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.

Pathologic evaluation of canine renal biopsies: methods for identifying features that differentiate immune-mediated glomerulonephritides from other categories of glomerular diseases.

BACKGROUND: Human renal biopsies are routinely evaluated with light microscopy (LM) using a panel of histologic stains, transmission electron microscopy (TEM), and immunofluorescence (IF) microscopy to obtain a diagnosis. In contrast, the pathologic evaluation of glomerular disease in veterinary medicine has relied mostly on LM and was of limited utility. To address this problem, recently established veterinary renal diagnostic centers have adopted methods used in human nephropathology for evaluation of renal biopsies. Three broad categories of disease, which have the greatest implications for clinical management of proteinuric dogs, have been established and include amyloidosis, immune complex-mediated glomerulonephritis (ICGN), and non-ICGN. OBJECTIVE: To demonstrate histopathologic, ultrastructural, and IF findings in renal biopsy specimens that experienced veterinary nephropathologists utilize to make accurate and clinically useful diagnoses in dogs with proteinuric glomerular disease and to provide guidelines for the proper evaluation of renal biopsies. METHODS: Renal biopsy specimens were routinely examined by LM, IF, and TEM. Samples were reviewed by members of the World Small Animal Veterinary Association Renal Standardization Study Group to identify lesions that were diagnostic for, or suggestive of, the presence of immune complexes (IC) or amyloidosis in all modalities. Ten guidelines for renal biopsy evaluation were formulated. RESULTS: Each method of investigation contributed important findings that were integrated to make an accurate final morphological diagnosis. The guidelines were validated by an independent group of veterinary pathologists. CONCLUSIONS AND CLINICAL IMPORTANCE: Routine evaluation of renal biopsies with LM, TEM, and IF is feasible and necessary for making accurate, morphologic diagnoses that can be used to guide clinical management of dogs with glomerular disease.

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.

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.

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.

The histologic and epidemiologic bases for prognostic considerations in canine melanocytic neoplasia.

The laboratory records from 384 dogs with a diagnosis of either melanoma or melanocytoma were selected for study. Significant negative determinants of patient survival for melanocytic tumors were: 1) metastasis, 2) mitotic index (MI), 3) nuclear atypia, 4) tumor score, 5) increasing size/volume, 6) the presence of deep inflammation, and/or 7) intralesional necrosis. In addition to these attributes, age was a significant determinant for tumors of the skin. For the feet and lips, 8) age and 9) junction activity negatively impacted survival. Mathematic models were constructed based on these significant determinants to predict the postsurgical outcome of melanocytic neoplasia. Melanocytic oral neoplasms comprised 19% (73/384) of the neoplasms; 92% of these were classified as malignant in the biopsy report, but malignant behavior (i.e., metastasis or recurrence) was observed in only 59% of cases. The prognostic model for oral tumors based on nuclear atypia provided the most accurate (89%) prediction of overall behavior. Melanocytic tumors of the feet and lips were also 19% (73/384) of the total population. Seventy-four percent were reported malignant, whereas only 38% actually demonstrated malignant behavior. The prognostic models based on both MI or nuclear atypia had an overall correct behavioral classification of 81%. Melanocytic tumors in the skin comprised 59% (227/384) of study specimens. Although 39% were reported as malignant, only 12% exhibited malignant behavior. A satisfactory predictive model that employed MI could not be constructed, but one using nuclear atypia gave an overall correct classification in 93.3% of the cases.

Isoniazid-induced seizures with secondary rhabdomyolysis and associated acute renal failure in a dog.

Isoniazid-induced seizures resulted in rhabdomyolysis and associated acute renal tubular necrosis in a dog. Rhabdomyolysis and myoglobinuric renal failure, although recognised in the dog, are reported infrequently as a consequence of seizures. The clinical presentation of isoniazid toxicity in a dog is described.

Splenic myeloid metaplasia, histiocytosis, and hypersplenism in the dog (65 cases).

Splenectomy specimens from 65 dogs with severe, diffuse, sustained, and progressive splenomegaly were examined. The clinical signs, hematology, and serum chemistry values in for the dogs were not useful diagnostic features. Microscopic changes in the spleens were distinctive and consisted of 1) myeloid metaplasia, 2) histiocytosis, 3) erythrophagocytosis, and 4) thrombosis with segmental infarction. Ultrastructural features suggested proliferative changes in the splenic reticular cells and macrophages (reticular meshwork) that described a continuum from reactive changes associated with immunologic damage of erythrocytes to neoplastic proliferation of histiocytic components. Thirty percent of the dogs survived 12 months. Approximately one half (53%) of the dogs with complete postmortem evaluations showed multiorgan involvement with a tissue distribution and cell morphology consistent with histiocytic neoplasia. For the remaining dogs (47%), only splenic pathology was consistently present, and a specific cause of death was often not evident. Distinctive histologic changes in the splenic tissues-including mitotic activity, erythrophagocytosis, giant cell formation, thrombosis/ infarction, and the proportion and distribution of histiocytic and hematopoietic cells-were statistically evaluated for prognostic relevance. The presence of giant cells was the only reliable prognostic feature, and that was indicative of a fatal outcome. These descriptive changes of myeloid metaplasia in the canine spleen are compared with the human clinical and pathologic syndromes of 1) agnogenic myeloid metaplasia, 2) hemophagocytic syndromes, and 3) hypersplenism. These diseases in humans produce histopathologic changes in the spleen that are similar to those observed in the canine splenic tissue we examined in this study.

Pathologic and prognostic characteristics of splenomegaly in dogs due to fibrohistiocytic nodules: 98 cases.

Ninety-eight canine splenectomy specimens consisting of combined nodular lymphoid and fibrohistiocytic cell proliferation were evaluated for seven light microscopic characteristics. Electron microscopic features in eight primary and two metastatic nodules (liver) were also evaluated. Nodular fibrohistiocytic proliferation in the canine spleen is characterized by a mixed population of histiocytoid and/or spindle cells in varying proportions intermixed with hematopoietic elements, plasma cells, and/or lymphocytes. These nodules seem to form a continuum between splenic lymphoid nodular hyperplasia and malignant splenic stromal neoplasms (malignant fibrous histiocytoma). Immunohistochemical methods used on 32/98 specimens showed uniform and strong positive staining among fibrohisiocytic cells for vimentin and desmin; S100 protein was similarly stained in general abundance. Individual cells strongly stained with smooth muscle actin were sparse but widely distributed. Proliferating cell nuclear antigen was not useful in the subjective differentiation of nodules taken from dogs that died of spleen-related causes and those surviving 12 months following splenectomy. A spectrum of cell types were observed by electron microscopy within each nodule. Fibroblasts, macrophages, intermediate fibrohistiocytic types, and several forms of splenic reticular cells were present. There were no consistent alterations in hematology or serum chemistry profiles of these dogs to provide useful diagnostic/prognostic information. Among the 93/98 dogs with complete (12 month) follow-up information, 48% (45/93) were alive and 52% (48/93) were dead. Dogs that died or were euthanatized during the follow-up period had a median survival of 5 and 5.5 months, respectively (range 0-15 months). Forty-four percent (21/48) died from causes linked to their splenic disease, and 35% (17/48) died from competing causes. The cause of death in 21% (10/48) was unknown. Lymphoid:fibrohistiocytic proportion and mitotic index in the nodules were anatomic features most predictive of postplenectomy mortality. A higher proportion of lymphoid to fibrohistiocytic type cells was associated with increased long-term survival, whereas lower lymphoid:fibrohistiocytic proportions and higher mitotic index indicated a probability of higher short-term mortality.

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.

Primary mesenchymal (nonangiomatous/nonlymphomatous) neoplasms occurring in the canine spleen: anatomic classification, immunohistochemistry, and mitotic activity correlated with patient survival.

Surgical submissions from canine splenectomy cases spanning a 3-year period (1988-1990) were evaluated. Eighty seven neoplasms of the spleen considered to be of nonangiomatous and nonlymphomatous origin were selected for morphologic classification, mitotic index determination, immunohistochemical analysis, and patient survival determination. In 76/87 cases, patient survival information was available, and the mitotic index was determined in 83/87 cases. Immunohistochemistry for selected antigens (vimentin, desmin, smooth muscle actin, myosin, and factor VIII-related antigen) was performed in 58/87 of the cases. Morphologic classification of these lesions in standard HE preparations yielded the following neoplastic groups: fibrosarcoma (19/87), undifferentiated sarcoma (19/87), leiomyosarcoma (14/87), osteosarcoma (8/87), mesenchymoma (7/87), myxosarcoma (6/87), histiocytic sarcoma (6/87), leiomyoma (3/87), lipoma-myelolipoma (2/87), liposarcoma (2/87), and malignant fibrous histiocytoma (1/87). A lack of distinct morphologic characteristics among many of the neoplasms that were classified as either fibrosarcoma, leiomyosarcoma, or undifferentiated sarcoma contrasted these groups with the relatively unambiguous features that distinguished the other sarcoma groups. Using immunohistochemical staining for muscle-specific antigens (desmin, smooth muscle actin, and myosin), specific staining often overlapped extensively within the neoplastic groups of fibrosarcomas, leiomyosarcomas, and undifferentiated sarcomas, suggesting either ambiguous morphologic findings or the possibility of a common histogenesis from smooth muscle trabeculae or a distinct population of splenic myofibroblasts. The biological behavior of all tumors examined could be placed into three categories of patient survival: (1) benign, noninvasive tumors (leiomyoma, lipoma) with prolonged survival intervals; (2) malignant tumors (fibrosarcoma, undifferentiated sarcoma, leiomyosarcoma, osteosarcoma, myxosarcoma, histiocytic sarcoma, and liposarcoma), showing severely truncated survival (median 4 months with 80-100% mortality after 12 months; and (3) intermediate survival periods (median 12 months with 50% 1 year survival) attributed to a single group of neoplasm, the mesenchymomas. The biological behavior of primary splenic nonangiomatous, nonlymphomatous sarcomas was most closely correlated with observed mitotic index. Splenic neoplasms of this type with a mitotic index < 9 showed significantly (P < 0.0001) longer survival intervals than those with an index > 9. With the exception of osteosarcoma, all anatomically defined tumor groups contained one or more specimens with a mitotic index < 9. The clinical prognosis given for splenic sarcomas should be modified according to the mitotic index as a predictive value for patient survival.

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)

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.

A retrospective clinicopathologic study of 212 dogs with cutaneous hemangiomas and hemangiosarcomas.

The relationship between skin pigmentation and piliation and the development of hemangiomas and hemangiosarcomas in the dermis and subcutaneous tissue was studied in 212 dogs. These 212 dogs had a combined total of 306 tumors; 38 of these 212 dogs had two or more of the same tumor in a different location or a combination of hemangioma and hemangiosarcoma. The average age of the dogs at the time of excision of these tumors was greater than 10 years. There was no sex predilection for the presence or absence of tumors. Cutaneous hemangiomas (73%) were more common than cutaneous hemangiosarcomas (27%). Hemangiomas had no predilection for dermis (51%) or subcutaneous tissue (47%), but hemangiosarcomas had a marked predilection for dermis (73%) over subcutaneous tissue (7%). Dogs with short hair coats and lightly pigmented skin had more hemangiomas and hemangiosarcomas of the dermis (65%) than did dogs with variable length hair coats and pigmentation (28%). Dogs with short hair coats and lightly pigmented skin had fewer hemangiomas and hemangiosarcomas of the subcutaneous tissue (10%) than did dogs with variable length hair coats and pigmentation (22%). Dogs with short hair coats and lightly pigmented skin also had more hemangiomas and hemangiosarcomas of ventral glabrous skin (65%) than did dogs with variable length hair coats and pigmentation (22%). In addition, there was no predilection of subcutaneous hemangiosarcoma for haired (33%) versus glabrous (33%) skin, but dermal hemangiosarcoma had a marked predilection for the glabrous skin (63%) when compared with haired skin (10%). The increased incidence of dermal hemangiomas and hemangiosarcomas in ventral glabrous skin suggests an association between solar radiation and the biologic properties of glabrous skin in the genesis of these tumors.

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.

Pancreatic response in rats and mice to trypsin inhibitors from soy and potato after short- and long-term dietary exposure.

The effects on the pancreas of chronic (95 wk) dietary exposure to protease inhibitors from soy and potato were compared in rats and mice. Soy and potato trypsin inhibitor (TI) concentrates were prepared from defatted raw soy flour and potato juice, respectively, by selective precipitation and ultrafiltration. Animals were fed a diet in which casein supplied approximately 20% protein. Each concentrate (less than 1% of the diet) was added to provide 100 and 200 mg of trypsin inhibitor activity per 100 g of diet. In short-term (28 d) experiments in rats, both sources of TI decreased the apparent nutritional quality of casein and produced pancreatic hypertrophy consistent with a hormonally mediated feedback mechanism for pancreatic adaptation to diet that is interactive with the nutritional status of the animal. After long-term feeding (95 wk), soy and potato TI produced dose-related pancreatic pathology in rats consisting of nodular hyperplasia and acinar adenoma, which was typical of that associated with raw soy flour. Although mice responded similarly to rats to soy TI in short-term (28-d) feeding experiments, they were resistant to the formation of these lesions following long-term feeding. This considerable species variation in propensity to develop preneoplastic and neoplastic lesions of the pancreas is not predicted by the short-term hypertrophic and hyperplastic response of the pancreas to TI.