Abstract
Summary
A 69-year-old woman presented with weight loss, fever, dizziness, exertional dyspnea, and drenching night sweats. Imaging showed a thyroid goiter at the left lobe that measured 5.6 × 3.4 × 3.5 cm in size. On computed tomography, she was found to have large adrenal masses. Core needle biopsy of the left thyroid mass revealed the presence of a mucosa-associated lymphoid tissue extranodal marginal zone B cell lymphoma. Non-Hodgkin’s lymphomas (NHL) typically develop in lymph nodes or other lymphatic tissues. There have been cases where the thyroid has been affected, and the secondary involvement of the adrenal gland is common. In reported cases, 7–59% of patients with NHL exhibited symptoms of thyroid dysfunction. Our patient presented no symptoms of thyroid dysfunction or Hashimoto’s thyroiditis. The patient had bilateral adrenal lymphomas that led to adrenal insufficiency. Immunochemotherapy provided a good response in this case, as seen by the rapid improvement in thyroid and adrenal mass on follow-up PET/CT.
Learning points
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Thyroid lymphoma requires a high index of suspicion for diagnosis in patients with a rapidly growing thyroid tumor, even in the absence of chronic inflammatory thyroid disease.
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Depending on the extent of involvement, adrenal lymphoma may rapidly cause adrenal insufficiency.
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In the setting of acute illness, appropriate levels of plasma cortisol are often unclear, necessitating early initiation of glucocorticoid therapy based on clinical suspicion, especially when features like bilateral adrenal masses and elevated ACTH levels are present.
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Treatment modalities include chemotherapy and radiation therapy for localized lesions, together with hormone replacement for organ dysfunction.
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The origin of the tumor influences the clinical outcome of patients with lymphoma simultaneously involving the thyroid and adrenal glands.
Background
Non-Hodgkin’s lymphomas (NHL) mostly arise in lymph nodes or other lymphatic tissues such as the thymus and spleen which can spread to extranodal sites. While secondary extranodal involvement is frequently seen in a variety of NHL subtypes, primary extranodal disease presenting in more than one extranodal site is not as common. Indeed, only a few cases of primary extranodal disease simultaneously involving the thyroid and adrenal glands have been reported. We present a case of bilaterally affected thyroid and adrenal glands caused by mucosa-associated lymphoid tissue (MALT) lymphoma. Massive masses engulfing the entire adrenal gland cause adrenal insufficiency to develop rapidly. Thyroid dysfunction and thyroid autoimmunity were absent. Thyroid and adrenal involvement from MALT lymphoma had a good clinical response to therapy.
Case presentation
A 69-year-old woman with a history of hypertension presented with weight loss, fever, dizziness, exertional dyspnea, and drenching night sweats and was referred to the cardiovascular clinic in March 2021 after the electrocardiogram documented atrial fibrillation. Her white blood cell count was 9900/mm3. Computed tomography revealed large masses in the bilateral adrenals. She was admitted to the hematology department for further evaluation in June 2021. Physical examination revealed a blood pressure of 82/44 mm Hg, a pulse of 103 beats/min, and a temperature of 38.8°C. She was 148 cm in height and weighed 86 kg. Her skin turgor was normal, and she had no mucocutaneous hyperpigmentation. She had a thyroid goiter localized at the left lobe and it measured about 5.6 × 3.4 × 3.5 cm. No hepatosplenomegaly, ascites, or edema were noted, but non-tender neck lymph nodes in left region IV were noted.
Investigation
Her peripheral blood counts were within normal limits. Her serum glucose, sodium, potassium, glutamic pyruvic transaminase, blood urea nitrogen, creatinine, calcium, and C-reactive protein were all normal. The alkaline phosphatase, uric acid, and lactic dehydrogenase levels were increased. Her morning plasma cortisol level was at 6.7 µg/dL; however, the plasma adrenocorticotropic hormone (ACTH) level was as high as 159 pg/mL. Her serum renin and aldosterone values were low and her thyrotropin and free thyroxine were within normal range, while she was negative for anti-thyroid peroxidase and anti-thyroglobulin antibodies. Plasma 17-hydroxyprogesterone, dehydroepiandrosterone sulfate, and urine 24-h vanillylmandelic acid and catecholamine were all within normal limits. Thyroid ultrasound showed a diffuse, irregular hypoechoic lesion and reduced vascularity (Fig. 1). A CT scan revealed a left thyroid tumor mass, 7.1 cm in diameter with central focal necrosis, and bilateral adrenal masses, measuring 13.8 cm on the right and 8.1 cm on the left, both with some central necrosis (Fig. 2). Small lymph nodes at the mesenteric root and aortocaval region were also noted. PET-CT revealed highly fluorine 18 fluorodeoxyglucose (FDG)-avid masses (SUV >30, SUVmax: 35.57) over the left thyroid and bilateral adrenal and lymph nodes through the right parotid, bilateral neck, superior diaphragmatic, gastric, hepatic, precaval, aortocaval, and mesenteric regions (Fig. 3). Considering the patient's acute clinical presentation, characterized by elevated ACTH levels and low morning cortisol values, we decided to start a 5-day regimen of corticosteroid therapy to address adrenal insufficiency, prior to conducting a bone marrow biopsy. The bone marrow biopsy showed no morphological evidence of infiltration of lymphoma. A core needle biopsy was performed, and pathology revealed monotonous neoplastic cells, focal lymphocytic thyroiditis as lymphocytic infiltration of the stroma, and oxyphilic change of the follicular epithelium (Fig. 4). The neoplastic cells resemble centrocytes with small nucleoli, irregular nuclei, and moderately basophilic cytoplasm, so a low-grade lymphoma was impressed. Positive immunohistochemical stains were observed for CD20 and bcl-2, while negative stains were observed for CD5 and CD10 (Fig. 5). Immunohistochemical stains negative for CD10, bcl-1, bcl-6, CD5, and CD23 excluded the other types of low-grade small B cell lymphoma. As a result, she was diagnosed with MALT extranodal marginal zone B cell lymphoma.
Thyroid echography image showing diffuse, irregular hypoechoic change.
Citation: Endocrinology, Diabetes & Metabolism Case Reports 2024, 1; 10.1530/EDM-23-0019
Whole-body CT with IV contrast. (A) A left thyroid tumor mass, 7.1 cm in diameter with central focal necrosis. (B) Bilateral adrenal masses, measuring 13.8 cm on the right and 8.1 cm on the left, both with some central necrosis. (C) A coronal view of a whole-body CT scan shows enlarged thyroid and adrenal masses.
Citation: Endocrinology, Diabetes & Metabolism Case Reports 2024, 1; 10.1530/EDM-23-0019
Whole-body 18F-FDG-PET/CT at diagnosis. (A) Large FDG-avid mass occupying left thyroid with necrotizing component and causing tracheal deviation (SUVmax 26.82). (B) Two large FDG-avid masses over right and left adrenal region (12.53 and 9.11 cm in diameter, SUVmax 33.12 and 35.57). (C) Several FDG-avid lymph nodes through right parotid, bilateral neck, superior diaphragmatic, gastric, hepatic, precaval, aortocaval, and mesenteric lymph nodes.
Citation: Endocrinology, Diabetes & Metabolism Case Reports 2024, 1; 10.1530/EDM-23-0019
Pathology findings of monotonous neoplastic cells, focal lymphocytic thyroiditis, and oxyphilic change of the follicular epithelium. (A) H&E ×100. (B) H&E ×400.
Citation: Endocrinology, Diabetes & Metabolism Case Reports 2024, 1; 10.1530/EDM-23-0019
Immunohistochemical markers confirm mucosal-associated lymphoid tissue lymphoma. (A) Positive of IHC stain of CD20 ×200. (B) Positive of IHC stain of bcl-2 ×400. (C) Negative of IHC stain of CD10, bcl-6, bcl-1, CD5, and CD23.
Citation: Endocrinology, Diabetes & Metabolism Case Reports 2024, 1; 10.1530/EDM-23-0019
Treatment
The patient received combined modality therapy with immunochemotherapy and radiation therapy consisting of cyclophosphamide, adriamycin, vincristine, prednisone, and rituximab (i.e. R-CHOP) for six cycles, followed by involved-field radiotherapy.
Outcome and follow-up
Tumors in the thyroid and adrenal glands substantially shrank after six cycles of R-CHOP therapy. The thyroid mass on the left shrank from 7.1 cm to 2.7 cm, while the adrenal mass on the right shrank from 13.8 cm to 3.3 cm and the left shrank from 8.1 cm to 2.1 cm at its largest diameter (Fig. 6). Repeat fine needle aspiration for the left thyroid tumor indicated that there was no sign of any disease remaining. Primary adrenal insufficiency was a consequence of bilateral lymphoma, with partial remission achieved through the implementation of several treatment modalities and adjunctive low-dose of corticosteroid supplementation.
Whole-body 18F-FDG-PET/CT after treatment. (A) The previous FDG-avid areas in the left thyroid, the bilateral neck, the superior diaphragmatic, gastric, hepatic, precaval, aortocaval, and mesenteric lymph nodes showed resolution. (B) The FDG-avid areas in the bilateral adrenal regions and showed significant regression.
Citation: Endocrinology, Diabetes & Metabolism Case Reports 2024, 1; 10.1530/EDM-23-0019
Discussion
As in our case, a rapidly growing neck mass is the most typical clinical manifestation in patients with primary lymphoma of the thyroid. Due to tumor involvement, thyroid dysfunction can be found in 7–59% of patients, and most of them have Hashimoto’s thyroiditis (1, 2). In Japan, 83% of thyroid lymphoma patients had serum anti-thyroid antibody tests that were positive, according to Aozasa report (3). No signs of Hashimoto’s thyroiditis or thyroid dysfunction were present in our patient. According to a report, the adrenal gland's secondary involvement happens frequently. According to autopsy studies, 25% of NHL patients show secondary adrenal gland involvement (4). However, primary adrenal lymphoma is extremely uncommon (5). There have been a few case reports of bilateral adrenal lymphomas resulting in adrenal insufficiency (6). Although we did not perform an ACTH stimulation test, the combination of relatively low serum cortisol and markedly elevated ACTH suggests primary adrenal insufficiency. It is worth noting that appropriate levels of plasma cortisol are unclear in the complex setting of acute illness, and glucocorticoid therapy should be commenced early on the basis of clinical suspicion.
Marginal zone lymphoma most often arises in extranodal sites and is thought to be mediated by antigenic stimulation from infections (i.e. Helicobacter pylori infection causing primary gastric MALT) or autoimmune disease (i.e. Sjogren’s disease causing parotid gland MALT). Most patients with extranodal MALT have localized (stage I or II) disease but disseminated disease can be seen in about 30% of cases (7). There have been only a few cases of extranodal NHL described in the literature, mostly diffuse large B cell lymphomas, simultaneously involving the thyroid and adrenal glands (8, 9, 10, 11).
In our case, it is challenging to determine the lymphoma’s primary site and if this represented transformation to a more aggressive lymphoma that was not captured on the available biopsy. The specific pathology of the thyroid mass was difficult to determine because the biopsy was performed using a needle guide rather than a surgical biopsy, leaving little tissue for examination. Although Hashimoto’s thyroiditis was preceded in the majority of thyroid lymphomas, thyroid autoimmunity was absent in our patient. Due to the significant regression of adrenal masses following treatment, we did not perform a biopsy to determine the nature of the adrenal mass. The pattern of primary adrenal lymphoma was described as bilateral involvement of the adrenal glands, enlargement of the retroperitoneal lymph nodes, and tumors occupying the entire adrenal gland that rapidly caused adrenal insufficiency, as observed in our patient (12). Lastly, given the highly PET avidity observed at the disease sites, a heightened suspicion was maintained for a transformation from indolent marginal zone lymphoma to aggressive B-cell lymphoma. However, the pathological findings revealed the presence of cells with small nucleoli, characterized by specific immunohistochemical staining patterns. Consequently, the patient received treatment comprising R-CHOP therapy in conjunction with radiation.
In summary, we present a case of NHL with simultaneous involvement of the thyroid and adrenal glands initially presenting as primary adrenal insufficiency. Our patient received a prompt diagnosis via core needle biopsy and went on to be successfully treated with combined immunochemotherapy and radiotherapy followed by subsequent recovery of adrenal function. Based on this case, we emphasize the need for high clinical suspicion for lymphoma among patients with rapidly growing thyroid mass and development of adrenal insufficiency, confirmation of the diagnosis on biochemical, imaging, and pathology findings, along with continued monitoring for recurrence and recovery of hormone deficiency.
Declaration of interest
The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the case study reported.
Funding
This work was supported by the Tungs’ Taichung Metro Harbor hospital research grant (grant number TTMHH-R1120048).
Patient consent
Written informed consent for publication of their clinical details and/or clinical images was obtained from the patient.
Author contribution statement
CTH drafted the manuscript. JTY and YHT reviewed and edited the manuscript prior to submission. CTH, JTY, and YHT were the physicians who contributed to the care of the patient. YHT also performed final editing of the manuscript and gave the approval to submit the manuscript for publication. All authors have read and agreed to the published version of the manuscript.
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