Melanoma Masquerading as Xanthogranuloma

Abstract

Melanoma can present with protean combinations and permutations of histologic features mimicking a plethora of nonmelanocytic benign and malignant proliferations. Anecdotal cases of melanoma closely simulating fibrohistiocytic proliferations have been reported. At times, the reliable differentiation between melanoma and histiocytic proliferations could be vexing histopathologically. We report an unusual presentation of melanoma in an 87-year-old man strikingly resembling xanthogranuloma both clinically and histopathologically. Histologic sections revealed a diffuse proliferation of pleomorphic cells some with foamy cytoplasm and occasional Touton-like giant cells in the dermis accompanied by inflammatory cells. Rare single-cell pagetoid scatter was evident within the epidermis. The infiltrate had patchy staining on CD163, interpreted as part of the inflammatory component but the atypical cells stained heavily with Melan A and tyrosinase confirming the diagnosis of malignant melanoma. Our case demonstrates yet another face of malignant melanoma and the critical but judicious use of immunohistochemistry in reliably distinguishing between melanoma and histiocytic tumors.

Metastatic melanoma with balloon/histiocytoid cytomorphology after treatment with immunotherapy: A histologic mimic and diagnostic pitfall

“…Furthermore, melanocytes may occasionally acquire nonmelanocytic differentiation, including schwannian, fibroblastic/myofibroblastic, smooth muscle, rhabdomyoblastic, osteocartilaginous, ganglionic/ganglioneuroblastic, neuroendocrine and epithelial features . Different combinations of the above features may result in ambiguous patterns that allow melanoma tom simulate virtually any epithelial, vascular, mesenchymal, neural, hematologic or germ‐line neoplasm, especially in the absence of an epidermal component and/or pigmentation …”

“…Accordingly, melanomas may rarely resemble reactive or neoplastic histiocytic lesions, including benign and malignant fibrous histiocytoma, atypical fibroxanthoma, dermatofibrosarcoma protuberans, Langerhans cell histiocytosis, reticulohistiocytoma and xanthogranuloma . Similarly, histiocytic proliferations including Langerhans cell histiocytosis and xanthoma have been uncommonly confused with melanoma .…”

“…Clues to the melanocytic rather than histiocytic origin of a tumor generally include the presence of an intraepithelial component, intracytoplasmic melanin pigmentation and nesting along the dermo‐epidermal junction . However, these findings must be interpreted with caution as epidermotropism and a tendency for dermal nesting have been rarely reported in histiocytic proliferations like xanthomas and xanthogranulomas .…”

“…Nevertheless, pathologists must be aware of the limitations of immunohistochemical stains in this setting. For instance, CD68 and CD163, which are typical markers of histiocytic differentiation, can show non‐specific staining in melanocytes, which has been observed in as much as 50% to 86% of melanoma cases for CD68. Moreover, histiocytic lesions may occasionally display focal S100 positivity and some melanomas may fail to stain for S100.…”

“…A potential diagnostic pitfall in the histologic assessment of melanoma is the inability to recognize its protean histologic manifestations, especially in the setting of post‐neoadjuvant therapy. Melanoma exhibits diverse cytomorphological features and architectural patterns that allow it to mimic many nonmelanocytic benign and malignant proliferations, and newer histologic variants continue to be reported in the scientific literature . Herein, we report a case of melanoma with foamy balloon/histiocyte‐like cells, metastatic to lymph nodes (LNs), cytomorphologically distinct from the primary melanoma and from the metastatic melanoma from the same LN basin prior to immune checkpoint inhibitor therapy.…”