Anatomic Pathology Selected Abstracts, 4/14

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Margin comments in dermatopathology reports on HDN and re-excision rates

Dermatopathology reports influence clinical management, but it is not clear to what extent comments on margin involvement of histopathologically dysplastic nevi (HDN) influence decisions about re-excision or complete excision. The authors sought to determine if standardized margin comments on HDN influence re-excision rates. By reviewing medical records, they compared re-excision rates of HDN reported with standardized margin comments from May 2011 to December 2012 and without from January 2007 to December 2010. They also surveyed clinicians to assess perceptions of the impact of margin comments on their management of HDN. Of 584 HDN, 302 had margin comments and 282 did not. Re-excision was recommended or performed at a significantly higher rate for patients in the group without comments (51.8 percent; 146 of 282) than in the group with comments (39.4 percent; 119 of 302; P=0.003), regardless of margin status. This difference was observed among HDN diagnosed as mildly and moderately dysplastic but not severely dysplastic. Forty percent of clinicians (16 of 40) responded that they are more likely to biopsy pigmented lesions with a clinical margin of normal-appearing skin than they were before margin comments were routinely included in dermatopathology reports. As a result of this retrospective study, the authors concluded that re-excision rates were significantly lower in patients who had HDN reported with standardized margin comments. These comments may help reduce re-excision rates and lead to a reduction in health care use, cost, and morbidity.

Comfere NI, Chakraborty R, Peters MS. Margin comments in dermatopathology reports on dysplastic nevi influence re-excision rates. J Am Acad Dermatol. 2013;69: 687–692.

Correspondence: Dr. Nneka I. Comfere, Dept. of Dermatology, Mayo Clinic, 200 First St. SW, Rochester, MN 55905

Comparison of two tests for low-grade, ER-positive invasive breast carcinomas

Several molecular tests have been developed to estimate risk of distant recurrence and aid clinical decisionmaking pertaining to adjuvant chemotherapy in patients with early stage breast carcinoma. Oncotype DX, a 21-gene expression profile, and Mammostrat, an immunohistochemistry-based assay, are validated to stratify patients into groups with low, intermediate, and high risk of distant recurrence. However, the tests have not been compared head-to-head, and little data are available regarding their correlation with clinicopathologic tumor features. The authors conducted a study in which they compared clinicopathologic tumor features with risk estimations by Oncotype DX and Mammostrat in 106 low-grade estrogen receptor-positive breast carcinomas. Double immunohistochemical stain for pancytokeratin and Ki-67 was performed to assess cell proliferation in cancer versus stromal/inflammatory cells. Tumors showing intermediate/high risk by Oncotype DX, but not by Mammostrat, showed increased stromal cellularity, presence of inflammatory cells, and increased proliferation in stromal/inflammatory cells. Discrepant cases showing intermediate/high risk by Oncotype DX but low risk by Mammostrat were associated with increased stromal cellularity, presence of inflammatory cells, and increased proliferation in stromal/inflammatory cells compared with concordant cases showing low risk by both assays. These results suggest that low-grade estrogen receptor-positive breast carcinomas with increased stromal/inflammatory cell proliferation may show an increased risk of distant recurrence as assessed by Oncotype DX, which uses RNA extracted from a mixture of tumor and stromal/inflammatory cells in the assay. Mammostrat, which examines cancer cells only, may provide a better estimation of likely tumor behavior in a subgroup of low-grade breast carcinomas.

Acs G, Kiluk J, Loftus L, et al. Comparison of Oncotype DX and Mammostrat risk estimations and correlations with histologic tumor features in low-grade, estrogen receptor-positive invasive breast carcinomas. Mod Pathol. 2013;26:1451–1460.

Correspondence: Dr. G. Acs at geza.acs@moffitt.org

P53 and BAF250a expression in endometrial clear cell carcinoma

TP53 mutation may be a negative prognostic marker in endometrial cancers, but its relevance in the rarer histologic subtypes, including clear cell carcinomas, has not been delineated. Preclinical studies suggest functional interactions between p53 and the BAF250a protein, the product of the tumor-suppressor gene ARID1A (adenine-thymine-rich interactive domain containing protein 1A), which is frequently mutated in ovarian clear cell carcinoma. The authors conducted a study in which they evaluated the significance of p53 and BAF250a expression, as assessed by immunohistochemistry, in a group of 50 endometrial clear cell carcinomas. Of 50 cases, 17 (34 percent) were p53+, and the remaining 33 cases had a p53 wild-type (p53-wt) immunophenotype. Of the 11 relapses or recurrences in the entire data set, 73 percent were in the p53+ group (P=0.008). On univariate analyses, the median overall survival rate for the p53-wt patients (83 months) was longer than the rate for the p53+ patients (63 months), and the median progression-free survival rate for the p53-wt group (88 months) was significantly longer than the rate for the p53+ group (56 months). On multivariate analyses, p53 expression was not associated with reduced overall or progression-free survival. Furthermore, p53 status was not significantly associated with pathologic stage or morphologic patterns. Of the 50 cases, 10 (20 percent) showed a complete loss of BAF250a expression. No significant correlation was noted between p53 and BAF250a expression. The p53+/BAF250a–, p53+/BAF250a+, p53-wt/BAF250a+, and p53-wt/BAF250a– composite immunophenotypes were identified in eight percent, 26 percent, 54 percent, and 12 percent of cases, respectively. Neither loss of BAF250a expression nor composite p53/BAF250a expression patterns were associated with reduced overall or progression-free survival. The authors concluded that a significant subset of clear cell carcinomas express p53, and these cases are not definable by their morphologic features. P53 expression may be a negative prognostic factor in this histotype and warrants additional studies. Loss of BAF250a expression has no prognostic significance in endometrial clear cell carcinomas.

Fadare O, Gwin K, Desouki MM, et al. The clinicopathologic significance of p53 and BAF-250a (ARID1A) expression in clear cell carcinoma of the endometrium. Mod Pathol. 2013;26:1101–1110.

Correspondence: Dr. O. Fadare at oluwole fadare@yahoo.comn