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 Table of Contents  
Year : 2017  |  Volume : 2  |  Issue : 3  |  Page : 71-73

Malignant and benign renal perivascular epithelioid cell tumors: A comparison and review of the literature

1 The Hui Qiao Medical Centre, Nan Fang Hospital, Southern Medical University, Guangzhou, Guangdong, China
2 Department of Urology, Nan Fang Hospital, Southern Medical University, Guangzhou, Guangdong, China

Date of Submission13-Jul-2017
Date of Acceptance16-Aug-2017
Date of Web Publication15-Sep-2017

Correspondence Address:
Pengliang Chen
The Hui Qiao Medical Centre, Nan Fang Hospital, Southern Medical University, Guangzhou, Guangdong 510515
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ts.ts_14_17

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While angiomyolipoma (AML) is a fairly common urological tumor, malignant AMLs rarely appear in clinical practice. As such, currently there exists little knowledge of malignant AMLs. This article discusses the differences between benign and malignant AMLs. Besides, we report two cases of AML with opposite nature in Nan Fang Hospital from 2010 to 2016 and discuss the key features based on clinical manifestation, pathogenesis, radiology, and pathology. Case 1 was a 44-year-old, asymptomatic female presenting with a mass measuring 4 cm in diameter in the inferior pole of the left kidney. Case 2 was a 23-year-old female presenting with abdominal pain for 1 month, a mass measuring 5.5 cm in diameter in the superior pole of the right kidney, regional infiltration, and enlarged retroperitoneal lymph nodes. Based on Folpe's grading scheme, the Case 1 tumor was benign due to the absence of criteria mentioned in the grade and the Case 2 tumor was malignant due to a tumor size >5 cm, infiltrative growth pattern, necrosis, high nuclear grade, and subsequent aggressive clinical behavior. Each patient underwent surgical resection: Case 1 demonstrated no evidence of recurrence at the 9-month follow-up; however, Case 2 died 3 years postoperation due to tumor recurrence. These results demonstrate that malignant AML has aggressive biological activities and almost always associates with unfavorable prognoses. Therefore, a strict follow-up should be given to “uncertain malignant potential” patients, and surgical resection should be performed.

Keywords: Antidiastole, clinical and pathological characters, malignant angiomyolipoma, perivascular epithelioid cell tumors

How to cite this article:
Chen P, Lai W, Chen Z, Zheng S. Malignant and benign renal perivascular epithelioid cell tumors: A comparison and review of the literature. Transl Surg 2017;2:71-3

How to cite this URL:
Chen P, Lai W, Chen Z, Zheng S. Malignant and benign renal perivascular epithelioid cell tumors: A comparison and review of the literature. Transl Surg [serial online] 2017 [cited 2021 Oct 17];2:71-3. Available from: http://www.translsurg.com/text.asp?2017/2/3/71/213956

Pengliang Chen, Wenjie Lai
These authors contributed equally to this work.

  Introduction Top

Angiomyolipoma (AML) belongs to a family of neoplasm known as perivascular epithelioid cell tumors (PEComas).[1] Malignant AML is rare and often associated with an unfavorable prognosis. We report two cases of AML treated at Nan Fang Hospital from 2010 to 2016 and compare the clinical and pathological characteristics between them. Further, we discuss the differentiation between benign and malignant AMLs, as indicated within the literature.

  Case Reports Top

Case 1

A 44-year-old asymptomatic female presented with a mass measuring 4 cm in diameter in the inferior pole of the left kidney, detected via computed tomography (CT) in January 2016. A partial left nephrectomy was performed, and the postoperative recovery process was uneventful. No adjuvant therapy was given to the patient. There was no evidence of recurrence at the time of the 9-month follow-up.

The resected tumor specimen appeared whitish and solid, with an unbroken capsule. Histologically absent of hemorrhage and necrosis, the tumor was composed of adipocytes, thin-walled blood vessels, and smooth muscle cells [Figure 1]a and [Figure 1]b. There was also spindled and epithelioid cells with clear cytoplasm-embraced vessels [Figure 1]c. Moreover, the tumor cells presented dispersedly immunoreactivity for Human Melanoma Black 45 (HMB 45) [Figure 2]a and strong immunoreactivity for actin and desmin [Figure 2]b and [Figure 2]c. Ki-67 only presented immunoreactivity in 2% of the cells. S-100 was negative in the tumor [Table 1]. The diagnosis of benign AML had been made ultimately.
Figure 1: Histological analyses. (a and b) Adipocytes, thin-walled blood vessels, and smooth muscle cells were observed in Case 1. (c) Spindled and epithelioid cells with clear cytoplasm embracing the vessels in Case 1. (d) Hemorrhage and necrosis were observed in Case 2. (e) Polygonal epithelioid cells showed a nested structure in Case 2. (f) Tumor cells showed pleomorphism with multinucleated giant cells and enlarged nucleoli in Case 2

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Figure 2: The immunohistochemistry staining. (a-c) The tumor cells of Case 1 presented immunoreactivity for (a) HMB 45, (b) actin, and (c) desmin. (d-f) Immunohistochemical analysis revealed that tumor cells expressed (d) HMB 45, (e) Melan-A, and (f) Ki-67 in Case 2

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Table 1: Expression of CK, SMA, actin, desmin, S100, Ki-67, HMB 45, and Melan-A in specimens

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Case 2

A 23-year-old female complaining of abdominal pain for 1 month presented with a mass measuring 5.5 cm in diameter in the superior pole of the right kidney, detected by CT in October 2011. Moreover, regional infiltration and enlarged retroperitoneal lymph nodes were also observed. A radical right nephrectomy was performed, the postoperative recovery process was uneventful, and no adjuvant therapy was given to the patient. In September 2013, a second CT examination demonstrated a neoplasm measuring 3.1 cm in diameter within the right kidney [Figure 3]a, as well as distant metastases in the liver, lung, bone, and lymph nodes [Figure 3]b. This patient consulted the Department of Oncology at our hospital and was immediately given sunitinib. However, therapeutic response was insufficient, and the patient died in 2014.
Figure 3: Contrast computed tomography showed tumor recurrence in abdominal formation for Case 2 after operation. (a) Tumor in the right kidney position. (b) The tumor broke the liver

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Hemorrhage and necrosis were observed in Case 2 [Figure 1]d. Microscopically, the tumor showed a nested structure and was primarily composed of polygonal epithelioid cells [Figure 1]e. Focal tumor cells showed pleomorphism with multinucleated giant cells and enlarged nucleoli [Figure 1]f. Few fat cells were found within the tumor without mitosis. Moreover, the tumor cells presented positive immunoreactivity for HMB 45 and Melan-A [Figure 2]d and [Figure 2]e, and the markers involving smooth muscle actin (SMA), cytokeratin (CK), actin, desmin, and S-100 were negative [Table 1]. Ki-67 was positive just in 1% of the cells [Figure 2]f. The diagnosis of malignant AML had been made ultimately.

  Discussion Top

Malignant AML is rare and associated with aggressive clinical course and unfavorable prognoses due to lack of efficient adjuvant therapy. Therefore, adequate differentiation of benign versus aggressive AML is important to evaluate patient outcomes. Herein, we discussed the methods of antidiastole via clinical manifestation, pathogenesis, radiology, and pathology.

Based on clinical manifestation, patients with benign AML are often asymptomatic and are diagnosed occasionally (e.g., Case 1). Patients with malignant AML usually have the symptoms of hematuria, anemia, hypertension, and flank pain, similar to Case 2 who complained of abdominal pain (possibly due to regional infiltration and retroperitoneal lymph node metastasis).

Based on pathogenesis, the TFE3 gene rearrangement and tuberous sclerosis complex (TSC) gene deletion may be relevant to AML.[2],[3] Notably, the absence of the TSC gene can lead to epithelioid AML (E-AML)[4] via breaking the regulation of the mammalian target of rapamycin (mTOR) pathway. E-AML is an extremely rare type of renal PEComas which generally results in malignant biological behavior in one of every three patients.[1] Hence, all E-AMLs should be strictly followed clinically.

Based on imaging examination, benign AML is usually markedly hyperechoic to renal parenchyma on ultrasound and almost hypoechoic to renal parenchyma on CT scan, but CT appearance often changes due to variable amounts of components of the neoplasm. Regarding aggressive AML, exophytic growth with hemorrhage and necrosis, large solid masses with an average size of 7 cm in diameter, higher density than normal renal parenchyma, completely capsulated with distinct edges, and occasional regional lymph node metastases are common characteristics observed on unenhanced CT.[5],[6] Moreover, markedly heterogeneous enhancement and “rapid wash-in and slow wash-out” patterns are the predominate presentation of aggressive AMLs on contrast CT.[7]

Based on pathology, malignant PEComas are characterized by mitotic activity, necrosis, marked nuclear atypia, and pleomorphism according to the pathological classification of WHO in 2013.[8] On immunohistochemistry, PEC expresses melanocytic (HMB 45, Melan-A) and myogenic markers (SMA, actin, and desmin) in both benign and malignant PEComas.[9],[10] Therefore, we rarely use the markers mentioned above to classify the biological characters of AML, but we could differentiate them from renal cell carcinoma by showing epithelial tumor markers (EMA, CK) positive and melanocytic and myogenic markers negative.[11]

In 2005, Folpe et al.[12] proposed a significant association between tumor size (>5 cm), infiltrative growth pattern, high nuclear grade, necrosis, and mitotic activity (>1/50 hpf) with subsequent aggressive clinical behavior of PEComas.[12] They conclude that small PEComas without any worrisome histologic features are most likely to be benign. PEComas with nuclear pleomorphism alone or large PEComas without other worrisome features have uncertain aggressive potential. PEComas with two or more worrisome histological features described above should be deemed malignant.[12] Based on this grade, Case 1 was benign and Case 2 was malignant [Table 2]. However, Folpe et al. reported a case consisting of a clear cell myomelanocyte tumor in the round ligament of the uterus, which barely possessed any malignant features, but distant metastases occurred finally.
Table 2: The relation between patients in our study and Folpe's standard

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Regarding malignant AML, the most effective treatment seems only to be surgical resection. Wagner et al.[13] reported three aggressive PEComas with TSC and showed therapeutic response to sirolimus, an inhibitor of mTOR. However, more data are needed to verify the true effectiveness of this drug.

In conclusion, although a majority of AMLs are benign and possess good outcomes, malignant cases – although rare – almost always have unfavorable prognoses due to a lack of comprehensive treatment options. Therefore, clinical focus should be given to preoperative diagnoses of the biological behavior of PEComas as well as to the adequate selection of suitable patients for follow-up and/or surgery.

This work was supported by Medical Science Foundation of Guangdong Province (No.A2015015).

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Martignoni G, Pea M, Reghellin D, Zamboni G, Bonetti F. PEComas: The past, the present and the future. Virchows Arch 2008;452 (2):119-32.  Back to cited text no. 1
Russell CM, Buethe DD, Dickinson S, Sexton WJ. Perivascular epithelioid cell tumor (PEComa) of the urinary bladder associated with Xp11 translocation. Ann Clin Lab Sci 2014;44 (1):91-8.  Back to cited text no. 2
Williamson SR, Bunde PJ, Montironi R, Lopez-Beltran A, Zhang S, Wang M, Maclennan GT, Cheng L. Malignant perivascular epithelioid cell neoplasm (PEComa) of the urinary bladder with TFE3 gene rearrangement: Clinicopathologic, immunohistochemical, and molecular features. Am J Surg Pathol 2013;37 (10):1619-26.  Back to cited text no. 3
Pan CC, Chung MY, Ng KF, Liu CY, Wang JS, Chai CY, Huang SH, Chen PC, Ho DM. Constant allelic alteration on chromosome 16p (TSC2 gene) in perivascular epithelioid cell tumour (PEComa): Genetic evidence for the relationship of PEComa with angiomyolipoma. J Pathol 2008;214 (3):387-93.  Back to cited text no. 4
Froemming AT, Boland J, Cheville J, Takahashi N, Kawashima A. Renal epithelioid angiomyolipoma: Imaging characteristics in nine cases with radiologic-pathologic correlation and review of the literature. Ajr Am J Roentgenol 2013;200 (2):W178-86.  Back to cited text no. 5
Chen J, Wang P, Wang CJ, Cai SL, Ren GP, Li YY. Highly aggressive epithelioid renal angiomyolipoma with a very poor prognosis. Chin Med J (Engl) 2010;123 (6):765-6.  Back to cited text no. 6
Cui L, Zhang JG, Hu XY, Fang XM, Lerner A, Yao XJ, Zhu ZM. CT imaging and histopathological features of renal epithelioid angiomyolipomas. Clin Radiol 2012;67 (12):e77-82.  Back to cited text no. 7
Zambo I, Veselý K. WHO classification of tumours of soft tissue and bone 2013: The main changes compared to the 3rd edition. Cesk Patol 2014;50 (2):64-70.  Back to cited text no. 8
Jungbluth AA, Busam KJ, Gerald WL, Stockert E, Coplan KA, Iversen K, MacGregor DP, Old LJ, Chen YT. A103: An anti-melan-a monoclonal antibody for the detection of malignant melanoma in paraffin-embedded tissues. Am J Surg Pathol 1998;22 (5):595-602.  Back to cited text no. 9
Zavala-Pompa A, Folpe AL, Jimenez RE, Lim SD, Cohen C, Eble JN, Amin MB. Immunohistochemical study of microphthalmia transcription factor and tyrosinase in angiomyolipoma of the kidney, renal cell carcinoma, and renal and retroperitoneal sarcomas: Comparative evaluation with traditional diagnostic markers. Am J Surg Pathol 2001;25 (1):65-70.  Back to cited text no. 10
Eble JN, Sauter G, Epstein JI, Sesterhenn IA. World Health Organization Classification of Tumors. Tumors of the Urinary System and Genital Organs. Pathology and Genetics. Lyon: IARC Press; 2004.  Back to cited text no. 11
Folpe AL, Mentzel T, Lehr HA, Fisher C, Balzer BL, Weiss SW. Perivascular epithelioid cell neoplasms of soft tissue and gynecologic origin: A clinicopathologic study of 26 cases and review of the literature. Am J Surg Pathol 2005;29 (12):1558-75.  Back to cited text no. 12
Wagner AJ, Malinowska-Kolodziej I, Morgan JA, Qin W, Fletcher CD, Vena N, Ligon AH, Antonescu CR, Ramaiya NH, Demetri GD, Kwiatkowski DJ, Maki RG. Clinical activity of mTOR inhibition with sirolimus in malignant perivascular epithelioid cell tumors: Targeting the pathogenic activation of mTORC1 in tumors. J Clin Oncol 2010;28 (5):835-40.  Back to cited text no. 13


  [Figure 1], [Figure 2], [Figure 3]

  [Table 1], [Table 2]


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