years ago. A broad panel of immunohistochemical stains is negative. Which of the following modalities would be most helpful in establishing a diagnosis of metastatic dedifferentiated / undifferentiated melanoma?

1. Investigations for melanoma associated mutations in BRAF or NRAS
2. Morphological comparison to the primary ankle melanoma
3. Performing immunohistochemistry for PRAME on multiple different regions of tumor
4. Performing special stains (e.g., Fontana-Masson / Schmorl stain) to identify intracytoplasmic pigmentation

A. Investigations for melanoma associated mutations in BRAF or NRAS. A dedifferentiated tumor in a nodal basin in a patient with a history of melanoma is suspicious for metastatic melanoma. There may only be focal conventional melanocytic differentiation present within dedifferentiated melanoma and sampling of numerous areas of the tumor may be required to identify these foci. A broad panel of immunohistochemistry is required to exclude other lines of differentiation and may be able to identify small foci of tumor that retain immunohistochemical features of melanoma. Identification of a melanoma associated mutation such as BRAF or NRAS may assist in rendering the diagnosis, especially if the mutational status of the primary tumor is known. Answer D is incorrect because dedifferentiated melanomas lack the morphological features of melanoma and are likely to lack evidence of pigmentation, with special stains negative. Answer B is incorrect because primary melanomas are rarely dedifferentiated at their primary site and morphological overlap is insufficient to render a diagnosis in an undifferentiated tumor. Answer C is incorrect because PRAME immunohistochemistry is not specific for a melanocytic lineage and can be positive in a range of high grade mesenchymal tumors; therefore, it cannot be relied upon to establish a diagnosis of dedifferentiated melanoma.

Comment Here

Reference: Metastatic melanoma

Which of the following presentations of melanoma is considered metastatic in nature?

1. Dermal nodule of melanoma seen within the perineural space, which on deeper levels is identified to be in continuity with the primary tumor invasive front
2. Dermal nodule of melanoma with an adjacent dysplastic compound nevus
3. Solitary subcuticular nodule of melanoma with adjacent lymphovascular space invasion
4. Thin rim of bland melanocytes within the fibrous capsule of an axillary lymph node

C. Solitary subcuticular nodule of melanoma with adjacent lymphovascular space invasion. Subcuticular deposits of melanoma without continuity to the dermis / epidermis and with evidence of nearby lymphovascular space invasion are classic for in transit metastasis. Answers A and B are incorrect because a focus of melanoma that remains in direct continuity with the primary tumor is not regarded as metastatic disease, nor are tumors that arise within an adjacent nevus (even if there is an absence of in situ component). Answer D is incorrect because lymph nodes draining the skin, which can contain capsular nevi, are located within the fibrous capsule and should not be regarded as metastatic melanoma. Care should be taken to ensure that no continuity exists with a nearby primary melanoma prior to establishing a diagnosis of metastatic melanoma.

Comment Here

Reference: Metastatic melanoma