Langerhans Cell Histiocytosis Mimicking Malignant Melanoma: A Diagnostic Pitfall

Abstract

Langerhans cell histiocytosis (LCH), especially with an involvement limited to the skin, is a rare entity in adults. In formulating a differential diagnosis of a solitary skin lesion, LCH is rarely considered. Morphologically, cells seen in LCH can mimic those seen in a melanocytic tumor; moreover, they both show S-100 protein reactivity with immunoperoxidase staining. A 63-year-old male presented to a dermatology clinic with a solitary hyperpigmented macule on his right calf. A biopsy specimen showed epithelioid cells within the dermis, singly and in small groups, surrounded and infiltrated by collections of histiocytes and lymphocytes. These cells were diffusely positive for S-100 and negative for Melan-A. A diagnosis of malignant melanoma, spitzoid variant, was rendered, and the patient was sent to our melanoma center for surgical treatment. On histologic examination, some of the lesional cells had reniform, vesicular nuclei with central grooves. Additional immunoperoxidase staining showed strong, diffuse positivity for CD1a, supporting the diagnosis of LCH. LCH is morphologically similar to and can be misdiagnosed as malignant melanoma. It is important to be aware of this pitfall and utilize immunohistochemical and ultrastructural analysis to achieve correct diagnosis.

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

“…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 . In a case series by Busam et al, 3 atypical cases of mononuclear xanthogranulomas with short fascicles and nests of epithelioid and spindled cells were mistakenly diagnosed as melanoma by experienced pathologists .…”

Localized eosinophilic (Langerhans' cell) granuloma of the lower lip. A lesion that may cause diagnostic error

“…Thus, one case reported on the vulva had been diagnosed as a malignant neoplasm, most likely amelanotic melanoma; 8 another genital case was initially diagnosed as an atypical infiltrate suspicious for malignant melanoma (MM); 9 a case on the buttock was interpreted as a cutaneous anaplastic large cell lymphoma; 10 and a diagnosis of malignant spitzoid melanoma was rendered in a case located on the calf. 11 To the best of our knowledge, labial ELCG has not previously been reported. The case is worth a publication as it can present a diagnostic challenge.…”

“…Morphologically, cells of ELCG can mimic those seen in a MM; 8,9,11 moreover, they both show epidermotropism and S100 protein reactivity. However, CD1a and CD207 positivity in the proliferating cells supports the diagnosis of ELCG.…”

“…In the past, this type of lesion has caused diagnostic problems in the elderly. Thus, one case reported on the vulva had been diagnosed as a malignant neoplasm, most likely amelanotic melanoma; 8 another genital case was initially diagnosed as an atypical infiltrate suspicious for malignant melanoma (MM); 9 a case on the buttock was interpreted as a cutaneous anaplastic large cell lymphoma; 10 and a diagnosis of malignant spitzoid melanoma was rendered in a case located on the calf 11 …”

Spindle cell melanocytic lesions—part I: an approach to compound naevoidal pattern lesions with spindle cell morphology and Spitzoid pattern lesions

“…S100 positivity is also seen in neural lesions (although MPNSTs are generally only focally S100 positive and often negative). Langerhans cell lesions are also S100-positive lesions and may reveal misleading pagetoid spread 14 85. Atypical fibroxanthomas and cellular dermatofibromas may show scattered S100-positive Langerhans cells 29.…”