Morphological Characteristics and Diagnostic Challenges of Primary Thyroid Lymphoma in Fine‐Needle Aspiration Cytology

ABSTRACT Background Fine‐needle aspiration (FNA) cytology is frequently employed as the first‐line diagnostic approach for thyroid nodules and plays a crucial role in the identification of primary thyroid lymphoma (PTL). This study aimed to elucidate the clinical and cytopathological characteristics, as well as the diagnostic challenges associated with PTL as determined by FNA. Methods A retrospective analysis was conducted on data collected from January 2014 to December 2025 from patients diagnosed with thyroid lymphoma or suspected lymphoma via FNA cytology at Xijing Hospital. The analysis encompassed clinical presentations, radiological findings, cytomorphological and histomorphological features, ancillary studies, treatment modalities, and follow‐up outcomes. Results Of 23 patients, 16 women and 7 men, with a median age of 68 (range, 21–86) years were included. Among the 23 cases identified as lymphoma or suspicious for lymphoma through thyroid FNA cytology, 19 had corresponding histological diagnoses, including 4 thyroid core needle biopsies, 5 thyroidectomies, 5 cervical lymph node core needle biopsies, and 5 cervical lymph node excisions. Concordance between cytologic and histologic diagnoses was observed in 84.2% (16/19) of cases, while 3 cases exhibited discordance. Cytological and/or histological evaluations identified three extranodal marginal zone lymphomas of mucosa‐associated lymphoid tissue (MALT lymphoma), six diffuse large B‐cell lymphomas (DLBCL) subdivided into three germinal center B‐cell (GCB) and three non‐GCB subtypes, one high‐grade B‐cell lymphoma with MYC and BCL2 rearrangements, two follicular lymphomas, and three Hodgkin lymphomas. Furthermore, four cases of B‐cell lymphoma and two cases of suspected lymphohematopoietic neoplasms lacked definitive histological subtyping. All patients exhibited a symptomatic enlarging thyroid mass, with or without associated local and regional lymphadenopathy, and had no prior history of lymphohematopoietic disorders. Thyroid ultrasonography revealed hypoechoic nodules in 14 cases, mixed‐echoic nodules in 2 cases, and heterogeneous nodules in one case. Four patients had only a thyroidectomy, nine received only chemotherapy, two underwent surgery plus either radiotherapy or chemotherapy, two had chemotherapy combined with either autologous hematopoietic stem cell transplantation (Auto‐HSCT) or radiotherapy, and one was treated with rituximab. The follow‐up period ranged from 2 to 126 months, with 18 patients remaining alive, 2 deceased, and 3 lost to follow‐up. Conclusion PTL is a rare condition mainly affecting elderly women and usually of B‐cell origin. Accurate cytological diagnosis of aggressive B‐cell lymphoma is crucial to avoid unnecessary surgeries. While ancillary studies aid in distinguishing Hashimoto's thyroiditis from MALT lymphoma, diagnosis remains challenging due to the limited cellularity of FNA samples.