PEComa of the colon resistant to sirolimus but responsive to doxorubicin/ifosfamide

Abstract

A 23-year-old male presented with a three-week-history of crampy abdominal pain and melaena. Colonoscopy revealed a friable mass filling the entire lumen of the cecum; histologically, it was classified as perivascular epithelioid cell tumor (PEComa). An magnetic resonance imaging scan showed, in addition to the primary tumor, two large mesenteric lymph node metastases and four metastatic lesions in the liver. The patient underwent right hemicolectomy and left hemihepatectomy combined with wedge resections of metastases in the right lobe of the liver, the resection status was R0. Subsequently, the patient was treated with sirolimus. After 4 mo of adjuvant mammalian target of rapamycin inhibition he developed two new liver metastases and a local pelvic recurrence. The visible tumor formations were again excised surgically, this time the resection status was R2 with regard to the pelvic recurrence. The patient was treated with 12 cycles of doxorubicin and ifosfamide under which the disease was stable for 9 mo. The clinical course was then determined by rapid tumor growth in the pelvic cavity. Second line chemotherapy with gemcitabine and docetaxel was ineffective, and the patient died 23 mo after the onset of disease. This case report adds evidence that, in malignant PEComa, the mainstay of treatment is curative surgery. If not achievable, the effects of adjuvant or palliative chemotherapy are unpredictable.

Unusual Pediatric Sigmoid Perivascular Epithelioid Cell Tumor with Regional Lymph Node Metastasis Treated Using Gemcitabine and Docetaxel: A Case Report and Literature Review

“…However, contrary results were observed when a female patient aged 58 years with metastatic PEComa was treated with a combination of topotecan, temsirolimus (mTOR inhibitor), and bortezomib [28]. Moreover, a male patient aged 23 years with colon PEComa demonstrated resistance to mTOR inhibitor therapy but maintained stable prognosis when treated with a combination of doxorubicin and ifosfamide for 9 months [13]. In accordance with the published literature and our institutional experience, we suggest surgical resection with adjuvant conventional cytotoxic chemotherapy as the rstline treatment for early-stage GI PEComas.…”

“…All of the pediatric patients [14,[16][17][18] were treated with surgery as an initial management strategy. However, the preferred adjuvant therapy, including doxorubicin, paclitaxel, gemcitabine, and oxaliplatin alone or in combinations, is a matter of contention [5,9,13,14,27,28]. For benign PEComa, no standardized regimen has been provided to avoid recurrence after surgery [3,4].…”

“…The mTOR pathway regulates cell growth and is associated with the inactivation of tuberous sclerosis complex 1 (TSC1) and TSC2 genes [1,12]. Characterization of TSC1 and TSC2, along with their downstream products [2,13], could help develop targeted therapeutic agents, such as sirolimus or tacrolimus. However, contrary results were observed when a female patient aged 58 years with metastatic PEComa was treated with a combination of topotecan, temsirolimus (mTOR inhibitor), and bortezomib [28].…”

“…Because of their unpredictable histopathological manifestation, patients with aggressive PEComas have poor prognosis and do not respond well to chemotherapy [5,12,13]. The mammalian target of rapamycin (mTOR) inhibitor treatment remains controversial in patients lacking the tuberous sclerosis complex (TSC) gene mutation [5,9].…”

Combination targeted therapy of VEGFR inhibitor, sorafenib, with an mTOR inhibitor, sirolimus induced a remakable response of rapid progressive Uterine PEComa

“…Recently the mammalian target of rapamycin (mTOR) inhibitor, sirolimus (rapamycin), has been used for treatment of the patients with metastatic PEComa with mixed results. [11][12][13] Sorafenib, a vascular endothelial growth factor receptor (VEGFR) inhibitor, showed some objective responses in patients with advanced soft tissue sarcomas. 14,15 However, because of its relative rarity, experience with mTOR inhibitor or VEGFR inhibitor in treating malignant PEComas is limited.…”