Regressive liver adenomatosis following androgenic progestin therapy withdrawal: a case report with a 10-year follow-up and a molecular analysis.
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.
Svrcek
Magali
M
Services d'Anatomie et Cytologie Pathologiques, AP-HP, Hôpital Saint-Antoine, F-75571 Paris Cedex 12, France. magali.svrcek@sat.aphp.fr
Jeannot
Emmanuelle
E
Arrivé
Lionel
L
Poupon
Raoul
R
Fromont
Gaëlle
G
Fléjou
Jean-François
JF
Zucman-Rossi
Jessica
J
Bouchard
Philippe
P
Wendum
Dominique
D
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
D003280:Contraceptives, Oral, Synthetic; D051538:Hepatocyte Nuclear Factor 1-alpha; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D008234:Lynestrenol