Systemic T Cell Large Granular Lymphocyte Lymphoma with Multifocal White Matter Degeneration in the Brain of a Japanese Domestic Cat

Abstract

ABSTRACT. A 10-year-old spayed female Japanese domestic cat exhibited clinical symptoms suggesting pancreatitis. One month later the cat exhibited Horner's syndrome and was euthanized. At necropsy, multiple neoplastic masses were found in the intestines, spleen, kidneys, urinary bladder, and lungs. On cytology, many neoplastic lymphocytic cells had fine to large cytoplasmic granules, suggesting large granular lymphocyte (LGL) lymphoma. Histopathological examinations revealed infiltrative proliferation of the neoplastic cells in almost organs. Immunohistochemically, the neoplastic cells were intensely positive for CD3 and granzyme B. In the brain, there were multifocal white matter lesions characterized by diffuse myelin loss with mild infiltration of the neoplastic cells. Based on these findings, the cat was diagnosed as LGL lymphoma presumptively of intestinal origin with systemic involvement.KEY WORDS: central nervous system, feline, large granular lymphocyte lymphoma, white matter lesion.

Large granular lymphoma in six cats

“…As was mentioned above, cytology is an excellent method of diagnosis in cases of large granular lymphomas (Karyia et al 1997, Derbes et al 1998, Roccabianca et al 2006, Tsuboi et al 2010. In all presented cases we were able to obtain the final diagnosis easily, and samples were rich in cells that had a distinct morphology.…”

“…Moreover, commonly the morphology of neoplastic cells, especially the presence of azurophilic cytoplasmic granules is more obvious in cytologic than histologic slides (Franks et al 1986, Roccabianca et al 2006, Tsuboi et al 2010). Because of the above mentioned points, it seems that cytopathology is a sufficient diagnostic method for large granular lymphomas.…”

“…In all cases recognized in this study typical features of large granular lymphocytes were clearly visible during cytological examination. In unequivocal cases precise diagnosis can be obtained based on immunohistochemical staining using antibodies detecting the CD3 antigen (present only in cytotoxic T lymphocytes but not in natural killer cells) or granzyme B present in normal large granular lymphocytes (Darbes et al 1997, Endo et al 1998, Tsuboi et al 2010, Moore et al 2012). However, because there is no information about the association between the presence of these markers and biological behavior, methods of treatment and prognosis, immunostaining has no additional benefit in routine practice.…”

“…LGLs originate from T cytotoxic (CD3 positive) or natural killer (CD3 negative) lymphocytes, cells which normally have cytoplasmic granules, containing various biologically active substances including granzyme, perforins, acid phosphatase and others (Kariya et al 1997, Neta et al 2008, Tsuboi et al 2010). In the majority of cases LGLs develop in intestinal mucosa producing segmental enlargement of the intestine, which with time progress into a tumoral mass easily detected during clinical examination.…”

Canine intravascular lymphoma with overt leukemia

“…Perforin and granzyme B are proteins contained in the granules of granular lymphocytes, both cytotoxic T‐cells and NK cells. Although perforin was not detected in the neoplastic cells, granzyme B, a serine protease that induces apoptosis by activation of cellular caspases, was identified using an anti‐human granzyme B polyclonal antibody shown to cross‐react with granzyme B in animals . Detection of granzyme B expression supported identification of the neoplastic cells as large granular lymphocytes, which have been shown in people to represent either CD3‐negative NK cells or CD3‐positive cytotoxic T‐cells .…”