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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- "50 or more C-cells in at least one low-power field (100!), a number greater than that found in most normal subjects (De Lellis & Wolfe 1981, Albores-Saavedra & Krueger 2001) and has been classified as physiologic/reactive or neoplastic (Perry et al. 1996, Matias-Guiu et al. 2004). Reactive CCH has been reported in neonates, the elderly, hyperparathyroidism , Hashimoto's thyroiditis, and follicular thyroid adenomas (Guyetant et al. 1994, Matias-Guiu et al. 2004) and can be defined, according to the growth "
ABSTRACT: The cut-off values able to differentiate between reactive or neoplastic C-cell hyperplasia (CCH) or to predict sporadic medullary thyroid cancer (MTC) are still debated both for basal and stimulated calcitonin (bCT and sCT). In the present study, the prevalence and the histological patterns of CCH in 15 patients with multinodular goiter (MNG), bCT>10 pg/ml and sCT levels >50 pg/ml were studied. As controls, 16 patients with MNG and bCT levels <10 pg/ml and 4 patients with familial (FMTC) were included. For each case, calcitonin (CT) immunoreactive cells were counted in 60 consecutive high-power fields (400x) and CCH classified as focal, diffuse, nodular, or neoplastic. RET genetic analyses were performed at the germline and tissue levels in MTC and CCH cases. In patients with MNG, sCT levels >50 pg/ml were associated with CCH or MTC, being the total number of C-cells/60 fields significantly higher than that found in MNG with normal bCT (P = 0.0008) and comparable with that detected in FMTCs. In the group with sCT>50 pg/ml, the C-cells displayed a neoplastic phenotype. Neither germline nor somatic RET mutations were found. In conclusion, sCT levels >50 pg/ml were always associated with CCH, without correlation between CT levels and the number of C-cells or the final diagnosis. The C-cells had a morphology and distribution pattern similar to those observed in FMTC. Thus, sCT levels >50 pg/ml indicate the presence of CCH with a possible preneoplastic potential, suggesting the opportunity to perform a prophylactic surgical treatment.Endocrine Related Cancer 07/2007; 14(2):393-403. DOI:10.1677/ERC-06-0053 · 4.91 Impact Factor
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- "One example of CCH in peritumoural tissue of a patient with a radiation-induced thyroid tumour is shown in Figure 1. A C-cell hyperplasia diagnosis was made when at least three low-power fields (6100 magnification) containing more than 50 calcitonin-immunostained C-cells were observed (Guyetant et al, 1994). "
ABSTRACT: The RET proto-oncogene encodes a protein structurally related to transmembrane receptors with an intracellular tyrosine kinase domain. In human thyroid gland, the RET proto-oncogene is normally expressed in parafollicular C-cells. Thyroid C-cell hyperplasia is associated with inherited medullary thyroid carcinomas and is considered as a pre-neoplastic stage of C-cells disease. It has also been observed in thyroid tissues adjacent to follicular and papillary carcinomas. In order to study the relationship between a misfunctioning of the RET proto-oncogene and the presence of C-cell hyperplasia, we compared a series of thyroid glands presenting sporadic or radiation-associated tumours, as well as samples of unrelated normal thyroid tissues, for alteration in exons 10 and 11 of the gene and for the presence or absence of C-cell hyperplasia. Here we report a significantly higher frequency of C-cell hyperplasia present in peritumoural thyroid tissues of radiation-induced epithelial thyroid tumours, than in peritumoural of sporadic thyroid tumours or in control normal thyroid tissues (P=0.001). A G691S RET polymorphism was present with a higher frequency in radiation-induced epithelial thyroid tumours (55%) than in sporadic tumours (20%) and in control normal thyroid tissues (15%). Interestingly, this polymorphism was associated in the majority (88%) of radiation-induced tumours with a C-cell hyperplasia in the peritumoural tissues. Several explanations for this association are discussed. British Journal of Cancer (2002) 86, 1929–1936. doi:10.1038/sj.bjc.6600371 www.bjcancer.com © 2002 Cancer Research UKBritish Journal of Cancer 07/2002; 86(12):1929-36. DOI:10.1038/sj.bjc.6600371 · 4.82 Impact Factor
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ABSTRACT: The measurement of basal serum calcitonin (CT) in patients with evidence of Hashimoto's thyroiditis (HT) has been proposed in a recent study demonstrating an increased prevalence of elevated basal and stimulated CT. The aim of this study was to evaluate the frequency and relevance of elevated CT levels in HT. The basal sera CT were measured in 568 consecutive HT patients using a chemiluminescent immuno-assay. Whenever the serum CT was > 10 pg/ml, a pentagastrin (PG) stimulation test was performed. Two patients with abnormal/pathological PG tests were identified. Total thyroidectomy and lymph node dissection revealed for the first patient medullary thyroid carcinoma (MTC) and for the second patient C cell hyperplasia (CCH), together with papillary thyroid carcinoma. Our data showed a low prevalence of MTC and its premalignant condition CCH in HT patients; nevertheless, the patient with MTC presented lymph node metastasis. The fact that both cases presented without evidence of nodular thyroid disease highlights the persistent diagnostic dilemma of CT screening programs.Anticancer research 01/2006; 26(1B):723-7. · 1.87 Impact Factor