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Sentinel Lymph Node Biopsy for Squamous Cell Carcinoma


In the head and neck, squamous cell carcinoma (SCC) encompasses two distinct clinical entities: aerodigestive tract SCC (commonly referred to as head and neck SCC; HNSCC) and cutaneous SCC (cSCC). It is a malignant tumor of keratinizing epidermal cells. For both HNSCC and cSCC, the most common route of metastasis is lymphatic. However, both the investigation and the treatment of a patient with a clinically N0 nodal basin remain controversial. Particularly in oral cavity SCC, up to 30% of patients have subclinical (not found on examination or imaging) metastases in the neck, and knowledge of lymph node disease alters surgical and postoperative management.

The sentinel lymph node

The sentinel lymph node (SLN) is the first lymph node to drain a metastatic tumor cell that drains via the lymphatic route. The concept of the SLN is based on the orderly progression of tumor cells within the lymphatic system. Mapping of the lymph flow from the tumor site to the regional lymphatic drainage area can be used to identify the primary draining lymph node (ie, SLN). If the SLN can be identified and examined for the presence of tumor metastases, an elective lymph node dissection for staging may not need to be performed.

The concept of the SLN originated in 1977 when Cabanas described mapping of the first lymph node–draining penile carcinoma. In 1977, Robinson et al described the use of cutaneous lymphoscintigraphy in the nodal basin for truncal melanomas using colloidal gold scanning. The development of lymphatic mapping at the end of the 1980s was a breakthrough in making the sentinel node concept applicable to various types of malignancies, particularly breast cancer and melanoma. In 1993, Alex et al introduced the use of technetium-99m sulfur colloid, a radioactive tracer, which is injected intradermally around a primary melanoma site, followed by an imaging study and subsequent intraoperative use of a gamma probe to localize the sentinel node.
This technique is now commonly practiced for early-stage melanoma without clinically evident nodal metastasis. Alex and Krag performed the first successful SLN biopsy (SNLB) of the head and neck on a patient with a supraglottic carcinoma.

Relevance of SLNB in SCC

Approximately 3.3 million patients are diagnosed with 5.4 million cases of keratinocyte skin cancer (cSCC or basal cell carcinoma) in the United States each year. Approximately 80% of ultraviolet light–induced SCCs develop on the arms, head, or neck. The frequency of cSCC, as with all nonmelanoma skin cancers, is increasing. Recent projections suggest 300,000-400,000 new cases of cSCC per year.

cSCC is the second leading cause of skin cancer death after melanoma, and it is the second most common type of nonmelanoma skin cancer after basal cell carcinoma. Most cSCCs occur on the sun-exposed areas of the head and the neck. Nodal metastasis is relatively uncommon, only occurring approximately 3% of the time, and it is even less likely in early-stage disease (T1-T2).
While it is uncommon, patients with aggressive disease have a high risk of development of nodal metastasis that may be subclinical at initial presentation.

By 2017 estimates (American Cancer Society Facts and Figures),
approximately 70,000 cases of HNSCC are diagnosed in the United States each year. SCC can occur in any mucosal area of the head and neck, including the nasal cavity and sinuses, nasopharynx, oral cavity (including lower lip), oropharynx, larynx, and hypopharynx. Smoking and alcohol use are historically the primary risk factors for HNSCC, but the incidence of human papillomavirus (HPV)–related cancers of the oropharynx is rising rapidly. The latter rarely present without nodal disease, so SLNB is unlikely to have a role in the management of HPV-related tumors of the oropharynx. SLNB has primarily been investigated in lesions of the oral cavity, given the historically high rates of nodal metastasis noted above and the accessibility of these tumors for radiotracer injection. It can have a significant impact on the need for lymph node dissection.

Positron-emission tomography (PET-CT), contrasted CT, and MRI are commonly used to classify tumors and nodal or distant metastases of SCC. Definitive staging of lymph node disease can only be achieved by performing a staging lymph node dissection. For mucosal disease in its early stages (T1-T3, N0), clinicians have to balance the benefit of performing an elective (prophylactic) lymph node dissection against the associated morbidity. For cSCC, elective neck dissection is uncommon.

For more information, see Head and Neck Cancer and Head and Neck Squamous Cell Carcinoma.


Any of the following may cause SCC:

Exposure to sunlight

Chemical carcinogens, such as arsenic and hydrocarbons


Ionizing radiation

Cigarette smoke

Chronic irritation or ulceration


In addition, immunocompromised patients have a much higher risk of developing SCC. Two genes, PATCHED and TP53, have been identified that usually prevent cancers but are inactivated in patients with SCC; TP53 is mutated in more than 90% of patients with SCC.

Clinical manifestations

cSCCs typically manifest on the head, neck, or arms. They usually have elevated and rolled edges with central ulceration. Well-differentiated SCCs are likely to manifest as firm erythematous nodules of varying sizes, sometimes with an area of central hyperkeratosis. The tumor is usually firm, although tumors in more advanced cases can be soft and friable. Erosion and ulceration are more common with SCCs. Poorly differentiated SCCs are more apt to manifest as faintly erythematous nodules or plaques that are not well defined; ulceration is also common.

See the image below.

Large, sun-induced squamous cell carcinoma (SCC) o

Large, sun-induced squamous cell carcinoma (SCC) on the forehead/temple. Image courtesy of Glenn Goldman, MD.

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HNSCC typically manifests as an irregular, at times ulcerated, friable mass of the oral, oropharyngeal, laryngeal, hypopharyngeal, nasopharyngeal, or sinonasal mucosa. Lesions appearing in the oral cavity are subclassified according to anatomic location; the lower lip can exhibit HNSCC on the mucosal surface or cSCC on the skin surface. Oral cavity HNSCC is most amenable to SLNB because of the generally easy accessibility of the primary lesions.

Successful SLNB

Defining a successful SLNB accurately is critical. Although some studies have examined the impact of an individual surgeon’s experience on the SLN identification rate, SLN identification is clearly not an appropriate endpoint; many studies have documented excellent SLN identification rates with unacceptably high false-negative rates, typically defined as a negative SLNB when there is either a metastatic lymph node at the time of surgery or recurrence in the nodal basin where the SLN was identified.
The more important issue is the experience required to achieve an acceptably low false-negative rate. Such rates are typically identified through prospective studies in which the neck is dissected after an SLNB to provide a point of comparison. In cases in which the pathology results from the scintigram are unclear or are negative, a formal elective neck dissection should be considered for staging purposes.

This procedure is multidisciplinary. As such, surgeons must ensure that experienced nuclear medicine specialists, radiologists, and pathologists are involved. The learning curve for individual surgeons is undoubtedly associated with the experience levels of specialists within the multidisciplinary team. The implications of the SLN procedure must be effectively communicated to radiation oncologists and medical oncologists. The coordination of effort among the various specialists in each discipline is an essential component of the learning process.

The role of the SLNB in the management of SCC of the head and the neck will evolve as more centers actively perform the technique.

Patient education

For patient education information, see the Cancer and Tumors Center, as well as Skin Cancer, Skin Biopsy, and Cancer of the Mouth and Throat.

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