JPC SYSTEMIC PATHOLOGY
DIGESTIVE SYSTEM
September 2021
D-M16

 

Signalment (JPC #3103040):  9-year-old male Cavalier King Charles spaniel 

 

HISTORY:  This animal had a history of diarrhea. The ileocecal junction appeared thickened on ultrasound.  Thickened segments were surgically resected.

 

HISTOPATHOLOGIC DESCRIPTION:  Small intestine:  Villi are multifocally expanded by dilated lacteals (dilated up to 250um diameter), the lamina propria and submucosa are edematous, and lymphatics are dilated transmurally. Multifocally, ectactic lacteals and lymphatics contain a variable amount of flocculent, pale eosinophilic, proteinaceous fluid and fibrin admixed with few erythrocytes and degenerate neutrophils.  Lymphatics within the submucosa, tunica muscularis, serosa and mesentery exhibit a continuum of changes from simple dilation to formation of lipogranulomas. Lipogranulomas are up to 2mm in diameter and are characterized by partial to complete obstruction of the lumen or complete replacement by amorphous, amphophilic to pale eosinophilic, lipid-rich material that often contains cholesterol clefts and/or basophilic granular material, surrounded by high numbers of lipid-laden macrophages, fewer lymphocytes, plasma cells, and foreign-body type multinucleated giant cells, further surrounded by a variably thick band of fibrosis.  In severely affected lymphatics, endothelial cells are either shrunken with hypereosinophilic cytoplasm and pyknotic nuclei (necrosis) or are lost.  Multifocally, there is hemorrhage, edema, and fibrin admixed with these inflammatory cells.  Moderate numbers of lymphocytes and plasma cells infiltrate the mucosa, submucosa, tunica muscularis, serosa, and mesentery.

 

MORPHOLOGIC DIAGNOSIS:  Small intestine:  Lymphangiectasia, chronic, diffuse, marked, with lipogranulomatous lymphangitis, Cavalier King Charles spaniel, canine.

 

GENERAL DISCUSSION: 

• Intestinal lymphangiectasia (IL) is the pathologic dilatation of lymphatic vessels and is the most commonly reported cause of malabsorption/protein-losing enteropathy in the dog
• Part of a syndrome characterized by chronic diarrhea, wasting, hypoproteinemia, lymphopenia, hypocalcemia, and hypocholesterolemia
• Breed predisposition: Yorkshire Terriers and the Norwegian Lundehund
  • Norwegian lundehund has inherited IL and is also predisposed to gastritis and gastric carcinoma that may coexist with IL

 

PATHOGENESIS: 

• Primary IL (Rare) – idiopathic or congenital condition in some breeds (lundehund, small terrier breeds (e.g. Yorkies, Maltese), and Rottweilers)
• Secondary IL – most common; caused by increased lymphatic pressure secondary to obstructive lesions in the lymphatic system (e.g., IBD, granulomatous inflammation or lymphoma in draining lymph nodes, neoplasm) or venous hypertension (e.g., congestive heart failure or congenital vascular anomalies in the liver such as A-V shunting)
• Etiology of the clinical syndrome may be more complex than simple lymphatic obstruction

 

TYPICAL CLINICAL FINDINGS:

• Anorexia, weight loss, diarrhea, steatorrhea, and lethargy
• Ascites and peripheral edema are often present due to hypoalbuminemia
• Clinical pathology: Panhypoproteinemia, lymphopenia, hypocalcemia, and hypocholesterolemia
• Coagulopathies may result from decreased absorption of vitamin K

 

TYPICAL GROSS FINDINGS: 

• Small intestinal mucosa/villi is thickened and contains white chyle-filled lacteals
• +/- Serosal and mesenteric lymphatics prominent, dilated, filled with white, milky fluid
• Generalized edema, hydrothorax, and ascites
• Mesenteric lymphadenopathy
• Nodular white masses up to 5-10 mm diameter (lipogranulomas) located on serosa at the mesenteric border of the small intestine (rarely on liver, diaphragm, abdominal organs, pleura)

 

TYPICAL LIGHT MICROSCOPIC FINDINGS: 

• Multifocal to diffuse lesions
• There is dilation of the lacteals and lymphatics of the submucosa, muscularis, and mesentery; lipid-laden macrophages may be present
• Blunt villi; crypt hypertrophy (+/-)
• Occasional lipogranulomas in and around lacteals: Collar of lipid-laden macrophages that surround centrally located amorphous lipid material +/- cholesterol clefts
• Edema in lamina propria, submucosa
• Crypt abscesses
• Normal to increased inflammatory cell population (lymphocytes, plasma cells, eosinophils) in lamina propria

 

ADDITIONAL DIAGNOSTIC TESTS: 

• Special stains to detect possible initiating fungal or bacterial infection

 

DIFFERENTIAL DIAGNOSIS:

For chronic diarrhea associated with panhypoproteinemia:

• Alimentary Lymphoma
• Inflammatory bowel disease
• Histoplasmosis
• Pythiosis

 

General causes of hypoproteinemia:

• Loss of proteins secondary to: Hemorrhage, protein-losing nephropathy, protein-losing enteropathy, severe exudative skin disease, burns, intestinal parasitism, high-protein effusions
• Decreased production or gastrointestinal absorption of proteins: Chronic liver disease, exocrine pancreatic insufficiency, cachexia secondary to neoplasia, malnutrition, intestinal malabsorption, lactation, pregnancy

 

COMPARATIVE PATHOLOGY: 

• Secondary (acquired) intestinal lymphangiectasia occurs in many animals such as nonhuman primates, cats, cattle, horses, and swine
• Secondary intestinal lymphangiectasia due to Johne’s disease (granulomatous serosal lymphangitis due to lymphatic obstruction)
• Soft coated Wheaten terriers have a familial predisposition for protein-losing nephropathy, protein-losing enteropathy, or both; intestinal lesions include inflammatory bowel disease, lymphangiectasia and lipogranulomatous lymphangitis; renal lesions include chronic glomerulonephritis/glomerulosclerosis

 

REFERENCES:

1. Gelberg HB. Alimentary system and the peritoneum, omentum, mesentery, and peritoneal cavity. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier; 2017:333, 336, 406.
2. Hall EJ, Day MJ. Diseases of the small intestine. In: Ettinger SJ, Feldman EC, Côté E eds. Textbook of Veterinary Internal Medicine. Vol 2. 8th ed. St. Louis, MO: Elsevier; 2017:1535; 1558-1559.
3. Miller LM, Gal A. Cardiovascular system and lymphatic vessels. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier; 2017:586-587, 615.
4. Simmerson SM, Armstrong PJ, Wunschmann A, Jessen CR, Crews LJ, Washabau RJ. Clinical features, intestinal histopathology, and outcome in protein-losing enteropathy in Yorkshire terrier dogs. J Vet Intern Med. 2014;28(2):331-337.
5. Tarpley HL, Bounous DI. Digestive system. In: Latimer KS, ed. Duncan & Prasse’s Veterinary Laboratory Medicine Clinical Pathology. 5th ed. Ames, IA: John Wiley & Sons, Inc.; 2011:242-243.
6. Watson VE, Hobday MM, Durham AC. Focal intestinal lipogranulomatous lymphangitis in 6 dogs (2008-2011). J Vet Intern Med. 2014;28(1):48-51.
7. Uzal FA, Plattner BA, Hostetter JM. Alimentary system. In: Maxie MG, ed. Jubb, Kennedy and Palmer’s Pathology of Domestic Animals. Vol 2. 6th ed. St. Louis, MO: Elsevier; 2016:90-91.

 

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