8-yearold male castrate mixed breed domestic dog, canine (Canis lupus familiars)The animal was admitted to the Small Animal Clinic of the University of Zurich after a history of
vomiting and diarrhea for two months. The animal had been operated on a year earlier because of a stenosis in the
ileocecal region. The histology of the resected tissue revealed a lymphangitis and eosinophilic ileitis. Now, the small
intestines were again severely dilated and congested with ingesta and a new stenosis in the mid jejunum was evident
through ultrasound investigation. The animal was submitted to surgery for a second time; the stenotic intestine was
resected and sent in for further histological investigation.
The wall of the jejunum and the attached mesenterium was severely thickened by firm
connective tissue.Â Multifocal, small, round, soft, whitish nodules of up to 0,5cm in diameter could be seen between
the longitudinal and circular muscle layers of the tunica muscularis.Â The lymphatic vessels on the mesenteric site of
the intestine were severely congested with lymph.
Jejunum: The shortened villi are diffusely blunted and the crypts are often elongated
and hypertrophied.Â The crypt to villus ratio is often 1:1.Â On the tips of the villi the enterocytes are often
desquamated (autolysis).Â Within the lamina propria there is mild edema, slightly dilated lacteals (not visible on all
slides) and on the tips of villi a mild infiltration of macrophages with foamy cytoplasm can be seen.Â In the mucosa,
mildly increased numbers of neutrophils and eosinophils are found.
The entire wall of the small intestine is thickened by up to 3 times due to severely congested lymphatics and multifocal necrotic areas with a width of up to 0.5 cm and proliferation of granulation tissue in the lamina and tunica muscularis and the mesentery.Â The necrotic areas consist of a foamy, slightly granular, protein rich fluid in the center, surrounded by numerous lipid-laden macrophages (lipophages) with a foamy appearance in their cytoplasm. The periphery is marked by infiltration of moderate numbers of lymphocytes and plasma cells, few neutrophils and marked proliferations of fibroblasts with broad collagen bundles.Â The collagen bundles lay perpendicular to the many newly formed capillaries (granulation tissue).
Small intestine: Lymphangitis, lipogranulomatous, severe, multifocal with moderate granulation tissue formation.
Jejunitis, neutrophilic and eosinophilic, mild diffuse.
(clinical pathology, microbiology, PCR, ELISA, etc.):
The animal had a slightly distended abdomen with a small amount of free, accumulated fluid.Â The fluid was characterized by a specific gravity of 1.015, protein content of 10 g/L and nucleated cell count of 7475 Lc/Î¼l.Â The leukocytes consisted mainly of viable neutrophils (95%), few lymphocytes (2%) and monocytes/macrophages (3%). No bacteria could be found within the fluid.
Protein-losing enteropathy is an idiopathic syndrome that occurs in dogs and to a lesser
extent in other species such as horses and cats and is characterized by weight loss, hypoproteinemia, and
malabsorption.Â Multiple different diseases such as inflammatory infiltrates in the lamina propria, neoplasia,
amyloidosis or lymphangiectasias eventually associated with villus atrophy are possible causes for this syndrome.
Often a biopsy is necessary to formulate a final diagnosis(3).
In our case, the lacteals within the villar tips are not the prominent feature, although the villi are shortened and the crypts elongated.Â The main feature of the lesion is the occurrence of numerous lipogranulomas in the mucosa and mesentery.Â These lipogranulomas occur adjacent to dilated mesenteric lymphatics, but are not usually a consistent feature of lymphangiectasia(2,3,4,6).Â They are often considered as secondary lesions due to lymphatic hypertension and fat leakage and to subsequent granulomatous reponse(3,4).Â Similar granulomas occurred in experimental chronic lymphatic obstruction in rats lacking in lymphatic recanalization.(4) Experimental ligation of lymph vessels in the dog did not cause an inflammatory reaction or granuloma formation.
The cause of lymphangiectasia is not always clear.Â Some cases appear to be acquired by a chronic inflammatory bowel disease, malignant lymphoma or granulomatous infiltrates but in others, neither a congenital or acquired obstruction of the lymphatic system nor an increase in the inflammatory population of cells in the bowel wall can be seen.Â This suggests the etiology of the clinical syndrome might be more complex than simple obstruction of the lymphactics(4).
In Basenjis and Soft Coated Wheaten Terriers (SCWT), a familial predisposition for both protein-losing enteropathy (PLE) and protein-losing nephropathy (PLN) is suspected.Â However Basenjis differ from SCWT in their clinical presentation.Â In Basenjis, PLN was not seen separately without intestinal lesions, whereas PLN occurred alone in the SCWT(2).
Small intestine and mesentery: Lymphangitis, lipogranulomatous, diffuse, severe, with mild villar
Lymphangiectasia is usually caused by obstruction of lymphatic flow, most commonly due
to inflammation(5).Â Other underlying mechanisms include neoplastic infiltration, fibrosis, congenital malformation, or
physiologic obstruction due to congestive heart failure.Â When the lymphatics become obstructed, Starlings law
dictates the leakage of excess protein and lipid, which incites granulomatous inflammation.Â This exacerbates the
obstruction of lymphatics, and the ensuing cycle may result in lipogranulomatous lymphangiectasia and
lymphangitis as seen in this case(1).
Clinical pathology abnormalities often associated with lymphangiectasia include panhypoproteinemia, which is seen in severe disease with failure of compensatory plasma protein production; lymphopenia, due to loss in lymphatic fluid or stress; hypocholesterolemia; and hypocalcemia.Â Hypocalcemia is attributed to hypoalbuminemia, and the majority of dogs have serum calcium levels in the normal reference range after correction for albumin(5); however, some dogs develop ionized hypocalcemia, which may be the result of vitamin D malabsorption, seen commonly with lymphangiectasia(1).
As mentioned by the contributor, the lesions in this case largely spare the mucosa and lack the dilation of lacteals classically described in lymphangiectasia-derived protein-losing enteropathy.Â As such, this case illustrates a major limitation of surgical mucosal biopsy, which would have failed to sample the diagnostic lesions in the submucosa and outer tunics.Â The conference moderator emphasized the distinction between lipogranulomatous lymphangitis and lipogranulomas.Â In two-dimensional cross section, an inflamed lymphatic vessel may appear as a characteristic discrete granuloma with the four typical layers (i.e.Â central necrosis surrounded by histiocytes, fibrosis, and lymphocytes); however, since the inflammation is actually tracking lymphatics, the term lipogranulomatous lymphangitis may be preferable to lipogranuloma.
1.Â Hall EJ, German AJ.Â Diseases of the Small Intestine.Â In: Ettinger SJ, Feldman EC eds., Textbook of Veterinary
Internal Medicine.Â 7th ed.Â St.Â Louis, MO:Saunders Elsevier; 2010:1076, 1566-7.
2.Â Littman M.P.; Dambach D.M.; Vaden S.L.; Giger U.: Familial Protein-losing Enteropathy and Protein-losing Nephropathy in Soft Coated Wheaten Terriers: 222 Cases (1983-1997).Â J.Â Vet Intern Med; 14:68-80 (2000).
3.Â Maxie M.G.Â In Jubb, Kennedy, and Palmers Pathology of Domestic Animals: Malassimilation and Protein-losing syndromes.Â 5th Ed, Vol.2:102-104 (2007)
4.Â Suter M.M.; Palmer D.G.; Schenk H.: Primary Intestinal Lymphangiectasia in Three Dogs: A Morphological and Immunopahtologial Investigation.Â Vet.Â Pathol.22: 123-130 (1985).
5.Â Tarpley HL, Bounous DI.Â Digestive System.Â In: Latimer KS ed.Â Duncan & Prasses Veterinary Laboratory Medicine Clinical Pathology. 5th ed.Â Ames, IA:Wiley-Blackwell; 2011:242-5.
6.Â Van Kruiningen H.J.; Lees G.E.; Hayden D.W.; Meuten D.J.; Rogers W.A.: Lipogranulomatous Lymphangitis in Canine Intestinal Lymphangiectasia.Â Vet.Â Pathol. 21:377-383 (1984).