Supplemental Table (online). Full clinical characteristics of cases of hepatic adenoma with malignant transformation in the current literature

Study (Author/year) / No. of patients with malignant change in HA / Gender / Age / OCP/Hormone therapy / Symptomatic / Solitary or multiple / Size (cm) / Treatment / Interval between diagnosis of adenoma and carcinoma / Notes
Case reports
Davis et al, 1975 69 / 1 / F / 21 / Yes / No/Anemia / Solitary / 14 cm / Liver resection / - / Features of FNH, Well differentiated HCC in adenoma
Pryor et al, 1977 70 / 1 / F / 32 / Yes / Yes / 30 cm / Irresectable / - / Well differentiated HCC, Normal AFP
Tesluk and Lawrie, 1981 71 / 1 / F / 34 / Yes / Yes / Solitary / 16 cm / Liver resection / 3 years
Gordon et al, 1986 72 / 1 / F / 36 / Yes / Solitary / 13 cm / Liver resection / 7 years / Normal AFP
Gyorffy et al, 1989 73 / 1 / F / 53 / Yes / Yes / Multiple (3) / 12 cm / Irresectable / 2 years
Korula et al, 199174 / 1 / F / 40 / Yes / Yes / Solitary / 6.5 cm / Liver resection / Unknown / Well-differentiated HCC in adenoma, normal AFP
Ferrell, 1993 75 / 1 / F / 29 / Yes / Yes / Solitary / - / - / - / Well differentiated HCC in multilobular adenoma
Janes et al, 1993 76 / 1 / F / 22 / Yes / Yes / Solitary / 13 cm / Transplant / 19 years / High AFP
Perret et al, 1996 77 / 1 / F / 24 / Yes / Yes / Solitary / 14 cm / Liver resection / - / HCC in multilobular adenoma, normal AFP
Ye et al, 1999 78 / 1 / F / Yes / Yes / Multiple (2) / - / - / - / One lesion was well differentiated HCC and the other HA, normal AFP
Burri et al, 2006 79 / 1 / F / 40 / Yes / Yes / Solitary / 6 cm / Liver resection / - / Normal AFP
Colovic, 2007 80 / 1 / F / 70 / No / No / Solitary / 11.5 mm / Liver resection / Eldest patient reported
Kim et al, 2009 81 / 1/1 / M / 53 / No / Yes / Single / 6cm / Liver resection / - / -
Toiyama et al, 2011 82 / 1/1 / M / 28 / No / Yes / Single / 5.5cm / Liver resection / - / FAP patient; HA showed HNF1α inactivation
Hechtman et al, 2011 83 / 1/1 / M / 53 / No / No / Single / 16 cm / Liver resection / - / Telangiectatic HA with β-catenin and glutamine synthase positivity; normal AFP
Single centre series
Lack et al, 1983 84 / 2 / 1M:1F / 11, 15 / No / Yes / Solitary / Liver resection in one patient; the other treated with radiotherapy and chemotherapy / 8 ½ years in one patient; the other patient has coexisting HA and HCC at the time of diagnosis
Kerlin et al, 198385 / 2/23 / - / - / - / - / Solitary / Liver resection / -
Leese et al, 1988 86 / 1/24 (4%) / M / 13 / No / Multiple (>50) / Transplant / 5 years / Acute rise in AFP
Belghiti et al, 1993 87 / 1/12 / F / <50 / Yes / Yes / Multiple / Liver resection / Well-differentiated HCC in adenoma
Herman et al, 1994 88 / 2 / 2F / 30, 37 / Yes / Solitary / - / Liver resection / -
Foster and Berman, 1994 89 / 1/13 (13%) / F / 56 / Yes / Yes / Multiple (3-4) / 8 cm / Irresectable / 5 years
Nagorney, 1995 90 / 2/24 / - / - / - / - / - / - / Liver resection / -
Ault et al, 1996 91 / 3/12 / - / - / - / - / - / 5.5cm -13 cm / Liver resection / - / 2 of 3 patients have high AFP
De Carlis et al, 1997 92 / 2/19 / - / - / - / - / - / Liver resection / -
Weimann et al, 1997 93 / 3/44 / - / - / - / - / Solitary: 2
Multiple:1 (GSDI patient) / - / Liver resection: 3
Liver resection followed by transplantation: 1 (GSDI patient) / - / Well-differentiated HCC in adenoma
Closset et al, 2000 94 / 1/16 / - / - / - / - / - / - / Liver resection
Ichikawa et al, 2000 95 / 2/25 / - / - / - / - / - / - / - / 7 years (1 patient) / 1 of 2 patients have high AFP
Reddy et al, 2001 96 / 1/25 / F / Mean: 33 / - / - / - / - / Liver resection / -
Chamy et al, 2001 97 / 1/12 / - / Mean: 34 / - / - / - / - / Liver resection / -
Marini et al, 2002 98 / 1/7 / - / Mean: 37 (23-52) / - / Yes (Rupture) / - / Mean 16 (6-30) cm / Well-differentiated HCC in adenoma
Van der Borght et al, 2007 37 / 8/33 / 29F / 37 / 17/30 / Unknown / 7.4cm (8-18 cm) / Liver resection / Resection series
Bioulac-Sage et al, 2007 34 / 6/98 / 4F/2M / 32-66 / 3/6 / Unknown / 4 Solitary /2 Multifocal / 6-18 cm / Liver resection / All had β-catenin activation
Micchelli et al, 2008 21 / 3/17 (17%) / 17F / 23-33 / 3/3 / Unknown / 4-9.5cm
Dokmak et al, 2009 99 / 10/122 (8%) / - / - / - / - / - / >8 cm / Liver resection / - / β catenin activation only present in 2/10 cases with malignant change
Farges et al, 2011 24 / 23/218 (10.5%) / 16M:7F / 20-75 / 4/7 F (OC)
3/16 M (androgens/steroids) / - / 3 Multifocal /
20 Solitary / 3-19cm / Liver resection / - / 2/3 of HAs with malignant transformation showed β catenin activation. Two malignant patterns were observed; either as macroscopic nodule >1cm or randomly distributed microscopic foci
Sasaki et al, 2011 100 / 1/14 / - / - / - / - / - / - / - / - / 1 case of HCC in inflammatory subtype of HA
Bellamy et al, 2013 101 / 4/64 / 3F: 1M / 25-72 / - / - / All Solitary / 2.2 - 18.4 cm / Liver resection / 1/4 of HAs with malignant change has β catenin activation
Fonseca et al, 2013 102 / 2/37 / 2M / - / - / - / - / - / Liver resection / - / β catenin activation present in both cases
Multicentre case series
Zucman-Rossi et al, 2006 20 / 5/96 / - / - / - / - / - / - / - / - / Pathological study; 46% of β catenin activated HA showed malignant change
Deneve et al, 2009 31 / 5/124 (4%) / 4F: 1M / 35 ±12 / 4/5 / 1/5 (rupture) / 4/5 Solitary 1/5 Multifocal / 11.6 ± 4 / Liver resection / - / Smallest lesion with malignancy is 8cm. No recurrence at median FU of 36 months

(-) indicates data unavailable/unknown