Immune reactivity to autochthonous ovine squamous cell carcinomata

The immune reactivity of tumor-bearing sheep to autochthonous tumor cells was investigated in the efferent lymph of a lymph node distant from the primary tumor site. This was done while the primary tumor was in situ and after its resection. The immune response to challenge with tumor cells while the primary tumor was in situ was associated with the detection of antibodies which were specific for the tumor cells but did not cause their demise. However, both humoral and cellular cytotoxic reactivities were detected in the lymph following removal of the primary tumor and rechallenge with tumor cells. This response had the characteristic of a secondary immune response which indicates sensitization to tumor antigens by the host. Thus the presence of the primary tumor has interfered with pre-existing host immunity.     

Spontaneous nephroblastoma in a Japanese giant salamander (Andrias japonicus)

An adult male Japanese giant salamander (Andrias japonicus) died accidentally, and necropsy showed a white mass (23 × 15 mm) in the left kidney and hepatorrhexis with hemoperitoneum. Histologically, the renal mass was mainly composed of immature nephroblastic tumor cells. In the tumor tissue, a trabecular pattern lined by oval to polygonal tumor cells with a rich interstitium, solid growth and a few tubular structures was observed. Nephroblastic tumor cells were strongly positive for vimentin and weakly positive, and epithelium-like tumor cells were strongly positive for cytokeratin. However, antibody for Wilms' tumor protein 1 did not react with the salamander's cells. On electron microscopy, a desmosome junction was observed between tumor cells. This is the first report of nephroblastoma in a Japanese giant salamander.     

A Case Report of a Malignant Fibrous Histiocytoma in a T-cell Receptor β Chain and p53 Double-knockout Mouse

A subcutaneous tumor was found in the right abdomen of a 16-week-old male TCRβ and p53 double-knockout mouse. The tumor had indistinct borders with the surrounding tissue. The cut surface after formalin fixation was pale yellowish white, partially dark red and partly white. Histologically, the tumor was composed of three distinct regions. The first region showed pleomorphic cells arranged in sheets. The second region showed spindle cells arranged in interlacing fascicles. The final region contained a mixture of the above mentioned two types of cells. Furthermore, a small amount of collagen fibers, round cells, multinucleated giant cells, and cells with eosinophilic granules were observed between these tumor cells. Immunohistochemical examination and electron microscopy identified that the pleomorphic cells and spindle cells were histiocytes and fibroblasts, respectively, and that the round cells were undifferentiated mesenchymal cells. Based on these findings, the tumor was diagnosed as a malignant fibrous histiocytoma.     

Anaplastic gangliocytoma with eosinophilic cytoplasmic granules in a cow.

In a 3-year-old Holstein cow, a tumor mass replaced the left olfactory bulb. The tumor was highly or moderately cellular, and consisted of tumor cells showing pleomorphism and anaplasia, sometimes with intracytoplasmic granules. The tumor showed weak reactivity for neurofilaments (NF) in most cells with distinct staining in a minority, and it was extremely rare to see neoplastic cells with positivity for glial fibrillary acidic protein (GFAP). The neoplastic cells displayed some ultrastructural features reminiscent of ganglionic cells, and the cytoplasmic granularity was due to the presence of numerous lysosomes. This tumor expressing both NF and GFAP may be histogenetically related to brain tumors of pluripotential cell origin in calves.     

Gastric pleomorphic leiomyosarcoma in a Shetland sheepdog

A solitary mass of 6 x 6 x 5 cm was found in the smooth muscle layer of the pyloric part in the stomach of a Shetland sheepdog. The excised mass was solid, gray-white in color, and had central necrosis with hemorrhages. Microscopically, the neoplasm was composed of irregular bundles of spindle-shaped tumor cells and round tumor cells. A few multinucleated cells and gangliocyte-like cells were observed. The nuclei exhibited a high degree of atypia and many cells contained mitotic figures. Immunohistochemically, tumor cells were positive for vimentin and desmin, but negative for c-kit antibody. Ultrastructurally, tumor cells contained cytoplasmic myofilaments and pinocytotic vesicles. Based on these pathological findings, the tumor was diagnosed as gastric pleomorphic leiomyosarcoma.     

High-grade myofibroblastic sarcoma of inguinal region in a dog

A subcutaneous tumor in the left inguinal region was present in an 11-year-old female bloodhound. Histopathologically, the tumor showed invasive growth and extensive necroses, and it was composed of spindle-shaped, elongated, and stellate neoplastic cells accompanied by occasional giant cells arranged in fascicular, herringbone, or irregular storiform patterns with abundant production of collagen fibers. The cytoplasm of most tumor cells was positive for vimentin, alpha-smooth muscle actin, and calponin, but was negative for desmin, smoothelin, and S-100. Furthermore, most of the tumor cells were negative for Iba1 while some tumor cells were weakly positive. Thus, this tumor was diagnosed as a high-grade myofibroblastic sarcoma according to the diagnostic criteria for human myofibroblastic sarcomas.     

Malignant Peritoneal Mesothelioma with a Sarcomatoid Growth Pattern and Signet-Ring-Like Structure in a Female F344 Rat

We report a biphasic malignant mesothelioma in an aged female F344/DuCrlCrlj rat. Macroscopically, multiple pale brown nodules were observed in the abdominal cavity with retention of bloody ascites. Histopathologically, the tumor cells spread over the peritoneum and formed masses on the surface and underlying adipose tissues. The tumor cells dominantly proliferated in a solid, nodular or nest-like pattern with modest amount of fibrillar connective tissues, which contained hyaluronan. The tumor consisted of ovoid, polygonal or spindle-shaped cells that possessed eosinophilic cytoplasms including glycogen; some tumor cells showed a signet-ring-like structure. Multinucleated cells and mitosis were found frequently, and direct invasion to intra-abdominal organs and intravascular metastasis to the liver were observed. Immunohistochemically, keratin and mesothelin were strongly positive in most of tumor cells, while vimentin was mainly positive in spindle-shaped cells. Podoplanin was also positive, particularly in the cell membrane of tumor cells. Electron microscopically, tumor cells showed an intercellular desmosome-like structure, basement membrane and microvillus. We diagnosed the case as a malignant peritoneal mesothelioma with a sarcomatoid growth pattern and signet-ring-like structure.     

Growth and morphological characteristics of canine venereal tumor cells in vitro

Canine venereal tumor cells were grown in monolayer and tumor tissue fragments were maintained in vitro for 56 days in medium-199. Attachment and cell replication were evident within 17 hours and monolayer was obtained by the tenth day. Growth at first comprised mainly round cells with abundance of cytoplasm and vesicular nuclei, and a few spindle-shaped cells. Later cells became more elongated and like fibroblasts. Cell degeneration started by the 17th day and most were degenerated by the 24th day. Necrosis and depletion of cell population were prominent in tumor explants during the first 2 weeks. Distinct cell multiplication was evident by the 21st day and tumor fragments were repopulated with cells resembling the original tumor by the 56th day. Two distinct morphological cell types were seen: small cells with vesicular, round to oval nuclei and acidophilic cytoplasm; and the large cells with large hyperchromatic nuclei and acidophilic cytoplasm.     

Spontaneous adenocarcinoma with giant cell formation in the accessory sex glands in a male Sprague-Dawley rat

In this study, we report the features of an adenocarcinoma with giant cell formation spontaneously occurring in the accessory sex glands of a male 10-month-old Sprague-Dawley rat. A milky white mass was found in the region corresponding to the left seminal vesicle and the left coagulating gland. Histologically, tumor cells exhibited diverse growth patterns, including glandular/trabecular, cystic, and sheet-like growth areas. The tumor cells were pleomorphic, with round- or oval-shaped nuclei and abundant eosinophilic cytoplasm. Mitotic figures were occasionally observed. Giant cells were also prominent in the sheet-like growth area, with intracytoplasmic vacuoles containing eosinophilic material. The stroma was rich in collagen fibers and fibroblasts. Numerous inflammatory cells were observed in the glandular and cystic lumina and stroma. Immunohistochemically, the tumor cells were positive for cytokeratin AE1/AE3 and proliferating cell nuclear antigen. In the sheet-like growth area, some of the tumor cells and giant cells were positive for vimentin in the cytoplasm adjacent to the nucleus. Electron microscopy revealed that the tumor cells contained a small number of mitochondria and rough endoplasmic reticulum, and had no basement membrane or desmosome. The giant cells occasionally contained variably sized intracytoplasmic lumina and globular filamentous bodies, probably corresponding to vimentin. Considering these morphological features, the tumor was diagnosed as an adenocarcinoma with the formation of giant tumor cells originating from the male accessory sex glands.     

Trientine, a copper-chelating agent, induced apoptosis in murine fibrosarcoma cells in vivo and in vitro

Anti-copper treatments have been investigated to determine whether they suppress angiogenesis and tumor development since Cu is widely accepted as being required for angiogenesis. We examined the effects of treatment with trientine, a copper-chelating agent, on tumor development in a murine xenograft model using fibrosarcoma-derived transplantable QRsp-11 cells and C57BL/6 mice and induction of apoptosis in tumor cells and endothelial cells in vivo and in vitro. The tumor volumes increased more slowly in trientine-treated mice than in untreated mice. Tumor volumes in the treated mice were significantly smaller than those in the untreated mice at 24 days postinoculation (d.p.i.) of tumor cells. A cluster of pyknotic tumor cells and morphological abnormalities in capillary endothelial cells were observed in the tumors of trientine-treated mice but not in the tumors of untreated mice. The proportions of apoptotic and necrotic cells in the tumors of treated mice were approximately 3.5-fold higher than those in the tumors of untreated mice at 14 d.p.i. When the cells were treated with trientine in vitro, mouse endothelial cells and bovine primary endothelial cells showed an approximately 10-fold higher sensitivity to trientine than QRsp-11 cells in terms of D37. However, the proportion of apoptotic cells in endothelial cells was significantly lower than that in QRsp-11 cells after treatment with trientine. These results show that apoptosis was induced in tumor cells by treatment with trientine in vivo and in vitro.     

Intracranial granular cell tumor in a dog

A 12-year-old female miniature poodle showed a 3-month history of neurological signs. Magnetic resonance imaging disclosed a high intensity tumor mass in the right cerebral hemisphere with compression of the lateral ventricle. At necropsy, a 2 x 3 cm white, friable mass was found in the right ventral pyriform lobe. Microscopically, the tumor cells were large, polygonal to round cells supported by a sparse fibrovascular stroma. The tumor cells typically possessed finely granular, pale eosinophilic cytoplasm with strongly positive periodic acid-Schiff (PAS) reaction. The tumor cells were immunopositive for vimentin, NSE and S-100. Ultrastructurally, the tumor cells showed large amounts of granules in the cytoplasm, and absence of basement membrane. Based on the above-mentioned findings, the intracranial granular cell tumor was diagnosed.     

实验性鸡马立克氏病羽髓病变研究

通过光镜1电镜等方法对鸡马立克氏病羽髓组织进行了形态学研究。结果显示，羽髓远端坏死，羽髓中有多量肿瘤细胞浸润，肿瘤细胞呈弥漫性或局部性浸润，电镜观察，肿瘤细胞核异型性明显，核膜凹陷，核内出现假核内包含物，在一些羽髓中，巨噬细胞吞噬肿瘤细胞较多见，而且观察到一些肿瘤细胞发生调亡，结果表明，鸡马立克氏病羽髓病变十分明显，羽髓的形态学变化可用于鸡马立克氏病的诊断。     

Spontaneous extraskeletal osteosarcoma with various histological growth patterns in the abdominal wall of an ICR mouse

Extraskeletal osteosarcoma is extremely rare in mice. This case report demonstrates a spontaneous murine extraskeletal osteosarcoma that exhibited various histological growth patterns in an ICR mouse. At necropsy, the tumor mass was located in the abdominal wall and was 45 × 30 × 25 mm in size. Histopathologically, the tumor showed the following four growth patterns: a solid pattern of polygonal cells embedded in an osteoid eosinophilic matrix with calcification, an irregular sheet pattern of short spindle cells accompanying some eosinophilic multinucleated cells, a fascicular pattern of spindle cells and a cystic pattern lined by short spindle cells. Immunohistochemically, most of the tumor cells were positive for vimentin, proliferating cell nuclear antigen and osterix. The multinucleated cells mentioned above were desmin positive and were regarded as regenerative striated muscles but not tumor cells. Since no clear continuity with normal bone tissues was observed, the tumor was diagnosed as an “extraskeletal osteosarcoma.”     

A malar granular cell tumor in a djungarian hamster

'Granular cell' tumor observed in the malar subcutis of a Djungarian hamster was examined to determine its cellular origin. Histologically, the tumor consisted of a solid growth of oval or spindle-shaped large cells with abundant cytoplasm filled with eosinophilic granules that were periodic acid-Schiff-positive and diastase-resistant. Immunohistochemically, the tumor cells were positive to anti-vimentin and anti-desmin antibodies and a few cells showed positivity to anti-actin antibody as well. They did not react to myoglobin, S-100 protein, and glial fibrillary acidic protein (GFAP). Electron microscopic studies revealed that the tumor cells had pinocytotic vesicles, dense plaque and microfilaments. The first granular cell variant of myogenic tumor reported here in Djungarian hamsters was differentiated from granular cell tumor of Schwann cell origin.     

Melanotic neurofibroma in a steer

A melanotic neurofibroma in a steer was investigated histologically, immunohistochemically and ultrastructurally. A very large tumor mass was located in the region of the head and right cheek. The tumor tissue consisted of an admixture of cells resembling Schwann cells and spindle-shaped cells, and they frequently contained melanin granules. Neoplastic Schwann cells were positive for S100 protein, with variation in intensity of staining, but most spindled cells were S100 negative. The tumor cells displayed ultrastructural features similar to those of Schwann cells or perineurial cells. The presence of melanosomes in varying stages of melanization in both cell types suggests that they have a common origin. This is a tumor of neural crest origin showing schwannian and perineurial differentiation, with ectopic production of melanin granules.     

A case of anaplastic meningioma in a dog

A tumor sized in 2.0x2.0x2.5 cm developed in the cerebellum of a female Beagle was pathologically investigated. Histopathologically, the tumor grew by compression and partially by infiltration into the adjacent cerebellar parenchyma. There were a large number of necrotic lesions and proliferation of collagen fibers. The tumor cells had oval nucleus showing cellular atypia and a high mitotic index. The tumor cells were reacted with vimentin antibody on immunostain. Electron microscopic examination revealed the tumor cells interdigitated with cytoplasmic processus where the desmosomes developed on cell junction. This tumor was diagnosed as anaplastic meningioma, which is rarely observed in dogs.     

A spontaneous thymic carcinosarcoma in a young Sprague Dawley rat

We encountered a case of spontaneous thymic carcinosarcoma in a young Crl:CD (Sprague Dawley) rat. Grossly, a white multinodular mass replaced the thymus in the thoracic cavity. Histologically, multiple nodules were separated by fibrous stroma, and each nodule included isolated regions that were composed of epithelial or non-epithelial tumor cells. The epithelial tumor cells were relatively large and round to polygonal cells with large nuclei and weakly eosinophilic cytoplasm. These cells were cytokeratin-positive and vimentin-negative. These cells infiltrated the lungs. The non-epithelial tumor cells were poorly differentiated, small, round to spindle-shaped cells with small nuclei and basophilic cytoplasm. These cells were vimentin-positive and mostly cytokeratin-negative. Many islands of cartilage were observed near non-epithelial cells. Based on these findings, the tumor was diagnosed as a primary thymic carcinosarcoma consisting of a malignant thymoma composed of epithelial tumor cells and a mesenchymal chondrosarcoma composed of non-epithelial tumor cells.     

Spontaneous Adenosquamous Carcinoma with Rapid Growth and EMT-like Changes in the Mammary Gland of a Young Adult Female BALB/c Mouse

This study histopathologically and immunohistochemically investigated a spontaneously occurring single mass subcutaneously located in the left lower abdomen of a female BALB/cAJcl−nu/+ mouse at 10 weeks of age. The mass was about 20 × 15 × 10 mm in size after formalin fixation; nevertheless, it was not detected by clinical observations at 9 weeks of age. H&E staining revealed the tumor origin was epithelial and probably arose from the mammary gland, and the tumor cells demonstrated a squamous, acinar or polyhedral/basal pattern. A cell kinetics analysis revealed that many of the tumor cells of the squamous, acinar or polyhedral/basal component were positive for PCNA and cyclin D1, although there were a few of TUNEL-positive tumor cells in all of the components. An epithelial/mesenchymal analysis demonstrated that most of the tumor cells of the squamous and acinar components contained keratin and E-cadherin; however, most of the tumor cells of the polyhedral/basal component were less or very weakly positive for these markers. The tumor cells of the squamous component were negative for vimentin and SMA; however, many of the tumor cells of the polyhedral/basal component exhibited vimentin. In addition, expression of SMA was confirmed in some tumor cells of the acinar and basal components. Based on the microscopic and immunohistochemical characterizations, the tumor was diagnosed to be adenosquamous carcinoma that originated from the mammary gland with rapid growth, and the tumor cells demonstrated epithelial-mesenchymal transition-like changes.     

A case of canine cutaneous clear cell adnexal carcinoma with prominent expression of smooth muscle actin

Cutaneous clear cell adnexal carcinoma was found in the right lip of a 14-year-old male castrated Shih Tzu. Histologically, the tumor mostly consisted of neoplastic cells with clear or vacuolated cytoplasms and contained frequent tubular structures. Neoplastic cells showed coexpression of pan-cytokeratin (CK) and vimentin by double-labeled immunofluorescence staining. In addition, immunohistochemistry revealed that the tumor cells were positive for pan-CK (AE1/AE3, KL1, CAM 5.2), CK-7, CK-8, CK-14, CK-15, CK-18, vimentin and alpha-smooth muscle actin (SMA) with varied intensity and positivity. Among these marker proteins, SMA was positive in 75% of the tumor cells. On the other hand, CK-15, which is a specific marker of follicular stem cells, was expressed in less than 1% of the tumor cells. Based on these findings, the tumor showed diverse differentiation in apocrine sweat glands and the inner and outer root sheaths of hair follicles, indicating the follicular stem cell to be the origin of this tumor.     

A rhabdomyosarcoma arising in the larynx of a dog

A neoplastic nodular lesion, 2 × 3 cm in diameter, was found in the larynx of a 6-year-old spayed female dog. The tumor was ill-circumscribed, consisting histologically of large round cells with abundant cytoplasm interspersed with small round cells with less cytoplasm and occasional multinucleated cells (myotubes). Immunohistochemically, tumor cells were positive for myoglobin, desmin and vimentin in varying degrees, but negative for S-100 protein, GFAP or cytokeratin. Cytoplasmic myofilaments/myofibrils with a dense Z-line-like structure were seen, the fine structures of which were complemented by PTAH stain. Based on these findings, the tumor was diagnosed as a rhabdomyosarcoma, a very rare tumor in the larynx of dogs.