Clinical characteristics and outcomes of patients with hepatic angiomyolipoma: A literature review

Table 1 Cases of spontaneous rupture of hepatic angiomyolipoma

Ref.	Sex	Age, yr	Symptoms	Abdominal radiological findings	Treatment	Outcomes
Huber et al[25] 1996	F	22	Hemorrhagic shock with clinical symptoms of acute abdomen	CT scan: multiple tumors of the liver (the largest in segment III measured 8 cm) and both kidneys and a splenic lesion with a diameter of 4 cm	Surgical resection of segments II and III	Postoperative course was uneventful. Discharge from hospital 12 d later
Guidi et al[26] 1997	M	74	Sudden onset of upper-quadrant pain	CT scan: liver tumor of 10 cm × 8 cm in the segments I and V and another small mass of 4 cm × 3 cm in segment IV. Fluid was present in the upper abdominal compartments	Surgical resection of the hemorrhagic hepatic mass	Postoperative course was uneventful. Discharge from hospital 8 d later
Tsui et al[27] 1999	F	41	Acute rupture of a subcapsular tumor	9 cm	Surgical resection	Patient in healthy condition 4 yr after surgery
Zhou et al[28] 2008	ND	ND	Hemorrhagic shock	Ultrasonography showed a 5-cm "cavernous hemangioma" in the right hepatic lobe	Emergency laparotomy for hemostasis	No tumor recurrence or metastasis was found during follow-up of 2-3 yr
Ding et al[8] 2011	F	56	ND	A rupture of the tumor measuring 6 cm × 6 cm in segment VI was confirmed by emergent laparotomy	Liver suture followed by segmentectomy	No serious morbidity in the postoperative course
Occhionorelli et al[29] 2013	F	25	Sudden onset of abdominal upper-quadrant pain and hypotension, after two recent syncopal episodes	CT scan showed a hepatic tumor in the left lobe (8.6 cm × 7.2 cm) with suspected peritoneal blood leakage	Hemorrhage initially managed by manual compression, followed by deep and pro-coagulant tissue adhesives. After 48 hours, the patient underwent left-liver lobectomy	Postoperative course was uneventful. Discharge from hospital 9 d later
Aoki et al[30] 2014	F	70	Sudden onset of back pain on the right side	CT scan: hepatic tumor in segment VII measuring 7 cm in diameter accompanied by subcapsular hematoma with extravasation	Transcatheter arterial embolization. Right hepatic lobectomy was carried out 39 d later	Five days after surgery, she had thrombi in the left popliteal vein and the left pulmonary artery. Insertion of an IVC filter which was removed due to sepsis. She was discharged 24 d after surgery. There was no recurrence 42 mo following surgery
Tajima et al[31] 2014	M	38	Upper abdominal pain	CT scan showed a tumor measuring 10.5 cm × 9.5 cm × 7 cm in the posterior segment of the right hepatic lobe that had ruptured into the space between the liver and the diaphragm	Transcatheter arterial embolization was performed. The patient developed fever and the hematoma surrounding the liver was drained. No infection was confirmed but right lobectomy was performed	ND
Kai et al[32] 2015	F	77	Sudden abdominal pain and transient loss of consciousness	CT scan: hemoperitoneum with subcapsular hematoma at the left lobe and a hepatic nodule measuring 2.3 cm in diameter in segment II	Conservative initial treatment with periodic imaging studies. Transcatheter arterial chemoembolization was performed because a diagnosis of HCC was suggested. Surgical resection (laparoscopic left lateral segmentectomy) was performed 4 mo later	Postoperative course was uneventful. Discharge from hospital 7 d later No signs of recurrence at 3.5 yr after surgery
Kim et al[33] 2017	M	31	Sudden onset severe abdominal pain in the right upper quadrant area	CT scan: Mass of approximately 12 cm in the right hepatic lobe with hemorrhage along the perihepatic space	Emergent angiography with embolization.Hepatic resection was performed 15 d later	Postoperative course was uneventful

F: Female; M: Male. ND: Not determined; CT: Computed tomography; HCC: Hepatocellular carcinoma; IVC: Inferior vena cava.

Table 2 Classification of perivascular epithelioid cell tumors according to their malignant potential[1,27]

Classification	Criteria
Benign	No worrisome features: (1) Tumor size < 5 cm; (2) No infiltration; (3) Non-high nuclear grade and cellularity; (4) Mitotic activity ≤ 1/50 HPF; (5) No necrosis; and (6) No vascular invasion
Uncertain malignant potential	Tumor with: (1) Pleomorphism/multinucleated giant cells only; or (2) Size > 5 cm only
Aggressive behavior	Two or more worrisome features: (1) Size > 5 cm; (2) Peripheral infiltration; (3) High nuclear grade and cellularity; (4) Mitotic activity > 1/50 HPF; (5) Ischemic tumor necrosis for large tumor; and (6) Vascular invasion
According to the WHO classification of tumors[1]	As with GISTs, the main predictors of a risk of metastatic behavior are marked nuclear atypia, diffuse pleomorphism and mitotic activity of more than 1 mitosis per 1 mm²

GIST: Gastrointestinal stromal tumor; HPF: High-power field.

Table 3 Reported cases of hepatic angiomyolipoma with aggressive behavior

Ref.	Sex	Age, yr	Size	Types	Treatment	Duration of follow-up	Outcome
Croquet et al[9] 2000	F	16	19 cm × 12 cm × 8 cm	Epithelioid	SR	6 yr	Recurrence in the liver, associated with renal angiomyolipoma
Dalle et al[10] 2000	F	70	15 cm	Epithelioid	SR	5 mo	Recurrence in the liver with a lesion measuring 15 cm and presence of multiple metastases in the liver
Flemming et al[11] 2000	F	51	2 nodules: 0.5 cm and 15 cm	Epithelioid	SR	3 yr	Recurrence in the right hepatic lobe and presence of multiple metastases
McKinney et al[12] 2005	F	14	11 cm × 7 cm × 8 cm	NS	SR, interferon α	1 yr	Recurrence with a hepatic lesion measuring 9 cm × 6 cm × 14 cm, appearance of lymph nodes and hepatic metastases. Death after disease progression
Parfitt et al[13] 2007	F	60	14 cm × 11 cm	Epithelioid	SR	9 yr	Recurrence in the liver and appearance of metastases in the trapezius muscle, the left lung and the tail of the pancreas
Yang et al[14] 2007	F	37	13 cm × 9 cm × 9 cm	Classic	SR	14 mo	Recurrence in the right hepatic lobe 6 months after SR, appearance of pulmonary metastases 11 mo after SR and death occurred at 14 mo
Deng et al[15] 2008	M	30	18 cm × 14 cm	Classic	SR, Chemotherapy	3 yr and 4 mo	Recurrence with a hepatic lesion measuring 11 cm and metastases in pancreatic tail and portal vein thrombosis 3 yr after SR. Chemotherapy was initiated but 4 mo later pulmonary metastases appeared. Death occurred after disease progression
Nguyen et al[16] 2008	F	43	11 cm × 7.5 cm × 7.5 cm	Classic	SR	6 mo	Recurrence in the liver 6 mo after SR, together with metastases in the peritoneum, omentum, stomach and spleen. Death after disease progression
Xu et al[17] 2009	F	33	2 nodules: 1 cm and 6 cm	Epithelioid	SR	1 yr	Recurrence in the left hepatic lobe
Zeng et al[18] 2010	NS	NS	6 cm	NS	SR	9 yr	Recurrence in the right hepatic lobe with a lesion measuring 6 cm
Butte et al[19] 2011	F;M	54; 41	NS; 9 cm	NS; Epithelioid	SR; SR	53 mo; 41 mo	Recurrence in the liver 53 mo after SR; Occurrence of pulmonary and retroperitoneal metastases 41 mo after SR
Hu et al[20] 2011	F	NS	NS	NS	SR	14 mo	Appearance of local and distant metastases 6 mo after SR. Death occurred 14 mo after SR
Ding et al[8] 2011	F	31	8 cm × 8 cm	NS	SR	7 yr	Recurrence in the right hepatic lobe 6 yr after SR and death occurred one year later
Wang et al[21] 2015	F	37	7 cm × 9 cm	Classic	SR	3 yr	Recurrence of two hepatic nodules in the right lobe (13 cm × 12 cm and 2.3 cm × 1.8 cm) 3 yr after SR. Arterial chemoembolization was performed, followed by liver transplantation
Fukuda et al[22] 2016	M	58	6.3 cm	Epithelioid	SR	9 yr	Metastases occurred in the right lung 7 yr after SR and were treated by pneumonectomy. No recurrence was observed after 2 yr of follow-up
Marcuzzi et al[23] 2018	F	47	3.8 cm × 4.6 cm × 4.7 cm+ 2 hepatic lesions measuring 6 mm and 5 mm	Epithelioid	SR	8 yr and 8 mo	CT scan was performed 6 yr and 4 mo after the initial presentation: the hepatic lesion had grown in size to an estimated 10.9 cm × 9.7 cm × 11.2 cm and the adjacent lesions had grown to 1.9 cm and 2.4 cm with a new lesion on the kidney of 4.6 cm × 5.1 cm. 16 mo later, MRI showed an increase in size of the hepatic lesion (12 cm × 11 cm), and kidney lesion (6.2 cm × 5.6 cm). SR performed 2 mo later. 6 mo after SR, recurrence in the resection line and in the hepatic segment II
Yan et al[24] 2018	NS	NS	15 cm	Epithelioid	SR	9 yr	Recurrence in the liver 9 yr after SR with invasion of the inferior vena cava and diaphragm, and appearance of pulmonary metastases

F: Female; M: Male; NS: Not specified; SR: Surgical resection; CT: Computed tomography; MRI: Magnetic resonance imaging.