Familial Nonmedullary Thyroid Carcinoma Characterized by Multifocality and a High Recurrence Rate in a Large Study Population

Abstract

First-degree relatives of persons with thyroid cancer are known to be at relatively high risk for the disease. To better understand the clinicopathologic characteristics of familial nonmedullary thyroid carcinoma (FNMTC), we carried out a retrospective study in which we identified individuals treated at our institution who had at least one first-degree relative with the disease. We used data obtained from our patient records to compare the features of 258 cases of the disease with the features of sporadic papillary or follicular thyroid carcinoma in another group of patients. The 258 patients represented 154 families and were selected from among 6458 patients with papillary or follicular thyroid carcinoma who underwent thyroidectomy between 1946 and 2000. Compared to the patients with sporadic disease, the FNMTC patients were more likely to have intraglandular dissemination (28.5% vs. 40.7%; p < 0.0001) and multiple benign nodules (29.8% vs. 41.5%; p <0.0001). There were no significant differences between the two types of patients in terms of gender, age, tumor diameter, adhesion to or invasion of the surrounding tissues, macroscopic metastasis observed at surgery, histology, presence of single benign nodules, presence of chronic thyroiditis, microscopic metastasis, or rate of lymph node metastasis. Recurrence was statistically frequent in the FNMTC patients compared with that in the sporadic disease patients (16.3% vs. 9.6%; p = 0.0005), and the disease-free survival rate was significantly poorer in the FNMTC patients (p = 0.0041 by the Wilcoxon test and p <0.0001 by the log-rank test). No significant difference in the overall survival rate was found between the two groups. Multivariate analysis by Cox's proportional hazards method showed FNMTC to be an independent predictor of shorter disease-free survival (risk ratio 1.88; confidence interval 1.35-2.54; p = 0.0003). Locoregional recurrence in the ipsilateral or contralateral lymph nodes and contralateral thyroid lobe was significantly more frequent in the FNMTC patients than in the sporadic disease patients, whereas no difference was found regarding distant metastases. We conclude that FNMTC is a clinically distinct entity with an aggressive nature. Because of the frequent presence of benign nodules, multifocality, and high rate of locoregional recurrence, total or near-total thyroidectomy with modified radical neck dissection in FNMTC patients is recommended.

Familial vs sporadic papillary thyroid carcinoma: a matched-case comparative study showing similar clinical/prognostic behaviour

“…Although some studies have reported a less favourable prognosis for FNMTC (3,16,17,18,19,20,21), others did not verify this (1,22,23,24,25), and therefore, the biological and clinical behaviour of this familial disease, as compared with the much more frequent sporadic forms, remains a matter of controversy. Furthermore, data on molecular biomarkers, e.g.…”

The polymorphism rs944289 predisposes to papillary thyroid carcinoma through a large intergenic noncoding RNA gene of tumor suppressor type

“…According to the largest of such studies published to date, the family risk ratio of PTC in first-degree relatives of a PTC proband is as high as 8-12, being the highest of all cancers (4-6). Some 5-10% of probands with PTC have at least one first-or second-degree relative with PTC (7,8). However, remarkably, large families with multiple cases of PTC are rare and often do not display Mendelian inheritance.…”

Microcarcinoma tiroideo de evolución agresiva: Report of one case

“…Además, existe agregación familiar de MCT, lo cual también se ve en la patología autoinmunitaria y podría constituir otro factor de error en la interpretación de la patología del paciente. La presencia de tiroiditis se ha planteado como un factor de mayor agresividad en dichos tumores, es relevante hacer notar que el motivo de estudio de esta familia (sólo la presencia de un familiar afectado) no es el estándar planteado hasta el momento 14,15 .…”