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- Presentation
Two Diagnostic Case Studies: Indeterminate Cell Neoplasm and BAP1-Associated Melanocytic Tumor Misdiagnosis
Description
The speaker presents two challenging dermatopathology cases. In the first, an 80-year-old woman with a dermal tumor showing monotonous epithelioid cells, marked mitotic activity, hemorrhage, and strong CD1a/S100 positivity initially seemed like Langerhans cell histiocytosis, but additional stains (CD207, CD4, lysozyme, CD68, CD56, CD11c, cyclin D1, BRAF) and the clinical history led to the conclusion that it was best classified as an indeterminate cell neoplasm, not classic Langerhans cell disease or blastic plasmacytoid dendritic cell neoplasm. The speaker emphasizes that CD207 is the best marker to distinguish Langerhans cells from indeterminate cells, and notes that CD56 and lysozyme may signal a worse prognosis. In the second case, a lesion originally diagnosed as a very deep melanoma was re-evaluated in a 41-year-old woman after immunostains and morphology showed a biphasic pattern with a peripheral bland rim and central epithelioid cells, low Ki-67, PRAME negativity, and loss of BAP1 in the central component. Genetic testing revealed only BAP1 and BRAF mutations, supporting a BAP1-inactivated melanocytic tumor rather than conventional melanoma. The case gained urgency when the patient disclosed concurrent brain tumors, which were ultimately diagnosed as glioblastoma, and the speaker notes that the lesion was likely part of BAP1 tumor predisposition syndrome. The main takeaway is to avoid overcalling deeply pigmented or unusual lesions as melanoma without adequate stains, consultation, and correlation with molecular findings.
View moreConclusions
- CD207 is the key immunohistochemical marker for distinguishing Langerhans cells from indeterminate cells, and the overall profile in the first case fit best with an indeterminate cell neoplasm rather than classic Langerhans cell histiocytosis, BPDCN, or myeloid sarcoma.
- Indeterminate cell tumors can be clinically and histologically aggressive, with marked atypia, frequent mitoses, CD56 positivity, and lysozyme/CD68 expression suggesting a worse course.
- BRAF positivity is not specific to Langerhans cell lesions because it can also be seen in indeterminate cell disorders, so diagnosis requires integrating a broader immunophenotype.
- A seemingly routine or symptomatic skin lesion should not be assumed benign or fully classified from limited data, because unexpected presentations may hide a more complex neoplasm.
- The second case showed that a biphasic melanocytic lesion with peripheral bland cells and a central atypical population should raise suspicion for a BAP1-inactivated melanocytic tumor rather than straightforward melanoma.
- Low PRAME expression, low proliferative activity, and only BAP1 and BRAF mutations argue against a typical high-burden nodular melanoma and support a BAPoma/BAP1-loss melanocytoma diagnosis.
- BAP1 loss can be syndromic, so an apparently isolated skin lesion may signal an inherited tumor predisposition syndrome that warrants broader clinical attention.
- Brain disease in the second patient was likely a separate glioblastoma rather than metastatic spread from the skin lesion, illustrating the need to avoid linking concurrent tumors without evidence.
- When pathology findings, clinical behavior, and molecular results do not align, additional stains, consultation, and re-review of all data are essential before rendering a high-stakes diagnosis.
- Fischer AS, Higin WA. The difficulty in interpreting gene expression profiling in BAP1 negative melanocytic tumors. Wiley, May 2018.#10.1111/cup.13277