关键词: 鼻腔鼻窦梭形细胞肿瘤, 二代测序, 误诊分析, 炎性肌成纤维细胞瘤, 基因融合, 鉴别诊断 

Abstract: Objective  To investigate the clinicopathological and molecular characteristics of a group of rare sinonasal spindle cell neoplasms that are morphologically prone to be misdiagnosed as inflammatory myofibroblastic tumor (IMT), and to analyze the diagnostic pitfalls and the clinical application of molecular testing in such challenging cases. Methods  A retrospective analysis was conducted on all cases initially diagnosed as sinonasal IMT in the Department of Pathology, Beijing Tongren Hospital, from January 2007 to December 2021 (21 cases). From this cohort, three rare and challenging cases were selected. These cases were initially diagnosed as IMT with malignant transformation but were characterized as an aggressive clinical course leading to death within a short period. Next-generation sequencing (NGS) was performed on archived formalin-fixed, paraffin-embedded tissue from these three cases to analyze their genomic profiles. Pathological diagnoses were re-evaluated in conjunction with clinical data. Results  Morphologically, all three tumors overlapped with IMT, showing spindle cell proliferation with inflammatory infiltration. However, all lacked IMT-characteristic ALK expression and gene rearrangements. NGS precisely identified distinct molecular drivers in every case: Case 1 harbored a novel SLC9A3::TERT fusion, leading to a revised diagnosis of undifferentiated sarcoma; Case 2 showed homozygous deletion of CDKN2A/B and loss of H3K27me3 expression, supporting a diagnosis of malignant peripheral nerve sheath tumor (MPNST); Case 3 was positive for the NAB2::STAT6 fusion, resulting in a revised diagnosis of malignant solitary fibrous tumor (SFT). All three patients died of progressive disease (median survival: 21 months), confirming the highly aggressive biological behavior consistent with the revised diagnoses. Conclusion  There exits a rare subset of sinonasal spindle cell neoplasms that morphologically mimic IMT but harbor distinct molecular drivers, representing a significant diagnostic pitfall. This pitfall should be suspected in cases with IMT-like morphology that are ALK-negative or exhibit an aggressive clinical course (rapid progression, recurrence, or metastasis). In such clinicopathologically discordant and challenging cases, molecular testing plays an indispensable role: it not only enables a precise diagnosis by rectifying misdiagnosis but also provides direct evidence for prognostic assessment and therapeutic decision-making.

Key words: sinonasal spindle cell neoplasms, next-generation sequencing, misdiagnosis analysis, inflammatory myofibroblastic tumor, gene fusion, differential diagnosis