2022 February Timely Topics

Submitted by: Patricia Shea, DVM

Vet Clin Pathol 2021; 50:52-56.

Morphological, cytochemical, and ultrastructural features of gray eosinophils in nine cats

Holmes E, Raskin R, et al.

When stained with common cytologic stains such as aqueous Romanowsky (“Diff-Quik”) or methanolic Romanowsky (modified Wright) stains, normal feline eosinophils have pink- to orange-colored rod-shaped granules that fill the cytoplasm. Gray eosinophils, common in sighthound dog breeds such as the Greyhound, and occasionally found in non-sighthound canines, have hitherto not been reported in cats.

Gray eosinophils, also known as “vacuolated” eosinophils, contain clear granules with a vacuolar appearance that do not assume a color when common cytologic stains are applied. A review of blood films from 2,641 cats evaluated at a veterinary teaching hospital from 2015 to 2018 found nine cases with gray eosinophils. When Romanowsky stains were used, the gray eosinophils identified on these blood films did not demonstrate the typical pink to red to orange coloring assumed by secondary granules in feline eosinophils. Moreover, these secondary granules were round rather than having the typical rod shape found in normal feline eosinophils. Use of additional cytochemical stains: Luna, Luxol fast blue, and alkaline phosphatase (ALP), did not result in any coloration in the granules of the suspected gray eosinophils. Granules in normal feline eosinophils will turn bright red with Luna, pink with ALP, and pale blue with Luxol fast blue stains.

Ultrastructural evaluation of eosinophils from two of the cases and a feline control was performed using transmission electron microscopy (TEM). The control cat’s eosinophil granules had the normal electron-dense core, while those from the two cats with gray eosinophils had a fragmented or amorphous core without any electron-dense areas.  The ultrastructure of the neutrophils and basophils from the cats with gray eosinophils were similar to those of the control cat. The TEM analysis of feline gray eosinophils did not suggest that granule release was responsible for the atypical ultrastructure of their granules. 

A variety of breeds were represented by the nine cats with gray eosinophils. None of these cases had typical eosinophils in any of their blood smears. The ages of the case cats ranged from two months to 15.6 years. Four of the nine cases were Domestic Shorthair, three were British Shorthair, there was one Ragdoll, and one Domestic Longhair. The cases comprised four neutered males, one spayed female, one intact male, and three intact females. 

Three of the nine case cats presented for congenital extrahepatic portosystemic shunts and two had neoplasia (lymphoma and hemangiosarcoma). Inflammatory bowel disease was diagnosed in one cat, peripheral vestibular disease in another, and two of the cats did not receive a definitive diagnosis. Other hematologic changes in these patients, besides gray eosinophils, were considered mild, including mild lymphopenia (3/9), microcytosis (2/9) associated with portosystemic shunts, and mild thrombocytopenia (1/9). In two of the nine cases, there were no other hematologic abnormalities.

The granules of normal eosinophils assume a color with common cytochemical stains due to the high cationic protein content of these granules. Major basic protein (MBP) is the predominant and most cationic constituent of eosinophil granules, and it forms the crystalline lattice structure of the core of eosinophilic granules, producing the central electron-dense core of these granules visualized with electron microscopy. MBP plays a key role in host defenses against helminths, is involved in the activation of mast cells, basophils, and neutrophils during inflammation, activates complement and platelets, and has antibacterial activity. Negative Luna staining of the granules in feline gray eosinophils compared to those of eosinophils in control cats implies a probable lack or significant reduction of MBP in the granules of feline gray eosinophils. The authors express an interest in developing an anti-MBP antibody to specifically stain for MBP in order to learn more about this.

In contrast, the granules in canine gray eosinophils are considered likely to be deficient in eosinophil peroxidase (EPO); this deficiency, called Presentey’s anomaly in humans, is not known to cause health problems in people. EPO deficiency would not explain the significant ultrastructural changes in the gray eosinophils of the study cats. Although the ultrastructural and cytochemical staining properties of the feline gray eosinophil granules point to a probable MBP deficiency or absence, the significance of gray eosinophils in cats is still not completely understood. None of the case cats had clinical signs associated with eosinophil dysfunction. If these cats’ eosinophils are truly MBP deficient, reduced immunity to parasites could be a concern. Awareness of the potential for the presence of gray eosinophils in cats, just as in dogs, is important to the cytopathologist or general practitioner, because these cells can be erroneously identified as toxic neutrophils. 

J Am Vet Med Assoc 2021;258:483-492.

Multicenter evaluation of decompressive cystocentesis in the treatment of cats with urethral obstruction

Reineke EL, Cooper ES, et al.

A significant number of feline emergency hospital admissions, almost always in males, are associated with urethral obstruction (UO). Resolving the obstruction involves a number of procedures to stabilize the patient and relieve pain, but ultimately results in urethral catheterization (UC). Often, before urethral catheterization takes place, a decompressive cystocentesis (DC) is performed. DC is generally considered to help relieve pain, ameliorate renal back pressure, improve perfusion of the urinary bladder wall, and facilitate UC by relieving some of the excessive intraluminal pressure within the urinary bladder. However, there are also potential deleterious effects of DC, such as hemorrhage, leakage of urine into the peritoneal cavity, and urinary bladder rupture.

There is actually little scientific evidence to support the alleged benefits of DC. In this study of 88 male cats, only four of whom were intact, with UO admitted to the emergency services of two university veterinary teaching hospitals, patients were randomly assigned to undergo DC prior to UC (DC group; n =44) or to have UC without DC (UC group; n =44). All cats were monitored with serial ultrasonographic examinations of the urinary bladder to identify any abdominal effusion: before DC and UC or before UC only, immediately after UC, and again four hours after UC. Every patient enrolled in the study received an intravenous (IV) catheter and IV fluids, initial bloodwork, and monitoring bloodwork every 8-12 hours while hospitalized. All patients were sedated following cardiovascular and electrolyte stabilization and prior to DC and/or UC. 

The veterinary staff performing UC, the board-certified veterinary radiologist who performed the ultrasound studies, and the cats’ owners were blinded to the assigned group of each patient. The investigator performing DC was not blinded to the patient’s group. The DC procedure in each cat was performed by a board-certified emergency and critical care specialist or a resident in training in emergency and critical care. Only one needle puncture was allowed in each patient. The urine volume removed from the patients via DC ranged from 15 to 162 mL, with a median of 68.5 mL.

No significant difference was found in the median time to place the urinary catheter between the two groups (120 seconds in the DC group and 132 seconds in the UC group). Also, not significant between the two groups was the median score for ease of UC, and the presence of urethral spasms, subjectively evaluated, during UC was also not significantly different between the DC and UC groups. One cat in the UC group developed uroperitoneum, and was later found to have a defect in the craniodorsal aspect of the urinary bladder; this cat was euthanized and a necropsy was not performed. Uroperitoneum was not diagnosed in any of the DC cats.

Of the 88 study patients, 67 (34 in the DC group and 33 in the UC group) had abdominal ultrasonographic videos of their urinary bladder available for review. Technical difficulties precluded retention of the ultrasonographic videos of 21 cats at one of the institutions, so these animals were excluded from the analysis of ultrasonographic videos for abdominal effusion. On the videos available for evaluation, the abdominal effusion score was rated from zero (no effusion) to 16 (extensive effusion).  Median total effusion scores for prior to DC and UC in all patients was three (range, 0 to 13). Only 7% (5/67) of the patients who had ultrasonographic videos available for review had no evidence of abdominal effusion before DC and UC. The other 62 cats had evidence of abdominal effusion in one or more sites on the urinary bladder; there was no significant difference in the median abdominal effusion score prior to DC and UC between the DC group and UC groups.

27 of the 67 cats (14 in the UC group and 11 cats in the DC group) had a positive change in the total abdominal effusion score from pre-DC and UC to immediately following UC. Right after UC, no significant difference in the median total abdominal effusion score between the DC and UC groups was found. The ultrasonographic evaluations obtained 4 hours after UC did demonstrate a significantly higher total abdominal effusion score in the DC group than in the UC group, but the median change in total abdominal effusion score immediately following UC to 4 hours post-UC was not significantly different between the UC and DC groups.

Only eight of the 88 cats did not survive to hospital discharge. All eight cats who did not survive, five in the DC group and three in the UC group, were euthanized in the hospital. Only one of these was euthanized due to recurrent urethral obstruction (rUO), while 7 others who developed rUO survived to discharge; there was no significant difference in the in-hospital rUO rate between UC and DC groups.

The BUN at hospital admission was significantly higher in the UC cats compared to the DC group cats, but none of the other hematologic parameters, systolic blood pressure, and the presence of cardiac arrhythmias were not significantly different between the two groups, so it is likely that both groups had a similar degree of illness. In this study, performing DC before UC as opposed to UC without prior DC did not affect the resolution of metabolic derangements associated with UO. In those cats with severe metabolic derangements present on admission to the hospital, the authors recommend that stabilization methods designed to ameliorate hyperkalemia and its effects on cardiac myocytes be a priority over decompression.

Follow-up contacts with owners one week after hospital discharge demonstrated no significant differences between the UC and DC cats with regard to dysuria or stranguria, periuria, or hematuria noted at home. Therefore, DC is unlikely to cause additional inflammation or contribute to continued signs of lower urinary tract disease following hospital discharge, but this study was not specifically designed or powered to evaluate the effects of DC on rUO and/or continued lower urinary tract disease signs post-discharge. 

In this study, the underlying causes of UO were not determined, and there can be a number of these: urethral plugs, urolithiasis, blood clots, or idiopathic causes. It may be true that DC prior to UC could be beneficial to a subset of cats with UO attributable to a specific etiology, but this would require additional studies to establish supportive evidence. Based on the findings in the present paper, there is no evidence for or against the use of DC as a standard treatment for cats with UO. Nonetheless, in individual cases, extenuating circumstances may exist where DC is indicated; for example, when there is a delay in urinary catheter placement, in cats not responding to stabilization therapy and who therefore are not good candidates for UC placement, when a UC cannot be passed, or if the patient is awaiting a surgical intervention such as a cystotomy or perineal urethrostomy.