Sentinel Lymph Node Mapping

Clinical staging is important for cats and dogs with malignant cancers. Clinical staging is a combination of physical exam and diagnostic imaging findings to determine the extent of cancers. This information is then summarized into the World Health Organization’s T-N-M classification scheme, where T represents the local tumor, N represents the regional lymph node, and M represents distant metastasis. Assessment of the regional lymph node is an essential step in clinical staging, but there is increasing evidence that palpation alone is insufficient and more invasive testing is required to assess lymph node status in animals with malignant cancers.

For example, in one study of 100 dogs with oral malignant melanoma, 40% of dogs with normal sized lymph nodes had metastasis and 49% of dogs with enlarged lymph nodes did not have metastasis.1 Furthermore, the regional lymph nodes include the mandibular, parotid, and medial retropharyngeal lymph nodes, however, only the mandibular lymph node is externally palpable. In another study of 31 cats and dogs with malignant oral tumors, only 55% had metastasis to the mandibular lymph nodes,2 meaning that metastasis would have been missed in 45% of animals if these nodes had not been extirpated. Similarly, lymph node metastasis has been identified in a relatively high percentage of palpably normal lymph nodes in animals with tumors which have a high risk of nodal metastasis, such as cats with mammary carcinomas and dogs mast cell tumors. These studies show that we cannot rely on palpation alone to assess lymph node status in animals with malignant cancers and we need fine-needle aspirates or biopsies and, in some cases such as oral tumors, imaging to assess non-palpable lymph nodes.

To further complicate the assessment of regional lymph nodes, the concept that the nearest lymph node downstream from the cancer is the draining lymph node is outdated and often incorrect. In a recent study of 19 dogs with cutaneous mast cell tumors, the lymph node draining the mast cell tumor was not the regional lymph node in 8 dogs.3 Other studies show that oral tumors can metastasize to either the ipsilateral or contralateral mandibular-medial retropharyngeal-parotid lymph nodes; thyroid carcinomas can metastasize upstream rather than downstream; and mammary carcinomas can metastasize either upstream to the axillary lymph nodes, downstream to the superficial inguinal lymph nodes, or skip these and metastasize to the sublumbar lymph nodes. This is also a common finding in human oncology and, in people, preoperative lymph node assessment is aimed at identifying and sampling the sentinel lymph node (SLN).

The SLN concept is based on the theory that the metastatic process occurs in an orderly progression within the lymphatic system with tumor cells draining into a specific lymph node (i.e., SLN) in a regional lymphatic field before draining into other regional lymph nodes. The SLN has an important role as a filter and barrier for disseminating tumor cells. Conceptually, distant metastasis should not be present if the SLN does not have evidence of a tumor burden, but distant metastasis is possible if the SLN is positive for tumor cells. Hence, the status of the SLN node may reflect the status of the entire regional lymphatic bed. Sentinel lymph nodes are successfully identified in over 95% of women with breast cancer and 97% of patients with gastric cancer and this is predictive of the status of the remainder of the regional lymph node bed in > 85% and 99% of patients, respectively. The SLN is not specific for tumor type or location, but is individual and changes from patient to patient. In people, identification of the SLN is important in the diagnosis of lymph node metastasis, early identification of patients requiring additional therapeutic options to manage metastatic disease (such as lymph node dissection and adjuvant chemotherapy or radiation therapy), and establishing a prognosis. Sentinel lymph nodes can be identified using a number of techniques, including contrast-enhanced ultrasonography, lymphoscintigraphy, pertitumoral injection of blue dye, and intraoperative cytology or histopathology. The most commonly used SLN mapping techniques involve radiation sources and hence their use is limited in most veterinary practices. Recently, at the 2014 European College of Veterinary Surgeons meeting, a SLN mapping protocol was presented which did not involve the use of radionucleides: a lipid-based iodonated contrast agent was injected peritumorally 24hrs prior to surgery and at surgery the animal was imaged with either radiographs or CT scan to identify the SLN and then this lymph node was identified intraoperatively using a peritumoral injection of methylene blue.

While SLN mapping is not frequently done in veterinary oncology, identification of clinically applicable protocols which do not involve radiation sources may allow SLN mapping to become more routinely performed. Sentinel lymph node mapping would result in the early identification of lymph node status in animals at risk of nodal metastasis and hence the need for additional therapies and hopefully a better prognosis.

Submitted by:

Dr Julius Liptak BVSc, MVetClinStud, FACVSc, DACVS, DECVS
ACVS Founding Fellow in Surgical Oncology

References

  1. Williams LE, Packer RA: Association between lymph node size and metastasis in dogs with oral malignant melanoma: 100 cases (1987-2001). J Am Vet Med Assoc 222:1234-1239, 2003.

http://www.ncbi.nlm.nih.gov/pubmed/12725311

  1. Herring ES, Smith MM, Robertson JL: Lymph node staging of oral and maxillofacial neoplasms in 31 dogs and cats. J Vet Dent 19:122-126, 2002.

http://www.ncbi.nlm.nih.gov/pubmed/12382529

  1. Worley DR: Incorporation of sentinel lymph node mapping in dogs with mast cell tumours: 20 consecutive procedures. Vet Comp Oncol 12:215-226, 2014.

http://www.ncbi.nlm.nih.gov/pubmed/22958227

 

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