No abstract

Summary Adrenocortical carcinoma (ACC) is an aggressive cancer that originates in the cortex of the adrenal gland and generally has a poor prognosis. ACC is rare but can be more commonly seen in those with cancer predisposition syndromes (e.g. Li-Fraumeni and Lynch Syndrome). The diagnosis of ACC is sometimes uncertain and it requires the use of precise molecular pathology; the differential diagnosis includes pheochromocytoma, adrenal adenoma, renal carcinoma, or hepatocellular carcinoma. We describe a case of a 57-year-old woman with Lynch Syndrome and metastatic ACC who was initially diagnosed as having pheochromocytoma. The tumor was first identified at 51 years of age by ultrasound followed by a CT scan. She underwent a left adrenalectomy, and the histopathology identified pheochromocytoma. Two years later, she had tumor recurrence with imaging studies showing multiple lung nodules. Following a wedge resection by video-assisted thoracoscopic surgery (VATS), histopathology was read as metastatic pheochromocytoma at one institution and metastatic ACC at another institution. She later presented to the National Institutes of Health (NIH) where the diagnosis of ACC was confirmed. Following her ACC diagnosis, she was treated with mitotane and pembrolizumab which were stopped due to side effects and progression of disease. She is currently receiving etoposide, doxorubicin, and cisplatin (EDP). This case highlights the importance of using a multi-disciplinary approach in patient care. Thorough evaluation of the tumor’s pathology and analysis of the patient’s genetic profile are necessary to obtain the correct diagnosis for the patient and can significantly influence the course of treatment. Learning points: Making the diagnosis of ACC can be difficult as the differential diagnosis includes pheochromocytoma, adrenal adenoma, renal carcinoma, or hepatocellular carcinoma. Patients with Lynch Syndrome should undergo surveillance for ACC as there is evidence of an association between Lynch Syndrome and ACC. Conducting a complete tumor immunoprofile and obtaining a second opinion is very important in cases of suspected ACC in order to confirm the proper diagnosis. A multi-disciplinary approach including genetic testing and a thorough evaluation of the tumor’s pathology is imperative to ensuring that the patient receives an accurate diagnosis and the appropriate treatment.

We recently qualitatively reviewed the literature on primary prevention strategies in BRCA 1 ⁄ 2 mutation carriers for chemoprevention and risk reduction surgery. The trials had to provide information on the effectiveness of primary prevention (bilateral mastectomy, bilateral salpingo-oophorectomy or tamoxifen) in terms of breast cancer risk reduction in BRCA 1 or 2 mutation carriers. This review focused on breast cancer incidence, total mortality and specific breast cancer mortality. The data from each study was descriptively summarized; a quantitative meta-analysis was not feasible in the absence of randomized controlled trials and with such heterogeneous study designs and insufficient data.Ten studies were retained. Six multi-center cohort studies evaluate the efficacy of bilateral prophylactic salpingo-oophorectomy (1-6). They report a reduction of approximately 50% in the incidence of breast cancer and one trial reveals a mortality reduction after bilateral salpingo-oophorectomy.Three cohort studies evaluate the incidence of breast cancer after bilateral prophylactic mastectomy (7-9). All of these studies report a significant reduction of more than 95% of the incidence of breast cancer in the BPM group. However these trials are of insufficient methodological quality and the data on the effectiveness of BPM on mortality is not available at present.One study evaluates the effectiveness of tamoxifen in healthy BRCA mutation carriers (10). This analysis shows a nonsignificant reduction of the incidence of breast cancer in BRCA 2 mutation carriers (RR: 0.38, 95% CI: 0.06-1.56). However, this study did not highlight a reduction of the incidence of breast cancer in BRCA 1 mutation carriers (RR: 1.67, 95% CI: 0.32-10.70). It is difficult to draw conclusions concerning the effectiveness of tamoxifen in BRCA mutation carriers given that the only study available is a (post hoc) analysis including too few cases.Primary prevention is a promising approach in the fight against breast cancer, especially for women at very high risk carrying BRCA mutations. More studies are necessary, especially to evaluate the effect of prevention on mortality. REFERENCES1. Domchek SM, Friebel TM, Neuhausen SL, et al. Mortality after bilateral salpingo-oophorectomy in BRCA1 and BRCA2 mutation carriers: a prospective cohort study. Lancet Oncol 2006;7:223-9. 2. Kramer JL, Velazquez IA, Chen BE, Rosenberg PS, Struewing JP, Greene MH. Prophylactic oophorectomy reduces breast cancer penetrance during prospective, long-term follow-up of BRCA1 mutation carriers. J Clin Oncol 2005; 23: 8629-35. 3. Rebbeck TR, Friebel T, Wagner T, et al. Effect of short-term hormone replacement therapy on breast cancer risk reduction after bilateral prophylactic oophorectomy in BRCA1 and BRCA2 mutation carriers: the PROSE Study Group. J Clin Oncol 2005;23:7804-10. 4. Eisen A, Lubinski J, Klijn J, et al. Breast cancer risk following bilateral oophorectomy in BRCA1 and BRCA2 mutation carriers: an international case-control study. J Clin Oncol 2005; 23:7491-6. 5. Rebbec...