Veterinary Oncology: Staging, Grading, Imaging, and Liquid Biopsy — Comprehensive Study Notes
Staging and Grading: Core Concepts
Goal: Use staging to determine local, regional, or systemic spread of tumors and guide treatment planning; differentiate staging from grading.
Staging framework: based on the World Health Organization TNM system: TNM where-
T = primary tumor characteristics (size/location)
N = regional lymph node involvement
M = distant metastasis
Staging purpose: prognosis and therapeutic planning; stage guides appropriateness of local tumor excision versus systemic treatment.
Distinction:
Staging: assesses extent of disease (metastasis, spread).
Grading: assesses histologic aggressiveness of the tumor using tissue architecture; requires a chunk of tissue for analysis.
Practical implication: without a definitive tumor name, you cannot accurately prescribe surgical dose or adjuvant therapy.
Early on, prioritize being the front-line clinician (surgeon/oncologist) rather than defaulting to immediate referral.
Important clinical rationale: recognizing the biologic behavior of a tumor helps in selecting appropriate staging and treatment, and in advising owners about prognosis and costs.
Case example introduction: Balto, a 12-year-old male castrated Siberian husky with a rapidly growing, firm, fixed soft-tissue mass at the proximal right hip region; used to illustrate the staging/diagnostic approach.
TNM System in Veterinary Oncology
T: primary tumor characteristics; most important variable is tumor size.
N: lymph node involvement; metastasis via lymphatic spread is common for many tumors; nodes may be assessed for exposure to tumor cells.
M: distant metastasis; systemic spread (e.g., to lungs, liver).
Practical tip: measure tumors in two dimensions for accurate documentation:-
Cranial
caudal (length)
Medial
lateral (width)
Use calipers; document in the medical record; size is often the most predictive prognostic factor.
Example measurement guidance: purchase a pair of calipers and record tumor size in two dimensions; this informs prognosis and helps determine resectability.
Staging Categories (Human and Veterinary Reference)
Stage 0: in situ (T0 N0 M0); tumor confined to the site of origin without invasion through basement membranes.
Stage 1: localized disease (T1–T2 with N0 M0, depending on tumor type); tumor palpable and measurable but without regional or distant spread.
Stage 2: locally advanced cancer with regional lymph node involvement (N1–N2) but no distant metastasis (M0).
Stage 3: locally advanced with more widespread regional spread (extensive regional nodal involvement) but no distant metastasis (M0).
Stage 4: systemic/metastatic disease (M1) with distant metastasis (e.g., to lungs, liver, other organs).
In veterinary practice, these stages help determine whether aggressive local therapy is warranted or if systemic therapy is indicated; stage 4 generally argues against invasive local tumor excision as a sole strategy.
Example reference: a maxillary melanoma in a dog was staged as a T2 tumor with movable regional lymph nodes (N2) and no distant metastasis (M0); used to illustrate staging terminology in a real case.
Local Control versus Systemic Assessment for Soft-Tissue Sarcomas
Soft-tissue sarcomas (STS) tend to infiltrate locally (the classic “crab-like” growth) and have relatively low metastasis rates, but are locally aggressive.
Staging philosophy for STS:-
Local control requires aggressive surgical excision tailored to tumor type.
Systemic risk assessment may be lower than for some other cancers, but staging should still determine metastatic risk.
Why staging matters: knowing the exact tumor name (histology) informs the extent of surgical dose and the need for adjuvant therapies.
Surgical planning emphasis: always consider tumor biology (type) to determine the surgical margin and approach; wrong or missing tumor typing leads to suboptimal treatment.
Grading: Histologic Aggressiveness vs Cytology vs Histopathology
Grading requires tissue, not cytology alone; cytology (cell samples) may provide a suggestive diagnosis but cannot reliably assess tissue architecture and other critical variables.
Saito grading: historical/alternative approach that can be done on cytology in some cases, but standard practice relies on tissue architecture from a biopsy or excised sample.
Grading scales commonly used by pathologists: 1 (least aggressive) to 3 (most aggressive), with 2 in-between.
Caveats:-
Not all tumor types are identical; a diagnosis like “soft tissue sarcoma” is not sufficient to determine prognosis or therapy without staging and grading.
After surgical removal, the grade may influence decisions about adjuvant therapy or further monitoring.
In practice:-
Must stage to determine if disease is localized or widespread before finalizing treatment plan.
Post-excision grading can alter recommended adjuvant strategies if a high-grade variant is identified.
Staging versus Grading: Practical Differences
Staging answers: Is the tumor localized, regional, or systemic? What is the burden of disease?
Grading answers: How aggressive is the tumor? What is the expected biologic behavior?
Together, staging and grading guide prognosis and treatment choices (e.g., surgery alone vs surgery plus chemotherapy/radiation).
Imaging and Staging: What Tests Do We Use?
Minimum database (as baseline):-
Complete blood count (CBC)
Chemistry panel
Urinalysis
Retrovirus status in cats (e.g., FeLV/FIV) relevance to cancer risk
Thoracic staging:-
Three-view thoracic radiographs: VD/ DV (or DV/VD), plus right and left lateral views, to survey lungs for metastasis
Note: using only two views risks missing metastases in 12–15% of cases; three-view radiographs are considered the standard baseline for thoracic staging.
Pulmonary nodules detectable by radiographs generally need to be about 1 cm in size to be visible; CT is more sensitive for detecting small nodules.
Abdominal imaging:-
Abdominal ultrasound to evaluate viscera (liver, spleen, kidneys) for metastasis
Cross-sectional imaging (CT or MRI) as needed
Cross-sectional imaging for staging and planning:-
CT (often full-body CT in oncology) provides millimeter-level detail and better detection of metastases
MRI for specific sites where soft tissue contrast is critical
Cost considerations and real-world practice:-
Minimum database costs: $250–$350
Lymph node cytology: a few hundred dollars
Abdominal ultrasound: around $500
CT scan: typically $1,500–$5,000 depending on location
In practice, owners may not opt for full staging due to cost; clinicians must prioritize tests based on tumor biology and likelihood of metastasis
In cats and dogs: the balance between comprehensive staging and cost is a practical consideration; not every patient undergoes every test, but the goal is to tailor testing to tumor biology and owner resources.
Real-world takeaway: comprehensive staging is ideal, but selective staging based on tumor type and biology is often necessary in general and specialty practice.
Liquid Biopsy: Advancements in Cancer Screening
Concept: liquid biopsy analyzes circulating tumor-derived material in blood to detect cancer noninvasively.
Available technology in veterinary medicine:-
The NewCU Cancer Screening Test (developed by Dr. Heather Robles at Texas A&M) and commercialized by Volition Veterinary; now marketed through AnTech (Antique) for canine use; in some cases, expanded to in-house analyzers (Element AI plus immunodiagnostic analyzer) for faster results.
The test detects circulating nucleosomes (nucleosome DNA) shed by tumors into the blood; aims to identify seven common canine cancers; development is ongoing for feline use.
In-house testing and turnaround time: with in-house analyzers, results can be obtained in about five minutes, enabling rapid decision-making during a visit.
Sensitivity and specificity:-
The test is highly specific (positive results are meaningful) but has limited sensitivity (risk of false negatives); overall sensitivity across all included cancers is around ~50% when considering multiple tumor types.
The highest sensitivity is for the two most common cancers: lymphoma and mast cell tumors; other cancers show lower sensitivity.
Clinical utility and recommendations:-
Consider liquid biopsy as a screening tool rather than a definitive diagnostic test; a positive result indicates potential cancer but not the exact type; a negative result does not rule out cancer, especially for less common tumors.
Suggested use: in dogs aged around 7 years or older, or in high-risk breeds, to screen for cancer during annual wellness exams alongside the minimum database.
The test price is around $120 in some providers, making it a relatively affordable screening option compared to full staging.
Caution: if owners cannot afford full staging, a liquid biopsy can still provide meaningful direction about pursuing further diagnostics.
Alternative liquid biopsy approaches in development:-
Calvary (CalVary) test: focuses on RNA-derived neoantigens and RNA errors (frameshift peptides) in cancer cells; shows promising specificity/sensitivity in early-stage cancer detection; not yet widely available; anticipated higher accuracy than current tests if it reaches the market.
Other liquid biopsy approaches include urine-based methods using nematodes that detect cancer-associated volatile compounds; encode-tact product marketed for at-home use; still largely exploratory and not widely adopted.
Limitations and interpretation considerations:-
Not a confirmatory test; it is a screening modality.
Results require interpretation in the context of the patient’s history, histology when available, and other diagnostic tests.
Positive results should prompt targeted workups to identify cancer type and stage; negative results do not definitively exclude cancer.
Practical deployment ideas:-
If liquid biopsy is used, consider starting in dogs over 7 years old or at-risk breeds during annual health checks, especially when owners want proactive screening.
In-house testing capabilities allow rapid triage and decision-making, potentially enabling earlier detection and improved outcomes if followed by targeted diagnostics.
Sentinel Lymph Node Mapping and Lymph Node Evaluation
Sentinel lymph node concept: the first lymph node downstream from a tumor where metastatic cells are likely to appear; sampling sentinel nodes provides a projection of metastasis risk for the downstream lymphatic system.
Why sentinel nodes matter: sampling only the nearby regional node may miss metastasis; sentinel node mapping improves accuracy in staging regional disease.
Early mapping technique (historical): Lipiodol (iodized poppy-seed oil) injection in four quadrants around the tumor; 24 hours later, regional radiographs identify the sentinel node as the node that takes up contrast:-
Example: a canine ear tumor with sentinel node sampling via Lipiodol mapping showed the ipsilateral superficial cervical lymph node as sentinel.
If sentinel node is negative: higher confidence that there is no downstream metastasis; if sentinel node is positive: suggests systemic dissemination and the need for additional therapy beyond local surgery.
Limitations of Lipiodol technique: can be unreliable or delayed; risk of multiple nodes taking up contrast, or not clearly identifying sentinel nodes.
Current practice (more reliable): use water-soluble contrast and immediate CT imaging of the region to map lymphatic drainage and identify sentinel lymph nodes; serial CT scans show real-time contrast leakage from the tumor into lymphatics and down to sentinel nodes.
Alternative intraoperative approaches:-
Lymphatic mapping with blue dye (e.g., methylene blue) to visually identify sentinel nodes during surgery.
In some scenarios, injecting the dye helps visually locate sentinel nodes when imaging is challenging or unavailable.
Surgical workflow with sentinel node guidance:-
Remove sentinel lymph node first, then the primary tumor after closing the site to preserve biopsy integrity.
Pathology evaluation of sentinel node informs prognosis and subsequent treatment decisions.
Contemporary practice and challenges:-
CT-based sentinel node mapping is increasingly used when resources permit; digital radiography can also help map sentinel nodes rapidly.
The provider should consider sentinel mapping for tumors known to metastasize via lymphatics (e.g., mast cell tumors, certain soft tissue tumors).
The sentinel node may not always be easily identifiable; imaging and dye-based techniques are used to improve localization accuracy.
Lymph Node Evaluation: Practical Considerations and Pathways
Goals:-
Determine if regional lymph nodes are involved by tumor cells.
Identify sentinel lymph node for sampling to infer pattern of spread.
Practical approach:-
Begin with sampling the regional node; then assess sentinel node to determine likelihood of further metastasis.
If sentinel node is negative, consider less extensive nodal sampling; if positive, broaden staging and plan systemic control.
Real-world constraints:-
Availability of radioactive materials and licensing limits routine use in many practices; creative alternatives include Lipiodol mapping, dye techniques, and CT-based mapping when feasible.
Summary: sentinel lymph node mapping is a critical tool to optimize staging accuracy and guide therapy decisions, balancing accuracy with practicality and safety.
Thoracic Imaging and Cross-Sectional Techniques
The lungs are a common site of metastasis in many tumors; thorough thoracic assessment is essential for stage determination.
Views and imaging modality:-
Three-view thoracic radiographs (VD/DV, right lateral, left lateral) are preferred for comprehensive screening; two-view radiographs miss metastases in a meaningful percentage of cases (12–15%).
CT of the thorax provides higher sensitivity, detecting smaller nodules with millimeter resolution; CT is superior for staging and planning.
Practical tip: whenever possible, use three-view radiographs or CT for accurate detection of metastasis; plan treatment accordingly.
Abdominal ultrasound: important for detecting hepatic metastases and other intra-abdominal disease; the liver is a common metastasis site for hematogenous spread.
Hematogenous vs lymphatic spread:-
Some tumors favor the hematogenous route (bloodborne spread) leading to liver or lung involvement; others spread through lymphatics with regional lymph node involvement and less hepatic involvement.
Cross-sectional imaging for localization and planning:-
CT or MRI can be used not only for staging but also for precise surgical planning and radiotherapy targeting.
Practical Considerations: Cost, Ethics, and Clinical Reasoning
Cost-benefit considerations:-
Full staging can be expensive; clinicians must balance owner resources with the potential benefit of early detection and improved outcomes.
Use a “test–based” approach: begin with the minimum database and imaging; escalate testing based on tumor type, suspected behavior, and owner willingness/ability to pursue care.
Ethical and practical implications:-
Avoid overtreatment when evidence suggests limited benefit, particularly in stage IV disease where invasive therapies may not improve outcome.
Strive to outsmart cancer using biologic knowledge to optimize treatment choices (e.g., margin size, adjuvant therapy) rather than applying a cookie-cutter approach.
Real-world summary of cancer screening and staging:-
In humans, cancer staging and long-term data facilitate prognosis and treatment planning; in veterinary medicine, we are increasingly adopting similar staging frameworks to improve outcomes.
Emerging liquid biopsy technologies and sentinel node mapping are driving faster, more precise staging and enabling earlier intervention.
Future directions described in the lecture:-
Liquid biopsy will continue to evolve; ongoing work aims to expand sensitivity, reduce cost, and enable feline applicability.
Cross-sectional imaging and sentinel node techniques will become more accessible and routine in practice, improving staging accuracy and guiding therapies.
Real-World Takeaways and Study Points
Always name the tumor (histology) to guide surgical dose and therapy decisions; do not rely on gross appearance alone.
Distinguish staging (extent of disease) from grading (biologic aggressiveness); both are essential for prognosis and treatment planning.
Caliper measurements in two dimensions should be standard documentation for tumor size, as size often drives prognosis and surgical planning.
Use three-view thoracic radiographs for staging; acknowledge the higher sensitivity of CT with regards to metastases detection, especially for small nodules (~1 cm or less in radiographs).
Sentinel lymph node mapping improves staging accuracy; consider imaging-guided or dye-based methods to identify sentinel nodes when feasible.
Liquid biopsy offers a promising screening tool, particularly for older dogs or high-risk breeds, but must be interpreted with context and used as a complement to, not a replacement for, conventional staging.
Cost considerations are real; tailor the staging plan to tumor biology and owner resources; prioritize tests that will change management.
The field is rapidly evolving: stay current with new tests (e.g., newer liquid biopsy assays, in-house analyzers) and emerging sentinel node techniques to provide cutting-edge care.
Key Numerical and Conceptual References
TNM system: T = primary tumor characteristics, N = lymph node involvement, M = distant metastasis
Stage 0–4 conceptual mapping:-
Stage 0: in situ (T0 N0 M0)
Stage 1: localized (T1–T2 N0 M0; tumor with no metastasis)
Stage 2: regional spread (N1–N2, M0)
Stage 3: extensive regional spread (N3 or multiple regional nodes, M0)
Stage 4: distant metastasis (M1)
Tumor size measurement guidance: document two dimensions; commonly, larger tumors correlate with poorer prognosis.
Pulmonary metastasis detection by imaging:-
Radiographs detect nodules roughly >=1 cm; CT is more sensitive for small nodules.
Procedure notes:-
Three-view thoracic radiographs (VD/DV, right lateral, left lateral) are recommended for thoracic staging.
Lipiodol-based sentinel node mapping involves four-quadrant injection and 24-hour radiographs to locate sentinel nodes.
CT-based sentinel node mapping provides real-time topology of lymphatic drainage.
Costs (range estimates):-
Minimum database: roughly 250–350 USD
Lymph node cytology: a few hundred USD
Abdominal ultrasound: around 500 USD
CT scan: roughly 1500–5000 USD
Liquid biopsy (NewCU): about 120 USD per test (can be run in-house with certain analyzers)
Final note
This set of notes covers staging, grading, imaging, sentinel lymph node mapping, and the emerging role of liquid biopsy in veterinary oncology, reflecting a shift toward more precise, biology-driven management and earlier detection opportunities. It provides practical workflow guidance, cost considerations, and the ethical context for applying these tools in clinical practice.