Diffuse Malignant Mesothelioma of the Peritoneum: An Immunohistochemical Study of 48 Cases
Michael P Lee, Allen P Burke. University of Maryland Medical Center, Baltimore, MD
Background: There are few studies describing the immunohistochemical profile of peritoneal mesotheliomas. p16 has been suggested to lose expression in poorly differentiated tumors, and D2-40 is a relatively recent mesothelial marker. In the current study, we review the immunohistochemical profile of 48 cases of peritoneal mesothelioma and study the utility of p16, D2-40 and CA125 expression in diagnosis.
Design: We retrospectively studied the cases of peritoneal mesothelioma accessioned as either cytoreductive surgery or biopsy at one institution from 2006 to 2011. Immunohistochemical staining was performed on representative paraffin embedded tumor blocks.
Results: There were 48 cases of peritoneal mesothelioma, 26 females (50 ± 14 years), 22 males (60 ± 12). 43 of these were classified as epithelioid and 5 were biphasic (with sarcomatoid areas). Of the 43 epithelioid ones, 28 were tubulopapillary, 9 showed solid growth (6 deciduoid and 3 myxoid), and 6 were well differentiated (4 multicystic, 1 papillary, 1 adenomatoid). All tumors but one were positive for calretinin, both nuclear and cytoplasmic staining, of which 97% were diffuse. 97% showed membranous positivity for EGFR in more than 3/4 of tumors cells. 94% were positive for CA125, mostly diffusely membranous staining. 86% were positive for p16, half of which were patchy positive (between 1/2 and 1/3 tumor cells), nuclear and cytoplasmic staining. 83% showed cytoplasmic staining with CK5/6, 1/3 of which were only focally positive. There was 67%, 57%, and 50% staining for HBME, EMA, and CK903, respectively. Only 47% of tumors stained with WT-1, and 33% with cytokeratin 7. 80% of tumors showed strong membranous positivity for D2-40. There was no correlation between differentiation and staining for any marker except D2-40, which was negative only for well differentiated tumors. The epithelial component in 4 of 5 sarcomatoid tumors showed strong (remaining one weak) and diffuse staining with calretinin in 100% of tumor cells; spindled areas displayed weak to moderate staining in 30-50% of cells. Strong staining with CK903 was seen in two cases, one deciduoid (membranous) and one sarcomatoid (cytoplasmic).
Conclusions: p16 is frequently positive in peritoneal mesothelioma, with no correlation between tumor differentiation and loss of expression. CA125 and EGFR are reliable markers. D2- 40 is nearly always positive in poorly differentiated tumors, which may pose diagnostic difficulties. The study confirms the high sensitivity for calretinin, and shows a high sensitivity for CA125 and EGFR for malignant mesothelioma.
Tuesday, March 20, 2012 9:30 AM
Poster Session III # 133, Tuesday Morning