A 14-year-old white British Caucasian boy presented with a 3-month history of malaise, lethargy, and weight loss. There was no history of fever or any other thyroid related symptoms. Past and family history were noncontributory and there was no recent foreign travel. On examination he was found to have a large predominantly left-sided firm thyroid swelling. Clinical examination was otherwise unremarkable with no lymphadenopathy or hepatosplenomegaly or signs of hypo/hyperthyroidism. Baseline haematological and biochemical investigations on admission were within normal limits (Hb 136 g/L, WCC 9.1 109/L, CRP <4 mg/dL). Levels of thyroxine, TSH, and calcitonin were normal. Lactase dehydrogenase (LDH) was slightly elevated at 352 U/L. Thyroperoxidase was elevated (1277 IU/mL) and thyroid stimulating hormone receptor antibodies (TRAb) of <5 U/L. CSF analysis showed no tumour cells. EBV PCR was negative as was HIV-I and HIV-II.\nA fine needle aspiration biopsy was carried out and was suspicious of NHL. The diagnosis of Burkitt type NHL (BL) was made following an open wedge biopsy. On microscopic examination, the tumour was composed of diffuse sheets of lymphoid cells () having round nuclei with coarse chromatin and conspicuous single to multiple nucleoli and scanty amphophilic cytoplasm. Numerous mitotic figures, apoptosis, and scattered tingible body type macrophages were also present. Tumour cells were positive for CD79A, CD20, and CD10 and negative for TdT and T cell markers (CD3, CD4, and CD8). Ki 67 showed proliferation index approaching 100%. Immunohistochemistry for EBV was negative. The diagnosis of BL was confirmed on fluorescence in situ hybridisation that showed tumour cell positivity for the t(8; 14) translocation.\nStaging CT () showed a large (6.7 cm × 5.8 cm × 6.1 cm) heterogeneous mass in the left lobe and isthmus of the thyroid which extended craniocaudally from level of C4/5 to T1/2, with some evidence of intratumoural necrosis. There was significant mass effect with displacement and compression of the trachea along with compression of the left carotid artery and lateral displacement of the left jugular vein. There were two small indeterminate lung nodules. Abdominally there were two focal cortical abnormalities in the right kidney and an ill-defined attenuation in the pancreatic head. There was no evidence of bone marrow involvement.\nHe was treated according to the Children's Cancer and Leukaemia Group guidelines for BL—Group B protocol. This consisted of initial induction chemotherapy with COP (cyclophosphamide [300 mg/m2], vincristine [1 mg/m2], and prednisolone [60 mg/m2—7 days]) followed by 2 courses of COPADM (doxorubicin 60 mg/m2, methotrexate 3 g/m2, cyclophosphamide 500 mg/m2/day—5 days, vincristine [2 mg/m2], and prednisolone [60 mg/m2—5 days]) and two courses of CYM (cytarabine 100 mg/m2/day—5 days and methotrexate 3 g/m2) chemotherapy. This was accompanied by intrathecal chemotherapy (the CSF contained no tumour cells at diagnosis). The patient had a good response to treatment with a rapid decrease in the size of the thyroid mass and resolution of the lung, kidney, and pancreas metastases. Reassessment after the first course of CYM showed a residual thyroid mass of 15 mm × 30 mm but with resolution of the lung, kidney, and pancreas metastases.\nBecause of residual radiological abnormality, and in accordance with the CCLG NHL protocol, a hemithyroidectomy was performed with the residual lesion showing no evidence of tumour cells on histological examination. Chemotherapy was then completed and he is now disease-free 3 years after end of treatment.
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.