Laboratory Medicine Program, University Health Network.
Department of Laboratory Medicine and Pathobiology, University of Toronto.
Am J Surg Pathol. 2020 Sep;44(9):1244-1250. doi: 10.1097/PAS.0000000000001498.
Primary squamous cell carcinomas (SCCs) of the middle ear and temporal bone are rare and usually keratinizing by morphology. Nonkeratinizing, basaloid SCCs arising in this area are exceedingly rare, and, due to the anatomic proximity to the skull base, nasopharynx, and nasal sinuses, the differential diagnosis is broad. Most tumors with squamous differentiation arising in these subsites are either viral-induced (human papillomavirus/Epstein-Barr virus) or rarely may have specific molecular alterations (BRD4-NUT, EWSR1-FLI translocations). Occasional tumors are negative for these findings, and their pathogenesis is unknown. A recently discovered DEK-AFF2 fusion was clinically detected in a series of 2 cases known to the authors. This fusion has been previously reported in the literature in a patient with a base of skull tumor who was an exceptional responder to programmed cell death protein 1 inhibitor therapy. We examine here the histomorphologic and molecular findings of 2 additional cases of an emerging entity. Two male patients were identified. Each had a primary middle ear/temporal bone mass with locally advanced disease. The histology was reviewed, and immunohistochemistry was performed. RNA-based next-generation sequencing was performed for clinical detection of diagnostic or actionable fusions. Both patients had basaloid/nonkeratinizing tumors on biopsy. They were positive for markers of squamous differentiation (HMWK, CK5, and p40). By RNA sequencing, they demonstrated the presence of a DEK-AFF2 fusion and were negative for EWSR1 and NUT translocations. The DEK-AFF2 fusion may define a novel diagnostic category of middle ear and temporal bone nonkeratinizing/basaloid SCCs. This fusion also may represent a potential avenue for immunotherapy in these patients. Further studies are needed to fully explore whether this fusion defines a location-specific clinicopathologic entity.
中耳和颞骨的原发性鳞状细胞癌（SCC）很少见，通常形态学上为角化。该区域发生的非角化、基底样 SCC 极为罕见，由于与颅底、鼻咽和鼻窦解剖位置临近，鉴别诊断广泛。这些部位发生的具有鳞状分化的大多数肿瘤要么是病毒诱导的（人乳头瘤病毒/Epstein-Barr 病毒），要么是罕见的可能具有特定分子改变（BRD4-NUT、EWSR1-FLI 易位）。偶尔也有肿瘤这些发现均为阴性，其发病机制尚不清楚。作者最近在一系列 2 例已知病例中发现了一种新的 DEK-AFF2 融合。该融合以前在文献中报道过一例颅底肿瘤患者，该患者对程序性细胞死亡蛋白 1 抑制剂治疗有显著反应。我们在此检查了 2 例新出现实体的组织形态学和分子发现。确定了 2 名男性患者。每位患者均有原发性中耳/颞骨肿块，伴局部晚期疾病。进行了组织学复习，并进行了免疫组织化学检查。进行了基于 RNA 的下一代测序，以临床检测诊断或可操作的融合。两名患者的活检均为基底样/非角化肿瘤。他们的鳞状分化标志物（HMWK、CK5 和 p40）阳性。通过 RNA 测序，他们发现了 DEK-AFF2 融合，且 EWSR1 和 NUT 易位阴性。DEK-AFF2 融合可能定义了一种新的中耳和颞骨非角化/基底样 SCC 诊断类别。该融合也可能代表这些患者免疫治疗的潜在途径。需要进一步研究以充分探讨该融合是否定义了特定位置的临床病理实体。
