The WHO has offered formal recognition to a group of neoplasms with perivascular epithelioid cell differentiation [2
]. These tumors have in common the presence of epithelioid to spindle cells with eosinophilic to clear cytoplasm that, with few exceptions, demonstrate positive immunostaining for markers of both myoid (smooth muscle actin, desmin) and melanocytic (HMB45, Melan-A, tyrosinase) differentiation. Pathologically, the main differential diagnoses include paraganglioma, melanoma, clear cell sarcoma of soft parts (CCSSP), metastatic carcinoma (especially from kidney or adrenal gland) and epithelioid sarcoma.
While distinct clinicopathological entities included within the PEComa group include AML, LAM and CCST, other PEC-derived tumors have been documented at an increasing number of anatomical sites, including pancreas, small and large intestine, ligamentum teres/falciform ligament, common bile duct, bladder, prostate, breast, uterus, cervix, vulva, ovary, broad ligament, heart, base of skull, and soft tissue [3
]. The term "PEComa" has become the popular umbrella term for this latter list of lesions. Only one case of primary bladder PEComa has been described previous to ours. Pan et al reported a case of PEComa occurring in the deep detrusor muscle of the bladder in a 33-year-old woman, which was an incidental discovery during work-up for dysmenorrhea [8
]. While there were no worrisome clinicopathological features of the tumor and the patient remained tumor free during the entire six-year follow-up period, there was no description of post-operative treatment.
PEComas demonstrate uncertain tumor biology and unpredictable clinical behavior. While the majority of reported "PEComas" have behaved in a benign fashion, an important minority have demonstrated malignant behavior with locally destructive recurrences, distant metastases and patient death, underscoring the need for accurate identification and effective treatment strategies [4
]. When Folpe et al combined results of 24 of their own cases of PEComa of soft tissue and gynecological origin with data from 45 previously reported cases of PEComa, they found that recurrence and metastasis were associated with tumor size >5 cm, infiltrative growth pattern, high nuclear grade, necrosis and a mitotic index of >1 per 50 high power fields [9
]. However, other authors feel that accurate criteria which reliably predict the behavior of PEComas remain lacking [10
]. In the present case, the surgical margins were not evaluable, due to the fragmented nature of the specimen, and lymph nodes were not sampled, since the intraoperative impression was that of a benign enterovesical fistula, rather than a potentially malignant neoplasm.
Optimal treatment for PEComas is not known at this time. Primary excision is usually curative, as most tumors are benign. However, locally advanced or metastatic disease portends a poor prognosis and strategies incorporating chemotherapy, radiation and immunotherapy have been reported. In this patient, a one-year course of adjuvant IFN-α 2b at 10 million units given subcutaneously three times per week was initiated based on the vascular nature of this tumor and IFN-α's additional anti-angiogenic effect [11
]. While IFN-α 2b therapy for the management of PEComa remains experimental, other authors have described the efficacy of IFN-α 2a in causing regression of life-threating hemangiomas in infants [12
]. While fever, neutropenia and skin necrosis have been reported as uncommon, short-term side effects of IFN-α 2a, no such effects were seen in the present case [12
]. As there was no evidence of residual tumor in the present case, a limitation of our report would be that the effect of IFN-α on PEComa morphology could not be documented. Thus, further studies are needed to clarify the clinical and pathological effects of IFN-α therapy in patients with PEComa and the risks of IFN therapy should be weighed against the potential benefits in any patient lacking detectable residual tumor. Partial, complete and absent responses have also been noted for dacarbazine, vincristine and imatinib mesylate, a tyrosine-kinase inhibitor [14
]. Adjuvant radiation for CCSSP has also been reported following wide surgical excision, with primary site irradiation appearing to confer a survival benefit for disease located in soft tissue of the extremities [15