Tumor-associated antigen on bovine leukemia virus-induced bovine lymphosarcoma

Specific tumor-associated antigen (TAA) was detected on enzootic bovine leukosis (EBL) cells by monoclonal antibodies against TAA. One of the monoclonal antibodies, c143, reacted with all EBL tumor cells tested but not with bovine leukemia virus (BLV) antigens. c143 reacted slightly with bovine fetal thymus and mitogen-stimulated lymphocytes from BLV-free cows but not with normal bovine lymphoid cells. TAA may be a good tumor marker of EBL tumor cells. We sacrificed eight TAA-positive but clinically normal animals and examined them in order to elucidate whether or not they had gross or histological tumors. At necropsy, four animals had tumors macroscopically. Three animals had no tumors histologically but had initial lesions showing follicular hyperplasia and the TAA on affected lymph nodes. The one remaining showed medullary hyperplasia in the spleen but there were no findings of tumors. Thus, c143 is a useful tool not only for diagnosing EBL, but also for screening of BLV-infected cattle with potential to develop tumors in the future.     

Canine sertoli cell tumor: a medical records search and literature review

Seventeen cases of Sertoli cell tumor in dogs were found by searching medical records from 1971 to 1985. The average age of affected dogs was ten years, and most animals were of mixed breed. Most of the dogs were presented for reasons unrelated to the Sertoli cell tumor, however, most dogs had one or more clinical signs associated with Sertoli cell tumor. These signs included prostatic changes, alopecia and hyperpigmentation, bone marrow suppression, gynecomastia, and behavioral changes. The association of Sertoli cell tumor with cryptorchidism was obvious in these records, as ten of the dogs had one or both testicles undescended. Histopathological features of the tumors were variable and had no consistent correlation with metastatic potential. Some interesting comparisons can be made regarding these tumors in other domestic animals and in man.     

Epididymal interstitial (Leydig) cell tumors in B6C3F1 mice

Six primary interstitial cell tumors of the epididymis were identified from 46,752 male B6C3F1 mice used in chronic toxicity and carcinogenicity studies. Five of the tumors occurred at the end of 2-year studies; none were attributed to treatment. None of the mice with epididymal tumors had a primary testicular tumor. Histologically, tumors were characterized by a nodular or diffuse proliferation of tumor cells in the epididymal interstitium. Most cells were polygonal with highly vacuolated cytoplasm (vacuolated cells) or eosinophilic cytoplasm (eosinophilic cells). Smaller hyperchromatic cells with scant basophilic cytoplasm (basophilic cells) and cells with yellow-brown pigment characteristic of lipofuscin (pigmented cells) were less common. In each tumor two or more cell types were present. Extension of these tumors through the capsule, invasion of the testis, or metastasis did not occur. By electron microscopy both eosinophilic and vacuolated cell types had a large round or oval nucleus with sparse heterochromatin, abundant mitochondria with tubulovesicular cristae, and frequent desmosome structures between cell membranes. Vacuolated cells contained numerous lipid droplets. Morphological features of the epididymal tumors are similar to those of the testicular interstitial (Leydig) cell tumor in mice and rats.     

Granular cell lesions in the distal female reproductive tract of aged Sprague-Dawley rats

During the review of a rat carcinogenicity study, a spectrum of granular cell lesions was recognized in the distal female reproductive tract. To verify the diagnoses, cell populations of nine granular cell alterations of the cervix or vagina were characterized immunohistochemically and four were evaluated ultrastructurally. Immunoreactivity was demonstrated in 8/9 cases with S100 protein, 6/9 cases with neuron-specific enolase, and 7/9 cases with Leu-7. Granular cells were negative for smooth muscle-specific actin and calretinin. The immunohistochemical profile of these lesions was similar to that previously reported in other species, including humans. Ultrastructurally, as expected many lysosomal bodies were present in the cytoplasm of granular cells in all specimens evaluated. Based on the detailed evaluation of a series of lesions, we adopted the following diagnostic criteria and nomenclature for the granular cell changes of the female reproductive tract of rats. Granular cell aggregates were non-space-occupying lesions composed of clusters of typical granular cells. Benign granular cell tumors were space occupying lesions that typically contained prominent interstitial collagen and were either discrete masses or were difficult to discern from the surrounding tissues. Some benign tumors also contained foci of spindle cells with decreased granularity. Malignant tumors exhibited pleomorphism and an increased nucleus: cytoplasm ratio morphologically but had the same biologic behavior as the benign tumors. We applied these diagnostic criteria during the review of controls from 9 carcinogenicity studies. Up to 23% of control females in those carcinogenicity studies had granular cell lesions that could be classified into one of the three categories. Granular cell lesions appear to be common in the cervix/vagina of the Sprague-Dawley rat, and tumors may develop from granular cell aggregates.     

Lymphocytic choriomeningitis in laboratory personnel exposed to hamsters inadvertently infected with LCM virus

Seven of 27 students and staff oa a university laboratory became ill with lymphocytic choriomeningitis (LCM) following exposure over an 18-month period to hamsters implanted with tumors. The clinical symptoms were compatible with LCM infection and all the patients' sera had fluorescent antibody to LCM virus; 5 of them also had complement-fixing (CF) antibodies. Complement-fixing antibodies were found in 9 of 9 hamsters with tumors and 16 of 31 without tumors (excluding 6 hamsters with anticomplementary sera) and in 8 of 14 rabbits, but in none of 49 rats. Lymphocytic choriomeningitis virus was isolated from 4 pools of liver and spleen, 2 each from hamsters with and without tumors, and from a frozen stored sample of the tumor cells. Interlaboratory transmission may have occurred via infected tumor cells. Control was achieved by destroying all animals in the project room as well as all hamsters in the building. The possibility that many tumor cell lines carried in hamsters may be infected with LCM virus has important implications for laboratory safety as well as for the validity of the research results obtained, inasmuch as the virus enhances the growth of some tumors and retards others.     

Spontaneous gastric squamous cell carcinomas and other neoplasms in Greenland collared lemmings (Dicrostonyx groenlandicus).

Malignant neoplasms were present in 39/66 Dicrostonyx groenlandicus of varying ages, examined from a laboratory colony. The presence of multiple neoplasms in some resulted in an overall average of 1.15 tumors/affected animal. Gastric squamous papillomas were present in nine, and locally invasive or metastatic gastric squamous cell carcinomas in a further 36 animals. Three mammary adenocarcinomas, one pancreatic islet cell tumor, one probable pancreatic adenocarcinoma and one adrenal cortical adenoma were also seen in lemmings with gastric tumors. Two others had mammary adenocarcinoma alone, and one animal had bilateral Harderian gland adenocarcinoma. Lesions resembling glomerulonephrosis of rats were seen in 23/51 animals whose kidneys were examined. These findings were not considered artefacts of captivity since concurrent gastric squamous cell carcinoma, mammary adenocarcinoma and glomerulonephrosis were present in the single animal examined directly from the wild at Eskimo Point, Northwest Territories.     

Ganglioneuromas of the thyroid gland in a colony of Sprague-Dawley rats.

Ganglioneuromas of the thyroid gland of Sprague-Dawley rats were found in 7.2% of 698 rats used in two, 2-year oncogenicity bioassays. The incidence of the tumor was unrelated to treatment or sex. Of the 52 ganglioneuromas of the thyroid gland identified in 50 animals, 40 (80%) had coincident C cell proliferations in the same or contralateral lobe. Ganglioneuromas were contiguous or commingled with C cell proliferations in 63.5% of the cases. The ganglioneuromas consisted of large ganglion cells and, in a few cases, cells thought to be less differentiated neuronal precursors, in a matrix of neurites and Schwann cells. They grew, infiltrating and expanding in the thyroid parenchyma, and did not metastasize. Immunohistochemical staining for calcitonin, S-100 protein, and neurofilaments, as well as electron microscopy, were used to further characterize the tumors. The close association of ganglioneuromas with C cell tumors supports the theory of neural crest origin of C cells and provides a parallel to the association of ganglioneuromas and pheochromocytomas in the adrenal medulla. This is the first report of ganglioneuromas occurring in the thyroid gland or occurring as a common entity in any species.     

Feline mammary sarcoma composed of cells resembling myofibroblasts

A recurrent mammary sarcoma from an 11-year-old, female domestic cat was studied by light and electron microscopy and immunohistochemistry. The tumor consisted of interlacing bands of spindle cells with elongated blunt-ended nuclei and variable amounts of stroma. Multinucleated tumor giant cells and mitoses were common. Ultrastructurally, tumor cells had abundant rough endoplasmic reticulum with dilated cisternae, a prominent Golgi complex, frequent mitochondria, bundles of intracytoplasmic filaments with focal densities, and discontinuous basal lamina-like material and cell junctions. These findings suggest that myofibroblast-like cells were the predominant type of tumor cell. Failure to demonstrate immunoreactivity for cytokeratins attested to the non-epithelial origin of these neoplastic cells. Uniform immunoreactivity with anti-vimentin antibodies and specific labelling of some tumor cells with antiserum to actin are compatible with an origin of this tumor from modified fibroblasts (i.e., myofibroblast-like cells). Tumors composed largely of myofibroblasts may be unique and warrant separate classification from other types of fibroblastic tumors in animals.     

Tumors and tumor-like lesions in the genitalia of sows

Of a total of 1445 sows, tumors were detected in the uterus of 11 animals and in the cervix/vagina of 1 animal. Tumor-like lesions were detected in the ovary of 56 animals. The incidence of tumors was higher than that mentioned in the literature, possibly because of the relatively high age of the sows (mean parity of 6.8) and the accuracy of investigation. Several tumors would not have been detected during routine slaughter examination. The uterine tumors were diagnosed as leiomyoma (6), fibroma (3), cyst-adenoma (1) and fibro-leiomyoma (1). The cervical/vaginal tumor appeared to be a fibroma. The ovarian lesions could not be satisfactorily classified. They consisted of connective tissue, blood vessels, and granulosa cells, which were present in variable quantities in different ovaries and in different sides of the same ovary. Sows with tumors were older than the mean determined age at slaughter (parity 6.8). Sows with uterine and cervical/vaginal tumors had a parity of 11.6; sows with ovarian lesions had a parity of 9.0. Sows with uterine- or a cervical/vaginal tumor were often slaughtered for infertility reasons.     

Chemotherapy and immunotherapy of bovine leukosis

To prevent the progression of the disease, we treated leukemic or preleukemic cows with (1) adriamycin (ADM) entrapped in liposomes conjugated with monoclonal antibody, c143, against tumor-associated antigens (TAA) of bovine leukemic cells and (2) an immunotherapy using an immunopotentiator consisting of the cell wall skeleton of Nocardia rubra (N-CWS). Five leukemic or preleukemic cows with TAA-positive peripheral blood lymphocytes (PBL) received four injections of ADM alone (0.4 mg/kg body weight) or c143-conjugated liposomes containing the same dose of ADM (L-ADM-c143) through the jugular vein at about 4-day intervals. In three animals treated with L-ADM-c143, the TAA-positive cells gradually decreased with treatment and finally two animals became TAA-negative during a 6-week period and a 14-week period after treatment, respectively. About 6 weeks later, however, TAA-positive cells gradually increased. In the control, two animals treated with ADM alone showed no decrease of TAA-positive cells. Five TAA-positive animals with enlarged subcutaneous lymphatic nodules, each nodule estimated to be from 1 to 4 cm3 in size, were treated by injection of N-CWS into the tumors. Complete regression of tumor was observed in seven out of ten tumors treated in five animals. Decrease of TAA-positive cells was also observed in PBL for all five treated animals. In one animal, the TAA-positive cells remained low for at least 280 days after treatment. This study documents that ADM treatment and intralesionally administered N-CWS are effective in the treatment of bovine leukosis.     

Extratesticular interstitial and Sertoli cell tumors in previously neutered dogs and cats: a report of 17 cases

Primary neoplasms derived from testicular tissue and in an extratesticular location are extremely rare. Clinical and surgical information was collected and verified from 15 different submitting practices for 12 dogs and 5 cats that spontaneously developed neoplasms of testicular origin after castration. Eleven dogs had Sertoli cell tumors in an extratesticular location. One dog and all 5 cats had an extratesticular interstitial cell tumor. Six animals (1 dog, 5 cats) had developed secondary sexual characteristics that reversed after removal of the tumor. All had a palpable mass in the scrotum or at the site of the original prescrotal incision. No animals died of neoplasia-related disease and no metastases were identified. Several possibilities, including the presence of embryological ectopic tissue or the presence of testicular tissue transplanted during castration, are considered as causal.     

Congenital and acquired melanocytomas (benign melanomas) in eighteen young horses.

In a retrospective study, cutaneous melanocytic tumors from 18 horses, less than 2 years old, were examined histopathologically and clinical follow-up requested. Melanocytomas (benign melanomas) occurred in a variety of breeds and in horses of varied coat color. The age of the horses at the time of biopsy ranged from 3 weeks old to 2 years old. Four melanocytomas were congenital, 11 melanocytomas were acquired by 1 year of age, and three were acquired prior to 2 years of age. Of the 18 horses, five were male, and 13 were female. All tumors were solitary and located on the legs or trunk; none were in the perineal region. Ulceration of the overlying epidermis was common. Tumors were generally localized and were not encapsulated. The tumors had a variety of cell patterns ranging from sheets, to streams, or nests of melanocytes. Cellular morphologic findings also ranged from epithelioid, to a mixture of epithelioid and spindle cells or to a spindle pattern. The nuclei were large and euchromatic, especially in the epithelioid cells. Several tumors had moderate cellular pleomorphism and binucleate cells. Mitotic activity was generally low (less than 1/high-powered field), but was readily detected (1-2/high-powered field) in bleached sections of four cases. Melanin pigmentation varied from mild to heavy. Melanophages were admixed with the tumor cells or in the adjacent tissue. Follow-up information was obtained on 15/18 horses and revealed that 14/15 horses were free of recurrence following excision. One neoplasm, that was poorly demarcated and had a spindle cell pattern, was not completely resected and continued to grow. These melanocytic tumors in young horses are distinct from melanomas in aged horses in their location, epithelial involvement, and age of horses affected. The majority of these tumors appear to be benign and share features of melanocytic nevi of human beings.     

Lipid-rich carcinomas of the mammary gland in seven dogs: clinicopathologic and immunohistochemical features

Lipid-rich carcinomas occurred in seven female dogs. Affected dogs were purebred (all but one), intact (all but one), and between 4 and 13 years of age. Five of them had a history of parity, one had pseudopregnancy, and none had received contraceptive steroids. The tumors were single (five cases) or multiple (two cases) well-circumscribed masses of different sizes (varying from 1 to 6 cm in diameter), composed of solid nests and cords of tumor cells separated by a moderate amount of stroma. The tumor cells contained either multiple and small or large and solitary vacuoles that pushed the nucleus to the periphery of the cell (signet-ring cell). A glandular epithelial immunophenotype (cytokeratins 5 and 8 and 8 and 18) was observed in the majority of tumor cells. All tumors lacked both estrogen and progesterone receptors, and five out of seven tumors gave rise to local recurrence and proximal or distant metastases or both.     

Primary cardiac granular cell tumor in a dog

The histological, histochemical, and ultrastructural features of a granular cell tumor in the wall of the right atrium of the heart in a nine-year-old dog are described. The histologic appearance of the mass varied from areas of spindle-shaped cells to sheets of globoid cells with foamy granular cytoplasm. The globoid neoplastic cells contained numerous cytoplasmic granules which were variably positive to periodic acid-Schiff staining, with and without disastase digestion. Ultrastructurally, the globoid cells had numerous various-sized, heterogeneous lysosomes with pleomorphic content. A granular cell tumor originating in the heart has not been reported previously in animals. The support for a neural origin of these tumors by the recent identification of several nervous tissue specific proteins in their granular cells is discussed.     

Renal tubular-cell neoplasms in black-footed ferrets (Mustela nigripes)--38 cases

Thirty-eight cases of renal tubular cell neoplasms were diagnosed in 184 captive, adult (>1-year-old), black-footed ferrets (Mustela nigripes) examined from 1985 to 1996. This prevalence (20.7%) is one of the highest reported for this neoplasm in a population of animals. These tumors rarely metastasized (1/38), and usually were incidental postmortem findings, associated clinical disease being present in only 3 (8%) of the 38 cases. The prevalence of renal tubular cell neoplasms found at postmortem examination increased linearly with age, up to 67% in ferrets >8 years old. Both males (prevalence = 19%) and females (prevalence = 24%) were affected. Multiple renal tumors were common, and seven ferrets (18.4% of affected animals) had bilateral tumors. The cause of this neoplastic syndrome could not be determined. Since most of the animals affected by this condition were in their postreproductive years of life, the impact of this neoplastic syndrome on the captive propagation of this species is negligible.     

Characterization of uterine granular cell tumors in B6C3F1 mice: a histomorphologic, immunohistochemical, and ultrastructural study

The granular cell tumor is most often a benign neoplasm of uncertain origin. Four uterine granular cell tumors in control and treated female B6C3F1 mice were identified in chronic studies at the National Toxicology Program. Two tumors occurred in untreated control animals and 2 in treated animals receiving different compounds. Tissue sections were evaluated histologically and stained with hematoxylin and eosin, periodic acid-Schiff with diastase resistance, Masson's trichrome, toluidine blue, phosphotungstic acid-hematoxylin, and stained immunohistochemically with a panel of antibodies to muscle (desmin, alpha smooth muscle actin), neural (S-100, neuron specific enolase), epithelial (wide-spectrum cytokeratin), and macrophage (F4/80) markers. The main histomorphologic feature of tumor cells was the presence of abundant cytoplasmic eosinophilic granules that stained positive for periodic acid-Schiff with diastase resistance. Tumors varied in appearance and were comprised of sheets and nests of round to polygonal cells with distinct borders. Nuclei were hyperchromatic, pleomorphic, and centrally to eccentrically located and often contained single nucleoli. Occasional multinucleated giant cells were observed. Tumors were pale pink and homogeneous with trichrome stain and negative with toluidine blue. Three tumors had positive to weakly positive immunoreactivity for desmin, and 1 was positive for alpha smooth muscle actin. Expression of S-100, wide-spectrum cytokeratin, and neuron-specific enolase was negative for all tumors. Ultrastructurally, prominent electron-dense cytoplasmic granules were abundant and contained secondary lysosomes with heterogeneous lysosomal contents. The characteristics of these uterine granular cell tumors were suggestive of a myogenic origin.     

Epithelioid variant of hemangioma and hemangiosarcoma in the dog, horse, and cow

Epithelioid hemangiomas, hemangioendotheliomas, and angiosarcomas are well recognized histologic variants of endothelial tumors in humans that in the past have been confused with neoplasms of epithelial or histiocytic origin. We describe 12 epithelioid endothelial vascular tumors in 8 dogs, 3 horses, and 1 cow that share microscopic features with these tumors in humans. Ten tumors were located within the dermis and subcutis, 1 in the gastrocnemius tendon, and 1 in the skeletal muscle of the thigh. Key histologic features were the plump, epithelioid appearance of neoplastic endothelial cells and occasional cytoplasmic vacuolation, which rarely contained a single erythrocyte. Patterns of epithelioid endothelial cell growth ranged from conventional vasoformative structures to glandlike acini and short ducts to solid, sheetlike arrangements. All tumors were positive for endothelial markers: 12/12 (100%) were positive for von Willebrand factor with variable intensity and distribution and 9/9 (100%) were positive for CD31. All 12 were negative for cytokeratin. We subdivided these tumors into epithelioid hemangiomas (n = 3) and hemangiosarcomas (n = 9) based on conventional morphologic criteria, growth pattern (invasive or not), and metastasis (known in 1 case at the time of biopsy). Additional follow-up information obtained by a written questionnaire was available for 6/12 (50%) animals and revealed local recurrence in 3 animals (1 epithelioid hemangioma and 2 epithelioid hemangiosarcoma) and regional metastasis in 3 animals (all epithelioid hemangiosarcomas). This series represents a novel group of vascular tumors in domestic animals of which there are only 3 previous cases reported in the veterinary literature.     

Four bovine meningeal tumors

Four bovine meningeal tumors from a total of 14 brain tumors were recorded in the files of the Ontario Veterinary College and the Ontario Veterinary Laboratory Services Branch from the years 1966 to 1984. The affected cattle ranged in age from 10 months to adult. They exhibited various nervous signs and, in each case, the animals became recumbent. Tumors were located in various areas of the central nervous system. Neoplastic cells had oval vesicular nuclei containing numerous cytoplasmic invaginations. Virus particles were not observed. A fibroblastic appearance, with the presence of loose whorls or bundles, was present in all. Three of the tumors were invasive and were classified as a fibroblastic meningioma.     

Mast cell tumors of the gastrointestinal tract in 39 dogs

Mast cell tumors (MCTs) of gastrointestinal origin that had been surgically removed from 39 dogs were examined to evaluate their pathologic features. Miniature breeds, especially Maltese, were most frequently affected. The average age of affected dogs was 9.7 +/- 2.6 years. No sex difference was apparent. The most frequently affected sites were in the upper digestive tract, and the prognosis was very poor. Grossly, the gastrointestinal wall was prominently thickened, and the lumen of the affected gut was usually narrowed. Microscopically, there was diffuse transmural invasion of round to pleomorphic tumor cells. Tumor cells had moderate to abundant cytoplasm, round to ovoid nuclei with scattered chromatin, and mitotic figures. Fibrous stroma was observed in about half of the tumors. There was variable infiltration of eosinophils. In all tumors, cytoplasmic granules showed weak metachromasia, but the number of granules was very small. Immunohistochemical staining for c-kit and mast cell tryptase was positive in 77% and 62% of tumors, respectively. All tumors were positive for at least two of these markers. Immunohistochemical staining for p53 was positive in 13% of the tumors. Reactivity for staining markers and p53 was unrelated to cell pleomorphism, vessel invasion, or survival time. Gastrointestinal MCTs have histologic and immunohistochemical features completely different from those of other primary or metastatic gastrointestinal tumors. The combination of immunostaining for mast cell tryptase and c-kit and histochemical staining for metachromasia appears to be a powerful tool for the diagnosis of gastrointestinal MCTs.