Primary Hepatic Leiomyosarcoma : a Case Report and Review of the Literature

A B S T R AC T Background/Aim: Primary hepatic leiomyosarcoma is an extremely rare type of liver sarcoma with relatively poor prognosis, with about 50 cases having been reported in the literature. Potential origins of this tumor in the liver are the smooth muscle cells in the round ligament, intrahepatic blood vessels and intrahepatic bile ducts. There is no apparent sex predilection and there is a wide age range. The clinical presentation is not specific and the diagnosis depends on the expression of markers such as smooth muscle actin, desmin and vimentin by tumor cells. Patients and Methods: Herein, we present a case of a bulky primary hepatic leiomyosarcoma in a 68-year-old female patient. The patient underwent resection of the exophytic mass en block with the hepatic segments III and IVB. Conclusion: Surgical resection is the most effective among the treatment options.


INTRODUCTION
Primary hepatic sarcomas are rare tumors including various types, such as angiosarcoma, fibrosarcoma, liposarcoma, embryonal sarcoma, malignant fibrous histiocytoma, carcinosarcoma and epithelioid hemangioendothelioma (1).Primary hepatic leiomyosarcoma is another extremely rare type of liver sarcoma with relatively poor prognosis, with about 50 cases having been reported in the literature.Herein, we report a case of a bulky primary hepatic leiomyosarcoma in a 68-year-old female patient.

CASE REPORT
A 68-year-old female patient was referred to our department in order to treat a bulky liver tumor.The patient has been complaining for right upper quadrant heaviness and discomfort for 1 year.She underwent an abdominal ultrasound scan which revealed the presence of a hepatic mass located in the left lobe of the liver.Subsequently, she underwent an abdominal and thoracic computed tomography and an abdominal magnetic resonance tomography that confirmed the presence of a bulky, exophytic and heterogeneously attenuated mass with irregular margins, originating from the hepatic segments III and IVB (Figure 1).The tumor was 13 cm in diameter.The imaging studies excluded the presence of other primary sites.The patient had a medical history of chronic hepatitis B, type 2 diabetes mellitus and cholelithiasis.The patient's complete blood count test, biochemical tests and levels of carcinoembryonic antigen, alpha fetoprotein and cancer antigen 19-9 were within normal range.
The patient underwent resection of the exophytic mass en block with the hepatic segments III and IVB, from which the tumor appeared to be originated, along with cholecystectomy (Figure 2).The postoperative course was uneventful and the patient was discharged on the 7th postoperative day.The histopathological examination showed the presence of a whitish tumor, 13 cm in diameter, with central cystic degeneration.The tumor was extended up to Glisson's capsule and up to 2 mm from the resection margins.The neoplasm was a sarcoma made of large, atypical cells with abundant cytoplasm that occasionally were multinucleated (Figure 3A).The tumor included regions of spindle-shaped cells with fascicular arrangement and foci of osteoid production (Figure 3B).Extensive regions of necrosis were also present.No intracellular globules or entrapped bile ducts were detected.The neoplasm encased small blood vessels without infiltrating them.The mitotic count was 10 mitoses per 10 high-power fields (HPF).Furthermore, the immunohistochemical examination of the sarcoma revealed extensive expression of smooth muscle actin (Figure 3C) and limited expression of desmin (Figure 3D), but did not detect any expression of myoD1, myogenin, S-100 protein, c-kit or cytokeratines 7, 8, 18, 19 and 20, excluding diagnoses such as rhabdomyosarcoma, melanoma, gastrointestinal stromal tumor (GIST), carcinoma, etc.Therefore, a diagnosis of primary pleomorphic hepatic leiomyosarcoma was established.
The patient received six cycles of chemotherapy postoperatively with cyclophosphamide, doxorubicin and vincristine.Due to the presence of advanced tumor, she also received pazopanib, a multi-targeted receptor tyrosine kinase inhibitor, per os, which has been added as a treatment option for the  advanced, metastatic and/or unresectable sarcomas, apart from liposarcomas (2, 3).An abdominal magnetic resonance tomography 18 months after the operation revealed four sites of recurrence, one between the liver and the first portion of duodenum, 5.5 cm in diameter, other two at the front of pylorus, 3 cm and 2.2 cm in diameter, and another one at the front of the body of stomach, 2.1 cm in diameter (Figure 4).The recurrent tumors were removed surgically, the postoperative course was uneventful and the patient was discharged from the hospital on the 7th postoperative day.She continued the per os treatment with pazopanib.
However, 3 months after the second operation, the patient presented melenas.An upper gastrointestinal endoscopy showed infiltration of the anterior wall of the first portion of duodenum by an ulcerated neoplasm.An abdominal computed tomography revealed three new sites of recurrence: one between the liver, the portal vein and the second portion of duodenum; another in contact with the anterior wall of the stomach and the first portion of duodenum, 5.5 cm in diameter; and another arising from the mesocolon and reaching the abdominal wall (Figure 5).The patient received conservative treatment and continued the per os treatment with pazopanib.There was gradual progression of the disease and the patient died 37 months after the initial diagnosis from acute upper gastrointestinal bleeding due to infiltration of the duodenum by the tumor.
The underlying pathogenetic mechanisms have not been identified yet.However, there are some cases of primary hepatic leiomyosarcoma in immunosuppressed patients, two of whom had acquired immunodeficiency syndrome (32,33).One of the patients with acquired immunodeficiency syndrome also had infection from Epstein-Barr virus (32).Another patient with primary hepatic leiomyosarcoma was under immunosuppressive treatment after renal transplantation (21).Furthermore, there are two cases of primary hepatic leiomyosarcoma in patients with chronic hepatitis, one with hepatitis C ( 19) and the other is our patient, who had hepatitis B.
In conclusion, primary hepatic leiomyosarcoma is a rare malignant disease with relatively poor prognosis.The most preferred type of treatment is surgical excision, which sometimes is combined with adjuvant chemotherapy and/or radiotherapy.However, very little is known about the effectiveness of the current treatment because of the rarity of the disease.More in-depth studies are needed to investigate and shed light on this uncommon clinical entity.

Fig. 1 Fig. 2
Fig. 1 Abdominal magnetic resonance imaging.The white arrow shows the liver tumor.

Fig. 4
Fig. 4 Abdominal magnetic resonance imaging.The white arrow shows one site of recurrence.

Fig. 5
Fig. 5 Abdominal computed tomography.The white arrow shows one site of new recurrence.