Andrews C, Operacz M, Maes R, et al. Cross Lineage Rearrangement in Feline Enteropathy-Associated T-cell Lymphoma. Vet Pathol. 2016 May;53(3):559-62.
Feline small intestinal lymphoma is most commonly a mucosal T-cell lymphoma (SCL) and confident diagnosis remains challenging, as it presents histologically similar to inflammatory bowel disease (IBD). Distinguishing between SCL and IBD is important since > 50% of cats with SCL die within 1 year while > 30% of cats with IBD are still alive after 1 year, and treatment may be different for the 2 conditions.
Diagnosis of SCL is most appropriately based on combination of histology, immunohistochemical phenotyping (CD3 – T cell, CD79a – B cell), and polymer chain reaction to assess antigen receptor gene rearrangements (PARR). PARR improves diagnosis by amplifying genes for T-cell receptor gamma (TCRG) in the case of T cell phenotype or genes for immunoglobulin heavy change (IGH) in case of B cell phenotype. Monoclonal expansion of TCRG or IGH with respect to T or B cells, respectively, is supportive of SCL diagnosis. However, there is a subset of cats that may show PARR polyclonal expansion. This false negative result could possibly arise due to concurrent inflammation that can mask the presences of SCL, inappropriate primers that don’t bind to their targets, or primer-binding sites may not be accessible, to name a few.
It is possible that T-cell lymphoma shows monoclonal expansion of IGH genes or B-cell lymphoma shows monoclonal expansion of TCRG. When this occurs, it is termed cross lineage rearrangement and it has been documented in humans and canine lymphoid cancers. The precise mechanism for cross lineage rearrangement in lymphocytes is unclear. In any event, this phenomenon may have diagnostic utility.
Researchers at Michigan State University in Lansing, MI, USA examined a total of 175 feline cases of suspect T cell gastrointestinal lymphoma presented at their clinic. These cases were further evaluated with a diagnostic algorithm including histopathology, immunohistochemical phenotyping and PARR for either TCRG or IGH genes. Based on this algorithm, 92 cases were consistent (and highly suggestive) with T cell lymphoma. Eight of these 92 cases had polyclonal expansion of TCRG but monoclonal expansion of IGH (8.7%).
PARR for the IGH gene may facilitate the diagnosis of cases histologically highly suggestive of T cell gastrointestinal lymphoma in which PARR polyclonality of the TCRG gene is detected. (GO)
Moore PF, Woo JC, et al. Characterization of feline T cell receptor gamma (TCRG) variable region genes for the molecular diagnosis of feline intestinal T cell lymphoma. Vet Immunol Immunopathol. 2005 Jul 15;106(3-4):167-78.