Endocrine Abstracts

Background: Medullary thyroid carcinoma (MTC) is a malignant tumor originating from C-cells producing calcitonin (CTN). Most of the MTC are sporadic and can potentially metastasize to lymph nodes and distant sites. High pre-operative CTN values and larger tumor dimension are usually associated with metastatic disease. However, anecdotal cases of large sporadic MTC with high pre-operative CTN values, without lymph nodes metastases, and completely cured after surgery have been described configuring a picture of non-invasive MTC (niMTC).

Aim: The aim of our study was to evaluate the prevalence and clinical behavior of these niMTC in a large series of sporadic MTC followed at the Unit of Endocrinology of the University of Pisa (2000- 2020).

Results: From a prospectively maintained database we evaluated data of 674 sporadic MTC patients. We excluded patients with lymph nodes and distant metastases at diagnosis, those with tumor diameter <2 cm and without controls after surgery. Then, 63 cases were included. Median age at diagnosis was 53 years. Pre-operative median CTN values were 730 ng/l (IQR 349-1890) and tumor median dimension at histology was 3 cm. All patients were N0 with a median of 8 removed lymph nodes (IQR 4-12). At first post-operative evaluation (median 4 months), most of patients (58/63-92%) were cured, conversely 5 (8%) showed detectable CTN values but negative imaging. After a median follow-up of 74 months (IQR 36-120), 77.8% (n = 49) remained cured. Conversely, 9 (14.3%) had biochemical disease, 3 (4.8%) had metastatic lymph nodes and 2 (3.2%) distant metastases. After a median of 100 months (IQR 64-181) of follow-up, two patients died for the disease. When evaluating the potential differences between cured and not cured (biochemical/metastatic) patients, no differences were highlighted in age at diagnosis, pre-operative CTN values and tumor dimension. However, patients not cured had more frequently histologic desmoplasia (P = 0.03), while although slightly different nor Ki-67 (P = 0.1) neither number of mitosis (P = 0.08) raised the significance. Lastly, in a subgroup (n = 34) in which somatic mutations were performed, no differences in the presence of RET somatic mutation were highlighted between cured and not cured patients (P = 0.9).

Conclusions: In our series, the presence of sporadic niMTC was 9.3%. Despite high pre-operative CTN levels and large tumors, most of these patients did not show metastatic lymph nodes at diagnosis and are cured early after surgery. However, few cases can develop metastatic disease also after several years, therefore follow-up should be careful pursued over time.