Perivascular epithelioid cell tumour-mimicking retroperitoneal leiomyosarcoma

Discussion

PEComa is a rare mesenchymal tumour with unclear precursor cells. Various theories exist regarding its origin, including derivation from undifferentiated cells of the neural crest, since they express many melanocytic and muscular markers. Another theory suggests an origin from telocytes as the markers expressed in telocytes (eg, S-100, SMA, Vascular Endothelial Growth Factor (VEGF)) are also expressed in PEComas.7 PEComas present with non-specific clinical signs. Symptoms rely on the different organs involved and can include abdominal pain, melena, bowel obstruction, weight loss and anaemia. Some primary sites of PEComa include the retroperitoneum, uterus, vulva, gastrointestinal tract (oesophagus, stomach, duodenum, jejunum, ileum, colon, rectum), heart, breast, urinary bladder, abdominal wall, skin, mesentery, oral cavity, pancreas and liver. Women are more commonly affected than men, and these tumours are more frequently seen in the fourth and fifth decades of life.8 Imaging studies are not sufficiently sensitive to make the diagnosis of PEComas. Most PEComas are well-circumscribed masses with homogenous density on CT and are hypodense to isodense on CT, hypodense to isointense on T1-weighted imaging and heterogeneously hyperintense on T2-weighted imaging. The enhancement characteristics of PEComas in general are very variable. Although one study found that 21of 32 PEComas showed intense enhancement, there are other case reports that describe PEComas as hypovascular masses.9 10 Necrosis, calcifications and haemorrhage within the tumour have also been described.11 Given its non-specific radiographic imaging characteristics, PEComas can be easily misdiagnosed.

PEComas are generally composed of a mixture of blood vessels, smooth muscle cells and adipose tissue. The tumour cells are either epithelioid or spindle arranged in bands, nests or swirls. The spindle tumour cells are usually arranged in bundles and have an eosinophilic cytoplasm. The epithelioid cells appear with bright and finely granulated cytoplasm. The nuclei tend to be relatively small and round-to-oval shaped and are centrally located within the cells. Blood vessels are distributed in clusters and arranged around tumour cells. The vessel lumen is irregularly dilated, twisted or dysmorphic. The vessel walls are not consistent in thickness and exhibit variable levels of hyalinisation or amyloidosis. PEComas demonstrate breakage in the elastic fibres in both the internal and external lamina of blood vessels, which causes the vessels to be prone to spontaneous rupturing and haemorrhaging. The amount of mature adipose tissue varies from predominant to absent and displays a grey-pink or pale coloration with a yellowish appearance.12 Immunohistochemical features demonstrate positive staining for Cathepsin K (100%), HMB-45 (98%), SMA (81%), caldesmon (75%), desmin (67–80%), MiTF (66–83%), MelanA/MART1(58–67%).13 14 Immunohistochemical features demonstrate negative staining for S-100 and AE1/AE3. The histologic description of PEComa bears a resemblance to that of an angiomyolipoma, which also has a classic triphasic composition: myoid spindle cells, mature adipose tissue and dysmorphic thick walled blood vessels without elastic lamina. However, the fat component in an angiomyolipoma is in the form of mature adipose tissue, the vascular component is in the form of thick walled hyalinized vessels, and the epitheliod cells contain a clear or densely eosinophilic cytoplasm with large hyperchromatic bizarre nuclei that is multilobated.

Our initial diagnosis of low-grade leiomyosarcoma on core needle biopsy was made based on the histologic identification of spindle cells with atypia and positive immunohistochemical staining for desmin, vimentin and SMA (figure 2). Our final diagnosis of PEComa was supported by the histologic finding of small bundles and nests of spindle to epithelioid neoplastic cells with clear to pale eosinophilic cytoplasm and a perivascular pattern of growth. The neoplastic cells did not demonstrate pleomorphism, mitosis or necrosis. Immunohistochemical stains showed that the neoplastic cells were positive for Cathepsin K, caldesmon, HMB-45, MiTF, desmin and SMA (figures 2 and 3). The specimen did not stain for S-100 distinguishing it from melanoma (figure 4).

Both leiomyosarcoma and PEComa present with nuclear atypia and tumour cell necrosis.15 An important histologic distinction between leiomyosarcoma and PEComa is the absence of thin and delicate vessels seen in leiomyosarcoma. Furthermore, leiomyosarcomas do not stain for melanocytic markers, which is unlike PEComas. Finally, the absence of mature adipocytes as the predominant cell type differentiates PEComas from angiomyolipomas.

Due to the rarity of PEComas, standardised treatment protocols are not available. Surgical excision remains the treatment of choice for localised PEComas while adjuvant chemotherapy, immunotherapy or radiotherapy has little efficacy. However, mammalian target of rapamycin inhibitors is emerging as promising targeted therapy for malignant PEComa.7 16 17 PEComas with two or more of the following characteristics are considered high risk for local recurrence and distal metastasis: size >5 cm, infiltrative growth pattern, high nuclear grade, tumour necrosis, mitotic activity >1/50 HPF and vascular invasion.18 Our patient met two criteria: tumour size and renal parenchymal invasion. Surveillance with routine imaging is recommended given the high-risk features for local recurrence and distal metastasis. However, optimal surveillance recommendations for PEComa are not available in the literature and each case should undergo surveillance based on a multidisciplinary evaluation, taking into account tumour characteristics and patient factors.

This case highlights the critical role of pathology in establishing the correct diagnosis when radiographic and clinical modalities are inconclusive. The microscopic features and immunohistochemical staining patterns are essential to the correct diagnosis of PEComa and play a central role in distinguishing PEComa from other disease processes such as angiomyolipoma, melanoma and leiomyosarcoma.