Atypical presentation and association of medullary thyroid carcinoma: reports from a tertiary care center in Northwest India.

Summary: Medullary thyroid carcinoma (MTC) constitutes 5-10% of thyroid malignancies but accounts for 15% of thyroid cancer-related mortality. Twenty percent of MTC are hereditary and are part of familial MTC or multiple endocrine neoplasia (MEN) syndromes. Classical MTC presents as a nodular goiter with or without lymphadenopathy, or occasionally diarrhea and metastatic symptoms. Several patients in our cohort had unusual features that delayed diagnosis. The standard management remains surgical resection, with tyrosine kinase inhibitors (TKIs) in RET mutation-positive or RET mutation-negative metastatic cases and/or Lutathera peptide receptor radionuclide therapy (PRRT) used in disseminated disease, and external beam radiotherapy for locally aggressive or infiltrative retaining a limited role. However, some patients developed therapy-related complications or exhibited resistance to treatment. Of the 80 MTC patients reviewed, this case series highlights 10 atypical presentations in nine cases : 3 unusual tumors along with MTC, namely chondrosarcoma, carcinoma prostrate, and ectopic Cushing's syndrome; 4 unusual associations or presenting manifestations: pneumoconiosis masquerading as lung metastasis, Marfanoid habitus in MEN-2A and VHL spectrum disease, 1 with skull metastasis, and 2 cases with TKI-related complications in the form of glomerulonephritis and one patient displayed Marfanoid habitus with a RET mutation but without MEN2B or fibrillin gene mutation, while another developed bowel perforation secondary to lenvatinib therapy emphasizing diagnostic and therapeutic challenges and rare tumor associations. This series underscores the heterogeneity of MTC and the need for thorough evaluation and personalized management. Greater clinician awareness of MTC's diverse presentations is essential to improve early diagnosis and optimize treatment outcomes. Learning points: Diverse and atypical clinical presentations can obscure the diagnosis of MTC. Management of MTC remains complex due to therapy-related complications and resistance. Molecular diagnostics enable better risk stratification and personalized care.