Correlation between cytologic and histopathologic diagnoses of bone lesions in dogs: a study of the diagnostic accuracy of bone cytology

Background: The diagnostic value of cytology compared with histopathology varies by tissue, but there is little information regarding this comparison involving canine bone. Objectives: The objective of this retrospective study was to compare primary pathologic processes for cytology and histopathology of canine bone lesions. We adopted a proposed standardized format for reporting studies of diagnostic accuracy. Methods: A computer search of canine medical records at the University of Minnesota Veterinary Medical Center from September 2002 through October 2006 identified 52 bone cytology samples that had incisional (IncB) and/or excisional (ExcB) biopsy performed. The primary pathologic process was determined by evaluation of original reports. Cytologic vs IncB and cytologic vs ExcB were compared pairwise for agreement. Agreement was compared for neoplastic and non-neoplastic processes using the combined IncB/ExcB data, which included all ExcB (n=21) and IncB when that was the only biopsy available (n=31). Combined data were used to determine the effect of cytology cellularity on the diagnostic correlation. Results: The correlation in primary process between cytology and IncB was 71%, and for ExcB was 71%. For lesions with a cytologic diagnosis of neoplasia compared with the combined IncB/ExcB data set, cytology and histopathology agreed in 92% of cases, which was significantly greater (P<.0001, chi(2)) than the 27% for non-neoplastic processes. Cytology cellularity significantly affected rates of correlation (P=.026), with high, moderate, and poor cellularity samples having concordant primary processes in 88%, 77%, and 47% of cases, respectively. Conclusions: Cytologic diagnosis of neoplasia for samples collected from canine bone correlates better with histopathology than cytologic diagnosis of non-neoplastic proliferative processes or inflammation. Cytologic diagnoses from highly cellular samples are more likely to correlate with histopathology than those from less cellular samples.     

Evaluation of brush cytology in the diagnosis of chronic intranasal disease in cats

Brush cytology was used as a diagnostic aid in 85 cats affected with chronic intranasal disease. Fifty-three of these cases, sampled over a five-year period, were included in this study, while the other cases were excluded due to poor cellularity of the cytological samples (nine cases) or a lack of histological or follow-up data (23 cases). Thirty-six brush samples were classified by cytology as inflammatory. Subsequent histological examination revealed a false negative diagnosis of neoplasia in six cats, two of which had malignant tumours (one adenocarcinoma and one lymphoma), the remaining four having benign tumours (two adenomas and two osteochondromas). Seventeen samples were classified by brush cytology as neoplastic. This was confirmed in 16 of these cases by histology or follow-up (nine epithelial malignant tumours, six lymphomas and one osteosarcoma). In the remaining case, a false positive diagnosis of lymphoma was made. The procedure had an overall 86.8 per cent (46/53) agreement between the diagnosis of inflammatory conditions versus neoplasia, with a sensitivity of 72.7 per cent, a specificity of 96.8 per cent, a predictive value of a positive test of 94.1 per cent and a predictive value of a negative test of 83.3 per cent.     

Imprint and brush cytology in the diagnosis of canine intranasal tumours

Fifty-four dogs with nasal tumours were included in this study. Based on histopathology, 52 tumours were malignant (36 epithelial and 16 mesenchymal) and two were benign (one oncocytoma and one pleiomorphic adenoma). Malignancy was significantly more frequently diagnosed by imprint cytology (81 per cent of the cases) than by brush cytology (56 per cent). Brush cytology was a significantly more sensitive technique in epithelial than in mesenchymal tumours, while the sensitivity of imprint cytology was not affected by the histological type. Brush cytology determined an epithelial origin in 88 per cent of epithelial tumours, and imprint cytology in 90 per cent. In mesenchymal tumours, the scores were significantly lower, the histological type being determined in only 20 per cent and 50 per cent, using brush and imprint cytology, respectively.     

Performance of 2 microtiter canine Coombs' tests

BACKGROUND: The Coombs' test, which detects immunoglobulin or complement on RBC surfaces, has long been the standard for laboratory confirmation of immune-mediated hemolytic anemia (IMHA), a common cause of hemolytic anemia in the dog. This test, however, suffers from relatively low sensitivity. Optimization of test sensitivity would lead to fewer discrepancies between laboratory results and clinical diagnoses, and in some cases institution of appropriate therapy in a timely manner. OBJECTIVES: The objectives of this study were to 1) characterize the sensitivity and specificity of 2 canine Coombs' tests for the detection of IMHA, 2) document the efficacy of using multiple antisera dilutions beyond what is directed by manufacturers, and 3) evaluate the necessity of monovalent antisera in the test protocol. METHODS: Sixty-five canine whole-blood samples submitted for Coombs' testing were evaluated. Patients were classified as IMHA positive or negative based on a set of predetermined criteria. IMHA classification was compared to Coombs' test results from 2 different Coombs' tests adapted to a microtiter-plate format. One Coombs' test (VMRD Coombs' test) utilized a single polyvalent antiserum (VMRD, Inc, Pullman, WA, USA), while a second Coombs' test (University of Minnesota [U of MN] Coombs' test) used both polyvalent and monovalent antisera. RESULTS: Sensitivity and specificity were 61% and 100% for the VMRD Coombs' test, and 82% and 95% for the U of MN Coombs' test. The use of multiple antisera dilutions resulted in 6 additional Coombs' positive test results. All positive Coombs' test results were positive by polyvalent antisera. CONCLUSIONS: When used in a microtiter-plate format, the U of MN Coombs' test was a more sensitive test for the detection of IMHA in canine patients when compared to the VMRD Coombs' test. The use of multiple antisera dilutions increased test sensitivity. Sensitivity, however, was not increased by the use of monovalent antisera in the Coombs' test protocol.     

Cytologic evaluation of inflammation in canine liver aspirates

Abstract: Liver aspiration cytology has been used routinely for more than a decade for the evaluation of canine and feline liver disease. However, the value of liver cytology in detecting inflammatory liver disease is poorly defined. We retrospectively reviewed 51 canine liver cytology reports and compared the conclusions with those from concurrent surgical biopsy reports. Overall sensitivity of cytology for diagnosis of inflammatory liver disease was 93% and specificity was 96%. For suppurative hepatitis (n = 14), the sensitivity of cytologic diagnosis was 100% and the specificity was 95%. For chronic active hepatitis (n = 13), the sensitivity of cytologic diagnosis was 100% and the specificity was 93%. For lymphocytic hepatitis (n = 3), the sensitivity of cytologic diagnosis was 33% and the specificity was 100%. We conclude that canine liver aspiration cytology is a highly sensitive test for the detection of suppurative and chronic active inflammation; however, it is insensitive for the detection of lymphocytic hepatitis.     

Cytologic examination of fine‐needle aspirates from mammary gland tumors in the dog: diagnostic accuracy with comparison to histopathology and association with postoperative outcome

Background: Mammary tumors are the most common neoplasms in female dogs. Malignant tumors may carry a poor prognosis and necessitate surgery. Few data are available on the value of cytologic examination as a diagnostic or prognostic tool for mammary tumors in dogs. Objectives: The objectives of this study were to determine whether cytologic findings in fine‐needle aspirate specimens of canine mammary tumors correlate with histopathologic results and whether the cytologic diagnosis is associated with postoperative outcome. Methods: In this prospective study, fine‐needle aspirate samples were obtained from 50 mammary tumors in 50 dogs. Results of cytologic and histopathologic examination were compared, using the histologic diagnosis as the reference method. Kaplan–Meier log rank analysis was used to evaluate univariate association of the cytologic diagnosis with duration of survival, local control, and metastasis‐free interval. Results: Adequate cytologic samples were obtained in 43/50 (86%) cases. The cytologic diagnosis correlated with the histologic diagnosis for benign and malignant tumors in 40/43 (93%) and 35/43 (81%) cases, respectively. Cytologic examination had a sensitivity of 88% and a specificity of 96% for the diagnosis of malignancy. The cytologic diagnosis had significant univariate association with duration of survival (P=.016), recurrence‐free interval (P=.003), and metastasis‐free interval (P=.014). Conclusions: Cytologic examination of mammary tumors in the dog has satisfactory accuracy, sensitivity, and specificity for the diagnosis of malignancy and is associated with postoperative outcome. Further studies on the diagnostic accuracy of cytology as well as multivariate analysis of its preoperative prognostic value in mammary tumors in the dog are warranted.     

MRI characteristics of canine prostatic neoplasia

Magnetic resonance imaging (MRI) has been used to evaluate dogs with suspected prostatic neoplasia, however, published studies describing MRI characteristics of canine prostatic neoplasia are currently lacking. The aims of the current retrospective case series study were to describe MRI findings of the pelvic region in dogs with a histopathologic or cytologic diagnosis of prostatic neoplasia. Retrospective analysis of these images was then performed by a board-certified veterinary radiologist for shared imaging characteristics. The most consistent characteristics were heterogeneous hyperintensity of the tumor on T2-weighted images (10/10) and short tau inversion recovery images (10/10), prostatic capsular margin distortion by the tumor (10/10), cavitations (10/10), complete effacement of the prostatic architecture (9/10), neurovascular bundle (NVB) compression or invasion (9/10), heterogeneous isointensity of the tumor on T1-weighted images (9/10), and strong contrast enhancement of the tumor (8/10). Additional features included an overlying pattern of distorted radiating striations (7/10), regional lymphadenomegaly (5/10), mineralization within the mass (5/10), urinary bladder trigone involvement (6/10), and post-prostatic urethral involvement (7/10). These findings supported the use of MRI as an adjunct imaging modality for diagnosis and therapeutic planning of prostatic neoplasia and including prostatic neoplasia as a likely differential diagnosis for dogs with these MRI characteristics.     

Clinical findings, rhinoscopy and histological evaluation of 54 dogs with chronic nasal disease

Nasal diseases are very common in dogs and rhinoscopy is often required for a definitive diagnosis. Rhinoscopy, while superficial in nature, can guide the clinician to the final diagnosis. In this study, rhinoscopy was performed on 54 dogs with symptoms of chronic nasopharyngeal disease. The endoscopic diagnosis of neoplasia or chronic nasal inflammation was validated with histological examination of pathological samples, in order to evaluate the degree of concordance between endoscopic findings and histological diagnosis. The agreement between endoscopy and histology was tested by application of Cohen''s kappa coefficient. We conclude that correlation between endoscopic results and histological diagnosis, expressed by a Cohen''s kappa coefficient of 0.73, is only possible with a constant cooperation between the clinician and the pathologist.     

Efficacy of stereotactic radiation therapy for the treatment of confirmed or presumed canine glioma

Intracranial gliomas are the second most common brain tumour in dogs. Radiation therapy provides a minimally invasive treatment option for this tumour type. Earlier publications reporting on the use of non-modulated radiation therapy suggested a poor prognosis for dogs with glioma, with median survival times ranging between 4 and 6 months; more recent literature utilizing stereotactic radiation therapy (SRT) demonstrates that the prognosis for canine gliomas may be more promising, with survival times closer to 12 months. A single institution retrospective study was performed between 2010 and 2020 investigating the outcomes of dogs with biopsy-confirmed glioma or a presumptive diagnosis of intra-cranial glioma based on MRI characteristics that were treated with SRT. Twenty-three client-owned dogs were included. Brachycephalic breeds were overrepresented, totalling 13 dogs (57%). SRT protocols included 16 Gy single fraction (n = 1, 4%), 18 Gy single fraction (n = 1, 4%), 24 Gy in 3 daily fractions (n = 20, 91%), or 27 Gy in four daily fractions (n = 1, 4%). Twenty-one dogs (91%) had improvement of their presenting clinical signs following SRT. Median overall survival time (MST) was 349 days (95% CI, 162–584). Median disease specific survival time was 413 days (95% CI, 217–717). When SRT is incorporated into the management plan for dogs with confirmed or presumed intracranial glioma, a median survival time of approximately 12 months may be achievable.     

Immunocytochemical study of Ki-67 as a prognostic marker in canine mammary neoplasia

Background: Canine mammary tumors are challenging for clinicians and pathologists because of complex histologic classification, low specificity of cytologic diagnosis, and unpredictable biological behavior. In histologic specimens, expression of tumor proliferation marker Ki‐67, a nuclear nonhistone protein, has been shown to have prognostic value for canine mammary tumors and to correlate with malignancy and low survival rates. Objective: The objective of this study was to measure the proliferation index of canine mammary tumors by immunochemical detection of Ki‐67 in cytologic specimens and to determine its relationship to clinical and pathologic variables and patient outcome. Methods: Spontaneous mammary tumors from 31 female dogs were surgically excised. Imprint specimens for cytologic evaluation were wet‐fixed in ethanol; histologic specimens were prepared routinely. Immunostaining was performed with the PH 177 monoclonal antibody against Ki‐67; proliferation index was graded from negative to +++. Dogs were followed for 18 months. Multivariate logistic regression analysis was used to determine correlations between immunocytochemical results, tumor and clinical variables, and patient outcome. Results: Ki‐67 proliferation indices in cytologic specimens were significantly lower for nonmalignant tumors than for malignant tumors. High index values of Ki‐67 were positively correlated with metastasis, death from neoplasia, low disease‐free survival rates, and low overall survival rate. With the exception of 4 specimens for which cellularity was insufficient, positive expression of Ki‐67 in cytologic specimens correlated with that of histologic specimens. Conclusions: The prognostic value of the Ki‐67 index in canine mammary tumors by using wet‐fixed cytology imprint specimens was similar to that observed previously for histologic specimens. Immunocytochemical detection of Ki‐67 could improve the accuracy and value of cytology by providing safe and rapid information about malignancy and patient outcome.     

Expression of E‐cadherin in canine anal sac gland carcinoma and its association with survival*

The objective of this study was to determine whether an association could be demonstrated between survival and the expression of the adhesion molecule E‐cadherin by the neoplastic cells in a group of dogs with anal sac gland carcinomas (ASGCs). Archived formalin‐fixed, paraffin wax‐embedded primary tumour specimens were obtained for 36 cases of canine ASGC with known clinical management and survival data. Immunohistochemical methods were used to evaluate E‐cadherin expression by the neoplastic cells and data were evaluated for an association between E‐cadherin expression and survival. On univariate analysis, the median survival time for cases with tumours expressing E‐cadherin in more than 75% of cells was significantly greater than that for cases with tumours expressing E‐cadherin in fewer than 75% of cells (1168 versus 448 days, P = 0.0246). Both E‐cadherin expression and presence or absence of distant metastases were significantly associated with survival on multivariate analysis. This study demonstrates that expression of E‐cadherin at the cytoplasmic membrane in canine ASGCs is variable and potentially predictive of survival.     

Histopathological retrospective study of canine renal disease in Korea, 2003~2008

Renal disease includes conditions affecting the glomeruli, tubules, interstitium, pelvis, and vasculature. Diseases of the kidney include glomerular diseases, diseases of the tubules and interstitium, diseases of renal pelvis, and developmental abnormalities. Renal tissue samples (n = 70) submitted to the Department of Veterinary Pathology of Konkuk University from 2003 to 2008 were included in this study. Tissue histopathology was performed using light microscopy with hematoxylin and eosin stains. Masson''s trichrome, Congo Red, and Warthin starry silver staining were applied in several individual cases. Glomerular diseases (22.9%), tubulointerstitial diseases (8.6%), neoplastic diseases (8.6%), conditions secondary to urinary obstruction (24.3%), and other diseases (35.7%) were identified. Glomerulonephritis (GN) cases were classified as acute proliferative GN (5.7%), membranous GN (4.3%), membranoproliferative GN (4.3%), focal segmental GN (2.9%), and other GN (4.2%). The proportion of canine GN cases presently identified was not as high as the proportions identified in human studies. Conversely, urinary obstruction and end-stage renal disease cases were relatively higher in dogs than in human populations.     

Major histocompatibility class II expression in the normal canine cornea and in canine chronic superficial keratitis

OBJECTIVE: To compare the expression of major histocompatibility complex (MHC) class II antigen in the corneas of normal dogs and dogs affected with chronic superficial keratitis (CSK). METHODS: MHC class II expression was determined in frozen sections of normal canine cornea and cornea from lesions of CSK by immunohistochemistry using a monoclonal antibody directed against the canine MHC class II molecule. Langerhans cell phenotype was determined morphologically and by histochemical determination of ATPase activity. To determine the influence of gamma interferon on expression of MHC class II molecules by corneal cells, corneal explants were cultured with the cytokine and MHC class II expression determined as above. RESULTS: Numerous MHC class II-expressing cells were demonstrated within the stroma and epithelium of the normal corneal limbus and conjunctival epithelium while very little MHC class II expression was detected in the central region of normal canine cornea. In limbal and conjunctival epithelium, cells expressing MHC class II antigen showed ATPase activity, suggesting that they were Langerhans cells. Corneas from dogs with CSK showed MHC class II expression associated with stromal cells, some of which exhibited a dendritic morphology while most were lymphocytic. Corneal epithelial cells within the lesion also aberrantly expressed MHC class II. Corneal explants expressed MHC class II to varying degrees after differing periods of incubation with the cytokine gamma interferon. CONCLUSIONS: While the normal central cornea has little MHC class II expression, aberrant expression occurs in CSK, associated with secretion of gamma interferon by infiltrating CD4-expressing lymphocytes. Although this change is likely to be a secondary feature of the CSK lesion, increased MHC class II expression may play a part in perpetuating the corneal inflammation seen in the disease.     

Blood–brain‐barrier disruption in chronic canine hypothyroidism

Background: Central nervous system (CNS) manifestations of hypothyroidism have been associated with cerebrovascular complications. Reports of cerebrospinal fluid (CSF) abnormalities are rare in hypothyroid dogs. Objective: The aim of this study was to determine if chronic hypothyroidism causes blood–brain‐barrier (BBB) abnormalities that are detectable using indirect CSF biomarkers. Methods: The study included 18 normal, euthyroid, female mixed‐breed dogs. Hypothyroidism was induced by ¹³¹iodine administration in 9 dogs; 9 served as untreated controls. Evaluations included physical and neurologic examination, complete CSF analysis, serum and CSF protein electrophoresis, measurement of plasma vascular endothelial growth factor (VEGF) and serum S‐100B concentrations, and calculation of CSF albumin quota (AQ) and were conducted at baseline and 6, 12, and 18 months after induction of hypothyroidism. Data were analyzed using repeated measures ANOVA. Results: At baseline, differences between groups were not detected for any variable. Throughout the study, controls dogs remained free of neurologic disease and had test variables that remained within reference intervals. Two hypothyroid dogs developed CNS signs during the study, and evidence of cerebrovascular disease was found at necropsy. At 12 and 18 months, the CSF total protein, VEGF, S‐100B, and fractional albumin concentrations, and AQ were significantly higher (P<.04) in hypothyroid dogs than controls. Among test variables assayed in serum or plasma, the only significant difference was a higher S‐100B concentration in hypothyroid dogs (P=.003) at 18 months. Conclusions: BBB integrity is disrupted in chronic hypothyroidism. Significant increases in CSF concentrations of VEGF and S100‐B in hypothyroid dogs indicate dysfunction in both endothelial and glial elements of the BBB.     

Squash-prep cytology in the diagnosis of canine and feline nervous system lesions: a study of 42 cases

BACKGROUND: The increased sophistication of imaging techniques in veterinary medicine allows the detection of a wide variety of intracranial and intraspinal lesions; however, imaging often does not provide a definitive diagnosis for nervous system (NS) lesions. Cytology is emerging as a useful diagnostic tool for obtaining a fast and accurate assessment of NS lesions, but little information is available for dogs and cats. OBJECTIVES: The purpose of this study was to assess the accuracy of cytologic evaluation of squash samples from NS lesions in dogs and cats and to consider cytology-based diagnostic guidelines and sources of misdiagnosis. METHODS: Cytologic specimens from masses localized in the central and peripheral NS taken during surgery or postmortem examination were classified into 3 groups according to the final histopathologic diagnosis: Group 1 = completely correct diagnosis, when the cytologic diagnosis and final histologic diagnosis were exactly correlated; Group 2 = partial correlation, when the cytologic diagnosis only partially correlated with the final histologic diagnosis, and Group 3 = no correlation, when the cytologic diagnosis was incorrect and there was no correlation with the general histologic type of lesion. The diagnostic accuracy of cytopathology was calculated by considering the histopathologic diagnosis as the "gold standard," and calculating a 95% confidence interval (CI). RESULTS: A total of 42 animals (33 dogs and 9 cats) were included in the study. The cytologic diagnoses were classified in Group 1 for 32 cases (76%; 95% CI 0.63-0.89), in Group 2 for 6 cases (14%; 95% CI 0.04-0.25), and in Group 3 for 4 cases (10%; 95% CI 0.006-0.18). Considering both complete and partial correlation as an adequate result, cytologic diagnosis was satisfactory in 90% of biopsies. CONCLUSIONS: Although the current series of cases is relatively small, cytologic evaluation of squash preparations can be considered a fairly accurate and reliable tool in the diagnosis of NS lesions.