Chapter 37 Unknown Head and Neck Primary Site
In a small percentage of patients with squamous cell carcinoma metastatic to the cervical lymph nodes, the primary lesion cannot be found, even after an extensive evaluation. Patients with metastatic adenopathy in the upper neck have a good prognosis when treated aggressively compared with patients with metastatic lymph nodes in the level IV nodes or supraclavicular fossa.1 The latter group is more likely to have a primary lesion located below the clavicles, and the probability of cure is remote. Most patients have either squamous cell carcinoma or poorly differentiated carcinoma. Patients with adenocarcinoma almost always have a primary lesion below the clavicles, although if the nodes are located in the upper neck, one must exclude a salivary gland, thyroid, or parathyroid primary tumor.
This chapter addresses the management of patients presenting with squamous cell or poorly differentiated carcinoma in the upper or middle neck. Squamous cell carcinoma in a parotid area lymph node is almost always metastatic from a cutaneous primary site, and this is not addressed in this chapter.2
Diagnostic Evaluation
Patients should be evaluated with a thorough physical examination including careful evaluation of the head and neck by multiple examiners. A needle biopsy of the lymph node should be performed; fine-needle aspiration is preferred to a biopsy because it is less traumatic, and there is a lower likelihood of seeding tumor cells along the needle track.3–7 Evaluation of the neck node biopsy specimen for Epstein-Barr virus DNA, via polymerase chain reaction, may be useful in detecting a nasopharyngeal primary tumor in geographic areas where this malignancy is prevalent.8 Similarly, evaluation of the biopsy specimen for high-risk human papillomavirus may be useful for detecting an oropharyngeal carcinoma.9 Most occult primary cancers that are detected in the United States are in the oropharynx, however, so, depending on the situation, testing the biopsy specimen for high-risk human papillomavirus may be unlikely to provide additional useful information.10
After chest radiography, computed tomography (CT) or magnetic resonance imaging (MRI) of the head and neck is obtained to detect an unknown primary lesion arising from the mucosa of the head and neck. We use CT initially and follow with MRI only in cases with equivocal findings in which MRI might yield additional useful information. A complete blood count is obtained to evaluate marrow reserve in patients who may be candidates for adjuvant chemotherapy. A chest CT scan should be considered for patents with N3 neck disease and patients with N2B to N2C disease and bulky adenopathy in the low neck to assess the lungs for pulmonary metastases.11 The recommended diagnostic evaluation12 is summarized in Table 37-1.
| General |
From Mendenhall WM, Parsons JT, Mancuso AA, et al: Head and neck: management of the neck. In Perez CA, Brady LW, editors: Principles and practice of radiation oncology, ed 3, Philadelphia, 1998, Lippincott, pp 1135-1156.
Preliminary evidence suggested that 18F-fluorodeoxyglucose single photon emission computed tomography (18F-FDG-SPECT) or 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) scans may identify primary lesions that would not otherwise be identifiable.13,14 Theoretically, tumor cells have a higher metabolic rate than normal tissues and take up more FDG so that they appear “hot” on a PET or SPECT scan. If 18F-FDG-SPECT or 18F-FDG-PET scan is obtained as part of the work-up, it should be performed before panendoscopy so that any suspicious areas of increased uptake can be biopsied. Limited data pertaining to the usefulness of 18F-FDG-SPECT and 18F-FDG-PET scans suggest these procedures may identify the primary site in a relatively small subset of patients.15–17 18F-FDG-SPECT scan correctly identified the occult primary site in only 1 of 26 patients (4%) at our institution10 (Table 37-2). Similarly, 18F-FDG-PET detected a primary site in none of 21 patients at the University of Florida10 (Table 37-3). At the present time, 18F-FDG-PET scans are not routinely obtained at our institution as part of the diagnostic evaluation of these patients.
TABLE 37-2 Detection of the Primary Site on 18F-Fluorodeoxyglucose Single-Photon Emission Computed Tomography (18FDG-SPECT)
| Patient Group | 18FDG-SPECT Negative* | 18FDG-SPECT Positive* |
|---|---|---|
| PE− and/or Radiol− | No data | 1/5 |
| PE+ and/or Radiol+ | 2/6 | 6/15 (40.0%) |
| Total | 2/6 | 7/20 (35.0%) |
PE, physical examination; Radiol, radiologic examination (CT and/or MRI); −, negative; +, suspicious, but not definitely positive.
* Number of primaries detected/number of patients.
From Cianchetti M, Mancuso AA, Amdur R, et al: Diagnostic evaluation of squamous cell carcinoma metastatic to cervical lymph nodes from an unknown head and neck primary site, Laryngoscope 119:2348-2354, 2009.
TABLE 37-3 Detection of the Primary Site by 18F-Fluorodeoxyglucose Positron Emission Tomography (18FDG-PET) or 18F-Fluorodeoxyglucose Positron Emission Tomography and Computed Tomography (18FDG-PET/CT)
| Patient Group | 18FDG-PET Negative* | 18FDG-PET Positive* |
|---|---|---|
| PE− and/or Radiol− | 3/4 | No data |
| PE+ and/or Radiol+ | 8/12 | 3/5 |
| Total | 11/16 (68.8%) | 3/5 (60%) |
PE, physical examination; Radiol, radiologic examination (CT and/or MRI); −, negative; +, suspicious, but not definitely positive.
* Number of primaries detected/number of patients.
From Cianchetti M, Mancuso AA, Amdur R, et al: Diagnostic evaluation of squamous cell carcinoma metastatic to cervical lymph nodes from an unknown head and neck primary site, Laryngoscope 119:2348-2354, 2009.
Direct laryngoscopy with fiberoptic endoscopic visualization under general anesthesia is performed with directed biopsies of the nasopharynx, tonsils, base of tongue, and piriform sinuses and of any abnormalities noted on CT or MRI or suspicious mucosal lesions observed during endoscopy. The primary tumor site is discovered at direct laryngoscopy in a subset of patients. The likelihood of discovering the primary site is related to whether or not a suspected (but not definite) primary site is discovered on physical examination or radiographic evaluation10 (Table 37-4). Most suspected primary sites are detected by pretreatment radiographic workup as opposed to physical examination.
TABLE 37-4 Detection of a Primary Site versus Patient Group
| Patient Group | No. Patients with PathologicallyProven Site in Tonsillar Fossa/No. Patients Having Tonsillectomy |
|---|---|
| PE− and/or Radiol− | 21/72 (29.2%) |
| PE− and/or Radiol+ | 51/82 (62.2%) |
| PE+ and/or Radiol− | 15/25 (60.0%) |
| PE+ and/or Radiol+ | 39/57 (68.4%) |
| TOTAL | 126/236 (53.4%) |
PE, physical examination; Radiol, radiologic examination (CT and/or MRI); −, negative; +, suspicious, but not definitely positive.
From Cianchetti M, Mancuso AA, Amdur R, et al: Diagnostic evaluation of squamous cell carcinoma metastatic to cervical lymph nodes from an unknown head and neck primary site, Laryngoscope 119:2348-2354, 2009.
An ipsilateral10,15,18 tonsillectomy should be performed in patients who have not had a prior tonsillectomy and who have adequate lymphoid tissue remaining in the tonsillar fossa. Although some authors recommend a bilateral tonsillectomy,19 the likelihood of finding the primary site in the contralateral tonsil for patients with ipsilateral neck nodes is probably quite low. Lapeyre and colleagues18 reported 87 patients who were evaluated during the period 1969-1992 and underwent a unilateral tonsillectomy; 26% of patients were found to have a tonsillar cancer. At the University of Florida, 79 of 236 patients underwent a tonsillectomy at the time of direct laryngoscopy; the primary site was detected in the tonsil in 35 patients (44%).10 The likelihood of detecting the primary site was related to whether there were suspicious findings on physical examination or radiographic evaluation10 (Table 37-5).
TABLE 37-5 Detection of the Primary Site on Tonsillectomy
| Patient Group | No. Patients with PathologicallyProven Site in Tonsillar Fossa/No. Patients Having Tonsillectomy |
|---|---|
| PE− and/or Radiol− | 9/22 (41.1%) |
| PE+ and/or Radiol+ | 26/57 (45.6%) |
| Total | 35/79 (44.3%) |
PE, physical examination; Radiol, radiologic examination (CT and/or MRI); −, negative; +, suspicious, but not definitely positive.
From Cianchetti M, Mancuso AA, Amdur R, et al: Diagnostic evaluation of squamous cell carcinoma metastatic to cervical lymph nodes from an unknown head and neck primary site, Laryngoscope 119:2348-2354, 2009.
Primary head and neck cancers were found in 126 of 236 patients (53%) in the University of Florida series.10
