Angiomyolipoma (AML) is a common subtype of PEComa. It is composed of curved thick-walled blood vessels, smooth muscle, and adipocytes in varying proportions. And about 80–90% of renal AML occurs sporadically, usually isolated and unilateral [6, 7]. Some studies [8] have pointed out that AML is a common disease associated with tuberous sclerosis. Typical AML is a benign mesenchymal tumor. However, part of EAML tends to be malignant. EAML is extremely rare, accounting for about 5% of AML surgically removed [9]. Mai et al initially reported that renal AML with epithelioid morphology and its relation to AML [10] in 1996. Over 100 cases of EAML have been reported to date, however, the majority of them have benign results. At present, the pathogenesis of EAML is not clear, and there are no objective diagnostic criteria. We have recently treated a female patient who had been diagnosed as renal PEcoma with lymph node involvement.
Nalan et al [11] considered the EAML as a malignant tumor after evaluating the characteristics of numerous cases. Previous studies [11, 12] revealed that 20–30% of EAML patients developed metastasis and recurrence, with the liver, lung, and peritoneum being the most frequently implicated locations. However, the definition of the proportion of epithelioid components in EAML is not defined explicitly. Based on the literature review, the proportion of epithelioid cells ranged between 10% and 100%, and studies indicated that more than 20% of epithelioid components are associated with recurrence and metastasis. The malignant risk seems to grow in direct proportion to the percentage of epithelioid components [13, 14]. At present, rigorous diagnostic criteria for malignant renal PEComa has not been established. Pure et al [11] discovered that tumors linked with associated TSC, size > 7cm, necrosis, infiltrative growth, or vascular invasion were associated with disease progression. In our case, around 30% of the cells are epithelioid, and the heterogeneity of some cells is pronounced. As a result, this patient should be continuously monitored.
Interestingly, there is no conclusive evidence that multiple AMLs are metastatic. Some researchers considered that multiple AMLs are polycentric in origin and that may be caused by the congenital presence of cell precursors in numerous locations [7] [15]. Tallarigo et al [16] considered that lymph nodes with regional or multiple involvements demonstrated multifocal development patterns rather than metastases. At present, there is no detailed research on the postoperative adjuvant therapy and prognostic factors of renal PEComa patient with lymph node involvement. Hence, we reviewed reported cases from 2001 to 2021. As illustrated in Table 1, 16 cases of PEcoma with lymph node involvement have been recorded. Among them, 43.8% (7/16) of patients experienced local recurrence or metastasis. The most common metastatic organs were the liver and lung. Besides, 6 out of 7 patients died, with a median PFS of 16 months. As shown, metastasis to lymph node may indicated a poor prognosis. However, we can only evaluate patients with lymph node metastasis retrospectively when they are reported and cannot combine them for additional analysis.
Table 1
The clinicopathological features and follow-up information of 16 malignant PEComa cases with lymph node metastasis from 2001 to 2020
Cases | Age | Sex | TSC | Location | Metastasis at the time of diagnosis | Rec | Location of metastasis | Tumor Size (cm) | Epithelioid cells | Number of Mitosis/50 HPF | Renal vein involvement | Follow up | PFS (months) | Ref |
1 | 21 | M | Yes | Both | Liver, spleen, peritoneum, pleura; retroperitoneal lymph nodes | No | | 0.5–17 | > 90% | NA | No | NA | NA | 21 |
2 | 78 | F | NA | Left | Lung, bone, regional lymph node | No | | 12.5 | NA | NA | NA | Died | NA | 22 |
3 | 31 | F | Yes | Both | Retroperitoneal lymph nodes | No | | 1–10 | < 50% | NA | Yes | Alive | NA | 23 |
4 | 48 | F | No | Right | Retroperitoneal lymph nodes | Yes | Liver, lung | 13 | NA | NA | Yes | Died | 16 | 24 |
5 | 14 | M | Yes | NA | Lymph nodes | No | | 11 | NA | 1 | NA | Alive | 24 | 11 |
6 | 25 | F | No | NA | Lymph nodes | Yes | Peritoneal, liver, lung | 8 | NA | 2 | NA | Died | 12 | 11 |
7 | 67 | M | No | NA | Lymph nodes | No | | 15 | NA | 2 | NA | NA | NA | 11 |
8 | 58 | M | No | NA | Lymph nodes | Yes | Liver | 37 | NA | 0 | NA | Died | 24 | 11 |
9 | 55 | F | No | NA | Lymph nodes | Yes | Extensive metastatic | 12.8 | NA | 4 | NA | Died | 12 | 11 |
10 | 11 | F | No | Left | Lymph nodes | No | | 10.5 | NA | NA | NA | Died | several months | 25 |
11 | NA | NA | NA | NA | Lymph nodes | No | | NA | NA | NA | No | Alive | 36 | 26 |
12 | 71 | F | NA | NA | Retroperitoneal lymph nodes | No | | 9 | 10% | 1/10HPF | No | Alive | 54 | 27 |
13 | 59 | M | NA | NA | Retroperitoneal lymph nodes | Yes | Retroperitoneal recurrence | 16 | 100% | 2/10HPF | Yes | Alive | 40 | 27 |
14 | NA | NA | NA | NA | Renal hilus and para-aortic Lymph nodes | Yes | Hepatic, lung | NA | > 90% | NA | NA | Died | 17 | 28 |
15 | NA | NA | NA | NA | Renal hilus lymph nodes | Yes | Local recurrence | NA | > 90% | NA | NA | Died | 14 | 28 |
16 | 42 | F | NA | Left | Lymph nodes | No | | 6.7 | 30% | NA | No | Alive | 4 | |
F: Female, M: Male, Rec: Recurrence, TSC: Tuberous sclerosis complex, HPF: High power field, Ref: Reference, |
Liu et al [17] analyzed the CT scan characteristics of EAMLs and discovered a tendency for super-attenuation on pre-contrast CT with or without fat components, as well as a dynamic enhancement-mode from rapid wash-in to slow wash-out. PEComa, mainly composed of epithelial cells, could be misdiagnosed as renal clear cell carcinoma if HMB45 and Melan-A are negative. HMB-45 and Melan A are the most sensitive immunohistochemical markers in PEComa [18]. In addition, renal PEcoma should be distinguished from pleomorphic rhabdomyosarcoma, malignant melanoma, alveolar soft part sarcoma, etc. Currently, tumor excision with negative tumor margins is still the recommended treatment strategy.
Many research indicated that malignant PEComa was associated with mutations in the TFE3 and P53 genes [19, 20]. Besides, activation of mTOR was related to the malignant potential of PEComa, for which mTOR inhibitors might be beneficial [4, 5]. Thus, a multi-modal therapy strategy for PEComa with malignant potential should be explored. However, there are few publications discussing the options and efficacy of postoperative adjuvant therapy, indicating an urgent require for further research.