|Year : 2014 | Volume
| Issue : 2 | Page : 404-406
Pure epitheliod perivascular epitheloid cell tumor (epitheliod angiomyolipoma) of kidney: Case report and literature review
PG Jayaprakash, Susan Mathews, M Biju Azariah, Geethu Babu
Department of Radiation Oncology, Regional Cancer Centre, Trivandrum, India
|Date of Web Publication||14-Jul-2014|
P G Jayaprakash
Department of Radiation Oncology, Regional Cancer Centre, Trivandrum
Source of Support: None, Conflict of Interest: None
Malignant kidney tumors are rare neoplasms accounting for 3% of adult malignancies. Majority of these arises in the renal parenchyma and are adenocarcinomas. Malignant mesenchymal tumors of kidney are extremely rare. We report on the clinical behavior, the radiological and histopathological details of one such case of malignant mesenchymal tumor, we encountered.
Keywords: Epitheloid angiomyolipoma, kidney, case report
|How to cite this article:|
Jayaprakash P G, Mathews S, Azariah M B, Babu G. Pure epitheliod perivascular epitheloid cell tumor (epitheliod angiomyolipoma) of kidney: Case report and literature review. J Can Res Ther 2014;10:404-6
|How to cite this URL:|
Jayaprakash P G, Mathews S, Azariah M B, Babu G. Pure epitheliod perivascular epitheloid cell tumor (epitheliod angiomyolipoma) of kidney: Case report and literature review. J Can Res Ther [serial online] 2014 [cited 2020 May 26];10:404-6. Available from: http://www.cancerjournal.net/text.asp?2014/10/2/404/136672
| > Introduction|| |
The term angiomyolipoma is used for a non-metastasizing renal tumor composed of fat, smooth muscle, and blood vessels. Although angiomyolipoma is usually well demarcated from normal kidney, it may extend into the surrounding retroperitoneum. Wide excision is curative.
Epitheloid Angiomyolipoma (Perivascular epitheloid cell tumor [PEComa]) of the kidney is defined as potentially malignant mesenchymal lesions that are closely related to classic angiomyolipoma. Approximately, 120 cases are published, with mean age group of 40.7 years and male to female ratio of 1:1.  Around 80% of the patient have disease progression, with most common site of metastasis to liver. We present a case of pure epitheloid PEComa, which progressed with liver and lung metastasis.
| > Case report|| |
A 60-year-old male underwent evaluation for dull aching left lumbar pain of 2 weeks duration. Physical examination was normal except for left varicocele. Computed tomography showed a large relatively hypodense mass of 7 cm × 5 cm, confined to left kidney involving upper and mid poles without calcification. Extensive tumor thrombus was seen in the left renal vein and inferior vena cava (IVC) extending up to the right atrium. There was no evidence of nodal or distant metastasis. A diagnosis of left renal cell carcinoma [Figure 1] with tumor thrombus in left renal vein and IVC reaching up to the right atrium [Figure 2] was given. There was no evidence of metastatic disease and hence, he was taken up for radical surgery. He underwent left radical nepherectomy, IVC tumor thrombectomy under the vascular bypass. Histopathological examination revealed it to be pure epitheliod PEComa (Epitheliod Angiomyolipoma) of the kidney [Figure 3] and [Figure 4]. Cytokeratin CK-negative, Vimentin-negative, Desmin-negative, Cluster of differentiation CD 10-negative. Human melanoma black HMB 45-diffuse strong positive, S100-diffuse strong to moderate positive, Smooth muscle actin SMA-positive, Micro villous membrane MVM 1-negative. It was decided to keep him on close follow-up since there was no standard adjuvant treatment recommended. Eight months after surgery, he was detected to have liver [Figure 5], and lung [Figure 6] metastasis on the routine follow-up visit.
|Figure 2: Relatively hypodense mass confined to left kidney with tumor thrombus involving the renal vein and IVC|
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|Figure 3: Sections from the kidney showing a neoplasm composed of sheets of epitheloid cells with moderate amount of eosinophilic cytoplasm and vesicular nucles with prominent nucleoli. (H and E, ×200)|
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|Figure 4: Higher power view showing cells resembling ganglion cells. (H and E, ×400)|
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| > Discussion|| |
Perivascular epithelioid cell (PEC) is the prototypic cell of PEComas, which has unique morphologic, immunohistochemical, ultrastructural, and genetic features, and of which a normal histologic counterpart is hitherto unknown. The family of tumors histogenetically linked to pecs, includes renal and hepatic angiomyolipomas, clear cell sugar tumor of the lung, pulmonary lymphangioleiomyomatosis, and clear cell myomelanocytic tumor of the falciform ligamentum teres. PEC tumors have a remarkable sability for phenotypic (smooth muscle, epithelioid, and lipid rich histology), and immunohistochemical (coexpression of myogenic [smooth muscle actin], and melanocytic [HMB45, melan A, microphthalmia transcription factor, tyrosinase]) modulation.
Tumors with spindled predominant histology have a greater tendency to express smooth muscle markers, whereas tumors with epithelioid morphology tend to more consistently express melanocytic markers in a widespread distribution pattern.  Although many names have been assigned to tumors that are characterized by PECs, the World Health Organization has recently introduced a unifying term "PEComa," defining it as "a mesenchymal tumor composed of histologically and immunohistochemically distinctive PECs." There is a strong association between nearly all types of PEComas and the genetic alterations of the tuberous sclerosis complex (TSC), an autosomal dominant genetic disease due to losses of TSC1 (9q34) and TSC2. 
Pure epithelioid PEComa of the kidney with predominant or pure epithelioid component and having minimal-to-no adipocytic component have a mean age of approximately 40 years with an almost even sex predisposition.
Grossly, these tumors are solid, hemorrhagic, and have variable necrosis or cystic changes.
Microscopically, Pure renal epithelioid PEComas had two major architectural patterns: PEComa with carcinoma-like growth (designated as pattern A) that is characterized by large cells arranged as cohesive nests, broad alveoli, and compartmentalized sheets separated by thin vascular-rich septae, and PEComa with epithelioid and plump spindled cells in diffuse growth (designated as pattern B) composed of predominantly epithelioid-to-plump spindled cells arranged in diffuse sheets. Sometimes PEComa with combined carcinoma-like and diffuse growth pattern can occur.
Immunohistochemically, these are negative for epithelial-associated markers (AE1/AE3, CAM5.2, or EMA), positive for melanocytic marker (HMB45, microphthalmia transcription factor, melan-A, and tyrosinase), and positive for actins (smooth muscle actin or muscle specific actin).
Recurrence is seen in around 17% of patients and metastasis in about 50% of patients, out of which about 30% has metastatic disease at presentation. Metastatic sites included the liver (63%), lung (25%), peritoneum/mesentery (18.8%), colon (6.3%), pelvis (6.3%), and diaphragm (6.3%). Regional lymphnode metastasis is also seen.
Univariate analysis has showed that the presence of tuberous sclerosis and/or concurrent angiomyolipoma, tumor size (>7 cm), morphologic pattern A, involvement of perinephric fat tissue and/or renal vein, and presence of necrosis are found to be associated with disease progression, recurrence, metastasis, or death due to disease. The frequency of these adverse prognostic parameters was correlated with disease progression, and a frequency based risk stratification model has been derived (low-risk, 0-1 parameters; intermediate-risk, 2-3 parameters; high-risk, 4 or more parameters).
Recent studies have shown functional activation toward the mTOR pathway and sirolimus as a potential therapeutic target underscoring the need for accurate diagnosis.  The meantime to metastases in patients developing metastatic disease during follow-up is 17-31 months, median 12-18 months. Despite dramatic advances in the appreciation of the morphologic spectrum, and molecular attributes of epithelioid PEComa of the kidney, the prognostic factors that determine an outcome are largely unknown. These tumors were consequently defined in the recent World Health Organization Blue Book as a potentially malignant mesenchymal neoplasm characterized by proliferation of predominantly epithelioid cells and is closely related to the triphasic (classic) angiomyolipoma.
In summary, pure epithelioid PEComas have significant overlap in morphology with more commonly occurring neoplasms in the kidney, such as clear cell renal cell carcinoma. Once the appropriate diagnosis of pure epithelioid PEComa is made by appropriate immunohistochemical support, these potentially malignant tumors may be stratified into low, intermediate, and high-risk for progression categories based on the documentation of clinicopathologic parameters. Unlike commonly benign classic agiomyolipoma, Renal epitheloid angiomyolipoma REA behaves aggressively. Resection alone may not be curative, and adjuvant therapy should be considered. A multimodality treatment approach needs to be explored for this newly recognized malignant variant renal angiomyolipoma.
| > References|| |
|1.||Nese N, Martignoni G, Fletcher CD, Gupta R, Pan CC, Kim H, et al. Pure epithelioid PEComas (so-called epithelioid angiomyolipoma) of the kidney: A clinicopathologic study of 41 cases: Detailed assessment of morphology and risk stratification. Am J Surg Pathol 2011;35:161-76. |
|2.||Martignoni G, Pea M, Reghellin D, Zamboni G, Bonetti F. PEComas: The past, the present and the future. Virchows Arch 2008;452:119-32. |
|3.||Pan CC, Chung MY, Ng KF, Liu CY, Wang JS, Chai CY, et al. Constant allelic alteration on chromosome 16p (TSC2 gene) in perivascular epithelioid cell tumor (PEComa): Genetic evidence for the relationship of PEComa with angiomyolipoma. J Pathol 2008;214:387-93. |
|4.||Bissler JJ, McCormack FX, Young LR, Elwing JM, Chuck G, Leonard JM, et al. Sirolimus for angiomyolipoma in tuberous sclerosis complex or lymphangioleiomyomatosis. N Engl J Med 2008;358:140-51. |
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]