Cytological Evaluation of Neoplasia: Understanding Exfoliation Patterns in Veterinary Practice

Cytological evaluation represents a fundamental diagnostic tool in veterinary medicine, offering rapid, minimally invasive assessment of various lesions. However, clinicians must understand which neoplastic processes reliably exfoliate diagnostic cells during fine needle aspiration (FNA) and which tumors typically require histopathological examination for definitive diagnosis. This distinction is critical for efficient diagnostic planning and appropriate client communication regarding expected outcomes of minimally invasive sampling techniques versus more invasive biopsy procedures.

Tumors with Favorable Exfoliation Characteristics

Round Cell Tumors

High Grade Lymphoma - Popliteal LN (8yr MN Mixed Breed Dog)

Round cell tumors consistently rank among the most amenable to cytological diagnosis due to their inherently loose cellular attachments and distinctive cytomorphological features.

• Lymphoma: Typically exfoliates abundantly with monomorphic lymphoid population (e.g. large lymphoblasts with prominent nucleoli and delicate chromatin in high grade lymphoma).

• Mast Cell Tumors: Readily diagnosed via cytology with distinctive purple metachromatic granules when stained with Romanowsky-type stains. Poorly granulated variants may pose challenges but nuclear characteristics remain diagnostic.

• Histiocytic Neoplasms: Both localized histiocytomas and other types of histiocytic tumors yield diagnostic samples with round cells displaying characteristic kidney-shaped nuclear features.

• Transmissible Venereal Tumors: Exfoliate well with distinctive large discrete vacuoles within cytoplasm.

• Plasma Cell Tumors: Typically yield diagnostic samples with eccentric nuclei and perinuclear clear zones (Golgi apparatus).

Epithelial Neoplasms

Squamous cell carcinoma with marked neutrophilic inflammation and necrosis - Submandibular LN (11yr old FS DSH)

Many epithelial tumors exfoliate well due to reduced intercellular attachment:

• Thyroid Carcinomas: Often yield highly cellular samples with distinctive follicular or compact epithelial arrangements.

• Hepatocellular Carcinomas: Generally provide diagnostic samples with hepatocyte features, including abundant granular cytoplasm and distinct nucleoli.

• Transitional Cell Carcinomas: Typically exfoliate well with angular cells displaying anisokaryosis and basophilic cytoplasm.

• Anal Sac Adenocarcinomas: Usually yield diagnostic samples with epithelial clusters and characteristic intracytoplasmic blue-gray granules.

• Trichoblastomas:

Mesenchymal Tumors

Lipoma - Subcutaneous mass on the left lateral thorax - 10yr MN Labrador Retriever

Mesenchymal tumor exfoliation varies. In some cases, a confident diagnosis can be made, but more often than not, histopathology is required to achieve a definitive diagnosis. 

• Lipoma: Typically yields characteristic mature adipocytes.

• Soft Tissue Sarcomas of Higher Grade: More anaplastic variants often exfoliate better than well-differentiated tumors.

Tumors with Poor Exfoliation Characteristics

Mesenchymal Neoplasms

Most mesenchymal tumors require histopathology due to poor exfoliation and the importance of architectural patterns in classification:

• Fibrosarcomas: Generally yield poorly cellular samples with indistinct features.

• Chondrosarcomas: Often yield acellular to poorly cellular material with occasional chondrocytes in lacunae.

• Osteosarcomas: While osteoblasts may exfoliate, diagnostic matrix production is difficult to assess cytologically.

• Peripheral Nerve Sheath Tumors: Typically yield sparse cellularity with indeterminate spindle cells.

• Well-differentiated Soft Tissue Sarcomas: Often produce minimal diagnostic material.

• Hemangiosarcoma: Varied success.

Other Challenging Entities

• Lymph Node Metastases with Desmoplastic Response: The reactive fibrosis often impedes the collection of diagnostic cells.

• Fibromatous Oral Lesions: Fibrous epulides and related lesions typically yield minimal cellular material.

• Poorly Differentiated Tumors: It may be difficult to determine the tissue origin without architectural context.

According to Cowell et al. (2020), the diagnostic accuracy of cytology for mesenchymal tumors averages only 50-60% compared to subsequent histopathology, emphasizing the need for tissue architecture evaluation in many cases.

Clinical Decision-Making Framework

When choosing between cytology and histopathology, clinicians should consider:

1. Suspected Tumor Type: Based on location, patient signalment, and imaging characteristics

2. Anatomical Location: Deep-seated masses may be more challenging to sample effectively

3. Risk Assessment: Balancing sampling risks against diagnostic yield

4. Treatment Planning Requirements: Some therapeutic protocols require histological grading

5. Client Preferences and Economics: Considering the cost-benefit ratio of staged diagnostics

Peleteiro et al. (2021) demonstrated that implementing systematic cytological evaluation before surgical intervention reduced unnecessary surgeries by approximately 23% in a retrospective analysis of 450 cases, highlighting the value of appropriate cytological triage. 

Practical Approaches to Challenging Cases

For lesions with historically poor exfoliation characteristics, consider:

• Multiple sampling techniques: Combining FNA with core needle biopsy.

• Ultrasound-guided sampling: Targeting specific regions of heterogeneous masses.

Conclusion

No diagnostic technique is perfect, so when choosing one, it is essential to understand both its benefits and limitations. Understanding the exfoliative characteristics of different neoplasms allows veterinarians to select appropriate diagnostic modalities, develop realistic expectations for cytological findings, and plan efficient diagnostic pathways. While round cell tumors and many epithelial neoplasms readily yield diagnostic cytological samples, mesenchymal tumors and architecturally complex lesions typically require histopathological examination for definitive diagnosis and classification.

Regardless of their characteristics, cytology is consistently like the preview to a movie. Sometimes the movie is just as the preview depicted; other times, it’s completely different from what was expected. 

References

1. Raskin, R.E., & Meyer, D.J. (2016). Canine and Feline Cytology: A Color Atlas and Interpretation Guide (3rd ed.). Elsevier.

2. Cowell, R.L., Valenciano, A.C., Rizzi, T.E., & Sykes, J.E. (2020). Diagnostic Cytology and Hematology of the Dog and Cat (5th ed.). Mosby.

3. Peleteiro, M.C., Marcos, R., Santos, M., Correia, J., Pissarra, H., & Carvalho, T. (2021). Atlas of Veterinary Cytology: Dog, Cat, Horse and Cow. John Wiley & Sons.