Non-Hodgkin lymphoma of the thyroid in a patient with hyperthyroidism.

Primary thyroid lymphoma is incredibly rare with an annual incidence of approximately 2.1 per million persons, accounting for 2% of thyroid malignancies. One of the only known risk factors is autoimmune thyroid disease, specifically Hashimoto's, although there have been a few cases of thyroid lymphoma associated with Graves' disease. Here, we present one such case of a patient with pre-existing hyperthyroidism who developed non-Hodgkin's lymphoma of the thyroid. The patient initially presented with rapidly progressing right-sided neck swelling. He was clinically and biochemically euthyroid with negative thyroid stimulating immunoglobulin, maintained on methimazole. Biopsy of the thyroid nodule with flow cytometry revealed non-Hodgkin lymphoma. Intervention included radiation therapy.

Introduction

Primary thyroid lymphoma is incredibly rare with an annual incidence of approximately 2.1 per million persons [1], accounting for 2% of thyroid malignancies [2]. When it does occur, it is far more often non-Hodgkin type with one study reporting only 16 cases of Hodgkin lymphoma of the thyroid over a 43-year period [3]. Thyroid lymphoma has a strong female predominance and typically occurs between the ages of 65–75 years old [1]. One of the only reported risk factors includes autoimmune thyroid disease, specifically Hashimoto’s [1,4] although per our literature review there have been a few cases of thyroid lymphoma associated with Graves’ disease [5,6]. Here, we present one such case of a patient with pre-existing hyperthyroidism who developed non-Hodgkin lymphoma of the thyroid.

Case presentation

A 61-year-old male with longstanding, ten-year history of hyperthyroidism presented with two months of right-sided neck swelling. The patient had been taking methimazole 10 mg daily with previous unsuccessful attempts to taper. He was clinically and biochemically euthyroid with negative thyroid stimulating immunoglobulin. He denied any B-type symptoms, including fever, weight loss, or night sweats. Computer tomography (CT) neck revealed an enlarged homogenously enhancing nodule under the right sternocleidomastoid concerning for pathologic lymph node, as well as a smaller satellite node. CT did not note any thyroid nodules. Biopsy of the lymph node showed low-grade B cell lymphoma consistent with marginal zone lymphoma and involvement of the bone marrow. Positron emission tomography (PET) scan demonstrated diffuse asymmetric thyroid activity prominent in the isthmus to the right of midline (Figure 1), thought to possibly represent Hashimoto’s thyroiditis. Subsequent thyroid ultrasound showed a heterogeneously enlarged thyroid with a 4 cm hypoechoic nodule within the lower pole of the right thyroid, as well as an 11 mm hyperechoic nodule in the lower left pole (Figure 2). Given the size and dark hypoechoic appearance of the thyroid nodule in the setting of known lymphoma, fine needle aspiration biopsy and flow cytometry of the right thyroid nodule was obtained (Figure 3). This revealed non-Hodgkin lymphoma of the thyroid. The patient was diagnosed with marginal zone lymphoma of thyroid and right cervical nodes, stage IIE and underwent radiation therapy. Given the negative TSI, the patient was tapered off of methimazole despite previous unsuccessful attempts. Thyroid function tests are being closely monitored.

Discussion

Primary thyroid lymphoma is incredibly rare with an annual incidence of approximately 2.1 per million persons, accounting for 2% of thyroid malignancies. It is primarily B-cell lineage with a majority being marginal zone type [1]. As noted above, the only known risk factor for primary thyroid lymphoma includes autoimmune thyroid disease. When it does occur, it is frequently in the setting of hypothyroidism, specifically Hashimoto’s, more so than hyperthyroidism. Despite the well-established relationship between primary thyroid lymphoma and hypothyroidism, there are very few cases of hyperthyroidism and thyroid lymphoma reported [1,4-7]. Lymphoid tissue isn’t native to the thyroid gland but it is theorized that chronic exposure to antigens, such as in Hashimoto’s, causes lymphoid tissue to migrate to the thyroid which may explain why the disease is highly associated [8]. Similar physiology may occur with antigens in Graves’ disease, although our patient had negative antibodies.

The classic thyroid lymphoma patient may present with an enlarging goiter, dysphagia, hoarseness, neck pain, and occasionally systemic symptoms such as fever, night sweats, weight loss [1,9]. These patients may have signs of either hypothyroidism or, less commonly, hyperthyroidism [5,6].

Fine needle aspiration cytology alone is not sufficient to diagnose thyroid lymphoma, given the common co-occurrence of Hashimoto’s thyroiditis which can appear very similar histologically. Definitive diagnosis includes biopsy with flow cytometry [10-12]. As such, clinicians may not easily recognize the importance of certain clinical testing, such as flow cytometry.

Disease is mostly often limited to the thyroid (~50%) or the thyroid and local lymph nodes (~45%), although there is rarely distant metastasis making staging evaluation of the utmost importance [1,13,14]. Diagnosis is critical, because treatment does not include a thyroidectomy for primary thyroid lymphoma [13-15]. Treatment depends upon staging, but typically includes radiation, chemotherapy, or a combination of the two [10,11,13-15]. Prognosis for stage I or II disease is usually excellent with one study citing a five-year survival rate of 73% [16] and another with 91% [17], both on patients treated with combined therapy.

Based on our case, we would like to highlight the importance of considering the association between primary thyroid lymphoma and hyperthyroidism, instead of the more common seen association with hypothyroidism. We would also like to stress obtaining flow cytometry based upon clinical context and imaging characteristics of the thyroid nodule since diagnosis would greatly alter treatment plan.

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