br Case report A year old man

Case report A 50-year-old man with no known systemic diseases presented to our facility with a growing huge mass at his left flank and numbness of the left leg. Five years earlier, there was only a small lump over his left flank. However, the soft tissue lesion gradually enlarged, accompanied by intermittent claudication. The patient presented to the Department of Orthopedics of Kaohsiung Medical University Hospital (Kaohsiung, Taiwan) in October 2015. Abdominal and pelvic computed tomography (CT) revealed a huge mass lesion noted in the left postero-lateral abdominal wall (16 × 14 × 15 cm) (Fig. 1). This lesion manifested heterogeneous density with peripheral soft tissue enhancement and central unenhanced cystic content. A subsequent chest CT showed multiple bilateral lung nodules and metastatic lymphadenopathy at the left supraclavicular region, mediastinum, and the bilateral hilar and subcarinal regions. Bone scan also showed multiple bone metastases. A CT-guided core needle biopsy was performed, and section showed tiny fragments of highly anaplastic A-366 with pleomorphic nuclei, prominent nucleoli, ample eosinophilic cytoplasm and frequent mitotic activity. Immunohistochemical (IHC) studies showed reactivity in HMB-45, and Melan-A, whereas cytokeratin, p63, Hep-Par 1, and CAM5.2 were all negative in tumor cells (Fig. 2). Due to limited specimen availability for further IHC study, the diagnosis of melanoma was considered but malignant PEComa or other malignant tumors with melanocytic differentiation could not be excluded. Wide excision of the tumor was then performed. Microscopic examination revealed an ungraded sarcoma with high mitotic rate, extensive necrosis and lymphovascular invasion. The IHC study revealed positive HMB45, Melan A, SMA, and desmin, while S-100 and CK were both negative. Ultimately, malignant soft tissue PEComa was diagnosed. Consequently, the patient was initially subjected to target therapy with sirolimus 2 mg per day. No severe adverse effect was noted, except a mild decrease of hemoglobin level (from 9.5 to 8.5 g/dL) was observed. The trough level of sirolimus was 5.5 ng/mL, and we titrated the dosage to 3 mg each day. However, severe pneumonia was encountered, the patient\'s clinical condition worsened after which he then received hospice care.
Discussion PEComa-NOS has been reported at a variety of anatomic locations, including the gastrointestinal tract, retroperitoneum, bone, soft tissue, and several other sites in a few cases. Among these cases, soft tissue PEComas are extremely rare. The differential diagnosis of PEComa-NOS largely depends on the specimen morphology, immunohistochemistry, cytogenetics and the molecular patterns. In our case, melanoma was once impressed according to the CT-guided biopsy result, which underscores the importance of adequate specimen acquisition to prevent misdiagnosis. Although most PEComas were generally considered to have benign behavior, the malignant potential of PEComas was proposed by Folpe et al. in 2005, and now can be classified into benign, uncertain malignant potential, and malignant types. The worrisome features of PEComas include tumor size (larger than 5 cm), infiltrative pattern, high nuclear grade and cellularity, high mitotic rate (equal or larger than 1/50 HPF), necrosis, and vascular invasion. If two or more worrisome features present, as in our case, malignant PEComas would be impressed. Bleeker et al. reviewed 234 cases of PEComa-NOS, and confirmed the utility of the Folpe criteria in this tumor subgroup, providing an important guidepost in our treatment. Variations in treatment approach were observed in these reviewed cases, and there was no conclusive efficacy of chemotherapy whether such treatment occurred in a neoadjuvant or adjuvant setting. For those patients with malignant PEComas, the disease can be highly invasive, with the most frequent sites of metastasis including the liver, lung, bone and brain.