Clinical, Histopathological, and Molecular Prognostic Factors Associated with Survival and Disease Progression in Adult Patients with Primary and Secondary Thyroid Lymphomas: A Scoping Review. (Preprint)

BACKGROUND Primary and secondary thyroid lymphomas are rare, and early recognition matters because their therapeutic approaches differ from other thyroid malignancies; however, the evidence base is heterogeneous (mostly retrospective studies, small series, and case reports). OBJECTIVE To examine the current literature on primary and secondary thyroid lymphomas and identify key factors associated with improved patient outcomes. METHODS We conducted a scoping review in accordance with the JBI methodology and reported the findings following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines. We systematically searched Scopus, Ovid MEDLINE, and EMBASE between June 1, 2024, and September 1, 2024. We included observational studies involving human patients aged 18 years or older with a diagnosis of primary and/or secondary thyroid lymphoma. Eligible studies reported adult cases of primary thyroid lymphoma or secondary thyroid lymphoma. We excluded studies involving tumors of non-thyroid origin, as well as studies reporting patients with concomitant diseases associated with high morbidity or mortality that could substantially influence prognosis. Two independent reviewers performed the screening, selection, and data extraction processes in a blinded manner. Disagreements were resolved by a third reviewer. Extracted data were managed and stored using REDCap (Research Electronic Data Capture) and synthesized descriptively using summary statistics. RESULTS Forty-two studies met all inclusion criteria and were included in the final analysis, providing data on 3,390 patients. Thyroid lymphoma most frequently presented with local compressive symptoms and showed a strong association with Hashimoto’s thyroiditis, whereas systemic autoimmune diseases and constitutional symptoms were uncommon. Imaging and diagnostic approaches were inconsistently reported, with infiltrative hypoechoic patterns and surgical or needle biopsy being the most commonly described findings. B-cell lymphomas predominated, although histologic subtyping and reporting of proliferative and molecular markers were limited. Treatment strategies were highly heterogeneous, with radiotherapy, surgery, and chemotherapy used alone or in combination. Mean survival was 40 months in primary thyroid lymphoma vs 32 months in patients with secondary thyroid lymphoma. CONCLUSIONS Clinical and histopathological factors, including age, compressive symptoms, autoimmune thyroiditis, histologic subtype, and proliferative indices, currently constitute the most reliable prognostic indicators in thyroid lymphoma. In contrast, molecular factors remain insufficiently characterized due to limited and inconsistent reporting. Prospective, multicenter studies with standardized reporting are needed to improve prognostic stratification and guide optimal management strategies for this rare but clinically significant disease CLINICALTRIAL Not applicable