We describe the clinical aspects of primary thyroid lymphoma, particularly diagnostic procedures and successful therapy based on our observation of 119 patients with primary thyroid lymphoma. Thyroid lymphoma occurred exclusively in the thyroid gland of patients with Hashimoto's thyroiditis as a rapidly growing mass in the thyroid gland. Therefore, progressively enlarging goiter and compression symptoms were the most common clinical manifestations. A significant number of patients in our series had subclinical hypothyroidism (14%) or overt hypothyroidism (27%) because of the coexistence of Hashimoto's thyroiditis. Whenever thyroid lymphoma is suspected, we recommend an ultrasound scan of the thyroid gland and fine needle aspiration biopsy as initial diagnostic procedures. Thyroid ultrasound showed characteristic asymmetrical pseudocystic pattern in 43 of the 46 patients (93%), and thyroid cytologic examination showed abundant monomorphic infiltration of lymphoid cells. Among 83 patients who underwent fine needle aspiration biopsy, 65 patients (78.3%) were diagnosed correctly and 10 patients (12%) had borderline cytologic results. Thus, 90% of patients with thyroid lymphoma were diagnosed or the diagnosis suspected based on fine needle aspiration biopsy. To confirm the diagnosis of lymphoma histologically and to determine the degree of malignancy, open biopsy taking 2-3 g tissue should be done for all cases. Treatment of thyroid lymphoma does not require resection of all lymphoma tissue or total thyroidectomy. Our successful treatment is radiation therapy combined with six courses of CHOP chemotherapy (cyclophosphamide, adriamycin, vincristine, prednisolone). This mode of therapy improved the 8-year survival rate to nearly 100% regardless of the histological type of malignancy.

We report 3 cases of intrathyroidal epithelial thymoma, a clinicopathologic entity distinct from squamous cell carcinoma of the thyroid. Two patients are long-term survivors among 5 postoperative patients with squamous cell carcinoma of the thyroid. One has been free from the disease for 17 years, and the other with local recurrence died of an unrelated disease 18 years after the surgery. The diagnosis in these 2 was corrected to intrathyroidal epithelial thymoma following a review of the histological findings. These 2 tumors consisted of tumor cell nests resembling poorly differentiated squamous cell carcinoma surrounded by many lymphocytes. Features discriminating thymoma from squamous cell carcinoma included the lack of foci of anaplastic carcinoma and papillofollicular tumor, which are seen in squamous cell carcinoma of the thyroid. Two of the 3 patients with squamous cell carcinoma died within 1 year. We have found recently another case of thymoma.The present observations indicate that: thymoma can arise in the thyroid gland presumably from aberrant thymic tissue, mimicking squamous cell carcinoma; and the prognosis of thymoma is favorable. Therefore, it is important to discriminate thymoma from squamous cell carcinoma of the thyroid, which is usually fatal.We had the opportunity to observe 3 patients with intrathyroidal epithelial thymoma and 3 with squamous cell carcinoma of the thyroid. To our knowledge, there has been no previous reports of epithelial thymoma in the thyroid gland. Squamous cell carcinoma rarely occurs in the thyroid gland, and is

Sickle cell disease (SCD) is an inherited disorder caused by a point mutation in the β-globin gene, leading to the production of abnormally shaped red blood cells. Sickle cells are prone to hemolysis and thereby release free heme into plasma, causing oxidative stress and inflammation that in turn result in damage to multiple organs. The transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2) is a master regulator of the antioxidant cell-defense system. Here we show that constitutive Nrf2 activation by ablation of its negative regulator Keap1 (kelch-like ECH-associated protein 1) significantly improves symptoms in SCD model mice. SCD mice exhibit severe liver damage and lung inflammation associated with high expression levels of proinflammatory cytokines and adhesion molecules compared with normal mice. Importantly, these symptoms subsided after Nrf2 activation. Although hemolysis and stress erythropoiesis did not change substantially in the Nrf2-activated SCD mice, Nrf2 promoted the elimination of plasma heme released by sickle cells' hemolysis and thereby reduced oxidative stress and inflammation, demonstrating that Nrf2 activation reduces organ damage and segregates inflammation from prevention of hemolysis in SCD mice. Furthermore, administration of the Nrf2 inducer CDDO-Im (2-cyano-3, 12 dioxooleana-1, 9 diene-28-imidazolide) also relieved inflammation and organ failure in SCD mice. These results support the contention that Nrf2 induction may be an important means to protect organs from the pathophysiology of sickle cell-induced damage.