Molecular Analysis of Adrenal Cortical Carcinomas in Clinical and Histologic Context.
Alexandra E Kovach, Quynh Lam, Dora Dias-Santagata, Peter M Sadow. Massachusetts General Hospital, Boston; Harvard Medical School, Boston, MA
Background: Adrenal cortical carcinomas (ACC) are rare, aggressive neoplasms that represent a small subset of all adrenal cortex-based masses. Iterations of the Weiss criteria remain the go-to standard for histologic parameters to help predict the biologic potential of an adrenal cortical neoplasm. More recently, due to consistently inconsistent data, we have been turning increasingly toward molecular criteria to supplement histologic findings.
Design: In this retrospective study approved by our internal review board (2009P002721), we identified 68 adrenal cortical carcinoma resections from 1976 to 2009; 35 cases were appropriate for further analysis. Clinical and morphologic review was performed, along with molecular studies on a subset of cases using a SNaPshot multiplexed PCR-based clinical assay developed in-house that tests for recurrent mutations in 13 known cancer genes.
Results: Patients included 24 women and 11 men, with a mean age at resection of 53 years (SD 15). Sixteen patients showed clinical signs related to supraphysiologic hormone production, including hypertension (9), concomitant Cushingoid features (4), or hypokalemia (3). Nineteen masses were left-sided, 1 bilateral, with a mean maximum dimension of 12.0 cm (SD 1.8). In 11 cases, the surgical margin was positive and/or metastases were apparent at the time of resection. Twelve patients died because of metastatic disease, including 5 of the 11 with positive surgical margins or metastases at presentation, with a mean time from resection to death of 1.9 yrs. Histologically, tumor necrosis was extensive in 24 cases and absent in 4. Lymphovascular invasion was identified on H&E sections in 14 cases, all but one of which also had extensive necrosis. Degree of necrosis paralleled degree of proliferation, with a mean mitotic rate of 20/50 HPF. Of a subset of 10 carcinomas characterized by rapid disease progression compared to other cases in the cohort, molecular analysis revealed 5 beta-catenin mutations and 1 mutation in APC.
Conclusions: Although universally associated with poor prognosis, ACCs with relatively favorable outcome had complete surgical resections and lack of metastases at presentation, independent of histologic parameters. Beta-catenin and APC mutations appear common in tumors with relatively unfavorable outcomes. Continuing studies include comparative molecular analysis in an expanded cohort including benign adrenal cortical adenomas and neoplasms where histologic parameters suggest equivocal biologic potential.
Monday, February 28, 2011 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 83, Monday Morning