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Renal cytology results in dogs and comparison to ultrasound findings | VETgirl Veterinary Continuing Education Podcasts

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In today’s VETgirl online veterinary continuing education podcast, we review the diagnostic utility of cytologic examination of renal fine-needle aspirates from dogs and the use of ultrasonographic features to inform cytologic diagnosis. When we do renal aspirates while we’re ultrasounding our veterinary patients, is it useful and helpful?

In veterinary medicine, assessment of kidney function can be achieved by non-invasive means such as evaluation of BUN, creatinine, SDMA, and urinalysis. However, the diagnosis of why kidney function is declining is much more challenging. Histopathology is the gold standard for diagnosis of renal pathology, but taking a chunk of tissue away from the kidney (in the form of a biopsy) could and should make us all just a bit nervous (Still worth doing, but just make sure to warn the owners about the risk of sedation and bleeding). Fine needle aspirates of tissues are less invasive than biopsies, but sadly, the smaller amount of tissue (e.g., cells) obtained by this route can result in non-diagnostic cytology samples. Since there is a healthy concern for hemorrhage when obtaining renal biopsies, McAloney et al out of the University of Minnesota wanted to determine if FNAs of the kidney could yield a good percentage of diagnostic samples. A secondary focus of this study was to evaluate renal ultrasound characteristics in patients with renal disease for their diagnostic value.

In veterinary medicine, fine needles aspirates have proven in the past to be effective in achieving diagnosis for infiltrative and infectious diseases (neoplasia and fungal infections), but have proven less effective in obtaining enough tissue sample to diagnose inflammatory or vascular lesions, and congenital conditions. Hence, the goal of this study. In this study, medical records from 100 dogs that had received renal FNAs via ultrasound guidance between 2005 and 2014 were reviewed retrospectively. Fifty-one breeds were represented with Labrador Retrievers, Golden Retrievers, and German Shepherds being the most common. Diagnoses obtained from cytologic review of renal FNAs were compared to either a concurrent histopathology sample (if available in the same patient), or PCR for Antigen Receptor Rearrangements (PARR). If the histopathology sample did not yield a diagnosis, then the case was excluded because the purpose of this study was to determine if cytologic review would be diagnostic as compared to the gold standard of histopathology. Cytology slides were prepared with Wright-Giemsa staining and were reviewed in blinded fashion by both a veterinary student and a board-certified veterinary clinical pathologist. (The purpose of having these slides reviewed by a veterinary student was not made clear in this paper). Cytologic findings were used to categorize the renal samples as inflammatory, neoplastic, hyperplastic, necrotic, cystic, hemorrhagic, or normal. Inflammatory processes were defined as suppurative (>80% neutrophils among other inflammatory cells), or mixed (<80% neutrophils with other inflammatory cells present). Cystic processes were defined as having proteinaceous fluid with minimal inflammatory cells and macrophages. Neoplastic processes were further categorized by cell type (round, epithelial, mesenchymal, neuroendocrine, or anaplastic) and then classified as benign or malignant based on the widely used criteria of malignancy. The authors make special note that information regarding criteria for veterinary renal tumors is currently lacking.

Most patients received sedation for the renal FNA with either butorphanol or a combination of butorphanol and midazolam. Both the patient’s skin and ultrasound transducer were aseptically prepared prior to FNAs being obtained. 22 gauge, 1.5 inch needles or spinal needles were used via a percutaneous, ultrasound-guided approach. Observers assessed for presence of hemorrhage before and after FNAs with color flow Doppler. Fine needle aspirate samples were used to make cytology preparations. Observers used ultrasound to characterize renal architecture for the medical record. If cytologic review suggested renal lymphoma or renal round cell tumor, the slides were sent to Colorado State University Clinical Immunology Laboratory for PARR testing.

This study included cytologic interpretations from 74 samples. Most samples were considered to have good cellularity with only 12% having minimal cellularity and acellular samples were uncommon at 4%. Cocci and rods were identified individually in only two separate cases. Urine culture grew Staphylococcus intermedius in the sample containing cocci, and tissue sample culture grew Escherichia coli in the FNA sample containing rods. Carcinoma was diagnosed via cytology in 17 dogs. The carcinoma FNA samples commonly contained additional cytologic findings such as inflammation, hemorrhage, and tubular hyperplasia. Seventeen dogs had cytologic diagnosis of lymphoma, 2 had sarcoma, 2 had anaplastic malignancy, and 1 had a round cell tumor. Those without neoplastic findings were classified as renal tubular hyperplasia (16), inflammation (3), necrosis (5), hemorrhage (1), renal cyst (1) or no abnormalities were seen (8).

Only 19 cases had histology reports available, and only 9 cases from dogs diagnosed with renal lymphoma or round cell tumor received adequate PARR testing. Six of the 9 samples submitted for PARR testing were consistent with lymphoma. One of the negative PARR samples ended up having histologic confirmation of renal lymphoma, thus indicating a false negative PARR. On the other side, one of the 7 “negative control” samples submitted for PARR testing had findings consistent with a false positive PARR result. Cytologic review resulted in false diagnosis of carcinoma in 2 samples. Histopathology diagnosed these two samples with acute tubular necrosis in one and fibrinosuppurative nephritis in the other. Cytologic review failed to correctly identify two cases of carcinoma that were instead confirmed on histopathologic review; clinical pathologist review had labeled the samples as hyperplasia and necrosis.

For the secondary focus of this paper, the authors wanted to know if ultrasonographic appearance can help us in diagnosing neoplastic processes. They found that all cases of confirmed carcinomas had ultrasonographic evidence of renal masses, whereas all cases with non-neoplastic pathology had no ultrasonographic evidence of renal masses. Therefore, ultrasonographic evidence of a renal mass appears to be highly consistent with a diagnosis of renal neoplasia. No other ultrasound characteristics (i.e. echogenicity or renal architecture) were consistent with neoplastic processes. Overall, renal aspirates yielded an adequate cellularity on slide preparations in 73% of samples. Due to the retrospective nature of this study, one cannot determine if low cellular samples were simply not submitted by clinicians, thereby skewing FNA diagnostic yield in a favorable light. In regards to PARR testing, this study found that 44% of their submitted specimens were non-diagnostic due to poor yield of DNA for the PARR test. The authors suggest that the preparation of submitted slides (air-dried and stained with Wright-Giemsa staining) may have contributed to low DNA yield. This study found that the presence of bilateral renal masses was more common in lymphoma than in other neoplastic processes. The authors also note that although loss of corticomedullary distinction has been found to be a common characteristic in previously studied cases of renal lymphoma, this study found that most renal neoplasms (not just renal lymphoma, but all renal neoplasms) had adequate corticomedullary distinction. Renal carcinomas have been previously described as the most common primary renal tumor and this study agrees with this assessment. This study showed that cytology alone could result in a lower sensitivity (missing some carcinoma diagnoses) for renal carcinoma. The reason for the lack of correct cytologic identification of renal carcinoma may be in part due to low cellularity in samples of this tumor, or due to conservative clinical pathologists not wanting to over-diagnose neoplasia. There were two false positive diagnoses of renal carcinoma in this study, which is concerning given the prognosis and medical pursuits taken with a diagnosis of this kind of tumor. The authors stress that a cytologic diagnosis of renal carcinoma is a challenging one and may be confused with benign renal adenomas.

So, what do we take away from this VETgirl podcast? Renal cytology should be used in conjunction with ultrasonography to determine which patients should go on to receive histopathologic testing of concerning focal lesions that have weak cytologic diagnosis versus those that should be watched and reevaluated with imaging over time. By combining ultrasound and cytology, the authors of this study propose that the diagnosis of renal carcinoma can be improved by ruling in/out reactive epithelial hyperplasia. Carcinomas were the most likely neoplasm encountered and were demonstrated to have a higher likelihood of being the culprit behind unilateral, hyperechoic lesions. Ultrasound findings of solitary or multifocal lesions, as well as disruption to the renal cortex by lesions, should prompt a recommendation for renal FNA.

Perhaps one of the biggest limitations to this study is the retrospective nature, as this can cause selection bias in samples. Clinicians may not have submitted all FNAs if they felt their slides had low cellularity, which then skews the percentage of adequately cellular renal FNA samples in a favorable light. The authors also note that perhaps histopathology was only pursued in a subset of animals that were either more clinically affected, or that had cytologic findings concerning enough to warrant histopathologic evaluation. When in doubt, know the limitations of cytology and ultrasound, and when in doubt, consider getting tissue for histopathology.

PS. Dr. Jody Lulich at the Minnesota Urolith Center (MUC) is investigating the connection between kidney stones and chronic kidney failure in cats. Help solve this common, costly and devastating problem. He needs whole, formalin-fixed kidneys of cats with nephroliths or chronic kidney disease. If cats have a kidney removed during therapy, succumb to their illness, or are humanely euthanized; place whole, intact kidneys (after carefully removing the outer capsule) in formalin. We’ll cover shipping; please email Dr. Jody Lulich at [email protected]. More information HERE.

Abbreviations:
FNA: fine needle aspirate
PARR: PCR for Antigen Receptor Rearrangements

References:
1. McAloney CA, Sharkey LC, Feeney DA, et al. Evaluation of the diagnostic utility of cytologic examination of renal fine-needle aspirates from dogs and the use of ultrasonographic features to inform cytologic diagnosis. JAVMA 2018;252(10):1247-1256.

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