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Malignant PEComa: a case report with emphasis on clinical and morphological criteria
© Selvaggi et al; licensee BioMed Central Ltd. 2011
Received: 19 April 2010
Accepted: 27 January 2011
Published: 27 January 2011
Malignant perivascular epitheliod cell tumor (PEComa) is a very rare entity composed of distinctive perivascular epitheliod cells with variable immunoreactivity for melanocytic and muscle markers. At present this neoplasm does not have a known normal cellular counterpart and the natural history is often unpredictable. Up to now, few cases of PEComa have been described and treatment modalities are still controversial, particularly in advanced conditions.
We handled the case of a 42-year-old man with unresectable PEComa of the abdomen. A 7 cm hepatic hypodense lesion between segment V and VIII of the liver and diffuse intraperitoneal nodules of 0,3-3,5 cm along the right subcapsular hepatic region, were documented by a CT scan. Radiological images showed abnormal lymph nodes of the right internal mammary chain and anterior mediastinum. The patient underwent an explorative laparotomy for uncontrolled intrabdominal hemorrhage without a well-defined preoperative tumor diagnosis. At surgery, multiple lobulated nodules containing hemorrhagic fluid on the liver surface, peritoneum and omentum were confirmed. The procedure had a palliative intent and consisted of hemostasis, hematomas evacuation and omentectomy. The diagnosis of PEComa was made after surgery on the basis of morphological and immunohystochemical criteria. Radiological and intra operative findings suggest that the mass has an hepatic origin with diffuse involvement of hepatic capsule and suspensory ligaments. The patient received medical support care with blood and plasma transfusions. In our experience, PEComa was clinically malignant, leading to a fatal outcome 25 days after hospital admission of patient.
Here we report and discuss the peculiar clinical, radiological and morphological presentation of unresectable PEComa. Although in the majority of the reported series, PEComas show a more better prognosis, our case presents with a particular aggressive biological behaviour. The importance of a correct preoperative diagnosis, the need for more effective targeted therapies based on tumor molecular knowledge and evidence-based clinical studies are emphasized together with a revision of the concerning scientific literature.
PEComa is a mesenchimal neoplasm, predominantly affecting young adults and female individuals . It includes clear cell "sugar" tumor of the lung and extrapulmunary sites, angiomyolipoma, clear cell myomelanocytic tumor of the falciform ligament/ligamentum teres and rare lymphangioleiomyomatosis-like tumors . PEComa has been identified at multiple anatomic sites, such as the liver, uterus, vulva, rectum, heart, breast, urinary bladder, abdominal wall and pancreas, and has been associated with few, if any symptoms, though abdominal pain and bleeding have been reported [1–4]. Preoperative differential diagnosis includes gastrointestinal stromal tumors, melanoma, clear cell sarcoma, leiomyosarcoma . A well-defined preoperative diagnosis is hard to make because of non-specific radiological features . Preoperative biopsy might overcome this limitation, but the data coming from current clinical practices suggest that PEComa diagnosis is usually confirmed after surgery [1, 3]. The biological behaviour of PEComa varied in different cases, some of which developed metastasis, local recurrence or death . We report our first case of malignant PEComa discovered in a young man who underwent an exploratory laparotomy for uncontrolled intrabdominal hemorrhage.
The histological diagnosis of malignant PEComa is based on the published criteria by Folpe and co-workers. In our case, the tumor is characterized by the proliferation of epitheliod and spindle cells. The neoplastic cells are arranged in small-nests or sheet-like patterns, traversed by a delicate vasculature consisting of a rich network of sinusoid-type blood vessels. The tumor cells showed a round to oval nucleus, often with prominent nucleolus and exhibited high nuclear pleomorphism. The tumor is comprised of a population of large polyclonal cells with abundant cytoplasm. The mitotic index is elevated (> 40 figures per 50 high power fields, HPF) and the coagulative necrosis, a prominent feature, appeared as multiple foci of variable sizes. Microscopically the tumor border was infiltrative.
The immediate post-operative course was uneventful and the patient received supporting therapy with blood and plasma transfusions. PEComa was clinically malignant, leading to a fatal outcome in our experience.
Discussion and Conclusions
In 1992, Bonetti proposed the concept of perivascular ephiteliod cells (PECs) and the term PEComa was first introduced by Zamboni four years later . Only in 2003, after the initial scepticism, the World Health Organization defined PEComas as mesenchymal tumors . One current hypothesis is that the neoplasm derives from undifferentiated cells of the neural crest with smooth muscle and melanocytic phenotype. A second hypothesis is that PEC has a myoblastic, smooth muscle origin. A third concerns the perycitic origin . PEComas have been described in different organs and are considered ubiquitous tumors. Clinical presentation is not specific and a correct pre-operative diagnosis is difficult to make. It might be often misdiagnosed with hepatocellular carcinoma, hemangioma, focal nodular hyperplasia and GIST tumor . CT scan is uninformative regarding the tumor nature. Histology with immunohistochemistry techniques are needed to make the correct diagnosis [5–7]. Usually, the diagnosis of PEComa is confirmed after surgery, as reported by the current clinical practice [1, 3]. About 100 PEComas has been reported, of which 38 involved the uterus . Recently, Folpe and colleagues have suggested criteria for malignancy, including a size greater than 5 cm, mitotic count of more than 1 per 50 high-power fields and necrosis . These criteria were observed in our clinical case. PEComa showed hypercellularity, hyperchromasia, high mitotic activity, atypical mitotic figures and coagulative necrosis. We have documented a strong and diffuse reactivity for melanocytic markers, such as HMB-45 and Melan-A, in the cytoplasm of tumor cells together with a focal positivity for SMA. In addition, we have documented a CD34 positive staining of the capillary network surrounding the tumor cells. Depending on specific microenvironment locations, PECs can modulate their morphology and immunophenotype. In some conditions, PECs can pronounce muscle features and in others they can exhibit more epithelioid morphology with strong positivity for HMB45 and weak or focal expression for SMA, as in our condition. On the basis of these peculiarities, the diagnosis of malignant PEComa was made. Interestingly, we have documented CD31 positivity in the cellular membrane of PECs. This result is not so unusual, because other reports have documented the reactivity of CD31 marker in a subset of malignant PEComa, termed PEComas not otherwise-specified . PEComa of the liver is extremely unusual and only a few cases have been reported to date. To the best of our knowledge, there are less than 10 reported cases of liver PEComas . The right lobe of the liver is the most common site and all cases occurred adjacent to the ligamentum teres and falciform ligament . Surgical resection represents the only curative approach for primary PEComa at presentation as well as for local recurrences and metastasis, as chemotherapy and radiotherapy have not demonstrated significant benefits [8, 10]. Only recently limited clinical studies have reported encouraging results in terms of therapeutic response after oral administration of mTOR inhibitor in patients with metastatic PEComa . Our case represents the clinical condition of malignant PEComa of the liver presented with intrabdominal metastases. Radiological pattern and intraoperative founding suggest that the mass has an hepatic origin with diffuse involvement of hepatic capsule and suspensory ligaments. Although the majority of clinical reports on PEComa shows a better outcome, our case highlights the aggressive biological nature of a malignant subset of PEComa characterized by an infaust evolution.
We thank Prof. C.D.M. Fletcher (Brigham and Women's Hospital, Boston) for critically analysis of morphological data.
Written informed consent was obtained for publication of this clinical case with accompanying imaging.
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