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Foci of spindle cell proliferation in multinodular goiter of thyroid: epithelial-mesenchymal transformation or embryonic remnants?

ABSTRACT: Foci of spindle cell proliferation of the thyroid gland have been documented in adenoma and carcinoma, but not much in multinodular goiter. We report a case of spindle cell proliferation detected in multinodular goiter in a 61-year-old female. Histological examination revealed foci of solid area around the normal thyroid follicles. There were two components in this solid area; the first one was composed of epithelial cells with small bland ovoid nuclei and the second one with spindle cells with short spindle-shaped nuclei. Immunohistochemical analysis revealed that the spindle cells were positive for thyroid transcription factor (TTF)-1, Vimentin, CK (AE1/AE3), and negative for p63, etc. The cells with ovoid nuclei had more abundant CK (AE1/AE3) immunoreactivity than those with short spindle-shaped nuclei. In addition, the transition between these two cell types was clearly identified. We hypothesized that this area represented embryonic remnant of developing thyroid gland and therefore evaluated histological features of developing fetal thyroid but this lesion by no means simulated histological features of any developing stages of fetal thyroid gland. The spindle cell foci of thyroid gland could possibly arise from epithelial-mesenchymal transformation of thyroid follicular epithelium in this thyroid gland but it awaits further investigations for clarification.

SUBMITTER: Gao Y

PROVIDER: S-EPMC6958209 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Foci of spindle cell proliferation in multinodular goiter of thyroid: epithelial-mesenchymal transformation or embryonic remnants?

Gao Yunhe Y Sun Ping-Li PL Yao Min M Sasano Hironobu H Gao Hongwen H

International journal of clinical and experimental pathology 20180401 4

Foci of spindle cell proliferation of the thyroid gland have been documented in adenoma and carcinoma, but not much in multinodular goiter. We report a case of spindle cell proliferation detected in multinodular goiter in a 61-year-old female. Histological examination revealed foci of solid area around the normal thyroid follicles. There were two components in this solid area; the first one was composed of epithelial cells with small bland ovoid nuclei and the second one with spindle cells with ...[more]

PMID: 31938325

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Project description:BackgroundThe most appropriate surgical procedure for multinodular goiter (MNG) remains under debate. Incidental thyroid carcinoma (ITC) is often identified on histopathological examination after thyroidectomy performed for presumed benign MNG.Aim of the studyThe aim of the study was to determine the value of radical surgery for MNG patients considering the prevalence of ITC diagnosed postoperatively.Materials and methodsWe conducted retrospective analysis of the medical records of 2,306 patients surgically treated for MNG between 2008 and 2013 at one center. None of the patients presented with any suspicion of malignancy, history of familial thyroid cancer, multiple endocrine neoplasia syndrome or previous head or neck radiation exposure.ResultsAmong the 2,306 MNG patients, ITC was detected in 49 (2.12%) (44 women and 5 men, with average ages of 52.2 (21-79) and 55.6 (52-62), respectively). Papillary thyroid carcinoma was significantly more frequently observed than other types of ITC (p<0.00001). Among the MNG patients, 866 (37.5%) underwent total/near total surgery, 464 (20.1%) received subtotal thyroidectomy, and 701 (30.3%) received the Dunhill operation. The remaining 275 (11.9%) patients underwent a less radical procedure and were classified as "others." Among the 49 (100%) patients with ITC, 28 (57.1%) underwent radical surgery. Another 21 (42.9%) patients required completion surgery due to an insufficient primary surgical procedure. A total of 21 (2.42%) patients in the total/near total surgery group were diagnosed with ITC, as well as 16 (2.48%) in the subtotal thyroidectomy group and 12 (1.71%) in the Dunhill operation group; 21 (100%), 4 (25%) and 3 (25%) of these patients, respectively, underwent radical surgery; thus, 0 (0%), 12 (75%) and 9 (75%) required completion surgery. The prevalence rates of ITC were comparable between the radical and subtotal surgery groups (2.42% and 3.44%, respectively, p = 0.4046), and the prevalence was higher in the radical surgery group than in the Dunhill operation group (2.42% and 1.71%, respectively, p = 0.0873). A significant difference was observed between the group of patients who underwent total/near total surgery, among whom all of the patients with ITC (100%) received primary radical surgery, and the groups of patients who received the subtotal and Dunhill operations, among whom only 25% of the patients with ITC in each group received primary radical surgery (p<0.0001).ConclusionsMore radical procedures for MNG result in a lower risk of reoperation for ITC. The prevalence of ITC on postoperative histopathological examination should determine the extent of surgery in MNG patients. In the future, total/near total thyroidectomy should be considered for MNG patients due to the increased prevalence of ITC to avoid the necessity for reoperation.

Project description:CONTEXT:Nontoxic multinodular goiter (MNG) is frequently observed in the general population, but little is known about the underlying genetic susceptibility to this disease. Familial cases of MNG have been reported, and published reports describe 5 families that also contain at least 1 individual with a Sertoli-Leydig cell tumor of the ovary (SLCT). Germline mutations in DICER1, a gene that codes for an RNase III endoribonuclease, have been identified in families affected by pleuropulmonary blastoma (PPB), some of whom include cases of MNG and gonadal tumors such as SLCTs. OBJECTIVE:To determine whether familial MNG with or without SLCT in the absence of PPB was associated with mutations in DICER1. DESIGN, SETTING, AND PATIENTS:From September 2009 to September 2010, we screened 53 individuals from 2 MNG and 3 MNG/SLCT families at McGill University for mutations in DICER1. We investigated blood lymphocytes and MNG and SLCT tissue from family members for loss of the wild-type DICER1 allele (loss of heterozygosity), DICER1 expression, and microRNA (miRNA) dysregulation. MAIN OUTCOME MEASURE:Detection of germline DICER1 gene mutations in familial MNG with and without SLCT. RESULTS:We identified and characterized germline DICER1 mutations in 37 individuals from 5 families. Two mutations were predicted to be protein truncating, 2 resulted in in-frame deletions, and 1 was a missense mutation. Molecular analysis of the 3 SLCTs showed no loss of heterozygosity of DICER1, and immunohistochemical analysis in 2 samples showed strong expression of DICER1 in Sertoli cells but weak staining of Leydig cells. miRNA profiling of RNA from lymphoblastoid cell lines from both affected and unaffected members of the familial MNG cases revealed miRNA perturbations in DICER1 mutation carriers. CONCLUSIONS:DICER1 mutations are associated with both familial MNG and MNG with SLCT, independent of PPB. These germline DICER1 mutations are associated with dysregulation of miRNA expression patterns.

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Foci of spindle cell proliferation in multinodular goiter of thyroid: epithelial-mesenchymal transformation or embryonic remnants?

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Foci of spindle cell proliferation in multinodular goiter of thyroid: epithelial-mesenchymal transformation or embryonic remnants?

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