Comprehensive analysis of primary thyroid lymphoma: a case report and review of diagnostic and treatment protocols

Introduction

Thyroid cancer is one of the most common malignancies worldwide. According to Global Cancer Statistics 2022, thyroid cancer was the seventh most common cancer worldwide, and its incidence rate is increasing each year (1). Primary thyroid lymphoma (PTL) is a relatively rare type of thyroid malignant tumor. A previous report indicated that non-Hodgkin lymphoma accounts for 98% of PTLs, while diffuse large B-cell lymphoma (DLBCL) accounts for 60–70% of PTLs based on histological examination, followed by mucosa-associated lymphoid tissue, which accounts for about 10–30% of the cases (2). In clinical practice, Hodgkin lymphoma, Burkitt lymphoma, and T-cell lymphoma are even rarer.

A common clinical feature of PTL is that it presents as a painless mass in the neck that grows rapidly over time (3), and most patients often experience compression symptoms in the anterior neck area, such as respiratory obstruction, hoarseness, and difficulty swallowing. Currently, an exact explanation for PTL pathogenesis is lacking, although most studies indicate that Hashimoto thyroiditis is the most important risk factor (2-4). Although the PTL diagnosis rate has been greatly improved by various diagnostic methods, such as ultrasound-guided fine needle aspiration (FNA) biopsy, most clinical reports still rely on pathological and immunohistochemical results after traditional surgical resection. PTL’s mode of treatment has evolved from a single surgical treatment to a combination of surgery, radiotherapy, chemotherapy, and targeted therapy (5).

This report provides a detailed description of a patient with PTL, who was admitted to the Department of General Surgery of The Fourth Affiliated Hospital of Harbin Medical University. The patient has a history of hypothyroidism, with long-term oral levothyroxine. Post-surgery, pathology confirmed right thyroid lymphoma and pyramidal lobe lymphoma, and both tumors were verified to be of homologous origin. Through the review and analysis of this case, this study explores the precise diagnosis and treatment of PTL, providing reliable evidence for the subsequent formulation of standardized treatment strategies. We present this article in accordance with the CARE reporting checklist (available at https://acr.amegroups.com/article/view/10.21037/acr-2025-214/rc).

Case presentation

A female patient aged 66 years was admitted to the Department of General Surgery at The Fourth Affiliated Hospital of Harbin Medical University in April 2024 following the discovery of a thyroid mass they had for three years. The main symptoms were a painless and progressive enlargement of the neck mass, with an occasional choking sensation when swallowing. However, there was no hoarseness, swallowing difficulties, palpitations, or other discomforts. The patient, who had a 16-year history of hypothyroidism with long-term oral levothyroxine, did not report having a history of hypertension or diabetes. During neck examination, a 5 cm × 4 cm mass, which was palpated on the right side of the thyroid, was tender and smooth, and it moved up and down with swallowing. A color Doppler ultrasound examination revealed a 5 cm × 3.6 cm solid mass on the right side of the thyroid. A 1.6 cm × 0.6 cm solid nodule, which was observed in the anterior neck, was considered to have originated from the thyroid’s pyramidal lobe. There was no lymph node enlargement on either side of the neck. Neck computed tomography (CT) (Figure 1) and magnetic resonance imaging (MRI) (Figure 2) revealed a significant enlargement of the thyroid’s right lobe. Based on laboratory examination, the levels of thyroid stimulating hormone, thyroid globulin antibody, anti-thyroid peroxidase antibody, thyroid globulin, parathyroid hormone, and calcium were 0.14 mIU/L, 1,439.91 IU/mL, 17.72 IU/mL, 0.23 ng/mL, 72.91 pg/mL, and 2.42 mmol/L, respectively. The remaining related examinations revealed no obvious abnormalities. At admission, the diagnosis was a right thyroid and pyramidal lobe mass and hypothyroidism.

Figure 1 The right thyroid gland was diffusely enlarged with an unclear boundary. The trachea was compressed and obviously narrowed.

Figure 2 These pictures show a significant compressive effect of the right thyroid mass on the trachea.

Next, the patient underwent a subtotal thyroidectomy of the right lobe and isthmus, as well as an anterior cervical conical lobe resection. In the operatively, the thyroid’s solid mass appeared to have a capsule-like smooth surface, with a slight adhesion to surrounding tissues and good mobility, and the trachea was compressed and displaced to the left. After surgical resection, cutting the thyroid open revealed a diffuse grayish-yellow solid part and a soft part at the cut surface. Based on immunohistochemistry, the postoperative pathological report of the right thyroid and pyramidal lobe confirmed DLBCL and the germinal center was considered the B-cell origin. The following immunohistochemistry results were obtained: Ki67 (80%+), CD3 (−), CD20 (diffuse+), CD43 (−), CD10 (+), CD38 (+), Bcl-2 (+), Kappa (+), CD5 (−), Bcl-6 (+), MUM1 (+), c-Myc (20%+), and TdT (−) (Figure 3).

Figure 3 Histological features of diffuse large B-cell lymphoma of the thyroid. (A) The thyroid follicular structure had disappeared, and there was lymphocytic infiltration and diffuse growth (hematoxylin and eosin, ×400). (B) Lymphocyte infiltrate positive for CD20 marker on the immunohistochemical stain (immunohistochemistry, ×100). (C) The Ki-67 proliferation index of tumor cells is greater than 80% (immunohistochemistry, ×100). (D) The MYC proliferation index of tumor cells is greater than 20% (immunohistochemistry, ×100). (E) Lymphocyte infiltrate positive for BCL-6 marker on the immunohistochemical stain (immunohistochemistry, ×100). (F) Lymphocyte infiltrate positive for BCL-2 marker on the immunohistochemical stain (immunohistochemistry, ×100).

After surgery, the patient visited the hematology department of our hospital and based on pathology, was diagnosed with diffuse DLBCL [stage IB, international prognostic index (IPI) score: 1, low-risk]. The rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) regimen was used for immunotherapy, including rituximab (600 mg, d0), cyclophosphamide (1.2 g, d1), pirarubicin (50 mg, d1), vincristine (2 mg, d1), and methylprednisolone (80 mg, d1–5). The patient recovered well after receiving 6 chemotherapy cycles and was followed up for 6 months after surgery. Relevant examinations revealed no recurrence in situ or metastasis to other areas.

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

In clinical practice, PTL, a lymphoma of the thyroid region with or without cervical lymph node involvement, is relatively rare, accounting for only 2–5% of thyroid malignancies (6). Patients usually present with an asymptomatic neck mass, which may be accompanied by local compressive symptoms, such as hoarseness, dysphagia, and wheezing. During disease onset, about 10% of the patients exhibit typical Group B lymphoma symptoms, such as fever, night sweats, and weight loss (3).

Currently, there is no clear explanation for PTL pathogenesis. Most scholars believe its onset is related to autoimmune diseases or long-term antigen stimulation since lymphoma usually originates from lymphocytes and lymphoid tissue (7). Under chronic antigen stimulation, lymphatic tissue induces immune responses, causing cell damage and gene mutations in surrounding tissues, which promote cell proliferation and tumor transformation and ultimately evolve into lymphoma. A study has shown that when compared with the general population, patients with Hashimoto thyroiditis have a 40- to 80-fold higher risk of developing lymphoma (8). A case report has described concomitant hypothyroidism, which may be caused by coexisting Hashimoto’s thyroiditis or diffuse thyroid infiltration by the tumor (9).

Thyroid ultrasound, the preferred method of PTL imaging examination, often shows significant thyroid lobe enlargement, low or extremely low echo areas, internal linear echoes, a lack of calcification, and enhanced posterior echoes (10). However, because of the lack of characteristic features in ultrasound images, it is difficult to distinguish it from thyroid cancer. CT and MRI have poor specificity and are rarely used in PTL diagnosis (11). However, when applied to effectively evaluate the extent and depth of lymphoma infiltration, and determine the presence of tracheal invasion and lymph node involvement, as well as other aspects, CT and MRI have certain advantages. Currently, pathology is the gold standard for PTL diagnosis. FNA has gained widespread favor among clinical physicians because of its portability and safety. While complete lymph nodes and a large amount of lymphoid tissue are required for accurate PTL diagnosis, FNA obtains less tissue with lower integrity and relies more on the operator’s experience and skill. Reports indicate that when combined with immunohistochemistry for PTL diagnosis, including suspected cases, FNA only achieves 65% accuracy (12-14). Using core needle biopsy (CNB), more cells can be obtained while preserving intact tissue structure. With the development of immunohistochemistry combined with CNB technology, CNB sensitivity in PTL diagnosis can be significantly improved. A retrospective study by González confirmed that combining CNB and immunohistochemistry increased PTL diagnosis sensitivity to 90.9% (15). More lymphomas can be diagnosed with certainty before surgery, avoiding unnecessary surgical resection biopsy. Because surgical biopsy can obtain sufficient specimens for immunohistochemistry, which clarifies pathological types and histological subtypes, while providing a reasonable plan for subsequent treatment, it still plays an irreplaceable role. Because PTL is rare, more than half of the confirmed cases are from pathological diagnosis after surgical resection (Table 1). In this case, because thyroid lymphoma was not preoperatively confirmed using pathological examination, surgery was performed with the main objective of alleviating local compression, and postoperative pathology was used to confirm right thyroid lymphoma and pyramidal lobe lymphoma. In thyroid lymphoma, the involvement of the pyramidal lobe is relatively rare. Its special anatomical and physiological characteristics and the low base rate further reduce the probability of involvement in this location. However, the clinical missed diagnosis and misdiagnosis rates of thyroid pyramidal lobe lymphoma are extremely high. In the clinic, ultrasound examination of the anterior midline neck region can be performed to detect suspicious signs of nodules in thyroid gland. If suspicious signs of tumors in the pyramidal lobe are present, prompt puncture biopsy or surgical resection biopsy can significantly reduce the risk of missed diagnosis and misdiagnosis, while avoiding potential postoperative tumor tissue residue and other dangers.

Most PTL pathological types are non-Hodgkin lymphomas, with DLBCL being the most common (2). Immunophenotypically, DLBCL is usually CD20 positive, with half of the cases being positive for Bcl-2 and Bcl-6 expression and lacking CD5, CD10, and CD23 (23). Ki-67 is often highly expressed in response to cell proliferation. When compared with other pathological types, this pathological type of lymphoma has stronger invasiveness and worse prognosis during the same period, as well as a shorter overall survival period (24). Yi et al. reported a correlation between the Ki-67 index and Myc/Bcl-2 protein expression and patient prognosis, although further research is needed to confirm this (24). The patient in this case had immune reactivity to Bcl-2 and CD20, confirming that the tumor was of B-cell origin.

Surgical PTL treatment remains controversial. On the one hand, the studies by Tang et al. and Zhang et al. have confirmed traditional surgical resection, and no significant difference was found in the overall survival rate of the thyroid resection combined with chemotherapy group vs. the chemotherapy alone group (25,26). However, Alnahas et al. found that applying radiotherapy, chemotherapy, and minimally invasive tracheal stent placement can effectively alleviate compression symptoms and relieve airway obstruction without surgical intervention (19). Currently, more scholars and clinical physicians apply surgical resection only to patients with unclear pathological types, early-stage tumors, or those who need to relieve neck compression. Moreover, the consensus among everyone is that combined radiotherapy and chemotherapy have significant benefits in disease control and improving long-term efficacy (5).

Regarding chemotherapy selection, PTL, with DLBCL as the main pathological type, is highly sensitive to rituximab, a CD20-targeting monoclonal antibody (27). A study also shows that rituximab can induce thyroid lymphoma cell lysis through direct and indirect mechanisms, including inducing apoptosis and complement-mediated cell lysis (28). In this case, the patient was diagnosed with thyroid lymphoma after thyroidectomy and subsequently received the R-CHOP regimen. The patient’s follow-up prognosis was good. In patients with PTL, the R-CHOP regimen can significantly prolong overall survival and progression-free survival (22,28,29). In clinical practice, to determine the appropriate chemotherapy regimen and achieve the best treatment effects, tumor staging and pathological classification should be comprehensively considered. For thyroid pyramidal lobe lymphoma, due to its characteristics of low proliferative activity and weak clonal dominance, even if this site is involved by lymphoma, there is currently no sufficient clinical data or multicenter studies to confirm that more aggressive pharmacologic interventions, beyond surgical resection, can effectively improve patient prognosis and prolong survival.

Conclusions

PTL is rare, difficult to diagnose early and pyramidal lobe is extremely prone to missed diagnosis. Currently, for its treatment, a plan mainly based on systemic chemotherapy combined with local radiotherapy is undoubtedly the best approach. Additionally, although surgical resection may not provide survival benefits to patients, its significant airway obstruction relief and local neck symptom alleviation are evident.

Acknowledgments

We are very grateful to the patient and her family for their trust, allowing us to share her illness and treatment information to help more patients with same disease to provide reliable experience and treatment options.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://acr.amegroups.com/article/view/10.21037/acr-2025-214/rc

Peer Review File: Available at https://acr.amegroups.com/article/view/10.21037/acr-2025-214/prf

Funding: This study was supported by the Provincial Natural Science Foundation of The Fourth Affiliated Hospital of Harbin Medical University (No. JJ2024LH1374, to J.L.Z.) and the Crosswise Tasks of the Heilongjiang Province Exchange Medical Research Institute of Harbin Medical University (No. PL2024H155, to J.L.Z.).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://acr.amegroups.com/article/view/10.21037/acr-2025-214/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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