Cohort study of COX-1 and COX-2 expression in canine rectal and bladder tumours

OBJECTIVES: To determine the role that cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) play in malignant transformation in canine transitional cell carcinoma and rectal tumours. METHODS: Histological sections of 21 canine rectal adenocarcinomas and 18 canine transitional cell carcinomas were stained for COX-1 and COX-2. Mann-Whitney non-parametric tests were applied to determine if there was any relationship between the percentage of cells expressing COX-1 or COX-2, and between COX-1 and COX-2 staining intensity and age, breed or sex. RESULTS: For rectal adenocarcinomas, 19.0 per cent of the sections were negative for COX-1 and COX-2. A further 38.1 per cent of the sections were negative for COX-2 but positive for COX-1, and 38.1 per cent of the sections had rare or occasional single cells positive for COX-2. No significant differences were found in COX staining when compared with age, breed or sex. For transitional cell carcinomas, all of the sections were positive for COX-1 and COX-2. For COX-2 staining, 16.7 per cent had more than 30 per cent positive cells. For COX-1 staining, 38.9 per cent had more than 30 per cent positive cells. There was a significant increase in the percentage of COX-1 positive cells in small breed dogs (P = 0.0337). CLINICAL SIGNIFICANCE: The variations in COX expression reported in this study may explain the differences in the clinical response of transitional cell carcinomas and rectal adenocarcinomas following treatment with non-steroidal anti-inflammatory drugs.     

An immunohistochemical study of cyclooxygenase-2 expression in various feline neoplasms

Cyclooxygenase (COX) enzymes catalyze the synthesis of prostaglandins and exist as two isoforms, COX-1 and COX-2. COX-2 is a potent inducible mediator of inflammation. COX-2 is also upregulated in several human tumors and in canine squamous cell, renal cell, and transitional cell carcinomas, prostatic adenocarcinoma, and intestinal neoplasia. The purpose of this study was to determine whether COX-2 is expressed in various feline tumors. Results of this study may help determine whether COX-2 is a potential target for therapeutic and preventive strategies in cats. Immunohistochemical studies were performed on paraffin-embedded tissues using the amplified streptavidin-biotin-horseradish peroxidase system. COX-2 was found in 7 of 19 (37%) feline transitional cell carcinomas and in 2 of 21 (9%) feline oral squamous cell carcinomas. No COX-2 immunoreactivity was detected in cutaneous squamous cell carcinomas (6), adenocarcinomas (nine mammary, eight pulmonary, seven intestinal), lymphomas (six nasal, six intestinal), or 10 vaccine-associated sarcomas. The widespread absence of COX-2 expression in most feline neoplasms might suggest that COX-2 inhibitors would have a low potential as anticancer agents.     

RADIOGRAPHIC APPEARANCE OF PRIMARY LUNG TUMORS IN CATS

The radiographic findings in 41 feline primary lung tumors are reported. Case material includes 29 adenocarcinomas, six bronchiolog-alveolar carcinomas, and six squamous cell carcinomas. Adenocarcinomas tended to occur as focal, solitary, well-circumscribed masses (eight cats), as localized consolidations (six cats), or as multiple, poorly circumscribed masses (five cats). Bronchiolo-alveolar cell carcinomas and squamous cell carcinomas were radiographically pleomorphic. Calcification was recognized in only five cats, four with adenocarcinomas and one with bronchiolo-alveolar carcinoma. Cavitation was identified in seven adenocarcinomas, one squamous cell carcinoma, and one bronchiolo-alveolar carcinoma. Nearly 50% (20 cats) of the patients had radiographic evidence of pleural involvement. Fifteen cats had evidence of regional lymph node involvement.     

Immunohistochemical detection of uroplakin III,cytokeratin 7, and cytokeratin 20 in canine urothelial tumors

Immunohistochemistry for uroplakin III (UP III), cytokeratin 7 (CK 7), and cytokeratin 20 (CK 20) using commercially available antibodies was done in normal canine urinary bladder and 72 canine urinary bladder tumors that had been fixed in formalin and embedded in paraffin. Prolonged fixation (3-28 days) did not significantly alter the immunostaining for UP III. There was moderate reduction in the intensity for CK 7 and CK 20 after 1 week of fixation. UP III was detected in superficial (umbrella) cells and some intermediate cells of the normal urinary bladder, 7 of 7 transitional cell papillomas (TCPs), 50 of 55 transitional cell carcinomas (TCCs), and 4 of 5 metastatic TCCs. Staining was typically outlined in the plasma membrane, but diffuse or focal cytoplasmic staining was also observed. Intracytoplasmic lumina were usually positive for UP III. One squamous cell carcinoma of the bladder, 4 nonepithelial bladder tumors, and 285 nonurothelial tumors from different nonurinary locations were negative for UP III. CK 7 was detected in 7 of 7 TCPs, 53 of 54 TCCs, and 5 of 5 metastatic TCCs. The staining for CK 7 was diffuse cytoplasmic. CK 20 was detected in 1 of 7 TCPs, 37 of 54 TCCs, and 1 of 5 metastatic TCCs. The staining with CK 20 was cytoplasmic and weaker than with antibodies to UP III or CK 7. There was concurrent expression of UP III, CK 7, and CK 20 in 36 of 54 TCCs. UP III is a specific and sensitive marker for canine transitional epithelial (urothelial) neoplasms, detecting 91% of TCCs. Negative results may be observed with anaplastic tumors.     

Carcinoma in the urinary bladder of a cat: cytologic findings and a review of the literature

Percutaneous fine needle aspiration biopsy (FNAB) was used to diagnose a urinary bladder carcinoma in an aged cat. The cytologic appearance of specimens collected initially was similar to that reported for canine transitional cell carcinoma. However, impression smears of the tumor made at necropsy 7 weeks later consisted predominantly of atypical squamous epithelial cells compatible with squamous cell carcinoma. Histologically, the malignancy was noted to have intermixed areas of abnormal squamous and transitional cell proliferation. The neoplasia was interpreted as a transitional cell carcinoma with extensive transformation to squamous cell carcinoma. This report examines the use and limitations of FNAB in the diagnosis of feline urinary bladder carcinoma and the incidence and behavior of these tumors in the cat.     

Nasal and paranasal adenocarcinomas with neuroendocrine differentiation in dogs

Tumors of the nasal cavity or paranasal sinuses of 18 dogs were examined histopathologically, immunohistochemically, and histochemically. The tumors were classified histologically as 13 adenocarcinomas, 3 transitional carcinomas, 1 squamous cell carcinoma, and 1 adenosquamous carcinoma. Tumor cells were strongly immunoreactive for broad-spectrum cytokeratins in all cases, for cytokeratin 8/18 in 16 cases, and for cytokeratin 19 in 17 cases. None of the 18 carcinomas had cytologic or histologic features indicative of neuroendocrine differentiation, yet tumor cells in 5 of the 13 adenocarcinomas were argyrophilic and immunohistochemically positive for synaptophysin and chromogranin A. Results of this study indicate that neuroendocrine markers may be detected immunohistochemically and histochemically in canine nasal or paranasal adenocarcinomas despite the lack of typical histologic features of neuroendocrine differentiation.     

Canine cutaneous neoplasms: prevalence and influence of age, sex and site on the presence and potential malignancy of cutaneous neoplasms in dogs from Zimbabwe

Histopathological examination was performed on cutaneous biopsies from 900 dogs with skin lesions from Zimbabwe, collected from 1996 to 2000. Clinical data were collected from medical records. Sixty per cent (540/900) of the cases were tumours and 40% (360/900) were non-neoplastic inflammatory or degenerative diseases. Thirty different histological types of tumour were diagnosed. The prevalence of epithelial, mesenchymal, lymphohistiocytic and melanocytic tumours was 39.4%, 44.4%, 7.4% and 8.7%, respectively. The 10 most common tumours, comprising 73.7% of all cutaneous neoplasms, were mast cell tumours, squamous cell carcinomas, perianal gland adenomas, lymphomas, benign melanomas, haemangiosarcomas, sebaceous gland adenomas, fibrosarcomas, lipomas and malignant melanomas. The prevalence of various neoplasms, age of affected dogs and sites of occurrence were similar to surveys in other countries, except that in Zimbabwe there was a greater prevalence of lymphomas and of tumours associated with increased exposure to ultraviolet light (squamous cell carcinomas, haemangiosarcomas and melanomas). For all classes of tumours the sex of the dog did not have any significant influence on the likelihood of developing a tumour. For a dog diagnosed with a tumour located on the trunk, the tumour was significantly more likely to be an epithelial tumour than a non-epithelial tumour The occurrence of melanocytic tumours on the trunk was significantly lower than at other sites. Lymphohistiocytic tumours were 10 times more likely to occur at multiple locations as opposed to single locations.     

A morphologic and immunocytochemical study of hepatic neoplasms in cats.

A retrospective study was done of 47 neoplasms of the hepatic and biliary systems from 47 cats brought to The Animal Medical Center over a period of 10 years (1980 to 1989). Histologic examination of specimens taken at necropsy revealed that 87% (41/47) of the hepatic neoplasms were epithelial and 13% (6/47) were nonepithelial. Of the epithelial tumors, 25/47 (53%) were of intrahepatic bile duct origin, 9/47 (19%) were of hepatocellular origin, 5/47 (11%) involved the extrahepatic bile ducts, and 2/47 (4%) were adenocarcinomas of the gall bladder. Of the nonepithelial neoplasms, hemangiosarcomas were more common, 5/47 (11%), than leiomyosarcomas, 1/47 (2%). Multiple liver lobes were involved in 21/34 (62%) of the epithelial and all six of the nonepithelial intrahepatic neoplasms. Most of the bile duct adenocarcinomas (6/9) were predominantly characterized by acinar structures with mucin production, diffuse necrosis, and little desmoplasia. The hepatocellular carcinomas were characterized by three patterns-trabecular (five tumors), pseudoglandular pattern (two tumors), and anaplastic (one tumor). The hepatic carcinoid was characterized by various-sized groups of acinar and rosettelike structures, some with lumens, separated by thin fibrovascular stroma. The extrahepatic bile duct adenocarcinomas (4/4) were acinopapillary with moderate desmosplasia, whereas the adenocarcinomas of the gall bladder had elongated tubular structures lined by anaplastic cells and a severe desmoplastic reaction. The neuroendocrine carcinoma of the extrahepatic bile duct, the hemangiosarcomas, and the leiomyosarcoma had morphologic features characteristic of these neoplasms. Two of the 16 (13%) bile duct adenomas had anaplastic and precancerous changes. Residual benign components were seen in 10/15 (67%) of the biliary adenocarcinomas, 4/9 (44%) of the intrahepatic bile duct adenocarcinomas, and all of the extrahepatic bile duct adenocarcinomas and gall bladder adenocarcinomas. Results of immunohistochemical studies of the biliary neoplasms were similar to those described in studies of biliary neoplasms in human beings. Results of this study revealed that the frequency of different types of hepatic neoplasms in cats varied from that seen in dogs and human beings, but the morphologic features were comparable.     

Primary and metastatic carcinomas in the digits of cats

In the period 1993-1998, digital carcinomas in 64 cats were examined. In all animals primary complaints were painful digit(s). Eight cats had a primary squamous cell carcinoma which involved one digit or two adjacent digits of one leg. Fifty-six cats had metastases of a pulmonary carcinoma in the digits, and in general multiple digits of different legs were involved. In many of these cats metastases also occurred in other organs, including the skin and muscles. No primary sweat gland carcinomas of the digits were seen. Primary squamous cell carcinomas of the digits were characterized by cornification and the absence of PAS-positive cells, PAS-positive secretory material. Immunohistochemically, these neoplasms stained negative with the monoclonal antibody CAM 5.2 directed against Keratin 8 (K 8). The metastases of pulmonary carcinomas to the digits showed one or more of the following histological features: goblet cells, ciliated epithelial cells, PAS-positive cells or lakes, and/or a PAS-positive lining of luminal membranes and no cornification. Immunohistochemically, they showed positive staining for CAM 5.2 (K8). Thoracic radiographs from three cats with a primary squamous cell carcinoma showed no abnormalities, whereas all cases of metastases from a pulmonary carcinoma to the digits available for follow-up showed evidence of a primary pulmonary carcinoma on radiography and/or postmortem examination (25 out of 56). The conclusion of this study was that most carcinomas in the digits of cats were metastases of a primary pulmonary carcinoma (87.5%). Primary squamous cell carcinomas occurred infrequently. The prognosis of metastases of a pulmonary carcinoma in the digits is poor with an average survival time of 4.9 weeks, in contrast to 29.5 weeks in cats with a squamous cell carcinoma. These data stress the importance of taking thoracic radiographs of cats with digital tumours before surgical intervention.     

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.     

Lectin histochemistry on squamous metaplasia in different epithelial tumors of dogs.

Biotinylated lectins and avidin-biotin-peroxidase complex were used to study the correlation between cellular glycoconjugates' expression and squamous maturation in normal canine skin and in various epithelial neoplasms. Normal skin tissue was obtained from five, male, random-source dogs, 5 to 7 years old. The tumors tested, selected from the files of our Department, were fifteen squamous cell carcinomas from different tissue origin, five hepatoid perianal gland adenocarcinomas with squamous metaplasia, and fourteen solid mammary carcinomas with and without histologic evidence of squamous metaplasia. Except for mammary gland carcinomas, all tumors had been surgically excised from male dogs. Intermediate filament aggregation of twelve solid mammary gland carcinomas were studied electron microscopically. The basal and the lower spinous cells in normal skin and the less differentiated cells in squamous cell carcinomas stained moderately with Griffonia simplicifolia agglutinin-I. Spinous and granular cell layers stained strongly with Phytolacca americana mitogen and Arachis hypogaea agglutinin. Both lectins stained well-differentiated cells in squamous cell carcinomas. The electron microscopic study carried out in solid carcinomas of mammary glands revealed some relationship between the presence of intracytoplasmic tonofibrils and the binding of Griffonia simplicifolia agglutinin-I and Phytolacca americana mitogen to the tumors tested. Our results suggest that the glycosylation pattern occurring during normal keratinocyte differentiation is conserved in squamous cell carcinomas and that Griffonia simplicifolia agglutinin-I and Phytolacca americana mitogen may represent useful tools in distinguishing poorly differentiated squamous cell carcinomas from other poorly differentiated mammary epithelial tumors.     

A survey on neoplasia in domestic species over a 40-year period from 1935 to 1974 in the Republic of South Africa. II. Tumours occurring in sheep

A survey was carried out on all ovine neoplasms recorded in the registration files of the Section of Pathology of the Veterinary Research Institute at Onderstepoort over a 40-year period from 1935 to 1974. The neoplasms were divided and tabulated into 8 groups according to body systems or tissue types. Out of a total of 673 neoplasms, 436 (64,8%) were cases of jaagsiekte (pulmonary adenomatosis). Of the remaining 237 neoplasms, 41,3% involved the skin. Eighty per cent of the cutaneous neoplasms were squamous cell carcinomas which varied from well-differentiated to anaplastic. The majority occurred on the head, in particular on the ears, frontal region and on the eyelids or nictitating membrane. Several factors have been suggested to explain the high incidence of squamous cell carcinomas on the head. Lymphosarcomas were the 3rd most commonly encountered tumours, whilst a significant number of hepatocellular carcinomas also occurred. A variety of tumours of connective tissue origin were recorded, the most common of which arose from fibrous tissue and cartilage.     

Primary neoplasms of the nasal cavity, paranasal sinuses and nasopharynx in the dog. A report of 16 cases from the files of the AFIP

Sixteen cases of primary neoplasms of the nasal cavity, paranasal sinuses and nasopharynx in the dog were reviewed from the files of the Armed Forces Institute of Pathology (AFIP). The mean age of affected dogs was 9.5 years. The presenting clinical signs were epistaxis, nasal discharge or facial swelling. Eleven of the affected dogs were purebred. Three of these were Collies and two German Shepherds. The nasal cavity was involved most often. All neoplasms were malignant (11 carcinomas and five sarcomas), and there was invasion of the adjacent bony structures in most dogs. Tumors were classified according to prominent cell type and degree of differentiation into respiratory epithelial carcinoma (four), adenocarcinoma (one), squamous cell carcinoma (one), mucoepidermoid carcinoma (two), undifferentiated carcinoma (three), chondrosarcoma (three) and undifferentiated sarcoma (two).     

Survey of neoplasia in red kangaroos (Macropus rufus), 1992-2002, in a zoological collection.

An increase in the proportion of cases with neoplasia observed in a collection of captive red kangaroos (Macropus rufus) when compared with historical records and the paucity of reported neoplasms in kangaroos in the literature prompted a 10-yr review of all red kangaroo necropsies. Individual necropsy, medical, and inventory records for all kangaroos at the Kansas City Zoo were reviewed for the period 1 January 1992 to 31 December 2002. Two squamous cell carcinomas of the oral cavity, two mammary gland adenocarcinomas, a multicentric T-cell lymphosarcoma, and one submucosal pyloric lipoma were diagnosed in six of 28 kangaroo deaths. Three neoplasms were diagnosed antemortem. Four of the six neoplasms were considered malignant, and all four had metastasized. The mean age at death was 11 yr. All six animals with neoplasms were female; however, the exhibit population was composed solely of females. Only 11 cases of neoplasia in red kangaroos have been reported in the literature. On the basis of these cases and a review of the literature, the most commonly observed neoplasms in red kangaroos are mammary gland adenocarcinomas and oral squamous cell carcinomas. Common denominators were not identified in these cases, although chronic gingivitis could have been a contributing factor in the development of the oral squamous cell carcinomas.     

Transitional cell carcinoma in the domestic cat.

In 17 cases of transitional cell carcinoma in cats the most common site for primary neoplasia was the urinary bladder; metastasis was recorded in five of the cases. Nine of the cases have been reported previously; the eight additional carcinomas from the files of the New York State College of Veterinary Medicine were highly invasive and had a desmoplastic response. According to WHO guidelines they were classified as nonpapillary, infiltrating; papillary, infiltrating; and variants of transitional cell carcinoma.     

Coordinate expression of cytokeratins 7 and 20 in feline and canine carcinomas.

Forty-seven feline and 60 canine epithelial tumors were studied to test the coordinate expression of cytokeratin 7 (CK 7) and cytokeratin 20 (CK 20) using commercially available monoclonal antibodies and an avidin-biotin immunoperoxidase staining technique. Previously, the distribution of both cytokeratins was examined in normal tissues from 4 cats and 4 dogs. The pattern of distribution of CK 7 in normal tissues was similar, with minor differences, to that described in humans, whereas the reactivity pattern of CK 20 in cats and dogs was wider than that in humans. The subset of tumors strongly expressing CK 7 and CK 20 included pancreatic adenocarcinomas (100%), transitional cell carcinomas (75%), and endometrial carcinomas (67%) in the cat. None of the canine tumors had this immunophenotype. Feline (50%) and canine (56%) mammary gland carcinomas and canine cholangiocarcinomas (67%) were the only tumors presenting the CK 7 +/CK 20- immunophenotype, whereas the CK 7-/CK 20+ immunophenotype included thyroid carcinomas (100%), intestinal adenocarcinomas (60%), bronchioloalveolar carcinomas (50%), and renal carcinomas (50%) in the cat and intestinal adenocarcinomas (56%), gastric adenocarcinomas (50%), and ovarian carcinomas (50%) in the dog. The CK 7-/CK 20- immunophenotype included the rest of the analyzed tumors. The immunohistochemical evaluation of coordinate expression of both CK 7 and CK 20 in feline and canine carcinomas using monoclonal antibodies provides important information that can help to discriminate among carcinomas from different primary sites and could be particularly helpful in the determination of the primary site of origin of carcinomas presenting as metastatic disease.     

Classification and behavior of canine mammary epithelial neoplasms based on life-span observations in beagles.

As part of a study of the effects of low-level radiation, 1,343 Beagles, including 671 males and 672 females, were evaluated over their full lifetime for the occurrence of mammary neoplasia; there were 139 control males and 138 control females and 532 irradiated males and 534 irradiated females. All nodules found in surgical specimens or at necropsy were evaluated histologically. The overall incidence, metastasis and recurrence rates, and contribution to mortality of mammary neoplasms were determined. Based on this unique opportunity to correlate morphologic characteristics with ultimate biological behavior of all mammary tumors in a defined canine population, we propose a histogenetically based reclassification of epithelial mammary tumors. Of the 672 female dogs, 70.8% (476) had at least one mammary neoplasm; 60.7% (408) had more than one. Two male dogs had mammary neoplasms. Of 1,639 mammary carcinomas in the 672 females, 18.7% (307) were classified as ductular carcinomas (arising from the small interlobular or intralobular ductules), whereas 80.7% (1,322) were classified as adenocarcinomas of other histogenetic origin. Of 73 fatal carcinomas, ductular carcinomas accounted for 48 fatalities (65.8%), whereas other adenocarcinomas accounted for only 20 fatalities (27.4%). Radiation had no effect on this ratio. Ductular carcinomas also had a higher rate of metastasis than did adenocarcinomas. Existing classifications of mammary carcinomas do not recognize the characteristic morphologic features, the degree of malignancy, and the prognostic importance of these ductular carcinomas. Metastasis rates did not differ between simple and complex carcinomas or between those lesions and adenocarcinomas in mixed tumors. True carcinosarcomas metastasized more frequently (100%, or 5/5) than did adenocarcinomas in mixed tumors (34.4%, or 22/64), emphasizing the importance of not lumping these tumors under the classification of malignant mixed tumors.     

Survey of equine cutaneous neoplasia in the Pacific Northwest.

A retrospective study examined data regarding equine cutaneous and mucocutaneous neoplasms submitted to the Veterinary Diagnostic Laboratory at Oregon State University in a 3.5-year period. A total of 536 neoplasms were identified, accounting for 30% of the total equine pathology submissions. Sarcoid, squamous cell carcinoma, melanocytic tumors, papillomas, and mast cell tumors were the most common neoplasms, constituting 87.5% of all cutaneous neoplasms. Sarcoids represented 51.4% of all neoplasms and 15.18% of total equine accessions. Sarcoid was most common in paints, quarter horses, and Arabians, and was the only common tumor in donkeys and mules. Mean age at diagnosis of equine sarcoid was 9 years. Squamous cell carcinoma constituted 18.3% of all neoplasms and 5.41% of total equine accessions. Ocular squamous cell carcinoma was most common in paints and quarter horses, and penile/preputial squamous cell carcinoma was most common in appaloosas and quarter horses. The mean age of horses with ocular squamous cell carcinoma (13 years) and squamous cell carcinoma of the skin (15 years) was significantly less (P < 0.5) than that of horses with squamous cell carcinoma of the penis and prepuce (21 years) or vulva, anal, and perianal skin (19 years). Findings suggest that equine sarcoid and squamous cell carcinoma occur more frequently in the Pacific Northwest than in the northeastern United States.     

Presence of p53 mutations in feline neoplasms

A region from exon 4 to 8 of the tumour suppressor gene p53 was analysed in 60 feline tumours (30 fibrosarcomas, seven malignant histiocytomas, three lymphosarcomas, five basal cell tumours, five squamous cell carcinomas, two adenocarcinomas of tubular skin glands, one undifferentiated carcinoma of the skin, seven mammary carcinomas). Missense mutations were detected in two fibrosarcomas, one malignant fibrous histiocytoma, the undifferentiated carcinoma of the skin and one mammary carcinoma. One nonsense mutation was detected in one fibrosarcoma and one deletion/frameshift-mutation was observed in one squamous cell carcinoma.     

Three cases of transitional cell carcinoma in the cat and a review of the literature

Only 47 cases of urinary bladder neoplasia have been reported in the cat. In this paper a further three are presented. They were received as post mortem specimens and were examined both macroscopically and microscopically. All three were transitional cell carcinomas, with squamous metaplasia in two. Dysplastic urothelial changes were a feature of two of the three tumours and one of these also showed two separate centres of malignancy. Various features of the three cases are discussed and attention is drawn to their possible aetiological significance. The authors suggest that the prevalence of transitional cell carcinoma in the cat may be greater than has hitherto been believed.