(18)F-FDG PET/CT for initial assessment and response monitoring in a case of high grade primary lymphoma of the thyroid gland: A case report and review of literature.

Thyroid lymphoma is a rare disease entity of elderly females. Chronic lymphocytic thyroiditis is said to be the precursor of thyroid lymphoma, suggesting a role of chronic antigen stimulation in the development of the disease. We present a case of male with lymphocytic thyroiditis who presented with painless progressive neck enlargement and pathology revealed features of high grade lymphoma. Staging and posttreatment (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) was performed. This report reemphasizes the role of (18)F-FDG PET/CT in the diagnosis, staging, and assessment of therapy response in patients with extranodal lymphoma, including the primary thyroid lymphoma.

INTRODUCTION

Primary thyroid lymphoma (PTL) is a relatively rare neoplastic entity affecting mainly elderly females. It accounts for 1-5% of all thyroid malignancies and 1-2.5% of all lymphomas.[1] Chronic lymphocytic (Hashimoto's) thyroiditis, characterized by lymphocytic infiltration of the thyroid gland predisposes to development of PTL.[2] It renders a very high risk (70-80-fold) of developing PTL when compared to the general population with one out of every 200 patients eventually developing PTL.[3] The usual clinical manifestations of PTL are that of a high grade malignant pathology. Pathologically it is usually a high grade B-cell lymphoma, though both high and low grades of lymphoma have been described.[14] The treatment usually consists of chemotherapy with or without radiotherapy. Surgery has little role in management of PTL, limited to making tissue diagnosis or very rarely in patients with severe airway obstruction. 18F-Fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) has been established as a standard investigative procedure in the initial evaluation and monitoring response to therapy in patients with both nodal and extranodal forms of lymphoma.[5] Intense tracer uptake is usually seen in high grade malignancies like the diffuse large B-cell lymphoma (DLBCL) compared to those of low grade neoplasms such as follicular lymphomas, which show a comparative lesser degree of FDG uptake.[6] 18F-FDG PET/CT shows excellent sensitivity and specificity in staging patients with DLBCL, especially in the detection of extranodal sites.[7] In addition, 18F-FDG PET/CT is also useful for prediction of prognosis and monitoring early therapeutic response, offering the clinicians a valuable tool to timely alter chemotherapy regimens in cases of treatment resistance.[8] We describe baseline 18F-FDG PET/CT findings in a case of primary DLBCL of the thyroid gland and follow-up findings after treatment completion reemphasizing the role of 18F-FDG PET/CT in the management of patients with PTL.

CASE REPORT

A 64-year-old man with a history of hypothyroidism and proven Hashimoto's thyroiditis presented with painless progressive asymmetric enlargement of the thyroid gland. Laboratory evaluation revealed an elevated erythrocyte sedimentation rate (ESR), elevated thyroid peroxidase antibody titer of 850 U/mL (normal <30 U/mL), free triiodothyronine (FT3) 2.34, free thyroxine (FT4) 0.97, and thyroid stimulating hormone (TSH) level of 22.11. A contrast enhanced CT (CECT) exam of the neck revealed a large heterogeneous mass lesion predominantly involving the left lobe of thyroid and partly involving the isthmus and anterior part of right lobe. A needle biopsy from the thyroid mass revealed features of non-Hodgkin's lymphoma (DLBCL) with the tumor cells staining positive for CD20, negative for cytokeratin (CK) and having a high proliferative index (MIB-1) of 35-40%. 18F-FDG PET/CT was performed for staging. It revealed a large heterogeneous mass lesion predominantly involving the left lobe of thyroid and partly involving the isthmus and anterior part of right lobe with intense radiotracer uptake in the thyroid mass (SUVmax-18.7) with no other abnormal identifiable areas [Figure 1a–c]. The patient underwent four cycles of combination chemotherapy (rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone) and was reevaluated with 18F-FDG PET/CT. Post therapy 18F-FDG PET/CT [Figure 2a–c] done 6 weeks after completion of chemotherapy revealed significant decrease in the size of the enlarged thyroid gland associated with no significant FDG avidity (SUVmax-2.0) of the residual thyroid mass (arrow), suggestive of complete metabolic response. The patient is in complete remission at 18 month follow-up.

Figure 1

Baseline 18F-fluorodeoxyglucose positron emission tomography/ computed tomography (18F-FDG PET/CT) images. Whole body maximum intensity projection (MIP) image shows a large area of abnormal tracer uptake in the neck with normal tracer distribution in rest of the body (a) Axial (b) and coronal (c) PET/CT section shows gross enlargement of the thyroid gland with a necrotic center and displacing trachea to the right with no evidence of compression or infiltration. The mass predominantly involves the left thyroid lobe along with part of the isthmus and anterior part of right thyroid lobe. Intense 18F-FDG uptake (SUVmax-18.7) in the peripheral part of the thyroidal mass is seen with no tracer uptake in the necrotic center (b and c)

Figure 2

Post-therapy (after 4 cycles of chemotherapy) 18F-FDG PET/CT images. Whole body MIP image shows normal tracer distribution throughout the body with no significant tracer activity in the neck (a) Axial unenhanced CT image of the neck reveals significant reduction in the size of the thyroid gland with only slight hypodensity appreciable in the marginally enlarged left thyroid lobe (b, arrow). Corresponding 18F-FDG PET/CT image shows no significant 18F-FDG uptake in the residual thyroidal mass (SUVmax-2) suggestive of complete metabolic response (c)

DISCUSSION

At least six different histologic subtypes of thyroid lymphomas have been described with most of them arising from the B-cell population. However, there appears to be two distinct clinical and prognostic groups. The more indolent lymphomas are the subgroup of mucosa-associated lymphoid tissue (MALT) lymphomas comprising approximately 6-27% of thyroid lymphomas, while the more common subtype, comprising up to 70% of cases, is DLBCL. DLBCL has an aggressive clinical course with almost 60% presenting with disseminated disease at diagnosis. Up to 40% of all DLBCL appear to have undergone transformation from a MALT lymphoma, but behave in a similar fashion to DLBCL.[9] High grade lymphomas like DLBCL although very aggressive, show a very good response to chemotherapy with a very good prognosis in limited forms of disease.[10] Although lymphomatous transformation of the thyroid gland in patients with lymphocytic (Hashimoto's) thyroiditis is limited to the thyroid gland, anecdotal reports do mention the involvement of other sites resulting in an extended disease spectrum.[11] Valadez et al., demonstrated extranodal involvement of the kidneys and lungs in a case of primary non-Hodgkin's lymphoma of the thyroid associated with Hashimoto's thyroiditis.[12] Detection of such sites has a bearing on both the management and subsequent prognosis.[13] This reiterates the importance of detection of additional sites, especially early in the course. Our patient presented with isolated involvement of the thyroid gland as evident on baseline 18F-FDG PET/CT which provides an important prognostic variable.

Few reports have been described in the past regarding the role of 18F-FDG PET/CT in patients with thyroidal lymphoma. Most of them represent isolated case reports and only one article concentrates on a small group of patients [Table 1].[11121415161718] 18F-FDG PET/CT has shown limited sensitivity in the assessment of low grade lymphomas such as those arising from MALT. In a report by Mikosch et al., the authors showed that intense 18F-FDG uptake noted in the thyroid gland in their case with MALT lymphoma of thyroid was due to coexisting lymphocytic thyroiditis rather than the lymphomatous part and concluded that, 18F-FDG PET imaging does not seem to be indicated in a patient with MALT lymphoma and known Hashimoto's thyroiditis.[14] Whether this holds true for other low grade entities such as follicular or mantle cell lymphomas remain only to be verified.

Table 1

Review of literature

18F-FDG PET/CT has also been routinely used to monitor therapy response in patients with lymphoma and can identify individuals with treatment resistance to certain forms of chemotherapy, early in the course which provides the clinician a sufficient time window to change the therapeutic strategy.[1719] In the present case, post therapy PET/CT showed complete response to therapy indicating good prognosis and the patient is fine at 18 month follow-up. Thus, this case report highlights the utility of 18F-FDG PET/CT for staging and restaging high grade PTL.