Molecular Characterization of Isolated Soft Tissue Deposits in Papillary Thyroid Carcinoma

INTRODUCTION: Isolated soft tissue deposits (ISTDs) are believed to be tumor emboli from lymphatic drainage pathways, discontinuous from primary tumors and lacking lymph node architecture. While associated with poor prognosis in various malignancies, characterization of ISTDs in papillary thyroid carcinoma (PTC) is limited. METHODS: This single-center cohort study examined 11 cases of PTC with ISTDs. Multi-platform next-generation sequencing analyzing driver mutations and tumor suppressor loss of heterozygosity (LOH) was performed on primary tumors, lymph nodes, and ISTDs. Clinical and histopathologic features were compared to a 3:1 matched control cohort. RESULTS: Genomic alterations were identical across paired tumors, lymph nodes, and ISTDs. LOH was present in 78% of cases with driver mutations. Compared to controls, ISTD cases demonstrated increased rates of high lymph node burden (p < 0.01), extranodal extension (p = 0.012), and lymphovascular invasion (p < 0.01). CONCLUSIONS: Associated with aggressive disease features, the molecular profiles of ISTDs mirror primary tumors and lymph node metastases.