Malignant hepatic perivascular epithelioid cell tumor: A case report and literature review

Abstract

Perivascular epithelioid cell tumors (PEComas) comprise a rare group of mesenchymal neoplasms, which can arise from almost any location in the body, but cases of primary hepatic PEComa are extremely rare. Here we report a hepatic PEComa in a 30-year-old man with abdominal pain . An extended left hepatectomy was proceeded and the results showed negative margins. Histologically, the tumor cells presented an epithelioid morphology with polymorphic nuclei and abundant eosinophilic cytoplasm and focal vascular infiltration. Necrotic tissue was present, closely resembling hepatocellular carcinoma. Immunohistochemistry demonstrated strong expression of HMB-45, CD34 and Ki67. Imaging findings and molecular analysis supported the malignant hepatic PEComa. Additionally, surgical resection is the first line treatment, and targeted therapy offers a viable therapeutic approach for individuals with inoperable malignant tumors and for those in the postoperative period.

Introduction

Perivascular epithelioid cell tumors (PEComas) are a rare group of mesenchymal neoplasms composed of histologically and immunohistochemically distinctive perivascular epithelioid cells, which have a perivascular distribution. The PEComa family comprises angiomyolipomas (AML), clear cell sugar tumors of the lung (CCST), lymphangioleiomyomatosis (LAM) and PEComas not otherwise specified (PEComa–NOS ) [1]. The incidence of hepatic PEComas is greater in women, with an incidence of approximately 0.3 per million and a peak between 20 and 40 years old. Due to PEComas are mesenchymal origin, they can be found anywhere in the body, and can arise from the kidney, lung, uterus and soft tissue. Hepatic PEComa is particularly rare, with the majority of cases being benign. The data of the patient with malignant hepatic PEComa are limited, and the multidisciplinary approach to manage these patients remains under debate. This article introduces a 30 years old patient with primary liver PEComa and discuss the relevant clinical considerations.

Case report

A 30-year-old Asian man presented with constant dull aching epigastric pain. On examination, contrast enhanced computed tomography (CT) of the abdomen showed a 12.4x9.9 cm lesion in the left liver, which demonstrated a rim enhancement in the early arterial phase and an isoenhancement in the portal venous and delayed phases, (Fig. 1, Fig. 2, Fig. 3). The lesion was supplied by the left hepatic artery. All laboratory investigations and tumor markers were normal. To sum up, the doctor thought that the possibility of mixed hepatocellular carcinoma was high. Finally, an extended left hepatectomy was performed.

Fig. 1.

Non-contrast CT scan shows homogeneous mild hypodensity.

Fig. 2.

Contrast-enhanced CT shows a 12.4x9.9 cm liver PEComa with heterogeneously enhancing lesion in the arterial phase.

Fig. 3.

In the portal phase, an isoenhancement of the lesion persists (black arrow), involvement of the left branch of the portal vein (blue arrow).

Macroscopically, the specimen contained a 17 × 11.5 × 9.5 cm liver fragment. The lesion showed hemorrhage, necrosis, focal cystic changes and a clear boundary with the surrounding liver tissue. Grayish-white tumor tissue was seen filling the bile duct, with an involved length of 3.5 cm and a duct diameter of 0.5–1.2 cm. Microscopically, the tumor cells presented an epithelioid morphology and focal vascular infiltration. The histologic examination revealed necrotic tissue and epithelioid cells that exhibited eosinophilic to clear, finely granular cytoplasm, polymorphic nuclei, and low mitotic activity (1/50 HPF). Immunohistochemistry showed HMB-45 (+) , TFE-3 (+), S-100 (+), vimentin (+), Ki67 (+), Inhibin-a (+) , CD34 (+), Syn (+), Melan-A (−), CK (pan) (−), Hepatocyte (−), Arg1 (−), CK19 (−), CK7 (−), CgA (−). Combined with immunohistochemistry, the tumor was diagnosed as malignant primary liver PEComa (Fig. 4). It was suggested that the patient complete the TFE3 and TSCI/TSC2 gene tests and receive postoperative radiotherapy, but the patient refused. There was no clinical or radiographic evidence of recurrence or metastases 6 months after surgery.

Fig. 4.

Predominantly clear cell tumor with epithelioid morphology. Areas of necrosis were also seen, and there was no obvious fatty component.

Discussion

This article presents a comprehensive review of the current literature regarding the management of primary PEComas. The occurrence of liver perivascular epithelioid cell tumor (PEComa) is extremely rare. The most common tumor with the hepatic PEComa spectrum is angiomyolipoma, which is characterized by adipocytic and prominent vascular components.

While most patients are asymptomatic and are discovered incidentally during routine physical examinations or imaging, others can have non-specific symptoms such as abdominal pain, nausea or loss of appetite. Additionally, there are no specific serological biomarkers or radiological findings. Therefore, a definite diagnosis relies on histological and immunohistochemical evaluation of resected specimens [2].

Some studies pointed out that only 10% of PEComas can be identified by radiology. On contrast-enhanced CT, these lesions showed significant arterial enhancement followed by washout in portal venous and delayed phases. These imaging findings are non-specific and can also be seen in similar imaging features in other hepatic lesions, including hepatocellular carcinoma (HCC), focal nodular hyperplasia (FNH) and hemangioma. However, there is evidence indicating that the presence of vascular proliferation and arteriovenous characteristics on contrast-enhanced CT or MRI can be important clues for PEComa [3]. Some studies [4] highlighted the specific characteristics of hepatic PEComa, including a “fast-in and slow-out” enhancement pattern, peripheral hyperechoic areas and large blood vessels. On color Doppler sonography (CDS), typical contrast-enhanced imaging patterns include marked arterial hyperenhancement, followed by isoenhancement in the portal venous phase and mild washout in the delayed phase [5]. Another distinctive characteristic of hepatic PEComa is the presence of both fatty and solid components. The presence of fat can be helpful in identification, especially in AML patients. Unlike PEComa, FNH generally lacks fat, whereas HCA contains only minimal fat. In the analysis of imaging manifestations, the doctor should focus on the size of the tumor and whether the adjacent blood vessels and tissues are invaded for evaluating the benign or malignant of PEComa.

However, the enhancement pattern depends on the proportion of its histological components, primarily adipose tissue (which can range from <10% to >90%), blood vessels, and smooth muscle, which can increase the likelihood of diagnostic errors by radiologists.

Most hepatic PEComas are diagnosed postoperatively through pathological analysis. Histopathological evaluation remains the cornerstone of diagnosis, characterized by perivascular epithelioid cells co-expressing melanocytic (HMB-45 and Melan-A) and smooth muscle (SMA) markers [6]. Molecular studies have linked PEComa pathogenesis to dysregulation of the mTOR signaling pathway, through TSC1/TSC2 mutations, TFE3 gene fusions, or other genetic alterations [7]. This finding has opened new avenues for targeted therapy of PEComas, as explored by Batereau et al. [8].

Recently, the treatment of liver PEComa remains controversial, most neoplasm were surgically treated and is effective. In this case, the patient remained recurrence-free 6 months after surgery. However, in light of evidence showing a 3.1% rate of recurrence and a 2.7% rate of metastasis after surgery [9], mTOR inhibitors have been gaining traction for the management of PEComas, both as primary treatment for inoperable cases and as postoperative adjuvant therapy [10]. In a phase II trial for patients with malignant PEComas, intravenous albumin-binding sirolimus demonstrated high response rate, low recurrence rate and no serious adverse events [11], which aids in the control of disease progression.

Although the majority of PEComas exhibit benign behavior, increasing evidence suggests a non-negligible malignant potential [12]. Until 2025, there were 145 studies related to this tumor and about 281 patients, of which only 30 showed features of malignancy. The median follow-up duration was 24 months (IQR: 12–48). Recurrence occurred in 17 patients, and 7 patient died as a result of the disease [13].

Most PEComa has a low recurrence rate after surgical resection, but one subgroup present malignant behavior. Folpe et al. [14] proposed a classification of PEComas into benign, uncertain malignant potential (UMP) and malignant neoplasm. The worrisome histological features: Less than 5 cm in size, noninfiltrative, high nuclear grade and cellularity, mitotic activity less than 1/50 high power fields (HPF), no coagulative necrosis and vascular invasion, are identified in resected specimens and categorize into benign. Tumors classified as UMP only have nuclear polymorphism or >5 cm size, while those with two or more worrisome features are considered malignant. The application of these criteria in future pathological assessments may help predict prognosis and guide treatment strategies.

Conclusion

This case and review demonstrates that hepatic PEComa lacks specific symptoms and radiological imaging, but doctors should consider differentiating it from PEComa when they observe specific imaging features. Surgical resection is the cornerstone of multimodal treatment. These nonsurgical methods (such as adjuvant treatment) should be considered when there are contraindications to surgery. The prognosis depends on histopathological risk factors, and requires strict and long-term follow-up.

Patient consent

The authors confirm that written informed consent was obtained from the patient after a comprehensive discussion regarding the purpose of this study and its potential publication in Radiology Case Reports. The patient understood and agreed to the publication of their clinical details and images. All identifiable information has been anonymized to protect the patient’s privacy.