title: Regressive liver adenomatosis following androgenic progestin therapy withdrawal: a case report with a 10-year follow-up and a molecular analysis.
abstract: OBJECTIVE
  The relationship between sex hormones and hepatocellular adenoma development is well established. On the contrary, their contribution to liver adenomatosis (LA) development is still a debatable issue. Recently, inactivating mutations of hepatocyte nuclear factor-1alpha (HNF-1alpha) transcription factor gene or activating mutations of beta-catenin have been demonstrated in some liver adenomas, and a possible link between HNF-1alpha gene mutations and oral contraceptives has been suggested. Only two cases of regressive LA after hormone withdrawal therapy have been described so far but without any information concerning the molecular characteristics of the tumours.
  
  
  METHODS
  We report the case of a 48-year-old woman with LA, who had been taking an androgenic progestin therapy (lynestrenol) for 10 years. A major regression in the number and size of the lesions was observed 6 months after complete withdrawal of this therapy.
  
  
  METHODS
  Hepatocellular adenomas were studied by immunohistochemistry for oestrogen, progesterone and androgen receptors (ER, PR and AR respectively), and for beta-catenin. Direct sequencing of the HNF-1alpha gene was also performed.
  
  
  RESULTS
  For the first time, we demonstrate significant immunostaining of AR in the hepatocellular adenomas. This staining was negative in the partially regressive adenoma. Immunostainings for ER and PR were negative. HNF-1alpha and the beta-catenin pathways were not involved in tumour pathogenesis.
  
  
  CONCLUSIONS
  Our case suggests a role of androgenic progestin therapy in some cases of LA. Hormone therapy withdrawal may induce a significant regression in lesions.
authors.affiliation: Services d'Anatomie et Cytologie Pathologiques, AP-HP, Hôpital Saint-Antoine, F-75571 Paris Cedex 12, France. magali.svrcek@sat.aphp.fr
authors.forename: Magali
authors.initials: M
authors.lastname: Svrcek
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Jeannot
authors.forename: Lionel
authors.initials: L
authors.lastname: Arrivé
authors.forename: Raoul
authors.initials: R
authors.lastname: Poupon
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Fromont
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Fléjou
authors.forename: Jessica
authors.initials: J
authors.lastname: Zucman-Rossi
authors.forename: Philippe
authors.initials: P
authors.lastname: Bouchard
authors.forename: Dominique
authors.initials: D
authors.lastname: Wendum
mesh_terms: D018248:Adenoma, Liver Cell / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology; D003280:Contraceptives, Oral, Synthetic / Q000009:adverse effects*; D005260:Female; D005500:Follow-Up Studies; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000235:genetics*; D006801:Humans; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology; D008234:Lynestrenol / Q000009:adverse effects*; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D011944:Receptors, Androgen / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D013375:Substance Withdrawal Syndrome / Q000235:genetics / Q000473:pathology
chemical_list: D003280:Contraceptives, Oral, Synthetic; D051538:Hepatocyte Nuclear Factor 1-alpha; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D008234:Lynestrenol