Massive simultaneous hepatic and renal perivascular epithelioid cell tumor benefitted from surgery and everolimus treatment: A case report.

Rationale:Perivascular epithelioid cell tumor (PEComa) is a mesenchymal tumor that arises from perivascular epithelioid cells and can differentiate into melanocytes and smooth muscle cells. Malignant renal perivascular epithelioid cell tumor is extremely rare. Due to the lack of specific clinical manifestations and imaging features, diagnosing PEComa depends on postoperative pathology and immunohistochemistry. Surgery is the primary treatment for malignant PEComa because the efficacy of radiotherapy and chemotherapy is uncertain. There is still a lack of unified diagnostic criteria and treatment guidelines for renal malignant PEComa, especially with vascular invasion. Hence, the treatment experience depends on a small number of cases reported worldwide.Patient concerns:A 68-year-old woman was admitted to our hospital due to intermittent hematuria for over 8 months. The color Doppler ultrasound and computed tomography scan revealed a mass in the lower middle part of the left kidney.Diagnosis:Rare renal malignant perivascular epithelioid cell tumor with renal vein cancerous thrombosis.Interventions:A laparoscopic radical left nephroureterectomy in the oblique supine lithotomy position was performed.Outcomes:The operation process went smoothly, and no pulmonary embolism occurred after the operation. The final pathological diagnosis was a renal malignant perivascular epithelioid cell tumor. After a 12-month follow-up, no recurrence or metastasis was found.Lessons:Renal malignant PEComa is an extremely rare mesenchymal tumor diagnosed mainly based on pathology. Surgery is currently the effective treatment for malignant PEComa. For the surgical treatment of malignant renal PEComa with vascular invasion, laparoscopic radical nephroureterectomy in the oblique supine lithotomy integrative position has many benefits, as exemplified by our current case.

Summary. The potential anti-proliferative effect of high-energy pulsed ultrasound (HEPUS) treatment on human pancreatic (PANC-1), hepatic (SK-HEP-1) and renal (CAKI-1) tumour cells was investigated in vitro. Sonication was carried out using an experimental piezoelectric burst-signal transducer, producing bipolar oscillations with a high negative pressure amplitude. In all three cell lines tested, HEPUS-application resulted in a significant reduction (P<0.05) of vital cells. After 100 pulses 35%, 20% and 41% viable pancreatic, hepatic and renal tumour cells were detected by means of the Trypan Blue Dye exclusion test, whereas after 1000 pulses only 1.3%, 1% and 0.5% were found. A post-exposure growth delay of surviving cells, compared to control cells and cells treated with 100 pulses, was only seen in case of the CAKI-1 cell line exposed to 1000 pulses.

Rats carrying the Eker tumor-susceptibility mutation (Eker rats) are predisposed to developing renal cell carcinoma. Rats heterozygous for the Eker mutation develop spontaneous multiple bilateral renal cell tumors by the age of 1 yr. In a previous study, Eker-mutation carrier and noncarrier rats were exposed to the renal carcinogen dimethylnitrosamine (DMN), and male rats carrying the Eker mutation exhibited a 70-fold increase in the induction of renal adenomas and carcinomas when compared with noncarrier rats. In this study, spontaneous and DMN-induced rat renal cell tumors (adenomas and carcinomas) were analyzed for mutations of the p53 gene by direct sequencing of cDNA polymerase chain reaction products. There were no mutations in p53 cDNA derived from renal tumors from six untreated rats. Mutations were found in one of 15 of the DMN-induced tumors: a transition at codon 140, CCT-->CTT, in a renal adenoma. Additionally, seven cell lines derived from spontaneous renal cell tumors did not contain mutations in p53. The low frequency of p53 mutations (one of 21 renal cell tumors and none of seven cell lines derived from renal cell tumors) indicates that the development of both spontaneous and carcinogen-induced renal tumors involved a non-p53-dependent pathway. As p53 is infrequently mutated in human renal cell carcinomas and in rat renal mesenchymal tumors, it is likely that a tumor suppressor gene or genes other than p53 are involved in the development of renal cancer.

Objective To evaluate the technique and efficacy of retroperitoneal laparoscopic partial nephrectomy. Methods From June 2002 to December 2009, 113 cases of renal tumor received retroperitoneal laparoscopic partial nephrectomy. The age ranged from 26 to 73 years. The tumor located in left side in 51 cases and right side in 62 cases with the mean diameter of 3.7 cm(1.2-6.3cm). During the procedure, the renal artery was separated and then clamped with bulldog. The renal parenchymal was incised with cold endoscissor and the tumor was totally removed. Pelvicalyceal repairing and parenchymal hemostasis were then performed. Renal defect closure was achieved with running suture or horizontal mattress suture. Results All the procedures were completed successfully.There was no open conversion. The mean operation time was 85 min(60- 125 min), the mean warm ischemic time was 24 min(19-43 min). The pathology studies revealed 87 cases of clear cell carcinoma, 9 cases of papillary renal cell carcinoma, 7 cases of chromophobe cell carcinoma, 6 cases of perivascular epithelioid renal cell tumor and 4 cases of renal oncocytoma. The surgical margin was negative in all cases. There was no complication of urine leakage. Gross hematuria occurred in 2 cases.During 3-41 months of following up, there was no recurrence. Conclusion Retroperitoneal laparo-scopic partial nephrectomy is safe and effective for the treatment of renal tumor, which becomes an alternative treatment to open procedure. Key words: Laparoscopes; Retroperitoneal space; Partial nephrectomy; Warm ischemia

The expression of two small stress proteins, alpha B crystallin and the 27-kDa heat shock protein (HSP27), was studied quantitatively and immunohistochemically in normal kidney and renal tumors in rats. Levels of alpha B crystallin in renal cell tumors tended to be higher than in normal kidney (P = 0.07), but with a wide range of values, whereas they were significantly lower in mesenchymal tumors (P < 0.0001). In contrast, HSP27 concentrations in both renal cell (mean +/- SD: 1790 +/- 940 ng/mg protein, n = 15) and mesenchymal (1260 +/- 1080 ng/mg protein, n = 10) tumors were significantly higher than the normal kidney value (142 +/- 30 ng/mg protein, n = 10, P < 0.0001). A positive correlation was found between alpha B crystallin and HSP27 levels limited to the renal cell tumor case (Pearson's correlation coefficient, r = 0.68, P < 0.01). Immunohistochemistry revealed the loops of Henle to be positive for alpha B crystallin, whereas HSP27 staining was positive in glomerular and interstitial vascular walls and epithelial cells of proximal and distal tubules. Positive immunostaining for alpha B crystallin was demonstrated in six of nine renal cell tumors (67%) studied and for HSP27 in all of the nine cases (100%).

Sinusoidal remodeling and angiogenesis: a new function for the liver-specific pericyte?

A 58-year-old man presented with the chief complaint of abdominal bloating and was incidentally found to have a liver tumor. As diagnostic imaging studies could not rule out malignancy, the patient underwent partial resection of segment 3 of the liver. The lesion pathologically showed eosinophilic proliferation, in addition to immunohistochemical positivity for human melanoma black 45 and Melan-A, thereby leading to the diagnosis of a hepatic perivascular epithelioid cell tumor (PEComa). A PEComa arising from the liver is relatively rare. Moreover, the name 'PEComa' has not yet been widely recognized, and the same disease entity has been called epithelioid angiomyolipoma (EAML), further diminishing the recognition of PEComa. In addition, PEComa imaging findings mimic those of malignant liver tumors, and clinically, this tumor tends to enlarge. Therefore, a PEComa is difficult to diagnose. We conducted a systematic review of PEComa and EAML cases and discuss the results, including findings useful for differentiating perivascular epithelioid cell tumors from malignant liver tumors.

肾脏血管周上皮样细胞肿瘤（PEComa）是肾脏一种良性间叶性肿瘤，临床较少见，生物学行为属于潜在恶性。PEComa较少复发和转移，预后良好。该文收集1例63岁女性发生的肾脏PEComa且发生肺转移，总结患者的临床资料、组织病理学特征、免疫表型及基因检测结果，以提高对本病的认识。

Progression of liver fibrosis to HCC (hepatocellular carcinoma) is a very complex process which involves several pathological phenomena, including hepatic stellate cell activation, inflammation, fibrosis and angiogenesis. Therefore inhibiting multiple pathological processes using a single drug can be an effective choice to curb the progression of HCC. In the present study, we used the mTOR inhibitor everolimus to observe its effect on the in vitro activation of hepatic stellate cells and angiogenesis. The results of the present study demonstrated that everolimus treatment blocked the functions of the immortalized human activated hepatic stellate cell line LX-2 without affecting the viability and migration of primary human stellate cells. We also observed that treatment with everolimus (20 nM) inhibited collagen production by activated stellate cells, as well as cell contraction. Everolimus treatment was also able to attenuate the activation of primary stellate cells to their activated form. Angiogenesis studies showed that everolimus blocked angiogenesis in a rat aortic ring assay and inhibited the tube formation and migration of liver sinusoidal endothelial cells. Finally, everolimus treatment reduced the load of tumoral myofibroblasts in a rat model of HCC. These data suggest that everolimus targets multiple mechanisms, making it a potent blocker of the progression of HCC from liver fibrosis.

Non-heat-stressed Method to Isolate Hepatic Stellate Cells From Highly Steatotic Tumor-bearing Liver Using CD49a.

Perivascular epithelioid cell tumor (PEComa), an uncommon mesenchymal neoplasm, arises from specialized perivascular epithelioid cells exhibiting distinct features of smooth muscle and melanocytic differentiation with unpredictable behavior. PEComa tends to occur more commonly in the uterus and kidneys; its occurrence in the liver is exceedingly rare. We presented a case of a 29-year-old woman with hepatic PEComa and evaluated the tumor with MRI, integrated 18F-fluorodeoxyglucose (FDG), and 68Ga-fibroblast activation protein inhibitor (FAPI) PET/CT scans at presentation. The patient had a history of intermittent utilization of oral contraceptive drugs for several years. An abdominal ultrasound in a physical examination from an outside institution revealed a mass in the liver. A contrast-enhanced abdominal MRI revealed restricted diffusion on diffusion-weighted imaging (DWI) and rapid contrast enhancement and washout patterns in the hepatic lesion, suggesting hepatic adenoma (HA) or hepatocellular carcinoma (HCC). Further assessment was carried out using 18F-FDG and 68Ga-FAPI PET/CT scans. The hepatic lesion was non-FDG avid, whereas increased tracer uptake was observed on the 68Ga-FAPI PET/CT. Subsequently, laparoscopic partial resection of liver segment V was performed. Immunohistochemical analyses demonstrated positive staining for HMB45, Melan-A, and SMA while showing negative results for AFP, glypican-3, hepatocyte, and arginase-1. The results were indicative of a hepatic PEComa diagnosis based on these findings. We also review the current literature on the clinical characteristics, pathological features, and challenges in the diagnosis of hepatic PEComa.

Perivascular epithelioid cell tumor (PEComa) is a family of mesenchymal tumors. Conventional chemotherapy has little activity in this disease, but case reports are available on the activity of mammalian target of rapamycin inhibitors (e.g. sirolimus and temsirolimus). Pharmacokinetic assays of sirolimus are available as this drug has a precise therapeutic window and blood levels might be influenced by CYP3A4 polymorphisms and drug interactions. We report on a case of a patient with metastatic, progressive PEComa who started sirolimus at a dose of 5 mg/day with evidence of grade (G) 3 mucositis, G2 thrombocytopenia, and G1 leucopenia 10 days after the treatment started, in absence of concomitant medications or prohibited food assumption. Elevated sirolimus blood levels were detected (156.8 ng/ml). Sirolimus was stopped, and toxicity resolved in 5 weeks. Computed tomography scan 2 months after the treatment started showed a partial response (RECIST). After toxicity resolution, the patient restarted sirolimus at a dose of 1 mg/day, with blood levels in the range of 10-20 ng/ml. Tumor response was confirmed and maintained, and the patient is still under treatment 18 months later, with no additional adverse effects. Genetic analysis of five selected polymorphisms (rs2740574, rs776746, rs1128503, rs2032582, and rs1045642) in drug metabolism enzymes and transporters did not provide a clear explanation of the observed unusual pharmacokinetic. This case confirms the activity of mammalian target of rapamycin inhibitors in PEComa and strengthens the importance of pharmacokinetic drug blood levels monitoring in patients treated with sirolimus. In our patient, after dose adjustment, sirolimus could be restarted with a prolonged clinical benefit and no additional toxicity.

Perivascular epithelioid cell tumor (PEComa) is a rare entity with unpredictable clinical outcome. It is a group of mesenchymal tumors with presence of perivascular epithelioid cells (PEC), known to stain positively with melanosome markers HMB-45. They may arise from many unusual sites including the kidneys. Renal PEComa was previously groupedas angiomyolipoma and its existence is rare too. Pediatric PEComas are even rarer with less than 40 cases described worldwide and none involving the kidney before. We report a case of a 7 year old boy who presented with incidental findings of an abdominal mass, which confirmed to be a renal PEComa of the atypical epithelioid angiomyolipoma (AAML) type. The clinical management and review of literature for this interesting entity is discussed.

Objective To discuss the clinical characteristics of hepatic perivascularepithelioid cell tumor (PEComa). Methods Clinical data of one patient with hepatic PEComa in the Second Affiliated Hospital, Zhejiang University School of Medicine in 2011 were analyzed retrospectively. The informed consent of the patient was obtained and the ethical committee approval was received. The patient was a 25-year-old female and was admitted in hospital for the physical examination finding of space occupying lesions in the liver. The results of physical and laboratory examinations were normal. Multiple round-like mass of low density with poorly defined borders were observed in the liver by CT scan. Significant enhancement was observed in the arterial phase by enhancement scan, and homo- or hypo-enhancement in the delayed phase. The liver lesions showed intermediated signal intensity on T1WI by MRI and slightly hyperintense on T2WI. Significant enhancement was observed in the arterial phase after enhancement and degraded in the delayed phase. The patient was primarily diagnosed with liver focal nodular hyperplasia clinically. Results After sufficient preoperative preparation, hepatectomy was performed on the patient under general anesthesia by tracheal intubation on December 8th , 2011. The tumor was observed composed of polygonal morphology cells of epithelial cells without lipocytes or abnormal blood vessels by pathological examination. The tumor was observed with strongly positive human melanoma black-45 (HMB-45), smooth muscle actin (SMA), and positive vimentin, cluster of differentiation (CD) 34. The diagnosis of hepatic PEComa was confirmed pathologically. The patient recovered well and was discharged from hospital 1 week after operation. No recurrence or metastasis was observed during the regular follow-up till the submission date. Conclusions Hepatic PEComa is extremely rare without specific clinical manifestation. The diagnosis depends on the pathological examination. Surgical resection is an effective method for the tumor with a good prognosis. Key words: Perivascular epithelioid cell neoplasms; Immunohistochemistry; Prognosis

Epithelioid angiomyolipoma (EAML) is an uncommon renal neoplasm with malignant potential. It is classified under the group of perivascular epithelioid cell tumors and can be sporadic or as part of the tuberous sclerosis complex. On imaging, unlike classical AML that contains fat, EAML has a very low percentage of fat which can mimic the imaging findings of renal cell carcinoma. We reported a 31-year-old female who had a history of renal failure and bilateral renal masses. Magnetic resonance imaging of the abdomen revealed bilateral large renal masses replacing renal parenchyma with features suggestive of bilateral renal AML. The patient underwent left nephrectomy, and histopathology examination findings were consistent with the diagnosis of EAML.