Dr Sue Cancer Vet PLLC, Oncology, Tarrytown, NY, USA; Animal Specialty & Emergency Center, Wappinger Falls, NY, USA
Lymphoma (LSA) is one of the most commonly occurring cancers in cats. Lymphoma is collection of cancers arising from the malignant transformation of lymphocytes and is a diverse group of neoplasms with the common origin of the lymphoreticular cells. In contrast to dogs, feline lymphoma most commonly affects the gastrointestinal (GI) tract. Like dogs, lymphoma is a systemic disease that requires chemotherapy in almost all cases. Outcomes for treated cats are, however, less predictable than dogs, but cats tend to tolerate chemotherapy better than dogs. Treated cats do live longer, and chemotherapy is generally well-tolerated. The diagnostic and treatment choices can be confusing and overwhelming, especially when distinguishing IBD, low grade lymphoma, and high grade lymphoma.
Feline Chronic Small Bowel Disease (CSBD)
CSBD includes inflammatory bowel disease (IBD) and enteropathy-associated T-cell LSA (EATL) type 2 (low grade lymphoma). EATL type 2 is the most common infiltrative GI LSA in cats, and treatment is different than IBD. In 2013 Norsworthy et al. reported that CSBD often is often considered normal by cat owners. Excuses by owners include: “He just eats fast,” “She is a nervous cat,” “He has a sensitive stomach,” “She gets hairballs,” “He’s always done this.”
In this study, the authors looked at the association of clinical signs and disease in 100 cats that had an AUS of small bowel >0.28 cm in >2 locations. These cats had >1: vomiting >2x/month for at least 3 months, several weeks of small bowel diarrhea, and weight loss >0.5 kg in last 6 months. Interestingly, 26 cats were getting wellness exams. Sixty-five cats did not have surgery and were excluded. Clinical signs included weight loss 70%, vomiting >2x 61%, diarrhea 11%, and V/D 13%. Ninety-two percent (92%) had at least 1 AUS measurement >0.3 cm, 8 cats 0.29–0.29 cm, and 76 cats 1 measurement <0.28 cm. Ninety-nine (99) of 100 had cats had IBD or LSA. Only 1 cat had normal histology. Forty-nine percent (49%) had IBD/chronic enteritis. Forty-six percent (46%) had LSA (n=44 EATL type 2). Cats <8 years old had enteritis, and cats >8 years old enteritis or cancer. The 1 normal cat was 5 years old.
Cats with GI clinical signs are common and should undergo diagnostics. Do not let clients make excuses, and get a good history. Chronic vomiting is often considered normal, but vomiting is not normal! Clinical signs should trigger abdominal ultrasound. One of the common excuses is vomiting hairballs is normal. Is vomiting hairballs is normal? Does chronic small bowel disease slow bowel movement and predispose to formation?
Pathology and Behavior
For alimentary/GI LSA, the LSA typically involved the intestines alone or intestines, lymph nodes (LN), and liver. In the GI tract, it can be solitary vs. diffuse. Fifty-five percent (55%) of GI tumors are LSA. Siamese are at increased risk. The GI form typically occurs in aged cats of 12 to 13 years old. The small intestines are four times more affected than the large intestines.
Enteropathy-associated T-cell LSA (EATL) has 2 forms. EATL Type I is intermediate to large B-cells, high grade, lymphoblastic lymphoma. This form often has a palpable mass. EATL Type II is called small cell, low grade, lymphocytic lymphoma. This form is more diffuse throughout the GIT and T-cell is more common.
For low grade small cell LSA, clinical signs include weight loss (83–100%), V/D (73–88%), anorexia (66%), and icterus (7%). Seventy percent (70%) have abnormal palpation on exam, either thickened GI or a palpable mass 33%. The history is usually chronic over several months, with a median 6 months.
For high grade LSA, the clinical signs are similar but icterus is more common and the onset is more rapid - days to weeks. A palpable mass is common. Rarely the cat will present with acute abdomen due to obstruction or perforation.
Diagnosis and Staging
Basic diagnostics include CBC, chemistry panel, and UA. For the GI forms, 23% have panhypoproteinemia and 76% are anemic. Test for FeLV/FIV status. Diagnosis typically made with cytology or histology of a LN or organ. Cytology may be inconclusive and be reported as benign hyperplastic and reactive, and histology will be needed. Other diagnostics may include abdominal ultrasound (AUS) and chest radiographs. Bone marrow cytology may be recommended especially for cases with anemia, leukopenia, or cellular atypia. Phenotype can be determined with PARR 80% sensitive or flow cytometry.
For high grade large cell (EATL type I), the diagnosis is typically more straightforward with GI masses, enlarged mesenteric LN, or liver involvement. The diagnosis is typically made with abdominal ultrasound and cytology/histology. Surgery is less commonly needed.
For low grade small cell (EATL type II), intestinal thickening is often modest or absent and similar to IBD.
Cytology alone is often insufficient and will come back as benign hyperplasia. To confirm the diagnosis, AUS and histopathology are typically needed, and may require phenotype and clonality.
It can be challenging to distinguish low grade vs. IBD with abdominal ultrasound. With low grade GI LSA, 60–90% have an abnormal AUS with 50–70% diffuse SI thickening, predominantly muscularis propria and submucosa layers. Mesenteric lymph nodes are abnormal in 45–80%. Focal GI masses are uncommon. For IBD, 10–50% have diffuse SI thickening and mucosal thickening more common. The incidence of mesenteric LN lymph nodes is lower at 15–20%, and other abnormal organs are typically normal.
Cytology is rarely useful for distinguishing low grade GI LSA vs. IBD. The debate rages on regarding endoscopy vs. full thickness biopsy (laparotomy vs. laparoscopy). On histopathology, lymphoma typically has lymphoid infiltration beyond mucosal layer, epitheliotropism, heterogeneity, and lymphocyte nuclear size consistent with malignancy. If diagnosis is still equivocal, phenotype or PARR is recommended.
There are less feline data than for canine lymphoma. Papers often lump together small number of cases of multiple subtypes of various anatomic, phenotype and histologic grades. Outcomes are less predictable in cats and there is greater variation in histologic type and anatomic location in cats. But cats tolerate chemotherapy well and better than dogs. Febrile neutropenia is rare. Most owners are happy they chose to treat and QOL improves.
Which protocol? For intermediate and high grade/EATL I, there is an overall response of 50–80%, a median remission of 4 months, and a median survival 6 months. Cats that achieve a complete remission have a MST of 1 year. I typically recommend a CHOP multiagent protocol such as the UW 25 week protocol. When using doxorubicin in cats, I use a lower dose (1 mg/kg). Cardiac toxicity is not clinical problem in cats in contrast to dogs, and renal function (BUN, Cr, USG) should be monitored in cats when giving doxorubicin. In dogs, data supports shorter maintenance-free protocol, but there is no data in cats, and some cats may need chronic chemotherapy.
An alternative protocol is the COP protocol with reported complete remissions of 50–70%. This is commonly used in used in Europe with similar results to CHOP in 1 study. While the protocol requires less frequent visits, it is a longer 1 year protocol. Other studies support the addition of doxorubicin to COP for durable responses.
For single agent options, Lomustine can be given at 50–60 mg/m2 every 4–6 weeks, which is given at a lower dose and less frequently than dogs. Single agent doxorubicin in cats is less successful with complete remission rates of <50%.
For low grade/EATL type II, less aggressive chemotherapy protocols are typically used. Oral chlorambucil (Leukeran®) can be dose with pulse dosing (20 mg/m2 every 2 weeks or 15 mg/m2 for 4 days every 3 weeks) or with chronic dose (>4 kg start @ 2 mg PO q 2 day, maintenance q 3 days; <4 kg start @ 2 mg PO q 3 day, maintenance q 4 days). For cats I prefer prednisolone, typically at 1–2 mg/kg orally daily and reduce to 0.5 to 1 mg/kg daily. In some cases, prednisolone may be discontinued.
For relapsed cases, cyclophosphamide, lomustine, and vinblastine are recommended. For severe or refractory cases, I will used CHOP or COP protocols.
Nutrition for EATL type II: With evidence of role of inflammation and many have concurrent IBD, there is thought to consider transition to a novel protein diet and add probiotics. I also recommend running B12 levels, and supplementing as indicated.
Prognostic factors: The prognosis and response in cats is more variable than in canine lymphoma. Prognostic factors include anatomic location, achieving a CR, FeLV status, substage, and a multi-agent protocol (CHOP vs. COP?). Factors that are not prognostic in cats include stage and immunophenotype, age, weight, gender, and FIV.
For GI forms, the prognosis is overall extremely variable. For EATL type I, response rates are 50–75%, median remission duration is 4–6 months, and expected survival is 6–8 months. Fifteen to 25% can live 1–2 years. For EATL type II, remission is generally defined as improvement or resolution of clinical signs, 70%–85% will respond for a median survival time of >2 years.
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