Endocrine Abstracts

Objectives: Coexistence of two different malignancies is frequently reported. Sometimes occurs in the context of well-established syndromes like MEN2. Rearranged during transfection (RET), is an oncogenic driver activated in different kinds of neoplasias such as: MTC, Differentiated Thyroid Cancer (DTC), Non-Small Cell Lung Cancer (NSCLC). We have previously reported an increased prevalence of DTC in familial MTC patients carrying the RET (G533C) mutation. Aim of this study was to record the extrathyroidal malignancies in MTC patients of our Unit.

Methods: 57/297 patients presented with second malignancy during a follow-up of 1–15 years. They were classified in 3 groups; Group 1: MTC+Extrathyroidal malignancy, Group 2: MTC+DTC, Group 3: MTC-alone.

Results: 19/57pts (Group1) were diagnosed with an extrathyroidal malignancy 2–10 years after MTC; location-type: Breast (5/19), Kidney-Bladder (3/19), Sarcoma (2/19), Lung-NSCLC (2/19), Prostate (1/19), Colon (1/19), Chronic Myeloid Leukemia (1/19). Prior to MTC, 4 patients were diagnosed with Head & Neck cancer and Melanoma. Group 2 (Concomitant MTC+DTC): 38/57pts. Group 1 patients vs Group 2 & 3 presented with worse disease stage at diagnosis (P=0.006). Accordingly they had more frequently lymph node infiltration (P=0.007), capsular & soft tissue invasion (P=0.001); higher pre- and post-operative Calcitonin levels were recorded in them (P=0.028). Tumor size was larger in Group 1 pts (P=0.003). C-cell hyperplasia was more frequent in Group 2 (P=0.003). No differences were found regarding sex, family history, multifocality or distant metastases.

Conclusions: Synchronous or asynchronous primary malignancies may occur with MTC. RET oncogenicity through several mechanisms (activating mutations, increased expression, risk-associated SNPs) has been proposed as a possible shared aetiopathogenic mechanism. Elucidation of the common genetic pathways possibly involved in coexistence of two phenotypically different types of malignancy could be crucial for precision medicine and tailor-made therapy.