The expression of cell differentiation and proliferation markers of canine neuroepithelial tumors was examined immunohistochemically to identify the histogenesis of these tumors. Astrocytomas (n ¼ 4) consisted of cells positive for glial fibrillary acidic protein (GFAP) and nestin and a few cells positive for doublecortin (DCX). Immunoreactive cells for receptor tyrosine kinases (epidermal growth factor receptor and c-erbB2) and their downstream molecules (phospho-extracellular signal-regulated kinase 1/2 and phospho-Akt) were often detected in astrocytomas, especially in medium-and high-grade tumors. Gliomatosis cerebri (n ¼ 3) consisted of cells positive for ionized calcium-binding adaptor molecule 1 and GFAP, including a minor population of cells positive for nestin, DCX, and beta III tubulin, suggesting their glial differentiation. In choroid plexus tumors (n ¼ 4), most tumor cells were positive for cytokeratins AE1/AE3 and 18, and few were positive for GFAP. The majority of cells of oligodendrogliomas (n ¼ 5) were DCX positive, but the tumors also contained minor populations of cells positive for GFAP, nestin, or beta III tubulin. Primitive neuroectodermal tumors (PNETs; n ¼ 2) consisted of heterogeneous cell populations, and the tumor cells were positive for nestin, beta III tubulin, and DCX, suggesting glial and neuronal differentiation. The major population of neuroblastoma cells (n ¼ 3) were positive for beta III tubulin and DCX, suggesting single neuronal differentiation. As for antiapoptotic cell death molecules, most tumor cells in the choroid plexus tumors, PNETs, and neuroblastomas were intensely positive for Bcl-2 and Bcl-xL, whereas those in gliomatosis cerebri were almost negative. In astrocytomas, Bcl-xL-positive cells predominated over Bcl-2-positive cells, but the opposite was observed in oligodendrogliomas. The immunohistochemical results were analyzed by hierarchical clustering, and the constructed dendrogram clearly indicated a novel position of oligodendrogliomas: the primitive glial and neuronal differentiation.

Abstract. Subdural histiocytic sarcomas from 15 dogs (mean age: 7.8 years) were histopathologically examined. Among the 15 dogs, there was a marked breed predominance (toward Pembroke Welsh Corgi dogs, 47%), but no gender predilection. Focal solitary subdural masses were detected in the cerebrum (12 cases) and spinal cord (1 case), whereas diffuse infiltrative lesions were observed in the cerebral leptomeninges in 2 cases. All neoplastic lesions had common histological features characterized by the proliferation of pleomorphic histiocytic cells combined with various inflammatory reactions. Multinucleated giant cells, phagocytosis, and atypical mitotic figures in the neoplastic cells were commonly observed. Most of the pleomorphic neoplastic cells in the present cases were immunopositive for monocytic, histiocytic, or both markers, such as human leukocyte antigen (HLA)-DR, ionized calcium-binding adaptor molecule 1 (Iba1), cluster of differentiation (CD)163, and CD204, except for the neoplastic cells in 2 focal and 2 diffuse histiocytic sarcomas. The findings suggest that differences in cell origin, molecular expression, or both patterns are responsible for the distribution patterns of canine subdural histiocytic sarcomas.

ABSTRACT. A mass lesion in the subependymal region of the lateral ventricle in a 13-year-old neutered male mongrel cat with a complaint of somnolence, right circling movement and posture abnormality was examined. The magnetic resonance image examination revealed a relatively large T1-hypointense and T2-hyperintense mass lesion in the left interventricular foramen region, and there were no abnormalities in the chest and abdominal x-ray radiographic, funduscopic, and electric retinogram findings. The cat was died 43 days after the initial referral, and the post-mortem examinations revealed a poorly demarcated subependymal mass. Histologically, the brain lesion consisted of complex proliferation of highly pleomorphic cells resembling histiocytes with atypia and abundant mitotic figures. Moderate infiltrates of small reactive lymphocytes were admixed with the pleomorphic cell population. Gemistcytic astrocytes were also intermingled with the periphery of neoplastic foci. Immunohistochemically, most of the pleomorphic cells were positive for HLA-DR alphachain and ionized calcium binding adaptor molecule 1, and few were positive for lysozyme and alpha-1 antichymotrypsin. The atypical pleomorphic cells were negative for CD3, IgG (H and L), glial fibrillary acidic protein and neurofilament, suggesting monocytic/histiocytic-origin of the cells. The number of Ki-67-positive cell nuclei was extremely large, reflecting the high growth activity of these cells. Based on the findings, the lesion was considered as histiocytic sarcoma.KEY WORDS: brain, feline, histiocytic sarcoma, immunohistochemistry.J. Vet. Med. Sci. 72(1): 99-102, 2010 In dogs, histiocytic disorders have been classified into 3 major categories: canine cutaneous histiocytoma; canine reactive histiocytoses (both cutaneous and systemic); and histiocytic sarcoma complex (both localized and disseminated histiocytic sarcoma) [10]. Cats, in contrast, are rarely affected by these diseases [6]. Histiocytic sarcoma (HS) in cats has been reported to date in the intestinal wall, femur, tarsus, spleen and liver, and mediastinal and vertebral canals [1,5,11,13,16]. A brief description of an HS in the central nervous system (CNS) of a cat was reported only in a review article [19], while malignant histiocytic disorders have been well demonstrated in the canine CNS [2,4,14,18,20]. This report documents the features of a brain tumor in a cat. The histological and immunohistochemical natures characterized by the proliferation of highly pleomorphic cells resembling histiocytes and immunoreactivity for HLA-DR and ionized calcium binding adaptor molecule 1 (Iba1) are consistent with HS [7,8,15].A 13-year-old neutered male mongrel cat was presented to a private animal hospital with a complaint of somnolence, blindness, right circling movement and posture abnormality. The neurological examinations revealed a postural reaction decrease, a left mydriasis and disappearance of a physiologic nystagmus. Complete blood cell count and serum biochemical analyses were within normal ranges...

Tumor cell invasion into the surrounding nervous tissue is one of the histologic hallmarks of anaplastic meningiomas. To identify other possible markers for aggression in canine meningiomas, the relationship between histologic features and the expression of molecules involved in cell adhesion, cell proliferation, and invasion was examined. Immunohistochemistry for epithelial cadherin (E-cadherin), neural cadherin (N-cadherin), b-catenin, doublecortin (DCX), and Ki-67 was performed for 55 cases of canine meningioma. DCX was preferentially expressed in tumor cells invading the brain parenchyma (12 of 14 cases), suggesting its involvement in the invasion process. Regardless of the histologic type, E-cadherin and N-cadherin expression was observed in 31 of 55 and 44 of 55 cases, respectively. There was a significant positive correlation between DCX and N-cadherin expression and a significant negative correlation between E-cadherin and N-cadherin expression, suggesting that decreased E-cadherin and increased N-cadherin expression induce DCX expression. Typical membranous b-catenin expression was observed in 10 of 55 cases, whereas nuclear translocation was observed in 33 cases. Nuclear b-catenin expression was frequently found in anaplastic meningiomas (12 of 14 cases). The Ki-67 labeling indices were significantly higher in anaplastic meningiomas than in other types. These findings indicate that the expression of N-cadherin and DCX and the nuclear translocation of b-catenin are closely associated with the presence of invasion and anaplasia in canine meningiomas. Notably, granular cell meningiomas were negative for almost all the molecules examined, suggesting that they have a different tumor biology than other meningiomas.