Endocrine Abstracts

Background: Medullary thyroid carcinoma (MTC) has a high predisposition to neck lymph node involvement, which correlates with worse outcome. Peritumoral stromal desmoplasia, defined as the presence of a newly formed stroma surrounding tumor cells, is a strong predictor of lymph node metastases in MTC.

Objective: The main purpose of the present study is to characterize peritumoral stromal desmoplasia in MTC, through the identification of other associated histopathological features and their possible molecular basis.

Methods: We performed a retrospective observational study on patients with histologically proven MTC diagnosed at our Institution from 2010 to 2024. Paraffin-embedded thyroid tumor tissue was collected for each patient for histopathological analysis. The selected patients’ medical records were revised up until the last follow-up visit in order to assess their disease status at the end of the study.

Results: The study population included 51 patients (32 female, 19 male), of which 44 with sporadic MTC. Desmoplasia was observed in 49% of patients (Table), who did not differ in age, sex and duration of follow-up compared to cases without desmoplasia. Desmoplasia was significantly associated with higher basal calcitonin and procalcitonin levels (P = 0.001 and 0.019, respectively), primary tumor size (P=0.007), lymph node metastases (P = 0.014) and angioinvasion (P = 0.007). There was no significant association with grade of intratumoral fibrosis (12.5% vs 8%), necrosis (12% vs 7.7%) and tumor capsule invasion (88.9% vs 61.5%), although these features were more represented in MTCs with desmoplasia. In cases with available molecular analysis (n = 20), somatic RET mutations were identified both in MTCs with and without desmoplasia (57.1% vs 66.7%), and there were no differences in the distribution of the type of mutation detected (M918T, C634 or others). At the end of follow-up (median 40.8 months), desmoplasia was significantly associated with a higher prevalence of disease persistence (P = 0.05).

Conclusions: Desmoplasia in MTC is associated not only with lymph node metastases but also with angioinvasion and increased tumor size, regardless of the presence and type of RET mutation. Further studies on larger series may clarify whether desmoplasia is associated with other pathological factors with a negative prognosis.