title: Uterine angiosarcoma associated with lymphangioleiomyomatosis in a patient with tuberous sclerosis complex: an autopsy case report with immunohistochemical and genetic analysis.
abstract: A 41-year-old woman carrying a germline tuberous sclerosis complex 2 (TSC2) mutation, whose regular medical follow-up for tuberous sclerosis complex and tuberous sclerosis complex-associated lymphangioleiomyomatosis had continued for 2 years, had uterine angiosarcoma concomitant with uterine lymphangioleiomyomatosis. Immunohistochemically, the uterine angiosarcoma cells showed an extremely skewed lymphatic differentiation; they were diffusely immunopositive for CD31 but negative for other vascular endothelial markers including factor VIII and CD34 yet strongly immunopositive for lymphatic endothelial markers including D2-40 and Prox-1. Loss of heterozygosity analysis demonstrated that not only lymphangioleiomyomatosis and renal angiomyolipoma but also the uterine angiosarcoma had loss of heterozygosity on TSC2. Furthermore, direct sequencing revealed a TP53 mutation in the uterine angiosarcoma. Collectively, the findings suggest that combined dysfunction of the p53 and TSC2 tumor suppressor proteins may contribute to the development of uterine angiosarcoma in this rare clinical setting.
authors: Department of Human Pathology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. tkhyz@juntendo.ac.jp
authors: Takuo
authors: T
authors: Hayashi
authors: Kengo
authors: K
authors: Koike
authors: Toshio
authors: T
authors: Kumasaka
authors: Tsuyoshi
authors: T
authors: Saito
authors: Keiko
authors: K
authors: Mitani
authors: Yasuhisa
authors: Y
authors: Terao
authors: Daiki
authors: D
authors: Ogishima
authors: Takashi
authors: T
authors: Yao
authors: Satoru
authors: S
authors: Takeda
authors: Kazuhisa
authors: K
authors: Takahashi
authors: Kuniaki
authors: K
authors: Seyama
mesh_terms: D000328:Adult; D001344:Autopsy; D005260:Female; D006394:Hemangiosarcoma / Q000150:complications / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D018192:Lymphangioleiomyomatosis / Q000150:complications / Q000235:genetics* / Q000473:pathology; D014402:Tuberous Sclerosis / Q000150:complications*; D000077005:Tuberous Sclerosis Complex 2 Protein; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics; D014594:Uterine Neoplasms / Q000150:complications / Q000235:genetics* / Q000473:pathology
chemical_list: C000624653:TSC2 protein, human; D000077005:Tuberous Sclerosis Complex 2 Protein; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins