Random Dermatology MCQ - Desmoplastic melanoma

A 75-year-old man with a long history of significant sun exposure presents with a firm, indurated, flesh-colored to lightly pigmented plaque on his right cheek. The lesion is slowly enlarging and has been present for over a year. It is non-tender and feels like a scar on palpation. A shave biopsy is reported as showing a dense, fibrous stroma with scattered, elongated, atypical spindle cells that are positive for S-100 and SOX10, but negative for Melan-A and HMB-45. What is the most likely diagnosis and the most critical prognostic factor?

A. Desmoplastic melanoma; the most important prognostic factor is the tumor thickness (Breslow depth).
B. Dermatofibrosarcoma protuberans; the most important prognostic factor is the presence of fibrosarcomatous change.
C. Scar tissue (keloid); the most important factor is the risk of recurrence after excision.
D. Atypical fibroxanthoma; the most important factor is ensuring complete excision.
E. Morpheaform basal cell carcinoma; the most important factor is achieving clear surgical margins.

Correct Answer: A. Desmoplastic melanoma; the most important prognostic factor is the tumor thickness (Breslow depth).

Answer and Explanation

The correct answer is A. This question describes the classic presentation and histology of desmoplastic melanoma (DM). The key clinical clues are the location on sun-damaged skin of an elderly patient, the scar-like or indurated plaque that is often amelanotic (flesh-colored), and the slow growth. The histology is diagnostic: a desmoplastic stromal response (dense collagen/fibrosis) containing atypical spindle cells that are S-100/SOX10 positive (confirming melanocytic origin) but frequently negative for more specific melanocytic markers like Melan-A and HMB-45. As with other melanomas, the single most powerful prognostic indicator is the Breslow thickness.

Why the Other Options are Incorrect:

• B. Dermatofibrosarcoma protuberans (DFSP): DFSP also presents as a firm plaque, but it is typically positive for CD34 and negative for S-100. Its growth pattern involves infiltration of subcutaneous fat in a "honeycomb" pattern. The prognosis is related to local recurrence, not thickness in the same way.

• C. Scar tissue (keloid): A scar would not contain atypical spindle cells. Keloids are composed of disorganized, thickened collagen bundles (hyalinized collagen) and are negative for S-100.

• D. Atypical fibroxanthoma (AFX): AFX is a pleomorphic dermal spindle cell tumor seen in the elderly. It is typically S-100 negative and may express histiocytic markers (CD68, CD10).

• E. Morpheaform basal cell carcinoma (BCC): This BCC subtype also presents as a firm, scar-like plaque. However, histology would show nests or cords of basaloid cells with peripheral palisading within a sclerotic stroma, and the cells would be cytokeratin positive, not S-100 positive.

Additional High-Yield Information for Exams:

• Clinical Features:

  • "Scar-like melanoma" – Often misdiagnosed as a scar, dermatofibroma, or BCC due to lack of typical ABCD melanoma features.

  • Location: Overwhelmingly on sun-exposed head and neck (especially cheek, nose, scalp) in elderly men.

  • Neurologic Symptoms: Desmoplastic melanoma has a strong propensity for perineural invasion (PNI), which can cause localized numbness, paresthesia, or pain. The presence of PNI is a critical finding to report.

• Histopathology & Immunohistochemistry:

  • Stroma: Prominent desmoplasia (dense, hypocellular collagen) dominates the picture, often obscuring the tumor cells.

  • Tumor Cells: Atypical, spindle-shaped melanocytes arranged singly or in small nests.

  • IHC: S-100 and SOX10 are diffusely and strongly positive (sensitivity >95%). Melan-A/MART1, HMB-45, and MITF are often negative or only focally positive, making S-100/SOX10 essential for diagnosis.

• Differential Diagnosis: The clinical and histological differential is broad, including scar, DFSP, AFX, sclerosing BCC, and neurotized nevus. S-100 positivity rules in DM.

• Associated Conditions & Prognosis:

  • Local Recurrence: Historically high (~20-50%) due to ill-defined clinical borders and perineural invasion. This emphasizes the need for wide local excision.

  • Metastasis: Lymph node metastasis is less common than in conventional melanoma (~10-15%), but DM has a higher rate of distant metastasis, particularly to the lungs. Prognosis is better stage-for-stage compared to other melanomas of the same thickness, likely due to the lower rate of nodal involvement.

• Management & Rationale:

  • Rationale: The goals are complete surgical excision with clear margins and accurate staging to guide adjuvant therapy.

  • First-line/Definitive Treatment: Wide local excision with 1-2 cm margins (depending on thickness and anatomical constraints). Due to the ill-defined nature and PNI risk, Mohs micrographic surgery with appropriate immunostains (S-100) is increasingly used, especially on the head and neck, to ensure complete excision while preserving tissue.

  • Staging: Sentinel lymph node biopsy (SLNB) is still recommended, though the yield is lower. A thorough clinical neurological exam is crucial.

  • Adjuvant Therapy: Consideration of adjuvant radiotherapy for cases with perineural invasion or narrow/positive margins to reduce the high local recurrence risk. Adjuvant immunotherapy (anti-PD1) may be considered for high-risk stages.

  • Follow-up: Long-term follow-up is essential due to the risk of late local recurrence and distant metastasis.