Differences in the aggressiveness of familial versus sporadic non-medullary thyroid cancer: An unresolved controversy

TL;DR

This study compares the aggressiveness of familial and sporadic non-medullary thyroid cancer, finding that familial cases tend to occur at a younger age and with more lymph node involvement.

Contribution

The study provides new evidence on the clinical differences between familial and sporadic non-medullary thyroid cancer, including younger age at diagnosis and higher metastasis rates in familial cases.

Findings

FNMTC patients were diagnosed at a younger age compared to SNMTC patients.

FNMTC patients had a 4.57-fold increased risk of lymph node metastases at diagnosis.

Long-term outcomes did not differ significantly between FNMTC and SNMTC groups.

Abstract

Familial non-medullary thyroid cancer (FNMTC) is defined as non-medullary
thyroid cancer occurring in two or more first-degree relatives, without
features of known hereditary syndromes. Although familial predisposition is
well established, its clinical behavior remains debated. This study aimed at
characterizing familial cases compared to sporadic non-medullary thyroid
cancer (SNMTC).

FNMTC and SNMTC patients were recruited from the Endocrine Division (SEMPR)
of the Federal University of Paraná, Brazil, and private endocrine
clinics in Curitiba, Paraná, Brazil (2000-2019). Baseline,
histopathological, and clinical data were analyzed using SPSS Statistics
26.0. Statistical comparisons employed chi-square, Student’s t test, and
Mann-Whitney U test, as appropriate. Post hoc power analysis was performed
using G*Power 3.1.9.7, and R 2025.05.0.

We analyzed 39 FNMTC and 119 SNMTC patients. Papillary thyroid carcinoma was
the predominant histological type in both groups. FNMTC patients were
diagnosed at a younger age (38.5 ± 14.2 vs. 46.6 ± 13.8 years,
p = 0.003) and more frequently presented with lymph node metastases at
diagnosis (46.2% vs. 21.8%, p = 0.007), with a 4.57-fold increased risk.
Despite these differences, long-term outcomes did not differ significantly
between groups. An earlier disease onset in subsequent generation suggests a
possible anticipation phenomenon.

These findings suggest that FNMTC patients may present with earlier onset and
higher rates of lymph node involvement, underscoring the need for thorough
preoperative lateral neck evaluation. In view of a possible anticipation
phenomenon, cervical ultrasound screening might be considered starting in
adolescence.

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