ArticleFrontiers in immunology2026
Case Report: Cytokeratin-positive interstitial reticulum cell tumor with HLA loss of heterozygosity.
Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Introduction: Cytokeratin-positive interstitial reticulum cell (CIRC) tumor, a subtype of fibroblastic reticular cell tumor (FRCT), is an extremely rare primary neoplasm of lymph nodes and soft tissue, with limited understanding of its clinicopathological and molecular features. This case is the first identification of human leukocyte antigen loss of heterozygosity (HLA LOH) in CIRC tumor, which provides novel insights into immune evasion mechanisms and potential therapeutic implications. Case presentation: A 67-year-old female presented with a local recurrence seven years after initial resection of a CIRC tumor on her right shoulder. Physical examination revealed a firm, poorly mobile subcutaneous mass (12cm×8cm). Imaging confirmed a right parascapular mass with bone destruction. Histologically, the recurrent tumor consisted of spindle and epithelioid cells arranged in storiform and sheet-like patterns, with extensive necrosis and a mitotic count of 3 per 10 high-power fields. Immunohistochemically, tumor cells diffusely expressed cytokeratins, vimentin, CD68, CD163, and EMA, with focal expression of SMA, S-100, calponin, and CD3, but were negative for CD21, CD35, CD1a, ALK, and HHV8. The Ki-67 index was 25%. Whole-exome sequencing identified 30 single-nucleotide variants and 7 indels (variant allele frequencies 2.17%-12.6%), copy number gains on chromosomes 7, 11, and 14, and microsatellite stability. Notably, two HLA LOH events affecting HLA-B39:01:01:01 and HLA-C07:02:01:01 were detected. No disease progression was observed during follow-up. Conclusion: This is the first report of HLA LOH in FRCT/CIRC tumor. The key take-away lesson is that HLA LOH represents a potential immune evasion mechanism, which may render single-agent immune checkpoint inhibitors ineffective and thus guide alternative immunotherapeutic strategies. Chromosomal instability appears to be a prominent genomic feature of FRCT. These findings expand the molecular landscape of this rare tumor and underscore the value of comprehensive genomic profiling in guiding individualized treatment.
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