Renal Perivascular Epithelioid Cell Tumor with Lymph Nodes Metastasis: A Case Report and Literature Review

Background: Perivascular epithelioid cell tumor (PEComa) is mesenchymal tumor that originated from perivascular epithelioid cells. Angiomyolipoma (AML) is a common benign PEComa, composed of blood vessels, smooth muscle and mature adipose tissue. Epithelioid angiomyolipoma (EAML) is a rare subtype of AML that has the potential to be malignant. Case presentation: The patient was a 42-year-old woman admitted to the hospital for her left low back swelling. The computed tomography angiography (CTA) revealed a 6.3*5.5*6.7cm cystic-solid tumor in the intermediate kidney. Then we performed a left nephrectomy. Postoperative pathology showed that the tumor was angiomyolipoma (PEComa) with necrotic formation and was 6cm*6cm*5.5cm in size. Additionally, lymph nodes involved (4/17) were observed in the left renal hilum. Immunohistochemistry staining indicated that tumor cells focally expressed MelanA and HMB45. No evidence of disease progression at the six-month follow-up after surgery. Conclusions: Lymph nodes involvement in renal PEComa was rare and was regarded as a type of metastasis. Lymph nodes metastasis might indicate a poor prognosis. that


Background
Perivascular epithelioid cell tumor (PEComa) was rst described in 1943, and it is a mesenchymal tumor that originated from perivascular epithelioid cells with the immunohistochemical characteristics of smooth muscle and melanocytes [1]. PEComa has been described in various anatomical locations. The liver, pancreas, uterus and kidney are frequently involved [2]. Additionally, the PEComa family includes angiomyolipoma (AML), pulmonary clear cell "sugar" tumor, lymphangiomyomatosis and soft-tissue clear cell myomelanocytic tumors, as well as other extremely rare malignancies [3]. Although the majority of PEComas have benign clinical characteristics, a small part of them have aggressive features and can evolve into distant metastases. At present, surgery is the primary technique of treating local diseases, and there is no universally accepted standard for postoperative adjuvant therapy [4]. Notably, mTOR inhibitors have been reported to be used in the treatment of advanced PEComa [5]. Here, we present a patient who suffered from malignant renal PEComa with renal hilum lymph nodes metastasis.

Case Presentation
The patient was a 42-year-old woman admitted to the hospital for 15 days because of left lumbus pain, but no positive signs were identi ed in the physical examination. She did not complain of hematuria, urinary tract irritation symptom, or dysuria and no abnormality was identi ed in laboratory examination. There was no history of tuberous sclerosis complex (TSC).
The computed tomography angiography (CTA) revealed a 6.3*5.5*6.7cm cystic-solid tumor in left kidney's middle and lower pole, with an obvious enhancement of solid components measuring approximately 1.8*1.7cm and a patchy hemorrhagic focus. The boundary of the mass is still visible." Then the "left nephrectomy" was performed, revealing several enlarged lymph nodes in the renal hilum, followed by renal hilar lymph node dissection. A solid mass with a clear border of approximately 6 cm was evident in the renal hilum, containing hemorrhagic and necrosis tissue.
"It is diagnosed as PEComa with necrotic formation, and tumor size was 6cm*6cm*5.5cm, " according to postoperative pathology. Additionally, the lymph nodes involved (4/17) were seen in the left renal hilum. Besides, we observed that epithelioid component comprised around 30% of total. And the heterogeneity of some cells is evident, as evidenced by large and deep nucleus staining and an increase in the nuclear to cytoplasmic ratio. Necrosis was observed within the tumor. Immunohistochemistry staining showed that tumor cells expressed MelanA, Vimentin, SMA, and CD24 and were focally positive for HMB45 and CD10. Ki67 expression was detected in roughly 20% of tumor cells. However, tumor cells lacked Pax-8, S-100, and CK-pan expression. Within the six months follow-up post-operation, no disease recurrence and progression were identi ed.

Discussion
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 de nition of the proportion of epithelioid components in EAML is not de ned 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 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. 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 bene cial

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All subjects have written informed consent; All presentations of case reports have consent for publication.

Availability of data and material
All data generated or analyzed during this study are included in this article.

Competing interests
The authors declare that they have no competing interests.

Funding
This work was supported by the National Natural Science Foundation of China (grantsNo.82072832,81772711), the "333" project of Jiangsu Province (LGY2016002), and Jiangsu Province's Key Provincial Talents Program (ZDRCA2016006).
The funder is corresponding author.
Authors' contributions LC: made substantial contributions to the conception, design of the work, acquisition, analysis, interpretation of data and has drafted the work. QC: made substantial contributions to the interpretation of data and has substantially revised it. HH: made substantial contributions to the data collection. QW,BY: made substantial contributions to the picture editing. JZ,KL,JH: made substantial contributions to the Patient treatment and care. HY,JL,DF,PL,PL: made substantial contributions to the manuscript revision. XY,QL: made substantial contributions to the conception, design of the work, analysis. All authors read and approved the nal manuscript. Figure 1 CT image of the patients' abdominal organs. A, several enlarged lymph nodes were also noted (white arrow). B, a cystic-solid mass of 6.3*5.5*6.7cm was seen in the middle and lower pole of the left kidney with a noticeable enhancement of solid components and a patchy hemorrhagic focus. C and D, the solid components and blood supply of the tumor can be well observed. CT =computed tomography.