NAVLE Hemic and Lymphatic

Feline Lymphoma and Leukemia – NAVLE Study Guide

📅 March 28, 2026 ⏱ 25 min read

Lymphoma is the most common neoplasm in cats, comprising approximately 30% of all feline tumors. It arises from malignant transformation of lymphocytes and can affect virtually any organ system.

Overview and Clinical Importance

Lymphoma is the most common neoplasm in cats, comprising approximately 30% of all feline tumors. It arises from malignant transformation of lymphocytes and can affect virtually any organ system. Feline leukemia virus (FeLV) infection remains an important associated factor, particularly for mediastinal and multicentric forms, though the prevalence of FeLV-associated lymphoma has declined significantly due to widespread testing and vaccination programs.

Understanding the classification, diagnosis, and treatment of feline lymphoma/leukemia is essential for the NAVLE, as these conditions represent high-yield topics with significant clinical implications for prognosis and therapy selection.

Anatomical Form	Prevalence	FeLV Association	Typical Age
Alimentary	50-70%	Low (usually FeLV-negative)	Middle-aged to older (10-13 years)
Mediastinal	12-17%	High (often FeLV-positive)	Young cats (2-4 years)
Multicentric	9-15%	High (FeLV/FIV associated)	Variable
Extranodal	12-37%	Variable by site	Variable by site

Anatomical Classification of Feline Lymphoma

Feline lymphoma is classified by anatomical location, with alimentary (gastrointestinal) lymphoma being the most common form in modern practice. The traditional classification includes four main anatomical forms:

High-YieldThe shift from mediastinal/multicentric to alimentary lymphoma as the predominant form reflects the decreased prevalence of FeLV infection due to testing and vaccination. Remember: Alimentary lymphoma is typically FeLV-negative and occurs in older cats, while mediastinal lymphoma is often FeLV-positive and occurs in younger cats.

Diagnostic Modality	Findings
Bloodwork	Often normal; hypocobalaminemia (low B12) in 78% of cases; hypoalbuminemia may be present
Abdominal Ultrasound	Mild-moderate diffuse small intestinal wall thickening; preserved wall layering; thickening of muscularis propria layer (approximately 2x normal); mesenteric lymphadenopathy possible
Cytology	Usually non-diagnostic; cannot distinguish from benign lymphoid hyperplasia or IBD
Histopathology	Gold standard; shows monomorphic small lymphocyte infiltration in lamina propria; epitheliotropism common; full-thickness biopsy preferred over endoscopic biopsy
PARR Testing	PCR for antigen receptor rearrangement; detects clonal lymphocyte population; 68-90% sensitivity; helps differentiate from polyclonal IBD
Immunohistochemistry	Usually CD3+ (T-cell); rarely CD79a+ or CD20+ (B-cell)

Alimentary Lymphoma

Alimentary lymphoma (AL) is the most common form of feline lymphoma, affecting the gastrointestinal tract with or without involvement of mesenteric lymph nodes and liver. AL is classified into three histological grades with distinct clinical presentations, treatments, and prognoses.

Low-Grade Alimentary Lymphoma (LGAL)

Synonyms: Small cell lymphoma, lymphocytic lymphoma, well-differentiated lymphoma

Clinical Presentation: LGAL has an indolent course with chronic clinical signs developing over months (median 6 months). Owners typically report weight loss (83-100%), vomiting and/or diarrhea (73-88%), anorexia (66%), and lethargy. Approximately 70% of affected cats have abnormal abdominal palpation findings, including diffuse intestinal thickening or mesenteric lymphadenopathy.

Pathophysiology: LGAL is characterized by infiltration of well-differentiated, small neoplastic T-lymphocytes primarily into the small intestine. The disease is predominantly T-cell in origin (greater than 90%) with frequent epitheliotropism. There is increasing evidence supporting progression from inflammatory bowel disease (IBD) to LGAL in some cases.

Diagnostic Features of LGAL

Treatment of LGAL

LGAL is treated with oral chemotherapy administered at home. The standard protocol combines chlorambucil and prednisolone:

NAVLE TipGreater than 90% of cats with LGAL respond to chlorambucil and prednisolone therapy. Treatment is typically continued for 1 year if complete clinical remission is achieved, then discontinued. If relapse occurs, the same protocol can be reintroduced as rescue therapy with good response rates. Median survival time is 2-3 years with treatment.

High-Grade Alimentary Lymphoma (HGAL)

Synonyms: Large cell lymphoma, lymphoblastic lymphoma, intermediate-high grade lymphoma

Clinical Presentation: HGAL has an acute onset with rapid progression of clinical signs over days to weeks. Signs include severe weight loss, anorexia, vomiting, diarrhea, and lethargy. A palpable abdominal mass is often present. Intestinal obstruction or perforation may occur.

Pathophysiology: HGAL is characterized by infiltration of large, poorly differentiated (lymphoblastic) neoplastic cells. It is predominantly B-cell in origin. The disease often presents as focal or multifocal intestinal masses with loss of normal intestinal wall layering and may involve multiple extraintestinal sites.

Diagnostic Features of HGAL

Treatment of HGAL

HGAL requires aggressive multi-agent chemotherapy. The two primary protocols are COP (Cyclophosphamide, Vincristine, Prednisolone) and CHOP (Cyclophosphamide, Doxorubicin, Vincristine, Prednisolone):

High-YieldUnlike dogs, cats with lymphoma do not respond as robustly to chemotherapy. Only approximately 38% achieve complete remission, and 25% achieve partial remission. Response to therapy is the most important prognostic factor. Cats achieving complete remission have median survival of 7-10 months; some survive greater than 2 years.

Large Granular Lymphocyte Lymphoma (LGLL)

LGLL is a distinct, aggressive subtype of alimentary lymphoma comprising 6-28% of feline GI lymphomas. It is characterized by large lymphocytes containing prominent intracytoplasmic azurophilic (magenta) granules visible on cytology (Romanowsky-type stains).

Key Features: Most commonly affects mesenteric lymph nodes and small intestine. Usually FeLV/FIV negative. Can be T-cell, B-cell, or non-T/B (null) cell origin. Diagnosis requires Giemsa or Wright-Giemsa staining for granule visualization, or immunohistochemistry for granzyme B.

Prognosis: LGLL carries a grave prognosis with poor response to chemotherapy. Median survival time is only 21-57 days with treatment. Surgical resection of localized disease combined with chemotherapy may improve outcomes in select cases.

NAVLE TipWhen you see a cat with alimentary lymphoma and intracytoplasmic granules on cytology, think LGLL. This is a high-yield NAVLE point because the prognosis is significantly worse than other alimentary lymphomas, and owners should be counseled accordingly. Special stains or immunohistochemistry for granzyme B may be needed for diagnosis.

Drug	Dosage	Administration
Chlorambucil	2 mg/cat PO every 48-72 hours OR 20 mg/m² PO every 2 weeks (pulse)	Oral at home
Prednisolone	2 mg/kg PO daily initially, then 1 mg/kg PO daily or every other day after remission	Oral at home
Cobalamin (B12)	250 µg SC weekly for 6 weeks, then every 2-4 weeks as needed	Subcutaneous or oral

Mediastinal Lymphoma

Mediastinal lymphoma involves the thymus, mediastinal lymph nodes, and sternal lymph nodes. It is strongly associated with FeLV infection and typically occurs in young cats (2-4 years). Siamese cats are predisposed to a distinct FeLV-negative form with a more favorable prognosis.

Clinical Signs: Dyspnea/tachypnea (due to mass effect and/or pleural effusion), regurgitation, coughing, decreased lung sounds, and non-compressible cranial thorax. Pleural effusion is common.

Diagnosis: Thoracic radiographs show cranial mediastinal mass and often pleural effusion. FNA cytology of the mass or fluid analysis (high lymphoblast count) is usually diagnostic. FeLV testing is essential.

Treatment and Prognosis: COP or CHOP chemotherapy. Median survival 2-3 months for FeLV-positive cats. Siamese cats with FeLV-negative mediastinal lymphoma may have median survival of 9 months with treatment.

Diagnostic Modality	Findings
Abdominal Palpation	Palpable abdominal mass; thickened intestinal loops; peritoneal effusion possible
Abdominal Ultrasound	Focal/multifocal hypoechoic intestinal mass(es); loss of wall layering; marked mesenteric lymphadenopathy; may have concurrent hepatic, splenic, or renal masses
Cytology (FNA)	Often diagnostic; monomorphic population of large, immature lymphoid cells (lymphoblasts) with high nuclear-to-cytoplasmic ratio; mitotic figures; greater than 70% lymphoblasts
Immunophenotype	Usually B-cell (CD79a+ or CD20+); less commonly T-cell (CD3+)

Other Extranodal Lymphomas

Renal Lymphoma

Typically bilateral kidney involvement presenting as renomegaly. Clinical signs mimic chronic kidney disease: increased thirst/urination, weight loss, vomiting, anorexia. Important: Renal lymphoma has a high rate of CNS extension (spinal cord and brain), so cytarabine is often added to the chemotherapy protocol (COAP protocol). Doxorubicin should be used cautiously due to nephrotoxicity concerns.

Nasal Lymphoma

Presents with sneezing, nasal discharge (often unilateral initially, then bilateral), epistaxis, facial deformity, and epiphora. Diagnosis via nasal biopsy. Treatment: Radiation therapy is the treatment of choice for localized nasal lymphoma. Response rates of 70-90% with median survival of 1.5-2 years. If staging reveals systemic disease, chemotherapy is indicated.

Protocol	Components	Outcomes
COP	Cyclophosphamide 200-250 mg/m² PO days 1,3 every 2-3 weeks; Vincristine 0.5-0.7 mg/m² IV weekly; Prednisolone 1-2 mg/kg PO daily	Response rate: 50-70%; Median survival: 2-4 months
CHOP	COP components plus Doxorubicin 25 mg/m² IV every 3 weeks (use with caution in cats due to nephrotoxicity concerns)	Complete response: 38%; Partial response: 25%; Median survival with CR: 318 days

Feline Leukemia Virus (FeLV) and Lymphoma/Leukemia

FeLV is a retrovirus that can directly cause malignant transformation of lymphocytes. The risk of developing lymphoma is increased approximately 60-fold in FeLV-positive cats. FeLV infection is more commonly associated with mediastinal and multicentric forms, as well as leukemia, while alimentary lymphoma is usually FeLV-negative.

FeLV Infection Outcomes

FeLV Diagnosis

High-YieldELISA detects antigen in serum (free antigen). IFA detects antigen within cells (intracellular). A positive ELISA with positive IFA indicates progressive infection with poor prognosis. ELISA-positive/IFA-negative cats may be in early infection or regressive infection - retest in 8-12 weeks.

Infection Type	Description
Abortive	Immune system clears infection before viremia; cat remains healthy and seronegative
Regressive	Initial viremia is cleared but proviral DNA persists in bone marrow; may test positive initially then negative; can reactivate with immunosuppression
Progressive	Persistent viremia; bone marrow infection; cat sheds virus and develops FeLV-related diseases; worst prognosis; 50% mortality by 2 years, 80% by 3 years

Feline Leukemia

Leukemia is characterized by neoplastic proliferation of hematopoietic cells originating in the bone marrow, with neoplastic cells circulating in peripheral blood. Feline leukemias are strongly associated with FeLV infection.

Classification of Feline Leukemia

Test	What It Detects	Clinical Use
ELISA (SNAP)	FeLV p27 antigen in blood; detects free antigen during viremia	In-clinic screening test; highly sensitive; positive results should be confirmed
IFA	FeLV p27 antigen within cells (WBCs, platelets); indicates bone marrow infection	Confirmatory test; IFA-positive cats are unlikely to clear infection and have poor prognosis
PCR	Proviral DNA integrated into host genome	Detects regressive infections with low or absent antigenemia; most sensitive

Staging and Prognostic Factors

Staging determines disease extent and guides prognosis. The WHO staging system for lymphoma uses stages I-V based on involvement of lymph nodes and organs. Clinical substage (a = asymptomatic; b = symptomatic) is also prognostic.

Recommended Staging Workup

Complete blood count (CBC) and serum chemistry panel
FeLV/FIV testing
Urinalysis
Thoracic radiographs (3 views)
Abdominal ultrasound
Bone marrow aspirate (if indicated)
Serum cobalamin (B12) and folate levels (for alimentary lymphoma)

Prognostic Factors in Feline Lymphoma

Type	Description	Prognosis
Acute Lymphoblastic Leukemia (ALL)	Immature lymphoblasts in bone marrow and blood; often FeLV-positive; young cats; acute onset	Poor; aggressive course; may respond briefly to chemotherapy
Chronic Lymphocytic Leukemia (CLL)	Well-differentiated small lymphocytes; older cats; indolent course; incidental finding possible	Better prognosis; survival of 2+ years possible with chlorambucil/prednisolone
Myeloproliferative Disorders	Includes erythroid, granulocytic, megakaryocytic, and myelodysplastic syndromes; associated with FeLV	Poor; minimal response to treatment; supportive care (transfusions)

Memory Aids and Board Tips

Mnemonic - "CATS with Lymphoma": C = Chlorambucil and prednisolone for low-grade AL A = Alimentary form most common (60-70%) T = T-cell for low-grade, B-cell for high-grade AL S = Staging includes FeLV/FIV testing always

Mnemonic - "FeLV = FAILS": F = Fatality (50% by 2 years, 80% by 3 years) A = Associated with mediastinal lymphoma (young cats) I = IFA positive = poor prognosis L = Leukemia and lymphoma risk increased 60x S = Saliva transmission; Siamese predisposition for FeLV-negative mediastinal

Quick Comparison - LGAL vs HGAL: LGAL: Older cat, chronic signs (months), T-cell, diffuse thickening, preserved wall layers, chlorambucil/pred, survival 2-3 years HGAL: Any age, acute signs (days-weeks), B-cell, focal mass, loss of wall layers, CHOP/COP, survival 2-4 months

Favorable Factors	Unfavorable Factors
Complete response to chemotherapy	Partial or no response to chemotherapy
FeLV-negative status	FeLV-positive status
Low-grade histology (small cell)	High-grade histology (large cell/lymphoblastic)
Substage a (asymptomatic)	Substage b (symptomatic/ill)
Nasal lymphoma (localized)	Large granular lymphocyte lymphoma (LGLL)
Normal body weight/good BCS	Severe weight loss/poor BCS

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Feline Lymphoma and Leukemia &ndash; NAVLE Study Guide