• CEUS
• Hepatic angiomyolipoma
• Hepatic perivascular epithelioid cell tumor
• Ultrasound

• Humans
• Perivascular Epithelioid Cell Neoplasms/diagnostic imaging
• Perivascular Epithelioid Cell Neoplasms/surgery
• Liver Neoplasms/diagnostic imaging
• Contrast Media
• Female
• Diagnosis, Differential
• Adult
• Ultrasonography/methods
• Liver/diagnostic imaging
• Ultrasonography, Doppler, Color/methods
• Middle Aged
• Image Enhancement/methods

• Case report
• Hepatic
• Perivascular epithelioid cell tumor
• Renal
• Surgery

• Humans
• Hemangioblastoma/genetics
• Hemangioblastoma/pathology
• Hemangioblastoma/chemistry
• Kidney Neoplasms/genetics
• Kidney Neoplasms/pathology
• Kidney Neoplasms/chemistry
• Female
• Mutation
• Male
• Tuberous Sclerosis Complex 2 Protein/genetics
• Adult
• Middle Aged
• TOR Serine-Threonine Kinases/genetics
• TOR Serine-Threonine Kinases/metabolism
• DNA Mutational Analysis
• Tuberous Sclerosis/genetics
• Tuberous Sclerosis/pathology
• Biomarkers, Tumor/genetics
• Biomarkers, Tumor/analysis
• Central Nervous System Neoplasms/genetics
• Central Nervous System Neoplasms/pathology
• Central Nervous System Neoplasms/chemistry
• Immunohistochemistry
• Tuberous Sclerosis Complex 1 Protein/genetics
• Aged
• Genetic Predisposition to Disease
• Adolescent
• Phenotype
• Young Adult
• Child
• High-Throughput Nucleotide Sequencing

• PTEN
• TFE3
• TFEB
• ccRCC
• clear cell renal cell carcinoma
• hamartin
• kidney cancer
• tuberin

• P50 CA196516 NCI NIH HHS
• P50CA196516 NIH HHS

• oncocytoma
• eosinophilic variant of chromophobe renal cell carcinoma
• rcc with cytoplasmic eosinophilia
• eosinophilic tumor
• unclassified oncocytic tumor
• hybrid oncocytic / chromophobe rccs
• lot
• low-grade oncocytic tumor
• tsc associated rcc

• kidney
• renal cell carcinoma
• targeted therapy
• tuberous sclerosis complex

• Angiomyolipoma
• Epithelioid
• Tuberous sclerosis
• mTOR inhibitor

• Epitheloide angiomyolipoma
• Kidney tumor
• Malignant degeneration
• Melanocyte marker HMB45
• Radical nephrectomy
• Turberous sclerosis

• geranylgeranyl pyrophosphate synthase
• mammalian target of rapamycin
• renal angiomyolipoma
• renal epithelioid angiomyolipomas

• metastatic disease
• recurrence
• renal epithelioid angiomyolipoma
• treatment

• Angiomyolipoma
• Epithelioid angiomyolipoma
• Magnetic resonance imaging
• Perivascular epithelioid cell neoplasms
• Renal neoplasms

• Adult
• Angiomyolipoma/diagnostic imaging
• Female
• Humans
• Kidney/diagnostic imaging
• Kidney Neoplasms/diagnostic imaging
• Magnetic Resonance Imaging/methods
• Male
• Middle Aged
• Retrospective Studies
• Young Adult

Renal epithelioid angiomyolipomas (EAML) are rare tumors with aggressive behavior. EAML can be sporadic or develop within the tuberous sclerosis complex syndrome, where mutations of TSC1 or TSC2 genes (critical negative regulators of mTOR Complex 1) result in an increased activation of mTOR pathway. Optimal EAML treatment, including mTOR inhibitors, remains undetermined.

Here we present the case of a young adult with a renal EAML that after radical nephrectomy developed metastases, first in liver and then in lumbar vertebrae. After complete surgical resection of these lesions, liver recurrence was detected, this time with incomplete surgical resection. After finding a new liver lesion, systemic treatment with sirolimus started. The patient exhibited a complete and durable response to this drug, being disease free at the time of publication, after 36 months of treatment. Targeted next generation sequencing (NGS) of MTOR, TSC1 and TSC2 genes in the primary tumor, metastasis and blood of the patient, revealed one inactivating TSC2 mutation (c.2739dup; p.K914*) in the tumor cells. Immunohistochemistry revealed decreased TSC2 protein content and increased phospho-S6 in the tumor cells, demonstrating mTOR pathway activation.

NGS on an EAML patient with an extraordinary response to sirolimus uncovered TSC2 inactivation as the mechanism for the response. This study supports NGS as a useful tool to identify patients sensitive to mTOR inhibitors and supports the treatment of malignant EAML with these drugs.

• Renal epithelioid angiomyolipoma
• Sirolimus
• TSC2 mutation
• mTOR pathway activation

Tuberous sclerosis complex (TSC) is a rare autosomal dominant genetic disorder characterized by the development of numerous benign tumors. Renal angiomyolipoma (RAML) occur in up to 80% of TSC patients, which is a leading cause of TSC-related death in adult patients. The aim of the study was to evaluate the efficacy and safety profiles of everolimus in Chinese patients of TSC associated with RAML(TSC-RAML).

In this 2-years, nonrandomized, open-label trial, 18 patients of TSC-RAML, with at least one RAML 3 cm or larger in its longest diameter, were enrolled to assess the efficacy and safety of everolimus therapy in Chinese patients. Everolimus was administered for the first 12 months only. The primary endpoint was a reduction of 50% or more relative in RAML volume to the baseline in the absence of new RAML ≥1 cm and no RAML-related bleeding of grade ≥ 2. The secondary endpoints included: safety, lung function and skin lesions response rate. Serial computed tomography of RAML, magnetic resonance imaging of brain lesions and pulmonary-function tests were performed. Adverse events were investigated using CTCAE v4.0. All analyses used a significance level of 0.05 and were generated in SPSS19.0 software.

The proportion of patients who achieved ≥50% reduction from baseline in the sum of volumes of target lesions increased from 52.94% at 3 months, to 58.82% and 66.67% at months 6 and 12, respectively. During the period of everolimus therapy, among patients with lymphangioleiomyomatosis, the mean forced expiratory volume in 1 s (FEV1) increased by 276 ± 78 ml (P < 0.001), the forced vital capacity (FVC) increased by 433 ± 170 ml (P < 0.001), and the residual volume decreased by 408 ± 243 ml (P = 0.009), as compared with baseline values. The angiomyolipoma volume and the lung function approached, but did not completely return to, the baseline values. The skin lesions response rate was 37.5% after 12 months of therapy falling to 21.4% at 12 months after stopping everolimus. The most common adverse events were mucositis oral, irregular menstruation, abdominal pain, hypertriglyceridemia and headache. The most common grade 3 adverse events were irregular menstruation and mucositis oral. In addition, one patient died from RAML spontaneous haemorrhage during treatment with everolimus, even with reduction in RAML volume of 60.68% at 3 months. A second death was due to epithelioid RAML progression, with metastasis to multiple retroperitoneal lymph node, who died from severe infection one month after surgery.

Angiomyolipomas regressed somewhat during everolimus therapy but tended to increase in volume after the therapy was stopped. Everolimus was well tolerated and showed promising activity in Chinese patients with TSC-RAML, however, we should alert the life-threatening hemorrhage of large RAML in the early period and the lymph node metastasis of epithelioid RAML.

ChiCTR-OPC-14005488. Registered November 17, 2014.

The online version of this article (10.1186/s13023-018-0781-y) contains supplementary material, which is available to authorized users.

• Angiomyolipoma
• Everolimus
• Safety
• Treatment outcome
• Tuberous sclerosis complex

Mammalian target of rapamycin (mTOR) complex 1 (mTORC1) acts as a downstream effector of phosphatidyl-inositol-3 kinase, which is frequently hyperactivated in glioblastoma multiforme and links to cell signaling in cellular proliferation, differentiation, metabolism, and survival. Although many studies have suggested the importance of mTORC1 in tumorigenesis, its role remains unclear in brain tumors other than glioblastoma.

In the present study, we evaluated the activation of mTORC1 in 24 cases of primary central nervous system lymphoma (PCNSL).

Immunohistochemical analysis showed overexpression of Rheb, which is immediately upstream of mTORC1, in 20 cases of PCNSL. Immunohistochemical analysis also showed overexpression of phospho-4E-BP1 (Thr37/46) and phospho-S6 (Ser235/236), which are increased after mTORC1 activation as mTORC1 downstream effectors in 17 and 21 cases, respectively.

Our data suggest that abnormal activation of the mTORC1 signaling pathway may cause tumor growth in patients with PCNSL.

• Rheb
• mTOR
• phospho-4E-BP1
• phospho-S6
• primary central nervous system lymphoma

Perivascular epitheloid cell tumors (PEComas) are rare tumors of malignant potential. There is no normal cell variant to these cells. The family is large and includes angiomyolipoma, clear cell “sugar” tumor amongst others. Imaging modalities are not very diagnostic. The diagnosis hence is often postoperative. A 55-year old female presented to us with ultrasonographic diagnosis of solid mass in the right infrarenal region. Contrast-enhanced computerized sonography (CECT) suggested paraganglioma or a soft tissue retroperitoneal tumor. Laparoscopic excision was successful. The rarity of this pathology and laparoscopic modality of excision prompted us to publish this report.

• Laparoscopy
• PEComa
• surgery

• Angiomyolipoma
• Clear cell myomelanocytic tumor
• Lymphangioleiomyomatosis
• Perivascular epithelioid cell tumor
• Sirolimus
• TFE3
• Tuberous sclerosis

Angiomyolipoma is the most common benign solid renal neoplasm observed in clinical practice. Once thought to be a hamartoma and almost always diagnosed by the imaged-based detection of fat, angiomyolipomas are now known to consist of a heterogeneous group of neoplasms. Although all are considered perivascular epithelioid cell tumors, many display different pathology, imaging features, and clinical behavior. The importance of understanding this group of neoplasms is emphasized by the fact that many types of angiomyolipoma contain little to no fat, and despite being benign, sometimes escape a pre-operative diagnosis. These types of angiomyolipomas can all be considered when encountering a renal mass that is both hyperattenuating relative to renal parenchyma on unenhanced CT and T2-hypointense, features that reflect their predominant smooth muscle component. We review recent developments and provide a radiological classification of angiomyolipomas that helps physicians understand the various types and learn how to both diagnose and manage them.

Epithelioid angiomyolipoma (E-AML), accounting for 8% of renal angiomyolipoma, is usually associated with tuberous sclerosis (TS) and demonstrates aggressive behavior. E-AML is macroscopically seen as a large infiltrative necrotic tumor with occasional extension into renal vein and/or inferior vena cava. However, without history of TS, renal sinus and venous invasion E-AML would be a challenging diagnosis, which may lead radiologists to misinterpret it as a renal cell carcinoma (RCC). In this case presentation, we aimed to report cross-sectional imaging findings of two cases diagnosed as E-AML and pathological correlation of these aforementioned masses mimicking RCC.

• Angiomyolipoma/diagnosis
• Angiomyolipoma/surgery
• Angiomyolipoma/therapy
• Diagnosis, Differential
• Diagnostic Imaging/methods
• Embolization, Therapeutic/methods
• Humans
• Kidney/diagnostic imaging
• Kidney/pathology
• Kidney Neoplasms/diagnosis
• Kidney Neoplasms/surgery
• Kidney Neoplasms/therapy
• Magnetic Resonance Imaging/methods
• Tomography, X-Ray Computed/methods
• Ultrasonography/methods

• Alveolar soft part sarcoma
• Chemotherapy
• Clear cell sarcoma
• Hemangiopericytoma
• Inflammatory myofibroblastic tumor
• Perivascular epithelioid cell tumor
• Sarcoma
• Solitary fibrous tumor

• CDK4/6 inhibition
• PEPI score
• drug resistance
• dual targeting
• neoadjuvant trials
• pertuzumab
• poly (ADP-ribose) polymerase inhibitors
• trastuzumab
• trastuzumab-emtansine

Epithelioid angiomyolipomas (EAMLs) are rare mesenchymal tumors whose malignant variant is extremely uncommon and highly aggressive. Treatment strategies include chemo radiation, transcatheter arterial embolization and surgical resection, which has remained the mainstay treatment. Targeted therapies including mammalian target of rapamycin (mTOR) inhibitors such as Temsirolimus may offer some hope for progressive malignant EAMLs that are not amenable to other treatment modalities. We report a fatal case in a young female who presented with rapidly progressive metastatic EAML that did not respond to mTOR therapy. The literature has shown reduction in tumor burden with the use of mTOR inhibitors, but unfortunately due to the rarity of malignant EAML, a meaningful approach to treatment remains challenging.

• malignant epithelioid angiomyolipomas
• perivascular epithelioid cell tumors
• targeted therapy

A 22-year-old female presented with back pain and was discovered to have a right-sided abdominal mass. Computed tomography (CT) scan revealed a 9 cm enhancing right upper pole renal mass with suspicion for tumor thrombus into the right renal vein and possibly the inferior vena cava (IVC). Magnetic resonance imaging (MRI) confirmed tumor thrombus into the inferior vena cava approximately 3 cm below the hepatic venous confluence. Open right radical nephrectomy with inferior vena cava thrombectomy was performed with removal of right kidney and tumor thrombus en bloc. Pathology revealed malignant epithelioid angiomyolipoma (EAML or PEComa). Epithelioid angiomyolipoma is a rare tumor of mesenchymal tissue that has the potential for local invasion and disease progression. Diagnosis of EAML was confirmed by pathology and immunohistochemistry. She was referred to medical oncology for discussion of surveillance versus potential adjuvant therapy and ultimately opted for close surveillance.

• Angiomyolipoma
• Imaging
• Kidney tumors
• Lymphoma
• Mammalian target of rapamycin

The rare variant of renal epithelioid/pleomorphic angiomyolipoma has been reported in approximately 120 cases. One of the most important characteristics to differentiate these tumors from other renal cell neoplasms is their typical reactivity to premelanosome antigens. If such a tumor does not stain for HMB-45 or Melan-A, a specific diagnosis of epithelioid pleomorphic angiomyolipoma cannot be made with certainty.

We present here what is, to the best of our knowledge, the first case of epithelioid/pleomorphic angiomyolipoma of the kidney in a 50-year-old Caucasian man with no history of tuberous sclerosis, and with a tumor marker profile negative for several premelanosome antigens. The tumor was composed of sheets of pleomorphic, round to polygonal epithelioid cells with prominent eosinophilic cytoplasm, large nuclei, many multinucleated, and very prominent nucleoli. There were prominent vessels and rare interspersed smooth muscle fibers, but adipocytes were not identified. A tumor marker profile showed tumor cell reactivity for CD68, calponin and focally for CD10. Intervening smooth muscle was reactive with smooth muscle actin. The tumor lacked reactivity for melanin-associated antigens HMB-45 and Melan-A, and for CD31, pan-cytokeratin (AE1/3) and desmin. Electron microscopic examination of tumor cells confirmed the presence of premelanosome-like granules.

Based on the characteristic microscopic appearance of this tumor, and its overall tumor marker profile, we concluded this was a renal epithelioid/pleomorphic angiomyolipoma with a negative premelanosome antigen phenotype.

• angiomyolipoma
• computed tomography
• magnetic resonance imaging
• renal cell carcinoma
• renal neoplasms

• epithelioid angiomyolipoma
• everolimus
• mammalian target of rapamycin inhibitors
• targeted therapy
• tuberous sclerosis complex