Introduction

Endometriosis is a common, benign, estrogen-dependent, chronic gynecological disorder associated with pelvic pain and infertility. It is characterized by the presence of ectopic endometrial tissue [1]. Endometriosis is usually confined to the pelvis and reproductive organs. However, endometriotic lesions have also been described to occur in several remote sites, including the omentum, gastrointestinal tract, umbilicus, lungs, kidneys, pancreas and liver [2–6]. Hepatic endometriosis has an extremely rare occurrence characterized by the presence of ectopic endometrium in the liver. An extensive review of the literature showed that only 14 cases of hepatic endometriosis have been previously reported. We herein report the 15th case of intraparenchymal endometriosis of the liver in a postmenopausal female who presented with epigastric pain and vomiting. Making a preoperative diagnosis of hepatic endometriosis remains difficult, despite performing a complete investigation, due to the absence of specific clinical and radiological characteristics. A diagnosis of hepatic endometriosis is established after surgery.

Case report

A 51-year-old multiparous female was referred to our unit for investigation of a liver tumor. The patient reported a 6-month history of epigastric pain and vomiting. She had undergone conservative hysterectomy for uterine leiomyomas several years earlier. Her ovaries were normal and left in place. Laparotomic and histological examinations did not find any endometriotic lesions. The patient was not currently undergoing menopause. The symptoms were not related to menses.

A physical exam revealed epigastric pain without any palpable masses. There were no other symptoms. Serological tests for hepatitis B and C were negative. The results of liver function tests and the levels of tumor markers (CA 19.9, CEA, CA125, αFP) were normal. An abdominal ultrasound scan revealed the presence of an 80 × 75 mm intraparenchymal hepatic necrotic tumor, while Doppler did not show any intratumoral vascularization. A computed tomography scan (Fig. 1) showed one well-limited, hypovascularized, cystic mass in the left liver lobe extending to the diaphragm with left hepatic vein compression and hemorrhagic contents in the lumen. No septation was observed. Magnetic resonance imaging (Fig. 2) showed a cystic mass in segments II and III of the liver with a high T1 signal and a heterogeneous T2 signal. Biopsies revealed necrotic tissue without malignant cells. The preoperative diagnosis included liver cystadenoma, liver cystadenocarcinoma or cystic metastasis of the liver.

Fig. 1
figure 1

Hepatic CT scan showing a cystic mass, hypovascularized, in the left liver lobe with a left hepatic vein compression, extending to the diaphragm

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Fig. 2
figure 2

Magnetic Resonance Magnetic (MRI) showing a cystic mass in segments II and III of the liver with hemorrhagic contents in the lumen

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A laparotomy was performed, which revealed a large cystic tumor in segments II and III with diaphragmatic infiltration. An abdominal cavity exploration revealed no other pathologic events. The intraoperative frozen sections suggested a diagnosis of endometriosis. Anatomical resection was performed, including left lobectomy with diaphragm resection. The patient’s postoperative course was uneventful. After 6 months of follow-up, the patient was asymptomatic.

Macroscopy revealed a unilocular, encapsulated, cystic mass measuring 8 × 4.5 × 4 cm with an irregular border and hemorrhagic contents (Fig. 3).

Fig. 3
figure 3

Macroscopic examination of the liver tumor: under the liver capsule was observed an 8 × 4 × 4.5 cm cystic mass with an hemorrhagic content and an irregular fibrous capsule

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On microscopic examination, we observed a thick fibrous capsule with residual hepatocytes and a ductular reaction. A cystic component was observed lined by cylindrical epithelium without atypia. The hemorrhagic-like contents corresponded to endometrial tissue with irregularly dispersed, occasionally cystic endometrial glands with characteristic endometrial stroma immunostained with CD10 (Fig. 4). The stromal and epithelial cells expressed estrogen and progesterone receptors. The epithelial cells were positive for CK7 and negative for CK20. No epithelial hyperplasia, atypia or invasive carcinoma was observed in the numerous examined tumor samples. The upper part of the capsule was adherent to the diaphragm.

Fig. 4
figure 4

Microscopic examination of the endometriosis cyst of the liver: at microscopic examination, we observe a fibrous capsule (a, arrows) with a ductular reaction, residual hepatocytes (b) and minimal lymphocyte infiltration. The solid hemorrhagic content of the cyst corresponded to endometrial tissue with irregularly dispersed endometrial glands (c) and characteristic stroma positive for CD10 immunostaining (d). Moreover, endometrial and stromal cells expressed both estrogen receptors (e) and progestative receptors (f). No hyperplasia no atypia was observed in epithelial or stromal component

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We concluded the diagnosis to be hepatic endometrioma without malignant transformation.

Discussion

Endometriosis is an estrogen-dependent disease that affects 5–10 % females of reproductive age in the United States [1]. Its defining feature is the presence of ectopic endometrial tissue. The histological features include the presence of endometrial glands and stroma with frequent inflammatory reactions and intramacrophagic iron deposits [7].

Endometriosis has been reported to be more likely to occur in the pelvic organs (ovaries, fallopian tubes, uterosacral ligaments, Pouch of Douglas). The gold standard for diagnosing pelvic disease is surgical assessment, and a scoring system has been developed to assess the extent of disease. Endometriosis has been described as occurring in every part of the body (heart, lungs, kidneys, gastrointestinal tract, diaphragm, legs, bones, incisional scars, umbilicus, liver), [8, 9] except the spleen [3]. The first case of intraparenchymal endometriosis of the liver was reported by Finkel [10].

The pathogenesis of endometriosis remains unknown. Different theories have been proposed, including retrograde menstruation, coelomic metaplasia, altered cellular immunity, metastasis, a genetic basis, an environmental basis, and a multifactorial mode of inheritance with interactions between specific genes and the environment [11, 12]. Retrograde menstruation causing transcoelomic spread and consequent invasion within the pelvis could explain most observed lesions, especially those in the pelvis. However, this theory cannot explain distant or intraparenchymal liver lesions. Therefore, another theory has been raised involving venous and lymphatic dissemination of endometrial tissue to distant sites of implantation and the formation of intraparenchymal lesions. A third theory implicates iatrogenic injury after pelvic surgery for endometriosis followed by secondary dissemination [13–15]. A fourth theory, that of coelomic metaplasia, suggests that endometriosis develops from secondary Müllerian systems that result from metaplasia of the embryologic coelomic epithelium [16, 17].

The increased cell survival, inflammation and deficient differentiation that occur in endometriosis have been linked to a stromal cell defect involving excessive formation of estrogen and prostaglandin in addition to progesterone resistance, all of which originate from two distinct epigenetic changes that affect the transcription factor SF1 and estrogen receptor β [6]. A working model is clinically relevant because targeting aromatase, COX-2, estrogen receptor β and progesterone receptors reduces pelvic pain and ablates visible endometriotic tissue [7, 18]. Serdar et al. [7] speculate that a genetic predisposition or exposure to environmental toxins by fetal progenitor cells destined to form adult female pelvic organs may result in epigenetic events, including promoter hypomethylation and the overexpression of SF1 and estrogen receptor β, which can play critical roles in the pathogenesis of endometriosis.

The first case of intraparenchymal endometriosis of the liver was reported by Finkel [10]. The patient was a 21-year-old female who complained of epigastric pain, nausea and vomiting. She was found to have an endometrial cyst measuring 13 cm in the left lobe of the liver. Since then, 13 cases have been described in the medical literature. We herein report the 15th case. In our case, the patient did not had a past of endometriosis; however, she had undergone hysterectomy for uterine leiomyomas several years previously and presented with a cystic mass measuring 8 cm in the left lobe of the liver. In this context, the most probable pathogenesis of endometriosis is a multifactorial mode of inheritance with interactions between specific genes and the environment with diffusion of endometrial cells. All cases of hepatic endometrioma are listed in Table 1. An analysis of this series reveals that hepatic endometriomas present with symptoms (93.33 %) corresponding to a cystic mass in all patients (100 %), unclear (86.67 %), measuring more than 5 cm (93.33 %) or more than 10 cm (53.33 %), often localized in the left lobe of the liver (53.33 %).

Table 1 Feature of reported cases of hepatic endometriosis in literature
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Consequently, we propose the following description of hepatic endometrioma: a symptomatic tumor occurring in young females that is a voluminous, cystic mass of the liver that must be considered in the differential diagnosis of cystic liver masses, particularly in patients with known endometriosis.

Hepatic endometrioma is an extremely rare lesion. Making a preoperative diagnosis of hepatic endometriosis is very difficult, despite conducting a complete investigation, in the absence of clinical and radiological characteristics. A diagnosis of hepatic endometriosis is established after surgery. The diagnosis is made according to a histological examination of the whole surgical sample.

This is the 15th case of hepatic endometrioma reported in the literature. The pathogenesis of the disease is unclear and requires elucidation with further clinical and experimental investigations. The clinical, biological and morphological characteristics of the disease need to be reported in the literature to allow for the creation of a better diagnostic approach. We propose the systematic use of intraoperative frozen sections to avoid radical hepatectomy in order to decrease morbidity and mortality.

A diagnosis of endometriosis must be considered in the differential diagnosis of cystic liver masses, particularly in patients with known endometriosis.