Thyroid lymphoma: Correlation of clinical, radiological, and pathological features

Primary thyroid lymphoma (PTL) comprises 5% of all thyroid malignancies. In this case series, we aim to review its clinical presentation, diagnosis, and treatment. We included five PTL patients. All were females (mean age of 59.8 years). All patients presented with a rapidly growing neck swelling, and only two had obstructive symptoms. All patients had solitary masses, aside from one patient who had two lesions. All were causing mass effect and two with invasion of the surrounding tissue. All were diagnosed with diffuse large B-cell lymphoma. Cytology examination for PTL demonstrates atypical lymphoid cells. Four patients in our series had chemotherapy and currently in remission. The fifth died early after the clinical presentation. Two had thyroid surgeries.

Keywords

Fine needle aspiration - lymphoma - oncology - thyroid

Introduction

Primary thyroid lymphoma (PTL) is a rare type of thyroid malignancy, representing 5% of all thyroid malignancies and 3% extranodal lymphomas.[[1]] It is most commonly diagnosed between 50 and 80 years, with a peak incidence in the sixth decade. Similar to differentiated thyroid carcinoma, it occurs more commonly in women than in men.[[2]] Histologically, B-cell Non-Hodgkin Lymphoma is the most common type. Clinically, the most frequent presentation of PTL is a rapidly enlarging thyroid mass causing obstructive symptoms.[[3]] The presence of Hashimoto's thyroid disease is an identified risk factor for PTL.[[4]] In this case series, we retrospectively reviewed five cases of PTL to determine the radiological and histopathological findings of thyroid lymphomas and the management course.

Case Reports

Case 1

A 66-year-old female presented to the clinic complaining of a gradually increasing neck swelling for 4 months. Ultrasonography of the neck revealed a diffusely enlarged left thyroid lobe with heterogeneous parenchyma. Further imaging by neck computed tomography (CT) scan showed a well-defined heterogeneous left thyroid mass measuring 7.5 cm × 4.2 cm × 7 cm, with multiple pathological-looking cervical lymph nodes bilaterally. The left supraclavicular group was particularly enlarged, causing significant mass effect and infiltrating the left sternocleidomastoid muscle. She was euthyroid. Thyroid fine needle aspiration (FNA) was done and showed atypical lymphocytes. She then underwent near-total thyroidectomy to exclude lymphoma or malignancy, and peritracheal lymph nodes were excised. Post-operative histopathology revealed diffuse large B-cell lymphoma (DLBCL) and Hashimoto's thyroiditis with immunohistochemistry (IHC) positive for human leukocyte common antigen (LCA) and CD20. She received rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP protocol) for seven cycles and did not require any radiotherapy. Eventually, she achieved complete remission and currently under surveillance for the past 9 years.

Case 2

A 59-year-old female sought medical attention after she developed a progressively enlarging tender neck swelling for 2 months. Neck CT scan revealed a 6 cm × 7 cm × 8 cm, heterogeneous hypoattenuated right thyroid mass, with no definite invasion of the surrounding structures but causing narrowing of the airway. There were no enlarged cervical lymph nodes. She was euthyroid. FNA from the thyroid showed atypical lymphocytes highly suggestive of lymphoma. She underwent right hemithyroidectomy. Her postoperative histology revealed DLBCL arising in a background of Hashimoto's thyroiditis with IHC positive for CD45, CD20, CD79a, and negative for CD3, CD9, CD23, and cyclin D1. She received four cycles of R-CHOP and three cycles of ESHAP protocols (etoposide, solumedrol, high-dose cytarabine, and platinum) without radiotherapy. Her repeated CT scan of the neck showed partial response, and she is currently under surveillance.

Case 3

A 75-year-old female came to the emergency room after she developed a rapidly enlarging neck swelling. A contrast-enhanced CT scan of the neck revealed a heterogeneously enhancing right thyroid lobe lesion. It measured 8.5 cm × 7.2 cm × 6.2 cm and was displacing the trachea to the left side and the right carotid artery laterally with focal partial encasement. There were also enlarged right cervical and retropharyngeal lymph nodes. Histology from thyroid biopsy showed DLBCL with IHC positive for CD45, CD79a, and PAX5 and negative for CD10, CD4, CD5, CD23, Bcl2, Bcl6, CD30, and proliferative index Ki-67 was 90%. She received an R-CHOP chemotherapy protocol for seven cycles and Involved-Field Radiation Therapy. She has been in remission for 1 year now. [[Figure 1]]a and [[Figure 1]]b demonstrates the CT scan images of the thyroid lesion before and after the chemotherapeutic treatment.

Figure 1: (a) Case 3 at presentation, the computed tomography scan of the head and neck demonstrated the presence of a large heterogeneously enhancing right thyroid lobe mass causing tracheal displacement and narrowing. (b) Case 3 after chemotherapy, computed tomography scan of head and neck postchemotherapy treatment showing marked improvement of the thyroid mass

Case 4

A 64-year-old female came to the emergency room with a newly developed neck mass in association with dyspnea and severe respiratory distress. Urgent tracheostomy was done. Neck ultrasound showed a left lobe mass with heterogeneous parenchymal echogenicity. CT scan of the neck showed an 8 cm × 7 cm × 6 cm heterogeneous mass with internal vascularity in the left thyroid lobe that was not separable from the left sternomastoid muscle. The mass was also involving the right thyroid lobe causing significant right-sided tracheal displacement. There was also left internal jugular vein occlusion along with multiple adjacent left cervical lymphadenopathy. The nodes at the posterior triangle were also involved. She was hypothyroid. Thyroid FNA revealed atypical lymphoid cells, and the histopathology of her Tru-cut core biopsy showed DLBCL with IHC positive for CD45, CD 20, CD10, and CD3 and negative for PAN CK and S100. Unfortunately, the patient's condition deteriorated rapidly, and she passed away before histopathology results came back.

Case 5

A 35-year-old female came to the emergency room complaining of a progressive neck mass for 1 year and stridor for 1 week associated with shortness of breath and difficulty swallowing. She is known for autoimmune hypothyroidism. Neck ultrasound showed the left lobe is enlarged and replaced by a large hypoechoic heterogeneous lesion measuring 6.6 cm × 3 cm × 5.4 cm with no prominent vascularity. The right thyroid lobe has heterogeneous echotexture and prominent vascularity, with a small hypoechoic nodule. CT scan of the neck showed a heterogeneously hypodense mass involving the left lobe, isthmus, and partially extending into the right thyroid lobe, measuring 5.5 × 4.5 × 9.1 cm. There was an associated deviation of the trachea to the right side, causing significant airway narrowing. The right cervical lymph nodes were enlarged and had a suspicious appearance, but there was no invasion of the adjacent structures. Thyroid FNA revealed DLBCL. Histopathology from an open biopsy of the thyroid lesion confirmed the diagnosis. IHA was positive for LCA, CD20, Vimentin and negative for S100, TTF-1, Thyroglobulin, and CD3. She recently started chemotherapy and required a tracheostomy to maintain a secured airway.

Discussion

In this case series, we demonstrate the clinical and pathological characteristics of PTL. In our study, most of our patients were elderly (mean age was 59.8 years), and all were females, which is in concordance with the global literature.[[5]] Reported presenting symptoms for PTL are usually neck swelling and symptoms related to compression of the surrounding structures such as dysphagia or hoarseness of the voice.[[6]] In our study, the presentation was similar, in which all patients presented with neck swelling and two had additional obstructive symptoms. Patients with Hashimoto's thyroiditis are 70–80 times more likely to develop thyroid lymphoma than the normal population,[[7]] and in fact, the two patients in our series who underwent thyroid surgery had evidence of Hashimoto thyroiditis in their histopathology. [[Table 1]] demonstrates the clinical characteristics of the patients in this series.

Table 1: Demographic and clinical characteristics of the patients at the case series

The histology of PTL is mostly of B-cell in origin in 50%–80% of the cases, DLBLC being the most common form is also evident by our five patients, while the rest (6%–27%) are mucosa-associated lymphoid tissue (MALT) lymphomas.[[3]]

The diagnosis of PTL has highly suspected if the presentation was rapidly progressive, which is not the case with the more indolent differentiated thyroid carcinoma.[[8]],[[9]] PTL tumors may present radiologically as a well-defined solitary nodule, multiple nodules, or homogenous hypodense enlargement of the thyroid gland. PTL was found to tend to compress, rather than invade, the surrounding structures. According to previous reports, most PTL presents as a solitary thyroid mass.[[10]] In our study, all CTs revealed solitary masses except for one, which had two lesions. All were causing mass effect, and only two with invasion into the surrounding tissue.

It is essential to differentiate between thyroid lymphoma from poorly differentiated or anaplastic thyroid carcinomas due to their similarities in clinical presentation and radiographic findings. All of them usually present over the age of 50 and clinically tend to present with advanced local disease and cervical lymph nodes metastasis but have entirely different management.[[11]] Therefore, the best way to distinguish between them is by flow cytometry, IHC staining, along FNA.[[12]]

The key features of thyroid lymphoma in FNA cytology are cellular smears that show a monomorphic population of atypical lymphoid cells in a background that contains sparse to absent follicular epithelial cells. Lymphoglandular bodies are also commonly present. In low-grade B-cell lymphomas, the small lymphocytes are admixed with plasma or plasmacytoid cells. In high-grade ones, other cells predominate (immunoblast/centroblast).[[13]] In most cases, diagnosis can be reached by FNA supported by flow cytometry and immunophenotyping the malignant lymphoid cells.[[14]] Morphologically, large cell lymphoma may simulate anaplastic thyroid carcinoma clinically and/or methodologically (large cell with prominent nucleoli). In challenging cases, ancillary studies are of great help.[[15]]

A previous study revealed that B-cell lymphomas tend to behave more aggressively than MALT lymphoma.[[1]] Out of all the PTL subtypes, DLBCL has the worst prognosis with a mean survival of 8.5 years, a 5-year survival rate of 70%, and a 10-year survival rate of 59%.[[16]] In our study, only one patient succumbed to her disease.

This case series showed that some patients were misdiagnosed with other types of malignant neoplasm of the thyroid gland and underwent unnecessary surgical excision and were later diagnosed with non-Hodgkin lymphoma by histology. PTLs generally have an excellent response to chemotherapy and radiotherapy; thus, surgery should not be performed without any critical compressive symptoms warranting immediate action.[[6]] In this study, four patients received chemotherapy, one of them received radiotherapy, and two underwent surgery. A retrospective review of 52 PTL patients in a tertiary care center in Saudi Arabia showed that the relapse-free survival and overall survival at 5 years were 72% and 88%, respectively. In the same study, similar to our case series, the median age was 59.5 years, and all were non-Hodgkin's lymphoma cases. A significant number of those patients had surgical intervention in their community hospitals before their confirmed diagnosis.[[17]]

In conclusion, thyroid lymphoma should be highly suspected in patients with rapidly enlarging neck mass, especially in elderly patients with a background of Hashimoto's thyroiditis. It is crucial to recognize it early, intervene with chemotherapy and radiotherapy if required, and avoid unnecessary surgery and morbidity.

Declaration of patients' consent

The authors certify that they have obtained the appropriate patient consent. The patients have given the consent for images and other clinical information to be reported in the journal. The patients understand that no names and initials will be published, and all due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Authors contribution

All authors participated in the clinical care, drafting and finalization of the manuscript.

Compliance with ethical principles

Prior formal ethical approval is not required in our institution for single case reports and small case series provided the patient provides informed consent for anonymous publication as stated above.

Data availability

Not applicable.

Conflict of Interest

There are no conflicts of interest.

Financial support and sponsorship

Nil.

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Publication History

Received: 11 June 2021

Accepted: 15 July 2021

Article published online:
06 July 2022