A Case of Spontaneous Malignant Hibernoma in a Crl:CD(SD)IGS Rat

A firm, tan, well-circumscribed mass that measured 25 × 30 × 35 mm was observed in the thoracic cavity of a 53-week-old male Crl:CD(SD) IGS rat. Histologically, the mass was encapsulated by fibrous tissue and contained fibrovascular septae. Tumor cells were compactly arranged, and most were oval to polygonal in shape with multivacuolated cytoplasm and a centrally located nucleus. In some parts of the tumor, marked cellular atypia and frequent mitoses were evident. Vacuoles in cytoplasm were positive for oil red O. The tumor cells were characterized ultrastructurally by abundant, round to oval mitochondria with transverse closely-packed cristae. Tumor cells were immunohistochemically positive for uncoupling protein 1 (UCP-1). Several thrombi and hemorrhagic or necrotic foci were also observed within the tumor mass. Vascular invasion of the tumor capsule was observed; however, invasion of surrounding tissues or metastases were not observed. Based on the pathology findings, this case was diagnosed as a malignant hibernoma.     

Pathological features of olfactory neuroblastoma in an axolotl (Ambystoma mexicanum)

A one-year-old, female Mexican axolotl (Ambystoma mexicanum) had a rough-surfaced, polypoid, pink tumor mass of approximately 10 mm in diameter in the oral cavity. Histologically, the tumor extended from the ethmoturbinate region and into the oral cavity and had replaced some of the maxillary bone tissue. The tumor mass was composed of a lobular architecture of small round-shaped tumor cells with occasional Flexner-Wintersteiner-like rosette formation. There were no metastatic lesions in the other organs. Immunohistochemically, the tumor cells were partly positive for several neural markers (class III beta-tubulin, S-100 protein, and doublecortin) and intensely positive for an epithelial marker (cytokeratin AE1/AE3). These results suggest that the present tumor originated from neuroectodermal tissue. Considering the location and histological and immunohistochemical features of the tumor, a diagnosis of olfactory neuroblastoma was made.     

Renal Cystic Adenocarcinoma in a Flowerhorn Cichlid with Metastatic Involvement of the Spleen

Abstract

A 480-g flowerhorn cichlid (an ornamental hybrid) with severe bilateral abdominal swelling, bulla-like structures on the skin, bilateral exophthalmia, and a prolapsed intestine was presented. Radiographs showed compression of the posterior part of the swim bladder and abdominal distention. Ultrasonography of visceral organs revealed a heterogeneous mass with hypoechoic to anechoic polycystic parenchyma and free fluid in the abdominal cavity. At necropsy, free fluid in the abdominal cavity and a large polycystic mass originating from the posterior kidney were observed. Histologically, the mass was composed of more cystic growth of tubules. The renal architecture was replaced by tubules, often irregular in shape, lined by simple to lightly stratified layers of neoplastic and pleomorphic cuboidal to columnar epithelial cells and the absence of glomeruli. Birefringent crystals were observed with polarized light within the lumen of some tubules. The apical border of the neoplastic cells was periodic acid–Schiff positive. Immunohistochemically, the neoplastic cells were positive for cytokeratin AE1/AE3 and proliferating cell nuclear antigen and were negative for p53 (tumor suppressor protein). Microscopic metastasis was seen in the spleen. The metastatic tumor was classified as a cystic adenocarcinoma of the kidney, originating from the proximal tubules.

Received October 7, 2016; accepted June 18, 2017 Published online July 31, 2017     

Pleural mesothelioma in a young cat

A mesothelioma was seen as an incidental finding in the thoracic cavity of an eleven-month old female cat. At necropsy, the pale nodular lesions were spread over the ventral parts of the lungs and their corresponding parts of the diaphragm and the thoracic wall. Microscopically, the tumor consisted of mesenchymal tissue with large amounts of collagenous fibers covered by a mainly unilayered, polymorphic, partly vacuolated line of cells with large nuclei. Mitotic figures were rare. Based on morphological appearance the lesion was classified as an early mesothelioma.     

Ovarian teratoma with a formed lens and nonsuppurative inflammation in an old dog

A 9-year, 7-month-old female German shepherd weighing 26.6 kg was admitted to the hospital for pica and diarrhea. A large mass was found in the right ovary and removed, and cross section of the mass revealed a multilobular tumor consisting of several cystic cavities which contained tufts of dark hair in thick creamy-white sebaceous fluid. Histologically, the tumor consisted of adipose tissue, central nervous tissue, crystalline lens, cartilage and bone. In the central nervous tissue, lens and lesions like nonsuppurative inflammation comprizing of accumulation of glial cells and lymphocytic perivascular cuffing were observed. The tumor was diagnosed as a mature cystic teratoma.     

Metastasizing fibrosarcoma in a Wistar rat--case report

A 19-month-old male control Wistar rat from a 30-month inhalation study showed a subcutaneous greyish-white mass extending from the throat to the thoracic cavity. The rat had been euthanized because of its poor general condition. Histologically, the mass was diagnosed as a fibrosarcoma infiltrating the masseter muscle with metastases in the lungs, liver and heart. The primary tumour was characterized by fusiform spindle cells producing various amounts of interlacing bundles of collagen. The cells formed a characteristic herringbone pattern and mitotic figures were frequent. The histological parameters of the metastases were practically identical to those seen in the primary tumour. The diagnosis was confirmed by trichrome staining and positive immunostaining for vimentin and was differentiated from leiomyosarcomas by its negative immunostaining for desmin, from schwannomas by its negative immunostaining for S-100 and from malignant fibrous histiocytomas by the absence of giant cells. The incidence of fibrosarcomas in Wistar rats is very low (up to 3%) and metastasis is rarely observed.     

Highly invasive intracranial malignant schwannoma in a rat

A highly invasive intracranial malignant schwannoma containing several masses was detected in a 28-week-old male Crl:CD(SD) rat. Macroscopically, 3 masses were noted in the cranial cavity; one was present at the bottom of the cranial cavity and involved the trigeminal nerve, and the other two were in the parietal bone. Histologically, each mass consisted of fusiform cells with interlacing fascicular, wavy and nuclear pseudopalisading arrangements and round cells with cystic lesions. The tumor cells invaded not only the brain but also the parietal bone. In the brain, the tumor cells infiltrated diffusely into the leptomeningeal and perivascular spaces and parenchyma, in which the tumor cell morphology and invasive pattern closely resembled those of malignant astrocytoma and malignant reticulosis. Immunohistochemically, the tumor cells in the masses showed positive reactions for both S-100 protein and GFAP, while those in the cerebral invasion sites were negative for GFAP and less positive for S-100 protein. Electron microscopically, a single basal lamina layer and short intricate cell processes were confirmed in the tumor cells. From these results, the present tumor was diagnosed as a malignant schwannoma arising in the cranial cavity, probably originating from the trigeminal nerve. The present tumor is considered to be a relatively unique malignant schwannoma based on its growth and invasion patterns.     

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.     

Osteolytic Osteosarcoma in a German Shepherd Bitch

Necropsy of a six year old female German Shepherd revealed the presence of a large oval mass in the thoracic cavity originating from the thickened proximal portion of the right fourth rib. Osteolytic osteosarcoma was diagnosed on the basis of gross appearance, presence of many pleomorphic spindle cells, containing pink stained intracytoplasmic granules in cytological preparations of impression smears of the tumor and histopathology. The tumor was considered highly malignant and was characterized by an abundant osteoblastic and connective tissue stroma with extreme cellular pleomorphism including giant cells, atypical mitoses and occasional trabeculae of tumor bone and osteoid. Metastases were found in the lung and spleen. Electron microscopy was carried out to support the diagnosis.     

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.     

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.     

Malignant Lymphoma with Severe Infiltrative Growth into Skeletal Muscles in WBN/Kob Rats

Although spontaneously occurring neoplasms have been reported repeatedly in F344, SD and Wistar rats, which are commonly used strains for routine toxicologic and carcinogenicity studies, there are only a few reports of malignant lymphoma or lymphatic leukemia except for large granular lymphocytic leukemia (LGL) in F344 rats. Malignant lymphoma (lymphosarcoma) is thought to be uncommon in F344 rats. The authors encountered malignant lymphomas of the non-LGL leukemia type with characteristic pathologic features in WBN/Kob rats. The mean age at onset of the disease in all 13 affected rats (8 males and 5 females) was about 60 weeks. Common and characteristic clinical signs were abnormal gait with hind limb paralysis. Macroscopically, the enlargement of the lymph nodes, spleen and liver was slight to moderate. Scattered multiple white-to-gray nodules encompassed the aorta and assumed a bead-like appearance near the thoracic and lumbar vertebrae. Histopathologically, neoplastic proliferative changes were predominant in the bone marrow tissue of the entire body, and many tumor cells infiltrated the spleen and several lymph nodes. The most striking histological features were constant and severe infiltration of tumor cells in the adipose tissue and skeletal muscle adjacent the thoracic and lumber vertebrae. Immunohistochemically, all tumor cells were positive for B-cell markers (PAX-5, CD79a and CD45) and negative for CD3. From the results of immunohistochemistry and morphological examination, these tumors were diagnosed as malignant B-cell lymphomas.     

Thymoma in a dog with a part of granular cell proliferation and concurrent lymphoma cells

A 12-year-old male Shiba dog showed anemia and the swelling of systemic lymph nodes. X-ray and post mortal examinations revealed a anterior mediastinal mass. Histologically, the tumor mass consisted of four different elements; cord-like proliferation of cuboidal epithelial cells, tubular or cystic structures lined with ciliated epithelial cells, proliferation of large round-shaped epithelial cells with PAS-slightly positive granular cytoplasm, and diffuse proliferation of neoplastic lymphocytes. Epithelial cells in cord-like or cystic structures were strongly positive for cytokeratin. Granular or foamy cells were negative for all markers examined and had myelin-like bodies in the cytoplasm by electron microscopy. The neoplastic lymphocytes in the tumor mass were considered being derived from concurrent multicentric lymphoma. Based on these findings, the present case was diagnosed as thymoma with a part of granular cell proliferation and concurrent lymphoma cells.     

A Case of Olfactory Neuroblastoma Induced in A Rat by N-Nitrosobis(2-hydroxypropyl)amine

N-nitrosobis(2-hydroxypropyl)amine (BHP) is a well-known carcinogen and induces tumors in various tissues. In the present paper, a case of olfactory neuroblastoma (ONB) induced in a rat by BHP is described. The tumor was observed in one out of 25 male rats that received 2000 ppm of BHP in drinking water from 6 to 18 weeks of age and were sacrificed at 26 weeks of age. Histologically, the tumor arose in the posterior nasal cavity and consisted of small round cells and elongate cells with scant basophilic cytoplasm. The neoplastic cells proliferated with compartmentalization into the lobules by fibrovascular septa. True rosettes, pseudorosettes and an intercellular fibrillar matrix were occasionally observed. Immunohistochemically, the tumor cells were positive for NF120/200 and β III-tubulin. These results indicate that the present tumor is the first case of ONB induced in a rat by BHP treatment.     

Spontaneous seminoma in medaka (Oryzias latipes)

Although spontaneous development of seminoma is rare in medaka, we encountered spontaneous testicular tumors located within the abdominal cavity in two adult medakas. The growth patterns of the tumors were a combination of solid and cord arrangements in one of the two cases (Case I) and lobular in the other case (Case II). The tumor cells resembled the cells at different stages of spermatogenesis, and a small number of oocyte-like cells were also scattered within the tumor. The tumor with solid and cord patterns showed loss of normal testicular architecture, and the tumor cells had partly invaded the dorsal muscular tissue and metastasized to the liver, kidney, and eye. The tumor with a lobular pattern did not exhibit local invasion or metastasis. The tumors were diagnosed as seminomas based on their histopathological characteristics, and the tumor in Case I was observed to be more malignant than that in Case II.     

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.”     

IMAGING DIAGNOSIS—ENDOMETRIAL MINERALIZATION IN A DOG

A 9‐year‐old intact female mixed breed dog was presented for mammary gland tumor surgery, and preoperative radiographs showed a tubular soft tissue opacity mass with multifocal mineralization in the caudoventral abdominal cavity. Subsequent ultrasonography demonstrated uterine dilation with echogenic fluid and endometrial acoustic shadowing consistent with mineralization. Resection of mammary gland tumors and ovariohysterectomy were performed. Pyometra was diagnosed on cytologic examination of uterine fluid. Histopathology of the uterine tissue confirmed a diagnosis of cystic endometrial hyperplasia with uterine mineralization.     

The time course of lymphatic routes emanating from the peritoneal cavity in rats

The lymph drainage routes from the abdominal cavity in rats were observed at 3 min, 1, 2 and 4 h after India ink was administered intraperitoneally. Four systems of lymph drainage routes from the peritoneal cavity were observed. Three minutes after injection, the drainage route travelled via the intrathoracic lymph vessels located along the internal thoracic artery and returned to the anterior mediastinal lymph nodes. One hour after injection, the drainage route travelled via the lymph vessel located along the left phrenic nerve in addition to the drainage route observed at 3 min. Two and four hours after injection, in addition to the above-mentioned routes, the drainage that had travelled via the thoracic duct continued along the right side of the aorta and was also observed in the lateral lymph vessel located on the vertebra. These findings suggest that lymph or cells absorbed into the peritoneal cavity at first travel towards the anterior mediastinal lymph nodes in the thorax via the ventral lymphatic channels, and then gradually course through the dorsal lymphatic channels. These routes may serve as a route for transporting cancer cells and other cells from the peritoneal cavity.     

Mixed Type of Malignant Mesothelioma in an Aged Male ICR Mouse

Multiple whitish nodules in the thoracic cavity at the site of the thymus were observed in a 101-week-old male ICR mouse. In a histopathological examination, the neoplastic cells were predominantly fusiform in shape and proliferated in sarcomatoid growth patterns. Some neoplastic cells showed epithelial growth patterns, such as the ductal structures. Mitotic figures were frequently seen, and small necrotic foci and invasion to adjacent thoracic organs were noted. In Alcian blue staining, bluish materials were observed between fusiform-shaped cells and in some of the lumens of the ductal structures. In immunohistochemistry, both fusiform-shaped and ductal structure-forming cells were positive for vimentin and weakly positive to positive for cytokeratin. Based on the aforementioned findings, the thoracic nodules were diagnosed as a mixed type of malignant mesothelioma. This case was thought to be rare because of the very low occurrence of spontaneous mesothelioma in mice.     

Renal adenocarcinoma in a ferret

A spontaneous case of renal tumor was observed in a 7-year-old ovariectomized female pet ferret (Mustela putorius furo). Clinical signs included exhaustion, emaciation, anorexia, and stooping position. At necropsy, a solid and cystic mass replaced the left kidney and adrenal gland. The tumor was composed of pleomorphic epithelial cells with a large number of giant cells. Metastases were recognized in the lung, liver, greater omentum, right renal pelvis, and systemic lymph nodes. Immunohistochemical stains revealed that the tumor cells were positive for CD10, cytokeratin (CAM 5.2), and Ki-67 (MIB-1). On the basis of morphologic and immunohistochemical features, the tumor was diagnosed as a pleomorphic renal adenocarcinoma. This type of neoplasm is very rare in all species and has never been reported in a ferret.