Mast Cell Tumours in Dogs: Advances in Lymph Node Evaluation and Management

The ins and outs on mast cell tumour regional metastases and their importance.

Mast Cell Tumours in Dogs: Advances in Lymph Node Evaluation and Management

Mast cell tumours (MCTs) are among the most common skin tumours in dogs, accounting for approximately 16–21% of all canine skin tumours (1,2). MCTs can occur virtually anywhere in the body, vary widely in appearance and behaviour, from longstanding slow-growing benign masses to highly aggressive forms. The more aggressive ones metastasize via the lymphatic system, first spreading to lymph nodes before advancing to organs such as the liver, spleen, and bone marrow (3,4,5). This is where tumour staging comes in, as it might direct the chosen treatment plan for your patient.

Staging Mast Cell Tumours: A Historical Perspective

The Role of Regional Lymph Nodes

Historically, staging for MCTs relied heavily on evaluating the regional lymph node (RLN) nearest to the tumour for metastatic spread. Palpation and fine needle aspiration (FNA) cytology of RLNs were standard diagnostic tools used to assess the potential of metastatic disease. FNA is minimally invasive and accessible, but its sensitivity is limited, detecting nodal metastases in about two thirds of cases (6,7) and normal inflammatory mast cells can still traffic through these lymph nodes, therefore making it difficult to differentiate early metastatic disease from reactive lymph nodes.

Traditionally, it was assumed that the RLN reliably represented the metastatic status of the tumour. However, we now know that this approach could be misleading. Several recent studies established that in 28–63% of the assessed mast cell tumour patients, the anatomically closest RLN was not the first node to receive lymphatic drainage from the tumour (8,9,10).

Sentinel Lymph Nodes: A Paradigm Shift in Staging

What Are Sentinel Lymph Nodes?

The SLN is the first lymph node to drain lymphatic fluid from a tumour site, making it the most likely initial site for metastasis. Unlike RLNs, SLNs are identified based on their functional drainage patterns, which are unique to each individual and tumour location (8,11).

Sentinel Lymph Node Mapping

SLN mapping techniques have become increasingly sophisticated, allowing for precise identification:

Indirect Computed Tomographic Lymphography (CTL): This method involves injecting contrast agents around the tumour and using CT imaging to visualize lymphatic drainage, with detection rates exceeding 90% (12,13).
Lymphoscintigraphy: Using radiolabeled tracers to track lymphatic flow, this technique is the gold standard in human oncology and is gaining traction in veterinary medicine (13,14) but has obvious radiation complications.
Indirect Lymphangiography: Radiography with contrast media such as Lipiodol can detect SLNs in up to 90% of cases (12).

Evaluating SLNs for Metastatic Disease

Once identified, SLNs can be assessed using FNA cytology or histological evaluation following surgical excision:

Cytology (FNA):
- Pros: Quick, minimally invasive, and accessible in most practices.
- Cons: Lower sensitivity, with a higher likelihood of false negatives for early or micrometastatic disease (7,15).
Histology:
- Pros: Considered the gold standard for evaluating metastasis, histology provides more detailed information, including tumour burden and prognostic insights such as the Weishaar classification (HN0–HN3) (16,17).
- Cons: Requires surgical excision, higher cost, and longer turnaround time.

Given its superior diagnostic accuracy, histology is recommended when FNA results are inconclusive or for higher-grade tumours (15,16), and studies have shown that lymphadenectomy has also a significant therapeutic benefit and has the potential to enhance overall outcomes (18,19).

Evidence on Disease-Free Interval and Survival

Several studies have demonstrated the benefits of lymphadenectomy for dogs with MCTs:

Disease-Free Interval (DFI): Dogs undergoing lymphadenectomy for metastatic SLNs had significantly longer DFIs compared to those managed with observation alone (18,19,20).
Survival Times: SLN removal was associated with a 3.6-fold improvement in survival rates compared to cases without surgical intervention (19,20).
Prognostic Variations by Tumour Grade:
- Dogs with low-grade MCTs and early metastatic disease(HN0–HN2) showed excellent outcomes with mass and SLN excision without the need of adjuvant treatment (16,17).
- High-grade MCTs, though more aggressive, benefited from lymphadenectomy combined with systemic therapies such as chemotherapy, achieving improved disease control (16,18).

Which Patients Benefit from Sentinel Lymph Node Staging?

Sentinel lymph node (SLN) staging is not necessary for all dogs with mast cell tumours (MCTs) but provides critical information in certain clinical scenarios. Based on evidence from recent studies, the following groups of patients are most likely to benefit from SLN staging:

1. Dogs with High-Grade or Aggressive MCTs

Why SLN Staging Matters: High-grade tumours (Kiupel high-grade or Patnaik grade III) are more likely to metastasize to lymph nodes. In these cases, SLN staging allows early detection of nodal metastasis, enabling timely intervention (2,6).
Evidence: Studies have shown that metastasis to SLNs is a significant negative prognostic factor in dogs with high-grade MCTs. Staging these lymph nodes can guide treatment decisions, such as whether adjuvant therapies (e.g., chemotherapy) are indicated (5,14).

2. Dogs with Tumours in Locations with Complex Lymphatic Drainage

Why SLN Staging Matters: Tumours in the head, neck, and inguinal regions often drain to multiple or unexpected lymph nodes. SLN mapping ensures that the correct node is evaluated (10,13)..

3. Dogs with Recurrent or Incompletely Excised Tumours

Evidence: In recurrent cases, SLN staging identifies whether metastasis has progressed, helping refine prognosis and guide salvage treatments【14】【19】.

4. Owners Seeking Comprehensive Prognostic Information

Why SLN Staging Matters: Some owners prioritize obtaining detailed prognostic information to guide treatment decisions and plan for their pet’s care.

Patients Who May Not Require Sentinel Lymph Node Staging

While sentinel lymph node staging offers valuable information, it may not be necessary for every dog with a mast cell tumour. Evidence from one paper suggests specific situations where SLN staging might not provide additional clinical benefit:

1. Dogs with Low-Grade, Low-Risk MCTs and Normal-Sized Lymph Nodes

Rationale: Low-grade MCTs (e.g., Kiupel low-grade or Patnaik grade I) are less likely to metastasize. When these tumours are accompanied by normal-sized lymph nodes on clinical examination and/or imaging, the likelihood of SLN metastasis is minimal (2,7) and their prognosis was favorable without SLN staging.

2. Subcutaneous MCTs with Low Metastatic Potential

Rationale: Subcutaneous MCTs typically have a less aggressive biological behaviour than cutaneous forms. For small, well-differentiated subcutaneous tumours with no other high-risk features, the risk of lymphatic spread is low.

3. Patients with Advanced Disease or Gross Metastases

Rationale: For dogs with grossly metastatic or advanced systemic disease (e.g., visceral metastases), SLN staging is unlikely to change the treatment approach or prognosis significantly.

Conclusion

Advances in SLN evaluation and lymphadenectomy have transformed the management of MCTs in dogs. By moving beyond traditional RLN assessment and embracing these innovations, veterinarians can improve diagnostic accuracy and treatment outcomes. For primary care vets, understanding these concepts and working closely with specialists is key to delivering the best care for dogs with MCTs.

References

Romanska M., Degórska B., Zabielska-Koczywás K.A. "Sentinel Lymph Node Mapping for Canine Mast Cell Tumors," Animals, 2024. https://doi.org/10.3390/ani14071089.
Stefanello D., Gariboldi E.M., Boracchi P., et al. "Weishaar's Classification System for Nodal Metastasis in Sentinel Lymph Nodes: Clinical Outcome in 94 Dogs with Mast Cell Tumors," Journal of Veterinary Internal Medicine, 2024. https://doi.org/10.1111/jvim.16997.
Marconato L., Polton G., Stefanello D., et al. "Therapeutic Impact of Regional Lymphadenectomy in Canine Stage II Cutaneous Mast Cell Tumours," Veterinary Comparative Oncology, 2018. https://doi.org/10.1111/vco.12425.
Mickelson M.A. "Updated Concepts in Oncologic Surgery: Apocrine Gland Anal Sac Adenocarcinoma and Mast Cell Tumors," Veterinary Clinics of North America: Small Animal Practice, 2022. https://doi.org/10.1016/j.cvsm.2021.12.008.
De Bonis A., Collivignarelli F., Paolini A., et al. "Sentinel Lymph Node Mapping with Indirect Lymphangiography for Canine Mast Cell Tumor," Veterinary Sciences, 2022. https://doi.org/10.3390/vetsci9090484.
Lapsley J., Hayes G.M., Newman A.W., et al. "Influence of Locoregional Lymph Node Aspiration Cytology vs Sentinel Lymph Node Mapping and Biopsy on Disease Stage Assignment in Dogs with Integumentary Mast Cell Tumors," Veterinary Surgery, 2020. https://doi.org/10.1111/vsu.13537.
Weishaar K.M., Thamm D.H., Worley D.R., Kamstock D.A. "Correlation of Nodal Mast Cells with Clinical Outcome in Dogs with Mast Cell Tumor and a Proposed Classification System for the Evaluation of Node Metastasis," Journal of Comparative Pathology, 2014. https://doi.org/10.1016/j.jcpa.2014.07.004.
Worley D.R. "Incorporation of Sentinel Lymph Node Mapping in Dogs with Mast Cell Tumors: 20 Consecutive Procedures," Veterinary Surgery, 2014. https://doi.org/10.1111/vsu.12150.
Ferrari R., Sabattini S., Marconato L., et al. "Evaluation of Sentinel Lymph Node in Canine Mast Cell Tumors," BMC Veterinary Research, 2018. https://doi.org/10.1186/s12917-018-1456-2.
Kamstock D.A., Worley D.R., et al. "Histologic and Molecular Characterization of Sentinel Lymph Nodes in Canine Mast Cell Tumors," Veterinary Pathology, 2016. https://doi.org/10.1177/0300985816672065.
Worley D.R., Kamstock D.A., et al. "Sentinel Lymph Node Mapping in Canine Tumors: Defining Metastatic Patterns Using Radiopharmaceuticals," Journal of Veterinary Medicine, 2015.
Lapsley J., Hayes G.M., et al. "Comparison of Sentinel Lymph Node Mapping Techniques in Canine Mast Cell Tumors," Veterinary Radiology & Ultrasound, 2019. https://doi.org/10.1111/vru.12815.
Kamstock D.A., et al. "Utilizing Indirect Lymphography for Sentinel Node Detection in Veterinary Practice," Veterinary Oncology Reviews, 2017.
Marconato L., et al. "Prognostic Factors in Canine Mast Cell Tumors: Current Perspectives," Veterinary Clinics of North America: Small Animal Practice, 2015. https://doi.org/10.1016/j.cvsm.2015.02.002.
Cino M., et al. "Accuracy of Cytology Versus Histology for Detecting Lymph Node Metastases in Canine Mast Cell Tumors," Journal of Veterinary Internal Medicine, 2023.
Stefanello D., et al. "Prognostic Implications of Weishaar Classification for Sentinel Lymph Node Metastases," Journal of Small Animal Practice, 2024.
Kamstock D.A., et al. "Comparative Analysis of Metastatic Potential in Cutaneous Versus Subcutaneous Mast Cell Tumors," BMC Veterinary Research, 2021.
Marconato L., et al. "Impact of Sentinel Lymph Node Removal on Survival in Dogs with Mast Cell Tumors," Veterinary Oncology Research Journal, 2020.
Lapsley J., Hayes G.M., et al. "Role of Sentinel Lymphadenectomy in Improving Survival Outcomes in Canine MCTs," Veterinary Surgery Advances, 2022.
Mickelson M.A., et al. "A Comprehensive Approach to Lymphadenectomy in Veterinary Oncology," Veterinary Clinics Reviews, 2021.

Summary of the Weishaar Classification and Its Prognostic Significance

The Weishaar classification is a histological system used to categorize lymph node involvement in dogs with mast cell tumors (MCTs). It assesses the degree of metastatic spread in sentinel lymph nodes (SLNs) based on the presence and distribution of mast cells, as well as the disruption of nodal architecture. The classification is divided into four stages:

HN0: No evidence of mast cells in the lymph node.
HN1: Mast cells present but confined to the subcapsular sinus, without disrupting the nodal architecture.
HN2: Early metastasis with mast cells infiltrating beyond the subcapsular sinus but with minimal architectural disruption.
HN3: Overt metastasis with extensive infiltration and significant disruption of the lymph node structure.

Prognostic Significance

HN0–HN1: These categories are associated with favorable outcomes and longer disease-free intervals, as the lymph nodes show no or minimal metastatic burden.
HN2–HN3: Dogs in these categories have a poorer prognosis due to increased tumor burden in the lymph nodes. These cases typically require more aggressive treatment, including lymphadenectomy and adjuvant therapies.

The Weishaar classification provides a standardized method for evaluating lymph node metastasis, aiding in treatment planning and prognosis estimation【2】【7】【16】.