Diagnostic Algorithm to Differentiate Lymphoma From Inflammation in Feline Small Intestinal Biopsy Samples

Abstract

Differentiating between inflammatory bowel disease (IBD) and small intestinal lymphoma in cats is often difficult, especially when only endoscopic biopsy specimens are available for evaluation. However, a correct diagnosis is imperative for proper treatment and prognosis. A retrospective study was performed using surgical and endoscopic intestinal biopsy specimens from 63 cats with a history of chronic diarrhea or vomiting or weight loss. A diagnosis of lymphoma or inflammation was based on microscopic examination of hematoxylin and eosin (HE)-stained sections alone, HE-stained sections plus results of immunohistochemical labeling (IHC) for CD3e and CD79a, and HE staining, immunophenotyping, and polymerase chain reaction (PCR) results for B and/or T cell clonality. In addition, various histomorphologic parameters were evaluated for significant differences between lymphoma and IBD using Fisher's exact test. The sensitivity and specificity of each parameter in the diagnosis of lymphoma were also determined. Results of Bayesian statistical analysis demonstrated that combining histologic evaluation of small intestinal biopsy specimens with immunophenotyping and analysis of clonality of lymphoid infiltrates results in more accurate differentiation of neoplastic versus inflammatory lymphocytes. Important histologic features that differentiated intestinal lymphoma from IBD included lymphoid infiltration of the intestinal wall beyond the mucosa, epitheliotropism (especially intraepithelial nests and plaques), heterogeneity, and nuclear size of lymphocytes. Based on the results of this study, a stepwise diagnostic algorithm that first uses histologic assessment, followed by immunophenotyping and then PCR to determine clonality of the lymphocytes, was developed to more accurately differentiate between intestinal lymphoma and IBD.

Relationship of the mucosal microbiota to gastrointestinal inflammation and small cell intestinal lymphoma in cats

“…The authors did attempt to circumvent this limitation by performing PARR on any sample that exhibited questionable lymphoid monomorphism. Furthermore, it has been suggested that although PARR is valuable as a differentiating diagnostic test, it should be considered as an adjunct to immunohistochemical and histologic diagnostics, as it also does have its limitations relative to false negatives 2, 74. It has been recommended that PARR be considered as part of a stepwise diagnostic strategy, indicating the importance of more advanced testing only as required in a true clinical setting 2, 74…”

“…Frequent identification of the disease continues today, most notably in cats with chronic weight loss, vomiting, decreased appetite and diarrhea. Small cell GI LSA closely resembles feline inflammatory bowel disease (IBD) in its clinical presentation,2 with both diseases having poorly defined etiologies. Various risk factors including genetic and molecular alterations,3, 4, 5 diet,3, 6, 7 and chronic inflammation8, 9, 10 have been linked to the development of both disorders.…”

When Tissue Antigens and Antibodies Get Along

“…Molecular demonstration of clonality supports a diagnosis of neoplasia, for example, in feline intestinal lymphoma, in which histologic distinction between neoplastic lymphocytes and reactive lymphocytes of inflammatory bowel disease is difficult. 185,190,246 Patterns of Specific Labeling. Antigens can be present in various organelles and intracellular locations or outside cells (Fig.…”

Beyond H&E

“…Specific histologic features that aid in this distinction have been well established in cats. 10,58,87 However, in many cases, histology alone or histology plus immunophenotyping is insufficient for diagnosis. PARR testing is especially helpful when only superficial endoscopic biopsy samples are available or in early cases of lymphoma that lack submucosal invasion or marked epitheliotropism (Fig.…”

“…A diagnostic algorithm, using histologic features, immunophenotyping, and PARR testing, has been established to aid in the diagnosis of feline intestinal lymphoma. 58 Just like many of the molecular tools described in this review, PARR testing should never be used as a stand-alone test. The pathologist needs to interpret the histologic features, immunophenotyping, and clinical findings in conjunction with one another.…”