An eight-year-old male presented with a mass in the right anterior neck that had been apparent for one week. Upon physical examination, blood pressure was recorded as 100/65 mmHg, heart rate was 80 beats per min, respiratory rate was 20 breaths per min and temperature was 36.1°C. A mass measuring ~4.0 cm in size, which caused difficulty in swallowing, was identified in the right anterior neck. The laboratory test results demonstrated a normal blood count and serum biochemistry, as well as normal levels of electrolytes and carcinoembryonic antigen. In addition, the test results for Epstein-Barr virus (EBV) viral capsid antigens immunoglobulin (Ig)M and IgG, human immunodeficiency virus (HIV) and hepatitis C virus antibodies, hepatitis B antigen and syphilis were negative. Furthermore, the thyroid hormone test results were as follows: Free thyroxine (FT) 4 levels of 11.8 pmol/l (normal range, 9–25 pmol/l); FT3 levels of 4.2 pmol/l (normal range, 3–9 pmol/l); thyroid-stimulating hormone levels of 0.720 μIU/ml (normal range, 0.34–5.60 μIU/ml); anti-thyroglobulin levels of 20 IU/ml (normal range, <115 IU/ml); and anti-thyroid peroxidase levels of 25 IU/ml (normal range, <34 IU/ml). The patient had no significant past medical or family history of disease. A B-mode ultrasound examination revealed a mass measuring 4.0×3.0×2.5 cm in the right lobe of the thyroid (), however, the lymph nodes surrounding the mass were normal (). The patient underwent a right lobe and isthmus thyroidectomy whereby two lymph nodes were excised simultaneously. Following the surgery, positron emission tomography-computed tomography scans showed normal metabolism in the left lobe of the thyroid and other parts of the body (). The patient’s bone marrow cytology was also normal, however, histological examination revealed diffuse infiltration of atypical lymphocytes and the observation of residual thyroid follicles and necrosis (). In addition, under low magnification, the ‘starry sky’ histology was observed in certain areas (). The atypical lymphocytes were medium-sized and consistent, with centrally located nuclei of irregular shape, displaying dispersed and deep basophilic chromatin and scanty cytoplasm. Additionally, certain neoplastic cells were visible, while varying numbers of nucleoli and apoptosis and mitosis were observed. Benign tissue cells engulfing apoptotic bodies were also observed under high magnification (), however, the isthmus of the thyroid was not infiltrated by the neoplastic cells. No reactive lymphocyte infiltration or fibrosis was identified in the stroma of the thyroid, and no oxyphilic change or squamous metaplasia was observed in the epithelial cells of the background thyroid tissues (). The only change in the two lymph nodes that were simultaneously excised, was the presence of reactive hyperplasia of the lymphoid follicles (). Immunohistochemical staining was then performed with the primary antibodies shown in (Zymed Corporation, Inc., San Francisco, CA, USA; Santa Cruz Biotechnology, Inc., Santa Cruz, CA, USA). The results showed that the neoplastic cells were diffusely positive for cluster of differentiation (CD)20 () and CD10 (), marginally positive for CD38, CD43 and B-cell lymphoma (Bcl)-6, but negative for Bcl-2 and terminal deoxynucleotidyl transferase (TDT). In addition, CD3 and CD5 stained the background T cells, and the Ki-67 proliferation index was >95% (). Analysis using an EBV-encoded small RNA (EBER) digoxin-labeled probe (PanPath B.V., Budel, Netherlands) was performed and revealed a negative result (), however, positive nuclei were observed in the nasopharyngeal carcinoma tissue, which was used as the positive control (). Analysis using the C-MYC break-apart detection probe (Guangzhou LBP Medical Science Technology Co., Ltd., Guangzhou, China) was also performed and the results revealed that ~90% of the neoplastic cells exhibited red and green signal separation, which indicated that chromosome breakage and translocation of the MYC gene had occurred in the neoplastic cells (). Immunoglobulin gene rearrangement assays were performed according to instructions of the Biomed-2 Polymerase Chain Reaction kit (Invivoscribe technologies, Inc., San Diego, CA, USA), followed by capillary electrophoresis, which was analyzed using Genemarker® v1.5. software (SoftGenetics, LLC, State College, PA, USA). Positive gene arrangements of IgH and IgK were observed in the tumor tissues, however, no positive gene rearrangements were observed for IgL (). Consequently, the patient was diagnosed with primary BL of the thyroid and underwent alternate R-B-NHL-BFM-90-A and R-B-NHL-BFM-90-B treatment, for four cycles each. The two regimens, including the dose and duration of chemotherapy, are described in . After almost four years of follow-up, the patient appears well and remains free of disease.
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 –]. 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 –] 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.