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Metastatic Squamous Neck Cancer With Occult Primary Treatment (PDQ®)

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Untreated Metastatic Squamous Neck Cancer With Occult Primary

Patients with neck nodes from a presumed unknown primary tumor should be evaluated as follows:

  1. Surgical biopsy or excision to establish a histologic diagnosis, but only after an aerodigestive tract primary has been carefully ruled out as in the following procedures:
    • Direct nasopharyngoscopy, laryngoscopy, bronchoscopy, and esophagoscopy, with biopsy of any suspicious area.
      • If no suspicious lesions are found, random biopsies of the nasopharynx, base of tongue, tonsil, and pyriform sinus on the side of the lesion should be performed.
      • If the tonsil is not present, biopsy of the tonsillar fossa should be performed.
      • Sinus x-rays are probably indicated; if an abnormality is found, it should be biopsied as well.
  2. Selected other studies if indicated. In the detection of head and neck tumors and in the distinction of lymph nodes from blood vessels, magnetic resonance imaging offers an advantage over computed tomography scans and should be considered in the initial evaluation of the patient with metastatic squamous cell cancer in cervical lymph nodes.[1] Positron emission tomography may be helpful in determining the primary site.[2]

    Patients should be managed with either a full course of radiation therapy or adequate neck dissection, when possible. In cases of massive homolateral adenopathy that is fixed or bilateral nodes, radiation therapy should be administered first. The radiation fields should also include the nasopharynx, base of tongue, and pyriform sinuses. If radiation therapy is the primary mode of treatment and the neck mass persists upon completion of radiation therapy, cervical lymph node dissection should be performed. Patients with metastatic carcinoma in the supraclavicular region are best managed with a full course of radiation therapy followed by surgical dissection if palpable tumor persists. Careful continued follow-up of these patients is of utmost importance. Depending on the likely site of origin and histology, chemotherapy appropriate to the most treatable site may be indicated.

    Accumulating evidence has demonstrated a high incidence (>30%–40%) of hypothyroidism in patients who received external-beam radiation therapy to the entire thyroid gland or the pituitary gland. Thyroid function testing of patients should be considered prior to therapy and as part of post-treatment follow-up.[3,4]

Standard treatment options:

  1. Radical neck dissection.
  2. Radiation therapy.[5,6] Intensity-modulated radiation therapy may have less short- and long-term toxicity than conventional radiation therapy in terms of xerostomia, acute dysphagia, and skin fibrosis.[7,8]
  3. Combined surgery and radiation therapy.[9]

Treatment options under clinical evaluation:

  1. Chemotherapy followed by radiation therapy.[10]
  2. Simultaneous chemotherapy and hyperfractionated radiation therapy.[11]
  3. Clinical trials for advanced tumors should be considered.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with untreated metastatic squamous neck cancer with occult primary. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.


  1. Consensus conference. Magnetic resonance imaging. JAMA 259 (14): 2132-8, 1988. [PUBMED Abstract]
  2. Rege S, Maass A, Chaiken L, et al.: Use of positron emission tomography with fluorodeoxyglucose in patients with extracranial head and neck cancers. Cancer 73 (12): 3047-58, 1994. [PUBMED Abstract]
  3. Turner SL, Tiver KW, Boyages SC: Thyroid dysfunction following radiotherapy for head and neck cancer. Int J Radiat Oncol Biol Phys 31 (2): 279-83, 1995. [PUBMED Abstract]
  4. Constine LS: What else don't we know about the late effects of radiation in patients treated for head and neck cancer? Int J Radiat Oncol Biol Phys 31 (2): 427-9, 1995. [PUBMED Abstract]
  5. Carlson LS, Fletcher GH, Oswald MJ: Guidelines for radiotherapeutic techniques for cervical metastases from an unknown primary. Int J Radiat Oncol Biol Phys 12 (12): 2101-10, 1986. [PUBMED Abstract]
  6. Mack Y, Parsons JT, Mendenhall WM, et al.: Squamous cell carcinoma of the head and neck: management after excisional biopsy of a solitary metastatic neck node. Int J Radiat Oncol Biol Phys 25 (4): 619-22, 1993. [PUBMED Abstract]
  7. Madani I, Vakaet L, Bonte K, et al.: Intensity-modulated radiotherapy for cervical lymph node metastases from unknown primary cancer. Int J Radiat Oncol Biol Phys 71 (4): 1158-66, 2008. [PUBMED Abstract]
  8. Sher DJ, Balboni TA, Haddad RI, et al.: Efficacy and toxicity of chemoradiotherapy using intensity-modulated radiotherapy for unknown primary of head and neck. Int J Radiat Oncol Biol Phys 80 (5): 1405-11, 2011. [PUBMED Abstract]
  9. Maulard C, Housset M, Brunel P, et al.: Postoperative radiation therapy for cervical lymph node metastases from an occult squamous cell carcinoma. Laryngoscope 102 (8): 884-90, 1992. [PUBMED Abstract]
  10. Thyss A, Schneider M, Santini J, et al.: Induction chemotherapy with cis-platinum and 5-fluorouracil for squamous cell carcinoma of the head and neck. Br J Cancer 54 (5): 755-60, 1986. [PUBMED Abstract]
  11. Weissler MC, Melin S, Sailer SL, et al.: Simultaneous chemoradiation in the treatment of advanced head and neck cancer. Arch Otolaryngol Head Neck Surg 118 (8): 806-10, 1992. [PUBMED Abstract]
  • Updated: October 31, 2014