Neoplasia of captive yellow sea horses (Hippocampus kuda) and weedy sea dragons (Phyllopteryx taeniolatus)

Syngnathidae is the family of fish that includes sea horses, pipefish, and sea dragons. To date, only a single publication has described neoplasia in syngnathids, a fibrosarcoma of the brood pouch in an aquarium-reared lined sea horse (Hippocampus erectus). From 1998 until 2010, the Toronto Zoo submitted 172 syngnathids for postmortem; species included the spotted or yellow sea horse (Hippocampus kuda), the pot-bellied sea horse (Hippocampus abdominalis) and the weedy sea dragon (Phyllopteryx taeniolatus). Seven neoplasms and two neoplastic-like lesions were identified from these cases. Under light microscopy, the neoplasms had morphological characteristics of a cardiac rhabdomyosarcoma, renal adenocarcinoma, renal adenoma, renal round cell tumors, which were likely lymphomas, exocrine pancreatic carcinoma, and intestinal carcinoma. Of these neoplasms, four had clear evidence of metastasis: the pancreatic and intestinal carcinomas and both round cell tumors. As syngnathids are highly fastidious animals, they can be difficult to maintain in captivity. In order to improve their husbandry, preventative and palliative care, as well as treatment, it is important to investigate and document the types of diseases affecting syngnathids.     

Morphologic changes in the mammary gland of megestrol acetate-treated and untreated cats: a retrospective study

Abnormal mammary gland growth is a side effect of progestin therapy in some cats. In this retrospective study, the nature and significance of morphologic changes in the mammary gland of 17 megestrol acetate (MA)-treated cats were compared to mammary lesions in 97 untreated cats. Fourteen out of 17 MA-treated cats had non-neoplastic mammary lesions including fibroepithelial hyperplasia (nine cats), lobular hyperplasia (three cats), and duct ectasia (two cats); whereas three MA-treated cats had mammary neoplasms including one adenoma and two carcinomas. Although MA has been causally linked to mammary cancer in cats, only mammary fibroepithelial hyperplasia was clearly associated with MA therapy in this study. Fibroepithelial hyperplasia occurred in older (average age 8.1 years) neutered male and female cats in the MA-treated group and in younger (average age 2.1 years) female cats in the untreated group. Morphologically, both intraductal and solid fibroepithelial growth patterns were seen. Intraductal fibroepithelial hyperplasia was further subdivided into papillary and circumferential types. An apparent greater association between MA therapy and the intraductal types of fibroepithelial hyperplasia was noted. Furthermore, it appears likely that mammary lobular hyperplasia also is linked to MA therapy. Possible mammatrophic effects of MA and other growth-promoting agents in the cat are discussed.     

CT characteristics of primary hepatic mass lesions in dogs

Little information is available on the relationship between computed tomography (CT) imaging findings and the pathologic diagnosis of canine hepatic tumors. Our purpose was to clarify the characteristic features of CT findings in liver tumors in dogs. Data from 33 dogs with either a hepatocellular carcinoma, n = 14, hepatocellular adenoma, n = 14, or nodular hyperplasia, n = 5 were summarized from medical records. CT features for each histologic diagnosis were characterized and analyzed statistically. Common findings in hepatocellular carcinoma included central (79%, P = 0.0030) and marginal enhancement (93%, P = 0.00043) in the arterial phase, cyst-like lesions (93%), capsule formation (93%), and hypoattenuation in the portal (86%), and equilibrium phases (93%). Hepatic adenoma was characterized by a characteristic diffuse enhancement pattern during the arterial phase (57%, P = 0.013), which was also found in nodular hyperplasia (60%), but never in hepatocellular carcinoma. Nodular hyperplasia was less likely to have a capsule structure (20%, P = 0.0087). Mass size was significantly smaller in nodular hyperplasia than in hepatocellular carcinoma and hepatic adenoma (P = 0.0033 and 0.038, respectively). Hyperattenuation in the arterial and the portal phase i.e. contrast retention, was more frequent in hepatic adenoma than in the other groups (P = 0.037 and 0.037, respectively). Nodular hyperplasia was more frequently isoattenuating in the equilibrium phase (P = 0.043).     

Histological and immunohistochemical identification of atypical ductal mammary hyperplasia as a preneoplastic marker in dogs

This study describes and evaluates the morphological and molecular relationship between canine mammary ductal hyperplasias with atypia and canine mammary neoplasias. Ductal hyperplasia was identified in association with malignant neoplasia in 56 of the 115 cases (48,8%), and although ductal hyperplasia without atypia was the type most frequently noted in the cases, most examples of hyperplasia with atypia were associated with mammary tumors. Estrogen receptor, E-cadherin, and cytokeratins 1, 5, 10 and 14 (CK34bE12) expression was quite lower than in normal mammary tissue, and HER2 overexpression was absent in all proliferative cells of ductal hyperplasia. The Ki-67 expression, epidermal growth factor receptor and progesterone receptor expression appeared higher in those hyperplastic lesions analyzed than in normal mammary glands. These findings suggest that canine mammary atypical hyperplasia may play an important role in the process of malignant neoplastic transformation, with molecular alterations that are similar to precursor lesions reported in humans.     

A Case of Metastatic Adrenocortical Carcinoma Diagnosed with Steroidogenic Factor-1 in a Sprague-Dawley Rat

This report describes the morphological and immunohistochemical characteristics of an adrenocortical carcinoma with distant metastasis in a Sprague-Dawley rat. Macroscopically, a single large mass was observed in the adrenal gland, and multiple nodules were noted in the lung, liver and thyroid. Histologically, the adrenal tumor consisted of a solid growth of eosinophilic round cells with nuclear atypia. Vascular invasion was present, and multiple metastatic lesions were also observed in the lungs, liver, and mediastinal lymph nodes. Immunohistochemically, the nuclei of these tumor cells were positive for Steroidogenic Factor-1 (SF-1). In the thyroid, tumor cells histologically resembling adrenal cells were immunohistochemically negative for SF-1 but positive for calcitonin; thus the lesion was diagnosed as thyroid C-cell carcinoma. From these results, the present case was diagnosed as adrenocortical carcinoma with distant metastases. SF-1 could be a valuable marker for the differential diagnosis of adrenocortical tumors versus other endocrine tumors such as C-cell carcinoma.     

HIGH-RESOLUTION PARATHYROID SONOGRAPHY

The purpose of this study was to assess the diagnostic utility of parathyroid ultrasonography to differentiate causes of hypercalcemia in dogs. We analyzed qualitative and quantitative ultrasound imaging findings and clinical pathology data from 33 dogs that underwent parathyroid ultrasound examination as part of the diagnostic evaluation for hypercalcemia. Diagnoses of the diseases causing hypercalcemia included parathyroid carcinoma (n = S), parathyroid adenoma (n = 15), parathyroid adenomatous hyperplasia (n = 6), chronic renal insufficiency (n = 3), and hypercalcemia of malignancy (n = 4). All parathyroid lesions were round or oval and hypoechoic compared with surrounding thyroid parenchyma. Adenomatous and adenocarcinomatous glands were 4 mm or larger in longest linear measurement on US examination and were statistically significantly larger than hyperplastic glands. (p < 0.001) Linear measurements of parathyroid glands acquired at the time of ultrasound examination correlated well with direct siz determination after surgical excision. (r²= 0.9, p < 0.0001) Parathyroid lesions <4 mm are highly suspicious for parathyroid adenoma or carcinoma, while US lesions <4 mm most likely represent primary adenomatous hyperplasia or secondary parathyroid hyperplasia. Parathyroid size estimation from ultrasound examination is an accurate predictor of true size.     

Familial protein-losing enteropathy and protein-losing nephropathy in Soft Coated Wheaten Terriers: 222 cases (1983-1997)

Records and pedigrees of Soft Coated Wheaten Terriers (SCWT) with protein-losing enteropathy (PLE) or protein-losing nephropathy (PLN) were studied retrospectively. Criteria for inclusion were defined based on analysis of blood (panhypoproteinemia for PLE, hypoalbuminemia for PLN) and urine (proteinuria for PLN) and histopathologic examination of tissue. Two hundred twenty-two affected dogs (female:male ratio = 1.6, P < .001) were clinically identified. Dogs were diagnosed with PLE earlier (P < .005; mean +/- SD age: 4.7+/-2.6 years, n = 76) than with PLN (6.3+/-2.0 years, n = 84) or with both diseases (5.9+/-2.2 years, n = 62). Clinical signs included vomiting, diarrhea, weight loss, pleural and peritoneal effusions, and less commonly thromboembolic disease. Dogs with PLE generally had panhypoproteinemia and hypocholesterolemia; intestinal lesions included inflammatory bowel disease, dilated lymphatics, and lipogranulomatous lymphangitis. Dogs with PLN generally had hypoalbuminemia, proteinuria, hypercholesterolemia, and azotemia; renal lesions typically showed chronic glomerulonephritis/glomerulosclerosis, and less commonly endstage renal disease. Dogs with combined PLE/PLN had intermediate mean values (P < .001) for serum total protein, albumin, globulin, and cholesterol but had a higher mean urine protein:creatinine ratio than did PLN dogs (P < .05); intestinal and renal lesions in these dogs were similar to those in the other groups. Two dogs had incidental mild renal dysplasia. Pedigree analysis from 188 dogs demonstrated a common male ancestor, although the mode of inheritance is unknown. Both PLE and PLN are common diseases in this small breed population. The prognosis is poor. Compared with previously reported intestinal and renal diseases in dogs, a new, distinctive familial predisposition for both PLE and PLN has been recognized in the SCWT breed.     

Strain differences in morphometrical characteristics of rat kidneys

To clarify the strain differences in the morphology of the rat kidneys, we investigated the morphometrical characteristics of the kidneys of Slc:Wistar, Slc:SD, and F344/NSlc rats. The diameter of the renal corpuscles in female F344/N rats is smaller than that in female Wistar rats. Although sex differences (males>females) were shown in SD and F344/N rats, no effects of castration were detected in any of the groups. Strain-dependent differences in the percentage of renal corpuscles with a cuboidal parietal layer were found in both male and female groups. The highest percentage of them was noted in male Wistar rats. Effects of castration were observed in female Wistar and male F344/N rats, and the values after castration were significantly higher than those in the intact animals. As for the number of proximal convoluted tubular nuclei, no strain differences were detected in either the male or female groups. Although a sex difference was found in SD rats (female>male), no effects of castration were detected in any of the groups. In female F344/N rats, numerous numbers of PAS-positive granules, which were observed in the proximal convoluted and straight tubular epithelia, were noted. Orchiectomy induced an increase of these granules in male SD and F344/N rats, but ovariectomy showed no effects on them in any strains. This is the first study to clarify the strain differences in the morphological characteristics of the kidneys in ordinary rat strains.     

Confounders for kidney carcinogenesis in rodent cancer bioassays

In the long-term safety testing of chemicals for carcinogenicity the toxicologist needs to be aware of a number of scenarios where renal tubule tumors, or their precursors, arise that are not due to a carcinogenic action of the test article. Situations producing false positive results in the kidney include exacerbation of chronic progressive nephropathy (CPN) in rats, confusion of atypical tubule hyperplasia (the obligate precursor of renal tubule tumor) with foci of benign CPN-related renal tubule cell proliferation, inclusion of spontaneous tumor entities, such as the amphophilic-vacuolar tumor, in the test article tumor count, the possibility of a link between spontaneous forms of tubule dilatation and renal tubule tumor formation in mice, and the supposed predictivity of chemically-induced karyomegaly for renal carcinogenicity in both rats and mice. Examples of these misleading situations are described and discussed.     

Carcinogenicity and chronic toxicity in mice and rats exposed by inhalation to para-dichlorobenzene for two years

Carcinogenicity and chronic toxicity of para-dichlorobenzene (p-DCB) were examined by exposing 50 BDF1 mice and 50 F344 rats of both sexes by inhalation to p-DCB vapor at a target concentration of 0 (control), 20, 75 or 300 ppm for 6 hr/day, 5 days/week and 2 years. Incidences of hepatocellular carcinomas, hepatoblastomas and hepatic histiocytic sarcomas in the 300 ppm-exposed male mice, and hepatocellular adenomas and carcinomas and hepatoblastomas in the 300 ppm-exposed female mice were increased. An increase in the incidences of most of those liver tumors was dose-related. No increase in tumor incidence was found in any p-DCB-exposed rat of either sex. Centrilobular hypertrophy of hepatocytes and papillary mineralization and pelvic urothelial hyperplasia of the kidney were noted in the 300 ppm-exposed male rats. Treatment- and age-related increases in incidences of the eosinophilic globules of the respiratory and olfactory epithelia in female rats and incidences of the respiratory metaplasia of the nasal gland epithelium in mice and rats and the olfactory epithelium in mice were noted. The nasal lesion was the most sensitive endpoint of chronic inhalation toxicity. Induction of the mouse hepatocarcinogenicity and lack of the rat nephrocarcinogenicity found in the present study were compared with the mouse liver tumors and the rat renal tumors reported by the NTP gavage study, and discussed in light of the estimated p-DCB uptake into the body through the inhalation and the oral administration.     

Follow-up studies by large intestinal biopsies and necropsy in dogs with clinical signs of large bowel disease.

The results of follow-up studies in 77 dogs with clinical signs of large bowel disease are presented. In 32 dogs colonic and/or rectal biopsy follow-up studies were done, combined with necropsy in seven dogs. In 45 dogs a follow-up necropsy only was done. The time between the first and the last series of biopsies varied from three to 729 days and between the first series of biopsies and necropsy from one to 980 days. Colitis found in 45 dogs in the initial biopsies was still present in 29 cases in the follow-up biopsy studies and/or at necropsy. Eleven cases showed hystiocytic ulcerative colitis. In general, adenoma, carcinoma and lymphosarcoma were confirmed in the follow-up examination, except for one adenoma, which appeared to be a carcinoma at necropsy. In cases in which the differential diagnosis was adenoma or carcinoma, the necropsy diagnosis was always carcinoma and in cases of a differential diagnosis of lymphosarcoma and/or colitis, lymphosarcoma was always diagnosed at necropsy. Several dogs without colonic changes in the initial biopsies had other gastric or small intestinal lesions at necropsy such as gastritis and enteritis of the small intestine, or tumors, in these areas.     

RETROSPECTIVE REVIEW OF THE ULTRASONOGRAPHIC FEATURES OF ADRENAL LESIONS IN 21 FERRETS

Clinical signs and follow-up information were recorded. Histopathologic diagnoses were obtained for 25 adrenal glands in 21 ferrets. Adrenal lesions included ten adenocarcinomas, nine adenomas, one hyperplasia and one cortical cyst. Four adrenal glands (all right-sided) were diagnosed as unspecified adrenal tumors but lacked a definite histopathologic diagnosis (adenoma vs. adenocarcinoma) due to incomplete surgical resection and consequent small sample sizes. Bilateral adrenal lesions were identified in 4 ferrets (19%). Adrenal shape, size, echogenicity, laterality, and the presence of vascular invasion were evaluated with ultrasound. Size and shape were variable and not specific to lesion type. Both benign and malignant adrenal tumors (adenomas, adenocarcinomas) appeared most often as masses with increased thickness and a normal length (11/23), less frequently as larger masses with increased thickness and length (4/23) or as nodules focally deforming the normal adrenal shape (6/23). The only cortical cyst appeared as a nodule. Three adrenal glands had a normal size and shape and were diagnosed as adenomas (2) or hyperplasia (1). Therefore treatment may be warranted based solely on clinical signs if adrenal glands are ultrasonographically normal. Vascular invasion was not identified ultrasonographically. However, focal absence of periglandular fat resulting in contact of 8 adrenal glands with either caudal vena cava (6), aorta (1) or liver (1) identified ultrasonographically, correlated with incomplete surgical resectability (6/8) and histopathologic diagnoses of carcinoma (4/8) or unspecified tumors (4/8). Therefore, a focal absence of periglandular fat between the adrenal gland and the large vessels or liver, deviation or compression of the large vessels by the adrenal lesion may indicate malignancy. Adrenal tumors (benign and malignant) were often associated with a prominent uterus, uterine stump or prostate with or without prostatic cysts.     

Gastroduodenal adenocarcinomas and rectal adenoma in a cougar (Felis concolor) infected with Helicobacter-like organisms and spirochetes

A 14-year-old female cougar died from gastroduodenal adenocarcinomas and rectal adenoma. At necropsy, polypoid tumor masses of various sizes were scattered on the mucosal surfaces of the stomach, duodenum, and rectum. Histologically, the gastric tumor was diagnosed as an intestinal type adenocarcinoma and the tumor cells metastasized to the mesenteric lymph nodes, spleen, and lung. Helicobacter-like organisms were detected in the lumina lined by foveolar epithelium. In the duodenum, the carcinoma cells were localized in the limina propria and many of them were intensely positive for proliferating cell nuclear antigen (PCNA). In contrast, the rectal adenoma had a lower number of PCNA-positive cells. In the rectum, chronic inflammation with numerous spirochetes was also noted. These results indicated that the occurrence of the gastrointestinal tumors might be associated with the bacterial infection described above.     

Hyperparathyroid disorders in the dog: primary, secondary and cancer-associated (pseudo)

Hyperparathyroid disorders were diagnosed in four dogs: one had primary hyperparathyroidism, characterized by parathyroid adenoma and hyper-calcaemia; one had renal secondary hyperparathyroidism, characterized by parathyroid gland hyperplasia, hypocalcaemia and renal failure; and two had cancer-associated hyperparathyroidism (pseudohyperpara-thyroidism), characterized by the presence of neoplasia, parathyroid gland atrophy, hypercalcaemia and absence of skeletal metastases. Significant clinicopathologic findings included serum concentrations of calcium, phosphorus and immunoreactive parathyroid hormone (PTH), presence or absence of parathyroid and bone lesions, and the presence of non-parathyroid neoplasia.     

Concurrent pituitary and adrenal tumors in dogs with hyperadrenocorticism: 17 cases (1978-1995).

OBJECTIVE: To describe the clinicopathologic characteristics of dogs with hyperadrenocorticism and concurrent pituitary and adrenal tumors. DESIGN: Retrospective study. ANIMALS: 17 client-owned dogs. PROCEDURE: Signalment, response to treatment, and results of CBC, serum biochemical analysis, urinalysis, endocrine testing, and histologic examinations were obtained from medical records of dogs with hyperadrenocorticism and concurrent adrenal and chromophobe pituitary tumors. RESULTS: On the basis of results of adrenal function tests and histologic examination of tissue specimens collected during surgery and necropsy, concurrent pituitary and adrenal tumors were identified in 17 of approximately 1,500 dogs with hyperadrenocorticism. Twelve were neutered females, 5 were males (3 sexually intact, 2 neutered); and median age was 12 years (range, 7 to 16 years). Hyperadrenocorticism had been diagnosed by use of low-dose dexamethasone suppression tests and ACTH stimulation tests. During high-dose dexamethasone suppression testing of 16 dogs, serum cortisol concentrations remained high in 11 dogs but decreased in 5 dogs. Plasma concentrations of endogenous ACTH were either high or within the higher limits of the reference range (12/16 dogs), within the lower limits of the reference range (2/16), or low (2/16). Adrenal lesions identified by histologic examination included unilateral cortical adenoma with contralateral hyperplasia (10/17), bilateral cortical adenomas (4/17), and unilateral carcinoma with contralateral hyperplasia (3/17). Pituitary lesions included a chromophobe microadenoma (12/17), macroadenoma (4/17), and carcinoma (1/17). CLINICAL IMPLICATIONS: Pituitary and adrenal tumors can coexist in dogs with hyperadrenocorticism, resulting in a confusing mixture of test results that may complicate diagnosis and treatment of hyperadrenocorticism.     

Natural occurrence of neoplastic lesions in young sprague-dawley rats

It is important for the assessment of toxicological effects of chemicals to know what kinds of neoplasms naturally occur in the early life of experimental animals. In the present study, we demonstrated spontaneous neoplasms in Sprague-Dawley rats used in 4-, 13- and 26-week toxicity studies conducted at Bozo Research Center in the last decade. The tumors, which were first observed in 19-week-old animals, included anterior adenoma of the pituitary, follicular cell adenocarcinoma and C cell adenoma of the thyroids, nephroblastoma of the kidneys, basal cell tumor of the skin and malignant lymphoma. Thereafter, hemangiosarcoma of the tongue, adenocarcinoma of the submandibular glands, histiocytic sarcoma of the spleen, oligodendroglioma of the brain and adenocarcinoma and fibroadenoma of the mammary glands were detected in 32-week-old animals. The incidences of mammary adenocarcinoma and pituitary anterior adenoma were higher than those of other tumors. The present results showed that the same tumors as reported in aged rats could also develop in younger rats.     

Falcon adenovirus infection in breeding Taita falcons (Falco fasciinucha).

Four female and 3 male Taita falcons (Falco fasciinucha) out of a breeding colony of 14 Taita falcons (7 pairs) died during the breeding season after showing lethargy and anorexia for 1 to 2 days. All animals were submitted for necropsy. Gross lesions in the female falcons were characterized by anemia secondary to marked hemorrhage into the ovary and oviduct, serofibrinous effusion into the cardioabdominal cavity and serosal petechiae. In addition, marked necrotizing splenitis and pulmonary hemorrhage were present. Histologically, the female falcons had mild necrotizing hepatitis with numerous intranuclear inclusion bodies and necrotizing splenitis with rare inclusion bodies. There were no gross lesions in the male falcons, and the histological lesions were characterized by urate deposition and rare intranuclear inclusion bodies in the renal tubular epithelial cells. Adenoviral particles were found by electron microscopy in the cloacal contents of the female Taita falcons but not in the male falcons. DNA in situ hybridization revealed widespread aviadenoviral nucleic acid within the nuclei of hepatocytes, renal tubular epithelial cells, and adrenal cells in the female falcons but no aviadenoviral nucleic acid in 1 male falcon and only a low quantity of adenoviral nucleic acid in the liver and kidney of another male Taita falcon. PCR amplified aviadenoviral DNA in the liver and intestine of all Taita falcons. The amplicons were sequenced, and the virus was identified as falcon adenovirus. The deaths of the female and male birds were attributed to the aviadenovirus infection.     

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.     

24例20种犬肿瘤的病理组织学观察

对犬的皮脂腺瘤、肛周腺腺瘤、肛周腺癌、毛基质瘤、间叶性软骨肉瘤、腺样型基底细胞上皮瘤、囊样型基底细胞上皮瘤、水母样型基底细胞上皮瘤、混合型基底细胞上皮瘤、基底鳞状细胞上皮瘤、甲状腺腺瘤、肥大细胞瘤、组织细胞瘤、乳腺良性混合瘤(软骨腺瘤)、乳腺良性混合瘤(肌上皮腺瘤)、恶性肌上皮细胞瘤、乳腺恶性混合瘤(癌肉瘤)、汗腺囊性增生、汗腺腺瘤、汗腺癌等20种24例肿瘤(良性肿瘤14种,恶性肿瘤6种)作了详细的病理组织学描述。