Feline Lymph Node Fine-Needle Aspirate With Ambiguous Cells
A 9-year-old Domestic Shorthair cat has a 2 cm firm left popliteal lymph node and mild weight loss. Fine-needle aspirate smears are moderately cellular. The population is mixed: small lymphocytes predominate, but there are scattered large cells (2-3x RBC diameter) with round nuclei, finely stippled chromatin, one to two prominent nucleoli, and moderate basophilic cytoplasm. Some cells contain multiple pale cytoplasmic vacuoles. There is no obvious lymphoid follicle architecture on the smears. The clinician calls asking whether this is lymphoma and whether to treat. The cat is FeLV negative, FIV negative, and otherwise stable.
1. How do you classify the large cells, and what features on the smear push you toward or away from lymphoma?
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The large cells are atypical lymphoid cells - the differential is lymphoma (large cell) versus reactive lymphoid hyperplasia with immunoblasts versus a non-lymphoid neoplasm (e.g., mast cell tumor, histiocytic sarcoma).
Features favoring lymphoma:
- Monomorphic population of large cells with high N:C ratio and prominent nucleoli.
- Loss of normal architecture (no small lymphocytes forming follicles).
- If the large cells exceed ~50% of the population, lymphoma is much more likely.
Features favoring reactive:
- Mixed population with many small mature lymphocytes and plasma cells.
- Tingible-body macrophages and a 'starry sky' pattern of reactive germinal centers.
- A few immunoblasts can look large and atypical - but they should be a minority.
Caveats:
- Cytoplasmic vacuoles can be seen in both reactive immunoblasts and some lymphomas; not decisive.
- Mast cell tumor cells can mimic lymphoid cells if granules are faint - check with Wright-Giemsa and consider toluidine blue.
- Aspirate alone cannot reliably grade lymphoma; architecture is needed for follicular vs diffuse.
Bottom line: the smear is suspicious but not definitive; I would not commit to lymphoma on cytology alone.
2. What is your next diagnostic step, and how would the result change the treatment recommendation?
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Next step: excisional lymph node biopsy with histopathology and immunohistochemistry (CD3, CD79a, and Ki-67 or similar proliferation marker).
Rationale:
- Histology preserves architecture, allowing distinction of follicular vs diffuse patterns and low- vs high-grade lymphoma.
- IHC/flow cytometry confirms lineage (B vs T) and clonality, which drives prognosis and treatment choice in cats.
How results change management:
- Reactive hyperplasia → no chemotherapy; investigate underlying cause (infection, inflammation, immune stimulation) and recheck node size.
- Low-grade/indolent lymphoma (e.g., small cell, follicular) → often good prognosis with prednisolone ± chlorambucil; less aggressive.
- High-grade large cell lymphoma → multi-agent chemotherapy (e.g., CHOP-based) or palliative steroids; discuss survival expectations and cost.
- Non-lymphoid neoplasm (mast cell, histiocytic) → different staging and treatment entirely.
Given the cat is stable, there is time to get a definitive diagnosis rather than starting empirical steroids, which could obscure histology and complicate future interpretation.