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 [].
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. ).