History

A 7-year-old 1.1-kg castrated male domestic shorthair cat was evaluated at a private clinic because of a 6-month history of vomiting, weight loss, and ingestion of foreign bodies.

Clinical and Gross Findings

Physical examination revealed slight ataxia. Abdominal radiography revealed a full and distended colon; findings on abdominal ultrasonography and echocardiography were unremarkable. A CBC and serum biochemical analyses revealed hypoalbuminemia and high creatine phosphokinase activity (values not available). During hospitalization, the cat had a voracious appetite. The owners elected euthanasia (via barbiturate overdose), and the cat was submitted for necropsy. Gross examination revealed a moderate body condition with adequate subcutaneous and visceral adipose tissue stores. The oral and ocular mucous membranes were pale yellow. The colon and cecum were distended with gas and dark brown, firm impacted fecal material (Figure 1). The liver was diffusely enlarged, friable, and yellow. No other gross changes were present.

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Photograph of the gastrointestinal tract of a 7-year-old 1.1-kg castrated male domestic shorthair cat that was euthanized after a 6-month history of vomiting, weight loss, and ingestion of foreign bodies. The small and large intestines are diffusely brown and distended with gas or fecal material. The mesentery fat is absent.

Citation: Journal of the American Veterinary Medical Association 259, S2; 10.2460/javma.19.07.0335

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Histopathologic Findings

Routine tissue samples were collected, fixed in neutral-buffered 10% formalin, routinely processed for histology, and stained with H&E stain. Histologically, the outer and inner muscle layers of the entire gastrointestinal tract had a striking tinctorial change that lent a distinct basophilic hue to the smooth muscle fibers (Figure 2). No changes were present in the submucosal muscle layer. These changes were more prominent in the small and large intestines, with the circular layers more prominently affected. No other changes were noted.

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Photomicrograph of a section from the small intestine of the cat described in Figure 1. A—The outer (white asterisk) and inner (black asterisk) muscle layers exhibit diffuse basophilic tinctorial changes. H&E stain; bar = 500 µm. B—A higher magnification of the inner muscle layer to illustrate the basophilic appearance of affected leiomyocytes. H&E stain; bar = 100 µm. C—A higher magnification of the inner intestinal muscle layer from a control cat. H&E stain; bar = 100 µm.

Citation: Journal of the American Veterinary Medical Association 259, S2; 10.2460/javma.19.07.0335

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Immunohistochemistry (IHC) for detection of α-smooth muscle actin (α-SMA) was markedly reduced (Figure 3) in these muscle layer areas, compared with less affected regions (internal control) and with normal feline intestinal tissue (external control). There were multifocal areas of mucosal ulceration with a small number of lymphocytes and plasma cells and variable degrees of fibrosis in the small intestine. The esophagogastric junction had multifocal mucosal ulcerations associated with hemorrhage, edema, and neutrophilic inflammation and had areas of deposition of granulation tissue, lymphocytes, and plasma cells. Hepatocytes were diffusely expanded by sharply demarcated, clear vacuoles (hepatic lipidosis). The right kidney contained a small medullary focus with an accumulation of degenerative neutrophils and necrotic debris surrounding a cluster of bacterial cocci. The white matter throughout the brain was mildly vacuolated, with scattered Alzheimer’s type 2 astrocytes. No notable changes were observed in the other examined organs.

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Photomicrograph of a section from the small intestine of the cat described in Figure 1 following immunohistochemical testing for α-smooth muscle actin (α-SMA). A—Smooth muscle cells exhibit weak cytoplasmic immunoreactivity to SMA. α-SMA immunohistochemical reaction (mouse monoclonal antibody M0851, Dako); bar = 500 µm. B—A higher magnification of the inner muscle layer illustrates the lack of α-SMA labeling. α-SMA immunohistochemical reaction; bar = 100 µm. C—A higher magnification of the inner intestinal muscle layer from a control cat. α-SMA immunohistochemical reaction; bar = 100 µm.

Citation: Journal of the American Veterinary Medical Association 259, S2; 10.2460/javma.19.07.0335

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Morphologic Diagnosis and Case Summary

Morphologic diagnosis: gastrointestinal smooth muscle α-actin deficiency with colonic and cecal fecal impaction; 2) diffuse hepatic lipidosis; 3) focal suppurative pyelonephritis with intralesional bacterial cocci; and 4) Multifocal cerebral status spongiosus and astrocytosis.

Case summary: gastrointestinal smooth muscle α-actin deficiency in a cat.

Comments

The pathological and IHC findings in the current case are consistent with those reported in cases of smooth muscle α-actin deficiency in veterinary medicine.^1,2 This disorder has been described in a cat and a dog that had clinical signs that were compatible with intestinal pseudo-obstruction, including anorexia, regurgitation, vomiting, diarrhea, and weight loss.^1,2 In human medicine, smooth muscle α-actin deficiency is associated with similar clinical signs, including chronic, recurrent episodes of abdominal pain, abdominal distension, constipation or diarrhea, vomiting, and weight loss.³ Intestinal pseudo-obstruction is clinically characterized by intestinal dysmotility in the absence of mechanical obstruction of the lumen.^4,5 Acute intestinal pseudo-obstruction has been associated with hypokalemia, anticholinergic opioid drug administration, pancreatitis, peritonitis, abdominal surgery, and viral enteritis.^4,6 Chronic intestinal pseudo-obstruction is rare and typically associated with visceral neurodegenerative disorders, dysautonomia,^7,8 idiopathic sclerosing enteropathy or fibrosing gastrointestinal leiomyositis, intestinal neoplasia, and smooth muscle α-actin deficiency.^5,9–11

Smooth muscle α-actin deficiency is a poorly understood disorder of unknown cause. A direct causal association between gastrointestinal dysmotility and smooth muscle α-actin deficiency has not been fully confirmed in human or veterinary medicine, but the deficient IHC labeling of gastrointestinal smooth muscle α-actin and the electron microscopic changes, such as loss of myofibrils, loss of organelle polarity, and presence of megamitochondria within leiomyocytes, appears to support some association.^1,2 It has been proposed that the lack of SMA immunolabeling in the gastrointestinal tract of affected patients may not reflect the cause of the intestinal pseudo-obstruction but may be a supportive diagnostic test for cases in which no other morphologic abnormalities were detected.⁵

The colonic and cecal distension with gas and impacted fecal material in the cat of the present report were similar to those described in the other animals with smooth muscle α-actin deficiency, in which the affected areas of the gastrointestinal system were dilated with either gas or fluid.^1,2 These changes are likely secondary to altered peristalsis due to gastrointestinal muscular dysfunction.^1,2 In veterinary medicine, megacolon is another common differential diagnosis to consider with the presence of colonic distension and often ensues with long-standing colonic obstruction. An underlying disturbance in the activation of smooth muscle myofilaments has been suggested for idiopathic megacolon in cats; however, no tinctorial changes in the colonic muscle layer have been observed in affected cats.¹²

In human medicine, the diagnosis of gastrointestinal smooth muscle α-actin deficiency is based on the clinical signs, clinical evidence of intestinal distension with no intestinal obstruction, manometry, and histology.³ In veterinary medicine, the diagnosis can be achieved based on the clinical signs, evidence of intestinal dilation via radiography, histology, IHC, and electron microscopy.^1,2 The diagnosis of gastrointestinal smooth muscle α-actin deficiency in the cat of the present report case was suspected based on the basophilic tinctorial changes within leiomyocytes in the muscle layers of the intestine.^1,2 Diagnostic confirmation was achieved with IHC for α-SMA, which revealed an absence of staining within affected leiomyocytes.^1,2

In human medicine, treatment for pseudo-obstruction secondary to neuromuscular dysfunction focuses on dietary adjustment, anti-inflammatory treatment in the case of concurrent inflammation, and surgery.³ Although treatment with glucocorticoids was attempted in 1 dog with smooth muscle α-actin deficiency, it was unsuccessful,² and too few cases have been reported in veterinary medicine to draw any conclusions in terms of treatment. Treatment was not attempted for the cat of the present report.