The World Health Organization defines PEComas as “mesenchymal tumors composed of histologically and immunohistochemically distinctive perivascular epithelioid cells.”11
These tumours have in common the presence of epithelioid to spindle cells with eosinophilic to clear cytoplasm, which demonstrate positive immunostaining for markers of both myoid (smooth muscle actin, desmin) and melanocytic (HMB-45) differentiation. The PEComa family of tumours includes tumours such as angiomyolipoma, clear cell “sugar” tumour and lymphangioleiomyomatosis.2,3,4,5
In addition, the PEComa family consists of a number of unusual visceral, intra-abdominal, soft tissue and bone tumours, which have been described under a variety of names, including “clear cell myomelanocytic tumor of the falciform ligament/ligamentum teres,” “abdominopelvic sarcoma of perivascular epithelioid cells” and “primary extrapulmonary sugar tumor,” among others.6
PEComas have been documented in a variety of anatomical locations, including the pancreas, small and large intestine, ligamentum teres/falciform ligament, common bile duct, kidney, bladder, prostate, breast, uterus, cervix, vulva, ovary, broad ligament, heart, base of skull and soft tissue.8,12,13,14,15
The major differential diagnosis of this tumour around the anatomical site of the urinary bladder, includes smooth muscle tumours. Smooth muscle tumours, including leiomyoma and leiomyosarcoma, are the most common mesenchymal tumours of the urinary bladder in adults.16
The cytoplasm of the neoplastic smooth muscle cells is usually more eosinophilic rather than the clear-to-pale cytoplasm in the tumour cells of PEComas. Both smooth muscle tumours and PEComas are known to express actin, however the smooth muscle tumour has not been reported to be immunoreactive for melanocytic markers. The strong immunoreactivity for HMB-45 in the present case can essentially rule out the possibility of a smooth muscle tumour.
Additional differential diagnoses to consider would be malignant melanoma, postoperative spindle cell tumour and sarcomatoid carcinoma. Each of these possibilities can be easily excluded on the basis of morphology and immunohistochemistry.
Only 3 other cases of primary PEComa involving the urinary bladder have been described before ours. The first report by Pan and colleagues described a 33-year-old Taiwanese woman who was found to have a PEComa of the bladder during a workup for dysmenoorhea.8
The patient did not have any lower urinary tract symptoms or gross hematuria. She underwent partial cystectomy with total excision of the tumour and remained without evidence of disease with 6 years of follow-up. Kalyanasundaram and colleagues reported the case of a 19-year-old woman who presented with gross hematuria and was found to have an intraluminal, polypoidal pedunculated mass in her bladder.9
She underwent transurethral resection of the bladder mass, which revealed primary PEComa of the bladder on pathological evaluation. The patient was later lost to follow-up. Parfitt and coauthors described a 48-year-old man who presented with dysuria, passage of urinary sediment and lower abdominal discomfort.10
The patient underwent laparotomy, partial cystectomy and partial small bowel resection for a presumed enterovesical fistula. Pathological evaluation revealed primary PEComa of the bladder. The patient subsequently underwent adjuvant interferon (IFN)-α immunotherapy. He remained without evidence of disease recurrence 48 months following surgery.
PEComas demonstrate uncertain tumour biology and unpredictable clinical behaviour. The majority of reported PEComas behaved in a benign fashion; however, a minority have demonstrated malignant behaviour with locally destructive recurrences, distant metastasis and death.7,12,13
One of the largest series of cases published in the literature included 26 patients with PEComas of soft tissue and gynecologic origin.17
Of the 26 patients, clinical follow-up data was available for 24 patients, with a median of 30 months. Three patients demonstrated local recurrence and 5 showed distant metastases. At the time of final clinical follow-up, 2 patients (8%) had died of disease, 4 patients (17%) were alive and had metastatic or unresectable local disease and 18 patients (75%) were alive with no evidence of disease. This paper also included a review of the literature combining their results of 24 cases with 45 previously reported cases of PEComa, with special attention to features predictive of clinical behaviour. They found that recurrence or metastasis (or both) were strongly associated with tumour size > 5 cm, infiltrative growth pattern, high nuclear grade, necrosis and a mitotic index of > 1 per 50 HPF.
The optimal treatment of PEComa is not known at this time. Surgical excision is the mainstay of therapy as most tumours are benign. For the minority of patients with locally advanced or metastatic disease, therapies incorporating radiation, chemotherapy and immunotherapy have been reported. Locally advanced and metastatic disease generally portends a poor prognosis.