PEComas are a rare type of mesenchymal tumor. In 1992, Bonetti et al. first defined “PEC” as an unusual cell type that was immunoreactive with melanocyte markers, and had an epithelioid appearance, a clear-acidophilic cytoplasm, and a perivascular distribution. In 1996, Zamboni G et al. reported that these tumors occurred in different sites and comprised perivascular epithelioid cells (PECs) with similar morphological characteristics and phenotypes as PEComas. In 2013, The World Health Organization (WHO)  defined PEComas as “mesenchymal tumors composed of distinctive cells that show a focal association with blood vessel walls and usually express melanocytic and smooth-muscle markers” in the fourth edition of the classification of soft tissue and bone tumors. The PEComa family include angiomyolipoma (AML), clear cell "sugar" tumor of the lung (CCST), lymphangioleiomyomatosis (LAM), and a group of tumors that is similar in histology and immunophenotype in various organs and soft tissues (NOS). Clinically, angiomyolipomas (AMLs) with little or no fat are usually termed PEComas [6, 7]. All 16 patients in this group were diagnosed with hepatic PEComas by pathology and immunohistochemistry, among whom 15 cases were found to be fat-free and 1 case contained less fat.
Hepatic PEComas mostly present in middle-aged women and are likely related to hormone levels . Most hepatic PEComas are single lesions, usually located in the right lobe of the liver, while multiple lesions are comparatively rare. The routine laboratory tests, including routine blood composition tests, live and renal function tests, and analysis of tumor biomarkers (including AFP, CEA, CA19-9 and CA125) are generally within the normal range. Most patients are asymptomatic and show no significant correlation with hepatitis virus history or cirrhosis , while some present nonspecific gastrointestinal symptoms, such as upper abdominal discomfort, abdominal pain, abdominal distension, loss of appetite, which may be caused by the increasing size of the tumor resulting in the tension of liver capsule or compression of surrounding organs [10, 11]. However, Da Tang  reported that the clinical symptoms are independent of tumor size, and patients with small tumors may also develop clinical symptoms. Consistent with our study, among the 16 female patients, the tumors of 12 patients were located in the right lobe of the liver. Eleven patients had no subjective symptoms and were incidentally detected during physical examination. Nonspecific upper abdominal discomfort was found in 4 patients, and 1 patient was found because of pain in the right kidney area. Among 16 patients, only 1 patient was complicated with hepatitis B virus infection.
There are no typical imaging findings of hepatic PEComa. Most tumors show heterogeneous low-density shadows in nonenhanced CT images, hypointense signals in T1WI images and hyperintense signals in fat-suppressed T2WI and DWI images in nonenhanced MRI images . Contrast-enhanced CT or MRI mainly shows marked heterogeneous enhancement in the arterial phase and washout in the portal and delayed phases, while persistent enhancement was observed in a few cases . Regarding our study, most lesions were hypoechoic in ultrasound images (12/16). On contrast-enhanced CT or MRI, all 16 cases presented heterogeneous enhancement in the arterial phase; among whom, 15 cases showed various enhancement attenuation patterns in the portal and delayed phases (15/16), and 1 case presented with persistent enhancement (1/16). The proportion of different components within the tumors may lead to different enhancement patterns, making it difficult to diagnose through radiological examination. For example, when contrast agent empties rapidly in the equilibrium phase, it is likely to be misdiagnosed with HCC or metastasis, a finding that may be related to hypervascularity and arteriovenous connections; however, when the contrast agent is slowly discharged or with persistent enhancement in the equilibrium phase, it will be difficult to distinguish it from other benign liver tumors, such as hepatic adenoma, hepatic hemangioma and FNH [10, 13].All 16 patients in our study were misdiagnosed with HCC, hepatic adenoma, hepatic hemangioma, hepatic metastasis or undiagnosed lesions before surgery. Therefore, hepatic PEComa should be considered for those patients with the above imaging features.
The diagnosis of hepatic PEComa is mainly dependent on pathology and immunohistochemistry . Microscopically, the tumor mainly comprises epithelioid cells (PECs) with abundant clear eosinophilic granular cytoplasm radially arranged around the vascular lumen [13–15]. However, the histogenesis and pathogenesis of PECs have not been elucidated; one hypothesis is that PECs may originate from undifferentiated neural crest cells that express melanocytes and smooth muscle cell phenotypes [8, 13, 16]. The PEComa family possesses similar immunohistochemical phenotypes. Almost all PEComas show positive expression of both HMB-45 and SMA markers. Nevertheless, studies have indicated only 80% of cases show co-expression of both; thus, the diagnosis of PEComa cannot be excluded only because SMA expression is negative. In addition to HMB-45 and SMA, some additional immunohistochemical markers with positive expression, such as Melan-A, SMA, vimentin, S-100, Desmin, CD31, and CD34, and those with negative expression, including CgA, Syn, CK, CD117, CD10, AFP and EMA, are helpful to confirm the diagnosis but not completely coincidental . Consistent with the above, all 16 cases in our group were positive for HMB-45 and Melan-A, 13 cases for SMA, and 15 cases for CD34. Twelve cases were negative for S-100.
PEComas possess a wide range of biological behaviors, and most are benign. However, the uniform standard to evaluate the malignant degree of PEComas has not yet been fully established . In 2005, Folpe et al.  proposed the criteria to classify PEComa of soft tissues into benign, malignant and uncertain malignant potential (UMP): 1, tumor size༞ 5 cm; 2, infiltrative; 3. high nuclear grade and cellularity; 4. mitotic rate ༞1/50 high-power fields (HPF); 5. Necrosis; 6. vascular invasion. PEComas with two or more of the above features were considered malignant, and only those with nuclear pleomorphism and a tumor size༞ 5 cm were considered to have an uncertain malignancy potential. However, studies have confirmed that, although these histological features suggest malignancy, distant metastases were not found . Hao b-b et al.  summarized the similarities and differences of benign and malignant hepatic PEComas, and pointed out that malignant hepatic PEComas should contain the following characteristics: 1. Female patient older than 50 years; 2. abdominal discomfort or pain; 3. tumor diameter > 10cm; 4, positive expression for CD34 and Ki67; 5. Negative expression for CD117. Because malignant cases of hepatic PEComa are rare, further studies are needed to improve the criteria to differentiate between benign and malignant cases.
Due to its rarity and malignant tendency, the treatment of hepatic PEComa has been controversial. Several literature sources have suggested that patients with hepatic PEComa with no clinical symptoms and serologic abnormalities, a tumor diameter ༜5 cm, and benign histological features, may only consider regular review . However, it has also been reported that postoperative recurrence and metastasis still occur in patients with hepatic PEComa with benign histologic features . Thus, for resectable tumors by preoperative evaluation, radical resection is a preferred therapeutic method with a favorable prognosis. Of the 16 patients with hepatic PEComa in this group, 11 had undergone “laparotomy for partial hepatectomy” or “laparoscopic partial hepatectomy”, and the postoperative pathological examinations were R0 resection; 3 patients had undergone “radiofrequency ablation of liver tumors” after the diagnosis by liver biopsy, and none of them had surgical complications or death. For temporarily unresectable hepatic PEComas, stereotactic body radiation therapy (SBRT) or transcatheter arterial embolization (TAE) can be used to shrink the tumor size to a resectable range for surgical treatment [14, 21]. A few PEComas may be associated with TSC [13, 16], and the pathogenesis of PEComa is mainly caused by the mutation or deletion of TSC1 (9q34) or TSC2 (16p13), leading to high expression of mTOR pathway components and promotion of excessive cell proliferation. Therefore, it is helpful to shrink the tumor size in patients of TSC-associated hepatic PEComa who accept preoperative neoadjuvant therapy with mTOR inhibitors. For advanced unresectable or metastatic hepatic PEComas, systemic therapies including anti-angiogenesis agents (sorafenib, apatinib, and sunitinib), cytotoxic chemotherapy (gemcitabine or anthracycline-based regimens) or mTOR inhibitors such as sirolimus, may be effective. However, due to the lack of published prospective clinical trials and sufficient retrospective cases, the reactivity to tumors and median progression-free survival (PFS) have not yet been determined . Considering the large size of the tumor and pathological indication of malignant lesions, 1 patient in this group accepted the chemotherapy regimen of "gemcitabine + nedaplatin + apatinib" and the tumor shrank by 2cm after 6 months. The natural history and prognosis of hepatic PEComa are not entirely clear at present, and malignant cases usually metastasize early; thus, all patients with hepatic PEComa need long-term close follow up [11, 12]. Fourteen of sixteen patients in this group were followed up regularly, and the longest follow-up time was up to 55months. During the follow-up period, only one case of intrahepatic recurrent lesion was found 14 months after radiofrequency ablation of liver tumors.