Long-acting recombinant human follicle-stimulating hormone (SAFA-FSH) enhances spermatogenesis.

Introduction: Administration of follicle-stimulating hormone (FSH) has been recommended to stimulate spermatogenesis in infertile men with hypogonadotropic hypogonadism, whose sperm counts do not respond to human chorionic gonadotropin alone. However, FSH has a short serum half-life requiring frequent administration to maintain its therapeutic efficacy. To improve its pharmacokinetic properties, we developed a unique albumin-binder technology, termed "anti-serum albumin Fab-associated" (SAFA) technology. We tested the feasibility of applying SAFA technology to create long-acting FSH as a therapeutic candidate for patients with hypogonadotropic hypogonadism. Methods: SAFA-FSH was produced using a Chinese hamster ovary expression system. To confirm the biological function, the production of cyclic AMP and phosphorylation of ERK and CREB were measured in TM4-FSHR cells. The effect of gonadotropin-releasing hormone agonists on spermatogenesis in a hypogonadal rat model was investigated. Results: In in vitro experiments, SAFA-FSH treatment increased the production of cyclic AMP and increased the phosphorylation of ERK and CREB in a dose-dependent manner. In animal experiments, sperm production was not restored by human chorionic gonadotropin treatment alone, but was restored after additional recombinant FSH treatment thrice per week or once every 5 days. Sperm production was restored even after additional SAFA-FSH treatment at intervals of once every 5 or 10 days. Discussion: Long-acting FSH with bioactivity was successfully created using SAFA technology. These data support further development of SAFA-FSH in a clinical setting, potentially representing an important advancement in the treatment of patients with hypogonadotropic hypogonadism.

Pediatric granular cell tumor in the posterior wall of the larynx extending to the trachea.

Granular cell tumor (GCT) is a slow-growing benign neoplasm that can be found in any organ. Pediatric laryngotracheal GCT is rare. We experienced a 6-year-old boy suffering from a barking cough and symptoms of stridor and croup for one month. Head and neck computed tomography revealed a protruding mass that occluded 60% of the airway lumen. Under the impression of hemangioma or papilloma, excision revealed a submucosal non-encapsulated mass. Histologically, the mass was composed of sheets of large polyhedralshaped tumor cells containing plump eosinophilic granular cytoplasm and centrally placed, small, bland-appearing nuclei. The tumor cells were positive for S-100 protein, and voluminous eosinophilic cytoplasm was stained by diastase-resistant periodic acid-Schiff. The present report describes a unique case of a huge pediatric laryngeal GCT extending to the subglottic trachea. We also review the clinical course of pediatric laryngotracheal GCT and emphasize the importance of diagnosing GCT in children.

Malignant glomus tumor of the thyroid gland where is heretofore an unreported organ: a case report and literature review.

Glomus tumors are relatively uncommon clinically benign tumors. Malignant glomus tumors are rare, and only a small number develop metastatic foci. The usual location is deep dermis or subcutis, but it has been reported in various locations. A 55-year-old man presented with an incidentally found thyroid mass. Neck ultrasound showed a mass with a heterogeneous hypoechoic calcific mass in the right lobe. Right lobectomy specimen showed the 3.6-cm-sized calcified mass composed of sheets of uniform round to polygonal cells and intervening staghorn-shaped vessels. Occasional cellular atypism and necrosis with increased mitotic activity (up to 7 per 10 high-power fields) were found. Infiltration to the residual thyroid parenchyma, vessel, thyroidal capsule, and strap muscle was found. These tumor cells were strongly positive for smooth muscle actin, collagen type IV, and vimentin with pericellular reticulin-cuffing. Ultrastructurally, closely packed oval-shaped tumor cells having cytoplasmic mitochondria, rough endoplasmic reticulums with pinocytotic vesicles along the plasmalemmal surface and thin filaments of 6 nm in diameter were surrounded by thick basal lamina. That mass was diagnosed as a malignant glomus tumor. Incidentally, a 0.5-cm-sized papillary carcinoma was found through entire embedding. Complete thyroidectomy with chemotherapy was done. Thirty months later, multiple metastases developed in the brain and lung, and he expired. To our knowledge, neither benign nor malignant thyroid glomus tumor has been previously described. Here, we describe the first case of a malignant glomus tumor in the thyroid gland.

Cytologic Features of ALK-Positive Pulmonary Adenocarcinoma.

BACKGROUND: The aim of this study was to determine the cytologic features of anaplastic lymphoma kinase (ALK) expressing pulmonary adenocarcinoma. METHODS: We analyzed the cytopathological findings of 15 cases of endobronchial ultrasound guided aspiration and a case of bronchial washing. These cases were selected based on the histomorphology of ALK-rearranged lung adenocarcinoma. RESULTS: Cytology showed mucinous (81.3%) and hemorrhagic (50%) backgrounds. The cells were arranged in tubulopapillary or tubulocribriform patterns (93.8%), and clusters (56.3%) admixed with signet ring cell features (87.5%). The tumor cells were monotonous and uniform with vesicular nuclei and a small nucleolus. CONCLUSIONS: The characteristic findings were sheets showing a tubulopapillary or tubulocribriform appearance, with vesicular nuclei and a bland chromatin pattern (p<0.001). Scattered signet ring cells were helpful in suggesting ALK-positive adenocarcinoma (p<0.001).