Thyroid-Presenting Plasmablastic Lymphoma Mimicking Anaplastic Thyroid Carcinoma

Background/Objectives: Primary thyroid lymphoma accounts for approximately 0.2–2% of thyroid malignancies. Plasmablastic lymphoma (PBL), an aggressive large B-cell neoplasm with plasma-cell differentiation and frequent loss of conventional B-cell markers, is a rare thyroid presentation. We report a thyroid PBL presenting as an acute surgical airway emergency in an immunocompetent patient and highlight the diagnostic and management pitfalls that distinguish this from anaplastic thyroid carcinoma. Case Presentation: A 75-year-old man without any significant past medical history presented with rapidly progressive right-sided neck swelling, dysphagia, inspiratory stridor, and respiratory failure. Imaging demonstrated a large, thyroid-centered mass with tracheal involvement, initially raising concern for anaplastic thyroid carcinoma. Histopathology revealed a diffuse infiltrate of large, atypical cells with immunoblastic and plasmablastic morphology. The neoplastic cells were CD20- and CD138-negative but strongly MUM1-positive, with lambda light-chain restriction, bright CD38 by flow cytometry, a Ki-67 proliferation index exceeding 95%, aberrant cytoplasmic CD3 expression, and a MYC::IGH rearrangement, supporting a diagnosis of PBL. Staging identified extranodal perinephric disease and mesenteric lymphadenopathy, consistent with disseminated extranodal Ann Arbor stage IV disease. The patient underwent systemic treatment and initially had an excellent response; however, one month after the last treatment cycle they presented to the hospital with a mass consistent with recurrence. Discussion: Rapid growth, fixation, and tracheal invasion strongly suggest anaplastic thyroid carcinoma in routine clinical practice. However, plasmablastic lymphomas can present similarly and require fundamentally different treatment. In this case, loss of conventional B-cell markers, CD138 negativity, and aberrant cytoplasmic CD3 expression created substantial diagnostic challenges. Light-chain restriction, plasma-cell-associated markers, flow cytometry, and MYC cytogenetics were vitally important. Conclusions: Thyroid-presenting PBL is exceptionally rare and may closely mimic anaplastic thyroid carcinoma, including presentation with life-threatening airway compromise and tracheal involvement. This case highlights several diagnostic pitfalls: CD138 negativity despite plasma-cell differentiation, and aberrant cytoplasmic CD3 expression. Prompt airway stabilization, adequate tissue acquisition, broad immunophenotyping, light-chain assessment, flow cytometry, EBV/HHV8/ALK testing, and MYC cytogenetics are essential for accurate diagnosis and lymphoma-directed treatment.