Familial Non-Medullary Thyroid Cancer Represents an Independent Risk Factor for Increased Cancer Aggressiveness: A Retrospective Analysis of 74 Families

Abstract

ObjectivesTo assess whether familial non-medullary thyroid cancer (FNMTC) represents an independent risk factor for increased aggressiveness of the tumor, as concern as the clinical presentation and the long-term follow-up in respect of sporadic differentiated thyroid cancer (SDTC).DesignRetrospective study; 1976–2014.Patients and MethodsSeventy-four FNMTC families (151 affected individuals): family relationship and number of affected family members were evaluated. Clinical and histopathological features and outcome were compared to that of 643 SDTC patients followed in the same period according to the same institutional protocols. Median follow-up was 57.7 months (range 12–136) in FNMTC and 59.7 (range 15–94.6) in SDTC patients.ResultsThree cases occurred in 3 families and 2 cases in the other 71. F:M was 3.7:1 in FNMTC and 4.3:1 in SDTC (NS). The family relationship was siblings in 62.2%. Mean age at diagnosis was lower in FNMTC than in SDTC (p < 0.005). Papillary/follicular histotype distribution was similar (86%). Papillary tumors were more frequently multifocal in FNMTC (p = 0.004) and with lymph-node metastases (p = 0.016). Disease-free survival (DFS) was shorter in FNMTC vs. SDTC (p < 0.0001) with 74.8 vs. 90.8% patients free of disease at the last control (p < 0.005). Three patients died in FNMTC group vs. 1 in SDTC (p = 0.02).ConclusionFamilial non-medullary thyroid cancer displays distinct characteristics as earlier age of onset and increased aggressiveness at diagnosis and a higher rate of persistent/recurrent disease and mortality with a shorter DFS in respect with SDTC. FNMTC patients, therefore, should be followed accurately. As the specific gene (or genes) responsible for susceptibility for FNMTC has not yet been identified, a low frequency periodic screening of relatives DTC patients may be useful to identify FNMTC patients at early stage of disease.

Screening guidelines and recommendations for patients at high risk of developing endocrine cancers

“…33 Recent data suggest that FNMTC is more likely to present with multifocal or advanced disease and is more likely to recur after resection. 34,35 While some studies have suggested benefit with US screening in these patients, 36 there are no current recommendations for thyroid screening in patients with suspected FNMTC. Annual physical exam findings should continue to guide work-up.…”

The impact of family history on non-medullary thyroid cancer

“…Many groups report no difference in age between familial and sporadic cases [52, 53, 55–58]. In contrast, other groups report a lower average age in familial disease [31, 54].…”

“…In terms of the pathological presentation of disease, many groups have shown that familial disease is associated with increased rates of multicentric papillary cancers [19, 57, 58, 61]. Although not all groups have found this to be statistically significant due to the already high rate of multifocality in sporadic NMTC [52], the majority of series report rates of multicentricity of approximately 50% in patients with a family history versus 30–40% in sporadic cases [50, 53–56, 59, 62, 63].…”

“…An Italian group [59] found that in familial disease, second generation papillary thyroid carcinoma was more likely to be associated with nodal metastases than disease in first generation cases (32% versus 5%, p=0.02). In addition, Tavarelli et al [58] found a significant presence of lymph-node metastases in familial tumors (40/151 vs. 113/643, respectively, p=0.016). In contrast to these findings, the majority of groups have found no association between family history and nodal disease [31, 50, 52, 53, 55].…”

“…These results are related to inclusion of de-differentiated disease and are unlikely to apply to well-differentiated tumors within the familial setting. Tavarelli et al [58] studied 74 FNMTC families (151 affected individuals) compared with 643 sporadic cases. They found a mean age at diagnosis lower in FNMTC ( p < 0.005); papillary tumors were more frequently multifocal in FNMTC ( p = 0.004) and with lymph-node metastases ( p = 0.016).…”