C-cell hyperplasia associated with chronic lymphocytic thyroiditis: A retrospective quantitative study of 112 cases
ABSTRACT Since the first description by Wolfe et al of C-cell hyperplasia (CCH) in asymptomatic relatives of patients suffering from a medullary thyroid carcinoma (MTC), several investigators have described CCH associated with a chronic lymphocytic thyroiditis (CLT) not within the context of MTC or multiple endocrine neoplasia (MEN). We report the study of C-cell density in 112 cases of CLT on retrospective surgical material to determine the frequency of the association between CCH and CLT. The cases of CLT were compared with 19 normal thyroid glands obtained at necropsy. C cells, immunoreactive with a polyclonal anti-calcitonin (CT) antibody, were counted at high magnification (×400) and the number of low-power magnification (×100) microscopic fields (LPFs) containing at least 50 C cells per slide was assessed. Image analysis was performed to determine the C-cell density expressed in number of C cells/cm2. C-cell hyperplasia was defined by the following criteria: C-cell density > 40 cells/cm2 and the presence of at least three LPFs containing more than 50 C cells. Twenty percent of the cases of CLT showed a CCH thus defined, and four of them had an elevated serum CT level. Statistical analysis showed no clinical or biological correlation with the presence of CCH. However, the frequency of CCH was higher if a follicular cell carcinoma was associated with CLT. This study confirms a pathological association between CCH and CLT, provides new criteria for the definition of CCH on surgical pathology material, and reports four cases with an elevated serum CT level not within the context of MTC or MEN.
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ABSTRACT: Mutations in the RET proto-oncogene have been implicated in the pathogenesis of several forms of medullary thyroid cancer (MTC). Multiple endocrine neoplasia type 2 (MEN-2) is an autosomal dominant syndrome caused by germline activating mutations of the RET proto-oncogene and has been categorized into three distinct clinical forms. MEN-2A is associated with MTC, bilateral pheochromocytoma, and primary hyperparathyroidism. MEN-2B is associated with MTC, bilateral pheochromocytoma, and mucosal neuromas. The rarest clinical form of MEN-2 is familial MTC (FMTC), which is also associated with MTC, but other endocrinopathies are characteristically not present. Each clinical form of MEN-2 results from a specific RET gene mutation, with a strong correlation of phenotype expression with regard to the onset and course of MTC and the presence of other endocrine tumors and a corresponding genotype. Recommendations for screening of RET mutations are necessary as their presence or absence will influence interventional strategies such as the timing of a prophylactic thyroidectomy and extent of surgery. Timing of screenings and development of interventional strategies are extremely important in caring for patients with certain RET mutations as evidence of metastatic MTC has been documented as early as 6 years of age. Interventional strategies should consider the risks of complications of these interventions based on certain characteristics of each individual case such as age of the patient, course of disease in affected family members, and the invasiveness of any proposed surgical procedure. Conflict of interest:None declared.Journal of Clinical Research in Pediatric Endocrinology 03/2013; 5 Suppl 1(Suppl 1):70-8. DOI:10.4274/Jcrpe.870
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ABSTRACT: The etiology of medullary thyroid carcinoma remains unknown. The aim of this study was to determine whether there is a significant association between medullary thyroid carcinoma and Hashimoto's thyroiditis in the histopathologic material of thyroidectomized patients. Retrospective cross-sectional study. In this study, we reviewed the medical records of all patients who underwent total thyroidectomy for different thyroid-related complaints between January 2000 and January 2012 at Jordan University Hospital-Amman, Jordan. To highlight relevant previously published studies addressing this topic, a literature search was conducted for English language studies reporting "medullary thyroid carcinoma" or "C-cell hyperplasia" in patients with Hashimoto's thyroiditis. Of the 863 patients with a mean age of 47.2 ± 12.3 years who underwent total thyroidectomy during the study period, 78 (9.04 %) were diagnosed with Hashimoto's thyroiditis, and 15 (1.74 %) had medullary thyroid carcinoma, 3 (20 %) of whom had coexistent Hashimoto's thyroiditis. A total of 683 (79.1 %) patients had benign thyroid disease, 67 (9.8 %) of whom had Hashimoto's thyroiditis. The difference between these rates was not statistically significant (p = 0.19). When examined by gender, 9 females had medullary thyroid carcinoma, 3 (33.3 %) of whom had coexistent Hashimoto's thyroiditis; by contrast, of 560 females with benign thyroid disease, 62 (11.1 %) had Hashimoto's thyroiditis (p = 0.04). Although this study population represents a small and single-institution experience, our results suggest that there might be an association between Hashimoto's thyroiditis and medullary thyroid carcinoma only in female patients who undergo total thyroidectomy.
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ABSTRACT: BACKGROUND Multiple endocrine neoplasia type 2 (MEN 2) is an inherited disease caused by germline mutations in the RET proto-oncogene, and is responsible for the development of endocrine neoplasia. Its prognosis is dependent on the appearance and spread of medullary thyroid carcinoma (MTC). Relatives at risk can be identified before clinical or biochemical signs of the disease become evident.METHODS Twenty-one families with MEN 2 (16 families with MEN 2A and 5 families with MEN 2B) were studied. Peripheral blood DNA was amplified by polymerase chain reaction. DNA sequence or restriction enzyme analysis was performed to detect mutations of RET proto-oncogene exons 10, 11, and 16. Molecular analysis was carried out in all index patients as well as in 98 relatives of MEN 2A patients (60 juveniles, ages 6 months to 21 years, and 38 adults, ages 22 to 81 years) and in 13 relatives (6 juveniles ages 10 to 21 years, and 7 adults ages 41 to 66 years) from MEN 2B families.RESULTSMolecular studies showed a mutation at codon 634, exon 11 in all MEN 2A patients. All MEN 2B patients showed an ATG to ACG (Met918Thr) mutation. In MEN 2A families, 42 out of 98 relatives were affected. Total thyroidectomy was performed in 18 juvenile carriers ages 17 months to 21 years. Histopathologic studies of the glands revealed parafollicular cell (C-cell) hyperplasia in all of these carriers, medullary thyroid carcinoma in 15 carriers, and only one carrier with lymph node metastases.CONCLUSIONS The consistent finding of C-cell disease in all the juvenile carriers who underwent preventive thyroidectomy emphasizes the relevance of early screening in children at risk of developing MTC. The presence of MTC in the specimen of prophylactic thyroidectomy from a 17 month old girl highlights the importance of thyroidectomy as soon as the molecular diagnosis is confirmed. Cancer 2002;94:323–30. © 2002 American Cancer Society.Cancer 01/2002; 94(2). · 4.90 Impact Factor