A nondiagnostic cytology report is about the slide, not the lump

Few phone calls from a veterinary clinic create as much confusion as the one following a fine-needle aspiration: "The cytology report came back, but the laboratory says it is nondiagnostic." Pet owners who spent several anxious days awaiting a definitive answer are suddenly left in diagnostic limbo. Does "nondiagnostic" mean the lump is harmless scar tissue? Does it mean the pathologist missed a malignancy? Or does it mean the animal has an undetectable cancer that cannot be identified?

A nondiagnostic cytology result is an evaluation of the slide, not a diagnosis of the patient. It means the clinical pathologist examined the glass slide under a microscope and determined that the collected material could not yield an interpretable or safe medical conclusion. The cells present on that specific piece of glass were insufficient in number, obscured by peripheral blood, damaged during collection or preparation, or simply unrepresentative of the underlying mass. It does not establish that the lump is benign, and it does not establish that cancer is present.

To understand why this happens, it is essential to distinguish fine-needle aspiration (FNA) cytology from surgical histopathology. FNA cytology is a rapid, minimally invasive screening tool. A veterinarian inserts a small-gauge needle into a mass, collects loose cells into the needle lumen or hub, expels those cells onto a glass slide, stains them, and examines their individual microscopic morphology. Histopathology, by contrast, evaluates an intact block of solid tissue removed via biopsy or surgical excision. Histopathology preserves tissue architecture, cellular arrangement, vascular invasion, and surgical margins—spatial details that loose cells alone cannot provide.

Because cytology examines only exfoliated cells, its diagnostic success relies on two distinct factors: first, whether the veterinarian's needle captured a well-preserved, representative sample of cells; and second, whether the underlying disease process is one that can be definitively identified from loose cells without architectural context. When a report returns without a diagnosis, the immediate operational task is to separate technical sample failures from biological tissue limitations, ensuring your pet receives the correct next diagnostic step rather than an unguided repeat procedure.

Read the exact wording: inadequate, inconclusive, or descriptive

Veterinary laboratories do not share one identical phrase list, but they do use a small set of overlapping clinical-pathology comments when a definitive diagnosis cannot be reached. When discussing the report with your veterinarian, ask them to read the pathologist's exact descriptive comments. Diagnostic laboratories generally separate non-definitive findings into three distinct categories:

1. Inadequate, Insufficient, or Acellular (Specimen Quality Failure): This indicates that the slide contained too few intact, well-stained, nucleated cells to perform an evaluation. The pathologist may note that the smear consists almost entirely of mature red blood cells (hemodilution), ruptured nuclear material (lysis artifact), acellular protein droplets, or bare glass. The failure lies in the sample itself, meaning no biological conclusion can be drawn about the lump.

2. Inconclusive or Non-Definitive (Biological or Overlap Limitation): In this scenario, abundant intact cells were present on the slide, but their microscopic characteristics did not allow a definitive diagnosis. For example, reactive inflammatory fibroplasia can look microscopically indistinguishable on individual cytology from low-grade fibrosarcoma. Similarly, benign follicular cysts and well-differentiated epidermal neoplasms may yield identical keratin squames. The sample was technically adequate, but cytology as a modality reached its natural diagnostic boundary.

3. Descriptive or Categorized (Partial Diagnostic Triage): The pathologist cannot name a specific tumor type or infectious organism, but provides critical directional triage. The report might identify marked suppurative inflammation (neutrophils indicating infection or foreign-body reaction), granulomatous inflammation (macrophages suggesting fungal or mycobacterial disease), or categorize a mass into one of the major tumor families: round cell, epithelial, or mesenchymal. Even without a definitive final label, this result guides immediate antimicrobial, anti-inflammatory, or staging decisions.

Understanding which category your pet's report falls into determines the logical next step. A technical adequacy failure often warrants a repeat aspirate with altered collection mechanics, whereas an inconclusive result on an adequate slide indicates that further needle aspirations will likely fail again, making tissue biopsy necessary.

Why slides fail: cellularity, blood, rupture, poor exfoliation, and shipping artifacts

When a cytology slide fails, it is rarely due to clinician negligence. Fine-needle sampling is a blind or palpation-guided micro-biopsy performed on an awake or lightly sedated animal. Cornell University's eClinPath teaching resource groups the main reasons a sample is non-diagnostic as poor cellularity (a poorly exfoliating lesion or poor collection), excessive blood contamination, and many smudged or ruptured cells from too much aspiration pressure or smear compression. Sampling the wrong structure, such as adjacent fat, is a separate collection error.

Hypocellularity and the Biology of Poorly Exfoliating Tumors

Hypocellularity occurs when the needle fails to dislodge enough intact cells. In some cases, the needle tip simply passes through a necrotic center, dense fat, or a fluid-filled cavity. But in many cases, hypocellularity is governed by tumor biology. Round-cell tumors (such as lymphoma, mast cell tumors, and histiocytomas) have minimal intercellular junctions and shed cells profusely upon needle contact. Epithelial tumors (such as carcinomas and adenomas) exfoliate in sheets and clusters.

In contrast, mesenchymal tumors (including fibromas, nerve sheath tumors, hemangiopericytomas, and soft-tissue sarcomas) produce abundant extracellular matrix, collagen fibers, and reticulin scaffolding. Their cells are tightly anchored in fibrous connective tissue and do not readily detach. An aspirate from a large, aggressive soft-tissue sarcoma can return almost completely acellular, yielding only a drop of clear fluid or scattered red cells despite vigorous needle movement. If a firm mass fails to exfoliate, the failure itself is a clinical clue pointing toward a mesenchymal or stroma-rich lesion.

Excessive Hemodilution and Cell Lysis Artifact

Hemodilution occurs when peripheral capillaries rupture, flooding the needle bore with blood. Under the microscope, dense carpets of red blood cells physically obscure nucleated tissue cells. Worse, circulating peripheral white blood cells (neutrophils and lymphocytes) enter the smear, which can mislead an evaluator into diagnosing inflammation when the actual lesion is neoplastic. Blood-associated leukocytes on a hemodiluted smear do not count toward diagnostic cellularity and can be mistaken for inflammation, which is why a bloody slide can be uninterpretable even when a mass is present.

Cell lysis and smudging artifact happen during slide preparation. When applying suction with a large syringe or compressing the aspirate between two glass slides with excessive force (the "squash prep" error), fragile cells rupture. Their cell membranes disintegrate and their nuclei stretch into parallel purple streamers known as nuclear crush artifact or "bare chromatin." Because nuclear and cytoplasmic borders are destroyed, pathologists cannot assess cellular criteria of malignancy such as anisokaryosis, macronucleoli, or nuclear-to-cytoplasmic ratios.

External Environmental and Shipping Artifacts

Several critical failure points occur after the needle leaves the patient's skin. Formalin fume contamination is one of the most common preanalytical hazards in veterinary practice. When unstained cytology slides are packaged in the same shipping box or transport bag as a biopsy container holding formalin, formaldehyde gas leaches through threaded plastic caps. Even minute airborne concentrations of formalin vapor partially fix the cytology cells, permanently blocking uptake of Romanowsky, Wright-Giemsa, and Diff-Quik stains. The resulting smear appears hazy, pale greenish-gray, and unreadable. Cornell AHDC instructs clinics to mail cytology in a separate container from formalin-fixed tissues because formalin leaches through caps and ruins staining, to label slides in pencil because ink can wash off, and not to refrigerate smears. MSU VDL similarly tells clinics to keep unstained smears away from formalin fumes—using separate bags if they must travel with a biopsy jar—and to stain and review at least one smear before submission.

Ultrasound acoustic coupling gel is another frequent culprit during ultrasound-guided aspirations. If the needle passes through residual acoustic gel on the skin without thorough wiping with alcohol, the gel enters the sample. On Romanowsky-stained slides, ultrasound gel creates distinctive bright magenta or purple amorphous granular precipitates that mimic mucinous matrix or necrotic debris, obscuring cellular details.

How often laboratories call samples nondiagnostic — and why that is not your pet's odds

Pet owners facing a nondiagnostic result often assume that an error occurred or that their pet's situation is extraordinarily unusual. Peer-reviewed veterinary literature demonstrates that nondiagnostic cytology submissions are a standard reality of laboratory clinical pathology.

A seminal study by Ghisleni and colleagues evaluated 292 cutaneous and subcutaneous FNAs from dogs and cats submitted to a veterinary clinical pathology service. Before analyzing diagnostic accuracy, the investigators excluded 49 of the 292 specimens—exactly 16.8%—because of poor cellularity, yielding a specimen retrieval rate of 83.2%. In other words, one in every six submitted mass aspirates did not contain enough cells to evaluate.

Anatomical location strongly influences diagnostic yield. In a large retrospective analysis of lymph-node aspirates by Amores-Fuster et al., 346 of 1,274 canine lymph-node samples (27.2%) and 28 of 199 feline samples (14.1%) were classified as nondiagnostic. The authors identified absence of cells, low yield, and cell disruption as the primary drivers of specimen failure. In cats, reactive lymphoid hyperplasia predominated, whereas in dogs, lymphoma was the most common definitive diagnosis.

More recently, large multi-center epidemiological datasets published in 2025 by Brilhante-Simões and co-authors confirmed these patterns across broader clinical practice. Among 3,068 feline cytology submissions in a Portugal multicentric laboratory series, 33.80% were non-diagnostic, mainly from insufficient cellularity or suboptimal quality; skin lesions and lymph nodes were among the more difficult sites. In a separate analysis of 12,671 canine laboratory submissions from 355 Portuguese practices (2010–2016), 30.97% were non-diagnostic. Cutaneous and subcutaneous samples had the lowest diagnostic yield in that canine series (66.12%), while fluid samples had the highest (80.21%). Those papers describe laboratory submissions in one country, not a U.S. clinic risk score, and the canine authors note that some lipomas and mast-cell tumors diagnosed in-house never enter the denominator.

Why these published percentages do not represent your pet's individual risk score: These figures represent commercial laboratory submission series. In everyday clinical practice, a substantial portion of straightforward masses—such as classic subcutaneous lipomas, sebaceous adenomas, and heavily granulated mast cell tumors—are identified by general practitioners on in-house clinic microscopes and never sent to external reference laboratories. The cases packaged and mailed to commercial laboratories disproportionately consist of ambiguous, firm, poorly exfoliating, or difficult lesions. Therefore, commercial laboratory nondiagnostic rates describe the difficulty of submitted caseloads; they do not mean your individual dog or cat has a one-in-three chance that this fine-needle aspirate failed.

A quiet or 'non-neoplastic' cytology is a weak cancer rule-out

Perhaps the greatest clinical danger following an uninformative cytology report is false reassurance. When a report reads "no neoplastic cells observed" or describes scattered mature neutrophils and erythrocytes, owners often assume that cancer has been ruled out. Clinically, that assumption is invalid.

In the Ghisleni et al. investigation, researchers compared cytologic diagnoses directly with subsequent surgical histopathology across all adequate specimens. For the detection of neoplasia—not specifically “cancer” versus a benign tumor—cytology had a specificity of 97.9% and a positive predictive value of 99.4%. Among 176 adequate samples diagnosed as neoplastic on cytology, one was a false-positive. A well-prepared slide that names neoplasia is therefore much more trustworthy than a quiet slide that appears to rule neoplasia out.

However, the study revealed a critical vulnerability: the negative predictive value (NPV) was only 68.7%. Out of 67 samples classified as non-neoplastic on cytology, 21 were neoplastic on histopathology. That is why the negative predictive value was only 68.7%. Those 21 cases were neoplasms, not automatically “missed malignancies”: some neoplasms are benign. The practical point for owners is narrower. A non-neoplastic or bland cytology is a weak rule-out of a tumor, because the needle may have sampled necrosis, surface inflammation, or adjacent stroma instead of the lesion that matters.

Cohen and colleagues compared cytology with histopathology obtained within three days in 269 cases (216 dogs, 44 cats, and a handful of other species). False-negative results were far more common than false-positive results. Overall sensitivity at complete agreement was 37.9% including insufficient specimens and 42.7% without them; combining complete and partial agreement raised sensitivity to 56.1% and 63.2%, respectively. Cutaneous and subcutaneous lesions were the most accurate location in that series (up to 66.1% sensitivity at general agreement); liver was among the least accurate. Those percentages answer a stricter “complete versus partial agreement” question than Ghisleni’s neoplasia yes/no analysis after inadequate slides were excluded, so the two papers should not be averaged into one “accuracy of FNA” number. Cohen’s clinical conclusion still holds for owners: if suspicion remains high, repeat cytology or choose another technique rather than treating a quiet slide as a clean bill of health.

Repeat the needle, change the method, or take tissue

When facing an unanswered slide, veterinarians and pet owners must choose between three distinct operational pathways: repeating the fine-needle aspirate with modified technique, modifying the collection modality (such as adding ultrasound guidance), or proceeding directly to surgical biopsy.

When Repeating FNA Makes Sense: Quality Failures on Accessible Targets

Repeating an aspirate is the logical choice when the original failure was purely technical and the lesion remains an appropriate cytology candidate—such as a superficial, freely movable dermal nodule, a suspected round-cell tumor, a cutaneous abscess, or an easily palpable lymph node. However, repeating the exact same motion that generated an acellular or hemodiluted smear will usually yield the exact same failure. The technique must change:

• Non-Aspiration (Capillary / Woodpecker) Technique: Today’s Veterinary Practice describes a needle-only fenestration or “woodpecker” method that uses capillary action instead of syringe suction. Cornell eClinPath notes that this non-aspiration method often matches or beats suction for lymph nodes, highly vascular masses, and fragile cells because it tends to draw fewer red cells. Ask whether the next sample will use that approach rather than the same suction motion.

• Optimizing Needle Gauge: Needle size is a clinic choice, not a home instruction. MSU VDL’s usual starting range for fine-needle biopsy is about 20- to 22-gauge; larger-bore needles tend to yield more blood. Ask which gauge and which motion the veterinarian will try next rather than repeating the same needle path.

• Multiple Geographic Sampling Angles: Large or ulcerated masses are heterogeneous. Sampling only the ulcerated surface captures surface bacteria; sampling only the soft center captures necrotic debris. Clinicians should redirect the needle into several peripheral, firm, non-ulcerated margins.

• In-House Adequacy Screening: In the survey by Skeldon and Dewhurst, 51.4% of surveyed veterinarians shipped cytology samples to commercial laboratories without any prior in-house microscopic review. Today's Veterinary Practice and MSU VDL recommend that clinics stain and screen at least one slide in-house with rapid Romanowsky stain. Confirming the presence of intact, well-preserved nucleated cells before sending the pet home or mailing the package prevents needless multi-day delays. Today’s Veterinary Practice advises leaving a few slides unstained because reference-laboratory stains can highlight mast-cell granules better than rapid stains; submit those unstained smears with any in-house stained smears. In-clinic stain and microscope workflow is covered separately in setting up a GP cytology station.

When to Stop Aspirating and Take Tissue

Repeating an FNA is counterproductive if the slide was cellular but inconclusive, if the mass is suspected to be a poorly exfoliating mesenchymal tumor (such as a feline injection-site sarcoma), or if the mass sits where tumor type or grade would change the surgery or drugs. Repeating an identical needle pass then mainly delays care. The veterinarian should discuss tissue biopsy for histopathology rather than assuming behavior from an unanswered slide.

The Role and Realistic Limits of Digital Telecytology

Some hospitals scan slides for remote pathologist review. Digital cytology can shorten waiting time, but only if intact cells are actually on the glass. The December 2025 ASVCP Digital Cytopathology Quality Guidelines (Fish et al., Veterinary Clinical Pathology 54(4):318–337) require procedures for assessing digital image quality, managing incomplete or low-quality scans, and deciding when glass-slide review is still required; the authors describe the evidence base as still limited. AAHA’s 2026 comparison table lists typical cytology turnaround as 0–2 days versus 3–7 days for histopathology—useful context, not a promise that a scan will invent cells that were never collected.

Digital telecytology cannot synthesize cells that were never deposited on the glass. If an in-house smear is acellular, hemodiluted, or lysed, scanning that smear creates a high-resolution image of an uninterpretable slide. Fast turnaround is invaluable, but only when preanalytical sample quality is rigorously maintained.

What histopathology adds that cytology cannot

When a cytology report fails to provide a definitive answer, veterinary medicine turns to histopathology as the diagnostic gold standard. While cytology provides loose cells out of context, histopathology evaluates thin stained sections of preserved tissue. That view shows architecture: how cells relate to vessels and neighboring stroma, whether they invade, and—when the entire mass is submitted—how close neoplastic cells sit to the surgical margin.

The 2026 American Animal Hospital Association (AAHA) Oncology Guidelines for Dogs and Cats (Section 3: Tumor Diagnostics & Staging, and JAAHA 62(1):1–37) explicitly emphasize that modern veterinary cancer therapy must be guided by identifying tumor type, tumor grade, and clinical stage. While cytology frequently provides a definitive diagnosis for benign lesions (such as epidermal cysts and lipomas) and round-cell tumors (such as lymphoma and mast cell tumors), it cannot provide the critical prognostic parameters required for complex treatment planning.

AAHA Table 3.3 is the practical split. Cytology is minimally invasive, often needs no sedation, and commonly places a mass into a category—epithelial, mesenchymal, or round cell—sometimes with a specific diagnosis and a benign-versus-malignant call. It does not, except in rare cytologic grading schemes, provide histologic grade. Histopathology more often names the specific tumor, judges benign versus malignant with higher confidence, reports surgical-margin width when the mass was excised, and supplies grade plus other prognostic factors when those factors matter for that tumor type. Those are the reasons AAHA says therapy planning needs a cytologic or histologic diagnosis, and why an inconclusive FNA should lead to biopsy rather than an assumed tumor behavior.

Critical prognostic information delivered exclusively by histopathology includes:

• Histologic Tumor Grade: Grading systems (such as the Patnaik and Kiupel two-tier grading systems for canine mast cell tumors, or the soft-tissue sarcoma grading scale) evaluate cellular differentiation, percentage of tumor necrosis, and mitotic activity. These systems predict metastatic risk and determine whether chemotherapy or radiation is necessary.

• Mitotic Count / Mitotic Index: Pathologists count mitotic figures in a standardized area of the tissue section. AAHA lists mitotic index among the histopathology findings cytology cannot supply; a high count is one of several features used to judge aggressiveness for some tumor types, not a stand-alone prognosis for every mass.

• Vascular and Lymphatic Micro-Invasion: Histopathology reveals whether neoplastic cells have breached endothelial linings and entered lymphatic vessels or capillaries, signaling that microscopic metastatic dissemination is already underway.

• Surgical Margin Evaluation: When an entire mass is excised, the surgical pathologist coats the outer margins with specialized colored inks. Under the microscope, they measure the exact distance between neoplastic cells and the ink, classifying margins as complete (clean), close, or incomplete (dirty). This single finding dictates whether a second surgery, scar revision, or adjuvant radiation therapy is required.

Veterinarians employ several standard biopsy techniques depending on the size, location, and vascularity of the mass:

• Punch Biopsy: Utilizes a circular skin-biopsy punch (typically 4 to 6 mm) to obtain a full-thickness core of skin and superficial subcutaneous tissue, ideal for ulcerated, inflammatory, or flat dermal plaques.

• Needle Core (Tru-Cut) Biopsy: A specialized spring-loaded needle harvests a thin cylinder of solid tissue. Often performed with local anesthesia or light sedation, it is particularly useful for deep, firm, poorly exfoliating muscle and subcutaneous masses.

• Incisional Wedge Biopsy: The surgeon removes a small, representative wedge of tissue from the mass while leaving the bulk in place. This is often chosen for large or fixed tumors when knowing the tumor type or grade beforehand would change the planned excision. AAHA’s histopathology options include needle-core, punch, and wedge biopsies as well as curative-intent surgery.

• Excisional Biopsy: Complete surgical removal of the mass with curative intent, followed by submitting the entire specimen for histopathology. While attractive to pet owners who want the mass gone immediately, excisional biopsy without prior cytologic or incisional diagnosis carries significant risk: if an unsuspected high-grade sarcoma is "shelled out" with narrow margins, tumor cells remain seeded in the wound bed, necessitating extensive revisions.

Questions to ask before you leave, and when not to wait

A nondiagnostic cytology result should conclude with a clear, collaborative plan between you and your veterinarian. Rather than leaving the exam room with open-ended uncertainty, use this structured checklist of clinical questions to establish your pet's immediate diagnostic trajectory:

1. "What was the exact wording used by the pathologist?" Confirm whether the sample was classified as inadequate (acellular, lysed, hemodiluted), inconclusive (adequate cells but overlapping features), or descriptive (inflammatory or family-level classification).

2. "Was a stained slide screened in-house for adequate cellularity before submission?" Inquire whether intact cells were verified microscopically prior to shipment, and whether unstained, intact slides remain available for an alternate clinical pathologist or specialized staining.

3. "Could preanalytical artifacts have affected the sample?" Verify that cytology slides were stored and mailed in complete isolation from formalin jars, and that ultrasound gel or crushing forces did not compromise cell preservation.

4. "Given this mass's consistency and location, is a repeat aspirate likely to succeed?" If the mass is firm and collagenous, ask whether repeating a needle aspirate will merely yield another acellular smear, or whether immediate needle-core or punch biopsy is clinically justified.

5. "Will our future treatment decisions require tumor grade or margin assessment?" Under the 2026 AAHA Oncology Guidelines, definitive therapy plans require histologic grade and stage. If surgical excision or chemotherapy is on the horizon, discuss transitioning directly to histopathology.

6. "Should we sample the regional draining lymph nodes now?" AAHA guidelines emphasize that lymph node palpation and normal physical size are unreliable indicators of metastasis. A normal-feeling lymph node can harbor micrometastatic disease that alters staging.

7. "If we elect to monitor this lump, what is our objective, written monitoring protocol?" "Watchful waiting" is an active medical strategy only when defined by objective metrics: measuring the lump with calipers, logging baseline photographs, and setting a mandatory calendar re-evaluation date.

Triage Red Flags: When Waiting Is Not an Option

While some slow-growing, soft, freely mobile subcutaneous masses can be monitored for short intervals, specific clinical warning signs demand immediate escalation to tissue biopsy or specialized oncology referral:

• Rapid Growth: Rapid, documented growth of a mass that was concerning enough to sample. For a lump at a feline injection site, the 3-2-1 criteria (persisting more than 3 months after injection, measuring more than 2 cm, or growing more than 1 month after injection) are a reason to stop waiting and discuss biopsy rather than another identical FNA.

• Tissue Fixation: A mass that feels tethered or fixed to underlying abdominal wall, ribs, skeletal muscle, or deep fascia, suggesting invasive infiltration.

• Ulceration and Necrosis: Spontaneous skin breakdown, persistent bleeding, non-healing discharge, or surface ulceration that does not respond to topical therapy.

• Pain, Heat, or Rapid Texture Changes: Tenderness upon palpation, local inflammation, or sudden firm nodular hardening within an otherwise soft mass.

• Regional Lymphadenopathy: Swelling or firm enlargement of the lymph nodes draining the anatomical region of the lump.

Understanding Financial and Logistical Realities: Diagnostic procedures involve variable marketplace costs. Published consumer ranges are not a national fee survey. PetMD’s secondary band for dog FNA is generally $50 to $200, with higher fees if sedation, ultrasound guidance, or reference-laboratory interpretation is needed. Surgical biopsy is described there as several hundred dollars to over $1,000 more depending on location, whether the mass is removed, surgical time, and difficulty. Insurance payment for FNA or biopsy is policy-specific—waiting periods and exclusions still apply—and is not this article’s job (see pet insurance cancer coverage rules and the oncology first appointment estimate checklist).

By treating a nondiagnostic cytology report as a branching point rather than a dead end, owners and veterinary teams can avoid repeating a failed motion, ask for tissue when architecture or grade is required, and keep monitoring from turning into an unspoken default. Disease-specific next reading includes lipomas in dogs, canine mast cell tumors, canine lymphoma diagnosis and staging, lymphoma in cats, canine mammary tumors, and feline injection-site sarcoma. Timing of specialist referral and the first oncology visit are covered in oncology referral timing and the first-appointment records and estimate checklist. Ear-swab treatment choices are a different job (dog ear cytology).

Sources

The clinical and laboratory principles in this guide are drawn from peer-reviewed veterinary clinical pathology literature, established veterinary oncology guidelines, and diagnostic laboratory standards:

• 2026 AAHA Oncology Guidelines for Dogs and Cats, Section 3: Tumor Diagnostics & Staging — American Animal Hospital Association (AAHA). Comprehensive consensus guidance on cytologic versus histopathologic indications, tumor grading requirements, and lymph-node staging protocols.

• AAHA Oncology Guidelines for Dogs and Cats — Journal of the American Animal Hospital Association (JAAHA 2026, 62(1):1–37). Primary peer-reviewed guideline establishing tumor type, grade, and stage identification as prerequisites for cancer therapy.

• Correlation between fine-needle aspiration cytology and histopathology in the evaluation of cutaneous and subcutaneous masses from dogs and cats — Ghisleni G, Roccabianca P, Ceruti R, et al. Veterinary Clinical Pathology, 2006; 35(1):24–30. Found 16.8% of mass aspirates excluded for hypocellularity; established 90.9% agreement on neoplasia, 99.4% positive predictive value, and 68.7% negative predictive value.

• Evaluation of sensitivity and specificity of cytologic examination: 269 cases (1999–2000) — Cohen M, Bohling MW, Wright JC, et al. Journal of the American Veterinary Medical Association (JAVMA), 2003; 222(7):964–967. Documented that false-negative cytology results substantially exceed false-positive results, requiring biopsy when clinical suspicion persists.

• The diagnostic utility of lymph node cytology samples in dogs and cats — Amores-Fuster I, Cripps P, Graham P, Marrington AM, Blackwood L. Journal of Small Animal Practice, 2015; 56(2):125–129. Identified 27.2% of canine and 14.1% of feline lymph-node aspirates as nondiagnostic, citing cell absence, cell disruption, and low yield.

• The perceived and actual diagnostic utility of veterinary cytological samples — Skeldon N, Dewhurst E. Journal of Small Animal Practice, 2009; 50(4):180–185. Analyzed 945 commercial cytology submissions with a 19.2% unacceptable rate, noting that 51.4% of surveyed practitioners shipped slides without in-house screening.

• What Comes from Cytology Diagnosis: A Comprehensive Epidemiological Retrospective Analysis of 3068 Feline Cases — Brilhante-Simões P, et al. Veterinary Sciences, 2025; 12(7):671. Multicentric analysis documenting a 33.80% non-diagnostic rate among 3,068 feline cytology submissions, with skin lesions and lymph nodes among the more difficult sites.

• Large-scale epidemiological and diagnostic assessment of canine cytology in Portugal: insights from 12,671 retrospective cases — Brilhante-Simões P, et al. Veterinary World, 2025; 18(10):2955–2968. Evaluated 12,671 canine laboratory submissions across 355 practices, showing a 30.97% overall non-diagnostic rate, 66.12% diagnostic yield for cutaneous/subcutaneous samples, and 80.21% for fluids.

• ASVCP quality assurance guidelines: control of preanalytical, analytical, and postanalytical factors for urinalysis, cytology, and clinical chemistry in veterinary laboratories — Gunn-Christie RG, et al. Veterinary Clinical Pathology, 2012; 41(1):18–26. American Society for Veterinary Clinical Pathology guidelines establishing quality control criteria for specimen adequacy.

• Quality Assurance and Laboratory Standard Guidelines — American Society for Veterinary Clinical Pathology (ASVCP QALS Committee). Standard protocols covering in-house clinical pathology stations, smear quality assurance, and laboratory standards.

• Digital Cytopathology Quality Guidelines — Fish EJ, et al. Veterinary Clinical Pathology, 2025; 54(4):318–337. Minimum standards for digital whole-slide scanning, image resolution verification, and criteria for mandatory glass-slide review.

• Cytologic patterns — Cornell University College of Veterinary Medicine eClinPath. Instructional pathology guidance defining the core specimen adequacy criteria: cellularity, blood contamination, and cell rupture.

• Sample collection — Cornell University College of Veterinary Medicine eClinPath. Best-practice collection protocols covering gentle slide smear preparation, air-drying mechanics, and avoiding crush artifact.

• Cytology (fluid samples only) — Cornell University Animal Health Diagnostic Center (AHDC). Mail cytology away from formalin-fixed tissues, label slides in pencil, and do not refrigerate smears. The laboratory’s page is written for fluid cytology; the formalin, labeling, and refrigeration rules still apply to smears generally.

• Solid Tissue Cytology – Hints to Avoid Poor Quality Samples — Michigan State University Veterinary Diagnostic Laboratory (MSU VDL). Stain and review at least one smear for intact cells, collect a new sample from a different region or with a different technique if that smear is not diagnostic, submit unstained smears with any in-house stained smears, and keep cytology away from formalin fumes.

• Cytology — Merck Veterinary Manual. Textbook clinical pathology reference emphasizing that cytology serves as a guide, requiring histopathologic confirmation before major invasive interventions.

• Fine Needle Aspiration (FNA) — VCA Animal Hospitals / LifeLearn. Client educational guide explaining sampling limitations, non-representative cellularity, and the transition to histology when cytology is non-definitive.

• Cytology - General — VCA Animal Hospitals / LifeLearn. Educational overview detailing why cytology remains valuable for category triage even when a definitive diagnosis cannot be established.

• Cytology, Biopsy, and Histopathology — VCA Animal Hospitals / LifeLearn. Explains why cytology cannot assess tissue invasion or tumor growth rate, and why surgical biopsies provide definitive architectural grading.

• Obtaining a Sample for Cytology Using Fine Needle Biopsy — Today's Veterinary Practice. Clinical review detailing non-aspiration capillary technique, in-house cellularity verification, and avoiding formalin fume staining inhibition.

• Small Animal Skin “Lumps and Bumps” Cytology — Today's Veterinary Practice. Reviews cytologic classification of cutaneous masses, architectural overlap limitations, and specimen adequacy management.

• Ultrasound-Guided Fine Needle Aspiration and Core Biopsy — Today's Veterinary Practice. Reviews imaging-guided sampling protocols, comparative diagnostic yields, and the clinical limitations of splenic and hepatic aspirates.

• Key takeaways from AAHA’s 2026 oncology guidelines — dvm360. Summary of the 2026 AAHA Oncology Guidelines emphasizing the requirement for cytologic or histologic confirmation prior to initiating therapy.

• Fine Needle Aspiration (FNA) for Dogs: What Is It, and Why Would a Dog Need It? — PetMD. Consumer veterinary guidance providing realistic marketplace cost ranges and procedural workflows for fine-needle aspiration versus biopsy.