Advanced Malignant PEComa

Fast Facts

Malignant PEComa is an ultra-rare sarcoma that appears to arise most commonly at visceral (especially gastrointestinal and uterine), retroperitoneal, and abdominopelvic sites1


Globally, there is ≤1 malignant PEComa diagnosis per 1,000,000 people annually,2 with an estimated 100-300 new patients per year in the US*

Patients are predominantly females and typically diagnosed between the ages of 45-65 years3

Advanced malignant PEComa is associated with a poor prognosis4

51% to 72% of patients with malignant PEComas develop metastatic disease within 12 to 23 months5-7

*Aadi analysis based on multiple sources, including Aadi internal data and external research conducted by Tessellon Group and Corsica Life Sciences.
PEComa=perivascular epithelioid tumor.

What is PEComa?

PEComas are a rare subset of soft tissue neoplasms composed of histologically and immunohistochemically distinctive epithelioid cells. Due to their rarity and relatively recent recognition, classification of PEComas has evolved; they may be broadly grouped into the following tumor types4,6:

Malignant and Benign PEComa in Context

Although most PEComas are localized and benign, malignant PEComa is characterized by locally invasive recurrence or distant metastatic lesions. Approximately 72% of patients with malignant PEComa will develop metastatic disease, most frequently to the lung or liver, over a median follow-up of 12-months.6,7

What does PEComa look like?

PEComas are characterized by the World Health Organization as mesenchymal tumors composed of distinctive perivascular epithelioid cells that show a focal association with blood vessel walls, and usually express both melanocytic and smooth muscle markers.6,8,9

Click on an image to enlarge.

Features of Malignancy

From the personal image library of Jason L Hornick, MD, PhD; 2020.

Diagnosis of advanced malignant PEComa is based on a pathological evaluation, though misdiagnosis may occur due to overlapping immunophenotype (characteristic co-expression of melanocytic and smooth muscle markers) and histologic overlap with other tumor types.6,7,10

Potential misdiagnoses may include5-7,10:

  • Leiomyosarcoma
  • Clear cell sarcoma
  • Metastatic melanoma
  • Gastrointestinal stromal tumor (GIST)
  • Renal cell carcinoma (RCC)

The mTOR Pathway and PEComa

The mTOR pathway controls key cellular processes. Alterations or deletions in mTOR pathway genes, like TSC1 and TSC2, may lead to mTOR overactivation, which prompts uncontrolled cell growth, metabolism, and survival. Advanced malignant PEComa tumors have the highest rate of TSC1 and TSC2 alterations among cancers.11-16

mTOR=mechanistic target of rapamycin; TSC1=tuberous sclerosis-1; TSC2=tuberous sclerosis-2.

mTOR=mechanistic target of rapamycin; TSC1=tuberous sclerosis-1; TSC2=tuberous sclerosis-2.

  1. Wagner AJ, Malinowska-Kolodziej I, Morgan JA, et al. Clinical activity of mTOR inhibition with sirolimus in malignant perivascular epithelioid cell tumors: targeting the pathogenic activation of mTORC1 in tumors. J Clin Oncol. 2010;28(5):835-840. doi:10.1200/JCO.2009.25.2981
  2. Stacchiotti S, Frezza AM, Blay JY, et al. Ultra-rare sarcomas: a consensus paper from the Connective Tissue Oncology Society community of experts on the incidence threshold and the list of entities. Cancer. 2021;127(16):2934-2942. doi:10.1002/cncr.33618
  3. Bourgmayer A, Nannini S, Bonjean P, Kurtz JE, Malouf GG, Gantzer J. Natural history and treatment strategies of advanced PEComas: a systematic review. Cancers (Basel). 2021;13(20):5227. Published 2021 Oct 18. doi:10.3390/cancers13205227
  4. Armah HB, Parwani AV. Perivascular epithelioid cell tumor. Arch Pathol Lab Med. 2009;133(4):648-654. doi:10.5858/133.4.648
  5. Bleeker JS, Quevedo JF, Folpe AL. “Malignant” perivascular epithelioid cell neoplasm: risk stratification and treatment strategies. Sarcoma. 2012;2012:541626. doi:10.1155/2012/541626
  6. Ben-Ami E, Hornick JL, Wagner H, Wagner AJ. The potential of emerging new therapeutics for the treatment of perivascular epithelioid cell tumors (PEComa). Expert Opin Orphan Drugs. 2018;6(9):537-543. doi:10.1080/21678707.2018.1493376
  7. Tirumani SH, Shinagare AB, Hargreaves J, et al. Imaging features of primary and metastatic malignant perivascular epithelioid cell tumors. AJR Am J Roentgenol. 2014;202(2):252-258. doi:10.2214/AJR.13.10909
  8. Data on file. Aadi Bioscience, Inc.; 2021.
  9. Folpe AL, Kwiatkowski DJ. Perivascular epithelioid cell neoplasms: pathology and pathogenesis. Hum Pathol. 2010;41(1):1-15. doi:10.1016/j.humpath.2009.05.011
  10. Chen Z, Han S, Wu J, et al. A systematic review: perivascular epithelioid cell tumor of gastrointestinal tract. Medicine (Baltimore). 2016;95(28):e3890. doi:10.1097/MD.0000000000003890
  11. Mossmann D, Park S, Hall MN. mTOR signalling and cellular metabolism are mutual determinants in cancer. Nat Rev Cancer. 2018;18(12):744-757. doi:10.1038/s41568-018-0074-8
  12. Hay N, Sonenberg N. Upstream and downstream of mTOR. Genes Dev. 2004;18(16):1926 – 1945. doi:10.1101/gad.1212704
  13. Gonzalez-Angulo AM, Meric-Bernstam F, Chawla S, et al. Weekly nab-rapamycin in patients with advanced nonhematologic malignancies: final results of a phase I trial. Clin Cancer Res. 2013;19(19):5474-5484. doi:10.1158/1078-0432.CCR-12-3110
  14. Saxton RA, Sabatini DM. mTOR signaling in growth, metabolism, and disease [published correction appears in Cell. 2017 Apr 6;169(2):361-371]. Cell. 2017;168(6):960-976. doi:10.1016/j.cell.2017.02.004
  15. Akumalla S, Madison R, Lin DI, et al. Characterization of clinical cases of malignant PEComa via comprehensive genomic profiling of DNA and RNA. Oncology. 2020;98(12):905-912. doi:10.1159/000510241
  16. Wagner AJ, Ravi V, Riedel RF, et al. nab-Sirolimus for patients with malignant perivascular epithelioid cell tumors [published online ahead of print, 2021 Oct 12]. J Clin Oncol. 2021;JCO2101728. doi:10.1200/JCO.21.01728
  17. Gennatas C, Michalaki V, Kairi PV, Kondi-Paphiti A, Voros D. Successful treatment with the mTOR inhibitor everolimus in a patient with perivascular epithelioid cell tumor. World J Surg Oncol. 2012;10:181. Published 2012 Sep 3. doi:10.1186/1477-7819-10-181