title: Malignant transformation of atypical endometrial hyperplasia after progesterone therapy showing germ-cell tumor-like differentiation.
abstract: A 31-year-old woman was treated for atypical endometrial hyperplasia (AEH) with high-dose medroxyprogesterone acetate (MPA) therapy to preserve fertility. The AEH was found by repeated cytologic and histologic examinations to have completely disappeared with the therapy, but 3 years after her last follow up she required emergency surgery to treat severe genital bleeding. The hysterectomied uterus consisted mostly of poorly differentiated adenocarcinoma, G3 endometrioid type. Minor AEH was present in the exophytic area, in which some glands were cystically dilated. Part of the AEH had transformed into other histologic features with germ-cell-like differentiation, demonstrated by immunohistochemical positive reaction of placental alkaline phosphatase, alpha-fetoprotein, and human chorionic gonadotrophin. Recurrent AEH had undergone malignant transformation, resulting in the development of well- and poorly differentiated adenocarcinoma and tumor exhibiting germ-cell-like differentiation. The patient died of a massive tumor extension 7 months after surgery. The AEH before MPA therapy and the recurrent tumors had genetically different characteristics based on evidence of a loss of heterozygosity, detected at D8S1132 (chromosomal locus, 8q22.1) in the latter but not in the former, by analysis of genetic alterations using microsatellite markers.
authors.affiliation: Department of Pathology, School of Medicine, Tokai University, Isehara, Japan. m-yasuda@is.icc.u-tokai.ac.jp
authors.forename: Masanori
authors.initials: M
authors.lastname: Yasuda
authors.forename: Naruaki
authors.initials: N
authors.lastname: Matsui
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kajiwara
authors.forename: R Yoshiyuki
authors.initials: RY
authors.lastname: Osamura
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Miyamoto
authors.forename: Masaru
authors.initials: M
authors.lastname: Murakami
authors.forename: Takao
authors.initials: T
authors.lastname: Shinozuka
authors.forename: Johbu
authors.initials: J
authors.lastname: Itoh
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D000328:Adult; D000469:Alkaline Phosphatase; D014408:Biomarkers, Tumor / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D006063:Chorionic Gonadotropin / Q000378:metabolism; D004714:Endometrial Hyperplasia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D016889:Endometrial Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D017809:Fatal Outcome; D005260:Female; D058851:GPI-Linked Proteins; D018237:Germinoma / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D006801:Humans; D007044:Hysterectomy; D007124:Immunoenzyme Techniques; D007527:Isoenzymes / Q000378:metabolism; D019656:Loss of Heterozygosity; D017258:Medroxyprogesterone Acetate / Q000627:therapeutic use*; D018895:Microsatellite Repeats; D000509:alpha-Fetoproteins / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D006063:Chorionic Gonadotropin; D058851:GPI-Linked Proteins; D007527:Isoenzymes; D000509:alpha-Fetoproteins; D017258:Medroxyprogesterone Acetate; D000469:Alkaline Phosphatase; C019839:alkaline phosphatase, placental