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.
A 49-year-old woman with a history of Hashimoto’s thyroiditis presented with a rapidly growing neck mass and upper airway compression symptoms. No B symptoms were present. The hematological test showed a white blood cell count within the normal range (51.5 × 102/μL). Interleukin-2 receptor (801 U/mL) and lactate dehydrogenase (228 U/L) levels were elevated, although serum thyroxine and thyroid-stimulating hormone levels were within their normal ranges. An elevated thyroid peroxidase antibody of 271.4 IU/mL was detected. Ultrasonography revealed a mass measuring 2.0 × 1.0 × 1.0 cm in the right lobe of the thyroid; the border of the nodule was indistinct. The patient underwent a right thyroidectomy after a core needle biopsy revealed a diffuse large B-cell lymphoma. Following the final histological diagnosis of primary thyroid BL, the patient received rituximab, cyclosphosphamide, doxorubicin, vincristine, and prednisone for 2 weeks, as well as rituximab, hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone including prophylactic intrathecal methotrexate for 3 months. Adjuvant treatments involving 22 cycles of linear accelerator (LINAC) therapy, 40 Gy each, were administered after the chemotherapy. Thirty months after the initial diagnosis, the patient had no evidence of recurrent disease.\nThe tumor cells were composed of round, intermediate-sized lymphoid cells admixed with scattered tingible body macrophages imparting a “starry sky” appearance (Fig. ). The nuclei were uniform and round-to-oval-shaped. The chromatin was coarsely clumped and had medium-sized paracentral nucleoli, while the cytoplasm was basophilic. Mitotic figures (12 per high-power field) were identified; there was no coagulative necrosis, although extrathyroidal extension was observed. Hashimoto’s thyroiditis was identified in the non-tumoral thyroid tissue.\nDiffuse membranous immunostaining for CD10, CD20, and CD79α, as well as diffuse nuclear staining for MUM-1 (Fig. a) and p16 (Fig. b), were noted in the tumor cells. The expression of MDM2 was focal and confined to the tumor cell nuclei (Fig. c), although the cells were negative for Bcl-2, Bcl-6, and p53. The Ki-67 labeling index exceeded 90% (Fig. ). The EBER in situ hybridization test was negative (Fig. ). Ninety-six percent of the tumor cells were found to have MYC/IgH gene fusion as determined by FISH (Fig. ).\nThe clinicopathological features of 21 thyroid BLs are summarized in Table . The median age at diagnosis was 39.3 years with a male-to-female ratio of 13/8. The majority (94.4%) of these patients presented with a thyroid mass; patients also presented with a rapidly growing nodule (66.7%), dyspnea (61.1%), dysphagia (16.7%), and thyrotoxicosis (5.6%). Four of the 14 described patients (28.6%) showed B symptoms (e.g., systematic symptoms of fever, night sweats, or weight loss). None of the reported patients presented with immunosuppressive conditions or the endemic form of BL. Regarding the treatment modalities, all of the 20 patients for whom data were available (data for 1 were missing) received multidrug chemotherapy regimens; 12 received chemotherapy only, 7 received chemotherapy with combined surgery, and 1 was administered chemotherapy combined with surgery and adjuvant radiotherapy (LINAC).\nFive of 7 patients with thyroid BL (71.4%) had morphologic evidence of Hashimoto’s thyroiditis. Regarding immunohistochemical features, all patients who were tested for CD10 (n = 14), CD20 (n = 18), and CD79a (n = 5) were positive for these respective proteins. IgM was positive in the lone patient who was tested. Additional factors measured are shown in Table . The Ki-67 labeling index exceeded 90% in all 19 patients for whom such staining was performed. We demonstrated that our patient had focal immunoreactivity for MDM2, but none of the other patients had been tested for this protein. All 12 patients who were tested for EBER in situ hybridization showed negative results, and flow cytometry immunophenotyping demonstrated CD10-positive monotypic B-cell populations in all 5 tested patients; moreover, MYC gene translocation was detected using FISH in all 12 patients whose samples were tested.\nOf 19 patients with available clinical outcome data, 14 (73.7%) were alive with complete remission, 1 (5.3%) was alive with persistent disease, and 4 (21.1%) died of the disease. Three of the 19 patients lacked follow-up data; hence, the median follow-up of the 16 remaining patients was 46.5 months (range, 0.5–361 months). Kaplan-Meier survival analysis showed that the 12- and 60-month overall survival rates were 87.5 and 70.7%, respectively (Fig. ).