Association of Li-Fraumeni Syndrome With Small Cell... : International Journal of Gynecological Pathology (original) (raw)

PATHOLOGY OF THE UPPER GENITAL TRACT: CASE REPORT

Association of Li-Fraumeni Syndrome With Small Cell Carcinoma of the Ovary, Hypercalcemic Type and Concurrent Pleomorphic Liposarcoma of the Cervix

Tandon, Bevan M.D.; Hagemann, Ian S. M.D., Ph.D.; Maluf, Horacio M. M.D.; Pfeifer, John D. M.D., Ph.D.; Al-Kateb, Hussam M.Sc., Ph.D.

Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO

Present address: Hussam Al-Kateb, M.Sc., Ph.D, Department of Pathology, University of Arizona School of Medicine, Life Science North Building, Room 549, 1501N Campbell Avenue, Tucson, AZ 85724.

The authors declare no conflict of interest.

Address correspondence and reprint requests to Hussam Al-Kateb, MSc, PhD, Department of Pathology, University of Arizona School of Medicine, Life Science North Building, 1501 N Campbell Avenue. Tucson, 85724. E-mail: [email protected].

Abstract

Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT), is a rare, highly lethal malignancy predominantly affecting young adult females. We report a patient with widely metastatic SCCOHT and concurrent uterine cervical pleomorphic liposarcoma. Clinical targeted next-generation sequencing was performed on both neoplasms and demonstrated hemizygous stop-gain TP53 mutations (p.R196*), and wild-type SMARCA4 in both tumors. Microarray analyses of both tumors revealed similar but not identical widespread loss of heterozygosity over most chromosomes associated with loss of chromosomal copy number in the SCCOHT and pleomorphic liposarcoma tumors, amplification of FGFR1 in both tumors, and amplification of MYC in the SCCOHT. Immunohistochemistry demonstrated that SMARCA4 and SMARCB1 were retained in both tumors, and that SMARCA2 expression was retained but TP53 expression was lost in the SCCOHT. Germline testing using Sanger sequencing showed heterozygous TP53 mutation, confirming the diagnosis of Li-Fraumeni syndrome. These findings are novel and for the first time associate SCCOHT with Li-Fraumeni syndrome.