Wright KZ, Hohenhaus AE, Verrilli AM, Vaughan-Wasser S. Feline large-cell lymphoma following previous treatment for small-cell gastrointestinal lymphoma: incidence, clinical signs, clinicopathologic data, treatment of a secondary malignancy, response and survival. J Feline Med Surg.2018 Jun 1;:1098612X18779870
Small cell lymphoma is a common cancer of the intestinal tract of cats. This is a diffuse, infiltrative neoplasm that generally follows an indolent course and may represent the majority of GI lymphoma. It often carries a reasonable long term prognosis and is usually managed with oral therapy (steroids and chlorambucil). Large cell (high grade, lymphoblastic) lymphoma is a more aggressive form of GI neoplasia that more commonly forms focal masses rather than diffuse infiltrates. This form of lymphoma has a significantly lower median survival time and generally requires aggressive intravenous chemo therapy (ie COP or CHOP) to treat. It has been understood for some time that a proportion of cats treated for small cell lymphoma (SCLSA) will go on to develop other cancer, including large cell lymphoma (LCLSA), however the rate at which this occurs is not known.
The purpose of this study was to determine the rate of development of LCLSA in cats undergoing therapy for lymphoma. Cats presenting to a referral hospital in a period from 2008 to 2017 with a diagnosis of SCLSA or LCLSA were included. Diagnosis of SCLSA was reach based on histopathology with or without clonality assessment of one or more segments of the GI tract. LCLSA diagnosis could be based on cytology or histology. Cats with large granular lymphoma were grouped with LCLSA. Cats were included if they were treated for both SCLSA and LCLSA with complete follow up.
740 cats were diagnosed with lymphoma, of which 290 were intestinal. 121 were treated for SCLSA, 146 for LCLSA, and 11 had both diagnosed simultaneously. Of the 121 cats with SCLSA, 12 were subsequently diagnosed with LCSLA, of which 9 received therapy. Data on age, weight, BCS, clinicopathologic signs, biochemical, hematologic and radiographic abnormalities were recorded. Chemotherapy protocols, response to therapy, and maximum survival were also recorded.
The most common locations for small cell LSA were the duodenum and the ileum. Vomiting was the most common clinical sign. Of the 9 cats included in final analysis; two received only glucocorticoid therapy, 6 also received chlorambucil, and one received CHOP transitioning to single agent mechlorethamine.
Mean event-free survival form diagnosis of SCLSA to diagnosis of LCLSA was 543 days. Median survival from diagnosis of SCLSA to death was 615 days. 5 of 9 cats became anemic between the diagnosis of SCLSA and LCLSA; median decrease in hematocrit , albumin, and total protein between diagnoses were statistically significant. Cats also had a significant decrease in weigh prior to presentation.
The paper suggests three separate reasons for the development of secondary large cell LSA: spontaneous generation of a novel cancer; mutation of small neoplastic lymphocytes into large neoplastic cells; or chemotherapy induced mutations resulting in oncogenesis. It is unclear is one or several of these contributed to secondary lymphoma in these cases.
There were several limitations to this study. The data was collected from a single referral institution, which may bias the results due to a lack of diversity in the sample population. The 3.7% of cats who presented with both small and large cell LSA may have also developed one before the other, but were unable to be included in the data analysis.
The authors suggest that 9.9% of cats diagnosed with small cell lymphoma will eventually develop large cell lymphoma. They further suggest that in cats with a diagnosis of small cell lymphoma; a sudden drop in weight, hematocrit, and/or total protein should prompt investigation for the development of large cell lymphoma. (MRK)