Activation of the mTOR pathway in sporadic angiomyolipomas and other perivascular epithelioid cell neoplasms

Kenerson, Heidi L.; Folpe, Andrew L.; Τakayama, Thomas K.; Yeung, Raymond S.

doi:10.1016/j.humpath.2007.01.028

Cited by 213 publications

(164 citation statements)

References 44 publications

Supporting

Mentioning

149

Contrasting

Unclassified

Order By: Relevance

“…1,2 The pathogenesis of angiomyolipoma is determined by mutations affecting TSC genes, with eventual deregulation of the RHEB/MTOR/ RPS6KB2 pathway. 3 It has been observed that angiomyolipomas regressed somewhat during sirolimus therapy, an MTOR inhibitor, but tended to increase in volume after the therapy was stopped. 4 Histologically, the common angiomyolipoma is characterized by the presence of a variable mixture of fat, spindle and epithelioid smooth muscle cells, and abnormal thick-walled blood vessels.…”

mentioning

confidence: 99%

Cathepsin K expression in the spectrum of perivascular epithelioid cell (PEC) lesions of the kidney

et al. 2012

View full text Add to dashboard Cite

The perivascular epithelioid cell (PEC) is a unique cell type coexpressing contractile proteins (mainly a-smooth muscle actin), melanocytic markers, including microphthalmia-associated transcription factor (MITF), and estrogen and progesterone receptors. It is constantly present in a group of tumors called PEComas. Renal PEComas include the common angiomyolipoma as well as less common lesions such as microscopic angiomyolipoma, intraglomerular lesions, angiomyolipoma with epithelial cysts, epithelioid angiomyolipoma, oncocytoma-like angiomyolipoma and lymphangioleiomyomatosis of the renal sinus. It has been demonstrated that most of these lesions are determined by mutations affecting genes of the tuberous sclerosis complex, tuberous sclerosis 1 (TSC1) and tuberous sclerosis 2 (TSC2), with eventual deregulation of the RHEB/MTOR/RPS6KB2 pathway, and it has been observed that some PEComas regressed during sirolimus therapy, an MTOR inhibitor. Recently, overexpression of MITF has been related to the expression of the papainlike cysteine protease cathepsin K in osteoclasts where it has inhibited MTOR. The aim of this study is to evaluate cathepsin K immunohistochemically in the entire spectrum of PEComa lesions in the kidney. The study population consisted of 84 renal PEComa lesions, including 5 composed predominantly of fat (lipoma-like angiomyolipoma), 15 almost exclusively composed of spindle-shaped smooth muscle cells (leiomyoma-like angiomyolipoma) and 31 common angiomyolipomas composed of a mixture of fat, spindle and epithelioid smooth muscle cells, and abnormal thick-walled blood vessels, 15 microscopic angiomyolipomas, 5 intraglomerular lesions, 2 oncocytoma-like angiomyolipomas, 8 epithelioid angiomyolipomas, 2 angiomyolipomas with epithelial cysts and 1 example of lymphangioleiomyomatosis of the renal sinus. In all of the renal PEComas, cathepsin K was found to be constantly and strongly expressed and seems to be a more powerful marker than other commonly used markers for their identification, especially to confirm the diagnosis on needle biopsies. Modern Pathology (2012) 25, 100-111; doi:10.1038/modpathol.2011.136; published online 26 August 2011Keywords: angiomyolipoma; cathepsin K; epithelioid angiomyolipoma; PEC; PEComa; tuberous sclerosisThe perivascular epithelioid cell (PEC) is a unique cell type coexpressing contractile proteins (mainly a-smooth muscle actin (a-SMA)), melanocytic markers, including microphthalmia-associated transcription factor (MITF), and estrogen and progesterone receptors. The PEC is constantly present in a group of tumors called PEComas including angiomyolipoma, clear-cell 'sugar' tumor of the lung and extrapulmonary sites, lymphangioleiomyomatosis, clear-cell myomelanocytic tumor of the falciform ligament and ligamentum teres, and rare clear-cell tumors of other anatomical sites. PEComas of the kidney include the common angiomyolipoma, microscopic angiomyolipoma, intraglomerular lesions, angiomyolipoma with epithelial cysts, epithelioid angiomyolipoma (pure epithelioid PEComa),

show abstract

mentioning

confidence: 99%

Cathepsin K expression in the spectrum of perivascular epithelioid cell (PEC) lesions of the kidney

et al. 2012

View full text Add to dashboard Cite

show abstract

“…This association is significantly stronger for the two members of the family AML and LAM. Kenerson et al [5] using western blotting and immunohistochemistry demonstrated upregulation of the mTOR signalling pathway with negative feedback inhibition of AKT, consistent with functional loss of TSC1/2 in sporadic renal AMLs and non-renal PEComas.…”

Section: Discussionmentioning

confidence: 73%

PEComa of the Nose: Report of a Case with Immunohistochemical and Ultrustructural Studies and a Review of the Literature

Afrogheh

Schneider

Bezuidenhout

et al. 2013

Head and Neck Pathol

View full text Add to dashboard Cite

show abstract

“…Genetic analysis demonstrated that the mTOR pathway is activated in PEComas 9 and therefore mTOR inhibitors (such as temsirolimus and rapamycin) have been administered in clinical trials to patients at higher risk with encouraging results. 10 In our case, the diagnosis of PEComa avoided an improper indication to chemotherapy for recurrent GCT, which could be indicated based only on clinical findings.…”

Section: Discussionmentioning

confidence: 99%

PEComa of soft tissues can mimick lymph node relapse in patients with history of testicular seminoma

Guglielmetti

Angelis

Mondino

et al. 2013

CUAJ

View full text Add to dashboard Cite

Perivascular Epithelioid Cell tumour (PEComa) is rare. We describe a 39-year-old man who underwent a left radical orchidectomy and adjuvant radiation therapy for a stage IA classical testicular seminoma. He was diagnosed with a mass lateral to the right common iliac artery that was considered suspicious for late lymph node relapse after 3 years of follow-up. Due to the unusual location of the mass and the equivocal findings of percutaneous biopsy, a laparoscopic pelvic lymphadenectomy was performed. Final pathology revealed PEComa of soft tissue. The patient is diseasefree after 38 months of follow-up without adjuvant treatment. The presence of rare soft-tissue neoplasm should be considered in differential diagnosis of retroperitoneal masses during follow-up of germ cell tumours. Suspicious isolated recurrences of these neoplasms in unusual locations can require surgical excision to confirm diagnosis and avoid inappropriate treatment. IntroductionPEComas (Perivascular Epithelioid Cell tumors) are rare mesenchymal neoplasms characterized by a myomelanocytic phenotype and frequently unpredictable clinical behaviour. 1They can involve many anatomical sites and very few cases are reported worldwide.2 When PEComas are diagnosed in soft tissues, they can mimic enlarged lymph nodes and represent a possible confounder during follow-up of other solid tumours. Case reportWe present the case of a 42-year-old man with a history of left testicular pure seminoma. The patient was diagnosed with a palpable left testicular mass in October 2005. Scrotal ultrasound revealed a left hypoechoic testicular lesion, with normal controlateral testis. The serum markers were negative. No retroperitoneal lymphadenopathy or distant metastases were detected at chest x-ray (CXR) and abdominal contrast-enhanced computed tomography (CT). An uneventful left radical orchidectomy was performed. The pathology showed a classical seminoma with necrotic areas and invasion of the rete testis (pT1,N0,M0,S0; stage IA according to the 2009 TNM classification). After we consulted with the interdisciplinary team, the patient underwent adjuvant radiotherapy (25.2 Gy) on the left lombo-aortic lymph nodes.Follow-up included physical examination, serum markers every 4 months and CXR and abdominal CT scan every 6 months for the first 3 years, with negative results.At the abdominal CT scan performed September 2008, we found a single, enlarged 2.5-cm mass lateral to the right common iliac artery consistent with lymphadenopathy ( Fig. 1, part A, part B). The scrotal examination, the serum markers and the CXR were negative and the patient had no complaints. A positron emission tomography (PET) with fluorodeoxyglucose showed a hot spot (maximum standardized uptake value 3.76) in the area of the right common iliac lesion, which led us to a likely diagnosis of a late relapse of the testicular germ cell neoplasm. (Fig. 2) To confirm this diagnosis, a CT-guided fine needle aspiration biopsy was performed. (Fig. 1, part C). Cytology revealed epitheliomorphic cells ...

show abstract

Activation of the mTOR pathway in sporadic angiomyolipomas and other perivascular epithelioid cell neoplasms

Cited by 213 publications

References 44 publications

Cathepsin K expression in the spectrum of perivascular epithelioid cell (PEC) lesions of the kidney

Cathepsin K expression in the spectrum of perivascular epithelioid cell (PEC) lesions of the kidney

PEComa of the Nose: Report of a Case with Immunohistochemical and Ultrustructural Studies and a Review of the Literature

PEComa of soft tissues can mimick lymph node relapse in patients with history of testicular seminoma

Contact Info

Product

Resources

About