Feline low-grade alimentary lymphoma: an emerging entity and a potential animal model for human disease

Abstract

Background: Low-grade alimentary lymphoma (LGAL) is characterised by the infiltration of neoplastic T-lymphocytes, typically in the small intestine. The incidence of LGAL has increased over the last ten years and it is now the most frequent digestive neoplasia in cats and comprises 60 to 75% of gastrointestinal lymphoma cases. Given that LGAL shares common clinical, paraclinical and ultrasonographic features with inflammatory bowel diseases, establishing a diagnosis is challenging. A review was designed to summarise current knowledge of the pathogenesis, diagnosis, prognosis and treatment of feline LGAL. Electronic searches of PubMed and Science Direct were carried out without date or language restrictions.

Results: A total of 176 peer-reviewed documents were identified and most of which were published in the last twenty years. 130 studies were found from the veterinary literature and 46 from the human medicine literature. Heterogeneity of study designs and outcome measures made meta-analysis inappropriate. The pathophysiology of feline LGAL still needs to be elucidated, not least the putative roles of infectious agents, environmental factors as well as genetic events. The most common therapeutic strategy is combination treatment with prednisolone and chlorambucil, and prolonged remission can often be achieved. Developments in immunohistochemical analysis and clonality testing have improved the confidence of clinicians in obtaining a correct diagnosis between LGAL and IBD. The condition shares similarities with some diseases in humans, especially human indolent T-cell lymphoproliferative disorder of the gastrointestinal tract.

Conclusions: The pathophysiology of feline LGAL still needs to be elucidated and prospective studies as well as standardisation of therapeutic strategies are needed. A combination of conventional histopathology and immunohistochemistry remains the current gold-standard test, but clinicians should be cautious about reclassifying cats previously diagnosed with IBD to lymphoma on the basis of clonality testing. Importantly, feline LGAL could be considered to be a potential animal model for indolent digestive T-cell lymphoproliferative disorder, a rare condition in human medicine.

Keywords: Cat; Comparative oncology; Human indolent digestive T-cell lymphoproliferative disorder; Inflammatory bowel disease.

Fig. 1

Ultrasonographic appearance of normal intestine (a) and low-grade alimentary lymphoma (LGAL) (b), longitudinal section. Note the marked thickening of the muscularis propria in the patient with LGAL (b) compared to a cat with a normal jejunal layering (a). The full thickness of both loops (between calipers) is within normal limits: normal jejunum 2.7 mm and LGAL jejunum 2.5 mm. Scale: 10 mm

Fig. 2

Ultrasonographic images depicting a diffuse intestinal wall thickening in low-grade alimentary lymphoma (LGAL) (a) and inflammatory bowel disease (IBD) (b). a Cat with advanced LGAL (duodenum): a moderate thickening of the muscularis propria is observed. Full-thickness (between calipers): 3.7 mm. b Cat with IBD, eosinophilic enteritis (small intestine): note the similar ultrasonographic appearance of the intestine compared to LGAL aspect. Full thickness (between calipers): 3.9 mm. Scale: 10 mm

Fig. 3

Histological features of low-grade alimentary lymphoma (LGAL) and plasmacytic enteritis (haematoxylin-eosin-staining, 400X). a LGAL: monomorphic dense infiltrate of small lymphocytic cells with discrete nuclear atypia; some plasma cells are present. b Plasmacytic enteritis: less compact infiltrate of small lymphocytes with dense nucleus; more plasma cells are present

Fig. 4

Histological (a) (haematoxylin-eosin-staining, 200X) and immunohistochemical (b) (anti-CD3, immunoperoxydase, 200X) features of low-grade alimentary lymphoma (LGAL) showing dense infiltration of the lamina propria composed of a mixture of small CD3⁺ T lymphocytes and plasma cells, with epitheliotropism (small intestine biopsies)

Fig. 5

Comparison of histological and immunohistochemical features of feline low-grade alimentary lymphoma (LGAL) and human indolent digestive T-cell lymphoproliferative disease (LPD). Top Panel: Human indolent CD4⁺ T-cell lymphoproliferative disease of the gastrointestinal tract. Biopsies of the antrum (a, b, c) and duodenum (d, e, f) show important CD3⁺ (b and e) and CD4⁺ (c and f) lymphoid infiltrate into the lamina propria (asterisk), mostly composed by small lymphocytes. Epitheliotropism is mostly absent, with however focal exceptions such as small CD4+ T-cells localized here in the duodenal epithelium (arrow). Bottom Panel: Feline T-cell low-grade alimentary lymphoma. Biopsies of the jejunum show epitheliotropic lymphocytic infiltrate involving the lamina propria (g), exhibiting a CD3⁺ phenotype (h)