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Squamous Cell Carcinoma Metastatic to Neck (Historical Perspective)

last modified on: Wed, 02/21/2024 - 15:59

See: Unknown Primary Cancer (Evaluation and Management)

Note this protocol, relevant over a decade ago, does not address lingual tonsillectomy, robotics, molecular testing of nodes and is therefore presented for historical perspective (5-21-2017)


  1. Definition
    1. The "unknown primary" refers to cancer identified in the neck suspected to represent metastasis from a primary site not readily determined. This discussion is limited to squamous cell carcinoma.
  2. Incidence
    1. The incidence of unknown primary cancers has diminished with the advent of advanced radiographic imaging (CT/MRI) and routine use of flexible fiberoptic endoscopic examination in the clinic. The patterns of presentation have similarly changed with expanded use of this improved technology.


  1. History
    1. Identify risk factors for malignancy:
      1. Tobacco use, alcohol use, age, associated symptoms
      2. Previous cancer or previous irradiation
    2. Identify duration of neck mass.
    3. Identify presence of other localizing head and neck symptoms.
  2. Physical Examination
    1. Examine all mucosal surfaces of the upper aerodigestive tract.
    2. Perform flexible fiberoptic nasopharyngoscopy and laryngoscopy.
    3. Examine skin surfaces (include scalp).
    4. Location of an isolated neck mass may predict the location of the primary site based on lymph drainage.
      1. Level I: oral cavity; skin
      2. Level II: oral cavity, oropharynx, supraglottic larynx, hypopharynx, or nasopharynx
      3. Level III: larynx, hypopharynx,
      4. Level IV: subglottic larynx, cervical esophagus, infraclavicular regions (lung, GI tract)
      5. Level V: nasopharynx
  3. Consider a Single Empiric Trial of Antibiotics
    1. The working diagnosis is cervical lymphadenitis.
    2. Take this approach only if history and physical exam strongly support infectious etiology.
    3. Persistence after single course of antibiotics warrants pathologic assessment (FNA).
  4. Blood Studies
    1. Provides little value in initial evaluation
    2. General evaluation includes
      1. General screen (electrolytes/LFTs/renal function)
      2. CBC and coagulation profile
  5. Fine Needle Aspiration Biopsy
    1. May be an initial step following history and physical or may defer to radiographic imaging.
    2. Radiographic imaging may help determine need for FNA and direct it anatomically.
  6. Radiographic Imaging
    1. Ultrasound may be helpful for selected masses.
      1. Ultrasound can be done in conjunction with FNA.
      2. Disadvantage: ultrasonography is a dynamic study, therefore, the permanent images provided are difficult to interpret for all but the radiologist performing the examination.
      3. Ultrasonography is not as comprehensive or definitive as CT or MRI.
    2. CT or MRI
      1. Perform with and without contrast.
      2. Request imaging: "skull base to clavicles ... with focus on ..." depending on site of lesion; either MRI or CT is usually sufficient for initial evaluation.
      3. MRI is better for salivary gland, soft tissue detail.
      4. CT is better for bone detail; also (currently) better for cervical adenopathy.
    3. Chest x-ray
  7. Pathological Considerations
    1. The FNA diagnosis of squamous cell carcinoma is generally uncomplicated.
    2. Open biopsy of a neck mass may be indicated to determine definitive histopathology. The dictum against open biopsy of squamous cell carcinoma has been modified.
      1. It remains good practice to avoid an open biopsy of a neck mass as an initial step in the evaluation.
      2. It is not clear that an open biopsy of a neck mass harboring squamous cell carcinoma compromises survival as long as timely and appropriate subsequent measures are taken.
      3. Following a detailed history and physical examination, an indeterminate FNA, adequate radiographic imaging, and a full survey of the upper aerodigestive tract mucosa, an open biopsy of a neck mass may be warranted (eg, to rule out lymphoma).
      4. The key to successful treatment is expeditious and comprehensive management immediately following the open biopsy if squamous cell carcinoma is identified.
  8. Consultations
    1. Radiation oncology
    2. Internal medicine: if needed to help address coexisting illnesses that are common in the group of patients with squamous cell carcinoma
    3. Dentistry: to coordinate dental care and timing of extractions if irradiation is part of management plan
  9. Panendoscopy is Indicated Before Treatment (see Panendoscopy protocol)
    1. "Pan" (everywhere) refers to:
      1. Nasopharyngoscopy and rhinoscopy: may actually visualize those sites better in the clinic with flexible fiberoptic endoscope
      2. Direct laryngoscopy
        1. Include oropharynx in survey
        2. Yield highest in pyriform sinuses, postcricoid region, supraglottic larynx, and base of tongue
      3. Esophagoscopy
        1. Cervical esophagoscopy done to identify potential site for neck metastasis
        2. Thoracic esophagoscopy done to survey for synchronous second primary (most commonly in lower esophagus)
      4. Bronchoscopy: done with washings if symptoms or radiographic imaging support pulmonary abnormality
      5. Inspection and palpation bimanually of the oral cavity and neck
      6. Deep palpation of the base of tongue
    2. Directed (not "blind") biopsies are done to sites most likely to harbor an occult neoplasm.
      1. Bilateral tonsillectomy: unilateral tonsillectomy leaves asymmetry to the oropharynx that may be perceived as a pathologic abnormality years later
      2. Bilateral or unilateral nasopharyngeal biopsies: fossa of Rosenmuller
      3. Ipsilateral base of tongue biopsy
      4. Consider pyriform sinus biopsy


  1. Assume that, despite an appropriately intense evaluation in the clinical setting, the site of the primary tumor remains elusive.
    1. The diagnosis of squamous cell carcinoma is made through FNA of neck mass.
      1. Under general anesthesia, perform panendoscopy with directed biopsies and neck dissection.
      2. Usual practice at the University of Iowa: If the primary site is found, it is likely to be classified T1 and hence will likely receive XRT as definitive therapy for the primary site and XRT to the neck as adjuvant postoperative therapy. Identification of the primary site helps to limit the extent of irradiation. If the primary site is not found, the neck and the mucosa of the upper aerodigestive tract is irradiated.
      3. Alternatives: if the primary site is not found despite appropriate biopsies
        1. The neck disease demonstrates extracapsular spread or multiple nodes at multiple levels; consider XRT to the neck following neck dissection, sparing irradiation of upper aerodigestive tract mucosal surfaces
        2. The neck disease is small without extracapsular spread (ie, one or two lymph nodes); consider treatment with neck dissection only and no irradiation
    2. The diagnosis was made elsewhere through open biopsy with resection of all gross residual disease as documented by subsequent CT imaging, but without a formal neck dissection.
      1. Under general anesthesia, perform panendoscopy with directed biopsies
      2. Consider neck dissection under the same anesthetic
        1. May be followed either with or without postoperative irradiation depending on pathologic findings
        2. May alternatively consider treatment with irradiation without neck dissection depending on pathologic findings from resected specimen


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Robbins KT. Detrimental effects of diagnostic cervical node biopsy: dogma vs science. Head Neck. 1991;13:175-176.

Wang RC, Goepfert H, Barber A, Wolf P. Squamous cell carcinoma metastatic to the neck from an unknown primary site. In: Lorson DL, Ballantyne AS, Guillamondegui OM, eds. Cancer in the Neck--Evaluation and Treatment. New York, NY: Macmillan Publishing Co; 1986.

Young T, Gluckman J. Tumors of upper aerodigestive tract: neck metastases--unknown primary. In: Medina J. ed. Clinical Practice Guidelines for the Diagnosis and Management of Cancer of the Head and Neck. Pittsburgh, Pa: American Society for Head and Neck Surgery and The Society of Head and Neck Surgeons; 1996:49-53.