Primary cutaneous extragenital canine transmissible venereal tumour with Leishmania‐laden neoplastic cells: a further suggestion of histiocytic origin?

The clinical signs and histopathological features of a primary extragenital canine transmissible venereal tumour (TVT) are described. Three subcutaneous round alopecic nodules were located on the anterior and caudal dorsal region and in the ventral area of the neck. Cytologically, tumour cells were intermediate in size with a moderate amount of cytoplasm, and the nuclei were immature with finely reticular chromatin. The cytoplasm was lightly to heavily basophilic and contained distinct small vacuoles at the periphery. On the basis of these characteristics, a diagnosis of TVT was made and confirmed by histological and ultrastructural investigations. Leishmania amastigotes were detected in the cytoplasm of macrophages and neoplastic cells of the tumoral mass. The presence of the parasite within neoplastic cells is consistent with a histiocytic origin of TVT.     

Angioinvasive lymphoma (lymphomatoid granulomatosis) in a cat,with cutaneous and ocular metastasis

Lymphomatoid granulomatosis (LYG) is a rare variant of an angioinvasive T-cell lymphoproliferative disorder that primarily affects the lungs, with common sites of metastasis including the skin and subcutis. In humans, it is a B-cell lymphoproliferative disorder associated with Epstein-Barr virus infection. Our case is a 7-y-old, spayed female, domestic longhair cat that decompensated and was euthanized following an initial diagnosis of angioinvasive lymphoma from a skin biopsy. Autopsy revealed nodules in the lungs and subcutis, and corneal thickening and cloudiness. Histologic examination of cutaneous nodules, lungs, and eye showed similar angioinvasive cellular infiltrates and pattern to that of the original skin biopsy, consistent with a diagnosis of LYG. The neoplastic cells displayed CD3-positive immunoreactivity in the skin, eye, and lung, and PCR for antigen receptor rearrangement (PARR) showed T-cell clonality in all tissues tested. This is the third case of LYG to be reported in cats and is the only case in which PARR analysis and immunophenotyping immunohistochemical staining was performed. LYG with ocular involvement has not been reported previously in cats, to our knowledge. Our case demonstrates the necessity for considering LYG when presented with a cat with respiratory signs in conjunction with subcutaneous nodules and ocular lesions.     

Ocular involvement of transmissible venereal tumor in a dog

A case of metastatic transmissible venereal tumor (TVT), with lesions on the penis, conjunctiva, buccal mucosa and skin (lips and trunk), is presented in this case report. The clinical picture is described along with the cytological and histopathological features of the tumor leading to definitive diagnosis of TVT. Possible reasons for the unusual metastatic behavior of TVT and full recovery of the dog after chemotherapy are discussed.     

A canine peripheral nerve sheath tumor including peripheral nerve fibers

Peripheral nerve sheath tumor was found in a 7-year-old male mongrel dog. The tumors were located in the right cheek subcutis and oral submucosa. Histologically, neoplastic cells were arranged in streaming bundles, occasionally interlacing bundles or whorls of elongated and spindle cells. Cellular atypia was poor and mitotic figures were rarely observed. Ultrastructurally, neoplastic cells had basement membrane, typical of Schwann cells. One bundle of normal peripheral nerve fibers and some myelinated axons were seen within the tumor tissues. Immunohistochemically, neoplastic cells reacted to vimentin, glial fibrillary acidic protein, S-100 protein and neuron specific enolase. In addition to the above immunoreactions, the included nerve fibers were positive for myelin basic protein and neurofilament protein. This paper also discusses immunohistochemical findings on differential diagnosis in comparison with those of canine hemangiopericytomas reported hitherto.     

Extragenital transmissible venereal tumour associated with circulating neoplastic cells in an immunologically compromised dog

An adult male intact boxer was presented because of diffuse cutaneous nodules. Fine‐needle aspirate revealed transmissible venereal tumour (TVT) cells. Neoplastic cells were also observed in the peripheral blood. Associated simultaneous diseases included leishmaniosis, demodicosis, papillomatosis and coccidiosis. Immunosuppression may have aggravated disease and triggered widespread metastases. The dog was hospitalized and administered oral amoxicillin/clavulanate, subcutaneous meglumine antimonite to treat leishmaniosis and oral chlortetracycline to treat coccidiosis. Intravenous injection of vincristine at weekly interval was used to treat TVT. A rapid regression of cutaneous nodules was noted; however, intractable diarrhoea developed, eventually leading to death after 18 days. This is the first report describing an unusual case of extragenital TVT associated with circulating neoplastic cells in an immunosuppressed dog presenting with multiple cutaneous nodules.     

Progression of an orbital T-cell rich B-cell lymphoma to a B-cell lymphoma in a dog

An 11-year-old Shetland Sheepdog was presented for exophthalmos caused by a locally extensive, poorly defined mass located behind the right eye. The primary orbital mass was identified by light microscopy and immunohistochemistry as a T-cell rich B-cell lymphoma (TCRBCL) composed predominantly of BLA.36-positive large neoplastic lymphoid cells admixed with fewer CD3- and CD79a-positive small lymphocytes. The dog was treated for lymphoma, but 6 months after presentation it was euthanatized for suspected hepatic and gastrointestinal metastasis. Gross findings revealed an enlarged liver with multiple well-demarcated, randomly distributed 0.1-1.5-cm white nodules, five firm white submucosal jejunal nodules, and ileocecal, mediastinal, and hilar lymphadenopathy. Metastatic liver lesions consisted of sheets of monomorphic large neoplastic lymphoid cells that effaced and expanded portal and centrilobular zones. These cells were morphologically similar to the large neoplastic cells of the original orbital tumor and were CD3-negative and variably BLA.36-positive, consistent with B-cell lineage. Similar cells comprised the jejunal nodules and effaced the lymph nodes. The progression of TCRBCL to a diffuse B-cell lymphoma in this case is consistent with reported human cases and has not been previously reported in the dog.     

Nasal and oral masses in a dog

A 5-year-old, intact male, stray dog was presented in poor body condition, with pallor, muzzle deformity, multiple oozing fistulas with grass awns, bilateral sanguinopurulent nasal discharge and a fleshy friable mass occupying part of the hard palate. A friable mass occupying both nasal cavities was found on rhinoscopy. The dog had moderate nonregenerative normochromic-microcytic anemia, thrombocytopenia, hyperglobulinemia, and hypoalbuminemia. Cytologic preparations of the nasal and oral masses contained a neoplastic population of round cells with intracytoplasmic and extracellular vacuoles. Leishmania amastigotes also were observed, in the cytoplasm of macrophages and, occasionally, within neoplastic cells. A diagnosis of transmissible venereal tumor and concurrent leishmaniosis was made. Treatment with vincristine and allopurinol resulted in complete resolution of clinical signs and disappearance of the masses. The presence of amastigotes in neoplastic TVT cells may suggest an alternative mode of transmission of canine leishmaniosis where these diseases co-exist.     

Feline cutaneous and visceral necrotizing panniculitis and steatitis associated with a pancreatic tumour

The association of pancreatic disorders with fat necrosis in domestic animals is rare. This report concerns a case of cutaneous/subcutaneous necrotizing panniculitis and steatitis associated with a pancreatic adenocarcinoma in an 11-year-old male Siamese cat. Clinical investigation revealed variably sized nodules on the trunk, limbs and abdomen. Some of them were ulcerated; others showed a shiny yellow necrotic background featuring irregular sinus tracts. The cat was euthanized at the owner's request before a diagnosis could be made. At necropsy, abundant oily material resembling mustard replaced the subcutaneous tissue and small yellow nodules were disseminated in the omentum, mesentery and serosa of the abdomen. A multilobulated mass arising from the anterior pancreatic head was found along with liver and lymph node metastasis. Histopathology showed wide fistulous tracts draining necrotic fat from the subcutis toward the surface and multifocal areas of necrotic adipocytes replacing the panniculus. Duct-like structures and tubules lined by neoplastic epithelial cells were observed in the primary pancreatic tumour and in the metastatic sites. The aetiology of the fat necrosis was possibly the result of systemic release of lipolytic pancreatic enzymes.     

Myeloblastic leukemia with massive neoplastic infiltration of the skin and mediastinum in a cow

An acute myeloblastic leukemia was found in a 3.5-year-old Holstein cow. The neoplasm was characterized by massive tumor growths, and there were multiple tumor nodules in the dermis or subcutis and a large tumor mass in the mediastinum. This tumor showed negative reactivity for CD3, CD79a, major histocompatibility complex class II and myeloid/histiocyte antigen. Ultrastructural features such as dispersed cytoplasmic granules and poorly developed organelles were compatible with those of early promyelocytes.     

Lymphangiosarcoma with systemic metastases in a Japanese domestic cat

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.     

A case of primary papillary disseminated adenocarcinoma of canine lung

Primary lung tumors are rare in dogs, whereas pulmonary metastatic neoplastic involvement is common. We describe a case of a 12-year-old male, mixed-breed dog with a 3-month history of coughing and dyspnea. The investigating protocol, which also includes transcutaneous pulmonary biopsy, allowed a diagnosis of lung adenocarcinoma that necroscopic findings confirmed as a primary neoplasia. The tumor exhibited a nodular-disseminated growth, mimicking the metastatic involvement of the lung, instead of the single-mass appearance that has been observed by other authors. The present report indicates that, although the incidence of canine primary lung neoplasms is markedly low, this condition must be considered in the differential diagnosis of lung diseases that cause coughing and dyspnea in older dogs.

     

Use of exfoliative cytology for diagnosis of transmissible venereal tumour and controlling the recovery period in the bitch

Transmissible venereal tumour (TVT) is a rare vaginal tumour that can be treated surgically or cryosurgically as well as by radiotherapy or chemotherapy. Vincristine has been found to be very effective for treating TVT. Since vaginal secretion or discharge may contain neoplastic cells, the cytological identification of TVT cells is possible. The present study was carried out in 12 bitches. Vaginal smears were obtained with cotton swab from the anterior vagina and TVT suspected structures. The smears were stained according to Papanicolaou and assessed by light microscopy. Additionally the general condition of the patients was evaluated by haematological and radiographic examinations. In bitches with TVT vincristine sulphate was administered intravenously at weekly intervals. The total treatment period was three to six weeks until no atypical cells were found in the smear. This was the case after an average of 3.2 +/- 1.3 applications. Tumour masses became smaller and by this non-visible from the rima vulva after 4.2 +/- 0.7 applications. During the treatment, two of the 12 bitches (16.7%) suffered from vomiting and diarrhoea while three (25%) showed neutropenia. Twelve months after completion of treatment, the bitches were examined again and vaginal smears were taken in order to control the recovery process or a possible recurrence of TVT. No atypical cells were found in any vaginal smear. By this exfoliative cytology has proved to be a safe and easy method for TVT diagnosis and for observing the recovery process.     

Establishment and characterization of the growth and pulmonary metastasis of a highly lung metastasizing cell line from canine osteosarcoma in nude mice.

Highly lung metastasizing model of canine osteosarcoma in nude mice was established from five subcutaneous implantation cycles of lung tumor deposits. The selection of cells with increased metastatic properties from the parent POS canine osteosarcoma cell line recovered medium sized and polygonal Highly Metastasizing POS cells (HMPOS). The doubling time of HMPOS and POS in culture averaged 30 +/- 1.2 hr and 32 +/- 1.3 hr respectively, and their cell growth patterns in vitro were comparable to their in vivo growth patterns. HMPOS cells produced more tumor deposits (> 20 nodules, > 1 -mm in diameter) of various sizes with replacement of lung tissues at 12 weeks after implantation. POS cells produced fewer and smaller lung deposits (< 10 nodules, 1-mm in diameter). Tumor size and number of metastatic tumor deposits showed a regular association. HMPOS cells developed an osteoblastic type of cellular differentiation subcutaneously and in the lungs. HMPOS micrometastasis along the alveolar walls and blood vessels at 4 weeks averaged 6-7 small tumor locus. Each micrometastatic locus contained an average of 5-7 tumor cells, and developed a pleomorphic osteoblastic type of cellular differentiation. An average of 4 macrometastatic nodules could be seen at 6 weeks, composed of an average of 23 tumor cells, 10 nodules at 8 weeks, 12 nodules at 10 weeks and 20 nodules at 12 weeks. These model provides an opportunity for the evaluation of new treatments against canine lung metastatic osteosarcoma in a nude mice model.     

Extensive cutaneous metastases in a dog with duodenal adenocarcinoma

Abstract: A 6-year-old Rottweiler was presented to the North Carolina State University College of Veterinary Medicine for evaluation of multiple cutaneous nodules. The dog had a history of anorexia, vomiting, and hind-limb paraplegia. Results of cytologic examination of the cutaneous nodules were consistent with a round cell tumor. At necropsy, primary tumors were found coalescing in the duodenum and the pancreas and extending into the associated mesentery. Numerous masses also were found throughout the skin, abdominal and thoracic viscera, and lumbar spinal cord. Histologically, the duodenal tumor had variable morphology, with some areas resembling adenocarcinoma and others resembling anaplastic round cell neoplasia; the skin and other metastatic lesions resembled round cell neoplasia. Immunohistochemistry of the cutaneous, duodenal, and pancreatic masses showed the neoplastic cells were positive for pancytokeratin, supporting an epithelial origin. In addition, low numbers of neoplastic cells were positive for periodic acid-Schiff and Alcian blue, consistent with acid mucin production by duodenal epithelium. These findings confirmed that the cutaneous nodules were metastatic lesions originating from the duodenal adenocarcinoma. Cutaneous metastasis of intestinal carcinoma is rare in domestic animals. This case demonstrates the potential difficulty in diagnosing metastatic lesions based on cytologic and histologic morphology alone, because the cutaneous metastases may not resemble the primary neoplasm morphologically.     

Highly metastatic ovarian yolk sac carcinoma in a rat

We investigated a highly metastatic ovarian yolk sac carcinoma in a 52-week-old female Crl:CD(SD) rat. Macroscopically, the present case had severe ascites, bilateral ovarian masses and numerous nodules in the abdominal and thoracic cavities. Histopathologically, these masses and nodules were generally composed of two types of cells mimicking a parietal and visceral yolk sac. The parietal cells were round to polygonal, contained eosinophilic droplets and were arranged in nests and cords in the eosinophilic matrix. Both the intracytoplasmic droplets and the matrix were stained positively with PAS. The visceral cells were cylindriform, and proliferated in papillary and tubular patterns and occasionally formed Shiller-Duval body-like structures. In the dissemination sites, the neoplastic cells proliferated on the surface of the various tissues and often infiltrated into deeper parts of the tissues. Immunohistochemically, both neoplastic cells were positive for α-fetoprotein and keratin, and the eosinophilic matrix was positive for laminin. Ultrastructurally, the parietal cells had dilated rough endoplasmic reticulums, which were filled with electron-lucent laminated structures. The visceral cells had poorly to moderately developed intracytoplasmic organelles and were interconnected with desmosomes. Taken together, the present tumor was diagnosed as yolk sac carcinoma arising from the ovary and was characterized by not only high metastasis but also invasive infiltration with biphasic proliferation of the parietal and visceral cells.     

CD34+, CD41+ acute megakaryoblastic leukemia in a dog

A clinically normal, 5-year-old intact female German Shepherd dog was presented to the local veterinarian to be spayed. Results of a preoperative CBC included mild nonregenerative anemia, severe thrombocytopenia, and 17% unclassified cells. On cytologic examination of aspirates from the dog's enlarged spleen and peripheral lymph nodes, a population of primitive round cells that occasionally resembled megakaryocytes was observed. A bone marrow aspirate specimen was markedly hypercellular with approximately 65% of marrow cells comprising a homogeneous population of immature hematopoietic cells similar to those found in the spleen, lymph nodes, and peripheral blood. Using immunocytochemical stains with canine-specific antibodies, all neoplastic cells strongly expressed cytoplasmic CD41 and 20-70% of the neoplastic cells expressed CD34 weakly to moderately. Rare (<0.5%) neoplastic cells weakly expressed vWF. The cells were negative for all other markers. Based on these results and the morphology of the neoplastic cells, a diagnosis of acute megakaryoblastic leukemia (AMegL) was made. In spite of treatment, results of a CBC performed 1 week later indicated progressive anemia and thrombocytopenia, and the dog was euthanized. To our knowledge, this report documents the first case of canine AMegL diagnosed with both anti-canine CD34 and CD41 antibodies.     

A neuroendocrine carcinoma of undetermined origin in a dog

In this report, we describe a case of neuroendocrine carcinoma of undetermined origin in a dog. Necropsy revealed scattered small neoplastic nodules in the bilateral lungs and a small nodule in the parapancreatic lymph node. Histopathologically, both pulmonary and lymph nodal nodules showed a similar histologic pattern, with neoplastic cells being arranged in diffusely proliferating sheet-like cellular nests separated by variable amounts of fibrous septa, sometimes forming rosettes and duct-like structures. Scattered small necrotic foci and invasion to fibrous septa were typically observed. Neoplastic cells showed round to oval-shaped nuclei with prominent nucleoli and abundant eosinophilic cytoplasm that were positive for Grimelius' silver impregnation staining and immunostaining with cytokeratin, synaptophysin, vasoactive intestinal peptide and chromogranin A, indicative of the development of a neuroendocrine carcinoma. However, judging from the distribution of tumors lacking the portion suggestive of the primary site in any organ examined, as well as no further indication of differentiation potential of neoplastic cells, this tumor has so far been diagnosed as neuroendocrine carcinoma of undetermined origin.     

Metastatic cholangiocarcinoma mimicking tuberculosis in a cow

Here we describe a metastatic hepatic cholangiocarcinoma (cholangiocellular carcinoma) in a 14-y-old Beefmaster cow that was euthanized because of depression and progressive weight loss. Gross changes included coalescing, white-to-yellow, firm-to-hard nodules with central areas of necrosis and mineralization that effaced much of the hepatic parenchyma, omentum, mesentery, ruminal serosa, and diaphragm. A fresh sample of a hepatic nodule was submitted for a modified acid-fast (MAF) stain during autopsy to rule out tuberculosis. The MAF stain was inconclusive, and the sample was subsequently submitted for a PCR assay for Mycobacterium spp. Histologically, all nodules consisted of a neoplastic proliferation of epithelial cells surrounded by extensive areas of desmoplasia, consistent with a metastatic cholangiocarcinoma. PCR for Mycobacterium spp. was negative. Although the histologic diagnosis in our case was metastatic hepatic cholangiocarcinoma, gross changes were strikingly similar to those described in cases of tuberculosis, highlighting the need to remain vigilant in the identification of zoonotic and suspected foreign animal diseases during autopsy to protect human health.     

Secretory carcinoma of the canine mammary gland

Secretory carcinoma is an uncommon variant of breast cancer, characterized by the presence of intracellular and extracellular eosinophilic secretion. Here, we report the cytologic, histologic, and immunohistochemical findings of a secretory carcinoma diagnosed in the left inguinal mammary gland of a 3-year-old female German Shepherd Dog. The fine-needle aspiration cytology showed numerous large branching sheets of neoplastic cells and isolated cells with cytoplasmic vacuoles. Histologically, the tumor was composed of cells with clear cytoplasm and prominent vacuoles that pushed the nuclei to the periphery, resembling signet ring cells. These cells were arranged in solid or tubular structures with lumenal spaces filled with eosinophilic secretion. Immunohistochemical reactions to cytokeratin (CAM 5.2) and alpha-lactalbumin were strongly positive in all neoplastic cells, and staining for vimentin and S100 protein was negative. The cytomorphologic and immunohistochemical features of this tumor are similar to those seen in tumors in women, hence enabling the diagnosis of a rare case of primary secretory carcinoma of the canine mammary gland.     

Aural carcinoma with chondroid metaplasia at metastatic sites in a dog

A case of aural carcinoma with chondroid metaplasia at metastatic foci in an 8-year-old male pug is described. Multiple metastases in both lungs and the right submandibular, parotid, retropharyngeal, cervical and prescapular lymph nodes were detected. Histologically, the skin of the right ear canal appeared to be diffusely infiltrated by cords and nests of neoplastic epithelial cells, showing multifocal contiguity with the overlying hyperplastic squamous epithelium. Most of the carcinomatous cells were arranged in a glandular-like pattern, with formation of lumens containing epithelial cells attached to the peripheral cell layer by elongated intercellular bridges. Scattered foci of keratinization with central accumulations of compact, laminated keratin were also observed, and histochemical stains failed to detect mucinous secretory material. Even though histological and histochemical findings were compatible with a diagnosis of acantholytic squamous cell carcinoma, CAM5.2 immunostaining was detectable in the majority, although not all, neoplastic cells, confirming a diagnosis of poorly differentiated ceruminous gland carcinoma. Pulmonary metastatic nodules revealed multifocal areas of cartilaginous metaplasia with apparent transition of carcinomatous cells to chondroid cells, showing nuclear atypia and focal cytokeratin immunostaining. Carcinomatous cells surrounding chondroid areas also revealed focal vimentin and S100 immunoreactivity. Histological evidence of transition between the two components, as well as the presence of intermediate cells displaying both epithelial and mesenchymal immunohistochemical features, strongly indicated a final diagnosis of carcinosarcoma, in which chondrosarcomatous elements were derived from carcinoma cells.