Background: Up to 10% of all cervical lymph node metastases present without a known primary site. Between 70 and 80% of the found primary tumors are located in the head and neck region, because cervical lymph nodes represent the lymph drainage of the head and neck. Patients and Methods: We demonstrate the clinic, diagnostic management and therapy of carcinoma of unknown primary (CUP) in this retrospective study of 75 patients who primarily presented cervical metastases with unknown primary tumor at the Otorhinolaryngological Department of the University of Leipzig, Germany. Results: A primary tumor was found in 44% of the patients, and 76% of the primary tumors were localized in the head and neck region. The overall 5-year survival rate was 13.3%. The 34 patients with pretherapeutically detected primary tumors showed a tendency towards better survival, with a 5-year survival rate of 21% compared to 10% in patients with undetected primary. Conclusions: Following a thorough physical examination, radiologic imaging, i.e., computed tomography and/or magnetic resonance imaging, of the head and neck region as well a chest X ray, panendoscopy with biopsy of the most probable tumor sites, and diagnostic tonsillectomy should be performed. Further diagnostic procedures as gastroenterologic, urogenital and gynecological examinations should be performed, depending on histology and location of the node and under consideration of cost-benefit analysis. Curative treatment should at least include ipsilateral neck dissection and adjuvant irradiation of the complete cervical lymph drainage. In the literature, radiation of the laryngopharyngeal mucosa is still discussed controversially: some authors recommend the irradation of the pharyngeal mucosa extending from the nasopharynx to the upper esophagus, whereas others regard the resulting side effects as too high compared to the expected benefit.

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