Hepatic perivascular epithelioid cell tumor:A case report

lNTRODUCTlON

Perivascular epithelioid cell tumor(PEComa)is a mesenchymal tumor with histologic and immunophenotypic characteristics of perivascular epithelioid cells.It has a low incidence rate and can involve multiple organs.PEComa originating in the liver is extremely rare,with most cases being benign,and only a few cases diagnosed as malignant[1-3].Good outcomes are achieved with radical surgical resection,but there is no effective treatment for certain large tumors and specific locations that are contraindicated for surgery[3,4].Targeted anti-angiogenic therapy through transarterial embolization(TAE)in combination with sorafenib is widely used for palliative treatment of unresectable hepatocellular carcinoma;however,this combination therapy has not been reported in PEComa.This article presents the therapeutic application and preliminary results of this combination therapy for PEComa in the liver in a patient in whom surgery was contraindicated.

CASE PRESENTATlON

Chief complaints

A 32-year-old female patient had palpable abdominal mass and progressive deterioration since the last one month.

History of present illness

The patient had an unremarkable past medical history,no history of recent illness and/or trauma,and was not receiving any medication at the time of referral.

History of past illness

Healthy in the past,denied hepatitis,tuberculosis,hypertension,diabetes,heart disease

.

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My mommy says that you lost your daughter and you re very, very sad with a broken heart. Susie held her hand out shyly. In it was a Band-Aid. This is for your broken heart. Mrs. Smith gasped5, choking back her tears. She knelt down and hugged Susie. Through her tears she said, Thank you, darling girl, this will help a lot.

Personal and family history

The patient stated that no personal or family history of chronic liver disease or hepatocellular carcinoma existed.

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Physical examination

Gansu Provincial Natural Science Foundation,No.21JR7RA417;Lanzhou Science and Technology Development guiding Plan Project,No.2019-ZD-72.

Laboratory examinations

Results of the laboratory evaluation were unremarkable.Serum tumor markers(alpha-fetoprotein,carcinoembryonic antigen,and cancer antigen 19-9)were all within reference ranges,and serology for hepatitis B and C was non-reactive.

Imaging examinations

Chest X-ray showed increased markings in both lungs and a small amount of exudate in the lower lobe of the right lung.Enhanced computed tomography(CT)of the abdomen showed a huge oval cystic solid space-occupying lesion(18 cm × 11 cm × 15 cm)in the hepatic S7 and S8 segments.Enhanced scan showed significant non-uniform enhancement with hepatic artery branch penetration;focal nodular hyperplasia of the liver combined with cystic lesion was considered(Figure 1).Ultrasonography results suggested that there were fluid-dominant mixed echogenic lesions in the liver,and the ultrasonography was consistent with a benign lesion enhancement pattern.

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FlNAL DlAGNOSlS

Ultrasound-guided puncture and drainage with simultaneous percutaneous liver biopsy were performed.Postoperative pathology resulted showed immunohistochemical staining: CKp(-),CD163(+/-),CD68(+),CK7(-),Glypican-3(-),smooth muscle actin(SMA)(+),HMB45(+),Melan-A(+),CK19(-),Hepatocyte(-),CEA(-),Ki-67 +2%.Diagnosis: Tumor with perivascular epithelioid cell differentiation(Figure 2).Digital subtraction angiography(DSA)showed a rich blood supply to the tumor(Figure 3A).

After multidisciplinary consultation and discussion,the patient was diagnosed with a huge liver tumor that was a potentially malignant progressive PEComa,which was currently too large for complete surgical resection.Digital subtraction DSA showed rich blood supply to the tumor(Figure 3A).Interventional embolization should be the first choice in patients with a rich blood supply tumor.Based on the characteristics of the tumor and lack of sensitive chemotherapeutic drugs,the treatment modality of TAE was chosen instead of transcatheter arterial chemoembolization(TACE).The hypoxia caused by TAE could potentially upregulate angiogenic factors and stimulate the proliferation of residual tumor cells,leading to tumor survival and recurrence[12].Thus,a treatment plan involving TAE combined with sorafenib was planned.The embolic agents used were 10 mL of iodine oil + 350-560 μm PVA embolic pellets to ensure the adequacy of embolization.Four TAEs were performed from January to August 2019,during which treatment was combined with sorafenib(0.4 g orally bid,subsequently changed to 0.2 g orally qd due to the development of diarrhea and hand-foot syndrome).The tumor shrank after treatment,and the tumor was evaluated according to RECIST1.1 to be partially responsive.The lesion shrank on repeat enhanced CT in August 2019(Figure 4).DSA was repeated,and no clear tumor staining was observed(Figure 3B).TAE treatment was suspended,and surgery was recommended,which the patient declined.The patient discontinued treatment with sorafenib on her own.Six months later,repeat abdominal enhancement CT showed no significant tumor growth(Figure 5).

TREATMENT

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PEComa of the liver is a rare disease with a high likelihood of misdiagnosis and needs to be confirmed by pathology and immunohistochemistry;surgery remains the primary treatment.However,TAE combined with anti-angiogenic targeted therapy may be an effective treatment in some cases involving large tumor size and a location contraindicated for surgery.

OUTCOME AND FOLLOW-UP

The patient was treated with four sessions of TAE combined with sorafenib therapy,which led to significant lesion reduction.Six months after cessation of treatment,an enhanced CT(Figure 5)review showed tumor shrinkage and disappearance of the cyst,and elective surgery was recommended.

DlSCUSSlON

Perivascular epithelioid cell tumors(PEComas)are a rare group of tumors of mesenchymal origin,defined in the 2002 edition of the World Health Organization Pathology Classification as "a mesenchymal tumor with histologic and immunophenotypic features of perivascular epithelioid cells."[1]The incidence of PEComa is low,and PEComas mostly occur in the uterus,followed by the kidneys,bladder,prostate,lung,pancreas and liver.Primary hepatic PEComa is rare[2],with a higher incidence in women than in men,the lesions mainly accumulate in the right lobe,the pathogenesis remains unclear,and the number of available cases does not accurately reflect the incidence of PEComas in the liver[2,4].

Biopsy is commonly used for the preoperative diagnosis of PEComa[3],where tumor cells are arranged around blood vessels and exhibit a pleomorphic nature with three main types of cells:Epithelioid,spindle,and adipocytes - which have different degrees of differentiation and are difficult to diagnose histologically.Immunohistochemistry is currently the only clinical method to confirm the diagnosis,with HMB-45,Melan-A,and SMA as specific immunomarkers[2,7,8].HMB-45 is associated with poor prognosis in more than 92% of livers with positive PEComa markers[3,9].This patient matched the pathological diagnosis described above.

Laboratory tests for hepatic PEComas are non-specific;there are no uniform criteria for imaging diagnosis,and preoperative imaging diagnosis is very difficult.Most patients are misdiagnosed with hepatocellular carcinoma,focal nodular hyperplasia,hemangioma,or hepatic adenoma.A hepatic PEComa presents on CT or MRI as well-defined with early enhancement in the arterial phase and nonuniform enhancement in the venous and delayed phases.Malformed vessels are usually present,and cystic lesions are extremely rare[3,5,6].Our patient had no specific clinical symptoms or laboratory test results other than an abdominal mass,which showed non-uniform enhancement on imaging.

Liver PEComas lack specific clinical symptoms and are mostly detected during routine physical examinations.They mainly present with gastrointestinal symptoms,such as abdominal pain,bloating,abdominal discomfort,and vomiting.The appearance of symptoms may be related to an increase in the tumor size.Local compression or liver capsule traction.A small number of patients present with painless masses[2,4].

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The vast majority of hepatic PEComas are benign,with 4%-10% of reported cases being malignant[10].In malignant lesions,the tumor size is greater than 5 cm in diameter and shows marked nuclear heterogeneity,pleomorphism,high nuclear division index,necrosis,and marginal infiltration,some of which are known to recur or metastasize[3,10].This patient had no significant malignant tendency with a tumor larger than 5 cm,which rapidly increased in size over a short period of time and had to be treated aggressively.Complete surgical resection of the lesion is the main treatment modality,but there is a lack of effective treatment for some patients with PEcomas of the liver that are large and in such a location where they cannot be surgically resected or surgery is contraindicated.At present,there is a lack of effective measures,and the results of chemotherapy and radiotherapy are uncertain.New targeted treatment with an mTOR inhibitor(sirolimus)has achieved some efficacy in clinical trials but has not been widely used[2,4,11].

Targeted anti-angiogenic therapy with TAE in combination with sorafenib is widely used in the palliative treatment of unresectable hepatocellular carcinoma.The tumor was huge,with rapid shortterm growth,marked malignant tendency,and significant contraindications to surgery.Thus,TAE combined with sorafenib was chosen for the following reasons.First,DSA of the liver showed an abundant blood supply for arterial administration.The tumor lacked sensitive chemotherapeutic agents;therefore,TAE replaced TACE.Second,TAE can cause ischemia and necrosis in the tumor tissue,but the resultant hypoxia could upregulate angiogenic factors and stimulate the proliferation of residual tumor cells,leading to tumor survival and recurrence[12].Sorafenib was selected for its dual antiangiogenic and anti-proliferative activity,as well as the fact that a previous case of malignant liver PEcoma that was misdiagnosed as hepatocellular carcinoma was treated with oral sorafenib for 10 years and demonstrated some therapeutic value[13].This patient was treated with four sessions of TAE combined with sorafenib for significant lesion reduction.Surgery was suggested after the follow-up.

CONCLUSlON

Crazed with grief and rage, he ran toward the street screaming, They have stolen my tulip bulbs! Albertha, watching from the doorway11, cried out and ran to stop him. Before she could reach Arnoldus, a German soldier raised his pistol and shot him. Although the German surrender had been signed, a curfew was still technically12 in effect, and my grandfather had violated it.

FOOTNOTES

Li YF was the patient’s physician,collected case information,reviewed the literature and contributed to manuscript drafting;Xie YJ analyzed and interpreted the imaging findings;Wang L was responsible for the revision of the manuscript for important intellectual content;all authors issued final approval for the version to be submitted.

Specialist abdominal examination: Abdominal distention,liver palpable 10 cm below the costal margin,umbilicus was flat and hard,tenderness was absent,spleen was not palpable below the costal margin,and no positive signs were seen in the rest of the physical examination.

Informed written consent was obtained from the patient for publication of this report and any accompanying images.

The authors declare that they have no conflict of interest.

The authors have read the CARE Checklist(2016),and the manuscript was prepared and revised according to the CARE Checklist(2016).

This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers.It is distributed in accordance with the Creative Commons Attribution NonCommercial(CC BYNC 4.0)license,which permits others to distribute,remix,adapt,build upon this work non-commercially,and license their derivative works on different terms,provided the original work is properly cited and the use is noncommercial.See: https://creativecommons.org/Licenses/by-nc/4.0/

China

Yong-Fang Li 0000-0003-3143-4090;Liang Wang 0000-0003-1620-7682;Yi-Jing Xie 0000-0003-0100-4487.

Liu JH

A

Liu JH

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