The diagnosis of an occult primary tumor is made only when no primary tumor is detected after careful search and when a primary tumor does not appear during therapy. Patients with cervical lymph node metastases histologically related to a previously treated primary tumor and patients
with lymphomas and adenocarcinoma are excluded. If the biopsy is an undifferentiated carcinoma (in particular, a lymphoepithelioma), the most probable primary site is in Waldeyer ring; for example, the nasopharynx, base of tongue, or tonsil. Most epidermoid carcinomas metastatic to lymph nodes of the upper half of the neck will originate from a head and neck primary site. Squamous carcinomas metastatic to the lower neck may represent a primary site in the head and neck, esophagus, lung, or
genitourinary tract. A search for primaries in these areas must be undertaken before assuming that the primary is occult. Primary tumors arising in the nasopharynx may be secondary to Epstein-Barr virus (EBV) infection, and EBV genomic material may be detectable in cervical nodal tissue after DNA amplification using the polymerase chain reaction. Such a finding should lead to an in-depth search for a primary in the
nasopharynx.[1] The extent of investigation and type of treatment must be individualized depending on the patient's age and wishes, and on the site, histology, and extent of metastatic lymph node involvement of the tumor. When a patient qualifies as having squamous carcinoma of the neck with occult primary, he or she should be
checked for other obvious metastatic disease, such as lung, liver, or bone, because this would affect the locoregional approach to therapy.[2] Three-year disease-free survival rates following surgery and/or radiation therapy for unknown squamous primaries range from 40% to
50% in patients with N1 disease, to 38% and 26% for patients with N2 and N3 disease, respectively. Patients who later develop primary lesions have poor survival rates compared with patients whose primaries remain occult, for example 30% versus 60%. Patients with neck metastases from an undetectable primary should be given the benefit of definitive treatment. Despite the ominous situation of an undiscovered
primary, a significant number of patients do achieve cure by both surgical and radiotherapeutic approaches. In some patients, long-term repeat examinations will eventually disclose the primary tumor, and at a treatable stage. Cellular Classification of Metastatic Squamous Neck Cancer With Occult PrimaryThis section helps lead the clinician and pathologist through a differential diagnosis for an unknown primary presenting with cervical node metastases. The therapeutic section, however, relates only to squamous carcinoma and assumes that the primary physician has worked with the pathologist as described below to eliminate other possibilities that would require alternative therapies. The pathologist plays a central role in evaluating an occult primary tumor. A thorough evaluation of an adequate specimen through histological or immunohistochemical techniques, and, when appropriate, electron microscopy (EM) provides guidance for the clinical evaluation that ensues. A critical interaction should exist between the pathologist, oncologist, and primary physician. The complexity of the pathological evaluation tends to be inversely related to the degree of differentiation of the tumor. For instance, for well or moderately differentiated tumors, the pathological diagnosis of an epithelial cancer is often readily apparent, in contrast to lymphoma, sarcoma, melanoma, or a germ cell tumor. Commonly used stains such as mucicarmine or diastase-sensitive Periodic Acid Schiff can be important in confirming the diagnosis of certain tumors of gastrointestinal or renal origin. If the clinician is faced with a male patient younger than 50 years with a poorly differentiated tumor, serum levels of beta-human chorionic gonadotropin (beta-hCG) and alpha-fetoprotein (AFP) should be obtained and specimens should be evaluated with immunohistochemical stains for beta-hCG and AFP. Some of these tumors respond to platinum-based combination chemotherapy in a manner similar to extragonadal germ cell malignancies, and this group of patients should be so treated unless other alternative diagnoses are made.[1] Special studies can help in differentiating more poorly differentiated tumors. Often, a generic distinction is important between a poorly differentiated tumor of epithelial, hematopoietic, neuroendocrine, or neuroectodermal origin (i.e., melanoma).
Stage Information for Metastatic Squamous Neck Cancer With Occult PrimaryAmerican Joint Committee on Cancer (AJCC) Stage Groupings and TNM DefinitionsFor metastatic squamous neck cancer with occult primary, the patient's human papilloma virus (HPV) p16 status or Epstein-Barr virus (EBV) status is used to determine which AJCC staging system is used, as follows:
Treatment of Untreated Metastatic Squamous Neck Cancer With Occult PrimaryUntreated metastatic squamous neck cancer with occult primary means that a patient is newly diagnosed and has had no previous treatment except supportive care. Patients with neck nodes from a presumed unknown primary tumor should be evaluated as follows:
Treatment options:
Current Clinical TrialsUse our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.
Treatment of Recurrent Metastatic Squamous Neck Cancer With Occult PrimaryThe prognosis for most treated cancer patients with progressing, recurring, or relapsing disease is poor, regardless of cell type or stage. Deciding on further treatment depends on many factors, including the specific cancer, previous treatment, site of recurrence, as well as individual patient considerations. Treatments that are under clinical evaluation are appropriate and should be considered when possible. Current Clinical TrialsUse our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available. Changes to This Summary (07/22/2022)The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above. Editorial changes were made to this summary. This summary is written and maintained by the PDQ Adult Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® - NCI's Comprehensive Cancer Database pages. About This PDQ SummaryThis PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed,
evidence-based information about the treatment of adult metastatic squamous neck cancer with occult primary. It is intended as a resource to inform and assist clinicians in the care of their patients. It does not provide formal guidelines or recommendations for making health care decisions. This summary is reviewed regularly and updated as necessary by the
PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH). Board
members review recently published articles each month to determine whether an article should: Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary. The lead reviewers for Metastatic Squamous Neck Cancer With Occult Primary Treatment are:
Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries. Levels of EvidenceSome of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations. Permission to Use This SummaryPDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as “NCI’s PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary].” The preferred citation for this PDQ summary is: PDQ® Adult Treatment Editorial Board. PDQ Metastatic Squamous Neck Cancer With Occult Primary Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/head-and-neck/hp/adult/metastatic-squamous-neck-treatment-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389364] Images in this summary are used with permission of the author(s), artist, and/or publisher for use within the PDQ summaries only. Permission to use images outside the context of PDQ information must be obtained from the owner(s) and cannot be granted by the National Cancer Institute. Information about using the illustrations in this summary, along with many other cancer-related images, is available in Visuals Online, a collection of over 2,000 scientific images. DisclaimerBased on the strength of the available evidence, treatment options may be described as either “standard” or “under clinical evaluation.” These classifications should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the Managing Cancer Care page. Contact UsMore information about contacting us or receiving help with the Cancer.gov website can be found on our Contact Us for Help page. Questions can also be submitted to Cancer.gov through the website’s Email Us. |