Case of primary hepatic leiomyosarcoma successfully treated with laparoscopic right hepatectomy

Abstract

We describe the case of a 77-year-old woman, presenting with non-specific epigastric pain. Physical examination and subsequent imaging revealed the presence of a large mass in the right liver lobe. This was shown to be a leiomyosarcoma on biopsy histology. Further investigation confirmed this to be a primary hepatic leiomyosarcoma with no evidence of metastases. The patient underwent successful surgical resection. She is currently under imaging follow-up, with no evidence of disease recurrence.

Background

Primary hepatic leiomyosarcomas are very rare tumours, with only about 70 cases reported in the literature. They usually confer a poor prognosis in view of being locally advanced at the time of diagnosis. Guidelines with regard to management of these tumours have yet to be established and large cohort studies are necessary to allow better understanding of disease behaviour and appropriate treatment.

Case presentation

We describe the case of a 77-year-old woman who was referred to a gastroenterology outpatient clinic with an approximate 4-year history of vague, intermittent epigastric pain, predominantly postprandially. She denied any loss of appetite, jaundice, weight loss or change in bowel habit. Her history was notable only for hypertension on treatment and cholecystectomy. She was a non-smoker and had no history of alcohol abuse. There was no family history of malignancy. On physical examination, the patient was noted to have a non-tender mass in the right upper quadrant. The examination was otherwise unremarkable.

Investigations

The patient’s serological profile revealed a mild increase in alkaline phosphatase but a complete blood count, serum electrolytes, hepatitis and HIV screen, as well as α-fetoprotein and carcinoembryonic antigen were normal. Computed tomography (CT) of the abdomen showed a partially solid/partially cystic large mass measuring 19.8×16.8×14.9 cm occupying most of the right liver lobe (figure 1). This mass was causing extrinsic compression of the biliary confluence, with mild dilatation of the left hepatic duct. Bland thrombosis of the right hepatic vein was also noted. The portal vein and superior mesenteric vein were patent. Ultrasound-guided biopsy revealed a malignant neoplasm composed of neoplastic spindle cells showing focally marked nuclear atypia and moderately brisk mitotic activity (at 5 mitotic figures/10 high-power field), organised in fascicles and whorls. The neoplastic cells strongly and diffusely expressed desmin and smooth muscle actin (SMA) and focally expressed epithelial membrane antigen (EMA). No expression of S100 protein, CD31, CD34, BRCK, MNF116, Melan-A or HMB45 was seen. The Ki-67 index was approximately 70%. The histological and immunohistochemical findings were in keeping with a leiomyosarcoma.

Figure 1.

Coronal (A) and axial (B) portovenous phase CT images of the abdomen demonstrate a partially solid/partially cystic large mass measuring 19.8×16.8×14.9 cm occupying most of the right liver lobe.

Differential diagnosis

Given the rarity of primary hepatic leiomyosarcoma, the possibility of metastasis from a distant primary tumour was entertained, for which reason positron emission tomography (PET)-CT was carried out (figure 2). This demonstrated a sizeable focus of uptake within the hepatic tumour, occupying most of the right liver lobe, with large central photopaenic areas in keeping with tumour necrosis. Notably there was no evidence of abnormal accumulation of radiolabelled glucose in the rest of the imaged body segments, confirming the tumour as a primary hepatic leiomyosarcoma.

Figure 2.

Fluorodeoxyglucose (FDG)-PET/CT scan demonstrating a sizeable focus of intense accumulation of radiolabelled glucose corresponding to the known hepatic leiomyosarcoma occupying most of the right liver lobe. Large central photopaenic areas within are in keeping with tumour necrosis.

Treatment

Considering the patient’s good performance status, she was planned for surgical resection. Magnetic resonance imaging (MRI) of the liver was performed to exclude satellite lesions and macrovascular invasion. This confirmed the presence of high-grade necrosis within the leiomyosarcoma, and evidence of previous bleeding with T2 hypointense areas in the central portion of the lesion (figures 3 and 4). The volume of the future liver remnant (in this case the left liver lobe) was calculated to be satisfactory, at 81% of the total estimated liver volume.¹ The patient underwent a laparoscopic right hepatectomy in a tertiary centre with resection of the lower root of the middle hepatic vein. Postoperative recovery was excellent.

Figure 3.

Fat-suppressed T1-weighted MR images at two levels in the upper abdomen, acquired in the precontrast (A), arterial (B) and portovenous (C) phases. Note is made of high-grade necrosis within the lesion together with peripheral enhancement. No satellite lesions are demonstrated.

Figure 4.

Coronal (A) and corresponding axial (B) T1-weighted MR images in the hepatobiliary phase demonstrating peripheral enhancement. Axial T2-weighted image (C) demonstrates areas of central hypointensity corresponding to previous bleeding. Diffusion-weighted imaging, b=50 (D) and b=800 (E) shows restricted diffusion.

Outcome and follow-up

Histopathological examination of the liver showed a 22×18×13 cm mass, weighing 2370 g, which was histologically confirmed as a leiomyosarcoma (figure 5), featuring myxoid areas and areas of regression. The background liver parenchyma showed mild periportal fibrosis and some glycogenated nuclei, with mild macrovesicular steatosis (<5%). No iron deposits were identified. The resection margin was free from neoplasia.

Figure 5.

Representative histology images; H&E ×20 (A) and smooth muscle marker desmin ×10 (B) demonstrating neoplastic, variably atypical spindled smooth muscle cells with cigar-shaped nuclei, organised in whorls and fascicles. Immunohistochemical staining for desmin is positive.

The patient is being followed up at outpatients and is well. Surveillance MRI done 8 months following surgery revealed no evidence of disease recurrence (figure 6).

Figure 6.

Coronal T2-weighted representative image from the surveillance MRI done 8 months following surgery, which showed no evidence of disease recurrence.

Discussion

Primary hepatic mesenchymal tumours are known to be rare. Hepatic sarcomas contribute to approximately 1%–2% of primary liver malignancies, with leiomyosarcomas accounting for only 8%–10% of all hepatic sarcomas, the remainder consisting of angiosarcomas, fibrosarcomas, epithelioid haemangioendotheliomas and undifferentiated embryonal sarcomas. Leiomyosarcoma of the liver has been shown to originate from smooth muscle cells in the vasculature, bile ducts or the ligamentum teres.^2–4

Review of the literature reveals only about 76 cases of primary hepatic leiomyosarcoma reported.^3–63 As in our case, an important prerequisite to its diagnosis is to exclude the possibility of an extrahepatic source of metastasis, with primary tumours being typically identified in the gastrointestinal tract, uterus or retroperitoneum.^64–67

The histological findings of these tumours conform to those of leiomyosarcomas at other sites, typically featuring neoplastic, variably atypical spindled smooth muscle cells with cigar-shaped nuclei, organised in whorls and fascicles. Immunohistochemical staining for the smooth muscle markers actin, desmin and SMA is typically observed and is essential for diagnosis.⁵

Interestingly many of these tumours occur in immunocompromised individuals, such as post-transplantation and AIDS patients. This is postulated to be secondary to the effect of the uninhibited Epstein-Barr virus (EBV) on smooth muscle proliferation.^{6 7} Our patient was immunocompetent and histology of the resected specimen was not reactive to EBV-encoded RNA.

Diagnosis of these tumours is challenging in view of the non-specific nature of their presentation and the absence of significant serological abnormalities, as in our case. Symptoms may include weight loss, anorexia, lethargy and abdominal discomfort. However, they are often asymptomatic until they grow to a large size and 40% of cases are metastatic at the time of diagnosis. In a case series by Matthaei et al,⁸ the most common site of metastases was found to be the lung.⁸

Imaging findings of hepatic leiomyosarcoma are also non-specific. They are usually hypodense, well-defined and heterogeneous on CT, and may demonstrate internal and peripheral enhancement. Cystic variants are seen to have an enhancing thick wall, which may lead to misinterpretation as abscess formation. On MRI, these lesions are seen to be homogeneously or heterogeneously hypointense on T1 weighting and demonstrate T2 hyperintensity. Encapsulation is sometimes observed.^{9 10}

Given the rarity of this entity, there are no established guidelines regarding treatment. Therapeutic options include surgical resection, chemotherapy and liver transplantation. Surgical resection with tumour-free margins has been shown to offer the best long-term survival. The use of chemoradiotherapy is not well established.^{11 68} Liver transplantation is also controversial, with a number of studies demonstrating significant recurrence rates and low overall survival.⁶⁹ Of note, transcatheter arterial chemoembolisation shows promise in the management of unresectable lesions, with a successful case reported by Zhu and Cai. This is presumably due to the tumour’s rich vascularity, however further studies are needed to establish the use of chemoembolisation in conjunction with surgery.¹²

Patient’s perspective.

I had never had any medical problems or been to the hospital in my life, so the diagnosis came as a great shock to me. It took a lot of convincing from my children to go ahead with the operation. The risks scared me and I did not want to be away from home for such a long time. However the doctors explained to me the benefits of the procedure and I decided to go ahead with it. I wanted to be able to see my grandchildren grow up for at least a few more years. I was treated well and the recovery didn’t take as long as I expected. I am now back to my normal life and hope for the best.

Learning points.

• Primary hepatic sarcomas contribute to approximately 1%–2% of primary liver malignancies, with leiomyosarcomas accounting for only 8%–10% of all hepatic sarcomas.

• Diagnosis of these tumours is challenging in view of the non-specific nature of their presentation and the absence of significant serological abnormalities.

• An important prerequisite to its diagnosis is to exclude the possibility of an extrahepatic source of metastasis.

• Surgical resection is currently the mainstay of treatment for these tumours, however larger cohort studies are needed to provide guidelines regarding management.