Renal Epithelioid Angiomyolipoma Research Articles

Giant Epithelioid Angiomyolipoma of Kidney - A Rare Case Report

Renal angiomyolipoma is a benign mesenchymal neoplasm of kidney and composed of varied proportions of adipose tissue, smooth muscle cells- spindled or epithelioid and dysmorphic thickened or hyalinised blood vessels. Epithelioid angiomyolipoma is one of the rare variants of angiomyolipoma with high degree of complications, recurrence and metastasis. Whereas classic angiomyolipoma does not show metastasis and recurrence. Giant epithelioid angiomyolipoma means tumor size measuring greater than10 cm, very few cases have been reported in literature. Epithelioid angiomyolipoma of size greater than 20 cm is extremely rare. Here we report a rare case of giant epithelioid renal angiomyolipoma of size greater than 20 cm in a 21-year-old female, presented with complaints of right flank pain and hematuria. The patient underwent nephrectomy with probability of malignancy given in ultrasonography and specimen was sent for histopathological examination. Gross examination revealed enlarged kidney of size 22×18×10 cm and cut section shows grey white to yellow lesion measuring 21×17×10 cm almost occupying entire kidney. Microscopic examination revealed interlacing fascicles of spindle cells, lobules of adipocytes and thickened blood vessels. Foci of pleomorphic epithelioid cells with illdefined cell borders, pleomorphic vesicular nucleus and prominent nucleoli are noted. Keywords: Epithelioid, angiomyolipoma, mesenchymal, giant, kidney

Differentiation between renal epithelioid angiomyolipoma and clear cell renal cell carcinoma using clear cell likelihood score.

Clear cell likelihood score (ccLS) may be a reliable diagnostic method for distinguishing renal epithelioid angiomyolipoma (EAML) and clear cell renal cell carcinoma (ccRCC). In this study, we aim to explore the value of ccLS in differentiating EAML from ccRCC. We performed a retrospective analysis in which 27 EAML patients and 60 ccRCC patients underwent preoperative magnetic resonance imaging (MRI) at our institution. Two radiologists trained in the ccLS algorithm scored independently and the consistency of their interpretation was evaluated. The difference of the ccLS score was compared between EAML and ccRCC in the whole study cohort and two subgroups [small renal masses (SRM; ≤ 4cm) and large renal masses (LRM; > 4cm)]. In total, 87 patients (59 men, 28 women; mean age, 55±11 years) with 90 renal masses (EAML: ccRCC = 1: 2) were identified. The interobserver agreement of two radiologists for the ccLS system to differentiate EAML from ccRCC was good (k = 0.71). The ccLS score in the EAML group and the ccRCC group ranged from 1 to 5 (73.3% in scores 1-2) and 2 to 5 (76.7% in scores 4-5), respectively, with statistically significant differences (P < 0.001). With the threshold value of 2, ccLS can distinguish EAML from ccRCC with the accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 87.8%, 95.0%, 73.3%, 87.7%, and 88.0%, respectively. The AUC (area under the curve) was 0.913. And the distribution of the ccLS score between the two diseases was not affected by tumor size (P = 0.780). The ccLS can distinguish EAML from ccRCC with high accuracy and efficiency.

The value of Computed Tomography in the Diagnostic and Prognostic Prediction of Renal Epithelioid Angiomyolipoma.

This study aimed to assess the importance of computed tomography (CT) imaging in the diagnostic and prognostic evaluation of renal epithelioid angiomyolipoma (EAML). This study comprised 63 patients diagnosed with renal EAML in the First Affiliated Hospital of Soochow University during 2010-2021, who met the inclusion criteria. The clinical, pathological, and therapeutic features were analyzed to determine the optimum diagnostic and therapeutic approaches. Of the 63 participants, 20 were men and 43 women aged 24-74 years (average, 45.5 years). In 35 and 28 participants, the tumor was located on the left and right sides, respectively. All the patients underwent CT scanning. Most of the patients (54/63) with EAMLs demonstrated hyperattenuation, one showed isoattenuation, and eight showed hypoattenuation compared with renal parenchyma on unenhanced CT images. The diameter of each tumor was 2-25 cm (average, 5.6 cm). All the participants underwent surgical treatment. Of these, 53 were followed up for 4-128 months (median, 64 months). Among the followed-up patients, one died of the tumor, one died due to acute severe pancreatitis, and two had an ipsilateral recurrence. EAML is a relatively rare renal angiomyolipoma depleted in fat. A characteristic of hyperattenuation on unenhanced CT images in EAML can help distinguish this tumor from clear cell renal cell carcinoma. Surgical resection is the main treatment. Most EAMLs are benign, and only a few have malignant potential. However, post-surgery recurrence and metastasis may occur, especially in elderly patients, and thus close follow-up is recommended.

P53 aberration and TFE3 gene amplification may be predictors of adverse prognosis in epithelioid angiomyolipoma of the kidney

BackgroundAlthough epithelioid angiomyolipoma of the kidney has been studied by several groups, the reported prevalence of malignant behavior remains uncertain and there are not yet definitive predictive biomarkers. We evaluated the behavior of renal epithelioid angiomyolipoma in a consecutive series in a single institution and investigated the prognostic value of aberrant p53 expression and TFE3 gene abnormality.MethodsWe retrospectively reviewed 14 epithelioid angiomyolipomas, most with pure or close to pure epithelioid components, comprising 12 consecutive cases who had attended our institution and two consultation cases. Fluorescence in situ hybridization with TFE3 break-apart probe was performed on 14 cases. The 14 cases were also labeled for p53 and TFE3 by immunohistochemistry. All cases were followed up.ResultsThree of the epithelioid angiomyolipomas were strongly positive for TFE3 and two had a mutant expression of p53. Although no TFE3 gene rearrangement was found, the two tumors with strong TFE3 expression showed TFE3 gene amplification. Follow-up details were available for seven of the 12 consecutive cases: two of them had developed metastases and died (29%), their mean overall survival was 41 months, and both had mutant p53 expression. The two consultation cases with TFE3 gene amplification developed recurrence/metastasis within 1 year after surgery.ConclusionsOur series study from a single institution presented the prevalence of malignant behavior in pure epithelioid angiomyolipomas, although the small number of cases with follow-up data greatly reduced the accuracy. p53 may be a prognostic marker for epithelioid angiomyolipoma. Cases with TFE3 gene amplification had poor prognoses.

Synchronous Papillary Thyroid Carcinoma and Renal Epithelioid Angiomyolipoma with Hepatic Metastasis or Concurrence: A Clinicopathological Characteristics and Outcome

Synchronous Papillary Thyroid Carcinoma and Renal Epithelioid Angiomyolipoma with Hepatic Metastasis or Concurrence: A Clinicopathological Characteristics and Outcome

♣Evaluation of clinicopathological profiles and development of a risk model in renal epithelioid angiomyolipoma patients: a large-scale retrospective cohort study

BackgroundTo identify the malignant potential and prognostic indicators of renal epithelioid angiomyolipoma (eAML), clinicopathological and molecular features as well as the drug efficacy of 67 eAML cases were analyzed.Materials and methodsSixty-seven renal eAML patients were enrolled and the immunohistochemical features of these patients were examined. FFPE slides of all patients were re-examined. 21 patients with metastasis received Everolimus 10 mg orally once daily. Responses were evaluated with RECIST criteria by three authors. A risk stratification model was constructed using the following factors: pT3 and pT4, presence of necrosis, mitotic count ≥ 2; the presence of atypical mitoses; severe nuclear atypia, SMA negative, Ki-67 ≥ 10%.ResultsThe average percentage of the epithelioid component was 85.6% (range 80–95%). Immunohistochemically, Ki-67 ≥ 10% and negative SMA staining were significantly correlated with malignant characteristics (Ki-67: p < 0.001; SMA: p = 0.001). Survival analysis suggested that pT3-pT4 stage, presence of necrosis, severe nuclear atypia, presence of atypical mitoses, mitotic count ≥ 2, Ki-67 ≥ 10% and negative SMA expression were significantly associated with poorer PFS and OS (p < 0.05). The risk model sufficiently discriminated recurrence/metastasis (AUC = 0.897) and cancer-specific mortality (AUC = 0.932) of renal eAML patients in different risk groups. 21 patients had received Everolimus targeted therapy after recurrence/metastasis. The best response for Everolimus treatment was 8/21 (38.1%) partial responses (PR), 9/21 (42.9%) stable disease (SD) and 4/21 (19.0%) progressive disease (PD).ConclusionThe risk stratification model could well distinguish eAML patients at high risk of recurrence/metastasis. Everolimus targeted treatment showed good efficacy in patients with recurrence/metastasis.

Advancements in the diagnosis and treatment of renal epithelioid angiomyolipoma: A narrative review.

Renal epithelioid angiomyolipoma (EAML) is a unique subtype of angiomyolipoma that contains a variety of cytoplasmic-rich, eosinophilic cytoplasm epithelioid cells in addition to mature adipocytes, hyaline thick-walled vessels, and smooth muscle-like spindle cells. In recent years, increasing evidence has shown that EAML is a potentially malignant tumor. Due to the lack of typical clinical manifestations and imaging features, it is difficult to diagnose before surgery, and the diagnosis mainly depends on postoperative histopathological examination. With the advancement of pathological diagnostic techniques, more EAML cases has been discovered, but clinicians still lack a comprehensive understanding of EAML. This review comprehensively describes some pathological and clinical features of EAML, with special attention to the pathogenesis and treatment of malignant EAML in order to assist with clinical diagnosis and treatment.

Differentiating renal epithelioid angiomyolipoma from clear cell carcinoma: using a radiomics model combined with CT imaging characteristics.

This study aims to assess the computed tomography (CT) findings of renal epithelioid angiomyolipoma (EAML) and develop a radiomics-based model for differentiating EAMLs and clear cell renal cell carcinomas (RCCs). This two-center retrospective study included 28 histologically confirmed EAMLs and 56 size-matched clear cell RCCs with preoperative three-phase kidney CTs. We conducted subjective image analysis to determine the CT parameters that can distinguish EAMLs from clear cell RCCs. Training and test sets were divided by chronological order of CT scans, and radiomics model was built using ten selected features among radiomics and CT features. The diagnostic performance of the radiomics model was compared with that of the three radiologists using the area under the receiver-operating characteristic curve (AUC). The mean size of the EAMLs was 6.2 ± 5.0cm. On multivariate analysis, a snowman or ice cream cone tumor shape (OR 16.3; 95% CI 1.7-156.9, P = 0.02) and lower tumor-to-cortex (TOC) enhancement ratio in the corticomedullary phase (OR 33.4; 95% CI 5.7-197, P < 0.001) were significant independent factors for identifying EAMLs. The diagnostic performance of the radiomics model (AUC 0.89) was similar to those of genitourinary radiologists (AUC 0.78 and 0.81, P > 0.05) and superior to that of a third-year resident (AUC 0.63, P = 0.04). A snowman or ice cream cone shape and lower TOC ratio were more closely associated with EAMLs than with clear cell RCCs. A CT radiomics model was useful for differentiating EAMLs from clear cell RCCs with better diagnostic performance than an inexperienced radiologist.

Osseous Metastases of Renal Epithelioid Angiomyolipoma with Dramatic Response Through mTOR Inhibitor Therapy

Osseous Metastases of Renal Epithelioid Angiomyolipoma with Dramatic Response Through mTOR Inhibitor Therapy

Renal epithelioid angiomyolipoma: computed tomography manifestation and radiologic-pathologic correlation depending on different epithelioid component percentages.

Renal epithelioid angiomyolipoma (EAML) is a rare and potentially malignant mesenchymal lesion mainly composed of epithelioid cells. Although some case reports or small case series have been published, the computed tomography (CT) manifestations and radiologic-pathologic correlation depending on different epithelioid component percentages have not been studied before. To investigate the CT manifestation and radiologic-pathologic correlation between renal EAML and angiomyolipoma (AML) with epithelioid component. The clinicopathologic and imaging data of 53 patients with an original diagnosis of EAML or AML with epithelioid component were retrospectively collected from three hospitals. All tissue specimens were re-sectioned and re-observed under the microscope. Samples were divided into an EAML group (≥ 80% epithelioid component, n = 25) and AML with epithelioid component group (5% ≤ epithelioid component < 80%, n = 28). Two radiologists reviewed the images in consensus, describing and comparing the CT manifestation, including the long diameter of the tumor, morphology, presence of necrosis or cystic change, hemorrhage, fat, calcification, enlarged blood vessels, and dynamic enhancement pattern according to the Hounsfield unit value of each CT phase between the two groups. The radiologic-pathologic correlation depending on the different percentages of epithelioid component were studied. The long diameter of the tumor, presence of necrosis or cystic change, fat, enhancement pattern, and tumor-to-cortex enhancement ratio of the cortical phase between the two groups were significantly different (z = - 2.932, P = 0.003; χ2 = 18.020, P < 0.001; χ2 = 16.377, P < 0.001; P = 0.020; and T = - 3.944, P < 0.001, respectively). In multivariate logistic regression analysis, the significant predictive factors of EAML included the presence of necrosis or cystic change [odds ratio (OR) 11.864, P = 0.001] and absence of fat (OR 0.095, P = 0.003). Correlation analysis found that the presence of necrosis or cystic change (r = 0.679, P < 0.001) and fat (r = - 0.603, P < 0.001) were both moderately related to the epithelioid component percentage. The combined model based on the presence of necrosis or cystic change and absence of fat yielded the best diagnostic performance in discriminating EAML and AML with epithelioid component with the highest area under the curve (0.887). EAML has characteristic CT signs; these characteristic CT signs are closely related to the epithelioid component percentage. The presence of necrosis or cystic change and the absence of fat were independent predictors of EAML.

Renal Epithelioid Angiomyolipoma with Aggresive Progression: A Case Report and Literature Review

Renal Epithelioid Angiomyolipoma with Aggresive Progression: A Case Report and Literature Review

Everolimus in Invasive Malignant Renal Epithelioid Angiomyolipoma.

BackgroundTo evaluate the efficacy and safety of everolimus, a mTOR inhibitor, on invasive malignant renal epithelioid angiomyolipoma (EAML).Materials and MethodsFrom Oct 2014 to May 2019, we collected data from seven patients with a definite (clinical and pathological) diagnosis of EAML received everolimus in our hospital. Targeted sequence capture array technique with next-generation of high throughput sequencing (NGS) were performed to detect mutations of TSC1/2 genes. All patients had received surgery and everolimus. The clinical efficacy and safety of the therapy were evaluated.ResultsMutations of TSC1 and TSC2 were detected in two and three patients though targeted sequence capture array technique with NGS, respectively. Among seven patients, three had missense mutations, one had nonsense mutation, and one had the large fragment deletion mutation. Five patients accompanied with tuberous sclerosis complex (TSC) were identified. All patients were administered 10mg everolimus once daily, the treatment duration lasted for 3 to 28 months. The objective response was assessed 3 months later, five partial response, two stable disease (SD), the mean greatest tumor diameter of all patients decreased from 9.6 to 5.2cm. Six patients stayed SD and one patient died during follow up. Patients accompanying with TSC had better responses to everolimus compared with non-TSC.ConclusionThe mTOR inhibitor can be an effective treatment for patients with invasive malignant renal EAML. Patients with TSC may benefit more from the therapy.

Renal Epithelioid Angiomyolipoma: A Case Report and Review of Literature.

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.

Renal Epithelioid Angiomyolipoma: A Case Report and Review of Literature

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.

Partial nephrectomy can be a successful treatment option for renal epithelioid angiomyolipoma: a case report and literature review.

Renal epithelioid angiomyolipoma is arare tumour which involves kidneys in most cases. It is known for its aggressive behaviour as asignificant number of cases have been associated with metastatic epithelioid angiomyolipoma. Usually, radical treatment with systemic therapy is recommended. Only asmall number of cases of epithelioid angiomyolipomas have been reported with thestandard treatment being radical or partial nephrectomy. We present a case report showing that partial nephrectomy can be asuccessful treatment option for renal epithelioid angiomyolipoma. This is thefirst case of this nature in Lithuania. In this case, a40-year-old male with epithelioid angiomyolipoma of theleft kidney is presented. In 2012, acystic left renal mass 40×41mm in size was diagnosed incidentally while performing ultrasound and later confirmed by MRI. Due to thesize of thetumour and thepossibility of renal cell carcinoma, surgery was scheduled. Left partial nephrectomy was performed successfully. Final pathology report came back with thediagnosis of renal epithelioid angiomyolipoma. Thepatient had yearly follow-up for six years by CT scan, and neither recurrence nor progression were observed. Early detection and diagnosis are crucial for treatment as thetumour tends to have malignancy potential. With early diagnosis, partial nephrectomy can be performed with yearly follow-up and no systemic treatment required.

Renal epithelioid angiomyolipoma: Incidence in a Japanese cohort and diagnostic utility of diffusion-weighted magnetic resonance imaging.

To show the epidemiological characteristics of epithelioid angiomyolipoma in a Japanese population, and to establish the preoperative diagnosis method of epithelioid angiomyolipoma. Among the 855 tumors of patients who underwent partial/radical nephrectomy or renal biopsy for presumed renal cell carcinoma between 2007 and 2018, 39 renal tumors were diagnosed as nonclassical angiomyolipoma, including epithelioid angiomyolipoma and fat-poor angiomyolipoma. We retrospectively evaluated the incidence of epithelioid angiomyolipoma. Furthermore, we analyzed computed tomography and magnetic resonance imaging results, including diffusion-weighted magnetic resonance imaging findings of epithelioid angiomyolipoma and fat-poor angiomyolipoma. The incidence of epithelioid angiomyolipoma (n=7) was 17.9% of surgically resected non-classical angiomyolipoma. The radiological appearance of epithelioid angiomyolipoma was hyperattenuating on unenhanced computed tomography images with iso or low intensity on T2-weighted magnetic resonance imaging. The mean apparent diffusion coefficient value of the solid component in epithelioid angiomyolipoma was significantly lower than that in fat-poor angiomyolipoma (median 0.79×10-3 vs 1.07×10-3 mm2 /s, P=0.0019). The proportion of epithelioid angiomyolipoma in our Japanese cohort was equivalent to that of the reported series in the USA. The apparent diffusion coefficient value is potentially useful to differentiate between epithelioid angiomyolipoma and fat-poor angiomyolipoma. Further research is required to establish the imaging diagnostic criteria for epithelioid angiomyolipoma.

Case report of everolimus-induced sustained partial response in metastatic renal epithelioid angiomyolipoma.

Epithelioid variant of angiomyolipoma (EAML) is a newly defined entity and a close mimicker of renal cell carcinoma. There is a growing body of evidence to suggest its aggressive behavior in terms of local recurrence, metastasis and death. The treatment for this subset of patients has posed challenges for the experts. Chemotherapy plays little active role and so molecular profiling to identify genomic alterations amenable to targeted therapies has paved the way. Recently, tyrosine kinase inhibitors and mTOR inhibitors have been utilised both in adjuvant and neoadjuvant settings and have shown promising results in terms of survival. We present a case of a metastatic epithelioid angiomyolipoma treated sequentially with imatinib, crizotinib and now maintaining a sustained partial response with everolimus.

PT193 - Renal epithelioid angiomyolipoma: Incidence in a Japanese cohort and diagnostic utility of diffusion-weighted MRI

PT193 - Renal epithelioid angiomyolipoma: Incidence in a Japanese cohort and diagnostic utility of diffusion-weighted MRI

Clinicopathologic analysis of renal epithelioid angiomyolipoma: Consecutively excised 23 cases.

Renal epithelioid angiomyolipoma (eAML) is considered a malignant variant of angiomyolipoma (AML). From 2001 to 2016, a total of 570 patients were diagnosed with renal AML in Linko Chang Gung Memorial Hospital, Taiwan, including 23 cases of renal eAML. All 23 eAML cases were made up of at least 10% of epithelioid cells histologically. Three of these cases were found with multiple tumors. Two cases developed distant metastasis: one had mediastinal lymph nodes and bilateral lung metastasis; the other one had tumor recurrence over liver and retroperitoneum 1 year after radical nephrectomy. They were then divided into invasive (n = 5) and noninvasive (n = 18) groups according to their clinical behavior. The invasive group showed more severe nuclear atypia and higher rates in tumor necrosis. There was statistically no significance in relation to a patient's age, tumor size, and mitotic count between two groups. After conducting a series of studies, we suggest treating eAML with the guideline of renal cell carcinoma.

Evidence for a role of geranylgeranylation in renal angiomyolipoma and renal epithelioid angiomyolipoma.

Research on mevalonate kinase deficiency has revealed that it may lead to the development of renal angiomyolipomas (RAMLs). Thus, it was suspected that geranylgeranyl pyrophosphate synthase (GGPPS), a key enzyme in the mevalonate pathway, may be involved in the development of RAMLs. In the present study, the expression of GGPPS in RAMLs and renal epithelioid angiomyolipomas (REAs) was assessed, and paraffin embedded specimens from 60 patients, including 9 cases with REA and 51 cases with RAML, were examined. Immunoreactivity was evaluated semi-quantitatively according to the intensity of staining and the percentage of positively stained cells. The results indicated that GGPPS was predominantly present in the cytoplasm, and REA tissues exhibited higher expression of GGPPS in the cytoplasm compared with RAML tissues. It was also identified that GGPPS was upregulated in TSC2-null cells, and inhibition of GGPPS could induce apoptosis of TSC2-null cells by autophagy. In conclusion, the increased expression of GGPPS in RAMLs and REAs indicated that mevalonate pathways may be involved in disease progression. GGPPS may serve as a potential therapeutic target and the current results may provide a novel therapeutic strategy for RAML and lymphangioleiomyomatosis.