Incidental Thyroid C Cell Hyperplasia: Clinical Significance and Implications in Practice

Abstract

Incidental C cell hyperplasia (CCH) following thyroidectomy for other indications may rarely be encountered, which may raise concerns about its clinical significance and proper management. CCH can be classified as physiological (reactive) or neoplastic. Reactive CCH has no malignant potential and can be observed in association with many other thyroid diseases (including differentiated thyroid cancer); in contrast, neoplastic CCH should be considered as a preneoplastic stage in the spectrum of C cell disease, ultimately leading to the development of medullary thyroid cancer (MTC). Neoplastic CCH is commonly observed in patients with germ-line mutations in the RET oncogene (commonly in families with a history of hereditary MTC, i.e. familial MTC or multiple endocrine neoplasia type 2 (MEN2)). CCH should be considered in patients with hypercalcitoninemia without nodular thyroidopathy. Total thyroidectomy, which is commonly performed for the majority of thyroid diseases, is an adequate treatment and achieves cure, even in patients with neoplastic CCH. There is no role for cervical lymph node dissection in patients with pure CCH. In conclusion, reactive CCH has no malignant potential, in contrast to neoplastic CCH. Total thyroidectomy achieves cure of patients with CCH.

Immunohistochemical characteristic of C cells in European bison thyroid gland

“…TSH overstimulation, hypercalcemia, paracrine factors). In humans, it was reported in newborns, elderly as well as in patients with hyperparathyroidism, hypergastrinemia due to Zollinger-Ellison syndrome, exogenous estrogen administration and in some thyroid diseases [19,20]. It was also described in tissue adjacent to thyroid tumors and as a preneoplastic condition [20].…”

Neoplasia endocrina múltiple tipo IIa (síndrome de Sipple) de diagnóstico incidental con feocromocitoma bilateral y carcinoma medular de tiroides. Reporte de un caso

“…El tercer tipo de manifestación se corresponde con aquel paciente con dolores articulares generalizados, dolor abdominal, depresión o urolitiasis en el que el protocolo delata la presencia de hipercalcemia, que lleva a la sospecha de hiperparatiroidismo y de adenoma paratiroideo 18 . Finalmente existe un tipo de pacientes en los que, de forma indirecta, uno o más de los tres componentes principales del síndrome de Sipple desarrolla manifestaciones que dirigen el protocolo diagnóstico hacia otras entidades como úlcera péptica 19 , liquen cutáneo amiloidótico 20 , síndrome de Cushing 21 , cardiomiopatía inducida por catecolaminas 22 e incluso se ha reportado que la tiroidectomía por una causa ajena a cáncer medular de tiroides arroja como resultado hiperplasia de las células parafoliculares, lo que desencadena la sospecha y posteriormente el diagnóstico 23 . Incluso existe un caso reportado por Casey, et al 24 en el que se decidió realizar un protocolo diagnóstico en una paciente de 35 años de edad con fatiga y pérdida de peso, descubriendo masas hepáticas que resultaron en metástasis de carcinoma de cáncer medular de tiroides, lo que lo diferencia de nuestro caso, ya que no se demostraron metástasis a distancia.…”

Incidentally-Diagnosed Multiple Endocrine Neoplasia IIA (Sipple Syndrome) with Bilateral Pheochromocytoma and Medullary Thyroid Carcinoma

“…The third type of manifestation corresponds to those patients with generalized joint pain, abdominal pain, depression, or urolithiasis, where the protocol reveals the presence of hypercalcemia, which drives to the suspicion of hyperparathyroidism and parathyroid adenoma 18 . Finally, there is a type of patients in whom one or more of the main Sipple syndrome components indirectly develop manifestations that direct the diagnostic protocol towards other entities such as peptic ulcer 19 , cutaneous lichen amyloidosis 20 , Cushing syndrome 21 , and catecholamine-induced cardiomyopathy 22 ; even thyroidectomy for causes other than medullary thyroid cancer has been reported to yield parafollicular cell hyperplasia as a result, which raises suspicion and subsequently leads to diagnosis 23 . There is even one case reported by Casey, et al 24 , who decided to implement a diagnostic protocol in a 35-year-old female patient with fatigue and weight loss, and discovered hepatic masses that turned out to be medullary thyroid cancer metastases, which differentiates this case from ours where no distant metastasis was demonstrated.…”