Distinguishing pseudoepitheliomatous hyperplasia from squamous cell carcinoma in mucosal biopsy specimens from the head and neck
Related Experiment Video
Updated: Aug 16, 2026

RNAscope for In situ Detection of Transcriptionally Active Human Papillomavirus in Head and Neck Squamous Cell Carcinoma
Published on: March 11, 2014
Elena Zarovnaya1, Candice Black
1Department of Pathology, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756, USA.
Context:
The differentiation of pseudoepitheliomatous hyperplasia from invasive squamous cell carcinoma is a difficult and frequently encountered distinction, especially in biopsy specimens from head and neck mucosa. The problem is compounded by inflamed and often poorly oriented tissue sections.
Objective:
To distinguish pseudoepitheliomatous hyperplasia from invasive squamous cell carcinoma, utilizing a panel of antibodies to various epithelial and stromal elements (p53, matrix metalloproteinase 1, E-cadherin, and collagen IV) that has been shown to be useful in differentiating intestinal adenomas with invasive adenocarcinoma from displaced adenomatous epithelium.
Design:
Thirty-three archival specimens (16 squamous cell carcinoma [12 with invasion and 4 with microinvasion] and 17 pseudoepitheliomatous hyperplasia) from head and neck mucosal locations were immunostained and examined by the authors.
Results:
We found increased nuclear staining of the invasive tumor cells with p53. There was decreased staining within invasive tumor nests with E-cadherin. There was highly significant increased staining within tumor cells and adjacent stroma with matrix metalloproteinase 1 (P < .001). The only antibody in our panel that did not show a reliable staining pattern was collagen IV. It appeared fragmented in benign inflamed and malignant areas and therefore was not useful.
Conclusions:
p53, matrix metalloproteinase 1, and E-cadherin showed significant staining trends independent of inflammation and suboptimal tissue orientation. Although a properly oriented hematoxylin-eosin-stained section was our gold standard, we found this immunoperoxidase panel useful as a diagnostic adjunct in difficult cases.

