Lymph node staging for oral tumors

THE IMPORTANCE OF STAGING LYMPH NODES

Lymph node staging of a veterinary cancer patient refers to the evaluation of lymph nodes draining the primary tumor to determine whether cancer cells are present. Cancer cells from malignant oral tumors may travel in lymph vessels from the primary tumor to lymph nodes, where they develop into a new tumor, or further metastasize. Lymph node staging is important in determining the animal’s prognosis as well as the optimal treatment plan (1,2). A treatment plan that does not consider lymph node involvement may adversely affect patient outcome, potentially shortening the length of remission and survival.

Regional lymph nodes are those that filter lymph from a primary tumor; these are the lymph nodes at risk of metastasis. Regional lymph nodes include lymph nodes that directly drain the tumor, but also lymph nodes that receive lymph from the directly draining lymph nodes. For example, parts of the oral cavity drain directly to the mandibular lymph nodes, which are then drained by the medial retropharyngeal lymph nodes, and metastases can arise in both lymph centers. Clinical decisions regarding lymph node staging for oral cancers require an understanding of the anatomy of the regional lymph centers as well as the lymphatic drainage patterns of the oral cavity.

Anatomy of the lymph centers draining the oral cavity (3)

There are 3 lymph centers of the head: the parotid, the mandibular, and the retropharyngeal. The parotid lymph center is composed of a single lymph node located just caudal to the temporomandibular joint and is unlikely to be involved in the drainage of oral tumors as it does not drain the oral cavity. It does, however, drain the skin of the rostral half of the dorsal head, including the skin of the bridge of the nose, the bones and muscles of the head, and the temporomandibular joint. If an oral tumor invades these regions, the parotid lymph node should be staged.

The mandibular lymph center is composed of a cluster of 2–5 lymph nodes on each side of the head, located caudolaterally to the angular process of the mandible underneath the skin, the facial skin muscle, and the superficial fascia (Figure 1). Lymph drains between ipsilateral mandibular lymph nodes; cancer cells in one lymph node can therefore spread to others in the lymph center. For this reason, surgical resection of a mandibular lymph center should include all the lymph nodes on that side (Figure 2). Most of the lymph vessels leaving the mandibular lymph center drain to the retropharyngeal lymph nodes on the same side; however, some of the vessels drain to the retropharyngeal lymph nodes on the opposite side. This is one of the reasons that oral tumors can metastasize to lymph nodes on the opposite side of the head, and the reason that retropharyngeal lymph nodes on both the right and left side should be assessed, regardless of the location of the tumor.

FIGURE 1.

Three-dimensional renderings from a computed tomographic scan of the head and neck region of a dog with normal-sized lymph nodes. Two mandibular lymph nodes (blue) on both the right and left side are visible on a lateral oblique view (top) and a ventral oblique view (bottom). A single medial retropharyngeal lymph node (red) is present on both sides; the location of this lymph node deep to the mandibular salivary gland (green, only right side shown) prevents manual palpation unless the lymph node is severely enlarged.

FIGURE 2.

A pre-contrast computed tomographic view in the dorsal plane, using a soft tissue window, of a 9-year-old mixed breed dog showing a severely enlarged right mandibular lymph node (white arrow) with 2 normal-sized left mandibular lymph nodes (white arrowheads). The mandibular salivary glands (black arrows) are visible caudal to the mandibular lymph nodes. The dog was diagnosed with oral malignant melanoma and underwent surgical removal of the right mandibular lymph center at the time of primary tumor resection. However, not all the right mandibular lymph nodes were removed, and the animal developed metastatic disease 4.5 mo after the surgery.

The retropharyngeal lymph center includes the medial retropharyngeal lymph node, and in about one-third of dogs, a smaller lateral retropharyngeal lymph node located dorsal to the medial retropharyngeal lymph node. The medial retropharyngeal lymph node lies adjacent to the lateral wall of the pharynx and medial to the mandibular salivary gland (Figure 1). The lateral retropharyngeal lymph node does not drain the oral cavity but does receive lymph from the mandibular lymph nodes and therefore should be considered in staging if present. The lymph vessels from the lateral retropharyngeal lymph node drain to the medial retropharyngeal lymph node. The lymph vessels leaving the medial retropharyngeal lymph node may drain to the cervical lymph nodes, if present, then to the right or left tracheal duct, which drain to the thoracic duct or directly into the venous system.

Lymphatic drainage patterns of the oral cavity (3)

The upper and lower lips, including skin, muscles, and mucosa, drain to the mandibular lymph nodes. The left half of the upper lip may drain to the right mandibular lymph nodes, and vice versa. This drainage pattern is another reason that oral tumors can metastasize to lymph nodes on the contralateral side. The tip of the tongue drains to both the mandibular and medial retropharyngeal lymph nodes, whereas the body and base of the tongue drain only to the medial retropharyngeal lymph node. The floor of the oral cavity drains to both lymph centers, whereas the cheek, including skin, muscles and mucosa, drains to the mandibular lymph center. Most of the hard palate drains to the mandibular lymph center, except for the caudal one-third, which also drains to the medial retropharyngeal lymph node. The rostral soft palate drains to both lymph centers, whereas the caudal soft palate drains only to the medial retropharyngeal lymph node.

Because the mandibular lymph nodes drain to the medial retropharyngeal lymph node, both lymph centers must be considered when a tumor drains to the mandibular lymph center. Oral tumors in locations that drain only to the medial retropharyngeal lymph node, in theory, will not metastasize to the mandibular lymph nodes. However, malignant oral tumors are invasive, and microscopic extension of the tumor must be considered in drainage patterns. For example, a tumor of the tonsil, which drains only to the medial retropharyngeal lymph node, may invade the mucosal fold around the tonsil, which drains to the mandibular lymph nodes.

Clinical staging

In veterinary medicine, the most common methods used to stage the lymph nodes draining the oral cavity include manual palpation, cytologic examination of fine-needle aspirates, imaging, and pathologic examination of biopsy samples (1,4). Manual palpation may reveal a severely enlarged lymph node, raising the suspicion for metastasis, but is often not sufficient for clinical staging. In one study of dogs with oral melanoma, 38% of dogs with enlarged lymph nodes on palpation did not have nodal metastases, whereas 40% of dogs with normal-sized lymph nodes on palpation did have metastases (5). No computed tomographic characteristics are reported to reliably predict lymph node metastases, although lymph node diameter and volume may be useful (6–8) (Figure 3). Ultrasonography is useful in guiding needle sampling of the retropharyngeal lymph nodes, which are too deep to be palpable unless severely enlarged. However, poor agreement between cytology and pathology in the diagnosis of lymph node metastasis has been reported; in dogs with oral melanoma, lymph nodes identified as negative for metastasis on cytology were positive on pathology, and vice versa (9). Pathological examination is considered the gold standard for staging lymph nodes in animals with malignant oral tumors that metastasize to regional lymph nodes (1). Due to the risk of metastasis to contralateral lymph nodes, removal of bilateral mandibular and retropharyngeal lymph nodes is recommended (1), and a surgical technique using a single ventral midline incision has been described for this procedure in dogs (10).

FIGURE 3.

A contrast-enhanced computed tomographic view in the dorsal plane, using a soft tissue window, of a 17-year-old domestic shorthair cat diagnosed with oral squamous cell carcinoma. The mandibular and medial retropharyngeal lymph nodes (white arrows) are severely enlarged with a heterogenous to ring-enhancing pattern of contrast enhancement. The mandibular salivary glands are indicated by the black arrows. Squamous epithelial cells with features of malignancy were visible on fine needle aspirates from the lymph nodes. For this cat, severe enlargement of regional lymph nodes and cytological evidence of cancer cells in the lymph nodes were considered adequate to diagnose metastases to the lymph nodes.

In summary, lymph center anatomy and drainage patterns of the oral cavity guide the staging of regional lymph nodes in animals with oral cancer. The method(s) used for lymph node staging depend on the metastatic potential of the tumor type and the treatment goals of the client. Minimally invasive staging methods, including manual palpation, cytology, and imaging, may not provide a definitive diagnosis of lymph node metastasis, and surgical excision of all regional lymph nodes should be considered if lymph node status will affect the treatment plan.

Questions

1. A malignant oral tumor located on the right lower lip of a dog may metastasize to which of the following lymph nodes?

   1. Right mandibular lymph node

   2. Left mandibular lymph node

   3. Right medial retropharyngeal lymph node

   4. Left medial retropharyngeal lymph node

   5. All the above

   Answer: E

2. Which of the following statements is incorrect?

   1. Spread of cancer from one mandibular lymph node to another in the same lymph center is possible.

   2. The left mandibular lymph node may drain to the right medial retropharyngeal lymph node.

   3. Computed tomographic examination is a reliable method to diagnose metastatic disease in normal-sized lymph nodes of the head.

   4. Diagnosis of lymph node metastasis using cytologic examination of needle aspirates has been reported to have poor agreement with pathologic examination of lymph node tissue.

   Answer: C