Primary Non-Hodgkin’s Lymphoma of the Thyroid Gland: A Case Report with Review of Literature

INTRODUCTION

Primary thyroid lymphoma (PTL) is an unusual to encounter in clinical practice, noted as lymphoma affecting only the thyroid gland and nearby lymph nodes, without any contiguous spread or metastasis at the time of diagnosis.¹ The significance of PTL lies in the potential to alter treatment strategies through early preoperative detection, thus avoiding unnecessary thyroidectomy and extensive lymph node dissections. Here, we present a case of PTL where early detection prior to surgery spared the patient from unnecessary procedures, and timely chemotherapy successfully controlled the disease.

CASE PRESENTATION

A gentleman aged 50 years from Haryana presented to the out patient department (OPD) with a painless, rapidly progressive swelling in the front of his neck for 2 months. This was associated with an evening rise in temperature and night sweats. There was no history suggestive of hypo- or hyperthyroidism, and no compressive symptoms. He had no previous radiation exposure and no known cancer history in the family.

On examination, there was a firm right solitary thyroid nodule (STN) measuring 6 × 7 cm and a palpable, firm 2 cm right level II cervical lymph node. There was no generalized lymphadenopathy. Thyroid function tests returned normal results, and both thyroid peroxidase (TPO) and thyroglobulin antibodies were negative. Ultrasound of the neck showed a right TIRADS 4 lesion measuring 6 × 2.9 cm with heterogeneous echotexture, a left TIRADS 3 lesion measuring 1.8 × 1.1 cm, and multiple bilateral necrotic cervical lymph nodes (Fig. 1). Fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) showed a large FDG-avid mass in the right lobe of the thyroid, along with a heterogeneous FDG-avid lesion in the left lobe. Additionally, multiple FDG-avid lymph nodes were identified in both the cervical and mediastinal regions (Fig. 2).

Fine-needle aspiration cytology (FNAC) of the thyroid revealed malignant lymphoid cells displaying significant pleomorphism, a high nuclear-to-cytoplasmic (N:C) ratio, open chromatin, and numerous mitotic figures, indicating a diagnosis of high-grade non-Hodgkin’s lymphoma (Fig. 3). Cervical lymph node excision biopsy demonstrated disruption of the lymph node architecture (Fig. 4A) and revealed large atypical lymphoid cells (Fig. 4B) that were positive for CD20 (Fig. 4C), MUM1, and cellular myelocytomatosis oncogene (CMYC), while negative for CD3, CD10, BCL2, and BCL6. The Ki67 proliferation index was measured at 90%, consistent with a diagnosis of diffuse large B-cell lymphoma (DLBCL), classified as clinically Ann Arbor stage IIE.

The patient was initiated on the R-CHOP treatment regimen and exhibited a complete response.

DISCUSSION

Primary thyroid lymphoma is an infrequent type of cancer, occurs in less than 5% of all thyroid cancers and not more than 2.5% of lymphomas.² The majority of PTL cases are classified as non-Hodgkin’s lymphoma, constituting 50–80% case of DLBCL, while mucosa-associated lymphoid tissue (MALT) lymphomas make up 20–30%.³ Other, less common subtypes include small lymphocytic lymphoma, Burkitt’s lymphoma, follicular and Hodgkin’s lymphoma. In rare instances, PTL can also arise from T-cells.³

In contrast to secondary thyroid lymphoma, which results from the metastatic spread of non-thyroidal cancers to the thyroid gland, PTL is localized to the thyroid and nearby lymph nodes at the time of diagnosis. This distinction is vital, as secondary thyroid lymphoma usually signifies advanced disease and carries a poorer prognosis compared to early-detected PTL.⁴ Primary thyroid lymphoma is staged using Ann Arbor criteria (Table 1).⁵ In this case, the patient was classified as stage IIE, indicating involvement of the thyroid gland and only the supra diaphragmatic lymph nodes.

The thyroid gland normally lacks lymphoid tissue; however, lymphocytes can infiltrate it under certain pathological conditions, such as Hashimoto’s thyroiditis, which significantly raises the risk of developing PTL by 40–80 times.⁶ Primary thyroid lymphoma is more common in females compared to males (4:1), and it typically manifests in individuals during their seventh decade, with an average age of 67 years. Patients often present with a rapidly growing neck mass, but may also experience symptoms resulting from the compression of nearby structures, such as breathlessness, dysphagia, and hoarseness. While the majority of patients are euthyroid, around 10% may be hypothyroid, and 10–20% may display systemic B symptoms, including fever, night sweats, and weight loss.⁷

Fine-needle aspiration cytology is essential for diagnosing thyroid nodular diseases; however, its effectiveness for PTL is limited due to challenges in distinguishing PTL from lymphocytic thyroiditis or anaplastic thyroid carcinoma. To enhance diagnostic accuracy for PTL, additional techniques such as flow cytometry, immunohistochemistry, or molecular methods like polymerase chain reaction (PCR) can be employed.⁸ A definitive diagnosis typically requires a trucut or incisional biopsy of the thyroid gland or any suspicious cervical lymph nodes. In cases of DLBCL, histological examination usually reveals cellular pleomorphism, distinctive nucleoli, a high number of mitotic figures, and lymphoglandular bodies, with immunohistochemistry positive for CD20.

Staging of PTL is generally performed using FDG PET-CT scans, and the Ann Arbor staging (Table 1) is used. Combined modality treatment (chemotherapy plus radiotherapy) is recommended over chemotherapy alone due to superior outcomes in reducing the risk of disease spread and local recurrence. The R-CHOP regimen, which includes Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisolone, is the established chemotherapy protocol for treating DLBCL and other aggressive lymphomas.⁹

Prognosis depends significantly on the histological subtype and disease stage. Mucosa-associated lymphoid tissue lymphomas, being indolent, respond well to therapy and have a favorable prognosis compared to aggressive subtypes like DLBCL. Accurate histological classification and staging are critical for determining the appropriate treatment and predicting outcomes.¹⁰ The 5-year survival rate is 90% for intra thyroidal disease but drops to 35% for extra thyroidal disease.⁶ Factors that are linked to a worse prognosis include a tumor size larger than 10 cm, advanced cancer stage, presence of obstructive symptoms, fast tumor progression, involvement of the mediastinum, age over 60, and increased levels of lactate dehydrogenase (LDH) and β2-microglobulin.¹¹

In our case, the patient presented with a swiftly enlarging thyroid nodule and cervical lymphadenopathy. Normal thyroid function tests and negative anti-TPO antibodies excluded Hashimoto’s thyroiditis. Fine-needle aspiration cytology suggested lymphoma, and PET-CT confirmed FDG-avid lesions in the thyroid and supra diaphragmatic lymph nodes, staging the disease as Ann Arbor IIE. A cervical lymph node biopsy confirmed DLBCL, sparing the patient from unnecessary thyroidectomy and extensive lymph node dissection. The patient was treated with the R-CHOP regimen and achieved a complete response, with no FDG uptake on follow-up PET-CT.

This case underscores the importance of accurate diagnosis and staging in PTL to guide effective treatment and avoid unnecessary surgical interventions.

CONCLUSION

This case report highlights that PTL is a rare malignancy of the thyroid gland with a challenging preoperative diagnosis. A biopsy is essential for diagnosis, and staging is performed using PET-CT. Treatment primarily involves chemotherapy (R-CHOP) and radiotherapy, with surgery reserved for cases resistant to chemotherapy or with residual thyroid disease. Studies on a larger scale are needed to standardize international guidelines, but as the disease is rare, each case should be diagnosed and managed individually.

ORCID

Muppana VVS Srikanth https://orcid.org/0009-0001-6768-9223

Anurag Kushwaha https://orcid.org/0009-0002-9979-3209

Devender Singh https://orcid.org/0000-0002-8219-355X

Ajay Mohan https://orcid.org/0000-0002-2125-5585

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