ALK1-Negative Epithelioid Histiocytoma: Lessons From a Rare Case

Area of Science:

• Oncology
• Genetics
• Dermatopathology

Background:

• Epithelioid cell histiocytoma (ECH) is a rare lesion, previously classified as a variant of fibrous histiocytoma.
• ECH's epithelioid morphology can mimic various neoplastic conditions, complicating diagnosis.
• Anaplastic lymphoma kinase (ALK) protein rearrangement is frequently observed in ECH, suggesting a distinct biological profile.

Purpose of the Study:

• To investigate the genetic underpinnings of an ECH case with unusual morphology and immunohistochemical findings.
• To identify specific gene fusions associated with epithelioid cell histiocytoma.
• To contribute to the diagnostic understanding of ALK-related neoplasms.

Main Methods:

• Morphological and immunohistochemical analysis of the ECH lesion.
• Next-generation sequencing (NGS) for comprehensive genetic profiling.
• Identification of gene fusions involving Anaplastic lymphoma kinase (ALK).

Main Results:

• Next-generation sequencing revealed a novel fusion between the Sequestosome 1 (SQSTM1) and Anaplastic lymphoma kinase (ALK) genes (SQSTM1::ALK).
• SQSTM1 is implicated in signal transduction and autophagy, while ALK is crucial for cellular communication and development.
• This finding supports the hypothesis that ECH may be biologically distinct from conventional fibrous histiocytoma.

Conclusions:

• The SQSTM1::ALK fusion represents a significant genetic event in this ECH case.
• Identifying specific ALK fusions aids in differentiating ECH from other epithelioid neoplasms.
• This case expands the spectrum of known ALK fusions and provides valuable data for future diagnostic efforts.