Measurement of Feline Alpha-1 Acid Glycoprotein in Serum and Effusion Using an ELISA Method: Analytical Validation and Diagnostic Role for Feline Infectious Peritonitis.

BACKGROUND: Alpha-1 acid glycoprotein (AGP) may support a clinical diagnosis of feline infectious peritonitis (FIP). In this study, we assessed the analytical and diagnostic performances of a novel ELISA method to measure feline AGP. METHODS: AGP was measured in sera and effusions from cats with FIP (n = 20) or with other diseases (n = 15). Precision was calculated based on the coefficient of variation (CV) of repeated testing, and accuracy was calculated by linearity under dilution (LUD). RESULTS: The test is precise (intra-assay CVs: <6.0% in individual samples, <15.0% in pooled samples; inter-assay CVs <11.0% and <15.0%) and accurate (serum LUD r2: 0.995; effusion LUD r2: 0.950) in serum and in effusions. AGP is higher in cats with FIP than in other cats in both serum (median: 1968, I-III interquartile range: 1216-3371 µg/mL and 296, 246-1963 µg/mL; p = 0.009) and effusion (1717, 1011-2379 µg/mL and 233, 165-566 µg/mL; p < 0.001). AGP discriminates FIP from other diseases (area under the receiver operating characteristic curve: serum, 0.760; effusion, 0.877), and its likelihood ratio is high (serum: 8.50 if AGP > 1590 µg/mL; effusion: 3.75 if AGP > 3780 µg/mL). CONCLUSION: This ELISA method is precise and accurate. AGP in serum and in effusions is a useful diagnostic marker for FIP.

Subcutaneous mast cell tumours: A prospective multi-institutional clinicopathological and prognostic study of 43 dogs.

BACKGROUND: Canine subcutaneous mast cell tumours (ScMCTs) reportedly have a good prognosis. However, biomarkers that can be used to predict outcome are currently limited. METHODS: A multicentre prospective study was conducted to identify new prognostic markers. Dogs with a first occurrence of ScMCT were enrolled upon primary tumour removal and regional lymphadenectomy. In the absence of metastasis, dogs were monitored, while dogs with overtly metastatic lymph nodes (histological node 3, HN3) received adjuvant vinblastine. RESULTS: Forty-three dogs were enrolled: 15 (34.9%) had at least one HN3 lymph node and received vinblastine, and 28 (65.1%) were monitored. Three tumours harboured exon 8 and 9 c-kit mutations. Eight (18.6%) dogs experienced tumour progression, and five (11.6%) died of MCT-related causes. The 1- and 2-year survival rates were 90% and 77%, respectively. Variables significantly associated with an increased risk of progression included high cytograde, a mitotic count (MC) greater than 4/10 high-power fields (hpf) and Ki67-index greater than 23. An MC greater than 4/10 hpf was also associated with an increased risk of tumour-related death. LIMITATIONS: Regional rather than sentinel lymphadenectomy was performed in these dogs. Dogs were enrolled in oncology referral centres, constituting a different population compared to previous studies. CONCLUSIONS: ScMCTs have a good prognosis. However, the metastatic rate at admission was higher in this study than previously reported, and a subset of tumours were associated with a fatal outcome despite multimodal treatment. Proliferative activity and cytograding may predict more aggressive behaviour in ScMCTs.

Utility of the Ratio between Lactate Dehydrogenase (LDH) Activity and Total Nucleated Cell Counts in Effusions (LDH/TNCC Ratio) for the Diagnosis of Feline Infectious Peritonitis (FIP).

BACKGROUND: We tested the hypothesis that the ratio between lactate dehydrogenase activity (LDH) and total nucleated cell counts (TNCC) in effusions may be useful to diagnose feline infectious peritonitis (FIP). METHODS: LDH/TNCC ratio was retrospectively evaluated in 648 effusions grouped based on cytology and physicochemical analysis (step 1), on the probability of FIP estimated by additional tests on fluids (step 2) or on other biological samples (step 3, n = 471). Results of different steps were statistically compared. Receiver Operating Characteristic (ROC) curves were designed to assess whether the ratio identify the samples with FIP "probable/almost confirmed". The cut-offs with the highest positive likelihood ratio (LR+) or Youden Index (YI) or with equal sensitivity and specificity were determined. RESULTS: A high median LDH/TNCC ratio was found in FIP effusions (step1: 2.01) and with probable or almost confirmed FIP (step 2: 1.99; 2.20 respectively; step 3: 1.26; 2.30 respectively). The optimal cut-offs were 7.54 (LR+ 6.58), 0.62 (IY 0.67, sensitivity: 89.1%; specificity 77.7%), 0.72 (sensitivity and specificity: 79.2%) in step 2 and 2.27 (LR+ 10.39), 0.62 (IY 0.65, sensitivity: 82.1%; specificity 83.0%), 0.54 (sensitivity: 82.1%; specificity 81.9%) in step 3. CONCLUSIONS: a high LDH/TNCC ratio support a FIP diagnosis.

Usefulness of squash preparation cytology in the diagnosis of canine urinary bladder carcinomas.

BACKGROUND: Epithelial cells show varying degrees of cytologic atypia in dogs with nonmalignant lesions (NML) and carcinomas (ubC) of the bladder, making histopathologic examination necessary for a definitive diagnosis. OBJECTIVES: This study aimed to investigate the diagnostic performance of squash preparation cytology and identify several cytomorphologic features of ubC to assist in diagnoses. METHODS: Squash preparations were made and reviewed in dogs that underwent transurethral cystoscopy. The results were compared with histopathologic diagnoses. Two cytopathologists performed blinded assessments using a scoring system established for 11 cytologic features, including the presence of macronuclei, abnormal nucleoli, atypical mitoses, signet ring cells, multinucleated cells, nuclear molding, anisokaryosis, cytoplasmatic microvacuolization, cell arrangements, and neutrophil and lymphocyte infiltrations. Based on cytologic and histopathologic diagnoses, dogs were divided into ubC and NML groups. Associations between cytologic and histopathologic diagnoses were investigated, and agreement between the cytopathologists was calculated. Cytologic features were analyzed with multivariate logistic regression models. The performance of predictors in the final model was evaluated in terms of Sensitivity (Se), Specificity (Sp), accuracy, positive predictive value (PPV), negative predictive value (NPV), likelihood ratio positive (LR+), and negative (LR-) values, and the diagnostic odds ratio (DOR). RESULTS: Forty-four dogs diagnosed with ubC, and 17 with NML were included in the study. Cytologic and histopathologic diagnoses were significantly associated with each cytopathologist. There was an almost perfect agreement between cytopathologists (κ = 0.88). The absence of neutrophilic infiltration, the presence of multinucleated cells, and nuclear molding were associated with ubC; using a combination of these features in parallel testing resulted in Se = 0.98, Sp = 0.65, accuracy = 0.89, PPV = 0.88, NPV = 0.92, LR + =2.77, LR- = 0.04, and DOR = 7.7. CONCLUSIONS: Squash preparation cytology could be a reliable technique to diagnose ubC in dogs. The best diagnostic combination was the absence of neutrophilic infiltration, multinucleated cells, and nuclear molding.

Extravascular papillary endothelial hyperplasia mimicking soft tissue sarcoma in 2 cats: a potential diagnostic pitfall.

Papillary endothelial hyperplasia (PEH) is a rare soft tissue lesion arising from excessive reactive endothelial cell proliferation described in humans, dogs, and horses. PEH is considered a diagnostic challenge in humans, in which it is frequently misdiagnosed as angiosarcoma. We describe here PEH that developed at injection sites in 2 cats that were initially misdiagnosed as feline injection-site sarcoma by cytology and as subcutaneous angiosarcoma by histopathology. Morphologic features included sharp demarcation from surrounding tissues, and a layered microscopic architecture with an outer fibrous capsule from which emerged fibrovascular stalks covered by a monolayer of factor VIII-related antigen and CD31-positive flat-to-plump endothelial cells. Both lesions had a cystic core containing abundant erythrocytes and fibrin. PEH lesions did not recur in either case. Immunohistochemistry for α-smooth muscle actin and desmin demonstrated that the capsule was devoid of smooth muscle cells, excluding an intravascular origin. PEH in these cats was hypothesized to have developed extravascularly following trauma related to injection. We wish to provide awareness of PEH in domestic cats and of the risk of misdiagnoses leading to overtreatment.

Performance of lymph node cytopathology in diagnosis and characterization of lymphoma in dogs.

BACKGROUND: Cytopathology is a minimally invasive and convenient diagnostic procedure, often used as a substitute for histopathology to diagnose and characterize lymphoma in dogs. OBJECTIVES: Assess the diagnostic performance of cytopathology in diagnosing lymphoma and its histopathological subtypes in dogs. ANIMALS: One-hundred and sixty-one lymph node samples from 139 dogs with enlarged peripheral lymph nodes. METHODS: Based only on cytopathology, 6 examiners independently provided the following interpretations on each sample: (a) lymphoma vs nonlymphoma; (b) grade and phenotype; and (c) World Health Organization (WHO) histopathological subtype. Histopathology and immunohistochemistry (IHC) findings were used as reference standards to evaluate diagnostic performance of cytopathology. Clinical, clinicopathologic, and imaging data also were considered in the definitive diagnosis. RESULTS: Classification accuracy for lymphoma consistently was >80% for all examiners, whereas it was >60% for low grade T-cell lymphomas, >30% for high grade B-cell lymphomas, >20% for high grade T-cell lymphomas, and <40% for low grade B-cell lymphomas. Interobserver agreement evaluated by kappa scores was 0.55 and 0.32 for identification of lymphoma cases, and of grade plus immunophenotype, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: Cytopathology may result in accurate diagnosis of lymphoma, but accuracy decreases when further characterization is needed. Cytopathology represents a fundamental aid in identifying lymphoma and can be used as a screening test to predict grade and phenotype. However, these results must be confirmed using other ancillary techniques, including flow cytometry, histopathology, and immunohistochemistry (IHC).

A retrospective study on prophylactic regional lymphadenectomy versus nodal observation only in the management of dogs with stage I, completely resected, low-grade cutaneous mast cell tumors.

BACKGROUND: While lymphadenectomy of metastatic lymph nodes (LNs) has been associated with improved outcome, the clinical utility of prophylactic lymphadenectomy in dogs with stage I cutaneous mast cell tumors (cMCTs) remains a controversial topic. To assess the therapeutic role of lymphadenectomy of uninvolved regional LNs, the long-term outcome of cMCT-bearing dogs with cytologically negative and surgically unresected regional LNs (observation only, OO) was compared with that of dogs with surgically resected and histologically negative regional LNs (prophylactic regional lymphadenectomy, PRL). RESULTS: A retrospective analysis of 64 dogs with a low-grade, completely resected stage I cMCT was performed: 35 (54.7%) dogs were subjected to OO and 29 (45.3%) underwent PRL. Dogs were monitored for a median of 813 and 763 days in the OO group and PRL group, respectively. The number of dogs undergoing MCT progression was significantly higher in the OO group (P = 0.028) and curve comparison revealed a tendency to a better time to progression in the PRL group (P = 0.058). No significant difference in survival time (P = 0.294) was observed between dogs in the OO and PRL groups. CONCLUSIONS: Our results showed that lack of immediate lymphadenectomy was associated with a higher risk for tumor progression. This preliminary judgement, reinforced by the findings that lymphadenectomy was well tolerated in all cases, and that histopathology provides the definitive assessment of the nodal pathological status, may suggest that prophylactic lymphadenectomy is indicated in the management of stage I MCTs. Larger prospective studies are warranted for generating clinical evidence of this latter hypothesis.

Molecular characterization of Prototheca in 11 symptomatic dogs.

Protothecosis is an uncommon disease caused by algae of the genus Prototheca. In dogs, the infection is usually first localized to the colon but has the propensity to later disseminate hematogenously to many other organs, with marked tropism for the eyes and central nervous system. Diagnosis is established by culture and/or evidence of Prototheca organisms in cytologic or histologic preparations. Species characterization, however, requires molecular investigations. Our laboratory set up a real-time PCR targeting portion D1/D2 of the 28S rRNA for identification of Prototheca species from both positive cultures (of rectal swabs and urine) and formalin-fixed, paraffin-embedded tissue. Prototheca bovis, P. ciferrii, and P. wickerhamii were characterized in 11 dogs with systemic or cutaneous protothecosis. Prototheca identifications were phylogenetically consistent with the new taxonomy proposed for this genus based on the mitochondrial cytochrome b gene. As a pilot study, we screened feces and rectal scrapes from 200 asymptomatic dogs, using 2 cohorts of stray and owned animals, to determine the prevalence of intestinal carriage of Prototheca spp. The Prototheca-negative results from both cohorts of healthy dogs suggest that predisposing factors related to the host probably contribute more to the acquisition of clinical disease than exposure to contaminated environments.

CD3-CD20-positive nodal lymphoma with cross-lineage rearrangement in a dog.

A 7-y-old mixed-breed male dog was presented with a history of generalized lymphadenopathy. Fine-needle aspirates of the enlarged peripheral lymph nodes were suggestive of lymphoma. Histologic examination of a retromandibular lymph node was suggestive of high-grade, medium large-cell lymphoma. Immunohistochemistry revealed concurrent expression of CD3 and CD20. The co-localization of the 2 antigens was confirmed by immunofluorescence. PCR for antigen receptor gene rearrangements (PARR) detected clonal rearrangements for both T-cell receptor gamma and B-cell receptor. The final diagnosis was CD3-CD20-positive anaplastic lymphoma with cross-lineage rearrangement.

Comparison of serum fructosamine and glycated hemoglobin values for assessment of glycemic control in dogs with diabetes mellitus.

OBJECTIVE: To evaluate the performance of 2 assays for measurement of serum fructosamine (SF) and glycated hemoglobin (HbA1c) values in dogs and to compare the usefulness of the 2 glycated proteins for assessment of glycemic control in dogs with diabetes mellitus (DM). SAMPLE: Blood samples from 40 healthy dogs, 13 diabetic dogs, and 23 anemic normoglycemic nondiabetic dogs and results of 200 assessments of glycemic control in 46 diabetic dogs. PROCEDURES: Colorimetric and immunoturbidimetric methods were used for measurement of SF and HbA1c values, respectively. Linearity and precision were determined. The usefulness of SF and HbA1c values for assessment of glycemic control was evaluated with a clinical scoring method used as the reference standard. Cutoff values obtained from receiver operating characteristic curves were used to identify the percentage of dogs correctly categorized by means of SF and HbA1c values. RESULTS: Mean intra-assay and interassay coefficients of variation were 3.8% and 2.5%, respectively, for the SF assay, and 1.2% and 1.8%, respectively, for the HbA1c assay. Excellent linearity (R2 > 0.99) was obtained for both assays. Values for SF and HbA1c were inversely correlated (r = -0.40 and -0.33, respectively) with clinical score and correctly indicated glycemic control in 99 of 200 (50%) and 88 of 200 (44%) assessments, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: The SF and HbA1c assays were precise, had good linearity, and appeared to be suitable for routine use in veterinary medicine. However, they performed poorly for classifying glycemic control in diabetic dogs.

Diagnostic Validation of a Whole-Slide Imaging Scanner in Cytological Samples: Diagnostic Accuracy and Comparison With Light Microscopy.

Digital slides created by whole-slide imaging scanners can be evaluated by pathologists located in remote sites, but the process must be validated before this technology can be applied to routine cytological diagnosis. The aim of this study was to validate a whole-slide imaging scanner for cytological samples. Sixty cytological samples, whose diagnoses were confirmed by gold-standard examinations (histology or flow cytometry), were digitalized using a whole-slide imaging scanner. Digital slides and glass slides were examined by 3 observers with different levels of cytopathological expertise. No significant differences were noted between digital and glass slides in regard to the number of cases correctly diagnosed, or the sensitivity, specificity, or diagnostic accuracy, irrespective of the observers' expertise. The agreements between the digital slides and the gold-standard examinations were moderate to substantial, while the agreements between the glass slides and the gold-standard examinations were substantial for all 3 observers. The intraobserver agreements between digital and glass slides were substantial to almost perfect. The interobserver agreements when evaluating digital slides were moderate between observers 1 and 2 and between observers 1 and 3 while they were substantial between observers 2 and 3. In conclusion, our study demonstrated that the digital slides produced by the whole-slide imaging scanner are adequate to diagnose cytological samples and are similar among clinical pathologists with differing levels of expertise.

Comparison of lente insulin and NPH insulin therapy for the treatment of newly diagnosed diabetic dogs: a randomised study.

Clinical studies that compare lente insulin and neutral protamine Hagedorn (NPH) insulin in diabetic dogs are lacking. This is a prospective, randomised, controlled clinical study aimed to compare the efficacy and safety of lente insulin and NPH insulin in diabetic dogs. Thirty client-owned, newly diagnosed diabetic dogs were included. Animals were randomised into two groups and received lente insulin or NPH insulin administered every 12 hours. Follow-up re-evaluations were done at 1, 2, 4, 6, 8 and 12 weeks. At each re-evaluation, a physical exam, blood glucose curve, and serum fructosamine concentrations were performed. At the end of the study, the median insulin dose per injection was 0.61 U/kg (range, 0.34-0.92 U/kg) and 0.49 U/kg (range, 0.23-0.68 U/kg) in the lente and NPH groups, respectively. There was a significant improvement of polyuria and polydipsia and glucose concentrations in both groups. At the end of the study, the glycaemic control was considered good in 9/15 (60 per cent) and 11/15 (73 per cent) in the lente and NPH groups, respectively. These differences were not significant. Lente insulin and NPH insulin were similarly effective in the treatment of dogs with diabetes mellitus.

Accuracy of cytology in distinguishing adrenocortical tumors from pheochromocytoma in companion animals.

BACKGROUND: The distinction between adrenocortical tumors and pheochromocytoma can be challenging using clinical findings, diagnostic imaging and laboratory tests. Cytology might be a simple, minimally invasive method to reach a correct diagnosis. OBJECTIVES: The purpose of this study was to assess the accuracy of cytology in differentiating cortical from medullary tumors of the adrenal glands in dogs and cats. METHODS: Cytologic key features of adrenocortical tumors and pheochromocytoma were defined by one reference author. Cytologic specimens from primary adrenal tumors were submitted to 4 cytopathologists who were asked to classify the tumors based on the previously defined key features without knowledge of previous classification. RESULTS: Twenty specimens from histologically confirmed adrenal tumors (Group 1) and 4 specimens from adrenal tumors causing adrenal-dependent Cushing's syndrome (Group 2) were evaluated by the 4 cytopathologists. Accuracy in differentiating cortical from medullary origin ranged from 90% to 100%, with a Kappa coefficient of agreement between cytopathologists of 0.95. CONCLUSIONS: The origin of an adrenal tumor can be easily determined by cytology alone in many cases. However, cytology was not reliable in distinguishing benign from malignant neoplasia. Additional studies are needed to assess possible risks and complications associated with fine-needle biopsy of adrenal tumors in dogs and cats.

Cation-leak stomatocytosis in standard schnauzers does not cosegregate with coding mutations in the RhAG, SLC4A1, or GLUT1 genes associated with human disease.

Autosomal dominant overhydrated cation-leak stomatocytosis in humans has been associated with missense mutations in the erythroid membrane transport genes AE1, RhAG, and GLUT1. Syndromic stomatocytosis has been reported in three dog breeds, but stomatocytosis in Standard Schnauzers is usually asymptomatic, and is accompanied by minimal if any anemia. We have extended the evaluation of a cohort of schnauzers. We found that low-level stomatocytosis was accompanied by increased MCV and increased red cell Na content, and minimal or no reticulocytosis. Red cells from two affected dogs exhibited increased currents in on-cell patches measured in symmetrical NaCl solutions, but Na,K-ATPase and NKCC-mediated cation flux was minimal. Three novel coding polymorphisms found in canine RhAG cDNA and three novel polymorphisms found in canine SLC4A1 cDNA did not cosegregate with MCV or Na content. The GLUT1 cDNA sequence was normal. We conclude that unlike human overhydrated cation-leak stomatocytosis, stomatocytosis in this cohort of Standard Schnauzers is not caused by mutations in the genes encoding RhAG, SLC4A1, or GLUT1.

Cytologic features and diagnostic accuracy of analysis of effusions for detection of ovarian carcinoma in dogs.

BACKGROUND: Presence of an abdominal effusion is a typical presenting sign associated with ovarian carcinoma (OC) in dogs. OBJECTIVES: The aims of this study were to describe the cytologic features of effusions associated with OC and to evaluate the diagnostic accuracy of such features for the diagnosis of OC in dogs. METHODS: Cytologic evaluations of 7 OC-associated peritoneal effusions in dogs were used to define cytomorphologic features of this neoplasm. Then, in a blinded study to evaluate the accuracy of these features in identifying OC, 2 independent board-certified clinical pathologists reviewed 82 pleural, pericardial, and abdominal effusions resulting from OC (n = 7), other neoplasms (n = 40), and non-neoplastic disorders (n = 35). The clinical pathologists were instructed to identify all samples containing papillary structures typically seen in OC and then apply the cytomorphologic criteria determined in the first part of the study to diagnose OC. RESULTS: Effusions associated with OC contained blood and had moderate to high cellularity, with neoplastic cells arranged in a prominent papillary pattern in which intercellular spaces were not clearly evident. Individual cells were approximately 30 µm in diameter, with mild anisocytosis and anisokaryosis, moderate amounts of pale blue cytoplasm, and round to oval paracentral nuclei with fine chromatin and poorly distinct small nucleoli. Using these cytologic features to identify OC in the 82 effusions, sensitivity was 86% and 100% and specificity was 57% and 97% for the 2 clinical pathologists. Overall accuracies in distinguishing OC from other effusions were 98.8% and 93.9%. CONCLUSION: Based on this preliminary study, effusion cytology from intact female dogs affected by OC appears to be useful in suggesting a diagnosis of neoplasia. The presence of cells with a prominent and uniform papillary pattern in peritoneal and pleural effusions in dogs with appropriate signalment and clinical signs should prompt a search for primary ovarian neoplasia.

Predictors of long-term survival in dogs with high-grade multicentric lymphoma.

OBJECTIVE: To determine factors predicting survival in dogs with high-grade multicentric lymphoma. Design-Retrospective cohort study. Animals-127 dogs with high-grade multicentric lymphoma evaluated at 4 veterinary hospitals from 2000 to 2009. PROCEDURES: Records were reviewed to identify dogs with completely staged high-grade multicentric lymphoma treated with chemotherapy. Data collected included signalment, history, hematologic findings, tumor characteristics, treatment, and outcome. Long-term survival was defined as surviving > 2 years after diagnosis. Variables were analyzed for associations with dogs living > 2 years. RESULTS: Among the 127 enrolled dogs, 13 (10%) survived > 2 years with a median survival time of 914 days (range, 740 to 2,058 days). Survival rates at 3, 4, and 5 years were 4%, 3%, and 1 %, respectively. At diagnosis, 11 of the 13 long-term survivors had a body weight ≥ 10 kg, PCV ≥ 35%, absence of ionized hypercalcemia, centroblastic lymphoma, immunophenotype B, absence of bone marrow involvement, and lymphoma stages I through IV and were not previously treated with corticosteroids. The same combination of factors was present in 26 of 114 (23%) dogs surviving ≤ 2 years, yielding a negative predictive value of 97.8% for long-term survivors. Four of the 6 long-term survivors that died during the study died of another cancer; 3 of them had osteosarcoma. CONCLUSIONS AND CLINICAL RELEVANCE: Absence of the aforementioned combination of variables at diagnosis may help identify dogs with lymphoma that will not survive > 2 years. Other types of neoplasia, in particular osteosarcoma, may develop in long-term-surviving dogs.

Detection of biclonal gammopathy by capillary zone electrophoresis in a cat and a dog with plasma cell neoplasia.

Gammopathies associated with plasma cell neoplasms in a 15-year-old female spayed domestic shorthaired cat and a 9-year-old female spayed Rottweiler dog were evaluated by serum protein electrophoresis. In the cat, the plasma cell neoplasm was found in the liver and spleen, and an evaluable sample of bone marrow was not obtained. Some of the plasma cells had the morphologic appearance of flame cells. The paraprotein was confirmed as IgG based on agar gel immunodiffusion precipitation and both immunocytochemical and immunohistochemical staining. The dog had multiple myeloma with production of IgG and IgA paraproteins. In both cases, serum proteins were evaluated by 2 methods of protein electrophoresis: cellulose acetate electrophoresis (CAE) and capillary zone electrophoresis (CZE). In the cat and the dog, CAE showed a single large oligoclonal-like peak, which occurred in the γ-region in the cat and the ß-γ-region in the dog, whereas CZE showed a biclonal gammopathy with 2 very close narrow spikes in the γ- and ß-γ-regions in the cat and dog, respectively. In selected cases, CZE may be more effective than routine CAE in distinguishing oligoclonal from monoclonal or biclonal paraproteinemia.