World Small Animal Veterinary Association Renal Pathology Initiative: Classification of Glomerular Diseases in Dogs.

Evaluation of canine renal biopsy tissue has generally relied on light microscopic (LM) evaluation of hematoxylin and eosin-stained sections ranging in thickness from 3 to 5 µm. Advanced modalities, such as transmission electron microscopy (TEM) and immunofluorescence (IF), have been used sporadically or retrospectively. Diagnostic algorithms of glomerular diseases have been extrapolated from the World Health Organization classification scheme for human glomerular disease. With the recent establishment of 2 veterinary nephropathology services that evaluate 3-µm sections with a panel of histochemical stains and routinely perform TEM and IF, a standardized objective species-specific approach for the diagnosis of canine glomerular disease was needed. Eight veterinary pathologists evaluated 114 parameters (lesions) in renal biopsy specimens from 89 dogs. Hierarchical cluster analysis of the data revealed 2 large categories of glomerular disease based on the presence or absence of immune complex deposition: The immune complex-mediated glomerulonephritis (ICGN) category included cases with histologic lesions of membranoproliferative or membranous patterns. The second category included control dogs and dogs with non-ICGN (glomerular amyloidosis or focal segmental glomerulosclerosis). Cluster analysis performed on only the LM parameters led to misdiagnosis of 22 of the 89 cases-that is, ICGN cases moved to the non-ICGN branch of the dendrogram or vice versa, thereby emphasizing the importance of advanced diagnostic modalities in the evaluation of canine glomerular disease. Salient LM, TEM, and IF features for each pattern of disease were identified, and a preliminary investigation of related clinicopathologic data was performed.

Histology and clinical outcome of benign and malignant vascular lesions primary to feline cervical lymph nodes.

A novel form of primary feline hemangiosarcoma and additional cases of plexiform vascularization in the cervical lymph nodes are reported. Sixteen cases of feline lymphadenopathy attributed to abnormal vascular proliferation were identified and evaluated. Most of these lesions were diagnosed histologically as hemangiosarcoma. However, lesions of plexiform vascularization, with and without areas of putative malignant transformation, were also identified. Mean age of the cats was 11 years (range, 3-16 years) with most being domestic shorthair and medium hair (13). Two domestic long hair and 1 Maine Coon were identified. Excisional nodal biopsy was performed in 15 cases and incisional biopsy in 1 case. Six cats were euthanized due to their disease. Survival times ranged from ≤ 1 month to ≥ 30 months. We provide a new clinical differential for cervical lymphadenopathy in cats that is not widely recognized. Proper identification of primary nodal vascular lesions in cats will enable further characterization of clinical features and biologic behavior to determine specific therapy.

Prognostic evaluation of Ki67 threshold value in canine oral melanoma.

Oral melanoma is a common canine cancer with a historically poor prognosis. Recent evidence suggests that a subset of cases may have a more favorable outcome, defined as long-term survival in the absence of intervention other than initial surgery. Traditional histological parameters have had prognostic significance in some studies but not in others, potentially due to interobserver variation. We evaluated the prognostic utility of Ki67 immunohistochemistry in a group of 79 canine oral melanomas using a technique easily applied in a veterinary diagnostic laboratory. A threshold Ki67 value of >19.5 had a sensitivity and specificity of 87.1% and 85.4%, respectively, at predicting death or euthanasia due to melanoma by 1 year postdiagnosis. Threshold values for classical histological parameters were also identified for most cases and were >4 (>30%; sensitivity = 83.9%, specificity = 86.0%) for the nuclear atypia score and >4/10 hpfs (sensitivity = 90.3%, specificity = 84.4%) for the mitotic index. In this study, the percentages correctly classified with respect to death by 1 year postdiagnosis were comparable for Ki67 (86.1%, 68/79), the nuclear atypia score (86.3%, 63/73), and the mitotic index (86.8%, 66/76). High pigmentation (>50%) had a high negative predictive value of 90.9% (18/20), but overall, only 61.0% (47/77) of cases could be correctly classified by this parameter. Based on these results, we recommend a panel of prognostic parameters, including the nuclear atypia score, the mitotic index, Ki67, and pigmentation quantification to more accurately predict the likely outcome of canine oral melanomas.

Prognostic markers for canine melanocytic neoplasms: a comparative review of the literature and goals for future investigation.

Many studies have evaluated various prognostic markers for canine melanocytic neoplasms either as primary or secondary goals; however, design, methodology, and statistical validation vary widely across these studies. The goal of this article was to evaluate and compare published canine melanocytic neoplasm studies in relation to the principals established in the Recommended Guidelines for the Conduct and Evaluation of Prognostic Studies in Veterinary Oncology. Based on this evaluation, we determined which parameters currently have the most statistically supported validity for prognostic use in canine melanocytic neoplasia. This information can also be used as part of evidence-based prospective evaluations of treatment regimens. Additionally, we highlight areas in which the current data are incomplete and that warrant further evaluation. This article represents an initiative of the American College of Veterinary Pathologists' Oncology Committee and has been reviewed and endorsed by the World Small Animal Veterinary Association.

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.

Safety of trypsin inhibitors in the diet: effects on the rat pancreas of long-term feeding of soy flour and soy protein isolate.

The effects on the pancreas of chronic dietary exposure to defatted soy flour and soy protein isolate have been studied in two two-year feeding trials in rats. Emphasis was placed on detecting changes that might accompany low levels of dietary trypsin inhibitor (TI) as might be found in edible grade soy products and on studying the influence of protein nutrition. The major pathological findings in the pancreas were nodular hyperplasia (NH), consisting of foci of hyperplastic acinar cells often grossly visible by six months, and the benign neoplastic lesion, acinar adenoma (AA), which developed more slowly. In the first feeding trial, the objectives were to obtain the dose-response relationship of pancreatic pathology to dietary TI provided by raw and heated soy flour and to study the nutritional interaction of protein level which was varied from 10% to 30% using casein supplementation. Also, the responses to raw and heated soy protein isolate were compared to determine whether the removal of more than 50% of the constituents found in soy flour would alter the development of pancreatic lesions. In the second trial, the effect of unusually low levels of TI in raw and heat-treated soy protein isolate, prepared through a salt extraction process and fed at 10% and 30% protein in the diet, was investigated. The incidence of both NH and AA was positively related to the TI content of the diet. The probit transformation of the percent incidence of AA was linearly related to the log of TI/g protein in the diet. A single curve best described the response to 20% and 30% protein, with a slope that was distinctly greater than that for 10% protein. The intersection of the two curves near the TI concentration of edible grade soy flour predicts that protein level in the diet can be expected to have essentially no effect on the incidence of AA when TI activity is in this range. But, for proteins containing greater concentrations of TI, increasing the level of protein in the diet will increase the incidence of pancreatic pathology, while for proteins with quite low levels of TI, increasing the protein in the diet above 10% will have a protective effect.(ABSTRACT TRUNCATED AT 400 WORDS)

Pathologic factors affecting postsplenectomy survival in dogs.

The apparently high prevalence of splenomegaly in dogs, along with the surgical accessibility of the spleen, results in a relatively large number of splenectomies in dogs in clinical veterinary practice. Splenic nodular lesions are widely considered to be indicative of hemangiosarcoma and thus a disease that is ultimately fatal. This study correlates the results of complete pathologic evaluation and classification of 500 spleens obtained by splenectomy with survival information for each dog. Among the spleens examined, 257 of 500 (51.4%) were classified nonneoplastic and 241 (48.2%) were neoplastic; 2 (0.4%) were unclassified. Miscellaneous non-nodular splenomegaly accounted for 46 of 257 (18%) of the nonneoplastic lesions; nodular splenomegaly accounted for 206 of 257 (79%) of nonneoplastic splenic lesions and was composed of lymphoid hyperplastic nodules and associated hematomas, hyperplastic lymphoid nodules alone, or hematomas with no apparent underlying cause. Nodular neoplastic diseases of the spleen were divided among benign tumors (11.5%) and a variety of primary sarcomas. Hemangiosarcoma made up 51% of splenic malignancies but accounted for less than 25% of the spleens evaluated. Survival of dogs with hematomas associated with nonneoplastic conditions of the spleen was markedly different from that in dogs with hemangiosarcoma-associated hematomas, even though most could not be effectively differentiated on gross inspection. Two month postoperative survival was 83% for dogs with nonneoplastic-related hematomas, whereas only 31% of dogs with hemangiosarcoma, with or without associated hematomas, were alive after 2 months. Twelve-month survival times were 64% and 7%, respectively. An overall postsplenectomy survival rate of 52% was based on the number of dogs surviving for a minimum of 6 months postoperatively.

Ultrastruct of the juxtaglomerular apparatus in the dog in a sodium-balanced state.

The ultrastructure of juxtaglomerular apparatuses (JGA) from four dogs in a state of sodium balance were examined. Plasma renin activity and urinary sodium excretion in the dogs were within normal values. At the vascular pole of the glomerulus, circumferentially oriented smooth muscle cells in the wall of the glomerular arteriole were abruptly replaced by modified smooth muscle cells with complicated interwoven cell processes. These modified cells were indistinguishable from the juxtaglomerular cells of the lacis region (extraglomerular mesangium). The basal lamina surrounding these modified smooth muscle cells in the wall of the glomerular arteriole was continuous with the basal lamina of the juxtaglomerular cells of the lacis (extraglomerular mesangium) and the macula densa. The most striking differences in the JGA of the dog, when compared with the JGA of other laboratory animals, are related to the observation that cytoplasmic secretory granules are less abundant in the dog, are generally smaller than the practical resolving capability of the light microscope, and are restricted to cells of the lacis area in the JGA.

Pathophysiologic response of the juxtaglomerular apparatus to dietary sodium restriction in the dog.

Pathophysiologic changes in the juxtaglomerular apparatus (JGA) of the dog were induced by 10 days of dietary sodium restriction (less than 1 mEq of Na+/day). Plasma renin activity increased 12-fold and plasma aldosterone values increased 60-fold, whereas urinary sodium excretion decreased precipitously. Urinary potassium excretion remained within normal values throughout the period of sodium restriction. The JGA cell counts, determined by light microscopy, were significantly (P = less than 0.05) increased after 2 days of sodium restriction and remained increased through day 10. Adrenal gland weights and the cross-sectional width of the zona glomerulosa were not altered. Ultrastructurally, JGA cells showed progressive hypertrophy and hyperplasia. The Golgi apparatus became more prominent. The endoplasmic reticulum increased, as did the number of ribosomes. Cytoplasmic secretory granules increased in number and size from day 2 through day 6. On days 8 and 10, fewer and smaller secretory granules were encountered, even though plasma renin and aldosterone values continued to increase. In the dog maintained in a balanced sodium state, little renin is stored in cytoplasmic granules of the juxtaglomerular cells. Short-term stimulation results in increased plasma renin values and increased production and storage of renin in JGA cells. Continued stimulation results in depletion of cytoplasmic stores, although plasma renin content continues to rise, suggesting that renin is produced and secreted directly during more prolonged stimulation.

Vitamin D intoxication and the pathogenesis of vitamin D nephropathy in the dog.

Dogs given excess vitamin D (500 or 1,000 micrograms/kg of body weight each day for 1 to 3 weeks were observed for clinical and pathologic changes of increased blood pressure and of characteristic nephropathy associated with vitamin D toxicosis or hypercalcemia. Serum calcium and serum urea nitrogen (UN) increased throughout the treatment period, but serum phosphorus remained within the normal range. Plasma renin activity increased markedly. Blood pressure showed only insignificnat changes (P = greater than 0.05). Gross and microscopic examination of the kidneys suggested vascular-oriented changes with an ischemic basis. Glomerular vascular poles showed hypertrophy and hyperplasia of juxtaglomerular cells. Ultrastructually, an increase in the number of secretory granules was noticed in these cells. A hypothesis regarding the mechanism of renal injury during vitamin D toxicosis is presented.

Seizure-induced rhabdomyolysis accompanied by acute renal failure in a dog.

Secondary complications from extreme and prolonged convulsive seizures occurred in a young dog. Physical exertion resulted in necrosis of a substantial amount of skeletal muscle. The release of large quantities of myoglobin into the circulation caused severe impairment of renal function. Anoxia, apparently associated with the inability to breathe during seizures, resulted in brain damage. It was concluded that, although primary therapy must be directed toward alleviation of intense seizure activity, subsequent screening for renal disease and corollary supportive therapy would be appropriate.

Prevalence, type, and importance of splenic diseases in dogs: 1,480 cases (1985-1989).

The prevalence data of splenic diseases from 3 sources were studied. Group 1 consisted of a general diagnostic survey of accessions submitted from private veterinary hospitals in California during a period of approximately 4 years and included 1,372 submissions of canine splenic tissue. Group 2 consisted of surgical splenectomy specimens from 92 dogs; the specimens were submitted to the laboratory for gross and histologic evaluation prior to fixation, and a questionnaire was subsequently sent to determine the outcome of the disease. Group 3 was made up of specimens of 105 splenic lesions derived from a large colony of Beagles with complete medical records and records of pathologic findings. In this study, splenic hematoma and hyperplastic nodule, not hemangiosarcoma, made up the bulk of splenic lesions. Hemangiosarcoma was the most frequent neoplasm of the canine spleen, but the combined prevalence of all other splenic neoplasms was similar to that of hemangiosarcoma alone. Splenic hematoma and hemangiosarcoma were grossly indistinguishable in most cases. Hyperplastic lymphoid nodules and hematomas of the spleen appeared to represent a continuum. If that finding was correlated with microscopic splenic blood flow, specific causal relationship could be suggested. Prognostically, the live/dead ratio and mean survival of dogs with various splenic lesions differed significantly.

Salivary gland disease in dogs and cats: 245 cases (1985-1988).

Diagnostic pathology records spanning 41 months (July 1985 through November 1988) were searched for diagnoses of salivary gland disease in dogs and cats. Review of 87,392 records from that period revealed 245 cases (0.3%) in which salivary gland tissue had been evaluated. During that period, salivary gland tissue was submitted to the laboratory almost twice as often from dogs (160 cases) as from cats (85 cases). On the basis of histologic examination, 89% of salivary gland submissions from small animal practices were allotted to 1 of 5 major categories: malignant neoplasms (30%; 74/245), sialadenitis (26%; 64/245), normal salivary gland (16%; 40/245), sialocele (9%; 21/245), and salivary gland infarction (8%; 20/245). The remaining 11% of submissions included various degenerative or fibrotic lesions, ductal ectasia, sialolithiasis, edema, benign neoplasia, and secondary salivary involvement with systemic or cervical lymphosarcoma or with fibrosarcoma in the head and neck.

Prevalence and type of splenic diseases in cats: 455 cases (1985-1991).

Retrospective data on the type and prevalence of splenic disease in cats were evaluated in a large number of feline splenic tissues (n = 455) submitted as surgical and necropsy specimens from private veterinary hospitals in California during a period of approximately 5.5 years. Primary and metastatic neoplasia accounted for 37% of all feline splenic lesions. Mastocytoma, lymphosarcoma, myeloproliferative disease, and hemangiosarcoma, in that order, accounted for the bulk of neoplasia. Submission of accessory splenic tissue from either the omentum or pancreas accounted for 4% (17/455), whereas hyperplastic nodules, hematomas, and the combination of these changes in the spleen accounted for 4% (19/455). Splenitis was found in 2% (8/455) of submissions. Thromboembolism with regional splenic infarction accounted for 1% (4/455) of splenic lesions in cats. The remaining splenic lesions each accounted for less than 1% of total splenic submissions, and as such, were considered incidental and of questionable clinical importance.

Blood pressure measurement in the dog.

An indirect method of blood pressure measurement was evaluated in 169 dogs, including 114 that were hospitalized because of a variety of diseases, 10 clinically normal dogs presented for neutering, and 45 privately owned, clinically normal dogs. Measurements correlated well with values obtained by simultaneous direct arterial puncture. Normotension was considered to be 130 to 180 mm of Hg, systolic, and 60 to 95 mm of Hg, diastolic. As a group, 20 dogs with advanced renal disease had significant (P less than 0.001) hypertension, compared with the groups of clinically normal dogs. Of 94 dogs with a variety of diseases exclusive of renal disease, 10 had hypertension and 2 had hypotension.

Epidemiologic evidence for a causal relation between vaccination and fibrosarcoma tumorigenesis in cats.

Within the past 2 years, a putative causal relationship has been reported between vaccination against rabies and the development of fibrosarcomas at injection sites in cats. A retrospective study was undertaken, involving 345 cats with fibrosarcomas diagnosed between January 1991 and May 1992, to assess the causal hypothesis. Cats with fibrosarcomas developing at body locations where vaccines are typically administered (n = 185) were compared with controls (n = 160) having fibrosarcomas at locations not typically used for vaccination. In cats receiving FeLV vaccination within 2 years of tumorigenesis, the time between vaccination and tumor development was significantly (P = 0.005) shorter for tumors developing at sites where vaccines are typically administered than for tumors at other sites. Univariate analysis, adjusted for age, revealed associations between FeLV vaccination (odds ratio [OR] = 2.82; 95% confidence interval [CI] = 1.54 to 5.15), rabies vaccination at the cervical/interscapular region (OR = 2.09; 95% CI = 1.01 to 4.31), and rabies vaccination at the femoral region (OR = 1.83; 95% CI = 0.65 to 5.10) with fibrosarcoma development at the vaccination site within 1 year of vaccination. Multivariate analysis, adjusted for age and other vaccines, also revealed increased risks after FeLV (OR = 5.49; 95% CI = 1.98 to 15.24) and rabies (OR = 1.99; 95% CI = 0.72 to 5.54) vaccination.(ABSTRACT TRUNCATED AT 250 WORDS)

Crystalline corneal opacities in the Siberian Husky.

Bilaterally symmetric opacities were detected in the corneal stroma of 78 (14%) of 560 Siberian Huskies, aged 7 months to 12 years, examined in ophthalmology screening clinics. The opacities were round or horizontally oval and consisted of a diffuse gray homogeneous haze in the anterior stroma or an array of fine polychromatic crystals in the posterior stroma, or both. The corneas were not inflamed. The frequency of occurrence and density of the opacities increased with age. Several affected dogs were closely related, but a specific inheritance pattern could not be established. Light and electron microscopy disclosed clusters of extracellular, thin, needle-shaped, crystalline clefts. Histochemical stains on frozen sections identified neutral fats, phospholipids, and cholesterol as components of the crystals.

Effects of brief exposure of domestic fowl to very intense acceleration fields.

Since biological responses to high sustained Gz (HSGz) are determined largely by field intensity and duration of exposure, a series of experiments was arranged to emphasize the effects of field intensity. Male Rhode Island Red chickens were given a single standard exposure of 1 min to a field, which increased from 5-18 +Gz for the series. Acceleration-induced changes were observed in heart rate during and after the treatment, and in lymphocyte frequency and body mass maintenance subsequently. Generally, there was an increasing bradycardia and lymphopenia, which was proportional to field strength. Above 13 G, normal growth and even the maintenance of a pre-treatment body mass were impaired.

Responses of domestic fowl to repeated +Gz acceleration.

The responses of domestic fowl to repeated exposures of 4 min to +6Gz (8 times daily, 5 d weekly) are reported. Survivorship curves for the test group of 48 birds divided into three response categories: mode I, highly susceptible, with all individuals dying on the first day; mode II, more tolerant, with mortality occurring within the first 20 d of treatment; and mode III, highly tolerant, with mortality occurring only after 20 d of treatment. Observations of lymphocyte frequency, an index of systemic stress, and postmortem observations indicate that this heterogeniety has a biological basis.