A 79-year-old Taiwanese woman came to the otolaryngologic clinic of our hospital due to an enlarging painless mass over the right neck region in the past 3 months. She denied fever, night sweats, dyspnea, hoarseness, dysphagia, dysphasia, or stridor. On physical examination, the right thyroid lobe was noted to be enlarged and firm. There was a palpable mass in the front of her neck, which moved during swallowing. She had no history of Hashimoto's thyroiditis or cervical irradiation, and her thyroid function test was within the normal range (thyroid-stimulating hormone: 2.01 nIU/mL; free T4: 1.24 ng/dL; thyroglobulin: 1.62 ng/mL; anti-thyroperoxidase: 1.03 IU/mL; and thyroglobulin antibody: 1.81 IU/mL).\nThe patient had received computed tomography (CT) at hospital outside, which revealed a hypodense nodule with minimal enhancement on the right lobe of thyroid gland []. Its size was approximately 4.1 cm × 3.6 cm, with a longitudinal dimension of 4.5 cm. The trachea, vessels, and soft tissues in the right neck were under pressure and displaced toward the left side. She underwent fine-needle aspiration (FNA) at that hospital, and the cytologic results were suspicious of lymphoma.\nIn order to obtain more definite results, this woman was referred to the radiological department of our hospital for core needle biopsy. During core needle biopsy, the neck color Doppler ultrasound showed a large heterogeneous hypoechoic mass with an irregular border in the right lobe of thyroid gland. There were twisted and chaotic intranodular vessels, but no defined calcification, hemorrhage, or necrotic portion was observed within the mass, which exhibited indistinct margins and posterior acoustic enhancement [Figure and ]. The pathology revealed diffuse large B-cell lymphoma (DLBCL). For staging the disease, a fluorodeoxyglucose (FDG) positron emission tomography (PET) scan was performed, revealing high-grade hypermetabolic lymphomatous disease, confined in the right thyroid gland, suggesting PTL Ann Arbor stage I [].\nAfter consulting oncology specialists, she started rituximab-based chemotherapy and received serial sonographic follow-up. After three cycles of rituximab plus bendamustine – rituximab (375 mg/m2) and bendamustine (Innomustine®, 90 mg/m2) by intravenous administration on day 1 were administered every 3 weeks for each cycle – neck color Doppler ultrasound showed a significant reduction of twisted blood flow signals in the PTL but no significant decrease (<25% extent) of the tumor size []. Therefore, chemotherapy regimen was adjusted to rituximab, cyclophosphamide, vincristine, prednisone (R–COP). After three cycles of R–COP, i.e., rituximab (375 mg/m2), cyclophosphamide (750 mg/m2), and vincristine (2 mg/m2) by intravenous administration on day 1 and prednisone (100 mg/m2) by oral administration on day 1–5 were administered every 3 weeks for each cycle, the PTL disappeared on the color Doppler and gray-scale ultrasonography []. The patient was treated with R–COP regimen until complete remission of the disease, confirmed on the following FDG PET-CT and whole-body PET examination [].
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.