Department of Pathology, University at Buffalo, Buffalo, NY, USA.
Department of Pathology, UT MD Anderson Cancer Center, Houston, TX, USA.
Head Neck Pathol. 2021 Dec;15(4):1246-1252. doi: 10.1007/s12105-021-01338-0. Epub 2021 May 31.
Integrase interactor 1 (INI1)-deficient carcinomas, recently described in several sites including the head and neck, are associated with basaloid or rhabdoid histology and aggressive behavior irrespective of origin. INI1-deficient thyroid carcinoma is extremely rare. We present here the phenotype and genotype of an INI1-deficient thyroid carcinoma and report on the INI1 protein expression in various thyroid lesions. Case report with clinicopathologic and molecular characterization and INI1 assessment in 184 thyroid lesions. A 67-year-old woman presented with globus sensation due to a large thyroid mass with extrathyroid extension, focal necrosis and cervical and mediastinal nodal involvement. Histologically, tumor cells had a solid, alveolar and pseudopapillary architecture in a myxoid stroma, exhibited monomorphic epithelioid and focal rhabdoid/plasmacytoid morphology and lacked glandular, squamous or follicular cell differentiation. Tumor cells were positive for AE1/AE3 and CK18 but negative for TTF1, thyroglobulin and PAX8. INI1 nuclear expression was absent. A frameshift SMARCB1/INI1 mutation was detected. In addition, TET2 and Notch1 mutations were present but alterations of BRAF, RET, PAX8/PPAR8 or RAS were not identified. Patient death occurred 14 months after diagnosis from post-therapeutic complications. None of the 184 benign and malignant thyroid lesions tested, including 12 poorly and undifferentiated thyroid carcinomas, were INI1-deficient. INI1-deficient thyroid carcinoma shares the phenotype, genotype and biology of other INI1-deficient tumors. Epithelioid and plasmacytoid/rhabdoid changes are most frequent whereas basaloid morphology is not reported, in contrast with sinonasal tumors. Poorly differentiated and undifferentiated thyroid tumors with epithelioid or rhabdoid morphology should be tested for INI1 protein expression to better characterize these aggressive neoplasms and identify patients eligible for targeted therapy.
INI1 缺陷型癌，最近在多个部位包括头颈部被描述，与基底细胞样或横纹肌样组织学和侵袭性行为相关，而与起源无关。INI1 缺陷型甲状腺癌极为罕见。我们在此介绍一例 INI1 缺陷型甲状腺癌的表型和基因型，并报告 INI1 蛋白在各种甲状腺病变中的表达。对 184 例甲状腺病变的临床病理和分子特征及 INI1 评估的病例报告。一名 67 岁女性因甲状腺巨大肿块伴有甲状腺外延伸、局灶性坏死和颈纵隔淋巴结受累而出现球状物感。组织学上，肿瘤细胞在黏液样基质中具有实性、腺泡状和假乳头状结构，表现出单形上皮样和局灶性横纹肌样/浆细胞样形态，缺乏腺体、鳞状或滤泡细胞分化。肿瘤细胞对 AE1/AE3 和 CK18 阳性，但对 TTF1、甲状腺球蛋白和 PAX8 阴性。INI1 核表达缺失。检测到框移 SMARCB1/INI1 突变。此外，还存在 TET2 和 Notch1 突变，但未发现 BRAF、RET、PAX8/PPAR8 或 RAS 的改变。患者在诊断后 14 个月因治疗后并发症死亡。在 184 例良性和恶性甲状腺病变中，包括 12 例低分化和未分化甲状腺癌，均未发现 INI1 缺陷。INI1 缺陷型甲状腺癌具有其他 INI1 缺陷型肿瘤的表型、基因型和生物学特性。上皮样和浆细胞样/横纹肌样改变最常见，而基底细胞样形态则未见报道，与鼻旁窦肿瘤相反。具有上皮样或横纹肌样形态的低分化和未分化甲状腺肿瘤应检测 INI1 蛋白表达，以更好地描述这些侵袭性肿瘤，并确定有资格接受靶向治疗的患者。
