Can Desmoplastic Stromal Reaction Guide the Extent of Lymph Node Surgery in Sporadic Medullary Thyroid Carcinoma?

Abstract

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. 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. 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. 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.