Management Strategies for Adults with Locally Advanced, Unresectable or Metastatic Malignant Perivascular Epithelioid Cell Tumor (PEComa): Challenges and Solutions

Figures & data

Table 1 Classification of PEComa

High-Risk Characteristic Tumour size greater than 5 cm High degree of histological malignancy and high cellularity High mitotic index (>1/50 HPF) Presence of necrosis Infiltration of blood vessels

Benign < 2 high risk characteristics and size < 5 cm Uncertain malignancy potential Size > 5 cm and no other high-risk characteristics OR nuclear pleomorphism/multinuclear giant cells Malignant 2 or more high-risk characteristics

Notes: Data from Fople and Kwiatkowski.¹⁵

Figure 1 PEComa tumor radiological imaging and resection. (a) Intraoperative picture of PEComa resection, (b) PEComa after resection, (c) CT scan of PEComa, (d) MRI scan of PECma.

Table 2 Drugs and Therapy Regimens Used in PEComa

Drug/Treatment Regimen			Dosing	Reference
mTOR inhibitors	Sirolimus		Therapy monitored by drug concentration in serum with therapeutic concentration: 10–20 ng/mL Dosage: 1–10 mg/d p.o. depending on drug concentration as above	[35,37–41]
	Everolimus		5–10 mg/d P.O.	[35,42–44]
	Temsirolimus		25 mg/week i.v.	[35,40,44–46]
	Nab-sirolimus		100 mg/m^2 once weekly for 2 weeks in 3-week cycles	[47]
Cytotoxics	AI	Doxorubicin + ifosfamide	Doxorubicin: 50–90 mg/m2 Ifosfamide: 5–10 g/m2 Infusion on day 1–3 or continuous infusion of drugs for 72 h, cycle every 21–28 days with mesna	[35,48]
	D	Doxorubicin	75 mg/m^2 every 21 days	[30,35,49]
	AD	Doxorubicin +dacarbazine	Doxorubicin: 60 mg/m^2 Dacarbazine: 750–1200 mg/m Bolus or continuous infusion of both drugs for 96 h, cycles every 21–28 days	[35]
	G	Gemcitabine + docetaxel	Gemcitabine (900 mg/m^2 day 1 and 8 every 3 weeks) and docetaxel (100 mg/m^2 on day 8 every 3 weeks)	[35,40]
VEGFR inhibitors	Pazopanib		800 mg /day P.O.	[35,50]
	Sorafenib		800 mg/day P.O.	[35]
	Sunitinib		37.5 mg/day P.O.	[35]
	Apatinib		500 mg /day P.O.	[51]

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

 PubMed Web of Science ®Google Scholar

Sanfilippo R, Jones RL, Blay J-Y, et al. Role of Chemotherapy, VEGFR Inhibitors, and mTOR Inhibitors in advanced perivascular epithelioid cell tumors (PEComas). Clin Cancer Res. 2019;25(17):5295–5300. doi:10.1158/1078-0432.CCR-19-0288

 PubMed Web of Science ®Google Scholar

Starbuck KD, Drake RD, Budd GT, Rose PG. Treatment of advanced malignant uterine perivascular epithelioid cell tumor with mTOR inhibitors: single-institution experience and review of the literature. Anticancer Res. 2016;36(11):6161–6164. doi:10.21873/anticanres.11208

 PubMed Web of Science ®Google Scholar

Wagner AJ, Ravi V, Riedel RF, et al. nab-sirolimus for patients with malignant perivascular epithelioid cell tumors. J Clin Oncol. 2021;39(33):3660–3670. doi:10.1200/JCO.21.01728

 PubMed Web of Science ®Google Scholar

Osei DA, Alvandi F, Brooks JS, Ogilvie CM. PEComa of the upper extremity: a unique case and description of an initial response to neoadjuvant chemotherapy. Sarcoma. 2007;2007:53056. doi:10.1155/2007/53056

 PubMedGoogle Scholar

Machado I, Cruz J, Lavernia J, Rayon JM, Poveda A, Llombart-Bosch A. Malignant PEComa with metastatic disease at diagnosis and resistance to several chemotherapy regimens and targeted therapy (m-TOR Inhibitor). Int J Surg Pathol. 2017;25(6):543–549. doi:10.1177/1066896917701245

 PubMed Web of Science ®Google Scholar

Flechter E, Zohar Y, Guralnik L, Passhak M, Sela GB. Long-lasting stable disease with mTOR inhibitor treatment in a patient with a perivascular epithelioid cell tumor: a case report and literature review. Oncol Lett. 2016;12(6):4739–4743. doi:10.3892/ol.2016.5231

 PubMed Web of Science ®Google Scholar

Alnajar H, Brickman A, Buckingham L, Arvanitis LD. Metastatic malignant PEComa of the leg with identification of ATRX mutation by next-generation sequencing. Virchows Arch. 2018;472(3):499–503. doi:10.1007/s00428-017-2208-x

 PubMed Web of Science ®Google Scholar

Xu J, Gong X-L, Wu H, Zhao L. Case Report: gastrointestinal PEComa With TFE3 Rearrangement Treated With Anti-VEGFR TKI Apatinib. Front Oncol. 2020;10:10. doi:10.3389/fonc.2020.00010

 PubMed Web of Science ®Google Scholar