Hepatocellular carcinoma with lung metastasis showing hemochromatosis in an Egyptian fruit bat (Rousettus aegyptiacus).

After an Egyptian fruit bat (Rousettus aegyptiacus) in a zoo became emaciated and died, a necropsy revealed multiple nodules on the liver and lung surfaces. Microscopy revealed that the liver nodules consisted of neoplastic hepatocytes and showed metastasis in the lung lobes. Most of the neoplastic cells in the liver and lung showed positive labeling for HepPar-1, cytokeratin 19, glypican-3, and Ki-67. Hepatocellular degeneration and necrosis were diffuse in the liver parenchyma. Berlin blue staining revealed large amounts of iron in normal and neoplastic cells. Based on these pieces of evidence, this case was diagnosed as hepatocellular carcinoma with hemochromatosis. This is believed to be the first report of hepatocellular carcinoma in an Egyptian fruit bat that has been immunophenotypically examined in detail by pathological examination.

Adenomyomatous uterine polyp in a Miniature Pinscher: histologic, immunohistochemical, and clinical aspects.

A 14-y-old Miniature Pinscher bitch was admitted to a veterinary clinic because of inappetence and a distended abdomen; ultrasound examination revealed a fluid-filled uterus with a single 1-cm hyperechoic nodule in its lumen. Ovariohysterectomy was performed. Grossly, the uterine horns were distended irregularly and asymmetrically, and the uterine lumen contained 200-300 mL of brown watery fluid. A single white polypoid 0.9-cm diameter nodule was present at the site of the distended uterine horn and arose from the endometrium with a narrow stalk. Histologically, the polyp consisted of dense, smooth muscle fascicles admixed with glandular components; its surface was covered by simple cuboidal epithelium with areas of squamous metaplasia. The myomatous cells expressed the myogenic markers smooth muscle actin and desmin. We interpreted the mass as an adenomyomatous uterine polyp, which is a rare variant of an endometrial polyp.

Production of granulomas in Mycoplasma bovis infection associated with meningitis-meningoencephalitis, endocarditis, and pneumonia in cattle.

Mycoplasma bovis, the most important primary pathogen in the family Mycoplasmataceae, causes pneumonia, arthritis, otitis media, and mastitis in cattle. Histopathologic pulmonary changes associated with M. bovis infection have been characterized as suppurative-to-caseonecrotic bronchopneumonia; infection in other organs has been reported in only a few studies that examined caseonecrotic endocarditis and suppurative meningitis. Granulomatous lesions associated with M. bovis infection have been reported only rarely. We studied the granulomatous inflammation associated with M. bovis infection in several organs of 21 Japanese Black cattle. M. bovis was detected by isolation and loop-mediated isothermal amplification methods; other bacteria were detected using culture on 5% blood sheep agar and a MALDI-TOF MS Biotyper. Tissues were examined by histopathology and by immunohistochemistry (IHC) using anti-M. bovis, anti-Iba1, anti-iNOS, and anti-CD204 antibodies. All 21 cases, which included 2 cases of meningitis-meningoencephalitis, 8 cases of endocarditis, and 11 cases of bronchopneumonia, had caseonecrotic granulomatous inflammation associated with M. bovis infection. The IHC for macrophages revealed a predominance of iNOS-labeled (M1) macrophages in the inner layer of the caseonecrotic granulomas associated with meningitis-meningoencephalitis, endocarditis, and bronchopneumonia in Japanese Black cattle naturally infected with M. bovis.

Neutrophil and M2-polarized Macrophage Infiltration, Expression of IL-8 and Apoptosis in Mycoplasma hyopneumoniae Pneumonia in Swine.

Mycoplasma hyopneumoniae (Mhp) is the primary pathogen of porcine enzootic pneumonia (PEP). Consolidated lung tissue from the cranioventral lung lobes of 15 pigs with PEP was collected for quantitative polymerase chain reaction, histopathology and immunohistochemistry. Histopathology revealed the co-existence of bronchial-associated lymphoid tissue hyperplasia with intra-alveolar neutrophils and macrophage infiltration in lesions of suppurative bronchopneumonia. Immunolabelling of infiltrated macrophages with CD163/CD204 indicated the presence of M2-polarized macrophages. Mhp antigen was detected on respiratory epithelial cells and in phagocytosed neutrophils. The intensity of Mhp immunolabelling and number of CD163/CD204-positive macrophages were correlated with the Mhp load in lung tissue (r = 0.87, 0.56, P <0.05). IL-8 immunolabelling was mainly found in neutrophils and correlated with Mhp load, Mhp immunolabelling and histological lesion score (r = 0.70, 0.66, 0.64, P <0.05), respectively. Apoptosis was seen in intra-alveolar cells and was correlated with Mhp load (r = 0.62, P <0.05). It is postulated that IL-8 attracts neutrophils to the lesions, while M2-polarized macrophages are a major source of IL-10 and promote a Th2-type immune response.

Antitumor effects of chloroquine/hydroxychloroquine mediated by inhibition of the NF-κB signaling pathway through abrogation of autophagic p47 degradation in adult T-cell leukemia/lymphoma cells.

Adult T-cell leukemia/lymphoma (ATLL) originates from human T-cell leukemia virus type 1 (HTLV-1) infection due to the activation of the nuclear factor-κB (NF-κB) signaling pathway to maintain proliferation and survival. An important mechanism of the activated NF-κB signaling pathway in ATLL is the activation of the macroautophagy (herafter referred to as autophagy in the remainder of this manuscript)-lysosomal degradation of p47 (NSFL1C), a negative regulator of the NF-κB pathway. Therefore, we considered the use of chloroquine (CQ) or hydroxychloroquine (HCQ) (CQ/HCQ) as an autophagy inhibitor to treat ATLL; these drugs were originally approved by the FDA as antimalarial drugs and have recently been used to treat autoimmune diseases, such as systemic lupus erythematosus (SLE). In this paper, we determined the therapeutic efficacy of CQ/HCQ, as NF-κB inhibitors, in ATLL mediated by blockade of p47 degradation. Administration of CQ/HCQ to ATLL cell lines and primary ATLL cells induced cell growth inhibition in a dose-dependent manner, and the majority of cells underwent apoptosis after CQ administration. As to the molecular mechanism, autophagy was inhibited in CQ-treated ATLL cells, and activation of the NF-κB pathway was suppressed with the restoration of the p47 level. When the antitumor effect of CQ/HCQ was examined using immunodeficient mice transplanted with ATLL cell lines, CQ/HCQ significantly suppressed tumor growth and improved the survival rate in the ATLL xenograft mouse model. Importantly, HCQ selectively induced ATLL cell death in the ATLL xenograft mouse model at the dose used to treat SLE. Taken together, our results suggest that the inhibition of autophagy by CQ/HCQ may become a novel and effective strategy for the treatment of ATLL.