Follicular Lymphoma in Companion Animals

Lymphoma is an enigmatic and fascinating disease complex that involves almost all vertebrates and can be of B, T, or NK cell of origin. More than 70% of canine lymphomas are of B cell origin. Since the discovery of Hodgkin’s lymphoma by an anatomist Thomas Hodgkin in 1832, all malignant lymphomas in humans were characterized as either Hodgkin lymphoma or non-Hodgkin lymphoma at the beginning of the twenty-first century [2]. Follicular lymphomas (FL) are the common subtype of non-Hodgkin lymphoma in humans and are associated with an indolent i.e, slowly progressive biological behavior in early stages. Follicular lymphoma in animals is rare with incidence ranging from 0.3-4%. This wide range likely reflects changing interpretations of follicular lesions and the use of immunohistochemical assistance in detecting poorly differentiated follicular lesions [1]. Follicular lymphoma has been reported mostly in dogs which are generally over 10-year-old. It is often noticed on incidental examination and may be present in multiple external and internal lymph nodes but those in head, neck, prescapular, and popliteal regionsare likely to be involved. Animals are generally active and have normal appetites. Spleen, liver and bone marrow may be involved in the late stage. Follicular lymphoma is a unique tumor because, in the early stages, cells do not die and keep on accumulating due to mutation of the anti-apoptotic (BCL-2) gene. As these cells proliferate they acquire additional mutations e.g. p53 which aid in tumor progression. In humans, FL is characterized by the chromosomal breaks at 18q21 and rearrangement of the BCL-2 gene. By this translocation, the BCL-2 gene in chromosome 18 is juxtaposed to the immunoglobulin heavy-chain region of the chromosome 14 that results in the BCL-2/Ig-H rearrangement and since the Ig heavy chain region is in active transcription, there is up-regulation of the BCL-2 gene. As a result of this translocation, the affected cells have constitutively high levels of anti-apoptotic protein BCL-2 [1,2]. Follicular lymphomas are derived from germinal center centroblast which is of B cell origin. In early stages, FL is composed of variable mixtures of centroblasts and centrocytes. Histologically, it is a nodular lymphoma which lacks light and dark poles of reactive germinal centers and is surrounded by a thin or fading rim of non-neoplastic mantle and marginal zone cells. In contrast to the reactive germinal centers, post-capillary venules are often displaced on the periphery of the neoplastic follicles. In early stages, neoplastic follicles,