• E Medini, A M Medini, C K Lee, M Gapany, and S H Levitt.
• Department of Radiation Oncology and Otolaryngology, University of Minnesota, and Veterans Administration Medical Center, Minneapolis 55417, USA.
• Am. J. Clin. Oncol. 1998 Apr 1; 21 (2): 121-5.

AbstractA patient is diagnosed with an unknown primary of the head and neck when metastatic disease is present in the cervical lymph node or nodes and no primary lesion is detected by thorough physical examination, directed biopsies of suspicious or most likely primary sites, and imaging studies. The optimal management of patients who have this syndrome is still unclear and controversial. We report our results and analysis of the management of 24 patients with this syndrome. From 1976 through 1992, 24 patients who had metastatic squamous cell carcinoma in the cervical lymph nodes were seen in our medical center. A thorough search did not detect a primary lesion in any of them. Patients underwent radical neck dissection of the involved neck; 23 had unilateral and I had bilateral neck disease. Postoperative radiotherapy was delivered to both sides of the neck and to the potential primary mucosal and submucosal sites. The relation between clinical N stage, histologic findings of numerous involved lymph nodes, presence of extracapsular tumor extension, and survival were statistically analyzed. The Kaplan-Meier method was used for the survival analysis. The p values of log-rank test for the comparison of the two groups 1) N1 and N2 versus N3, and 2) presence of extracapsular tumor extension versus its absence are less than 0.005, with extracapsular tumor extension versus nonextracapsular tumor extension slightly smaller. The 5- and 10-year disease-free survival rate for the entire group was 54.2% (70.5% for N1 and N2, and 14.2% for N3). Three patients had locoregional failure, two in the primary sites, one in the nasopharynx, and the other in the oropharynx (the latter also had recurrent disease in the undissected neck). In 8 patients, distant metastases developed 7 to 38 months after radiotherapy. All 11 patients (45.8%) who had recurrent disease had advanced clinical N stage, microscopic findings of numerous involved lymph nodes, and prominent extracapsular tumor extension to the surrounding soft tissue and blood vessels. The high incidence of distant metastases shortly after treatment suggests a hematogenous spread before treatment in patients who had extensive nodal and extranodal disease. Our long-term disease-free survival beyond ten years seems to indicate combined treatment modalities, including radical neck dissection with postoperative radiotherapy of the neck, and the potential primary site in patients with N2 and N3 disease (our N1 group is too small for analysis). Further improvement of cure rate can be expected in the future with early detection and treatment.

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