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. ).
A 52-year-old woman presented to our Endocrinology Unit with a growing thyroid mass, which had enlarged so rapidly she had become unable to wear her motorcycle helmet in the weeks prior to her visit. She suffered from Hashimoto’s thyroiditis for which she was taking levothyroxine. There was no history of neck irradiation or family history of thyroid cancer. On examination, there was a large, firm thyroid nodule on the right side of the neck, without palpable cervical lymphadenopathy. TSH was 4.79 μU/mL with FT3 and FT4 within the reference range. Otherwise, there was only a mild thrombocytopenia. Thyroid ultrasonography showed a solid hypoechoic nodule in the right lobe of the gland, with significant internal vascularity and absence of calcifications (Figure ). FNA cytology with rapid on-site evaluation of the material adequacy showed that there were only atypical lymphoid cells with no thyrocytes and the specimens were considered suggestive of a lymphoproliferative disorder but insufficient to make a diagnosis, such that a CNB was scheduled for the following day.\nAfter checking the blood coagulation profile, the patient underwent a CNB, which allowed histological/morphological tissue analysis. This showed that normal thyrocytes were virtually all replaced by homogeneous medium-sized lymphocytes with scanty blue cytoplasm, round nuclei, coarse chromatin, and multiple small nucleoli. There were frequent mitotic figures and scattered macrophages ingesting apoptotic cells, giving to the tissue section the so-called ‘starry sky’ appearance (Fig. ). Overall, these features were consistent with the presence of a thyroid Burkitt’s lymphoma, and further investigations were ordered to confirm the diagnosis and evaluate the disease extent. A CT of chest and abdomen showed the 44x43x87 mm thyroid nodule with left tracheal deviation (Figure ) without other visible masses or lymph nodes. Bone marrow biopsy showed almost 100% lymphoid infiltration, consisting of a population of intermediate-sized blast-like cells, with prominent nucleoli, which were replacing all normal cells. These cells expressed CD10, CD20, and were negative for Bcl2, CD34, and TdT. Altogether these results led us to the final diagnosis of stage IV Burkitt’s lymphoma [].\nThe patient was admitted to our hospital’s Haematology Unit and was successfully treated with 3 cycles of Hyper-CVAD chemotherapy (cyclophosphamide, vincristine, doxorubicin and dexamethasone) completed in five months. The thyroid mass disappeared (Fig. ) and the platelets returned to baseline levels. At 60 months after diagnosis the patient is alive, and remains disease-free at regular follow-up.