Conference 06 - 2009 Case: 2 20091021

Signalment:

6-year-old castrated, male domestic shorthair cat (Felis catus).Anorexia, soft tissue abdominal mass, no response to medical treatment.

Gross Description:

Jejunum: Marked transmural expansion by a firm, homogenous tan mass with mucosal ulceration.

Histopathologic Description:

Jejunum: Expanding and infiltrating the ulcerated mucosa, submucosa, tunica muscularis, and extending to the serosa is a poorly demarcated and unencapsulated mass. Neoplastic cells are arranged in a trabecular pattern separated, surrounded, and dissected by variably dense bands of stromal collagen (sclerosis). Neoplastic cell morphology varies from round to polygonal to spindled with variably distinct cell borders and a moderate amount of eosinophilic cytoplasm that very rarely contains basophilic granules. Nuclei range from round to oval to elongate with dispersed chromatin and one to two prominent nucleoli. Mitoses are infrequent, ranging from zero to one per 400X field. There is moderate to marked anisocytosis and anisokaryosis with occasional karyomegalic cells. Admixed throughout the neoplastic population are moderate to marked infiltrates of eosinophils.

Morphologic Diagnosis:

Jejunum: Sclerosing mast cell tumor.

Lab Results:

Moderate leukocytosis and eosinophilia.

Condition:

Feline visceral sclerosing mast cell tumor

Contributor Comment:

This case was selected from a series of a unique and unreported sclerosing variant of feline intestinal mast cell tumor (MCT) recognized at the Colorado State University Veterinary Diagnostic Laboratory. Visceral forms of MCT are relatively common in the cat, with intestinal MCT being the third most common primary intestinal tumor following lymphoma and adenocarcinoma.(10) Furthermore, visceral forms (splenic and intestinal) of mast cell tumor are more often reported in the cat compared to the dog.(5) While these tumors typically display similar microscopic features regardless of anatomical location(7,8), a sub-group of intestinal MCT in the cat is presented here which is morphologically and biologically distinct from other mast cell tumors in this species, characterized by a significant stromal component. Massons trichrome stain was pursued to confirm the stromal collagen composition of the sclerosing component, which is characterized by intense blue staining. Poorly discernible intracytoplasmic granules, which demonstrated metachromasia and enhanced visibility with giemsa and toluidine blue stains, suggest mast cell origin. Immunohistochemical staining for mast cell-specific tryptase further supported mast cell origin.(3)

Howl and Petersen (1995) described a single case report of an intestinal mast cell tumor in a cat that presented with eosinophilic enteritis. In addition to the marked eosinophilic infiltrate, this case was characterized by a marked scirrhous response surrounding the neoplastic population similar to the case presented here.(6) This demonstrates the diagnostic challenge the eosinophilic infiltrate may introduce. Thus, when confronted with a significant eosinophilic intestinal population, close attention to all histological features is necessary in order to differentiate feline intestinal sclerosing mast cell tumors from other lesions such as eosinophilic granulomatous disease(6) and feline gastrointestinal eosinophilic sclerosing fibroplasia.(2) While the marked eosinophilic infiltrate in these tumors may pose a diagnostic challenge, the presence of eosinophils is not uncommon with mast cell disease. Mast cells promote eosinophilic inflammation by producing eosinophil-directed cytokines, such as IL-4 and IL-5. These cytokines subsequently induce chemokines that specifically attract eosinophils, such as eotaxin-1 and 2.(9) In addition, the mucosal ulceration may be due, in part, to local vasoconstriction in response to the release of vasoactive substances from the mast cells, such as histamine, and subsequent devitalization of the overlying mucosal epithelium as well as by direct infiltration and mucosal effacement by the neoplastic cells.

The sclerotic component was a unique feature in all cases evaluated. There is increasing evidence that mast cells play a central role in tissue remodeling in chronic inflammatory reactions. Among the numerous substances released by mast cell tumors are the fibrogenic cytokines fibroblast growth factor and transforming growth factor β1.(1,4) These cytokines promote activation, proliferation, and migration of fibroblasts with subsequent collagen production and contraction. In addition to mast cells, eosinophils have also been shown to play a role in fibrosis. Eosinophils are similarly involved in tissue remodeling and fibrosis in allergic reactions via the release of fibrogenic cytokines such as TGF-β and IL-1β.(2,4) The release of these fibrogenic cytokines by mast cells and/or eosinophils suggests a possible mechanism of mast cell-induced sclerosis in this tumor.

JPC Diagnosis:

1. Jejunum: Malignant round cell neoplasm.
2. Jejunum: Enteritis, ulcerative, eosinophilic and mastocytic, sclerosing, transmural, severe, with mixed bacteria and anisotropic foreign material.

Conference Comment:

This very intriguing case stimulated a vibrant discussion during the conference. While conference participants carefully considered the contributors diagnosis of mast cell tumor, most participants favored the less specific diagnosis of malignant round cell neoplasm. Further, most participants considered the malignant neoplasm to be a separate, albeit possibly related, lesion from the eosinophilic and sclerosing fibroplasia. At the AFIP, additional histochemical and immunohistochemical stains did not further elucidate the histogenesis of the neoplasm. The Giemsa and toluidine blue histochemical stains demonstrated numerous metachromatic cytoplasmic granules within many mast cells throughout the areas of sclerosis in the section; the mast cells were interpreted as non-neoplastic, as they lack features of malignancy and are relatively evenly spaced within bands of collagen and fibroblasts. Furthermore, metachromatic granules were not demonstrable in the population interpreted as neoplastic cells, i.e. the sheets of monomorphic round cells with atypia and increased mitotic rate. Immunohistochemical staining with CD117a (c-kit) was noncontributory. While poorly-differentiated mast cell tumor with lack of typical cytoplasmic granules remains a possibility, many participants considered lymphoma in the differential diagnosis and attributed the prominent eosinophilic infiltrate secondary to cytokines released by neoplastic lymphocytes. Immunohistochemical staining with CD3 and CD79a revealed moderate numbers of intralesional T- and B-lymphocytes, respectively; however, the overtly neoplastic cells were negative for these markers. Based on histomorphology, and histochemical and immunohistochemical findings, participants ultimately favored the histologic diagnoses indicated above. This case demonstrates the diagnostic difficulties sometimes encountered when attempting to determine the histogenesis of poorly differentiated tumors.

The eosinophilic and sclerotic lesion in this case is remarkable, and the contributor offers a sound hypothesis for its pathogenesis. In a recent case series involving 25 cats, Craig and co-authors(2) proposed the term feline gastrointestinal eosinophilic sclerosing fibroplasia for a distinctive gastrointestinal lesion characterized by the mural presence of thick trabeculae of collagen separated by dense aggregates spindled cells. As in the present case, eosinophils and mast cells were numerous, and evenly scattered throughout the lesion. Immunohistochemical positivity for vimentin and smooth muscle actin was consistent with myofibroblastic differentiation and the authors speculated that bacteria were important in the pathogenesis of this condition. Additionally, the authors hypothesized that some cats may have a genetic predisposition to the development of this lesion, as has been proposed for other feline eosinophilic inflammatory conditions, in response to a variety of antigens. As a result, eosinophilic sclerosing fibroplasia may be thought of as a nonspecific reaction pattern to foreign antigen in genetically susceptible cats. In this case, the round cell neoplasm may have incited eosinophilic sclerosing fibroplasia by a number of mechanisms. Neoplastic cells, regardless of origin, may have directly recruited eosinophils and fibroblasts through cytokine production as hypothesized by the contributor. Alternatively, the neoplasm may have rendered the intestine vulnerable to antigen exposure by causing ulceration, partial obstruction, or altered peristalsis, allowing bacteria and digesta to penetrate the mucosa. This is supported by the presence of ulceration, numerous mixed bacteria, and embedded anisotropic foreign material (i.e. hair and food material) in many of the sections. We thank the contributor for this interesting submission.

References:

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