Primary pleural angiosarcoma as a mimicker of mesothelioma: a case report
© Kao et al; licensee BioMed Central Ltd. 2011
Received: 12 November 2011
Accepted: 30 December 2011
Published: 30 December 2011
Primary pleural angiosarcoma is a rare and clinically aggressive tumor. Patients usually present with chest pain, dyspnea, hemoptysis and/or cough. Radiologic studies reveal diffuse pleural thickening and pleural effusion with or without mass lesion. The clinical and radiological features both resemble those of mesothelioma, and its definite diagnosis requires careful histologic examination. However, frequent epithelioid feature and immunoreactivity to cytokeratin in primary pleural angiosarcoma further complicate the pathologic diagnosis. The use of proper immunohistochemical stains is often needed to support endothelial differentiation in the tumor cells and to exclude metastatic carcinoma and mesothelioma. We report the case of a 49-year-old male patient with primary pleural angiosarcoma, who presented with initial hemothorax, followed by a rapid progress to an inoperable status.
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Keywordsangiosarcoma pleura mesothelioma sarcoma pathology
Angiosarcoma is an uncommon malignant tumor of endothelial differentiation. It accounts for about 1% of all soft tissue malignancies and most commonly arises in skin, soft tissue, breast, liver, bone and spleen .
Primary pleural angiosarcoma (PPA) is a rare occurrence. Since its first description in 1943, only 39 reported cases of PPA have been published [1–22]. Patients almost always die of the disease within months. Definite diagnosis is usually not possible using the examination of cytology or small biopsy specimens, but often requires that of decortication or resection specimens. The histologic picture of biphasic spindle and epithelioid tumor cells along with immunoreactivity to epithelial markers, such as cytokeratin and CK7, may lead to an erroneous diagnosis of mesothelioma or metastatic sarcomatoid carcinoma. Identifying areas showing vasoformative tendency and immunostains with endothelial markers, such as CD31, CD34, factor VIII and FLI-1, are diagnostically important.
We describe herein a case of PPA, to highlight its aggressive clinical behavior and the diagnostic pitfalls.
One month later, open thoracotomy revealed tumor mass extending along the previous surgical wound and encasing the right pulmonary hilum. Curative resection could not be done, and the patient received an excisional biopsy of the tumor.
The effusions are usually bloody. Cytologic examination of the pleural effusion is rarely helpful in making the diagnosis. In the seven cases with available cytologic examination results,[1, 8, 9, 13, 19, 20, 22] presence of atypical cells was described in only one case . Most patients were diagnosed by surgical excision (32.5%, including debulking excision, pleurectomy and decortication) [3, 5, 7, 9, 12, 13, 15, 17, 18, 20] or autopsy in rapidly lethal cases (27.5%) [2, 4, 5, 8, 10, 21, 22]. Using non-invasive biopsy and surgical biopsy, the patients were diagnosed as PPA in a smaller proportion of cases (17.5% and 10%, respectively) [1, 5, 6, 14, 16, 19]. Six out of 40 patients received a non-diagnostic biopsy [8, 9, 13, 19, 21, 22]. Thus, in the context of refractory bloody pleural effusion of uncertain etiology, we suggest that surgical biopsy or excision should be considered even without mass lesion.
The histologic features show malignant spindle and/or epithelioid neoplasm with areas of vasoformative nature, such as vascular spaces lined by atypical tumor cells and intracytoplasmic lumen containing RBCs. Epithelioid features were mentioned in the majority of cases (72.5%) and constituted variable proportion of the tumors [1, 5–15, 17–19]. The differential diagnosis of a biphasic pleural tumor mainly includes mesothelioma and sarcomatoid carcinoma. In general, mesothelioma shows more monotonous tumor cells with less degree of cytologic atypia. Intracytoplasmic lumen can be seen both in angiosarcoma and mesothelioma, but intraluminal RBCs are not seen in mesotheliomas . Sarcomatoid carcinoma less likely manifests as diffuse pleural involvement. The carcinomatous component and clinical history would aid in diagnosis.
Immunohistochemical stains have an important role in differential diagnosis. Expression of at least one of the endothelial markers including CD31, CD34, factor VIII and FLI-1, is required to confirm the diagnosis of angiosarcoma. Among them, CD31 is considered to be the most sensitive and specific . Epithelial markers can be expressed in angiosarcoma, especially in the epithelioid variant . Positive cytokeratin staining was found in 60.9% cases of PPA (14 of 23, including our patient) [1, 5, 11, 14, 15]. Immunoreactivity to CAM5.2, CK7, CK8 or CK18 has also been reported [1, 13, 14]. Epithelial membrane antigen was negative in all those 14 cases with available results [5, 6, 12, 16, 19, 20]. The expression of epithelial markers can be misleading in pathologic diagnosis. One should bear in mind that cytokeratin is also frequently expressed in epithelioid vascular tumors. Although the expression pattern of cytokeratin can range from diffuse and strong to focal and weak in distribution, it is usually not as strong as that in carcinoma or mesothelioma . Mesothelial markers such as calretinin, CK5/6, HBME-1 and WT-1, are used to exclude malignant mesothelioma.
The etiologic factors in most cases of PPA are still unknown. Some case reports from Japan indicated the relationship with tuberculous pyothorax (n = 11), [5, 15, 21] while some cases from western countries had history of asbestos exposure (n = 4)[7, 10] or radiotherapy (n = 1) . Association with tuberculosis has been first described by Myoui et al. in 3 out of 4 PPA patients . Based on a series of autopsy cases, Aozasa et al. later reported six additional PPA patients associated with tuberculosis and postulated 3,600-fold increased risk of PPA in pyothorax patients . But, Hattori et al. suggested that pyothorax-associated angiosarcoma often manifest as chest wall soft tissue tumors instead of diffuse pleural involvement and should be separated from PPA . Attanoos et al reported three PPA patients with history of asbestos exposure . However, only one of them had typical asbestos bodies in the lung and increased asbestos fiber content by mineral analysis. One patient with history of previous radiotherapy for ovarian carcinoma developed simultaneous pleural and peritoneal angiosarcoma . Our patient did not have any history of tuberculosis, asbestos exposure or radiotherapy.
In conclusion, PPA is a highly malignant disease, which may mimic mesothelioma clinically, radiologically and even pathologically. The diagnostic pitfalls include mesotheliomatous growth pattern with diffuse pleural involvement, biphasic histomorphologic pattern and immunoreactivity to cytokeratin. An accurate diagnosis requires careful pathologic examination to identify the evidence of endothelial differentiation aided with immunohistochemical stains.
Written informed consent was obtained from the patient for publication of this Case Report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal
List of abbreviations used
primary pleural angiosarcoma
red blood cells.
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