Conference 5 - 2016 Case: 3 20160928

Signalment:

Ten-year-old, ovariohysterectomized female, miniature dachshund (Canis familiaris).The animal had a one-month history of hematochezia. A rectal mass was found and surgical excision of the mass was performed by the rectal pull-through technique.

Gross Description:

There was a polypoid mass (5×3×1 cm) on the rectal mucosa.

Histopathologic Description:

The large polyp showed severe cellular infiltration, granulation tissue, epithelial cell proliferation, interstitial mucus accumulation, hemorrhage, and osteoid formation. At the base of the polyp, goblet cells proliferated without cellular atypia and crypts were dilated due to abundant mucinous material accumulation. Mucous inflammation consisted of predominant neutrophil infiltration and less frequent macrophage, plasma cell, and lymphocyte infiltration. There are similar small lesions in the adjacent polyps.

Morphologic Diagnosis:

Rectum: Polyp, with severe inflammation, epithelial cell proliferation, mucus accumulation in crypts (Inflammatory polyps of miniature dachshunds).

Lab Results:

N/A

Condition:

Rectal polyp

Contributor Comment:

Colorectal polyps are relatively common in dogs. These polyps include non-neoplastic (hyperplastic or inflammatory) polyps and neoplastic polyps such as adenoma and adenocarcinoma. In Japan, Miniature Dachshunds show a significantly higher tendency to develop multiple polyps than other breeds. ⁵ Recently, it was proposed to refer to these polyps as inflammatory polyps of miniature dachshunds. ⁷ These polyps are nonneoplastic single or multiple polypoid lesions arising from the rectum and distal colon, and are characterized by mucosal proliferation without cellular atypia and significant inflammatory cell infiltration.⁵ Microscopically, the inflammatory polyps show inflammatory cell infiltration, hyperplastic goblet cells with dilated crypts, mucus accumulation in crypts, granulation tissue, and occasional osteoid formation.^1,8

In comparisons based on epithelial composition, the polyps displayed a thickened mucosa containing increased goblet cells, dilated crypts filled with a large amount of mucus, and mild inflammatory infiltration (mainly lymphocytes and macrophages) in the early stage.⁸ In later stages, leukocyte infiltration was more severe and consisted of mostly neutrophils and macrophages. Additionally, interstitial mucus accumulation, granulation tissue, and occasional osteoid formation were seen.⁸ In this case, predominant neutrophil infiltration, interstitial mucus accumulation, granulation tissue and osteoid formation were observed in the polyp; therefore, the lesion is comparable to that in late stage.

Although the pathogenesis remains unclear, some studies suggested that the arachidonic acid cascade, increased IL-8 production in macrophages, dysregulation of toll-like receptors and proinflammatory cytokines, and IL-17A upregulation in T cells are associated with the lesion formation.^2,6,7 Additionally, 80% of cases responded to immunosuppressive therapy with prednisolone and cyclosporine.⁵ These findings indicate that inflammatory polyp of miniature dachshunds is an immunemediated disease. However, Igarashi et al reported that two cases developed adenomas secondary to inflammatory colorectal polyps during long-term medical therapy.⁴ Further investigations are required to elucidate the pathogenesis, oncogenesis, and prognosis in inflammatory polyps of miniature dachshunds.

JPC Diagnosis:

Rectum: Inflammatory polyp, miniature dachshund, Canis familiaris.

Conference Comment:

The contributor provides a compelling example and concise summary of colorectal inflammatory polyps of miniature dachshunds (IPMD). It is unknown why inflammatory polyps occur much more commonly in miniature dachshunds than any other breed of dog in Japan. ⁸ Colorectal polyps are commonly present as single or multiple friable, lobulated, sessile, or pedunculated lesions on the mucosa.^1-8Among the polypoid masses present in the intestinal tract of dogs, the major histopathologic subtypes include nonneoplastic and hyperplastic polyps, papillary adenomas, and papillary adenocarcinomas.⁸ Most conference participants agreed that the late-stage inflammatory polyp, in this case, was difficult to differentiate from a neoplastic papillary adenoma or mucinous papillary adenocarcinoma.

In a recent study by Uchida et al. published in Veterinary Pathology, they classify IPMD into early (stage 1) and late (stages 2 and 3) lesions based on the histopathology of the mucosal epithelial components and inflammatory cells present.⁸ In addition, they use immunohistochemistry to distinguish inflammatory polyps from neoplastic cells of adenomas and adenocarcinomas using cytokeratin 20 (CK20) and beta-catenin. Normally, intestinal goblet cells and enterocytes are strongly immunopositive for CK20. The markedly hyperplastic goblet cells, which is a key histologic feature of IPMD, are also strongly immunopositive for CK20, while neoplastic cells of adenomas and adenocarcinomas were immunonegative. This indicates that inflammatory polyps are a proliferation of well-differentiated epithelial tissue and non-neoplastic. The authors also demonstrate that IPMD expressed only intracytoplasmic betacatenin, while neoplastic cells of adenomas and adenocarcinomas expressed both intracytoplasmic and intranuclear betacatenin.⁸ There have been reports of dogs with later stage (stage 3) IPMD developing rectal adenomas secondary to neoplastic transformation.⁵ Chronic inflammation and the production of pro-inflammatory cytokines can induce mutations in oncogene and tumor suppressor genes. In humans, the connection between chronic inflammatory bowel disease and development of both inflammatory polyps and colorectal carcinoma is well established.⁵ Aberrant activation of the Wnt/beta-catenin pathway occurs in the vast majority of colorectal cancers in humans and dogs and likely plays a role in neoplastic transformation of late stage IPMD. ^5,8 Inflammatory colorectal polyps are typically treated with immunosuppressive therapy and endoscope guided polypectomy.^1,5,8 Unfortunately, recurrence after polypectomy is common. Recent research suggests that dysbiosis of the gastrointestinal tract is associated with IPMD and may be a potential future therapeutic target.³

References:

1. Fukushima K, Eguchi N, Ohno K, et al. Efficacy of leflunomide for treatment of refractory inflammatory colorectal polyps in 15 miniature dachshunds. J Vet Med Sci. 2016; 78(2):265-9.

2. Igarashi H, Ohno K, Maeda S, et al. Expression profiling of pattern recognition receptors and selected cytokines in miniature dachshunds with inflammatory colorectal polyps. Vet Immunol Immunopathol. 2014; 159(1-2):1-10.

3. Igarashi H, Ohno K, Horigome A. Fecal dysbiosis in miniature dachshunds with inflammatory colorectal polyps. Res Vet Sci. 2016; 105:41-46.

4. Igarashi H, Ohno K, Ohmi A, et al. Polypoid adenomas secondary to inflammatory colorectal polyps in 2 miniature dachshunds. J Vet Med Sci. 2013; 75(4):535-538.

5. Ohmi A, Tsukamoto A, Ohno K, et al. A retrospective study of inflammatory colorectal polyps in miniature dachshunds. J Vet Med Sci. 2012; 74(1):59-64.

6. Ohta H, Takada K, Torisu S, et al. Expression of CD4+ T cell cytokine genes in the colorectal mucosa of inflammatory colorectal polyps in miniature dachshunds. Vet Immunol Immunopathol. 2013; 155(4):259- 263.

7. Tamura Y, Ohta H, Torisu S, et al. Markedly increased expression of interleukin-8 in the colorectal mucosa of inflammatory colorectal polyps in miniature dachshunds. Vet Immunol Immunopathol. 2013;156(1-2):32-42.

8. Uchida E, Chambers JK, Nakashima K, et al. Pathologic features of colorectal inflammatory polyps in miniature dachshunds. Vet Pathol. 2016; 53(4):833-839.