背景:恶性血管周围上皮样细胞肿瘤(PEComas)是极其罕见的恶性间充质肿瘤,具有特征性的形态学和免疫组织化学(IHC)模式。然而,一些恶性PEComas分化差,具有非典型的组织病理学特征,很难做出明确的诊断。PEComas最常见于女性,通常显示TSC1或TSC2改变。导致mTOR通路的激活,或TFE3融合。鉴于这些分子特征,mTOR抑制剂最近已被FDA批准用于治疗恶性PEComas,特别是那些有TSC1/2改变。因此,在恶性PEComas病例中,分子分析可能有助于mTOR抑制剂的诊断性检查和预测对mTOR抑制剂的反应.
方法:这里,我们报告了一个侵略性的案例,一名年轻男性患者的23厘米肠系膜恶性PEComa伴多发腹膜转移。最初活检的病理检查显示恶性上皮样肿瘤,具有高度形态和非典型免疫特征,排除了明确的诊断。由于患者因肿瘤内出血而需要过度输血,进行了姑息性R2切除术.肿瘤的组织病理学检查显示Melan-A的局灶性免疫反应性,HMB-45,desmin,CD117尽管恶性PEComa的诊断是有利的,其他实体,如上皮样胃肠道间质瘤(GIST)或黑色素瘤,不能明确排除。鉴于有利的诊断,病人开始服用西罗莫司,一种mTOR抑制剂,而不是化疗。进行了分子分析,发现肿瘤在TP53和TSC2中存在突变,支持对恶性PEComa的明确诊断。然后患者改用nab-西罗莫司,随着疾病的初步稳定。
结论:本报告详细介绍了一种多学科方法,用于诊断和管理高侵袭性,一名年轻男性患者的转移性恶性PEComa。使用最近FDA批准的mTOR抑制剂治疗恶性PEComas的基础,nab-西罗莫司,也进行了审查。总之,这个案例凸显了分子分析的重要性,特别是TSC1/2改变,用于明确诊断恶性PEComas并预测其对nab-西罗莫司的反应。
BACKGROUND: Malignant perivascular epithelioid cell tumors (PEComas) are exceedingly rare malignant mesenchymal neoplasms with characteristic morphological and immunohistochemical (IHC) patterns. However, some malignant PEComas are poorly differentiated with atypical histopathological features, making a definitive diagnosis difficult. PEComas are most commonly found in females and often show either TSC1 or TSC2 alterations, which result in the activation of the mTOR pathway, or TFE3 fusions. Given these molecular characteristics, mTOR inhibitors have recently been approved by the FDA in the treatment of malignant PEComas, particularly in those with TSC1/2 alterations. Therefore, molecular analyses may be helpful for both the diagnostic workup of and predicting response to mTOR inhibitors in cases of malignant PEComas.
METHODS: Here, we report a
case of an aggressive, 23 cm mesenteric malignant PEComa with multiple peritoneal metastases in a young male patient. Pathological examination of the initial biopsy showed a malignant epithelioid neoplasm with high-grade morphology and atypical immunoprofile, which precluded a definitive diagnosis. Because of the patient\'s excessive transfusion requirements due to intra-tumoral hemorrhage, a palliative R2 resection was performed. Histopathological examination of the tumor revealed focal immunoreactivity for Melan-A, HMB-45, desmin, and CD117. Although a diagnosis of malignant PEComa was favored, other entities such as epithelioid gastrointestinal stromal tumor (GIST) or melanoma could not be definitively ruled out. Given the favored diagnosis, the patient was started on sirolimus, an mTOR inhibitor, rather than chemotherapy. Molecular analyses were performed and the tumor was found to harbor mutations in TP53 and TSC2, supporting a definitive diagnosis of malignant PEComa. The patient was then switched to nab-sirolimus, with initial stabilization of the disease.
CONCLUSIONS: This report details a multidisciplinary approach for the diagnosis and management of a highly aggressive, metastatic malignant PEComa in a young male patient. The basis for the treatment of malignant PEComas with the recently FDA-approved mTOR inhibitor, nab-sirolimus, is also reviewed. In summary, this
case highlights the importance of molecular analysis, particularly TSC1/2 alterations, for both the definitive diagnosis of malignant PEComas and predicting their response to nab-sirolimus.