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Ophthalmic Pearls: Ocular Oncology
Sentinel Lymph Node Biopsy for Conjunctival and Eyelid Cancers
By Aaron Savar, MD, and Bita Esmaeli, MD
Edited by Sharon Fekrat, MD, and Ingrid U. Scott, MD, MPH
 
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Sentinel lymph node biopsy (SLNB) is a technique for identifying subclinical, microscopic nodal metastasis from a malignant neoplasm. This technique involves removing and histopathologically assessing the first draining—or “sentinel”—node(s) in proximity of a tumor. SLNB is based on the principle that some tumors will spread through the lymphatics before they spread to distant sites hematogenously. If the sentinel node can be proven to be tumor free, the risk of distant metastases is lower. In the absence of SLNB, patients can be observed for clinical and radiographic evidence of nodal metastasis, but nodal disease may be present for a long time before it becomes apparent through these methods.

Previously, elective lymphadenectomy was used for certain tumors that had a high risk for lymphatic spread. Since this was a potentially morbid procedure, an alternative was sought to provide a less invasive and more selective procedure to biopsy the few lymph nodes at the highest risk for harboring microscopic metastases. SLNB offers such an alternative. It has been evaluated in large multicenter trials1 and has become a standard part of the management algorithm for cutaneous melanoma and breast cancer. For cutaneous melanoma, the lymph node status is the most important piece of prognostic information.1 SLNB has also proven safe and feasible for tumors of the eyelid and conjunctiva that have the potential risk for lymph node metastasis. SLNB has identified microscopically positive regional lymph nodes that were not detected on clinical and radiographic evaluation in patients with periocular melanomas and carcinomas. The histological status of the sentinel lymph node for these tumors of the eyelid and conjunctiva can provide useful prognostic information. And SLNB can provide an opportunity for earlier intervention in patients with eyelid or conjunctival tumors who harbor subclinical lymph-node metastasis.

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Indications

As with any procedure, appropriate patient selection is crucial. SLNB has been used in the periocular region for eyelid and conjunctival melanoma,2,3 sebaceous carcinoma4 and Merkel cell carcinoma.5 It has also been used for squamous cell carcinoma in the head and neck region. At this point, the most extensive experience in the periocular region is with melanoma.3

Among patients with melanoma, the histopathological findings from a biopsy of the tumor can help determine if the patient will benefit from SLNB. The thickness of the tumor is most important. Patients with very thin tumors, such as those with in-situ disease alone, typically do not have nodal metastasis. Therefore, SLNB is of little utility for these patients. Similarly, patients with extremely large tumors and patients with distant metastases at the time of presentation need not undergo SLNB. Patients with tumors of intermediate thickness are most likely to benefit. For conjunctival melanoma, specifically, tumor thickness of greater than 2 mm may give the highest yield of positivity for SLNB. A finding of histopathological ulceration may also indicate the presence of a high-risk tumor with a higher likelihood of nodal and systemic metastases.3

SLNB is only appropriate for patients who have no clinical evidence of nodal disease based on examination and radiographic imaging. Usually, CT or lymph-node ultrasonography can be used to identify suspicious nodes. If palpable nodes or suspicious nodes are identified during imaging, they can be biopsied by fine-needle aspiration, and SLNB can be avoided.

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Technique

SLNB is usually performed at the time of tumor excision, though it can be done at a later time. A tracer molecule is injected into the tissue immediately surrounding the tumor. Usually, this is technetium-labeled sulfur colloid. The tracer travels through the lymphatics to the lymph nodes. After about an hour, the tracer molecule collects in the sentinel node, although faster travel time in the head and neck region may be observed. A handheld gamma probe is then used to identify where the sulfur colloid has accumulated. An incision is made over the area, and the node is identified. The node is removed and confirmed to contain the radiolabeled tracer. In some cases, the tracer will accumulate in more than one node so that multiple nodes will need to be removed until the nodal basin is no longer “hot.”

Before a planned SLNB, preoperative lymphoscintigraphy is usually done to determine the expected site of the sentinel lymph node.3 This can be important in the head and neck region where there are multiple nodal basins. Lymphoscintigraphy can also identify patients in whom drainage of the tracer is inadequate because of multiple previous surgeries and the presence of significant scar tissue. In those patients, SLNB may not be possible. As with SLNB, lymphoscintigraphy involves injection of a tracer. Serial radiographic images are obtained to follow the drainage of the tracer. More recently, single photon emission computed tomography/computed tomography (SPECT/CT) is used to provide finer detail (Figs. 1 and 2), but conventional lymphoscintigraphy is also quite adequate for performing SLNB and may be less expensive.

The nodal basins that drain the periocular region include the preauricular, parotid, submandibular and cervical regions. Because of the risk of facial nerve injury in the parotid region, as well as the many sensitive structures in the neck, it is important that SLNB be performed by a surgeon with experience operating in these regions. After SLNB, the node(s) are then cut serially in thin sections and evaluated histologically. Immunohistochemical markers can aid in this process.

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Use of the Results

The presence or absence of microscopic nodal metastasis identified by SLNB is important prognostic information and can help guide treatment. If the SLNB is positive for nodal metastasis, surgical resection of all nodes in the basin must be considered. In patients with high-risk findings in lymph nodes removed during complete lymph-node dissection or in patients who cannot undergo lymphadenectomy, radiation treatment may also be appropriate. The presence of nodal metastasis upstages the tumor. More accurate staging allows the physician to give the patient the most accurate prognostic information and offer additional treatments for nodal metastasis. If the SLNB is negative, observation is still important, as false negatives may occur in nearly 10 percent of patients.

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Controversy

There remain opponents of SLNB who feel that this procedure does not alter long-term survival. Indeed, proving an overall survival benefit, especially in the case of relatively rare tumors such as conjunctival melanoma or sebaceous carcinoma, is difficult. SLNB, however, is a safe procedure that provides useful prognostic information and can provide an opportunity for early detection and earlier intervention for patients who harbor subclinical, microscopic nodal metastases associated with high-risk conjunctival and eyelid cancers.
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1 Morton, D. L. et al. N Engl J Med 2006;355(13):1307–1317
2 Esmaeli, B. et al. Arch Ophthalmol 2003;121(12):1779–1783.
3 Savar, A. et al. Ophthalmology 2009;116(11):2217–2223.
4 Ho, V. H. et al. Arch Otolaryngol Head Neck Surg 2007;133(8):820–826.
5 Esmaeli, B. et al. Arch Ophthalmol 2002;120(5):646–648.
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Dr. Savar is a fellow and Dr. Esmaeli is a professor of ophthalmology and director of the ophthalmic plastic and reconstructive surgery fellowship program in the section of ophthalmology in the department of head and neck surgery at the University of Texas M.D. Anderson Cancer Center, Houston.

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