No abstract

A 7-year-old Italian girl with juvenile colloid milium was studied with histological, immunohistochemical, and electron microscopic methods. This patient had a well-documented history of severe sunburn and developed the lesions on the face shortly afterward. Numerous apoptotic keratinocytes were observed in the lower epidermis. These cells began their degeneration with filamentous whorl formation (or filamentous degeneration) of tonofilaments. In the papillary dermis the colloid substance was resolved by the electron microscopy into either wavy, thin filaments derived from the epidermal keratinocytes or typical amyloid filaments. Many desmosomes and gap junctions were found in the colloid substance. Polyclonal antikeratin antibody (DAKO) was positive in the colloid substance, particularly in the parts close to the epidermis. These findings suggested that juvenile colloid milium is different from adult colloid milium despite clinical similarities and that the former belongs to the group of actinic amyloid K, i.e. amyloidoses due to actinic degeneration of keratinocyte and its keratin.

Granular cell tumors (GCTs) are histologically characterized by polygonal neoplastic cells with abundant eosinophilic cytoplasmic granules. In humans, these cells are considered to be derived from Schwann cells, and the cytoplasmic granules are assumed to be autophagosomes or autophagolysosomes. However, the origin and nature of the cytoplasmic granules in canine GCTs have not been well characterized. The present study examined 9 canine lingual GCTs using immunohistochemistry, transmission electron microscopy (TEM), and cell culture and xenotransplantation experiments. In some cases, the tumor cells expressed S100, CD133, and desmin. The cytoplasmic granules were positive for LC3, p62, NBR1, and ubiquitin. TEM revealed autophagosome-like structures in the cytoplasm of the granule-containing cells. The cultured GCT cells were round to spindle shaped and expressed S100, nestin, Melan-A, CD133, LC3, p62, NBR1, and ubiquitin, suggesting that they were of neural crest origin, redifferentiated into melanocytes, and exhibited upregulated autophagy. The xenotransplanted tumors consisted of spindle to polygonal cells. Only a few cells contained cytoplasmic granules, and some had melanin pigments in their cytoplasm. The xenotransplanted cells expressed S100, nestin, Melan-A, and CD133. P62 and ubiquitin were detected, regardless of the presence or absence of cytoplasmic granules, while LC3 and NBR1 were detected only in the neoplastic cells containing cytoplasmic granules. These findings suggest that some xenotransplanted cells redifferentiated into melanocytes and that autophagy was upregulated in the cytoplasmic granule-containing cells. In conclusion, canine lingual GCTs originate from the neural crest and develop cytoplasmic granules via autophagy. In addition, the microenvironment of GCT cells affects their morphology.

Abstract. Tumors at the cranial base in 2 cats (a 9½-year-old, castrated male Chinchilla and a 7-year-old, castrated male American Shorthair) were diagnosed as malignant craniopharyngioma. The tumor lesion was histopathologically divided into four parts: 1) a small acinus part, in which relatively large cells with a pale cytoplasm composed small acini; 2) a duct part, in which small cuboidal cells composed ducts; 3) a cyst part, in which there were large cysts lined with flat cells; and 4) a pavement part, in which large multiangular-shaped cells proliferated in a pavement pattern. The epithelial cells of some parts were positive for keratin by immunohistochemistry. Histopathologic findings of the present feline cases were identical to those of malignant craniopharyngioma in other animal species.

We recently developed a polydimethylsiloxane (PDMS)-based three-compartment microfluidic cocultivation device enabling real-time interactions of different cell populations as an advanced physiologically-relevant cell-based assay. This device had valves and small magnetic stirrer-based internal pumps for easy and flexible perfusion operations. In this study, we applied this device for the evaluation of Irinotecan (CPT-11) toxicity to the lung, because it is detoxified by the liver and accumulated in the fat in humans. We successfully cultured representative three different tissue model cells in each compartment under the individual culture conditions and also in entire perfusion. Growth inhibition of rat lung epithelial cell line L-2, was measured when administered with 50 μM CPT-11 under various cocultivation conditions with respect to the presences and absence of primary rat hepatocytes (liver tissue model) and adipocyte-like cells (fat tissue model) induced from a mouse fibroblast cell line, 3T3-L1. Although CPT-11 showed moderate toxicity to the pure culture of L-2 cells in the device after 72 h of perfusion culture, this was lowered mainly in the presence of the liver tissue. Inhibition of the L-2 cell growth agreed with the area under curve (AUC) values obtained from fluorescent image-based analyses in each compartment. These results demonstrate that developed simple and flexible microfluidic cocultivation device, with appropriate image-based analyses, can be used in evaluating toxicokinetic behaviors of drug candidates in systemic levels.