Department of Pathology, All India Institute of Medical Sciences, New Delhi 110029, India.
Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi 110029, India.
Hum Pathol. 2019 Jan;83:59-67. doi: 10.1016/j.humpath.2018.08.008. Epub 2018 Aug 16.
A significant proportion of sinonasal malignancies comprise poorly differentiated/undifferentiated carcinomas that defy accurate histologic classification and behave aggressively. Recent years have seen a refinement of this spectrum by inclusion of novel entities harboring specific genetic alterations, including SMARCB1 (INI1)-deficient sinonasal carcinoma (SDSC), characterized by inactivating alterations in SMARCB1 gene, as demonstrated by loss of INI1 immunoexpression. Cyclin D1 is a cell-cycle regulatory protein downstream of INI1. Loss of INI1 leads to derepression of cyclin D1 transcription, suggesting its role as a putative therapeutic target. However, cyclin D1 expression has not been assessed in SDSCs. We retrieved all sinonasal carcinomas, including sinonasal undifferentiated carcinoma, undifferentiated carcinoma, poorly differentiated squamous cell carcinoma, and adenocarcinoma. Histopathologic features were reviewed. INI1 immunohistochemistry was performed. Cyclin D1 was performed in cases showing INI1 loss. Loss of INI1 staining was seen in 13 cases (5.8%), including 11 males and 2 females (age range, 11-65 years). Original diagnoses included SDSC (3/13), sinonasal undifferentiated carcinoma (3/13), adenocarcinoma (3/13), poorly differentiated squamous cell carcinoma (2/13), and poorly differentiated carcinoma (2/13). Tumors were predominantly basaloid in 6 cases and plasmacytoid/rhabdoid in 5 cases. We identified 2 cases having oncocytoid cells arranged in a gland-like pattern. Significant cyclin D1 immunoexpression was absent. SDSC is a rare, emerging entity that resembles a poorly differentiated carcinoma. Histomorphologic spectrum of these tumors is evolving. In addition to basaloid and plasmacytoid/rhabdoid cells, oncocytoid/adenocarcinoma-like pattern can also be seen in SDSC and predicts INI1 loss. These histologic patterns can further be subjected to INI1 immunohistochemistry for correct diagnosis.
相当一部分的鼻腔鼻窦恶性肿瘤为低分化/未分化癌，其难以进行准确的组织学分类，且侵袭性强。近年来，由于纳入了具有特定遗传改变的新型实体，对这一谱系进行了细化，包括 SMARCB1（INI1）缺陷型鼻腔鼻窦癌（SDSC），其特征为 SMARCB1 基因失活改变，表现为 INI1 免疫表达缺失。Cyclin D1 是 INI1 下游的细胞周期调节蛋白。INI1 的缺失导致 cyclin D1 转录去抑制，提示其可能作为治疗靶点。然而，SDSC 中尚未评估 cyclin D1 的表达。我们检索了所有的鼻腔鼻窦癌，包括鼻腔鼻窦未分化癌、未分化癌、低分化鳞状细胞癌和腺癌。对组织病理学特征进行了回顾，进行了 INI1 免疫组化检测，对 INI1 缺失的病例进行了 cyclin D1 检测。结果显示 13 例（5.8%）出现 INI1 染色缺失，包括 11 例男性和 2 例女性（年龄 11-65 岁）。最初的诊断包括 SDSC（3/13）、鼻腔鼻窦未分化癌（3/13）、腺癌（3/13）、低分化鳞状细胞癌（2/13）和低分化癌（2/13）。6 例肿瘤以基底样为主，5 例以浆细胞样/横纹肌样为主。我们发现 2 例具有腺样排列的嗜酸性细胞瘤样细胞。Cyclin D1 免疫表达明显缺失。SDSC 是一种罕见的新兴实体，类似于低分化癌。这些肿瘤的组织形态谱正在不断发展。除了基底样细胞和浆细胞样/横纹肌样细胞外，SDSC 中还可见嗜酸性细胞瘤样/腺癌样模式，提示 INI1 缺失。这些组织学模式可进一步通过 INI1 免疫组化进行正确诊断。
