Background
Perivascular epithelioid cell tumor (PEComa) is a rare subtype of mesenchymal origin tumors, and is composed of perivascular epithelioid cells with specific histologic and immunohistochemical features [
1]. PEComa of the female gynecological tract is a rare entity presenting with variable symptoms and different prognosis for each individual case. The uterus is one of the most commonly involved sites. Preoperative distinction may at times be problematic, as the symptoms of uterine PEComa are nonspecific and similar to those of other uterine tumors, and some patients may be asymptomatic.
Radiologically, uterine PEComas can be highly homogeneous, resembling small, benign smooth muscle lesions, and thus, their differential diagnosis is almost impossible based on imaging features alone [
2]. However, their preoperative diagnosis may be assisted by biopsy and subsequent immunohistochemistry, which is nearly always immunoreactive for both melanocytic (HMB-45, melan-A, MiTF) and smooth muscle markers (SMA, desmin, caldesmon) [
3]. Herein, the authors present two rare cases of uterine PEComa diagnosed postoperatively.
Discussion
Perivascular epithelioid cell tumor (PEComa) is recently described entity in the gynecological tract. It occurs most commonly in the retroperitoneum, abdominopelvic region, and uterus. To date, around 78 case reports have been issued on uterine PEComas and the most com-mon site in the female genital tract. We present two cases of PEComa of the uterus with different clinicopathological features (Table
1).
Clinical, radiological, and preoperative pathological features of PEComa cases are diagnostic challenge. In most of the PEComa cases, the diagnosis was confirmed after hysterectomy for a presumed benign disease. The proper preoperative diagnosis of uterine PEComa is difficult because of the lack of a reliable method to distinguish uterine PEComa from benign leiomyomas and uterine sarcoma preoperatively in addition to the rarity of such cases. Clinical manifestations are not useful to distinguish between uterine PEComas and other uterine tumors, since most of the patients with uterine PEComas show abnormal uterine bleeding or lower abdominal pain with a palpable mass, which is similar to the symptoms and signs of other uterine tumors. PEComa can be associated with tuberous sclerosis complex (TSC). Some PEComas occur in TSC patients in sites, such as, kidney, liver, and lung. However, uterine PEComa associated with tuberous sclerosis is very rare.
Imaging features of PEComas are nonspecific and mimic other benign and malignant neoplasms. One study by Tan et al. [
4] reported the largest imaging series of 36 patients with malignant PEComas. Ultrasound showed a heterogeneous echotexture with no cystic areas or significant vascularity on Doppler examination. By a comparison with skeletal muscle, CT scans revealed a rather well-defined hypo- or isointense structure, and MRI also displayed a hypo- to isointense structure on T1-weighted imaging and a heterogeneously hyperintense structure on T2-weighted imaging. In general, the characteristics of contrast-enhanced CT or MRI of malignant PEComas were very variable, but their results showed significant enhancement on CT and MRI [
2]. Despite such radiologic features, the differential diagnosis of these diseases from other uterine tumors is almost impossible based on imaging features alone. In our two cases, we performed imaging with MRI but failed to distinguish between uterine PEComas and other uterine tumors. One of these two tumors was diagnosed as a degenerative fibroid or leiomyosarcoma because of the large tumor size and the presence of necrotic areas. The other was diagnosed as leiomyoma because of the homogeneous enhancement (Fig.
2a, b). MRI did not provide a definitive diagnosis in our cases.
Since PEComas are nearly always immunoreactive for both melanocytic (HMB-45, melan-A, MiTF) and smooth muscle (actin, desmin, caldesmon) markers, characteristic histologic and immunohistochemical findings provide the most accurate means of diagnosis [
3]. Preoperatively, biopsy is not usually performed in uterine tumors, and it is very limited in many cases. In our case 1, we failed to differentiate uterine PEComa and leiomyosarcoma despite a preoperative punch biopsy and immunohistochemical analysis of the metastatic vaginal mass. Preoperative diagnosis was malignant tumor suggestive of leiomyosarcoma, mainly based on the immunohistochemical results (positive for SMA, but negative for HMB45). However, the final immunohistochemical result showed patchy expression for HMB45. Therefore, it was finally diagnosed as malignant PEComa in conjunction with histologic and immunohistochemical findings. To prevent diagnostic error, multiple pieces of biopsy should be sampled in case of metastatic disease. However, morphology- and immunohistochemistry-based diagnosis may lead to incorrect or inconclusive diagnoses due to patchy expression of HMB45 in tumor cells and a marked necrotic background [
5].
Although uterine PEComas represent a spectrum of histologies ranging from benign to malignant lesions, the tumor aggressiveness has not yet been fully explained. Malignant uterine PEComas can spread to the vagina, fallopian tubes, ovaries, bladder, and ureters. Distant metastasis to the lungs or liver has also been reported. Up to 20% of women with malignant uterine PEComa have an additional uterine disease at presentation [
2]. Folpe et al. reported that PEComas are divided into benign, uncertain malignant potential (UMP), or malignant tumors according to the following six risk factors: tumor size ≥5 cm, infiltrative growth pattern, high nuclear grade cellularity, mitotic rate >1/50 high power fields (HPF), necrosis or vascular invasion [
3]. Schoolmeister et al. revised the classification of PEComas. The tumor is considered as malignant when there are more than four unfavorable prognostic indicators (size ≥5 cm, mitoses ≥1/50 HPF, significant nuclear atypia, necrosis, and lymphovascular invasion) [
6]. Bleeker et al. suggested revised risk stratification criteria utilizing only size ≥5 cm and high mitotic rate, which were the only high-risk histopathologic features significantly associated with recurrence [
7].
The most adequate management of gynecological PEComas has not been well established owing to the paucity of the cases. Surgical resection remains the treatment of choice. The vast majority of patients received a total hysterectomy with or without bilateral salpingo-oophorectomy. Radical hysterectomy with bilateral salpingo-oophorectomy should be considered in patients with PEComas spreading or localized in the uterine cervix [
8].
Authors’ contributions
DSS, YJS, and BSK performed the operation. NKL and KUC were involved in acquisition of data and preparing the figures. BSK wrote the manuscript. KHK and DSS proofread and revised the manuscript. All authors read and approved the final manuscript.