Complete resection of the tumor with negative margins
Complete resection of the tumor with negative margins at the time of diagnosis appears the most preferred mode of intervention towards favorable prognosis. It is worth mentioning that the germline receptor tyrosine kinase of DICER1 is believed as the genetic cause in the majority of PPB; consequently, earlier detection of PPB (type I, cystic) may be facilitated with surveillance of DICER1 carriers. That said, margin-free resection appears challenging in a majority of the patients (i.e., type II and III PPB) due to involvement of vital structures by the aggressive tumor. Alternatively, partial resection typically fails to prevent local recurrences or metastases. In our case (type II PPB), complete resection of the tumor was not attempted due to involvement of vital structures (i.e., lungs, aorta, and pleura) by the tumor. Nevertheless, patients with initially unresectable tumors are suggested to be treated with neoadjuvant chemotherapy to reduce the tumor size to the point where complete resection becomes possible. In fact, this has been ascertained in some studies. For instance, a 2.5-year-old girl patient diagnosed with type II PPB (tumor size = 10 × 9 × 7 cm3) was given neoadjuvant chemotherapy (ICE/VAC regimes) that reduced the tumor size by 90%. Afterwards, the mass was completely excised via wedge resection. Our patient also received six courses of the same neoadjuvant chemotherapy that resulted in a 60% reduction in tumor size; however, this tumor reduction did not achieve complete tumor resection, as radiologically assessed by the surgeon (Fig. 1b). These observations are consistent with recently published data, where complete resection of type II and III PPB after neoadjuvant chemotherapy was concluded to be “not easy to achieve”, possible in less than 33% of cases.
Several multi-agent chemotherapy regimens have been employed in the treatment of PPB; these regimens typically include VA, IVA, VAIA, CEV/AIE, and IVAD. We administered alternating ICE/VAC regimes in the neoadjuvant setting, which resulted in 60% tumor size reduction. However, recent findings suggest significantly improved (p = 0.01) 5-year PFS of doxorubicin containing regimens such as IVAD.
The role of radiotherapy in management of PPB remains unclear. Specifically, radiotherapy (30–54.8 Gy) has been delivered in adjuvant settings with the aim of targeting the residual tumor. However, it has been suggested to limit radiotherapy to high-risk patients only due to possible long-term cardiac damage. It is also noteworthy that radiotherapy to 16/50 patients did not provided an advantage in survival. Alternatively, based on the poor response of chemotherapy, Indolfi et al. indicated that chemotherapy should be given with local radiotherapy in the majority of patients. In the present study, it was decided to follow the patient without administration of radiotherapy due to the large tumor size involving vital structures, as it may cause significant morbidity.
Conflict of interest
Introduction The term “perivascular epithelioid cell” was first introduced in 1992 by Bonetti et al., describing a group of tumor cells sharing similar characteristics between angiomyolipoma (AML), clear cell “sugar” tumor of the lung (CCST) and lymphangioleiomyomatosis (LAM). Upon immunohistochemical staining, both myogenic and melanocytic markers are frequently reactive, including HMB45, HMSA-1, Melan A/Mart1, microphthalmia transcription factor (MiTF) and actin. In 2002, the World Health Organization (WHO) defined PEComas as a family of mesenchymal neoplasms presenting histological and immunohistochemical characteristics of perivascular epithelioid cell tumors (PECs). The hyperactivity of the mTOR pathway is observed in PEComas, which supports the application of mTOR inhibitors in PEComa treatment. Bissler et al. have reported promising treatment response; since then, mTOR inhibitors have been widely included in the treatment of malignant PEComa. Herein we have presented a rare case of a malignant PEComa at flank with multiple lung and bone metastases, and have performed a literature review for the mTOR inhibitor as the primary treatment in malignant PEComa.