Pathology in Practice

Sara Soto Departament de Sanitat i d'Anatomia Animals, Facultat de Veterinària, Universitat Autònoma de Barcelona, 08193, Bellaterra-Barcelona, Spain.

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Natalia Majó Departament de Sanitat i d'Anatomia Animals, Facultat de Veterinària, Universitat Autònoma de Barcelona, 08193, Bellaterra-Barcelona, Spain.

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Albert Lloret Hospital Clínic Veterinari, Facultat de Veterinària, Universitat Autònoma de Barcelona, 08193, Bellaterra-Barcelona, Spain.

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Josep Pastor Hospital Clínic Veterinari, Facultat de Veterinària, Universitat Autònoma de Barcelona, 08193, Bellaterra-Barcelona, Spain.

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Carmen Díaz-Bertrana Sánchez Hospital Clínic Veterinari, Facultat de Veterinària, Universitat Autònoma de Barcelona, 08193, Bellaterra-Barcelona, Spain.

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Alberto Marco Departament de Sanitat i d'Anatomia Animals, Facultat de Veterinària, Universitat Autònoma de Barcelona, 08193, Bellaterra-Barcelona, Spain.

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History

Two dogs were evaluated because of chronic digestive problems. One dog (dog 1) was a 6-year-old sexually intact female Rottweiler that had diarrhea (watery to loose feces) and sporadic vomiting of 3 months' duration. Dog 1 had lost 10 kg (22 lb) of body weight during this period. The other dog (dog 2) was a 4-year-old sexually intact female French Bulldog that had vomiting and weight loss (unknown value) of 4 weeks' duration. According to the information provided by the owners, there was no geographic or domestic connection between the 2 dogs.

Clinical and Gross Findings

At the initial evaluation, dog 1 had very poor body condition. Results of a CBC were within reference intervals; serum biochemical analyses revealed slightly high concentrations of creatinine (1.7 mg/dL [reference range, 0.5 to 1.5 mg/dL]) and urea (62 mg/dL [reference range, 21.4 to 59.9 mg/dL]) and mild panhypoproteinemia (total protein concentration, 4.62 g/dL [reference range, 6 to 8 g/dL]; albumin concentration, 2.14 g/dL [reference range, 2.6 to 3.3 g/dL]). Abdominal ultrasonography revealed ileal wall thickening with indistinct layering. During exploratory laparotomy, the intestinal wall of the distal portion of the ileum appeared thickened; there was severe distension of the ileal serosal lymphatic vessels. Dog 2 had signs of abdominal pain. Results of a CBC and serum biochemical analyses were within reference limits. An intestinal mass with abnormal intestinal wall layering was detected via abdominal ultrasonography. During exploratory laparotomy, marked enlargement of the distal portion of the ileum and the cecum (affected region was approx 5 cm in length) was visible.

In dog 1, the ileum was resected but euthanasia was elected because of poor healing of the enterectomy (following 3 abdominal surgeries to correct suture dehiscence). The affected ileum and cecum of dog 2 were surgically removed. The dog died as a result of complications during the postoperative period. Necropsies were not permitted by the owners of the 2 dogs.

The distal fragment of the ileum from dog 1 and the distal portion of the ileum and the cecum from dog 2 were fixed in neutral-buffered 10% formalin. Macroscopically, severe intestinal wall thickening, luminal narrowing, and a diffusely irregular folded mucosal surface with few multifocal erosions were present in all samples. In addition, the intestinal walls had numerous transmural, white, multifocal to coalescing (0.2- to 1-cm-diameter) foci (Figure 1).

Figure 1—
Figure 1—

Photographs of transverse and longitudinal views of the distal portion of the ileum (removed during exploratory laparotomy and formalin fixed) from a 6-year-old dog that had diarrhea, sporadic vomiting, and weight loss of 3 months' duration (dog 1). In panel A, the intestinal wall is thickened and there are numerous transmural white foci. In panel B, notice the diffusely irregular intestinal mucosa with multifocal erosions.

Citation: Journal of the American Veterinary Medical Association 237, 12; 10.2460/javma.237.12.1377

Formulate differential diagnoses from the history, clinical findings, and Figure 1—then turn the page

Histopathologic Findings

Several tissue samples from both dogs were processed, embedded in paraffin, sectioned (5-μm-thick sections), and stained with H&E, periodic acid-Schiff, Ziehl-Neelsen, Gram, and Grocott methenamine silver stains. Microscopically, both dogs had similar intestinal lesions. The lymphatic vessels were distended in all intestinal layers and frequently associated with perivascular fibrosis. Some of these lymphatic vessels also had evidence of acute segmental lymphangitis with fibrinoid necrosis (Figures 2 and 3). The macroscopic white foci corresponded with large lipogranulomas, which were most often associated with lymphatic vessels. The lipogranulomas each had a central area of nonstained amorphous lipids and acicular crystals (morphologically compatible with cholesterol crystals) that was surrounded by numerous lipid-laden foamy macrophages (Figures 2 and 4). Examination of sections stained with periodic acid-Schiff, Ziehl-Neelsen, Gram, or Grocott methenamine silver stains failed to reveal microorganisms in any of the lesions.

Figure 2—
Figure 2—

Photomicrograph of a section of the ileum obtained from a 4-year-old dog that had vomiting and weight loss of 4 weeks' duration (dog 2). In this low-magnification image, lipogranulomas (asterisks) and dilated lymphatic vessels are visible. Numerous lymphatic vessels have perivascular fibrosis (arrowheads) and fibrinoid necrotizing lymphangitis (arrow). H&E stain; bar = 500 μm.

Citation: Journal of the American Veterinary Medical Association 237, 12; 10.2460/javma.237.12.1377

Figure 3—
Figure 3—

Photomicrograph of a section of the ileum obtained from dog 2. A submucosal lymphatic vessel with fibrinoid necrotizing lymphangitis is present. H&E stain; bar = 50 μm.

Citation: Journal of the American Veterinary Medical Association 237, 12; 10.2460/javma.237.12.1377

Figure 4—
Figure 4—

Photomicrographs of a section of the ileum obtained from dog 2. In the main image, several lipogranulomas are visible in the mucosal layer. A higher magnification image of a lipogranuloma is provided in the inset. Notice the central area of nonstained extracellular amorphous lipids and cholesterol crystals that is surrounded by lipid-laden foamy macrophages. H&E stain; in the main and inset images, bar = 250 and 50 μm, respectively.

Citation: Journal of the American Veterinary Medical Association 237, 12; 10.2460/javma.237.12.1377

Morphologic Diagnosis

Severe chronic ileal (dog 1) or ileal and cecal (dog 2) lymphangiectasia with lipogranulomatous and fibrinoid lymphangitis.

Comments

Intestinal lymphangiectasia (IL) is one of several processes that are classified in veterinary medicine as protein-losing enteropathies. It commonly develops in dogs.1,2 Intestinal lymphangiectasia is characterized by dilatation of intestinal lymphatic vessels and is associated with a congenital or acquired disorder of the lymphatic system.3 Leakage of lymph into the intestinal lumen causes the clinical signs and clinicopathologic abnormalities associated with IL.2 These findings are variable and can include vomiting and loss of weight (signs detected in both dogs of this report); diarrhea, as evident in dog 1, is the most characteristic clinical sign.3 Hypoproteinemia, hypocholesterolemia, hypocalcemia, and lymphopenia may also develop in association with IL, although the latter 3 abnormalities are inconsistent findings.2,3

The diagnosis of IL depends on detection of hypoalbuminemia and IL-compatible lesions.2 However, IL-affected animals may not develop severe protein loss,2 as highlighted by the dogs of this report; this may occur when the intestine is partially damaged and the nonaffected portion can compensate for the protein loss.2 Ultrasonographic findings and macroscopic lesions associated with IL can vary and are not always conclusive.2,3 In each dog of this report, the appearance of the affected portion of intestine during ultrasonographic examination and exploratory laparotomy was compatible with severe inflammation or malignancy. In addition, the ultrasonographic diagnosis of a mass-like intestinal lesion and the absence of diarrhea, as in dog 2, is an uncommon combination of findings in dogs with IL. These facts emphasize the importance of histologic evaluation of intestinal tissue samples, preferably full-thickness biopsy specimens, for confirmation of the diagnosis of IL.3

Microscopically, IL is characterized by the distension of the villi lacteals, which is usually also evident in the vessels of the underlying intestinal layers.1,4 As illustrated by the 2 dogs of this report, chronic lymphangiectasia can be followed by development of perivascular lymphatic fibrosis and lipogranulomatous inflammation of lymphatic vessels.5 Lipogranulomas appear as a result of the interstitial leakage of rich-lipid chyle. The extravasated fats and calcium salts act as a local irritant, thereby generating a granulomatous foreign body reaction with lipid-laden macrophages as its main component.5 Intestinal lymphangiectasia is infrequently associated with lipogranulomatous lymphangitis; in 2 retrospective studies3,4 of IL in dogs, lipogranulomatous lymphangitis affected up to 2.6% (1/38) and 11.8% (2/17) of animals. The low frequency of lipogranulomas supports the hypothesis that lipogranulomas are more likely a consequence rather than a cause of IL in dogs.4 Although lipogranulomatous lymphangitis associated with IL has been known since at least 1973,6 this pathological entity is still a matter of discussion. Changes in commercial diets for dogs have been related with the development of the lipogranulomas,7 and new controversial interpretations of lipogranulomatous lymphangitis in dogs have recently been published.6,8,9

Acquired IL may be attributable to obstructive lesions in the lymphatic system (ie, neoplasia or inflammation) or venous hypertension (ie, congestive heart failure).3 However, experimental obstruction of mesenteric lymphatic vessels does not result in all of the clinical signs associated with IL, suggesting that the etiology of the clinical syndrome may be more complex than simple lymphatic obstruction.1 The prognosis of IL is usually uncertain.2 However, the coexistence of IL with lipogranulomatous inflammation is associated with a poor prognosis.5 The inflammatory process, in addition to lymph leakage, interferes with the normal healing of the intestine, as illustrated by dog 1 of this report.

In dogs, IL can be associated with lipogranulomatous inflammation and can cause partial or complete intestinal obstruction. Macroscopically and ultrasonographically, it is not possible to differentiate IL from neoplasia, and results of histologic examination of affected tissues are needed for a definitive diagnosis. Because healing of an intestinal wall affected by IL is not easily accomplished (a process made more difficult yet when associated with lipogranulomatous inflammation), these cases present a challenge for veterinary clinicians.

References

  • 1 Brown CCBaker DCBarker IK. Alimentary system. In: Grant Maxie M, ed. Jubb, Kennedy, and Palmer's pathology of domestic animals. Vol 2. 5th ed. Edinburgh: Elsevier Saunders 2007;1296.

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  • 2 Peterson PBWillard MD. Protein-losing enteropathies. Vet Clin North Am Small Anim Pract 2003; 33:10611082

  • 3 Kull PAHess RSCraig LE, et al. Clinical, clinicopathologic, radiographic, and ultrasonographic characteristics of intestinal lymphangiectasia in dogs: 17 cases (1996–1998). J Am Vet Med Assoc 2001; 219:197202

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  • 4 Kleinschmidt SMeneses FNolte I, et al. Retrospective study on the diagnostic value of full-thickness biopsies from the stomach and intestines of dogs with chronic gastrointestinal disease symptoms. Vet Pathol 2006; 43:10001003

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  • 5 Van Kruiningen HJLees GEHayden DW, et al. Lipogranulomatous lymphangitis in canine intestinal lymphangiectasia. Vet Pathol 1984; 21:377383

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  • 6 Van Kruiningen HJ. Xanthogranulomatous inflammation (lett). Vet Pathol 2009; 46:155.

  • 7 Van Kruiningen HJColombel JF. The forgotten role of lymphangitis in Crohn's disease. Gut 2008; 57:14

  • 8 Romanucci MMalatesta DGuardiani P, et al. Xanthogranulomatous inflammation of the small bowel in a dog. Vet Pathol 2008; 45:207211

  • 9 Della Salda L. Xanthogranulomatous inflammation (lett). Vet Pathol 2009; 46:155.

  • Figure 1—

    Photographs of transverse and longitudinal views of the distal portion of the ileum (removed during exploratory laparotomy and formalin fixed) from a 6-year-old dog that had diarrhea, sporadic vomiting, and weight loss of 3 months' duration (dog 1). In panel A, the intestinal wall is thickened and there are numerous transmural white foci. In panel B, notice the diffusely irregular intestinal mucosa with multifocal erosions.

  • Figure 2—

    Photomicrograph of a section of the ileum obtained from a 4-year-old dog that had vomiting and weight loss of 4 weeks' duration (dog 2). In this low-magnification image, lipogranulomas (asterisks) and dilated lymphatic vessels are visible. Numerous lymphatic vessels have perivascular fibrosis (arrowheads) and fibrinoid necrotizing lymphangitis (arrow). H&E stain; bar = 500 μm.

  • Figure 3—

    Photomicrograph of a section of the ileum obtained from dog 2. A submucosal lymphatic vessel with fibrinoid necrotizing lymphangitis is present. H&E stain; bar = 50 μm.

  • Figure 4—

    Photomicrographs of a section of the ileum obtained from dog 2. In the main image, several lipogranulomas are visible in the mucosal layer. A higher magnification image of a lipogranuloma is provided in the inset. Notice the central area of nonstained extracellular amorphous lipids and cholesterol crystals that is surrounded by lipid-laden foamy macrophages. H&E stain; in the main and inset images, bar = 250 and 50 μm, respectively.

  • 1 Brown CCBaker DCBarker IK. Alimentary system. In: Grant Maxie M, ed. Jubb, Kennedy, and Palmer's pathology of domestic animals. Vol 2. 5th ed. Edinburgh: Elsevier Saunders 2007;1296.

    • Search Google Scholar
    • Export Citation
  • 2 Peterson PBWillard MD. Protein-losing enteropathies. Vet Clin North Am Small Anim Pract 2003; 33:10611082

  • 3 Kull PAHess RSCraig LE, et al. Clinical, clinicopathologic, radiographic, and ultrasonographic characteristics of intestinal lymphangiectasia in dogs: 17 cases (1996–1998). J Am Vet Med Assoc 2001; 219:197202

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4 Kleinschmidt SMeneses FNolte I, et al. Retrospective study on the diagnostic value of full-thickness biopsies from the stomach and intestines of dogs with chronic gastrointestinal disease symptoms. Vet Pathol 2006; 43:10001003

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5 Van Kruiningen HJLees GEHayden DW, et al. Lipogranulomatous lymphangitis in canine intestinal lymphangiectasia. Vet Pathol 1984; 21:377383

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6 Van Kruiningen HJ. Xanthogranulomatous inflammation (lett). Vet Pathol 2009; 46:155.

  • 7 Van Kruiningen HJColombel JF. The forgotten role of lymphangitis in Crohn's disease. Gut 2008; 57:14

  • 8 Romanucci MMalatesta DGuardiani P, et al. Xanthogranulomatous inflammation of the small bowel in a dog. Vet Pathol 2008; 45:207211

  • 9 Della Salda L. Xanthogranulomatous inflammation (lett). Vet Pathol 2009; 46:155.

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