Recommended guidelines for submission, trimming, margin evaluation, and reporting of tumor biopsy specimens in veterinary surgical pathology.

Neoplastic diseases are typically diagnosed by biopsy and histopathological evaluation. The pathology report is key in determining prognosis, therapeutic decisions, and overall case management and therefore requires diagnostic accuracy, completeness, and clarity. Successful management relies on collaboration between clinical veterinarians, oncologists, and pathologists. To date there has been no standardized approach or guideline for the submission, trimming, margin evaluation, or reporting of neoplastic biopsy specimens in veterinary medicine. To address this issue, a committee consisting of veterinary pathologists and oncologists was established under the auspices of the American College of Veterinary Pathologists Oncology Committee. These consensus guidelines were subsequently reviewed and endorsed by a large international group of veterinary pathologists. These recommended guidelines are not mandated but rather exist to help clinicians and veterinary pathologists optimally handle neoplastic biopsy samples. Many of these guidelines represent the collective experience of the committee members and consensus group when assessing neoplastic lesions from veterinary patients but have not met the rigors of definitive scientific study and investigation. These questions of technique, analysis, and evaluation should be put through formal scrutiny in rigorous clinical studies in the near future so that more definitive guidelines can be derived.

Recommended guidelines for the conduct and evaluation of prognostic studies in veterinary oncology.

There is an increasing need for more accurate prognostic and predictive markers in veterinary oncology because of an increasing number of treatment options, the increased financial costs associated with treatment, and the emotional stress experienced by owners in association with the disease and its treatment. Numerous studies have evaluated potential prognostic and predictive markers for veterinary neoplastic diseases, but there are no established guidelines or standards for the conduct and reporting of prognostic studies in veterinary medicine. This lack of standardization has made the evaluation and comparison of studies difficult. Most important, translating these results to clinical applications is problematic. To address this issue, the American College of Veterinary Pathologists' Oncology Committee organized an initiative to establish guidelines for the conduct and reporting of prognostic studies in veterinary oncology. The goal of this initiative is to increase the quality and standardization of veterinary prognostic studies to facilitate independent evaluation, validation, comparison, and implementation of study results. This article represents a consensus statement on the conduct and reporting of prognostic studies in veterinary oncology from veterinary pathologists and oncologists from around the world. These guidelines should be considered a recommendation based on the current state of knowledge in the field, and they will need to be continually reevaluated and revised as the field of veterinary oncology continues to progress. As mentioned, these guidelines were developed through an initiative of the American College of Veterinary Pathologists' Oncology Committee, and they have been reviewed and endorsed by the World Small Animal Veterinary Association.

Acquired amegakaryocytic thrombocytopenia--four cases and a literature review.

Acquired amegakaryocytic thrombocytopenla was diagnosed in four dogs. Initial platelet counts in all four dogs were less than 50,000 x 10(9)/litre and initial bone marrow examinations revealed megakaryocytic hypoplasia with minimal changes in the erythroid and myeloid cell lines. Two dogs had evidence of idiopathic immune-mediated disease and two dogs had evidence of associated infectious disease. One dog had a positive antibody titre to Borrella burgdorferi, and one dog had positive titres to both Ehrlichia canis and B. burgdorferi. Treatment consisted of prednisone and cyclophosphamide for the dogs with presumptive immune-mediated disease, and prednisone and tetracycline for the dogs with positive antibody titres to the Infectious organisms. Both dogs with evidence of associated infectious disease responded to treatment. A postmortem examination did not reveal the underlying aetiology in the two dogs with presumptive idiopathic immune-mediated disease.

The accuracy of intraoperative cytopathological diagnosis compared with conventional histopathological diagnosis.

To determine the accuracy of intraoperative cytopathological diagnosis compared with conventional histopathological diagnosis, the authors obtained 100 specimens from masses of various organ systems chosen randomly from 65 dogs, 30 cats, and five exotic animals. Of the 100 specimens, a specific diagnosis was obtained in 42%, the correct pathological process (i.e., mesenchymal neoplasia, epithelial neoplasia, round cell neoplasia, or inflammation) was identified in 41%, in 1% the diagnosis was deferred, and in 16% an incorrect diagnosis was obtained. The overall accuracy rate of intraoperative cytopathological examination was 83%, which increased to 90% by the exclusion of splenic masses. The accuracy rate of diagnosing neoplasia was 87%, with a sensitivity of 89% and a specificity of 100%. Intraoperative cytopathological examination is an accurate diagnostic method with good sensitivity and specificity for the identification of neoplasia.

Metabolic and hormonal alterations in cats with hepatic lipidosis.

Hepatic lipidosis in cats is a commonly diagnosed hepatobiliary disease of unknown cause. The purpose of this prospective study was to characterize the blood hormone and lipid status of cats with hepatic lipidosis, and to compare this status to that of cats with other types of liver disease and to control cats. Twenty-three cats with hepatic disease were assigned to 1 of 2 groups on the basis of cytopathologic or histopathologic examination of the liver: group 1, hepatic lipidosis (n = 18); or group 2, cholangiohepatitis (n = 5). Ten healthy young adult cats were used as controls. Food was withheld from control animals for 24 hours before blood collection. Concentrations of plasma glucagon and serum insulin, cortisol, thyroxine, triglycerides, cholesterol, phospholipids, and nonesterified fatty acids (NEFAs) were determined in all cats, in addition to routine hematologic and serum biochemical testing. Cats with hepatic lipidosis had higher serum NEFA concentrations than cats with cholangiohepatitis or control cats (P < .05). Cats with cholangiohepatitis had higher serum cholesterol and phospholipid concentrations than those of cats with lipidosis or control cats (P < .05); their plasma glucagon concentrations were higher than those of control cats (P < .05), but were not different from those of cats with hepatic lipidosis. Serum insulin concentrations were significantly higher in control cats than in diseased cats (P < .05), but neither serum insulin nor the insulin to glucagon ratio was significantly different among the cats with hepatic disease. The high concentration of NEFAs in cats with hepatic lipidosis suggests that at least 1 factor in the pathogenesis of this syndrome may involve the regulation of hormone-sensitive lipase.

Prognostic value of argyrophilic nucleolar organizer region (AgNOR) staining in feline intestinal lymphoma.

Limited information is available on prognostic factors for cats with lymphoma. The quantity of argyrophilic nucleolar organizer region (AgNOR) proteins can be used as a measurement of cellular proliferative activity. To determine if AgNORs were of prognostic value for feline intestinal lymphoma, the silver staining technique was performed on paraffin-embedded sections of 31 cases. Mean number of AgNORs per nucleus ranged from 1.02 to 4.32. Twenty-four (78%) cats had small AgNORs and 7 (22%) had large AgNORs. All cats were treated identically with a combination chemotherapy protocol. Response to chemotherapy was 87%. Median remission duration and survival times were 120 days and 201 days, respectively. No significant correlation was found between mean number of AgNORs per nucleus or AgNOR size and remission rate, remission duration, or survival time. This study indicates that AgNOR staining is not a useful prognostic factor for cats with intestinal lymphoma.

Serum fructosamine concentration as an index of glycemia in cats with diabetes mellitus and stress hyperglycemia.

The purpose of this study was to evaluate fructosamine concentrations in clinically healthy cats, sick cats with stress hyperglycemia, and untreated diabetic cats to determine the usefulness of this test in diagnosing diabetes mellitus in cats, and in differentiating the disease from stress-induced hyperglycemia. In addition, we evaluated if the degree of glycemic control in cats treated for diabetes influenced their serum fructosamine concentrations. In the 14 sick cats with stress hyperglycemia, the median serum fructosamine concentration (269 mumol/L) was not significantly different from the median value in the 26 clinically normal cats (252 mumol/L). Two of the 14 cats with stress hyperglycemia (14.3%) had serum fructosamine concentrations above the upper limit of the reference range (175 to 400 mumol/L); on the basis of these results, the test specificity was calculated as 0.86. In 30 cats with untreated diabetes mellitus, the median serum fructosamine concentration was 624 mumol/L, markedly higher than the value in either the normal cats or the cats with stress hyperglycemia. All but 2 of the 30 untreated diabetic cats (6.7%) had serum fructosamine concentration above the upper limit of the reference range; on the basis of these results, the sensitivity of serum fructosamine concentration as a diagnostic test for diabetes mellitus was 0.93. When 30 diabetic cats receiving treatment were divided into 3 groups according to their response to treatment (i.e., poor, fair, and good), the 16 cats that had a good response to treatment had significantly lower serum concentrations of both glucose and fructosamine compared with cats that had either a fair or poor response to treatment. A significant correlation (rs = .70, n = 100, P < .001) was found between serum concentrations of glucose and fructosamine. Results of this study indicate that quantification of serum fructosamine concentration is a meaningful test for the diagnosis of diabetes, for differentiating diabetes from stress hyperglycemia; and for monitoring the metabolic control in treated diabetic cats.

Diagnosis and treatment of insulin-secreting pancreatic islet cell tumors in ferrets: 57 cases (1986-1994).

OBJECTIVE: To evaluate clinical, laboratory, radiographic, ultrasonographic, surgical, and histologic findings in ferrets with insulinoma and to determine their long-term outcome. DESIGN: Retrospective study. ANIMALS: 57 ferrets with a histopathologic diagnosis of pancreatic islet cell tumor. PROCEDURE: Medical records of ferrets with pancreatic islet cell tumors were reviewed. RESULTS: Lethargy, weakness, and collapse were the most common clinical signs. All ferrets had hypoglycemia, and hyperinsulinemia was documented in 39 of 47 (83%) ferrets. Ultrasonographic examination of the abdomen revealed pancreatic nodules in 5 of 23 ferrets. Surgical treatment was performed in 50 ferrets, 3 were treated by medical management alone, and 4 did not have treatment. At the time of surgery, 1 pancreatic nodule was found in 13 (26%) ferrets and multiple nodules were found in 37 (74%) ferrets. Pancreatic carcinoma alone was found in 34 ferrets. Whereas a combination of carcinoma and either hyperplasia or adenoma was found in 23 ferrets; 4 ferrets had metastasis to regional lymph nodes or liver. In 26 (53%) ferrets, hypoglycemia persisted after surgery, necessitating medical treatment with prednisone, diazoxide, or both. Sixteen (33%) ferrets had redevelopment of hypoglycemia at 1 to 23.5 months (median, 10.6 months) after surgery. Only 7 of the 50 (14%) ferrets remained euglycemic after surgery. CLINICAL IMPLICATIONS: In ferrets, surgical removal of insulin-secreting pancreatic islet cell tumors is recommended as definitive treatment; however, multiple pancreatic nodules are common, making complete excision of all tumor tissue difficult. Persistent hypoglycemia after surgical treatment indicates that lifelong medical management with prednisone or diazoxide or both may be necessary in many ferrets. Finally, because the insulin-secreting tumors are malignant, long-term cure and survival are not likely.

Evaluation of dogs with digit masses: 117 cases (1981-1991).

Medical records of 117 dogs with digit masses were reviewed. Of 124 digit masses, 76 (61%) were malignant neoplasms, 25 (20%) were benign neoplasms, and 23 (19%) were pyogranulomatous inflammation. Of 29 digits with radiographic evidence of bone lysis, 24 (83%) were affected by malignant masses, whereas only 5 of 29 (17%) digits with radiographic evidence of bone lysis were affected by benign or pyogranulomatous masses. Only 1 of 19 (5%) dogs with melanoma had radiographic evidence of lysis, but 20 of 25 (80%) dogs with squamous cell carcinoma had radiographic evidence of bone lysis. Thoracic radiographs of 95 dogs were available. Six of 19 (32%) dogs with melanoma had radiographic evidence of pulmonary metastasis at the time of diagnosis, whereas 3 of 24 (13%) dogs with squamous cell carcinoma had radiographic evidence of pulmonary metastasis at the time of diagnosis. Twenty-nine digit neoplasms were squamous cell carcinoma, and 19 of 29 (66%) arose from the subungual epithelium. Of 19 dogs with squamous cell carcinoma originating from the subungual epithelium, 18 (95%) survived for at least 1 year, whereas only 6 of 10 (60%) dogs with squamous cell carcinoma originating in other parts of the digit survived for at least 1 year. Furthermore, of 19 dogs with squamous cell carcinoma originating from the subungual epithelium, 14 (74%) survived at least 2 years, whereas only 4 of 9 (44%) dogs with squamous cell carcinoma originating in other parts of the digit survived for 2 years. Dogs with melanoma of the digits had a median survival time of 12 months, with 10 of 24 (42%) alive at 1 year and 3 of 23 (13%) alive at 2 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Hyperadrenocorticism associated with adrenocortical tumor or nodular hyperplasia of the adrenal gland in ferrets: 50 cases (1987-1991).

Adrenocortical adenoma, nodular hyperplasia, or carcinoma was diagnosed in 50 ferrets. Thirty-five (70%) ferrets were female and 15 (30%) were male. The mean age at which clinical signs were first noticed was 3.4 years (range, 1 to 7 years). Clinical signs included large vulva (n = 31; 89% of females), alopecia (n = 43; 86%), pruritus (n = 20; 40%), and increased consumption of water and increased urine output (n = 4; 8%). A mass was palpated at the cranial pole of the kidney during physical examination of 17 (34%) ferrets. Ultrasonography, performed on 39 of 50 ferrets, revealed a unilateral adrenal gland mass in 19 (49%). Four ferrets were anemic, and 2 ferrets were thrombocytopenic. Baseline plasma concentrations of cortisol and corticosterone were within or below the reference range in all 17 ferrets tested, whereas baseline plasma estradiol concentrations were high in 4 of the 11 ferrets (36%) tested. AFter adrenocorticotropic hormone (ACTH) administration, only 1 ferret had a slightly exaggerated response on the basis of plasma cortisol concentrations, and all 17 had normal responses on the basis of plasma corticosterone concentrations. There was little or no increase in plasma estradiol concentrations after ACTH administration. Of the 50 ferrets, 39 were treated by adrenalectomy. Unilateral adrenalectomy was performed in 34 ferrets in which 1 adrenal gland was large, whereas subtotal bilateral adrenalectomy was performed in 5 ferrets with bilateral adrenal disease. Five ferrets died in the immediate postoperative period, and follow-up information was available for the remaining 34, 1 to 34 months after surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenomatous polyps of the duodenum in cats: 18 cases (1985-1990).

Medical records were reviewed for 18 cats with adenomatous polyps of the proximal portion of the duodenum. Cats of Asian ancestry were over represented (8/18), and male castrated cats were common (15/18). The median age was 11.8 years. Common clinical signs were acute and chronic vomiting and hematemesis. Nine cats were anemic. Contrast radiography was performed in 12 cats, and a mass of the proximal portion of the duodenum was identified in 10 cats. Endoscopy was used to confirm existence of the mass in 3 cats. Complete excision of the duodenal mass was performed in 17 cats. One cat died before abdominal exploratory surgery, and a duodenal adenomatous polyp was identified at necropsy. Fifteen cats survived the immediate postoperative period, with 13 of 15 having complete resolution of clinical signs. Five cats had concurrent disease, which caused 4 of them to die between 3 and 26 months after surgery. Redevelopment of adenomatous polyps was not detected in any cat during the follow-up period of 1 to 49 months. Results of the study indicated that benign, adenomatous polyps of the duodenum in cats can be safely excised and that the prognosis for return to normal function is excellent.

Infiltrative urethral disease in female dogs: 41 cases (1980-1987).

Forty-one cases of infiltrative urethral disease in female dogs were reviewed. The cause was epithelial neoplasia in 29 dogs, granulomatous (chronic active) urethritis in 10 dogs, and leiomyoma in 2 dogs. Clinical signs of disease were similar in dogs with neoplastic and inflammatory disease and included strangury (36/41), hematuria (30/41), pollakiuria (20/41), vaginal discharge (16/41), and complete urinary obstruction (7/41). Results of aspiration biopsy of the urethra correlated with those of surgical biopsy in 11 of 15 dogs. In 4 of 15 dogs, results of cytologic and histologic examinations differed. Granulomatous (chronic active) urethritis is an infiltrative urethral disease in female dogs. Clinical findings are similar, but the prognosis is more favorable than that in dogs with urethral epithelial neoplasia.

Acromegaly in 14 cats.

Acromegaly was diagnosed in 14 middle-aged to old cats of mixed breeding. Thirteen (93%) of the cats were male and one was female. The earliest clinical signs in the 14 cats included polyuria, polydipsia, polyphagia, all of which were associated with untreated diabetes mellitus. All developed severe insulin resistance within a few months; peak insulin dosages required to control severe hyperglycemia ranged from 20 to 130 U per day. Other clinical findings weeks to months after diagnosis included enlargement of one or more organs (e.g., liver, heart, kidneys, and tongue) (n = 14), cardiomyopathy (n = 13), increase in body size and weight gain (n = 8), nephropathy associated with azotemia and clinical signs of renal failure (n = 7), degenerative arthropathy (n = 6), and central nervous system signs (i.e., circling and seizures) caused by enlargement of the pituitary tumor (n = 2). The diagnosis of acromegaly was confirmed by demonstration of extremely high basal serum growth hormone concentrations (22 to 131 micrograms/l) in all cats. Computerized tomography disclosed a mass in the region of the pituitary gland and hypothalamus in five of the six cats in which it was performed. Two cats were treated by cobalt radiotherapy followed by administration of a somatostatin analogue (octreotide), whereas two cats were treated with octreotide alone. Treatment had little to no effect in decreasing serum GH concentrations in any of the cats. Eleven of the 14 cats were euthanized or died four to 42 months (median survival time, 20.5 months) after the onset of acromegaly because of renal failure (n = 2), congestive heart failure (n = 1), concomitant renal failure and congestive heart failure (n = 3), progressive neurologic signs (n = 2), persistent anorexia and lethargy of unknown cause (n = 1), the owner's unwillingness to treat the diabetes mellitus (n = 1), or unknown causes (n = 1). Results of necropsy examination in ten cats revealed a large pituitary acidophil adenoma (n = 10), marked left ventricular and septal hypertrophy (n = 7), dilated cardiomyopathy (n = 1), arthropathy affecting the shoulder, elbow, or stifle (n = 5), and glomerulopathy characterized by expansion of the mesangial matrix and variable periglomerular fibrosis (n = 10).

IgA deficiency in shar-pei dogs.

Two shar-pei puppies examined because of signs of sinopulmonary disease, one of which also had skin disease, had deficient IgA concentrations. Deficient serum IgA concentrations also were confirmed in 30 of 39 (76.9%) clinically normal adult dogs in two colonies of shar-peis. Both courses of disease--sinopulmonary signs and chronic skin disease and a benign clinical course--have been reported in human patients with IgA deficiency. Thus, the shar-pei might be an appropriate model for studying the immunopathology of IgA deficiency in man.