A general practitioner referred an asymptomatic 39-year-old man to our center for thyroid ultrasonography. The patient had no evidence of thyroid disease, and his past medical history was unremarkable. However, his mother and his uncle had both been diagnosed with papillary thyroid cancer (PTC). Both had been treated with thyroidectomy followed by radioactive iodine (RAI) remnant ablation (RRA), and the uncle also had had multiple RAI therapies for RAI-avid lung metastases. At the time of the patient’s referral, they had been disease-free for 5 and 1.5 years, respectively. There was no documentable history of radiation exposure.

The patient’s physical examination was negative, but thyroid and neck ultrasonography revealed multiple hypoechoic lesions in both lobes of the thyroid. The largest nodule, which was located in the left lobe, measured 10 mm and exhibited intranodular punctate hyperechogenicity and signs of central and perilesional vascularity. There was no clinical or sonographic evidence of lymph node involvement. The patient was euthyroid (serum TSH: 1.4 mIU/L). The dominant nodule was subjected to fine-needle aspiration biopsy (FNAB), and the cytology findings were consistent with PTC (Bethesda class VI) [1]. A total thyroidectomy was performed. The pathology showed multifocal, bilateral, classic variant PTC (lesion diameters: left lobe, 9 and 2 mm; isthmus, 4 mm; right lobe, 5 mm). There was no evidence of extrathyroidal extension or vascular invasion (pT1am, Nx—AJCC/TNM VII Edition Stage 1) [2]. Based on the 2009 American Thyroid Association (ATA) Initial Risk Stratification System [3], the patient’s disease was considered at low risk for recurrence. Because the case met the current criteria for familial nonmedullary thyroid cancer (FNMTC), however, the possibilities that the patient might actually be at higher risk than he seemed to be, and that other members of his family might be genetically predisposed to thyroid cancer, had to be considered.

Approximately 3–10 % of all NMTCs appear to be familial [4, 5]. Excluding those tumors linked to familial adenomatous polyposis, Gardner’s syndrome, Cowden disease, Werner’s syndrome, or Carney’s complex, most of these cases have not been linked to specific genetic causes [4]. Therefore, the diagnosis is generally made when NMTC has been found in two or more first-degree relatives. When cases are defined in this manner, the probability that affected family members actually have sporadic tumors has been estimated at about 30–40 %, but when three of more members of a kindred are affected, the probability of hereditary disease climbs to over 96 % [6].

Management of patients with FNMTC should be based for the most part on the ATA risk class of the individual patient, although a positive family history is a potential risk modifier. In terms of surgery, for example, the 2015 ATA guidelines list familial disease as one of the possible indications for choosing thyroidectomy over lobectomy (others being age >45 years, the presence of nodules in the contralateral lobe, or a personal history of radiation therapy to the head and neck) [5]. The issue of RRA in this context is even more of a gray area. Our patient had multiple foci of PTC, each with a maximum diameter of less than 1 cm, and his risk for recurrence was thus classified as low. There is an appreciable difference between the risks of recurrence associated with unifocal and multifocal papillary microcarcinomas (1–2 % vs. 4–6 %, respectively), especially when the sum of the diameters of the tumor foci exceeds 1 cm (as it did in our patient) [7]. Nonetheless, the risk remains low in both cases, and there is no evidence that RRA improves the disease-specific or disease-free survival in either case—unless there are other high-risk features [5].