Patients with cancer of the upper aerodigestive tract (UADT) commonly present to their primary caregivers with a mass in the neck. It is important that an appropriate evaluation be undertaken to include a search for the primary tumor from which the cervical metastasis developed. It is the inability to find the source that has led to the concept of the unknown primary. However, the meaning of unknown primary has a great deal to do with the extent of the treating physician’s ability to search for this often elusive lesion. The staging of the tumor is TX when complete evaluation has not been accomplished. This is changed to T0 if a complete evaluation has not revealed the primary tumor.1 Frequently, surgical excision of a neck mass is carried out to secure a diagnosis after a course or two of antibiotics has failed to cause resolution without consideration of a neoplastic cause for the mass. Several deleterious effects can arise from this course of treatment if the disease process proves to be malignant. Violation of the fascial planes of the deep neck may give a decreased rate of control in the neck when compared to formal neck dissection, especially if radiotherapy is not employed. Perhaps more distressing is the potential for the primary lesion to go undiagnosed until local symptoms prompt further investigation. It was this very situation that prompted warnings from Martin as early as 1961 when he wrote, “excisional or incisional lymph node biopsy should be used only as a last resort and then preferably by the surgeon who accepts responsibility for the treatment himself if the diagnosis eventually proves to be cancer.”²

The pivotal question that lies at the heart of this subject is: How should the head and neck surgeon approach a patient with a neck mass? This process begins with establishing a diagnosis. The evaluation includes a physical examination, a careful history, radiologic studies, histologic studies, and often examination under anesthesia.

A thorough history and physical examination includes specific questioning regarding exposure to potentially carcinogenic agents such as ethanol and tobacco products. A complete exam is carried out to visualize all visible surfaces of the UADT possible during an office examination. This exploration includes an exam with a flexible fiberoptic nasopharyngoscope to evaluate otherwise difficult to visualize areas such as the fossae of Rosen-mueller and the pyriform sinuses. A modified Valsalva maneuver may be performed with the fiberoptic laryngoscope in place to maximally expose the hypopharynx.

In most patients in whom the cervical mass is suspected to be malignant, the primary site will be apparent on physical exam in the office setting. When the primary is not visible, additional effort is necessarily spent to search for the source of the neck metastasis. Identification of the primary site at the time treatment has begun has been shown to improve ultimate rates of disease control.³ Several tools are available to help with this search.

Histologic evaluation of the neck mass is best first approached with fine needle aspiration biopsy (FNAB). This technique has been shown to be both sensitive and specific for detecting many of the common histologic entities responsible for head and neck neoplasms.⁴ Accuracy approaching 100% has been described in diagnosing squamous cell carcinoma (SCC).⁴ This technique is easily carried out in the office and for this reason the histology of the cervical disease is usually known by the time the patient is evaluated under anesthesia. It is our practice to attempt histologic diagnosis in patients with a neck mass on the day of their first presentation. In most cases involving neoplasm, SCC will be the histologic class of cancer. There are other entities that can present as masses in the neck. These include tumors of thyroid or salivary gland origin, lymphoma, benign masses, and rare tumors such as sarcoma. If FNAB does not suggest carcinoma, open biopsy may be required to make a diagnosis. The remainder of this discussion focuses on SCC presumed to be metastatic to the neck.

A new dimension was added to this diagnostic scheme during the 1970s with the advent of computed tomographic (CT) scanning. This modality has continued to evolve with advancements in computer software and now is capable of providing the clinician with images with quite good resolution. This three-dimensional imaging technique, as well as the techniques of magnetic resonance imaging (MRI) and positron emission tomography (PET) scanning, extends the evaluation beyond that accomplished through physical inspection of mucosal surfaces.^{5, 6} As early as 1983, Muraki et al.⁷ were convinced that CT evaluation “should be used as part of the routine evaluation of patients with this clinical problem (unknown primary).” This group was able to find a primary site in four cases among 17 patients who had been previously evaluated with a negative endoscopic examination under anesthesia. We routinely obtain a CT for all patients with a neck mass thought to be neoplastic in origin. The information gained from contrast-enhanced CT scan from skull base to clavicles often provides crucial information beyond that gained by physical examination, especially for patients with short or bulky necks with difficult physical examinations. Continuous refinement of additional imaging techniques has given rise to new modalities such as MRI and PET scanning that hold future promise in helping to find an unknown primary. Great effort is now under way to explore physiochemically based imaging that can differentiate normal and malignant tissue.

In contrast to CT and MRI, PET scanning capitalizes on the different physiochemical properties of tumor and nontumor cells.8 Imaging is possible because tumor cells have been shown to have increased glycolysis (compared with normal cells) as monitored by PET using¹⁸F-labeled 2-deoxy-D-glucose. Work done by Braams et al. has shown this modality to have approximately 30% sensitivity for detecting an unknown primary as we have defined above.⁸ It is still difficult to recommend PET scanning as the standard of care in the search for an unknown primary because of its low sensitivity.

MRI scanning has allowed greater resolution for evaluating soft tissue structures than does CT. As a result, MRI is most useful when there is question of whether a soft tissue structure is fluid trapped in a paranasal sinus or a solid anatomically abnormal tissue mass as often presents a dilemma when evaluating anomalies of the paranasal sinuses. Additionally, resolution afforded by MRI is unsurpassed when evaluating intracranial structures for metastatic involvement because MRI is able to show subtle differences between similar soft tissues that are not discernible with CT.

Molecular genetics has received attention as a potential tool in the evaluation of patients with a cervical metastasis. This approach has found greatest application through the association between Epstein-Barr virus (EBV) and nasopharyngeal carcinoma. Macdonald et al.⁹

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