Submitted by: Patricia Shea, DVM
J Am Vet Med Assoc 2019; 255:1117-1119. DOI: 10.2460/javma.255.10.1117
Pathology in practice.
Scales TR, Krotec K.
This case series reviews the finding of a parovarian nodular mass identified in 6 domestic cats undergoing ovariohysterectomy in high-volume spay-neuter practice. Of 5,825 spay surgeries performed by a single surgeon over 4 years, unilateral, single nodular masses were found in the mesovarium of these cats, who ranged in age from 7 months to 3 years of age. In 5 of the 6 cats, the masses were in tissue associated with the left ovary. All 6 cats were normal historically and clinically prior to surgery.
In each case, the masses, which were cream to tan in color and 2-3 mm in diameter, were excised completely during ovariohysterectomy and submitted for histopathology. Although the masses were all found in the mesovarium, they were definitely distinct from the ovary itself, and were found 6 to 10 mm away from the ovary, adjacent to the ovarian arteriovenous complex. In several cases their presence presented a technical challenge to the surgeon because they were located in the area of the ovarian pedicle where hemostatic forceps are typically placed and ligatures are made.
Differential diagnoses for the masses included ectopic ovarian tissue or luteoma; histopathology of the masses revealed that they all had a fibrous capsule, and a set of two layered cellular populations: the layer closest to the outer fibrous capsule had cells identical to those of the zona glomerulosa of the adrenal cortex, and the inner assemblage of cells was histologically consistent with those of the adrenal cortical zona fasciculata. Neither cells of the zona reticularis nor adrenal medullary tissue were identified in any of the masses. Therefore, these mesovarian masses were diagnosed as ectopic adrenal rests, which are congenital abnormalities found in many mammalian species: cats, horses, cattle, and humans.
Tissues of the adrenal gland originate in 2 separate embryonic tissues. The adrenal cortex is of mesodermal origin adjacent to the urogenital ridge. The adrenal medulla arises from the ectoderm of the neural crest. Because the adrenocortical and gonadal tissues come from adjacent embryonic sites, small pieces of adrenocortical tissue may fragment and migrate with the embryonic testes or ovaries, ultimately resulting in adrenocortical rests near the mature gonads. As cells of the adrenocortical medulla have a different origin, they do not have the potential to migrate with the embryonic gonads.
In humans and horses, these adrenocortical rests may be functional in that they can either secrete hormones or be hormone responsive. So far, functional adrenocortical rests have not been identified in cats, and therefore in this species they are considered benign, clinically insignificant, incidental findings. However, grossly they appear identical to ectopic ovarian tissue, which is likely to be functional, and consequently they should be removed.
Based on the statistics in this report, the prevalence of ectopic adrenal rests in a population of female cats undergoing ovariohysterectomy is 0.1%. They are therefore likely to be encountered occasionally in high volume spay-neuter practice, and in general small animal practice in which significant numbers of feline gonadectomy surgeries are performed.
J Sm Anim Pract 2021; 1–11. DOI: 10.1111/jsap.13332
Feline chronic enteropathy
Marsilio S.
Chronic enteropathies are among the most common feline health problems, particularly in older cats. Cats with clinical signs of feline chronic enteropathy (FCE), which is characterized by the presence of such signs for more than 3 weeks in the absence of extraintestinal causes, or infectious, obstructive, or localized neoplastic intestinal diseases, are seen almost daily in clinical practice. Feline chronic enteropathy comprises food-responsive enteropathy (FRE), idiopathic inflammatory bowel disease (IBD), and small cell alimentary lymphoma (SCL). In this review article, the author discusses these diseases in detail, while touching on a few other, less common, enteropathies. The diagnostic testing options that may help distinguish these diseases, which have similar clinical signs, as well as therapeutic recommendations, are reviewed.
The etiopathogenesis of the FCE family of diseases is still unclear, but is considered to involve a confluence of patient genetics, the immune system, environmental factors, and the individual microbiome. Moreover, it is very likely that SCL often represents progression of IBD over a period of months to years, as feline patients diagnosed with IBD are sometimes later found to have SCL. In addition, based on histopathology, both diseases are frequently found to coexist in an individual animal.
Clinical signs of FCE include weight loss (noted in 80-90% of affected animals), vomiting (70-80% of cats with FCE), anorexia (60-70%), and diarrhea (50-65%). This is in contrast to dogs, in which diarrhea is the most common sign of chronic enteropathy. Weight loss in affected cats may be slow and subtle, and the patient will tend to lose muscle mass first, before adipose tissue begins wasting. Physical examination signs besides weight loss may include segmentally or diffusely thickened intestinal loops, palpable abdominal lymphadenopathy, and pain elicited on cranial abdominal palpation; the latter may be associated with concurrent pancreatitis and/or cholangiohepatitis.
The diagnostic dilemmas in distinguishing the FCE subtypes are considerable. Signalment, clinical signs, laboratory evaluation, and even abdominal ultrasonography are unlikely to distinguish the various diseases in this family. Fine needle aspirates do not provide information about lesion architecture, and biopsies obtained through various methods (endoscopy, laparoscopy, or exploratory surgery) access different layers of the intestine and may not be definitively diagnostic of a specific subtype, even with additional testing beyond histopathology such as immunohistochemical staining and clonality assays. The fact that several subtypes of chronic enteropathy can coexist in the same patient further complicates the situation.
Clinical signs are often not useful in distinguishing IBD from SCL. Intermediate (ICL) or large cell lymphomas (LCL), which are more aggressive and less treatable than SCL, usually have an acute onset and more rapidly progressive clinical signs than SCL and often will be associated with discrete abdominal masses, intussusception, obstruction, and possibly even intestinal perforation. Discrete abdominal masses, lymphadenomegaly, or organomegaly are the main instances when fine needle aspirates can be useful, and may help identify LCL or fungal disease.
Patient signalment can be useful in developing clinical suspicion regarding the subtype of FCE present. Although the age ranges of patients with FCE subtypes overlap significantly, the youngest cats (median age 7.7 years) are most likely to have FRE, whereas IBD is the most common disease in those somewhat older (median age 10.4 years); cats with SCL had a median age of 12.4 years. Domestic shorthair cats are the predominant breed identified with FRE and IBD, but to date no studies have identified specific breed predilections for any of the FCE subtypes.
Laboratory findings are also not definitively diagnostic in distinguishing the FCE subtypes, and in some cases do not help identify FCE in general. Common laboratory abnormalities include hypoalbuminemia, often with concomitant hyperglobulinemia, hypocobalaminemia, inorganic hypophosphatemia, and decreased vitamin D. Combined hypocobalaminemia and hypofolatemia are markers of significant small intestinal disease, and represent malabsorption of these nutrients and probably many others. Supplementation of cobalamin and folate in patients with deficiencies of these vitamins has been demonstrated to be beneficial in both cats and humans.
Given that chronic pancreatitis is often present in cats with the FCE family of diseases, evaluation of feline pancreatic lipase immunoreactivity (fPLI) and feline trypsin-like immunoreactivity (fTLI) are useful in identifying concurrent chronic pancreatitis. Exocrine pancreatic insufficiency (EPI) is increasingly identified in cats, and in contrast to canine EPI, usually is found in older individuals, and may represent the result of fibrosis of functional pancreatic tissue due to chronic pancreatitis.
The author reviews in detail the various methods of obtaining biopsies, as histopathology is currently still the most reliable diagnostic test to identify chronic enteropathy in general as well as the subtype. Clinicians are advised to pay attention to the description of architectural changes demonstrated in the biopsies, as these can be very useful in distinguishing IBD from SCL. In IBD, a mixed infiltrate of lymphocytes and plasma cells is present, while with SCL, a monomorphic population of small mature lymphocytes infiltrating and effacing intestinal layers, including the lamina propria, the epithelium (if the disease is epitheliotropic), and sometimes the submucosa and muscularis, is seen. However, SCL can also involve an inflammatory component, so severe lymphoplasmacytic enteritis (LPE), which can also be associated with endoparasitism, adverse reactions to food, or hyperthyroidism, is hard to distinguish from IBD or from SCL. In cases where biopsies reveal minimal to no architectural changes and mild cellular infiltrates, decisions regarding diagnosis and treatment need to be considered carefully in the light of patient history and clinical findings.
Interestingly, a previous study by the author of endoscopic gastric and duodenal biopsies of 20 healthy, client-owned cats in the age range of those likely to have signs of chronic enteropathy (median age 9.5 years; range 3-18 years) showed that these biopsies demonstrated histopathological criteria of FCE as defined by the World Small Animal Veterinary Association Gastrointestinal Standardization Group. Yet only 3 of these cats actually developed gastrointestinal disease later on. The other 17 were clinically normal after a median follow-up time of 709 days.
Eosinophilic infiltrates, which may or may not be accompanied by peripheral eosinophilia, can occur with endoparasitism, adverse reactions to food, T-cell lymphoma, or eosinophilic syndrome. Neutrophilic (suppurative) and/or histiocytic infiltrates may point to infectious etiology, which requires special staining of biopsies and testing for infectious diseases.
A very useful feature of this review paper is the information provided regarding how to take samples for biopsy, whether surgical or endoscopic, that are representative of the disease process. The importance of sample orientation so that the slides will show a transverse plane through the intestinal wall, by mounting the specimens on cucumber slices or moisturized synthetic foam sponges, rather than sending them floating free in formalin, is emphasized. Also included are a number of useful summary tables, including a scoring system for clinical signs and laboratory testing (FCEAI; Feline Chronic Enteropathy Activity Index), differential diagnoses for hypocobalaminemia, pros and cons of endoscopically or surgically acquired biopsies, and pros and cons of different dietary therapies for FCE.
Therapies for FCE diseases are discussed briefly; IBD and SCL are often treated similarly, but other diseases with similar clinical signs, such as ICL, LCL, eosinophilic syndrome, deep mycoses, and other gastrointestinal neoplasms, require very different treatments and often have a different prognosis. This is why biopsies are essential—to diagnose and exclude other diseases. For IBD, treatment usually involves glucocorticoids and possibly dietary therapy with a novel protein or hydrolyzed protein diet. Those cats that respond to a dietary trial only are likely to have FRE.
Ancillary therapies for IBD involve nutritional support of any kind, appetite stimulants, or even placement of an esophageal feeding tube if the cat is fully or partially anorexic. Probiotics or synbiotics may be helpful, but there are currently no systematic studies of the efficacy of these supplements in cats with FCE. Subcutaneous dexamethasone injections can initially be helpful in those animals with severe malabsorption or inflammation until better control of the disease is attained. Although in the author’s experience, just as with IBD, SCL will often respond to glucocorticoid therapy only, severe IBD or SCL are likely to require addition of chlorambucil to the glucocorticoid treatment.