Cytologic evaluation of cervical lymph node metastases from cancers of unknown primary origin

Semin Diagn Pathol. 2015 Jan;32(1):32-41. doi: 10.1053/j.semdp.2014.12.002. Epub 2014 Dec 20.


Fine-needle aspiration biopsy (FNAB) is often the first diagnostic procedure performed in patients with head and neck (HN) masses. Metastatic squamous cell carcinoma (SCC) to cervical lymph nodes is by far the most common malignancy aspirated in the HN, but in approximately 3-10% of patients, a primary tumor will not be found even after complete clinico-radiological workup. Several HN cancers are associated with oncogenic viruses, including HPV-associated SCC and EBV-associated nasopharyngeal carcinoma (NPC). While the primary tumor is sometimes small or undetectable, patients often present initially with cervical lymph node metastases. HPV-associated SCC and EBV-associated NPC are typically non-keratinizing carcinomas that can mimic several other poorly differentiated HN cancers by FNAB but have a significantly better prognosis. Therefore, the precise classification of the metastatic disease in the FNAB material is very useful since it can facilitate the subsequent location of the primary tumor, and it can provide prognostic and therapeutic information as well. In this review, we discuss the major entities that can present as a metastatic cancer of unknown primary in cervical lymph node other than supraclavicular, including their cytologic features and the role of ancillary studies.

Keywords: Cervical lymph node metastases; EBV; Fine-needle aspiration; HPV; Oropharynx; Squamous cell carcinoma.

Publication types

  • Review

MeSH terms

  • Biomarkers, Tumor / analysis
  • Biopsy, Fine-Needle*
  • Carcinoma, Squamous Cell / chemistry
  • Carcinoma, Squamous Cell / pathology*
  • Carcinoma, Squamous Cell / virology
  • Epstein-Barr Virus Infections / metabolism
  • Epstein-Barr Virus Infections / pathology*
  • Epstein-Barr Virus Infections / virology
  • Head and Neck Neoplasms / chemistry
  • Head and Neck Neoplasms / pathology*
  • Head and Neck Neoplasms / virology
  • Herpesvirus 4, Human / isolation & purification
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Lymph Nodes / chemistry
  • Lymph Nodes / pathology*
  • Lymph Nodes / virology
  • Lymphatic Metastasis
  • Neoplasms, Unknown Primary / chemistry
  • Neoplasms, Unknown Primary / pathology*
  • Neoplasms, Unknown Primary / virology
  • Papillomaviridae / isolation & purification
  • Papillomavirus Infections / metabolism
  • Papillomavirus Infections / pathology*
  • Papillomavirus Infections / virology
  • Predictive Value of Tests
  • Prognosis
  • Squamous Cell Carcinoma of Head and Neck


  • Biomarkers, Tumor