Cui Min, Lemmon Kayla, Jin Zhicheng, Uboha Nataliya V
Department of Pathology, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA.
Division of Hematology and Oncology, Department of Medicine, University of Wisconsin, Madison, WI, USA.
Pathol Res Pract. 2023 Aug;248:154692. doi: 10.1016/j.prp.2023.154692. Epub 2023 Jul 15.
Esophageal carcinoma with SMARCA4 deficiency or dysfunction is a recently recognized entity. This study describes the clinicopathologic features of four cases of esophageal carcinoma with SMARCA4 mutation, three with deep deletion and one with missense mutation. Patients include 3 males and 1 female, with an age range of 45-68 years old. Histologically, the neoplasms showed frequent mitotic activity, large nucleus and prominent nucleoli. Glandular differentiation was variable from not identifiable to approximately 20% in the biopsy material. Percentage of rhabdoid morphology was also variable from not identifiable to 20% of the biopsy material. For these cases, one case was diagnosed SMARCA4 deficient esophageal carcinoma based on the biopsy of a retroperitoneal lymph node showing loss of BRG1 by immunostain, and next generation sequencing confirmed deep deletion of SMARCA4. The other three cases had diagnosis of undifferentiated carcinoma or poorly differentiated carcinoma, and the SMARCA4 deep deletion or mutation was discovered by next generation sequencing. Molecular analysis showed TP53 mutation in all the three cases with SMARCA4 deep deletion. Two of the patients deceased 72 and 78 days after diagnosis, and the other two patients showed limited or no treatment response to chemotherapy. In conclusion, esophageal carcinoma with SMARCA4 mutation may pose significant diagnostic challenge for surgical pathologists due to its variable morphology and immunoprofile, and accurate classification of this entity requires recognition of the spectrum of morphology and utilization of BRG1 immunostain and next generating sequencing.
伴有SMARCA4缺陷或功能障碍的食管癌是一种最近才被认识的实体。本研究描述了4例伴有SMARCA4突变的食管癌的临床病理特征，其中3例为深度缺失，1例为错义突变。患者包括3名男性和1名女性，年龄范围为45 - 68岁。组织学上，肿瘤显示有频繁的有丝分裂活性、大核和明显的核仁。腺性分化程度不一，在活检材料中从无法识别到约20%不等。横纹肌样形态的比例在活检材料中也从无法识别到20%不等。对于这些病例，1例基于腹膜后淋巴结活检免疫染色显示BRG1缺失而被诊断为SMARCA4缺陷型食管癌，二代测序证实SMARCA4深度缺失。另外3例诊断为未分化癌或低分化癌，通过二代测序发现SMARCA4深度缺失或突变。分子分析显示，所有3例SMARCA4深度缺失的病例均有TP53突变。2例患者在诊断后72天和78天死亡，另外2例患者对化疗的反应有限或无反应。总之，伴有SMARCA4突变的食管癌因其形态和免疫表型多变，可能给外科病理学家带来重大诊断挑战，准确分类该实体需要认识其形态谱并利用BRG1免疫染色和二代测序。
