Perivascular epithelioid cell neoplasms (PEComas) are an uncommon class of tumors consisting on histology of perivascular epithelioid cells occurring in both localized and metastatic forms at various body sites. The approach to treatment of these tumors generally involves a combination of surgical resection, chemotherapy, and/or radiation therapy.1
Case presentation and summary
A 46-year-old man presented to our institution with a non-tender, slowly enlarging, 8.3 cm mass in his right popliteal fossa. Upon biopsy, the pathologic findings were consistent with an epithelioid malignancy with melanocytic differentiation most consistent with a PEComa. Discussion of the pathologic diagnosis of our patient has been reported by the pathology group at our institution in a separate case report.2
Our patient was initially offered and refused amputation. He was started on therapy with the mechanistic Target of Rapamycin (mTOR) inhibitor everolimus, but was unable to tolerate the side effects after the first week of treatment. He then elected to monitor his symptoms clinically.
Approximately one year after his initial diagnosis, he presented to our facility with sepsis and bleeding from a now fungating tumor on his right knee. At this time, emergent above-knee amputation was performed. Re-staging images now showed the presence of multiple pulmonary nodules in his right lung as well as a lytic rib lesion, a concerning finding for metastatic disease. Video-Assisted Thorascopic Surgery (VATS) and right lower lobe wedge resection were performed and findings confirmed metastatic PEComa.
Given the patient’s intolerance to everolimus, he was started on the growth factor inhibitor, pazopanib. His disease did not progress on pazopanib, and improvement was noted in the dominant pulmonary nodule. Subsequently, however, he developed significant skin irritation and discontinued pazopanib. Repeat imaging approximately 2 months after stopping pazopanib showed significant disease progression.
We elected to start the patient on a non-standard approach to therapy with nivolumab infusions once every 2 weeks and concurrent radiation therapy to the rib lesion. At 2 and 5 months after initiating this treatment approach, CT imaging showed improvement in disease. At 12 months, significant disease response was noted (Figure 1).
The patient is now at 12 months of nivolumab therapy with progression free survival and no new identifiable metastatic lesions. He has been tolerating the medication with minimal side effects and has had an overall improvement in his pain and functional status. He continues to work full time.
Discussion
Our patient’s response presents a unique opportunity to talk about the role of immunotherapy as a treatment modality in patients with PEComa. The efficacy of check-point blockade in soft tissue sarcoma is still unclear predominantly because it is difficult to assess the degree of expression of immunogenic cell surface markers such as programmed cell death protein 1 (PD-1).1,3 Nivolumab has been tried in small cohorts for treatment of soft tissue sarcomas that express PD-1 and results showed some clinical benefit in about half of patients.4 Further, the expression of PD-1 has been assessed in soft tissue sarcomas and has been reported to suggest a negative prognostic role.5
To our knowledge, there has not yet been another reported case of PEComa that has been treated with immunotherapy and achieved a sustained response. Further clinical studies need to be done to assess response to agents such as nivolumab in the treatment of PEComa to bolster our observation that nivolumab is a viable treatment option that may lead to lasting remission. Our patient’s case also brings to light the need for further inquiry into assessing the immune tumor microenvironments, particularly looking at the expression of cell surface proteins such as PD-1, as it ultimately affects treatment options. TSJ
Correspondence
REFERENCES
1. Burgess, Melissa, et al. “Immunotherapy in Sarcoma: Future Horizons.” Current Oncology Reports, vol. 17, no. 11, 2015, doi:10.1007/s11912-015-0476-7.
2. Alnajar, Hussein, et al. “Metastatic Malignant PEComa of the Leg with Identification of ATRX Mutation by next-Generation Sequencing.” Virchows Archiv (2017). https://doi:10.1007/s004280172208-x.
3. Ghosn, Marwan, et al. “Immunotherapies in Sarcoma: Updates and Future Perspectives.” World Journal of Clinical Oncology, vol. 8, no. 2, 2017, p. 145., doi:10.5306/wjco.v8.i2.145.
4. Paoluzzi, L., et al. “Response to Anti-PD1 Therapy with Nivolumab in Metastatic Sarcomas.” Clinical Sarcoma Research, vol. 6, no. 1, 2016, doi:10.1186/s13569-016 0064-0.
5. Kim, Chan, et al. “Prognostic Implications of PD-L1 Expression in Patients with Soft Tissue Sarcoma.” BMC Cancer, BioMed Central 8 July 2016.