Histiocytic sarcoma is a progressive and fatal malignant neoplasm that mainly occurs in middle- to old-aged dogs. This study describes clinicopathological, histological and immunohistochemical characteristics of intracranial histiocytic sarcomas in 23 dogs. Magnetic resonance imaging and/or computed tomography of the brains revealed that the tumors mainly located in the cerebrum, particularly the frontal lobe. Seizure was a predominant clinical sign in most of the cases. Histologically, the tumor cells were morphologically classified into round/polygonal- and spindle-shaped cell types. There was a significant association between tumor cell types and hemophagocytic activity (P<0.05). However, there was no significant difference in other clinicopathological parameters and mitotic index between the 2 types. Immunohistochemically, tumor cells were strongly positive for HLA-DR, Iba-1 and CD204 in all the 23 cases, for iNOS in 20, for CD163 in 17, for CD208 (DC-LAMP) in 9, for lysozyme in 8 and for S100 in 5 cases. In addition, the Ki67-proliferative index showed range of 0.50–64.33% (Average 26.60 ± 3.81%). These observations suggest that canine primary intracranial histiocytic sarcomas tend to exhibit both dendritic cell and macrophage phenotypes of histiocytic differentiation.

Two newly established canine histiocytic sarcoma (HS) cell lines, designated as PWC-HS01 and FCR-HS02, were obtained from brain and articular tumors, respectively. These 2 HS cell lines had phagocytic ability and modal chromosome aberrations. Although morphologic features of both HS cells were similar, immunocytochemical examinations revealed that the PWC-HS01 cell line expressed both dendritic cell (ie, S100, CD208, CD1, and CD4) and macrophage (ie, CD68, CD163, and CD204) markers. In contrast, the FCR-HS02 cell line was immunonegative for CD204 and CD68 but consistently positive for the dendritic cell markers. Moreover, reverse transcription polymerase chain reaction analyses confirmed histiocytic differentiation of both HS cell lines. These results suggest that HS from the central nervous system may have a tendency to be more undifferentiated compared with cases from other organs. In addition, the 2 newly established HS cell lines were also tumorigenic and metastatic in immunodeficient mice, supporting that these cell lines can be used as new tumor models for investigating canine histiocytic diseases.

Oligodendroglioma is a common brain tumor in dogs, particularly brachycephalic breeds. Oligodendrocyte precursor cells (OPCs) are suspected to be a possible origin of oligodendroglioma, although it has not been well elucidated. In the present study, 27 cases of canine brain oligodendrogliomas were histologically and immunohistochemically examined. The most commonly affected breed was the French Bulldog ( n = 19 of 27, 70%). Seizure was the most predominant clinical sign ( n = 17 of 25, 68%). The tumors were located mainly in the cerebrum, particularly in the frontal lobe ( n = 10 of 27, 37%). All cases were diagnosed as anaplastic oligodendroglioma (AO) and had common histologic features characterized by the proliferation of round to polygonal cells with pronounced atypia and conspicuous mitotic activity (average, 10.7 mitoses per 10 high-power fields). Honeycomb pattern ( n = 5 of 27, 19%), myxoid matrix ( n = 10, 37%), cyst formation ( n = 6, 22%), necrosis ( n = 19, 70%), pseudopalisading ( n = 5, 18.5%), glomeruloid vessels ( n = 16, 59%), and microcalcification ( n = 5, 19%) were other histopathologic features of the present tumors. Immunohistochemically, the tumor cells were positive for Olig2 in all cases and for other markers of OPCs in most cases, including SOX10 ( n = 24 of 27, 89%), platelet-derived growth factor receptor α ( n = 24, 89%), and NG2 ( n = 23, 85%). The present AO also consisted of heterogeneous cell populations that were positive for nestin ( n = 13 of 27, 48%), glial fibrillary acidic protein ( n = 5, 19%), doublecortin ( n = 22, 82%), and βIII-tubulin ( n = 15, 56%). Moreover, cultured AO cells obtained from 1 case retained expression of OPC markers and exhibited multipotent characteristics in a serum culture condition. Overall, the findings suggest that transformed multipotent OPCs may be a potential origin of canine AO.

A cell line named FB‐LCH01, derived from a dog diagnosed with Langerhans cell histiocytosis (LCH), was established and characterized. FB‐LCH01 had C‐shaped nucleoli, characterized by modal chromosome aberrations. The original tumour cells as well as established FB‐LCH01 cells were immunopositive for human leukocyte antigen‐DR, Iba‐1 and E‐cadherin, and immunonegative for CD163 and CD204, suggesting Langerhans cell origin. Furthermore, the characteristics of FB‐LCH01 were compared with those of two canine histiocytic sarcoma cell lines (PWC‐HS01 and FCR‐HS02) established previously. Expression of E‐cadherin was detected only in FB‐LCH01, but not in PWC‐HS01 and FCR‐HS02. All (n = 9) the severe combined immunodeficiency mice inoculated with the FB‐LCH01 cells developed subcutaneous tumour masses after 3 weeks. Eight of nine mice also developed metastatic lesions in the lymph nodes (8/8; 100%), lung (5/8; 62.5%), stomach (5/8; 62.5%), heart (4/8; 50%), pancreas (4/8; 50%), kidney (3/8; 37.5%), skin (3/8; 37.5%) and bone marrow (1/8; 12.5%). Tumour cells were pleomorphic and round‐ to polygonal‐shaped with prominent anisocytosis and anisokaryosis. The xenotransplanted tumour cells maintained the immunohistochemical features of the original tumour with persistent E‐cadherin expression at injection site and some visceral organs. In conclusion, the established cell line as well as the mice xenotransplant model in this study reflect the nature of canine LCH and may serve as promising models for investigating the patho‐tumorigenesis and therapy of the disease.

Canine Lafora disease (LD) is an autosomal recessive genetic disorder causing nonfatal structural epilepsy, mainly affecting miniature wirehaired dachshunds. Repeat expansion in the EPM2B gene causes a functional impairment of the ubiquitin ligase malin which regulates glycogen metabolism. Abnormally structured glycogen accumulates and develop polyglucosan bodies predominantly in the central nervous system. The authors performed a comprehensive clinical, genetic, and pathological study of 4 LD cases affecting miniature wirehaired dachshund dogs with EPM2B repeat expansions, with systemic distribution of polyglucosan bodies and accumulation of laforin and other functionally associated proteins in the polyglucosan bodies. Myoclonic seizures first appeared at 7-9 years of age, and the dogs died at 14-16 years of age. Immunohistochemistry for calbindin revealed that the polyglucosan bodies were located in the cell bodies and dendritic processes of Purkinje cells. Polyglucosan bodies were also positive for laforin, hsp70, α/β-synuclein, ubiquitin, LC3, and p62. Laforin-positive polyglucosan bodies were located in neurofilament-positive neurons but not in GFAP-positive astrocytes. In nonneural tissues, periodic acid-Schiff (PAS)-positive polyglucosan bodies were observed in the heart, skeletal muscle, liver, apocrine sweat gland, and smooth muscle layer of the urinary bladder. In the skeletal muscle, polyglucosan bodies were observed only in type 1 fibers and not in type 2 fibers. The results indicate that although the repeat expansion of the EPM2B gene is specific to dogs, the immunohistochemical properties of polyglucosan body in canine LD are comparable to human LD. However, important phenotypic variations exist between the 2 species including the affected skeletal muscle fiber type.

Four cases of histiocytic sarcoma in domestic ferrets (Mustela putorius furo) are described in the present study. Tumor samples obtained from the abdominal viscera, including the spleen, were submitted for histologic examination. Microscopically, poorly demarcated masses contained numerous round- to pleomorphic-shaped cells with coarsely vacuolated and eosinophilic cytoplasm. Bizarre, binucleated tumor cells and multinucleated giant tumor cells with low phagocytic activity were commonly observed. Immunohistochemically, tumor cells in all of the cases were positive for vimentin, human leukocyte antigen-DR, ionized calcium-binding adapter molecule-1, and lysozyme, but some of them lacked cluster of differentiation (CD)163 or CD208 expression. The survival time after surgical resection was 9 days to 5 months. Histiocytic sarcoma in the ferret is a rare, but highly aggressive, tumor commonly found in the spleen.

A 4-year-2-month-old female Japanese domestic cat was diagnosed with lymphangiosarcoma through tissue biopsy of an amputated leg. Two months later, the cat was euthanized, and postmortem findings revealed edema, and bruising at the caudal region of the trunk, pulmonary hemorrhage, pulmonary nodules and mediastinal lymphadenopathy. Microscopically, neoplastic tissues were observed in the dermis and subcutis of the trunk, lung, mediastinal lymph nodes, diaphragm, omentum and mesentery. The tumor cells were spindle to polygonal-shaped with nuclear pleomorphism aligning along pre-existing collagen bundles and forming irregular vascular channels in which the erythrocytes were rarely observed. These cells were immunopositive for vimentin, von Willebrand factor and CD31. Based on the histopathological and immunohistochemical features, the neoplasia was diagnosed as lymphangiosarcoma with systemic metastases.

Running head: HISTIOCYTIC SARCOMA IN CIVET This case study had focused on a male, 7-year-old Asian palm civet (Paradoxurus hermaphroditus) with a history of biting its tail and the development of skin masses around its inguinal area, prior to its death. Macroscopically, multiple firm white nodular masses of 0.5-5 cm in diameter were found in the subcutis of the inguinal area, and in the lungs, spleen and liver. Microscopically, masses in the skin, lungs and spleen were composed of neoplastic spindle cells admixed with mononuclear cells and multinucleated giant cells. The neoplastic cells were arranged in a sheet pattern. Immunohistochemically, the neoplastic cells were immunohistochemically positive for vimentin, Iba-1, CD 204 and Human leukocyte antigen (HLA)-DR, while the cells were negative for cytokeratin and smooth muscle actin. Based on the histopathological and immunohistochemical results, disseminated histiocytic sarcoma was diagnosed.