Inflammatory hepatocellular adenoma in a patient with Turner’s syndrome: A case report

Highlights • Contraceptive pill induced hepatocellular adenoma with Turner’s syndrome patient is extremely rare.• However Turner’s syndrome patient requires a lifetime hormone replacement therapy.• Proper diagnosis and treatment plan is necessary for hepatocellular adenoma.

* with reduced height and gonadal dysgenesis; thus, patients with TS require a hormone replacement therapy (HRT), including a contraceptive pill, to support growth and maintain QOL [4,5]. To date, there is only one report of a patient with TS who developed HCA [1]. Here we report an extremely rare case of contraceptive pillinduced HCA with TS. The work in this case has been reported in line with the SCARE criteria [6].

Case presentation
The patient was a 36-year-old woman with Turner's syndrome (TS) diagnosed at 9 years of age. She received an oral contraceptive pill as a hormone replacement therapy (HRT) from the age of 16 years. She was referred to our department in July 2017 after presenting at a local hospital with fatigue and liver tumors detected on computed tomography (CT).
Her physical examination and blood tests showed no remarkable findings. Abdominal ultrasonography showed a low echoic tumor, which was 60 mm in diameter, in the posterior section of   the liver and an isoechoic tumor, which was 6 mm in diameter, at the root of the right hepatic vein (RHV; Fig. 1).
CT showed a 60-mm tumor in the posterior section of the liver. This tumor showed high density in the arterial phase and isodensity in the portal and late phases. Another small 10-mm tumor at the root of RHV also showed high density in the arterial phase and isodensity in the portal and late phases (Fig. 2).
Gadoxetic acid ethoxybenzyl magnetic resonance imaging (Gb-EOB-MRI) of the large tumor showed high intensity on T2-weighted images and in the arterial and portal phases, and low intensity in the late and hepatobiliary phases, while the small tumor showed low intensity in the hepatobiliary phase (Fig. 3).
Based on the diagnosis of multiple HCAs or hepatocellular carcinomas (HCCs), segmentectomy of No 7 of the liver was performed. The operation time was 178 min, and blood loss was 681 mL.
Macroscopic findings showed a whitish and brownish tumor, which was 61 mm in diameter and without capsula and another small, whitish, 11-mm tumor without capsula. Pathological findings of the larger tumor showed hepatocytes without atypia, with sinusoid dilatation and a single vessel seen within the tumor. This tumor was diagnosed as HCA. Immunohistochemistry findings of the larger tumor showed that the hepatocytes were positive for C-reactive protein (CRP) and liver fatty acid-binding protein (LFABP) and negative for ␤-catenin, glutamine synthetase (GS), and glypican-3 (Fig. 4). The small tumor showed same pathological and immunohistochemistry findings; therefore, both the tumors were diagnosed as inflammatory HCA (IHCA).
The patient was discharged on postoperative day 14. At the 13month postoperative follow-up, she was doing well and there was no evidence of recurrence of HCA without the pill.

Discussion
TS requires various HRTs, with the contraceptive pill often administered [4,5], which is associated with the very rare benign liver tumor HCA [2,3]. The incidence rates of HCA with the longterm use of oral contraceptive pills are approximately 3-4 per 100,000 individuals [7]. There is only one report of HCA in patients with TS [1]; we reported a case of multiple HCAs in a patient with TS.
Patients with TS experience various complications [4], commonly including abnormal liver function [11,12], congenital portal vein deficiency, focal nodular hyperplasia (FNH), nodular regenerative hyperplasia (NRH), and HCC [13][14][15]. However, imaging and pathological findings for FNH, NRH, HCA, and HCC are similar, which can result in difficulties in the differential diagnosis. Therefore, the risk of not only benign liver tumors (FNH, NRH, and HCA) but also HCC should be considered in TS.
Indication of treatment for HCA has been reported [16][17][18]. When the tumor size is <5 cm in diameter, follow-up is recommended after discontinuing the medication, including the pill. When the tumor size is ≥5 cm, hepatectomy is recommended because HCAs pose a risk of rupture and can transform into HCC [16,18,19]. In the present case, hepatectomy was performed because there were multiple tumors, and the largest tumor measured 6 cm. The contraceptive pill as a female HRT was discontinued postoperatively to prevent the recurrence of HCA.

Conclusion
We experienced a case of multiple inflammatory HCAs in TS that were related to the long-term use of a contraceptive pill. There-fore, careful attention is required for HCA in patients with TS taking contraceptive pills as a long-term female HRT.

Conflicts of interest
No conflict of interest.

Sources of funding
No funding.

Ethical approval
This case report is exempt from ethical approval by our institution.

Consent
Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in -Chief of this journal on request.

Author contribution
Satoshi Nemoto: treated and helped operation, collected the data, and drafted the manuscript.
Shun-ichi Ariizumi: conducted the examinations on this patient as well as treated and operated, drafted the manuscript, pathological examination and contributed to the diagnosis of this patient.
Hiroto Egawa: conducted the manuscript. Masakazu Yamamoto: conducted the manuscript and operate the patient.
All authors read and approved the final manuscript.

Registration of research studies
No registration of research studies.

Guarantor
On behalf of all author, Yamamoto Masakazu M.D. is guarantor for this paper.

Provenance and peer review
Not commissioned, externally peer-reviewed.