Lymphoma is the most common haematopoietic (blood and lymph) cancer in cats and one of the most frequently diagnosed feline malignancies overall. It is not a single disease but rather a diverse group of cancers arising from lymphocytes — the immune cells that populate lymph nodes, the gastrointestinal tract, the spleen, the liver, the thymus, and virtually every other tissue in the body.

The clinical behaviour of feline lymphoma ranges enormously. At one end of the spectrum, low-grade small-cell lymphoma of the gastrointestinal tract may progress so slowly that cats live comfortably for two to three years with oral chemotherapy. At the other end, high-grade large-cell lymphoma is an aggressive malignancy requiring combination chemotherapy and carrying a significantly shorter prognosis. Understanding where a particular cat’s lymphoma sits on this spectrum — which requires histopathological and often immunophenotypic analysis — is the foundation of appropriate treatment planning.

Classification of Feline Lymphoma

By Anatomical Location

Feline lymphoma is classified primarily by the anatomical location of the tumour mass, which correlates closely with biological behaviour and prognosis:

• Gastrointestinal (GI) lymphoma: The most common form in cats, accounting for approximately 50 to 75% of all cases. Affects the small intestine primarily, though the stomach, large intestine, and associated lymph nodes may also be involved.
• Mediastinal lymphoma: Arises from the thymus or cranial mediastinal lymph nodes in the chest. More common in young cats and strongly associated with feline leukaemia virus (FeLV) infection. Presents with respiratory signs from pleural effusion and mediastinal mass effect.
• Multicentric lymphoma: Affects multiple lymph node groups simultaneously. Less common in cats than dogs.
• Extranodal lymphoma: Affects specific organs including the kidneys (renal lymphoma), nasal cavity (nasal lymphoma), eyes (ocular lymphoma), central nervous system, and skin. Prognosis varies by site.

By Cell Grade and Immunophenotype

Histopathological grading is the most important prognostic determinant in feline lymphoma. Tumour grade reflects the size and proliferative activity of the malignant lymphocytes:

• Low-grade small-cell lymphoma (LGSCL): Composed of small, well-differentiated lymphocytes. Slow-growing, often T-cell in origin (T-cell LGSCL). The most common form of GI lymphoma in cats. Responds well to oral chlorambucil and prednisolone; median survival 18 to 36 months or longer.
• High-grade large-cell lymphoma (HGLCL): Composed of large, poorly differentiated lymphocytes. Rapidly progressive. Requires combination chemotherapy (CHOP-based protocol); median survival 3 to 9 months with treatment.
• Intermediate-grade lymphoma: A heterogeneous category with prognosis intermediate between the two extremes.

Immunophenotyping (determining whether the tumour is B-cell or T-cell in origin) provides additional prognostic information. In general, B-cell lymphomas respond better to chemotherapy and carry a more favourable prognosis than T-cell lymphomas in cats.

Clinical Signs

Clinical signs vary considerably depending on anatomical location:

Gastrointestinal Lymphoma

GI lymphoma — particularly the low-grade form — may produce subtle, chronic signs of disease that owners initially attribute to normal ageing or transient gastrointestinal upset:

• Chronic weight loss (often the most prominent sign in LGSCL)
• Intermittent vomiting, often small volumes
• Diarrhoea, which may be chronic or episodic
• Decreased appetite or food selectivity
• Palpable intestinal thickening or abdominal masses on physical examination

Mediastinal Lymphoma

• Progressive dyspnoea (breathing difficulty) from pleural effusion
• Muffled heart and lung sounds on auscultation
• Regurgitation (oesophageal compression)
• Facial or forelimb oedema from cranial vena cava compression
• Young adult cats; FeLV positivity common

Renal Lymphoma

• Bilaterally enlarged, irregular kidneys on palpation
• Signs of acute kidney injury: polyuria/polydipsia, vomiting, lethargy
• Central nervous system involvement occurs in up to 40% of renal lymphoma cases

Diagnosis

Accurate diagnosis — including grade, location, and immunophenotype — requires tissue sampling. This is not optional; treatment protocols differ fundamentally between low-grade and high-grade disease, and empirical treatment based on clinical suspicion alone risks using an inappropriate protocol.

Cytology

Fine needle aspirate cytology from accessible masses, enlarged lymph nodes, or effusions can provide rapid preliminary information and may be sufficient to confirm lymphoma in straightforward cases. However, cytology cannot reliably distinguish low-grade from high-grade disease and cannot provide complete architectural information. It is best viewed as a triage tool.

Histopathology

Full-thickness intestinal biopsy (obtained endoscopically or surgically) is the gold standard for GI lymphoma diagnosis and grading. It provides tumour architecture, cell morphology, and tissue for immunophenotyping. Endoscopic biopsy has the advantage of avoiding surgical risk but provides smaller samples that may be less representative — transmural surgical biopsies are preferred when feasible.

PARR (PCR for Antigen Receptor Rearrangements)

PARR is a molecular technique that detects clonal expansion of lymphocyte populations, helping to distinguish lymphoma from reactive (inflammatory) lymphoid hyperplasia — a distinction that can be extremely difficult on histopathology alone, particularly for low-grade GI lymphoma versus inflammatory bowel disease (IBD). It is an increasingly valuable adjunct test in ambiguous cases.

Staging

Complete staging includes thoracic radiographs or CT scan, abdominal ultrasound, full blood count, biochemistry panel, urinalysis, and FeLV/FIV testing. Bone marrow evaluation may be indicated in multicentric disease. Staging determines whether disease is localised or disseminated, guides prognosis, and informs treatment selection.

Chemotherapy Protocols

Low-Grade GI Lymphoma: Chlorambucil and Prednisolone

The oral chlorambucil and prednisolone (COP-lite) protocol is the standard of care for low-grade small-cell GI lymphoma. It is well tolerated in cats, can be administered entirely at home after initial veterinary instruction, and produces response rates of 70 to 96% with median survival times of 18 to 36+ months in responders.

• Chlorambucil: 2 mg per cat every 48 hours (pulse dosing) or 20 mg/m2 every 2 weeks. Myelosuppression is the primary risk; complete blood count monitoring every 3 months is standard.
• Prednisolone: 1–2 mg/kg/day initially, tapered over 4 to 8 weeks to the lowest effective dose. Anti-inflammatory and lympholytic; also improves appetite and quality of life.

Response to treatment is assessed by improvement in clinical signs, body weight gain, and resolution of ultrasound abnormalities. Full remission may not be achieved for 6 to 12 weeks. Cats that respond well may remain in remission for years on low-dose maintenance therapy.

High-Grade Lymphoma: CHOP-Based Protocols

High-grade lymphoma requires multi-agent combination chemotherapy. The CHOP protocol — named for its components cyclophosphamide, doxorubicin (hydroxydaunorubicin), vincristine (Oncovin), and prednisolone — is the most widely used protocol in cats with high-grade disease. Modified versions (e.g., Madison-Wisconsin protocol adapted for cats) are commonly used in veterinary oncology practice.

• Response rates: Approximately 50 to 70% of cats with high-grade lymphoma achieve complete or partial remission with CHOP.
• Median survival: 3 to 9 months with treatment; significantly shorter without chemotherapy.
• Toxicity: CHOP carries a higher toxicity burden than the chlorambucil protocol. Common adverse effects include neutropenia (requiring dose delays or reductions), gastrointestinal signs, and alopecia (rare in cats). Doxorubicin carries a risk of nephrotoxicity in cats and requires renal function monitoring.

Lomustine (CCNU) Protocol

Lomustine is an alkylating agent used as rescue therapy for cats with relapsed or refractory lymphoma after first-line treatment failure. It is administered orally every 3 to 6 weeks. Hepatotoxicity and delayed myelosuppression are the primary concerns; liver enzyme monitoring is essential.

Lymphoma Type	Protocol	Response Rate	Median Survival
Low-grade GI (LGSCL)	Chlorambucil + prednisolone	70–96%	18–36+ months
High-grade GI / multicentric	CHOP protocol	50–70%	3–9 months
Mediastinal	CHOP or COP	60–75%	3–12 months
Renal	CHOP + intrathecal	40–60%	3–6 months
Nasal	Radiation + CHOP	70–80%	12–18 months

Palliative Care and Quality of Life

Not every cat is a candidate for aggressive chemotherapy, and not every owner chooses it. Palliative care — focused on symptom management and maintaining quality of life rather than tumour elimination — is a legitimate and compassionate approach, particularly for elderly cats, cats with significant concurrent disease, or when owners cannot manage the logistical and financial demands of intensive chemotherapy.

Palliative Pharmacotherapy

• Prednisolone alone: In cats not receiving combination chemotherapy, prednisolone alone can produce partial remission and symptom relief in both low-grade and high-grade lymphoma. Expected median survival is shorter than with specific chemotherapy protocols but often measured in weeks to months with good quality of life.
• Anti-nausea medications: Maropitant (Cerenia), ondansetron, or metoclopramide for vomiting. Critical for maintaining appetite and nutritional status.
• Appetite stimulants: Mirtazapine (transdermal formulation available) is widely used and effective for stimulating appetite in cats with cancer cachexia.
• Pain management: Buprenorphine, gabapentin, and meloxicam (with renal function monitoring) are used as appropriate. Cats are stoic and pain is frequently under-recognised and undertreated in feline oncology.
• Nutritional support: High-quality, highly digestible food; assisted feeding via syringe or feeding tube when voluntary intake is insufficient.

Quality of Life Assessment

Structured quality of life (QoL) assessment is an important component of palliative care. The HHHHHMM scale (Hurt, Hunger, Hydration, Hygiene, Happiness, Mobility, More good days than bad) and the Feline Quality of Life scale provide frameworks for regular, objective assessment. Owners should complete these assessments at home and share them with their veterinary team to inform treatment decisions and end-of-life planning.

The goal of palliative care is ‘more good days than bad.’ When the balance tips — when a cat is spending the majority of its time withdrawn, anorexic, in pain, or unable to perform normal behaviours — a compassionate end-of-life conversation becomes appropriate and necessary.

Key Takeaways

• Feline lymphoma is not one disease — grade and location determine treatment protocol and prognosis
• Low-grade small-cell GI lymphoma is manageable with oral chlorambucil and prednisolone for median survival of 1.5 to 3+ years
• High-grade lymphoma requires CHOP-based combination chemotherapy; response rates are meaningful but prognosis is shorter
• Histopathology and immunophenotyping are essential before starting treatment — grade determines everything
• Palliative care centred on prednisolone, anti-nausea drugs, appetite stimulants, and pain management is a legitimate alternative to intensive chemotherapy
• Regular quality of life assessment guides treatment decisions and end-of-life planning

References

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