p16 expression in follicular dendritic cell sarcoma: a potential mimicker of human papillomavirus-related oropharyngeal squamous cell carcinoma

Hum Pathol. 2017 Aug:66:40-47. doi: 10.1016/j.humpath.2017.05.019. Epub 2017 May 26.


Follicular dendritic cell sarcoma is a rare mesenchymal neoplasm that most commonly occurs in cervical lymph nodes. It has histologic and clinical overlap with the much more common p16-positive human papillomavirus (HPV)-related squamous cell carcinoma of the oropharynx, which characteristically has nonkeratinizing morphology and often presents as an isolated neck mass. Not surprisingly, follicular dendritic cell sarcomas are commonly misdiagnosed as squamous cell carcinoma. Immunohistochemistry is helpful in separating the 2 entities. Follicular dendritic cell sarcoma expresses dendritic markers such as CD21 and CD23 and is almost always cytokeratin negative. However, in many cases of HPV-related oropharyngeal carcinoma, only p16 immunohistochemistry as a prognostic and surrogate marker for HPV is performed. p16 expression in follicular dendritic cell sarcoma has not been characterized. Here, we investigate the expression of p16 in follicular dendritic cell sarcoma and correlate it with retinoblastoma protein expression. A pilot study of dendritic marker expression in HPV-related oropharyngeal squamous cell carcinoma was also performed. We found that 4 of 8 sarcomas expressed p16 with strong and diffuse staining in 2 cases. In 2 of the 4 cases, p16 expression corresponded to loss of retinoblastoma protein expression. Dendritic marker expression (CD21 and CD23) was not found in HPV-related oropharyngeal squamous cell carcinomas. As such, positive p16 immunohistochemistry cannot be used as supportive evidence for the diagnosis of squamous cell carcinoma as strong and diffuse p16 expression may also occur in follicular dendritic cell sarcoma. Cytokeratins and dendritic markers are critical in separating the two tumor types.

Keywords: Follicular dendritic cell sarcoma; Human papillomavirus; Nonkeratinizing; Oropharyngeal; Squamous cell carcinoma; p16 immunohistochemistry.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Biomarkers, Tumor / analysis*
  • Carcinoma, Squamous Cell / chemistry*
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / virology
  • Cyclin-Dependent Kinase Inhibitor p16 / analysis*
  • Dendritic Cell Sarcoma, Follicular / metabolism*
  • Dendritic Cell Sarcoma, Follicular / pathology
  • Diagnosis, Differential
  • Female
  • Head and Neck Neoplasms / chemistry*
  • Head and Neck Neoplasms / pathology
  • Head and Neck Neoplasms / virology
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Missouri
  • Oropharyngeal Neoplasms / chemistry*
  • Oropharyngeal Neoplasms / pathology
  • Oropharyngeal Neoplasms / virology
  • Papillomavirus Infections / metabolism*
  • Papillomavirus Infections / pathology
  • Papillomavirus Infections / virology
  • Pilot Projects
  • Predictive Value of Tests
  • Receptors, Complement 3d / analysis
  • Receptors, IgE / analysis
  • Retinoblastoma Protein / analysis
  • Squamous Cell Carcinoma of Head and Neck
  • Tennessee


  • Biomarkers, Tumor
  • CDKN2A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • Receptors, Complement 3d
  • Receptors, IgE
  • Retinoblastoma Protein