Squamous and Neuroendocrine Specific Immunohistochemical Markers in Head and Neck Squamous Cell Carcinoma

A Tissue Microarray Study

J. S. Lewis, R. D. Chernock, J. A. Bishop

Research output: Contribution to journalArticle

Abstract

The performance characteristics of neuroendocrine-specific and squamous-specific immunohistochemical markers in head and neck squamous cell carcinomas (SCC), in particular in oropharyngeal tumors in this era of human papillomavirus (HPV)-induced cases, are not well-established. The differential diagnosis for poorly differentiated SCCs, for nonkeratinizing oropharyngeal SCCs, and for other specific SCC variants such as basaloid SCC and undifferentiated (or lymphoepithelial-like) carcinomas includes neuroendocrine carcinomas. Given that neuroendocrine carcinomas of the head and neck are aggressive regardless of HPV status, separating them from SCC is critically important. In this study, we examined the neuroendocrine markers CD56, synaptophysin, and chromogranin-A along with the squamous markers p40 and cytokeratin 5/6 in a large tissue microarray cohort of oral, oropharyngeal, laryngeal, and hypopharyngeal SCCs with known HPV results by RNA in situ hybridization for the oropharyngeal tumors. Results were stratified by site and specific SCC variant. The neuroendocrine stains were rarely expressed in SCC (<1% overall) with CD56 the least, and chromogranin-A the most, specific markers. Further, p40 and cytokeratin 5/6 were very consistently expressed in all head and neck SCC (>98% overall), including very strong, consistent staining in oropharyngeal HPV-related nonkeratinizing SCC. Undifferentiated (or lymphoepithelial-like) carcinomas of the oropharynx are more frequently p40 or cytokeratin 5/6 negative or show only weak or focal expression. In summary, markers of neuroendocrine and squamous differentiation show very high specificity and sensitivity, respectively, across the different types of head and neck SCC.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalHead and Neck Pathology
DOIs
StateAccepted/In press - May 20 2017

Fingerprint

Squamous Cell Carcinoma
Keratin-6
Keratin-5
Neuroendocrine Carcinoma
Carcinoma
Chromogranin A
Synaptophysin
Oropharynx
In Situ Hybridization
Carcinoma, squamous cell of head and neck
Neoplasms
Differential Diagnosis
Coloring Agents
Neck
Head
RNA
Staining and Labeling
Sensitivity and Specificity
adjuvant P40

Keywords

  • Head and neck
  • Human papillomavirus
  • Immunohistochemistry
  • Neuroendocrine
  • Oropharyngeal
  • p40
  • Squamous cell carcinoma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Otorhinolaryngology
  • Oncology

Cite this

Squamous and Neuroendocrine Specific Immunohistochemical Markers in Head and Neck Squamous Cell Carcinoma : A Tissue Microarray Study. / Lewis, J. S.; Chernock, R. D.; Bishop, J. A.

In: Head and Neck Pathology, 20.05.2017, p. 1-9.

Research output: Contribution to journalArticle

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abstract = "The performance characteristics of neuroendocrine-specific and squamous-specific immunohistochemical markers in head and neck squamous cell carcinomas (SCC), in particular in oropharyngeal tumors in this era of human papillomavirus (HPV)-induced cases, are not well-established. The differential diagnosis for poorly differentiated SCCs, for nonkeratinizing oropharyngeal SCCs, and for other specific SCC variants such as basaloid SCC and undifferentiated (or lymphoepithelial-like) carcinomas includes neuroendocrine carcinomas. Given that neuroendocrine carcinomas of the head and neck are aggressive regardless of HPV status, separating them from SCC is critically important. In this study, we examined the neuroendocrine markers CD56, synaptophysin, and chromogranin-A along with the squamous markers p40 and cytokeratin 5/6 in a large tissue microarray cohort of oral, oropharyngeal, laryngeal, and hypopharyngeal SCCs with known HPV results by RNA in situ hybridization for the oropharyngeal tumors. Results were stratified by site and specific SCC variant. The neuroendocrine stains were rarely expressed in SCC (<1{\%} overall) with CD56 the least, and chromogranin-A the most, specific markers. Further, p40 and cytokeratin 5/6 were very consistently expressed in all head and neck SCC (>98{\%} overall), including very strong, consistent staining in oropharyngeal HPV-related nonkeratinizing SCC. Undifferentiated (or lymphoepithelial-like) carcinomas of the oropharynx are more frequently p40 or cytokeratin 5/6 negative or show only weak or focal expression. In summary, markers of neuroendocrine and squamous differentiation show very high specificity and sensitivity, respectively, across the different types of head and neck SCC.",
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