# Cytology of Lymph Nodes: Diagnostic Approach to Lymphadenopathy


## Key Takeaways

- Lymph node cytology is a critical first-line diagnostic tool for lymphadenopathy and tumor staging in dogs and cats, with non-diagnostic rates of 27.2% in dogs and 14.1% in cats primarily due to sample quality issues like cell absence or disruption.
- Lymphoma is the most frequent neoplastic diagnosis in canine lymph node aspirates (27.5%), whereas reactive hyperplasia is the most common diagnosis in feline lymph node aspirates (31.6%), necessitating careful morphologic assessment to differentiate these conditions.
- Cytologic evaluation follows a structured approach: assessing sample quality, low-power survey for cellularity and pattern, and high-power differential count (200-300 cells) to distinguish between monomorphic neoplastic populations and mixed reactive or inflammatory infiltrates.
- Inflammatory patterns, such as neutrophilic, eosinophilic, or granulomatous lymphadenitis, require identification of specific inflammatory cells and can indicate underlying bacterial, parasitic, fungal, or protozoal infections, with canine leishmaniosis demonstrating significant cytologic abnormalities in clinically affected dogs (59.4%).
- Metastatic neoplasia is identified by non-lymphoid cells, such as epithelial clusters in carcinomas or granulated cells in mast cell tumors, and its detection is crucial for staging, particularly in conditions like anal sac adenocarcinoma where altered ultrasonographic appearance correlates highly with cytologic confirmation.
- Molecular adjuncts like PCR for antigen receptor gene rearrangements can detect lymphoid clonality on cytologic smears, aiding in the diagnosis of lymphoma and potentially identifying minimal residual disease during clinical remission, though it complements rather than replaces morphologic interpretation.

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Lymph node cytology is a first-line diagnostic procedure for dogs and cats presenting with lymphadenopathy, and it also serves a central role in tumor staging. This article provides a systematic framework for sample collection, smear preparation, cytologic interpretation, and diagnostic decision-making. It is written for practicing veterinarians who perform in-house cytology or who interpret laboratory submissions. The content focuses on distinguishing reactive, inflammatory, and neoplastic lymph node processes using morphologic criteria alone, and it does not cover histopathology or immunophenotyping as confirmatory techniques.

The clinical questions this article addresses are practical ones. When is lymph node aspiration indicated? How should a smear be assessed systematically? Which cytologic patterns reliably separate reactive hyperplasia from lymphoma, and when should cytology be considered non-diagnostic? The answers draw on published evidence from veterinary referral populations and on established laboratory standards.

## At a Glance

| Parameter | Decision or Fact |
|---|---|
| Sample quality | Non-diagnostic rates reach 27.2% in canine and 14.1% in feline lymph node aspirates, absence of cells, cell disruption, and low yield are the most common causes |
| Most common canine diagnosis | Lymphoma, reported in 27.5% of diagnostic canine lymph node aspirates |
| Most common feline diagnosis | Reactive hyperplasia, reported in 31.6% of diagnostic feline lymph node aspirates |
| Staging role | Lymph node cytology is recommended by 88% of surveyed veterinarians for initial staging of canine high-grade multicentric lymphoma |
| Leishmaniosis pattern | Abnormal lymph node cytology occurs in 59.4% of dogs with clinical leishmaniosis but only 4.2% of subclinically infected dogs |
| Metastasis detection | Altered ultrasonographic lymph node appearance is highly consistent with metastatic disease as assessed by cytology in canine anal sac adenocarcinoma |
| Molecular adjunct | PCR clonality testing can be performed on cytologic smears and may detect minimal residual disease during clinical remission |

## Indications for Lymph Node Aspiration

Lymph node fine needle aspiration is performed for two principal reasons: investigation of palpable or ultrasonographically detected lymphadenopathy, and staging of known or suspected malignancy. In a retrospective review of 1473 canine and feline lymph node aspirate submissions, investigation of lymphadenopathy alone or in combination with other clinical signs, and tumor staging, were the most common reasons for sampling in both species. Submission of a clinical history did not affect the probability of reaching a cytologic diagnosis in that study.

The staging indication deserves emphasis. In a survey of veterinarians attending a veterinary cancer society conference, lymph node cytology was recommended by 88% of respondents as part of initial staging for dogs with substage-a high-grade multicentric lymphoma, alongside complete blood count, chemistry panel, urinalysis, and imaging. For tumors with predictable regional lymphatic drainage, such as anal sac adenocarcinoma, cytologic assessment of draining lymph nodes is a standard component of preoperative staging. In one referral population of 52 dogs with anal sac adenocarcinoma, altered ultrasonographic appearance of lymph nodes was highly consistent with metastatic disease as confirmed by cytology and histopathology.

## Anatomy and Physiology of the Lymph Node

A lymph node is a structured collection of lymphocytes, macrophages, and stromal cells enclosed within a fibrous capsule. Afferent lymphatics deliver antigen and antigen-presenting cells to the subcapsular and cortical regions, where B lymphocytes populate lymphoid follicles. Paracortical zones contain T lymphocytes, and medullary cords and sinuses contain plasma cells, macrophages, and recirculating lymphocytes. The node functions as a filter and an immune induction site, and its cellular composition changes dynamically in response to antigenic stimulation.

Cytologic sampling disrupts this architecture. Fine needle aspiration harvests cells from the subcapsular sinus, cortex, and medulla, but it does not preserve follicular structure. Interpretation therefore depends on the relative proportions and morphology of the cell populations present, not on tissue organization. This is the fundamental limitation that distinguishes cytology from histopathology, and it explains why some processes, particularly partial or early follicular involvement by neoplasia, can be missed on aspirate samples.

## The Cytologic Examination

### Sample Quality Assessment

The first step in interpreting a lymph node smear is determining whether the sample is adequate. Non-diagnostic samples are common. In a large retrospective series, 27.2% of canine and 14.1% of feline lymph node aspirates were non-diagnostic, with absence of cells, cell disruption, and low yield identified as the most frequent causes. A sample that contains only peripheral blood, or that shows extensive cellular rupture with free nuclear material and no intact cell populations, cannot support a cytologic diagnosis. Re-aspiration should be performed instead of attempting interpretation of a technically inadequate smear.

### Low-Power Survey

At low magnification, assess cellularity and overall pattern. A normal or reactive lymph node smear is highly cellular, with a mixed population of small lymphocytes predominating. Large lymphocytes, plasma cells, macrophages, and tingible-body macrophages are present in variable numbers. The smear should show a relatively uniform distribution of cells without large sheets of epithelial cells, which would suggest inadvertent sampling of adjacent tissue or a metastatic epithelial neoplasm.

### High-Power Differential Count

At high magnification, perform a differential count of at least 200 to 300 nucleated cells. The key distinction is between a mixed, predominantly small-cell population and a monomorphic population of large or intermediate cells. Reactive hyperplasia typically shows a spectrum of lymphoid maturation, with small lymphocytes remaining the majority population. Lymphoma, particularly high-grade forms, produces a monomorphic population of medium to large lymphoid cells with visible nucleoli, increased mitotic figures, and often a high nuclear to cytoplasmic ratio. The presence of tingible-body macrophages supports an active reactive process, whereas their absence in a monomorphic large-cell population favours neoplasia.

### Non-Neoplastic Patterns

Reactive lymphoid hyperplasia is the most common cytologic diagnosis in feline lymph node aspirates and is also frequent in dogs. The smear shows increased cellularity with a mixed population including small lymphocytes, medium lymphocytes, large lymphocytes, plasma cells, and macrophages. The pattern reflects antigenic stimulation and is non-specific with respect to the inciting cause.

Inflammatory patterns may be superimposed on reactive changes. Neutrophilic inflammation suggests bacterial infection or necrosis. Eosinophilic inflammation can be seen with parasitic or hypersensitivity responses. Granulomatous or histiocytic lymphadenitis is characterized by increased macrophages, often with epithelioid morphology, and may be associated with fungal or protozoal infection. Canine leishmaniosis provides a well-documented example: dogs with clinical leishmaniosis show cytologic abnormalities in 59.4% of cases, whereas subclinically infected dogs show abnormalities in only 4.2%, and the cytologic pattern is typically reactive or granulomatous. Amastigotes may be identified within macrophages when organizm density is high.

## Neoplastic Patterns

### Lymphoma

Lymphoma is the most common neoplastic diagnosis in canine lymph node aspirates, accounting for 27.5% of diagnostic samples in one large series. Cytologically, lymphoma is suspected when a monomorphic population of lymphoid cells predominates. High-grade lymphomas are usually straightforward to recognize because the cells are large, have prominent nucleoli, and show frequent mitotic figures. Low-grade lymphomas are more challenging because the neoplastic cells may resemble small lymphocytes and can be difficult to distinguish from reactive hyperplasia on morphology alone.

### Metastatic Neoplasia

Metastatic epithelial neoplasia is identified by the presence of cohesive clusters or sheets of epithelial cells within a lymphoid background. The cells often differ markedly from the surrounding lymphocyte population, showing criteria of malignancy such as anisocytosis, anisokaryosis, prominent nucleoli, and nuclear pleomorphism. Cytology can confirm nodal metastasis in conditions such as anal sac adenocarcinoma, where altered ultrasonographic lymph node appearance correlates highly with cytologic evidence of metastatic disease. Mast cell neoplasia metastatic to lymph nodes is recognized by the presence of mast cells, which may be granulated or poorly granulated, and requires careful examination because degranulated mast cells can be mistaken for other cell types.

## Limitations and Adjunctive Testing

Cytology has recognized limitations. Low-grade lymphoma can be cytologically indistinguishable from reactive hyperplasia. Partial lymph node involvement by lymphoma may yield a mixed population that appears reactive. Non-diagnostic samples are common enough that a negative or equivocal result should not be accepted without considering sample quality. Molecular testing can complement cytology: polymerase chain reaction assays for immunoglobulin and T-cell receptor gene rearrangements can be performed on cytologic smears, and clonality has been demonstrated in canine lymphoma samples during clinical remission, indicating minimal residual disease. However, clonality testing is an adjunct, not a replacement for morphologic interpretation, and its prognostic significance requires further investigation.

Laboratory quality standards, including those published by the American Society for Veterinary Clinical Pathology, provide guidance on sample handling, smear preparation, and quality assurance that apply to in-house and referral laboratory cytology alike.

## Pattern-Based Diagnostic Algorithm

The cytologic evaluation of a lymph node aspirate should follow a structured interpretive sequence. Begin with sample quality assessment, then survey the smear at low power to establish the overall cellularity and architecture, and finally perform a high-power differential count of at least 200 to 300 nucleated cells. The pattern that emerges from this sequence, instead of any single cell type, drives the diagnostic conclusion.

### Step 1: Classify the Dominant Population

Determine whether the smear is dominated by small lymphocytes, a mixed population, large lymphoid cells, or non-lymphoid cells. This single decision branches the algorithm.

- **Small lymphocyte predominance** with a uniform appearance suggests a normal or mildly reactive node, but also raises the possibility of a small cell lymphoma. Assess for heterogeneity of lymphocyte size and the presence of tingible-body macrophages. A mixed population with tingible-body macrophages supports reactive hyperplasia. A monomorphic small lymphocyte population with minimal cytoplasm and no other cell types warrants consideration of indolent lymphoma, particularly in cats.
- **Mixed lymphoid population** with small lymphocytes, medium and large lymphocytes, plasma cells, and tingible-body macrophages defines reactive hyperplasia. The presence of neutrophils, macrophages, or eosinophils in addition to this mixed population shifts the interpretation toward inflammatory lymphadenitis.
- **Large cell predominance** where medium to large lymphocytes exceed 50 percent of the nucleated cell population is the hallmark of high-grade lymphoma. These cells have round nuclei, coarsely stippled to vesicular chromatin, prominent nucleoli, and a variable amount of basophilic cytoplasm. Nuclear size exceeding two red blood cell diameters is a useful threshold.
- **Non-lymphoid cell predominance** indicates metastatic neoplasia, although a careful search for a concurrent reactive lymphoid population is essential. Epithelial cells often exfoliate in clusters or acinar arrangements, mast cells appear as round cells with purple granules, and melanoma cells may contain melanin pigment.

### Step 2: Assess for Inflammation

When neutrophils, macrophages, or eosinophils are present in significant numbers, classify the inflammatory pattern. Neutrophilic inflammation with degenerate neutrophils suggests bacterial lymphadenitis, although extracellular bacteria are identified in only a subset of cases. Pyogranulomatous inflammation with epithelioid macrophages and neutrophils is characteriztic of fungal infection and mycobacterial disease. Eosinophilic inflammation occurs with parasitic migration, hypersensitivity reactions, and mast cell neoplasia.

In regions where leishmaniosis is endemic, lymph node cytology can identify amastigotes within macrophages. One study of dogs with clinical leishmaniosis found cytologic abnormalities in 59.4 percent of affected dogs, with amastigote density correlating with the severity of cytologic change. Subclinically infected dogs rarely showed cytologic abnormalities, so a normal lymph node aspirate does not exclude latent infection. [Cytologic patterns of lymphadenopathy in dogs infected with Leishmania infantum](https://pubmed.ncbi.nlm.nih.gov/16134072/)

### Step 3: Evaluate for Metastatic Disease

Metastatic cells are identified by their foreign appearance relative to the lymphoid background. Carcinomas exfoliate as cohesive clusters of cells with distinct cell borders and abundant cytoplasm. Sarcomas are more variable and often exfoliate poorly, yielding low cellularity with scattered spindle cells. Mast cell metastases appear as sheets of granulated round cells, and the granules may be sparse in poorly granulated variants.

The clinical context determines which lymph nodes warrant aspiration. For anal sac adenocarcinoma, altered ultrasonographic appearance of the medial iliac lymph nodes was highly consistent with metastatic disease as confirmed by cytology and histopathology in one case series. [Surgical management of primary, metastatic and recurrent anal sac adenocarcinoma in the dog](https://pubmed.ncbi.nlm.nih.gov/28245066/) Ultrasonographic changes therefore guide sampling decisions, but cytologic confirmation remains necessary before treatment planning.

### Step 4: Integrate Clinical Findings

The cytologic pattern must be interpreted alongside signalment, physical examination findings, and clinicopathologic data. Lymphoma is the most common cytologic diagnosis in canine lymph node aspirates, accounting for 27.5 percent of diagnostic samples in one large retrospective series, while reactive hyperplasia predominates in cats at 31.6 percent. [The diagnostic utility of lymph node cytology samples in dogs and cats](https://pubmed.ncbi.nlm.nih.gov/25482570/) These frequencies inform pretest probability but do not replace cytologic interpretation.

Generalized lymphadenopathy with large cell predominance supports lymphoma. Localized lymphadenopathy with a mixed population supports reactive change, particularly when the draining region has inflammation or neoplasia. Fever, weight loss, and lethargy increase concern for lymphoma or systemic infection.

## Decision Points That Change the Diagnostic Path

| Cytologic Finding | Primary Consideration | Secondary Consideration | Action That Changes |
|---|---|---|---|
| Monomorphic small lymphocytes | Indolent lymphoma | Normal node, early reactive change | Submit for PCR clonality testing |
| Mixed population, no inflammation | Reactive hyperplasia | Early lymphoma, especially in cats | Repeat aspirate in 2 to 4 weeks if clinical concern persists |
| Large cell predominance | High-grade lymphoma | Metastatic round cell neoplasia | Stage disease, consider immunophenotyping |
| Neutrophilic inflammation | Bacterial lymphadenitis | Fungal infection, foreign body | Culture and sensitivity, special stains |
| Epithelial cell clusters | Metastatic carcinoma | Contamination from skin or thyroid | Compare with primary tumor cytology |
| Eosinophilic inflammation | Parasitic or allergic response | Mast cell neoplasia | Search for mast cells, evaluate draining region |

## Sampling Technique and Equipment

Fine needle aspiration is performed with a 22 to 25 gauge needle attached to a 6 to 12 mL syringe. The node is immobilized between two fingers, and the needle is inserted with a rapid in-and-out motion while maintaining negative pressure. Release the pressure before withdrawing the needle to avoid drawing blood into the syringe. For highly vascular or small nodes, capillary sampling without suction often yields superior cellularity with less hemodilution.

Non-diagnostic samples occur in 27.2 percent of canine and 14.1 percent of feline lymph node aspirates, with absence of cells, cell disruption, and low yield as the most common causes. [The diagnostic utility of lymph node cytology samples in dogs and cats](https://pubmed.ncbi.nlm.nih.gov/25482570/) Submission of clinical history did not affect the probability of reaching a cytologic diagnosis in that study, but providing the reason for sampling remains good practice because it guides the cytologist's search pattern.

Smear preparation determines diagnostic quality. Use a gentle squash preparation with minimal pressure to preserve cell morphology. Thick smears obscure nuclear detail and resist staining. Air-dry immediately and stain with a Romanowsky-type stain. If granulomatous disease is suspected, reserve an unstained smear for special stains.

## Documentation and Reporting

Record the sample quality, the dominant cell population, the estimated differential count, and the presence of any non-lymphoid cells. Describe nuclear morphology, nucleolar prominence, and cytoplasmic features of atypical cells. Note the presence of tingible-body macrophages, plasma cells, and inflammatory cells.

Report the cytologic interpretation using standardized categories: non-diagnostic, reactive hyperplasia, inflammatory lymphadenitis with the predominant cell type specified, lymphoma with cell size and grade specified, metastatic neoplasia with the cell type described, or normal lymphoid tissue. Include a differential list when the pattern is ambiguous. Recommend follow-up aspirates when the sample is non-diagnostic or when the pattern does not match the clinical picture.

## Species and Clinical Context Modifications

Feline lymph nodes present specific challenges. Reactive hyperplasia is common and can be marked, with large lymphoid cells that mimic lymphoma. The presence of a mixed population with tingible-body macrophages favors reactivity even when large cells are numerous. Cats with suspected small cell lymphoma often have normal or minimally enlarged nodes, and cytology may be falsely reassuring.

Bovine and equine lymph node cytology follows the same interpretive principles, but the differential list expands. Bovine lymphoma associated with enzootic bovine leukosis typically presents with marked lymphocytosis and generalized lymphadenopathy. Equine lymph node aspirates may show pyogranulomatous inflammation with Streptococcus equi infection.

When the cytologic pattern is equivocal, polymerase chain reaction for antigen receptor rearrangement can distinguish reactive from neoplastic lymphoid populations. One study demonstrated clonality in 7 of 10 canine lymphomas using cytologic smears, while no hyperplastic nodes were clonal. [Clonality and phenotyping of canine lymphomas before chemotherapy and during remission](https://pubmed.ncbi.nlm.nih.gov/20357946/) This adjunctive test is most valuable when cytology is suspicious but not diagnostic, and it can be performed on archived stained smears.

## Recognized Complications and Failure Modes

Fine needle aspiration of lymph nodes is a low-morbidity procedure, but failures occur at predictable points. The most common complication is a non-diagnostic sample, reported in 27.2% of canine and 14.1% of feline submissions in a large retrospective series. Absence of cells, cell disruption, and low yield accounted for most of these failures. Blood contamination is the next most frequent problem, diluting the nucleated cell population and obscuring the true cytologic pattern.

Hemorrhage and hematoma formation are uncommon but occur more often when the clinician aspirates with negative pressure in highly vascular or inflamed nodes. Pneumothorax is a recognized risk when sampling axillary or deep cervical nodes, particularly in thin patients. Needle tract seeding of neoplastic cells is a theoretical concern with metastatic disease, though clinically significant implantation is rare. The evidence base for this complication in veterinary patients is limited.

Early detection of a failing sample begins at the bedside. A smear that appears grossly bloody or fails to spread with a feathered edge should prompt immediate recollection. The slide should be examined for cellularity before the patient is released, not after the sample has been submitted. A sample with fewer than 10 intact nucleated cells per high-power field is unlikely to yield a diagnostic interpretation and should be repeated.

| Observation | Likely Cause | Discriminating Check |
|---|---|---|
| Acellular smear, blood only | Missed node, aspiration of vessel | Repalpate, redirect needle, use capillary action without suction |
| Crushed nuclei, chromatin streaming | Excessive smearing pressure | Prepare fresh smear with lighter touch, use squash technique |
| Sheets of cohesive epithelial cells | Metastatic carcinoma | Confirm cell clusters have distinct borders, compare with primary tumor cytology |
| Monomorphic large lymphocytes | Lymphoma versus reactive blast response | Perform differential count, assess for tingible-body macrophages, consider PCR for clonality |
| Extracellular granules, free nuclei | Mast cell degranulation | Scan low power before granules disperse, use Diff-Quik for rapid assessment |

## Common Errors in Interpretation

Less experienced clinicians frequently overcall reactive hyperplasia as lymphoma. A reactive node shows a mixed population with small lymphocytes predominating, plasma cells present, and tingible-body macrophages scattered throughout. Lymphoma, by contrast, produces a monomorphic population of medium or large lymphocytes that exceeds 50% of the nucleated cells. Counting 300 cells systematically reduces this error.

The reverse error, undercalling lymphoma in a node with partial effacement, occurs when the clinician focuses on residual follicles. Survey the entire smear at low power before committing to a diagnosis. A single population of atypical lymphocytes in any field warrants suspicion even if other areas appear reactive.

Metastatic disease is missed when the clinician assumes that a node with reactive changes cannot also contain neoplastic cells. Carcinoma cells may be sparse, particularly in early metastasis. Ultrasonographic alteration of lymph node appearance is highly consistent with metastatic disease in dogs with anal sac adenocarcinoma, and cytology should be interpreted alongside imaging findings instead of in isolation.

Inflammatory patterns are frequently misclassified. Neutrophilic inflammation with intracellular bacteria suggests suppurative lymphadenitis, but sterile neutrophilic inflammation occurs with immune-mediated disease and necrosis. Macrophage-rich smears with intracellular organizms such as *Leishmania* amastigotes require careful high-power examination. In one study, abnormal lymph node cytology was found in 59.4% of dogs with clinical leishmaniosis but only 4.2% of subclinically infected dogs, indicating that cytologic abnormalities correlate with clinical disease status.

## Evidence Limitations and Areas of Contested Opinion

The published evidence on lymph node cytology is largely retrospective and single-center. The largest series, covering 1473 samples from dogs and cats, provides useful frequency data but does not report sensitivity or specificity for individual diagnoses. Studies comparing cytology with histopathology as the reference standard are limited, and the true accuracy of cytologic grading for lymphoma remains uncertain.

Expert opinion differs on several points. The threshold for diagnosing lymphoma on cytology alone varies, with some clinicians requiring greater than 50% large lymphocytes and others using 70% or higher. The role of PCR for antigen receptor rearrangement in cytologic samples is established for confirming clonality, but its prognostic value during remission is still under investigation. Flow cytometry and immunophenotyping are widely recommended, with 76% of surveyed veterinarians using immunophenotyping in initial staging of canine lymphoma, yet the clinical impact of phenotype-based protocol selection remains debated.

Sampling technique is another area of disagreement. Some authorities advocate aspiration with suction, others prefer capillary action without suction to reduce blood contamination. No controlled trial has resolved this question, and the choice often reflects institutional preference.

## Referral, Consultation, and Reporting

Referral to a clinical pathologist is warranted when the cytologic pattern is ambiguous, when a neoplastic diagnosis would change treatment recommendations, or when the sample quality is poor but recollection is not feasible. A second opinion on the same slides is often more useful than a repeat aspirate, particularly when the question is lymphoma versus reactive hyperplasia.

Specialist consultation should occur before invasive staging procedures are performed. Advanced imaging such as 18FDG-PET can identify metastatic disease in lymph nodes that appear normal on palpation and cytology, and this modality is increasingly available at referral centers. The decision to pursue PET imaging should be made in consultation with an oncologist.

Laboratory involvement extends beyond slide interpretation. The American Society for Veterinary Clinical Pathology provides quality assurance guidelines for sample handling, staining, and reporting that should be followed to ensure consistent results. When a sample is non-diagnostic, the laboratory should be contacted to determine whether the problem lies in collection, smear preparation, or staining.

Regulatory reporting is rarely triggered by lymph node cytology alone. However, cytologic evidence of certain infectious agents, including *Leishmania* species in endemic or non-endemic regions, may carry reporting obligations under national or international animal health standards. The World Organization for Animal Health maintains the terrestrial animal health code that governs notification of listed diseases, and clinicians should consult current regional requirements when an infectious cause is suspected.

## Frequently Asked Questions

### How should I proceed when a lymph node aspirate yields only blood or scant cellular material?

Repeat the aspiration with a smaller-gauge needle and apply gentle suction only after the needle is within the node. Redirect the needle through different planes to sample multiple regions. If the node is small or mobile, stabilize it with one hand and use a non-aspiration capillary technique. Non-diagnostic samples most often result from absent cells, cell disruption, or low yield, so improving sampling technique is the most direct remedy. If repeat sampling remains acellular, consider ultrasound guidance for deeper or partially cystic nodes. Submit the sample regardless, and note the sampling difficulty on the submission form so the pathologist can interpret the limited material appropriately.

### What is the minimum equipment needed to obtain a diagnostic lymph node aspirate in general practice?

A 22 to 25 gauge needle, a 3 to 6 mL syringe, and clean glass slides are sufficient for most peripheral nodes. No syringe is required for the capillary technique, which often yields less hemodilution. Diff-Quik or Wright-Giemsa stains are adequate for routine interpretation. If a microscope with oil immersion is unavailable, refer the stained slide to a commercial laboratory, air-dried unstained slides transport well. Submission of the history does not change the probability of reaching a cytologic diagnosis, so prioritize sample quality over paperwork when resources are limited.

### How does the diagnostic approach differ when aspirating a lymph node in a cat versus a dog?

Cats yield diagnostic samples more frequently than dogs, with one study reporting 85.9% diagnostic feline samples versus 72.8% canine samples. Reactive hyperplasia is the most common feline diagnosis, whereas lymphoma predominates in dogs. Feline nodes are often smaller and firmer, requiring firmer stabilization and smaller needles. In cats, always consider infectious causes such as Mycoplasma hemofelis, fungal organizms, and feline leukemia virus-associated lymphoma. Aspirate multiple nodes when possible, as regional variation can occur. For cats with peripheral lymphadenopathy and concurrent fever or weight loss, submit additional samples for infectious disease testing instead of relying on cytology alone.

### What should I record in the medical record after performing lymph node cytology?

Document the node or nodes sampled, needle gauge, technique used, whether aspiration or capillary method, and any complications such as hemorrhage or patient intolerance. Record the cytologic findings using standardized terminology: sample quality, predominant cell population, presence of inflammation, and any atypical or metastatic cells. Note whether the sample was diagnostic or non-diagnostic and what follow-up is recommended. If slides are submitted to a reference laboratory, record the laboratory name, submission date, and accession number. This documentation supports staging decisions and provides a baseline for monitoring response to therapy, particularly in lymphoma cases where serial sampling may be performed.

### How do I explain cytologic findings to an owner when the result is inconclusive or non-diagnostic?

Use plain language that distinguishes between what the sample showed and what it could not show. State that the sample contained too few cells or was disrupted to make a definitive diagnosis. Explain that a repeat aspirate, a biopsy, or additional tests such as PCR for clonality may be needed. Reassure the owner that a non-diagnostic result does not mean the node is normal or abnormal, only that the sample was inadequate. Provide a concrete timeline for follow-up, such as rechecking in 7 to 14 days if the node persists or enlarges. Avoid speculative language about cancer until a definitive diagnosis is established.

### When is it appropriate to skip cytology and proceed directly to excisional biopsy?

Proceed directly to biopsy when the node is fixed to underlying tissue, rapidly enlarging, or associated with systemic signs such as unexplained fever, weight loss, or hypercalcemia. Cytology may be nondiagnostic in fibrotic or necrotic neoplasms, and biopsy provides architectural information that cytology cannot. For solitary nodes in a region where surgical excision is low risk, biopsy may be more efficient than a cytology-biopsy sequence. However, cytology remains valuable for staging and for guiding biopsy site selection. In dogs with suspected anal sac adenocarcinoma, altered ultrasonographic appearance of lymph nodes is highly consistent with metastatic disease, so cytology can confirm metastasis before surgical planning.

## Related Clinical & Scientific Guides

* [Peripheral Blood Smear Evaluation: A Step-by-Step Guide](/knowledge/veterinary-medicine/clinical-pathology/peripheral-blood-smear-evaluation-guide)
* [Reticulocyte Counts in Veterinary Medicine: Clinical Utility and Interpretation](/knowledge/veterinary-medicine/clinical-pathology/reticulocyte-counts-veterinary-medicine)
* [Cerebrospinal Fluid Analysis in Veterinary Neurology: Collection and Interpretation](/knowledge/veterinary-medicine/clinical-pathology/cerebrospinal-fluid-analysis-veterinary)


## References and Further Reading

- [The diagnostic utility of lymph node cytology samples in dogs and cats.](https://pubmed.ncbi.nlm.nih.gov/25482570/). 2015.
- [Diagnostic evaluation and treatment recommendations for dogs with substage-a high-grade multicentric lymphoma: results of a survey of veterinarians.](https://pubmed.ncbi.nlm.nih.gov/22380460/). 2013.
- [18FDG-PET imaging in canine lymphoma and cutaneous mast cell tumor.](https://pubmed.ncbi.nlm.nih.gov/19400472/). 2009.
- [Surgical management of primary, metastatic and recurrent anal sac adenocarcinoma in the dog: 52 cases.](https://pubmed.ncbi.nlm.nih.gov/28245066/). 2017.
- [Cytologic patterns of lymphadenopathy in dogs infected with Leishmania infantum.](https://pubmed.ncbi.nlm.nih.gov/16134072/). 2005.
- [Clonality and phenotyping of canine lymphomas before chemotherapy and during remission using polymerase chain reaction (PCR) on lymph node cytologic smears and peripheral blood.](https://pubmed.ncbi.nlm.nih.gov/20357946/). 2010.
- [American Society for Veterinary Clinical Pathology Guidelines](https://www.asvcp.org/page/QALS_Guidelines). American Society for Veterinary Clinical Pathology.
- [MSD Veterinary Manual, Professional Edition](https://www.msdvetmanual.com/). MSD Veterinary Manual.
- [American Veterinary Medical Association Practice Resources](https://www.avma.org/resources-tools). American Veterinary Medical Association.

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> This article is educational professional reference material for veterinary audiences. It is not a substitute for veterinary diagnosis, individual clinical judgment, current product labeling, or applicable regulatory requirements.