Lymphadenopathy refers to enlargement of lymph nodes, which can be solitary, regional, or generalized.
Overview and Clinical Importance
Lymphadenopathy refers to enlargement of lymph nodes, which can be solitary, regional, or generalized. In feline patients, lymphadenopathy is an important clinical finding that signals underlying disease processes ranging from reactive hyperplasia to neoplasia. Unlike dogs, where multicentric lymphoma commonly presents with generalized peripheral lymphadenopathy, cats more often develop
alimentary lymphoma affecting the gastrointestinal tract. Understanding the differential diagnoses and diagnostic approach to feline lymphadenopathy is essential for NAVLE success.
High-YieldIn cats, peripheral lymphadenopathy is much more commonly reactive than neoplastic. Always confirm a cytologic diagnosis of lymphoma in a feline peripheral lymph node with a pathologist before initiating treatment.
| Lymph Node |
Location |
Drainage Area |
| Mandibular (Submandibular) |
Ventral to angle of mandible, rostral to mandibular salivary gland |
Head, oral cavity, nasal passages, skin of face |
| Superficial Cervical (Prescapular) |
Cranial to shoulder, under trapezius muscle |
Neck, forelimb, lateral thorax |
| Axillary |
Armpit region, medial to forelimb |
Ventral thorax, forelimb, mammary tissue |
| Superficial Inguinal |
Groin region, medial aspect of hindlimb |
Caudal abdomen, hindlimb, mammary tissue, perineum |
| Popliteal |
Caudal to stifle, in popliteal fossa |
Distal hindlimb, paw |
Feline Lymph Node Anatomy
Palpable Peripheral Lymph Nodes
The following peripheral lymph nodes are routinely palpable in healthy cats and should be evaluated during every physical examination:
NAVLE TipWhen performing FNA for generalized lymphadenopathy, prefer popliteal or prescapular lymph nodes over mandibular nodes. Mandibular nodes are frequently reactive due to constant antigen exposure from the oral cavity and may yield misleading results.
Abdominal Lymph Nodes
Abdominal lymph nodes cannot be palpated unless markedly enlarged. Ultrasound is essential for evaluation. Key abdominal lymph nodes include:
| Lymph Node |
Location |
Clinical Significance |
| Jejunal (Mesenteric) |
Root of mesentery, near mesenteric artery |
Often enlarged with IBD, alimentary lymphoma, FIP |
| Medial Iliac |
Near aortic trifurcation |
Most consistently identified on ultrasound (100%) |
| Ileocolic |
Near ileocecal junction |
Commonly enlarged with colonic disease, FIP |
| Hepatic |
At porta hepatis |
Hepatobiliary disease, metastatic neoplasia |
Classification of Lymphadenopathy
Lymphadenopathy is classified into three main categories based on underlying pathophysiology:
High-YieldIn a UK retrospective study, reactive hyperplasia was the most common cytologic diagnosis in cats (31.6%), compared to lymphoma being most common in dogs (27.5%). This species difference is critical for exam purposes.
| Category |
Mechanism |
Common Causes in Cats |
| Reactive Hyperplasia |
Proliferation of lymphocytes and plasma cells from antigenic stimulation |
Vaccination, chronic skin disease, dental disease, IBD |
| Lymphadenitis |
Inflammatory cell influx due to infection |
Bacterial infection, fungal infection, FIP, mycobacteria |
| Neoplastic Infiltration |
Primary lymphoid neoplasia or metastatic disease |
Lymphoma, mast cell tumor, carcinoma, melanoma |
Differential Diagnosis
Infectious Causes
Retroviral Infections (FeLV and FIV)
Feline Leukemia Virus (FeLV) and Feline Immunodeficiency Virus (FIV) are major causes of generalized lymphadenopathy in cats. FeLV is historically linked to lymphoma development, particularly mediastinal lymphoma in young cats. FIV causes immunosuppression leading to secondary infections and lymphadenopathy.
Key clinical features: Generalized lymphadenopathy, weight loss, anemia, immunosuppression, secondary infections
Feline Infectious Peritonitis (FIP)
FIP is a coronavirus-induced disease characterized by pyogranulomatous inflammation. Abdominal lymphadenopathy is a prominent feature, especially in the non-effusive (dry) form. Approximately 16% of cats with FIP present with isolated intramural intestinal masses and regional lymphadenomegaly, which can mimic neoplasia.
Key clinical features: Young cats (often less than 2 years), fever unresponsive to antibiotics, hyperglobulinemia, mesenteric lymphadenopathy, ocular or neurologic signs
Systemic Mycoses
Histoplasmosis: Caused by Histoplasma capsulatum. Endemic to Mississippi and Ohio River valleys in the US. Causes peripheral and abdominal lymphadenopathy with respiratory signs, weight loss, fever, anemia, and hepatosplenomegaly. Organisms may be seen within macrophages on cytology.
Sporotrichosis: Caused by Sporothrix species. Has significant zoonotic potential from cat scratches. Presents with nodular, ulcerated skin lesions and regional lymphadenopathy. Endemic in South America and increasingly reported in the US.
Cryptococcosis: Upper respiratory and CNS involvement common. Can cause submandibular lymphadenopathy with nasal disease.
NAVLE TipSporotrichosis in cats is a ZOONOTIC emergency. Cats shed large numbers of organisms in exudates. Always wear gloves and warn owners about transmission risk from scratches. Treatment requires systemic antifungals (itraconazole) for 6-12 months.
Other Infectious Causes
Neoplastic Causes
Lymphoma
Lymphoma is the most common hematopoietic neoplasm in cats, accounting for approximately one-third of all feline tumors. Unlike dogs, alimentary (gastrointestinal) lymphoma is the most common form in cats, followed by mediastinal, multicentric, and extranodal forms.
High-YieldLow-grade alimentary lymphoma (small cell) is often indistinguishable from IBD on ultrasound and even endoscopic biopsies. Full-thickness surgical biopsies with immunohistochemistry or PARR testing may be needed for definitive diagnosis. Treatment with chlorambucil and prednisolone yields median survival times greater than 2 years.
Metastatic Neoplasia
Regional lymph nodes should be evaluated when staging any malignancy. Common tumors that metastasize to lymph nodes include:
- Squamous cell carcinoma (SCC): Oral and cutaneous forms metastasize to regional lymph nodes
- Mammary carcinoma: Metastasizes to inguinal and axillary lymph nodes
- Mast cell tumor: Can metastasize to regional nodes; cytology shows characteristic granulated round cells
- Melanoma: Oral melanoma metastasizes to mandibular and retropharyngeal nodes
| Agent |
Clinical Features |
Diagnosis |
| Bartonella |
Uveitis, fever, lymphadenopathy, gingivitis, neurologic signs. Flea transmission. |
PCR, serology, culture |
| Toxoplasma gondii |
Fever, anorexia, dyspnea, mesenteric lymphadenopathy. Focal intestinal masses. |
IgM/IgG titers, PCR |
| Mycobacteria |
Ileocecal and mesenteric lymphadenopathy. Granulomatous inflammation. |
Acid-fast stain, culture, PCR |
| Listeria monocytogenes |
Marked mesenteric lymphadenomegaly. Associated with raw meat diets. |
Culture, 16S rRNA sequencing |
Diagnostic Approach
Initial Assessment
History: Duration of lymphadenopathy, associated clinical signs (weight loss, lethargy, GI signs), vaccination history, geographic location, diet (raw food increases risk of Listeria, Salmonella), outdoor access, FeLV/FIV status
Physical examination: Palpate all peripheral lymph nodes systematically. Assess size, consistency, mobility, symmetry, and pain on palpation. Evaluate for concurrent findings (fever, skin lesions, ocular changes, abdominal masses)
Laboratory Evaluation
Minimum Database
- CBC: May reveal cytopenias (bone marrow involvement), eosinophilia (parasitic, allergic, mast cell tumor), or circulating neoplastic cells
- Serum chemistry: Hyperglobulinemia suggests FIP or chronic inflammation; hypercalcemia is rare in feline lymphoma but can occur
- FeLV/FIV testing: Essential in all cats with lymphadenopathy
- Urinalysis: Baseline renal function; Histoplasma antigen testing on urine
Fine Needle Aspirate Cytology
FNA cytology is the first-line diagnostic test for lymphadenopathy. It is quick, inexpensive, minimally invasive, and often diagnostic.
Technique: Use a 22-gauge needle and 6-12 mL syringe. Apply slight negative pressure and redirect in fan-like pattern. Avoid pumping which damages fragile lymphoid cells. Use roll preparation to minimize cell lysis.
NAVLE TipIn cats, T-cell lymphomas (including alimentary low-grade lymphoma) often consist of small, mature-appearing lymphocytes that can be cytologically indistinguishable from reactive hyperplasia. When clinical suspicion is high but cytology is equivocal, pursue histopathology, PARR (clonality testing), or flow cytometry.
Diagnostic Imaging
Abdominal Ultrasound
Ultrasound is the preferred modality for evaluating abdominal lymph nodes and is more sensitive than radiography. Key findings include:
- Size: Enlarged nodes appear rounded rather than elongated
- Echogenicity: Most abnormal nodes are hypoechoic; reactive nodes often surrounded by hyperechoic fat
- Architecture: Loss of normal elongated shape, heterogeneous echotexture
- Associated findings: Intestinal thickening (IBD, lymphoma), effusion (FIP, carcinomatosis)
Key point: Mesenteric lymphadenopathy is present in 33-50% of cats with alimentary lymphoma and correlates with IBD severity. However, ultrasound cannot reliably differentiate IBD from low-grade lymphoma.
Additional Diagnostics
| Lymphoma Type |
Characteristics |
Prognosis with Treatment |
FeLV Association |
| Alimentary (Low-grade/Small cell) |
Elderly cats. Chronic vomiting, diarrhea, weight loss. T-cell origin. |
Good: MST greater than 2 years |
Low |
| Alimentary (High-grade/Large cell) |
Rapid onset. Mass formation. B-cell origin more common. |
Guarded: MST 2-4 months |
Variable |
| Mediastinal |
Young cats. Dyspnea, pleural effusion. T-cell origin. |
Fair: MST 6-9 months |
High |
| Renal |
Usually bilateral. Azotemia. Risk of CNS metastasis. |
Guarded: MST 7 months |
Moderate |
| Nasal |
Nasal discharge, facial swelling, sneezing |
Fair-Good: MST approximately 12 months with radiation |
Low |
Treatment
Treatment by Etiology
Chemotherapy for Lymphoma
High-YieldUnlike dogs, cats tolerate chemotherapy well with rare febrile neutropenia. Monitor renal function when using doxorubicin (potential nephrotoxicity). Cats often lose whiskers but rarely develop significant alopecia. Achieving complete remission (CR) is a major positive prognostic factor.
| Finding |
Interpretation |
| Painful lymphadenopathy |
Suggests lymphadenitis over reactive hyperplasia or neoplasia |
| Fixed, firm lymph nodes |
Suggests neoplastic infiltration with capsular invasion |
| Solitary node enlargement |
Consider regional infection, metastatic disease, or primary lymphoma |
| Generalized enlargement |
Consider systemic disease (FeLV, FIV, systemic mycosis, lymphoma) |
| Cytologic Pattern |
Key Features |
Differential Diagnosis |
| Reactive Hyperplasia |
Greater than 85% small lymphocytes. Less than 5% lymphoblasts. Increased plasma cells (Mott cells). |
Antigenic stimulation, vaccination, chronic infection |
| Large Cell Lymphoma |
Greater than 50% large lymphoblasts (greater than 1.5x RBC size). Fine chromatin, visible nucleoli. Lymphoglandular bodies. |
High-grade lymphoma |
| Small Cell Lymphoma |
Monomorphic small lymphocytes. May see hand-mirror cells (cytoplasmic pseudopods). |
Difficult to distinguish from reactive. Requires PARR, flow cytometry, or histopathology. |
| Suppurative Inflammation |
Greater than 5% neutrophils (degenerate or non-degenerate). May see intracellular bacteria. |
Bacterial lymphadenitis, abscess |
| Pyogranulomatous |
Mixed neutrophils and macrophages. Multinucleated giant cells. Look for organisms. |
FIP, mycobacteria, fungi, toxoplasmosis |
| Eosinophilic |
Increased eosinophils (greater than 3%) |
Allergic dermatitis, eosinophilic granuloma complex, mast cell tumor, parasites |
| Metastatic Neoplasia |
Non-lymphoid cells: epithelial clusters (carcinoma), round cells with granules (mast cell), melanin-laden cells (melanoma) |
Carcinoma, mast cell tumor, melanoma |
| Test |
Indication |
Key Information |
| Histopathology (Biopsy) |
Equivocal cytology, suspected small cell lymphoma, staging for surgery |
Gold standard for architecture. Core or excisional biopsy. Include IHC for B/T cell markers. |
| PARR (Clonality Testing) |
Small cell lymphoma vs reactive hyperplasia |
PCR-based. Detects monoclonal lymphocyte population. Supports but does not definitively diagnose lymphoma. |
| Flow Cytometry |
Immunophenotyping of lymphoma |
Requires fresh cells. Determines B-cell vs T-cell origin. Detects aberrant marker expression. |
| Thoracic Radiography |
Staging for neoplasia, respiratory signs |
Mediastinal lymphadenopathy, pulmonary metastases, pleural effusion |
| Bone Marrow Aspirate |
Lymphoma staging, unexplained cytopenias |
Detects marrow infiltration. Prognostic for high-grade lymphoma. |
| Condition |
Treatment |
Notes |
| Reactive Hyperplasia |
Treat underlying cause. Monitor for resolution. |
Usually self-limiting if stimulus removed. Anti-inflammatories if needed. |
| Bacterial Lymphadenitis |
Broad-spectrum antibiotics based on culture. Drainage if abscess. |
4-6 weeks antibiotic therapy. Re-evaluate if no improvement. |
| Histoplasmosis |
Itraconazole 10 mg/kg PO q24h for 6-12 months |
Monitor urine antigen for response. Fluconazole also effective. |
| Sporotrichosis |
Itraconazole 10 mg/kg PO q24h for 2 months past clinical resolution |
ZOONOTIC. Wear gloves. Warn owner. Treatment for 6-12 months typically. |
| Bartonellosis |
Doxycycline 10 mg/kg PO q12h for 4-6 weeks. Azithromycin alternative. |
Flea control essential. Zoonotic potential (cat scratch disease). |
| FIP |
GS-441524 or GC376 antiviral protocols. Supportive care. |
Previously fatal. New antivirals show promising cure rates. |
| Protocol |
Components |
Indication and Response |
| CHOP |
Cyclophosphamide, Doxorubicin (use 1 mg/kg in cats), Vincristine, Prednisolone |
High-grade lymphoma. Overall response 50-80%. MST 6 months (CR: approximately 1 year). 25-week UW protocol. |
| COP |
Cyclophosphamide, Vincristine, Prednisolone |
High-grade lymphoma when doxorubicin contraindicated. Similar efficacy in some studies. |
| Chlorambucil + Prednisolone |
Chlorambucil 15-20 mg/m2 PO q2-3 weeks or 2 mg PO q2-3 days. Prednisolone 1-2 mg/kg daily. |
Low-grade alimentary lymphoma. 70-85% response. MST greater than 2 years. |
| CCNU (Lomustine) |
60-90 mg/m2 PO q3-4 weeks |
Alternative for high-grade lymphoma. MST approximately 8 months. Monitor hepatic function. |