Adult case of langerhans cell histiocytosis (LCH) misinterpretation in fine needle aspiration (FNA): a case study

Abstract

nephroma and secretory carcinoma of the breast and salivary gland. However, NTRK rearrangements are being increasingly identified in a range of soft tissue neoplasms. Due to their morphological heterogeneity, recognition of these NTRK fusion-driven sarcomas is problematic, with a wide range of histological features reported. Thus far, several broad patterns have been described, including an inflammatory myofibroblastic-like pattern, a fibrosarcoma-like pattern and a lipofibromatosis-like pattern. Aims: We present two cases of retroperitoneal NTRKfusion associated sarcoma demonstrating a distinct perineurioma-like pattern and discuss features that should prompt immunohistochemical evaluation with pan-TRK, a surrogate marker of tumours harbouring NTRK fusions, and/or fluorescence in situ hybridisation (FISH) for NTRK gene rearrangement. Methods: Immunohistochemical staining on formalinfixed, paraffin-embedded tissue was performed for pan-TRK as well as a panel of other immunostains. Subsequent FISH analysis was performed to identify NTRK gene rearrangement. Electron microscopy was also used to examine the ultrastructural features in one of the tumours. Results & Conclusions: In both cases, the sarcoma demonstrated spindle cell morphology reminiscent of a perineurioma. Case 1 showed positive nuclear and cytoplasmic staining with pan-TRK but Case 2 was negative for this immunostain. Subsequent FISH analysis showed NTRK1 gene rearrangement in each case, confirming the diagnosis of NTRK-fusion associated sarcoma. Electron microscopy examination of Case 2 concluded ultrastructural features of a mesenchymal spindle cell neoplasm with perineurial differentiation. We therefore report findings of a new perineurioma-like morphological pattern of NTRKrearranged sarcoma. Pathological identification of these tumours is now critical since NTRK-rearranged tumours are one the few translocation-associated sarcomas amenable to the recent advent of highly effective targeted TRK inhibitor therapy.