Morphological, histochemical and immunohistochemical analysis of primary signet ring cell (vacuoleted) neoplasms of the thyroid gland

Our knowledge about primary thyroid tumors showing signet ring cell (SRC) morphology is quite limited. In this study, we aimed to describe the morphological, histochemical, and immunohistochemical features of primary thyroid neoplasms with SRCs. Sections were taken from the paraffin blocks formed by the tissue microarray method using cores taken from primary thyroid tumors with SRCs/vacuolated cytoplasm that are examined in the pathology laboratory of our hospital between 2011 and 2019. Various histochemical special stains (PAS, PAS-D, and mucicarmine) and immunohistochemical biomarkers (thyroglobulin, TTF-1, PAX8, HBME-1, CK19, CD56, cyclin-D1, ALK, PTEN, NTRK, NRAS, SDHB, AMA, GRIM-19 and adipophilin) were applied and the data obtained were analyzed with the conjunction of clinical and morphological findings. Our study group -which has the largest number of primary thyroid tumors with SRCs [n=43] in the literature consisted of 5 follicular adenomas, 15 micro noninvasive follicular thyroid neoplasms with papillary like nuclear features (NIFTP), 17 NIFTP, 2 papillary microcarcinoma, 3 papillary thyroid carcinoma and 1 follicular thyroid carcinoma. As a result of our study, the biological features (diagnosis of tumors, diagnostic criteria and differential diagnosis, basic clinical features, possible etiological mechanisms, macroscopic and microscopic morphological features, histochemical and immunohistochemical aspects) of primary thyroid tumors with SRCs were defined. Primary thyroid neoplasms with SRCs should be differentiated from each other&metastatic lesions as well as from other clear cell lesions. We propose to name non-invasive follicular thyroid neoplasms with papillary nuclear features that are exhibiting SRC as "signet ring cell NIFTP" and "signet ring cell micro-NIFTP" according to tumor diameter, since these tumors have innocent clinical course. Keywords: Thyroid gland, Signet ring cell neoplasia, NIFTP, Micro-NIFTP, Histochemistry, Immunohistochemistry