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Tumor Suppressor Gene Alterations in Respiratory Epithelial Adenomatoid Hamartoma (REAH): Comparison to Sinonasal Adenocarcinoma and Inflamed Sinonasal Mucosa

Ozolek, John A. MD*; Hunt, Jennifer L. MD

The American Journal of Surgical Pathology: December 2006 - Volume 30 - Issue 12 - p 1576-1580
doi: 10.1097/01.pas.0000213344.55605.77
Original Articles

Respiratory epithelial adenomatoid hamartoma (REAH) is an unusual benign sinonasal glandular proliferation. REAH is not considered a neoplasm, although, no molecular evidence exists to support or refute this possibility. Microdissection of 10 cases of REAH, 9 cases of sinonasal adenocarcinoma (SNAC) and 10 cases of chronic sinusitis was performed. DNA was extracted and polymerase chain reaction performed using fluorescently labeled primers flanking known tumor suppressor genes on chromosomes 9p (CDKN2/p16), 11p (H-ras), 17p (p53), and 18q (DCC/DPC4). Polymerase chain reaction products were analyzed semiquantitatively by capillary electrophoresis. Allele ratios were calculated using the peak height from the shorter allele divided by the peak height from the longer allele. The loss of heterozygosity (LOH) ratio was calculated as the allele ratio from tumor tissue divided by the allele ratio from normal tissue. The fractional allelic loss (FAL) was calculated as the percentage of loci that harbored LOH divided by the number of loci that were informative. REAH demonstrated an intermediate FAL of 31% compared with SNAC (64%) and chronic sinusitis (2%). REAH and SNAC had the highest LOH for multiple loci located on 9p (p16) and 18q (DCC/DPC4). The molecular profile of REAH shows a mean FAL of 31%, which would be considered unusually high for a non-neoplastic entity. Appreciable allelic loss within REAH suggests the possibility that REAH may be a benign neoplasm rather than a hamartoma.

*Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA

Department of Anatomic Pathology, Cleveland Clinic Foundation, Cleveland, Ohio

Reprints: John A. Ozolek, MD, Department of Pathology, Children's Hospital of Pittsburgh, 3705 Fifth Avenue, Pittsburgh, PA 15213 (e-mail:

This study was awarded Best Poster Presentation in Otorhinolaryngology Pathology at the United States and Canadian Academy of Pathology Annual Meeting in San Antonio, TX, February 28, 2005.

© 2006 Lippincott Williams & Wilkins, Inc.