A 35-Year-Old Woman with Progesterone Implant Contraception and Multiple Liver Masses

A 35-year-old woman presented to an outside hospital in January 2000 with epigastric and right upper quadrant abdominal pain that radiated to the right shoulder. There was no history of antecedent trauma. By physical examination, the abdomen was tender but nondistended. There were no stigmata of chronic liver disease. Past medical history was significant for occasional use of alcohol and estrogen-based oral contraception from 1978 to 1981. The patient had four children, ages 7 to 15 years. No medical contraceptive was used from 1981 until 1998, when a subcutaneous levonorgestrel implant (Norplant) was placed in her arm.

Laboratory values were as follows: hemoglobin 13.7 g/dL, alanine aminotransferase (ALT) 114 U/L, aspartate aminotransferase (AST) 107 U/L, and albumin 4.4 g/dL. Computed tomography (CT) of the liver with intravenous contrast was significant for a 16-cm subcapsular hematoma in the right lobe of the liver, and multiple focal lesions in both lobes ranging from a few millimeters to 5 cm. These latter lesions did not demonstrate increased blood pool activity on delayed images and were interpreted as most consistent with metastases. CT of the thoracic cavity showed a large right pleural effusion and compressive atelectasis of the right lung. There was no clinical intervention at this time.

Three months later, the patient was referred to St. Louis University Hospital for further evaluation. Results of the physical examination were unchanged. Pertinent laboratory values at this time were as follows: hemoglobin 14.2 g/dL, albumin 3.2 g/dL, prothrombin time 15 seconds (12.6-15), ALT 21 U/L, AST 19 U/L, alkaline phosphatase 84 U/L, and total bilirubin 0.6 mg/dL. Serum tumor markers were negative, including carcinoembryonic antigen 1.3 ng/mL (0-3), CA-125 23 U/mL (0-35), α-fetoprotein 1 ng/mL (0-5), and CA 19-9 11 U/mL (0-37).

A repeat CT of the liver with oral and intravenous contrast confirmed multiple hyperdense lesions with rapid washout of the contrast material (Fig. [1]). These findings were interpreted as unlikely to represent metastatic disease and more consistent with hepatic adenomas. Because of the concern of rebleeding and possible capsular rupture, the patient underwent resection of the hematoma and two of the larger subcapsular lesions. During surgery, gross observations of lesions in segments V-VIII resulted in a partial resection of the right lobe of the liver.

REFERENCES

• 1 Gokhale R, Whitington P F. Hepatic adenomatosis in an adolescent.  J Pediatr Gastroenterol Nutr . 1996;  23 482-486
• 2 Lui A FK, Hiratzka L F, Hirose F M. Multiple adenomas of the liver.  Cancer . 1980;  45 1001-1004
• 3 Ribeiro A, Burgart L J, Nagorney D M. Management of liver adenomatosis: results with a conservative surgical approach.  Liver Transplant Surg . 1998;  4 388-398
• 4 Chiche L, Dao T, Salame E. Liver adenomatosis: reappraisal, diagnosis, and surgical management.  Ann Surg . 2000;  231 74-81
• 5 Flejou J F, Barge J, Menu Y. Liver adenomatosis. An entity distinct from liver adenoma?.  Gastroenterology . 1985;  89 1132-1138
• 6 Howell R R, Stevenson R E, Ben-Menachem Y. Hepatic adenomata with type 1 glycogen storage disease.  JAMA . 1976;  236 1481-1484
• 7 Sale G E, Lerner K G. Multiple tumors after androgen therapy.  Arch Pathol Lab Med . 1977;  101 600-603
• 8 Boyd P R, Mark G J. Multiple hepatic adenomas and a hepatocellular carcinoma in a man on oral methyl testosterone for eleven years.  Cancer . 1977;  40 1765-1770
• 9 Leese T, Farges O, Bismuth H. Liver cell adenomas. A 12-year surgical experience from a specialist hepato-biliary unit.  Ann Surg . 1988;  208 558-664
• 10 Arsenault T M, Johnson C D, Gorman B. Hepatic adenomatosis.  Mayo Clin Proc . 1996;  71 478-480
• 11 Kalra P A, Guthrie J A, Dibble J B. Hepatic adenomas induced by norethisterone in patients receiving renal dialysis.  BMJ . 1987;  294 808
• 12 Porter L E, Elm M S, Van Thiel H D. Hepatic estrogen receptor in human liver disease.  Gastroenterology . 1987;  92 735-745
• 13 Choi B I, Han J K, Kim S H. MR findings in liver adenomatosis.  Gastrointest Radiol . 1991;  16 234-236
• 14 Khan S S, Fink M, King S. Liver adenomatosis presenting as multiple calcified masses.  Clin Radiol . 1992;  45 206-207
• 15 Lee R G. Diagnostic Liver Pathology.  St. Louis: Mosby-Year Book; 1994
• 16 Le Bail B, Jouhanole H, Deugnier Y. Liver adenomatosis with granulomas in two patients on long-term oral contraceptives.  Am J Surg Pathol . 1992;  16 982-987
• 17 Foster J H, Berman M M. The malignant transformation of liver cell adenomas.  Arch Surg . 1994;  129 712-717
• 18 International Working Party. Terminology of nodular hepatocellular lesions.  Hepatology . 1995;  22 983-993
• 19 Fina L, Molgaard H V, Robertson D. Expression of the CD34 gene in vascular endothelial cells.  Blood . 1990;  75 2417-2426
• 20 Park Y N, Yang C P, Fernandez G J. Neoangiogenesis and sinusoidal ``capillarization'' in dysplastic nodules of the liver.  Am J Surg Pathol . 1998;  22 656-662
• 21 Cordes B G, Brown K E, Brunt E M. Zonal localization of alpha-smooth muscle actin and CD34 immunoreactivity in chronic cholestatic liver disease.  Mod Pathol . 2000;  13 182[Abst]
• 22 Brunt E M, Fazel A, Brown K E. Lack of zonal association between α-smooth muscle actin (SMA), CD34 and fibrosis in a variety of liver diseases.  Hepatology . 1999;  30 554[Abst]
• 23 Propst A, Propst T, Waldenberger P. A case of hepatocellular adenomatosis with a follow-up of 11 years.  Am J Gastroenterol . 1995;  90 1345-1346