Malignant perivascular epithelioid cell tumor (PEComa) of the femur: a case report and literature review
© Lao et al.; licensee BioMed Central. 2015
Received: 10 February 2015
Accepted: 5 May 2015
Published: 29 May 2015
We describe a case of malignant perivascular epithelial cell tumor (PEComa) arising primarily in the distal left femur of a 47-year-old male.
The patient presented with pain accompanied by progressive swelling of his left thigh. Computed tomography (CT) scan and magnetic resonance imaging (MRI) revealed an osteolytic lesion. Curettage of the lesion was reported as a clear cell tumor with recommendation for exclusion of a metastatic clear cell carcinoma. However, thorough examinations did not find any primary site elsewhere, apart from the presence of bilateral pulmonary metastases. Evaluation of the submitted H & E slides identified a malignant PEComa which was further confirmed by subsequent immunohistochemical study.
The occurrence of PEComa as a primary bone lesion is extremely rare. We present here a malignant PEComa of the distal left femur, and summarize the clinicopathological characteristics of this rare entity with literature review.
The virtual slide (s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5729035221600545.
Perivascular epithelioid cell tumor (PEComa) represents a family of closely related entities showing both melanocytic and myoid differentiation, including angiomyolipoma, lymphangioleiomyomatosis, clear-cell ‘sugar’ tumor of the lung, and neoplasms arising in a wide variety of locations including skin, soft tissue and visceral organs called PEComa not otherwise specified (PEComa-NOS) . PEComa manifesting as a primary bone lesion is extremely rare. To date, only 10 convincing cases of primary bone origin have been reported in the English literature [2–8]. Although the majority of PEComas behave in a benign or indolent fashion, a minority of tumors exhibit aggressive behavior. The malignant variant may cause diagnostic pitfalls, particularly in interpretation of biopsy specimens. In this report, we describe a case of malignant PEComa arising primarily in the femur to broaden the anatomic spectrum of primary bone PEComas.
Clinical features of 11 cases of primary bone PEComa
Insabato et al. 
Right proximal tibia
Osteolytic with cortical destruction
Torri et al. 
Right 6th rib
ANED, not reported
Righi et al. 
Lian et al. 
Right mid-shaft fibula
Extension through the cortex forming a soft-tissue mass
Yamashita et al. , case 1
7th thoracic vertebra
Bilateral leg weakness, back pain
Osteolytic, destructive enhancing lesion (MRI)
Pelvic bone metastases, AWD,12mo
Yamashita et al. , case 2
Enhancing mass with areas of breakthrough of the cortex forming a soft-tissue mass
RT + Excision
Yamashita et al. , case 3
Right distal tibia
Permeable destructive lesion with soft tissue extension (recurrent lesion)
Excisional biopsy, amputation
Recurred 3 times in 3 y, ANED, 3y
Kazzaz et al. 
5th lumbar vertebra
Lower back pain, left leg weakness
Destructive lesion with extra-osseous mass
Lung metastases, ANED, not reported
Desy et al. , case 1
Right distal fibula
Progressive pain, swelling
Expansile lytic lesion
Desy et al. , case 2
Progressive hip pain
Extensive lytic with soft tissue expansion
Left hemipelvectomy + temsirolimus
Lung metastases, DOD, 8mo
Lao et al. (our case)
Pain, progressive swelling
Osteolytic mass, destruction of cortex forming a soft-tissue mass
Curettage + CRT
Lung metastases, AWD, 3.5y
Clinically, patients with bone PEComas typically presented with pain. Three patients were accompanied with swelling [3, 8], one of whom had a pathologic fracture of the distal fibula . One patient was accompanied with bilateral leg weakness because of cord compression . Radiologically, primary PEComas of bone frequently appeared as osteolytic lesions. In more aggressive cases, destruction of cortex with forming of soft tissue mass could be noted [2, 6–8]. On MR imaging, the tumor was usually hypointense on T1-weighted imaging and hyperintense on T2-weighted images [6, 8]. In a biopsy-proven malignant PEComa, F-18 FDG PET demonstrated intense hypermetabolism . Of note, FDG PET scans were often negative in patients with benign PEComas and positive in malgiant PEComas . However, a benign PEComa of the lungs with extensive FDG uptake has also been described .
Histologically, most bone PEComas were composed of epithelioid perivascular cells that exhibited characteristic nesting or organoid arrangement. Two case were composed of both epithelioid and spindle cells . Of 11 cases, 3 were considered to be benign which were also supported by the clinical outcome [2, 4, 6, 8]. One case was supposed to have malignant potential based on the invasion into the surrounding connective tissues and overexpression of cyclinD1 . The remaining 7 cases were recognized histologically as fully malignant. Besides permeative growth pattern, marked nuclear atypia was present in all 7 cases, necrosis was seen in 2 cases (including the current case) , and mitotic activity was noted in 6 cases, ranging from 5/50HPF to 36/50HPF . Vascular invasion was identified in 2 cases [3, 6]. It is worthy to note that although most cases of malignant PEComa fulfilled the morphological criteria for malignancy proposed by Folpe et al. , rare example existed which was not clearly malignant on histological ground, especially on biopsy specimens . In such instance, the malignancy was usually betrayed by its aggressive clinical behaviour.
The major differential diagnosis in the current case includes metastatic clear cell carcinoma, especially of renal origin. However, immunohistochemical study ruled out this possibility as the tumor cells failed to express epithelial markers. Alveolar soft part sarcoma (ASPS), a sarcoma characterized by organoid pattern and sinusoidal-type vasculature, may cause confusion with PEComa. In particular, both tumors can express TFE3 [4, 12]. The absence of melanocytic differentiation in ASPS is helpful in the separation of these two entities. The other lesions that may enter the differential diagnoses are metastatic malignant melanoma and clear cell sarcoma. In addition to morphological differences, strong S100 protein and negative staining of myogenic markers in most melanomas and clear cell sarcomas (CCS), the presence of specific EWSR1 ATF1 fusion transcripts resulting from t (12:22) (q13; q12) in CCS are helpful features to distinguish the lesions from PEComa.
It seems that malignant PEComa of bone has a tendency to develop metastatic disease. Of 7 malignant bone PEComas, four developed metastatic disease, including pelvic bone metastases in one case , and lung metastases in other 3 cases (including the current case) [7, 8]. At present, the optimal therapy for malignant PEComa remains a challenging practice. The activation of the mTOR signaling pathway was thought mechanistically to be linked to the development of both TSC-associated and non-TSC-associated PEComa . Based on this pathologic mechanism, mTOR inhibitors (sirolimus/rapamycin) was applied in small number of cases and considered to be a rational molecular target for therapy in malignant PEComa . One patient with a malignant PEComa of the left acetabulum tried five cycles of temsirolimus with a favorable response of the suspected pulmonary metastases. However, the patient passed away eight months postoperatively despite several months of additional treatment .
We have described the clinicopathological and immunohistochemical features of a malignant PEComa arising primarily in the femur of an adult male. Although very rare, PEComa can present as a primary bone lesion. Clinical and pathological correlation is mandatory in arriving at the correct diagnosis.
Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.
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