Can desmoplastic stromal reaction guide the extent of lymph node surgery in sporadic medullary thyroid carcinoma?

Abstract

Background: Medullary thyroid carcinoma (MTC) frequently presents with lymph node metastases (LNMs), and the extent of lymph node (LN) surgery remains controversial. The desmoplastic stromal reaction (DSR) has emerged as a potential histopathological predictor of metastatic spread. Methods: We retrospectively analyzed 63 patients with sporadic MTC treated between 2016 and 2025 at four tertiary centers. Histopathological specimens were re-evaluated for DSR, which was graded as absent, low, moderate, or high. Clinicopathological features, biochemical markers, and oncologic outcomes were compared across groups. Results: DSR was absent in 27.0% and present in 73% tumors. DSR positivity was significantly associated with higher calcitonin (Ctn) and carcinoembryonic antigen (CEA) levels, increased LNM (87% vs. 0%), lymphovascular invasion, advanced nodal stage, and stage IV disease. Biochemical cure was achieved in 94.1% of DSR-negative patients compared with 56.5% of DSR-positive patients. The extent of tumor desmoplasia levels correlated with higher metastatic burden. Conclusion: DSR negativity reliably identifies an indolent subgroup with negligible metastatic risk, whereas increasing desmoplasia stratifies patients into higher-risk categories. The incorporation of DSR alongside established biomarkers such as Ctn may refine surgical decision-making and may help tailor the extent of LN dissection in sporadic MTC.