SMARCA4 (BRG1) and SMARCB1 (INI1) expression in TTF-1 negative neuroendocrine carcinomas including merkel cell carcinoma.

SMARCA4 and SMARCB1 loss of function has been implicated in many different tumors. The objective of this study was to investigate the loss of BRG1 and INI1 expression in TTF-1 negative neuroendocrine carcinomas to see if they are analogous to small-cell carcinoma of the ovary, hypercalcemic type. The potential role of these tumor suppressor genes in high-grade neuroendocrine carcinoma largely remains unknown. Cases of previously diagnosed Small cell carcinoma (SmCC), Large cell neuroendocrine carcinoma (LCNEC) and Merkel cell carcinoma (MCC) were selected. Immunohistochemical expression patterns for BRG1 and INI1 were interpreted as: intact, hybrid and complete loss of nuclear staining. SmCC and LCNEC cases were divided as TTF-1 positive and TTF-1 negative subsets. One case of TTF-1 negative SmCC (lung) showed loss of SMARCA4(BRG1) expression. Amongst TTF-1 negative LCNEC, one case (lung) showed complete loss of SMARCA4(BRG1) and partial loss of SMARCB1(INI1) and one case (lymph node) had hybrid expression of SMARCA4(BRG1) with intact SMARCB1(INI1) expression. All TTF-1 positive cases and all MCC cases showed intact expression of SMARCA4(BRG1) and SMARCB1(INI1). Our study highlights that SMARCA4(BRG1) is deficient in a subset of NEC. Inactivation of SMARCA4 in a subset of TTF-1 negative neuroendocrine carcinomas especially of pulmonary site can be further studied for their therapeutic response to targeted therapy e.g. EZH2 inhibitors. In addition, our study is the first to show that BRG1 and INI1 expression are intact in MCC and hence the biology of MCC might be completely exclusive of these two tumor suppressor genes.

Prevalence of Lymphoid Neoplasia in a Retrospective Analysis of Warthin Tumor: A Single Institution Experience.

Warthin tumor is one of the most common benign salivary gland tumors. Overt lymphoma is known to occur in the lymphoid stroma of Warthin tumor. In situ follicular neoplasia is difficult to identify in routine histologic examination of lymphoid tissue and has not been reported in association with Warthin tumor. Our objective is to determine the prevalence of overt malignant lymphoma and in situ follicular neoplasia in Warthin tumor. We conducted a retrospective histological evaluation of 89 sequential Warthin tumor cases with available slides and blocks from the years 2010-2019. Of these, 84 cases were subjected to immunohistochemical testing, while 5 cases had been previously worked up for the suspicion of lymphoma. We identified two additional cases of lymphoid neoplasia associated with Warthin tumor including small lymphocytic lymphoma/chronic lymphocytic leukemia (n = 1) and in situ follicular neoplasia (n = 1) in addition to previously reported case of follicular lymphoma included in this study. The prevalence rate of first-time detected lymphoid neoplasia in Warthin tumor is 3.4%. The prevalence rate of overt lymphoma is 2.2%, while the prevalence of in situ follicular neoplasia is 1.1%. We propose histologic criteria to identify small lymphocytic lymphoma and follicular lymphoma in Warthin tumor. These include a monotonous interfollicular expansion of small lymphocytes and germinal centers composed of a monotonous population of lymphocytes without polarity or tingible body macrophages respectively. It is very important for pathologists to perform a diligent morphological examination and perform immunohistochemistry in suspected cases to identify subtle involvement of Warthin tumor by lymphoma. In patients with involvement of Warthin tumor by in situ follicular neoplasia, concurrent lymphoma in the same tissue and other sites should be considered. Patients without overt lymphoma elsewhere likely have a low risk of progression to follicular lymphoma. The low prevalence of in situ follicular neoplasia in Warthin tumor, combined with the low rate of clinical progression to lymphoma, make routine screening of Warthin tumor for in situ follicular neoplasia unnecessary.