Many patients with squamous cell carcinoma of the head and neck (SCCHN) present with metastasis to the cervical lymph nodes. Of these, patients with metastatic carcinoma in the cervical lymph nodes, generally excluding the supraclavicular region without an identifiable primary cancer, are defined as patients who harbor a squamous cell carcinoma of the head and neck of unknown primary origin (SCCHNUP). Patients with isolated supraclavicular metastatic carcinoma usually have a primary source from the skin or infraclavicular areas (breast, lung, esophagus, and ovary), entities that are not described here. Retrospective studies suggest that SCCHNUP is a relatively rare disease, affecting between 1% and 3% of new cases of SCCHN. These patients provide a particularly challenging clinical problem to the head and neck surgeon, and thorough physical examination and evaluation are necessary to identify the site of the primary tumor.

Patients who present with SCCHNUP can be treated either with surgery, followed by adjuvant treatment, or with primary nonsurgical therapy. However, the identification of a primary site is enormously helpful in better defining the targeted areas for radiation therapy and provide more accurate staging and prognostic information for these patients. This chapter delineates the evaluation and management of patients with squamous cell carcinoma (SCC) metastatic to the neck from an unknown primary and provides new insights into the application of transoral robotic technologies for the treatment and diagnosis of patients with SCCHN of unknown primary of the head and neck.

A thorough examination of the head and neck is mandatory in all patients who present with occult lymph node metastasis. The physical examination should include palpation of the neck to determine whether the lymph nodes are fixed to underlying structures or if it is freely mobile. Palpation should also include examination of the thyroid and tracheal regions, as well as the nodal lymphatic basins of levels I through VI. Many cases of SCCHNUP are initially diagnosed by excision of a mass in the neck, which is ultimately confirmed to be SCCHN. In these patients, the physical examination can be challenging, since postsurgical scarring and induration can impact palpation and examination of the residual cervical lymph nodes. An examination of the oral cavity and oropharynx should be performed, ideally with indirect mirror laryngoscopy to examine the base of tongue (BOT) and tonsil fossae. Bimanual palpation of the BOT and tonsil fossae is also required. The physical examination should also include a careful evaluation of the cutaneous structures of the head and neck, since previously treated primary malignancies of the skin can present with isolated metastatic SCC. It should be noted that a prior history of skin cancer or skin excisions should also be included, and physical stigmata of prior skin resections, such as scars or liquid nitrogen-induced cryoablation, should also be documented.

Once this portion of the physical examination is concluded, these patients should all be examined with a flexible fiberoptic nasopharyngolaryngoscopy. This provides a better view of the BOT, tonsil fossae, glottis, hypopharynx, and supraglottic structures. It is important to evaluate the mobility of the vocal fold and look for areas of salivary pooling or submucosal masses in the postcricoid area. The nasopharynx should also be examined to exclude the possibility of a nasopharyngeal carcinoma.

There are no contraindications to surgery based on anatomic factors. However, patients who have significant medical comorbidities that may preclude the administration of general anesthesia may not be candidates for surgery. Those patients who have a demonstrable primary cancer that appears deeply invasive on preoperative imaging do not require robotic surgery to identify the primary cancer.

Patients in whom the unknown primary cancer remains occult despite having a tonsillectomy and directed biopsies of the BOT may benefit from a robotic BOT resection to identify the primary cancer. It should be noted that these patients typically have HPV-related cancers, and the surgeon should have a high index of suspicion for a primary cancer in the oropharynx. The overall goal of the robotic BOT resection procedure is to use an en bloc resection approach under high magnification to remove all lingual tonsil tissue from the inferior portion of Waldeyer ring in order to identify the primary cancer.