Recurrent Solitary Fibrous Tumor of the Pleura With Malignant Transformation Open Access

Solitary fibrous tumor of the pleura mainly affects adults in their sixth and seventh decades of life. Solitary fibrous tumor has also been described in other parts of the body. In contrast to malignant mesothelioma, this tumor occurs independently of previous exposure to asbestos. It is almost impossible to clinically discriminate this tumor from malignant localized mesothelioma preoperatively. Lack of distinctive histologic features to permit exclusion of all other differential diagnoses has led pathologists to use immunophenotypic analysis in an effort to characterize this tumor. The lack of distinctive histologic features results in the most common microscopic pattern, that of the “patternless pattern of Stout.” Other descriptions include a hemangiopericytoma-like appearance and a diffuse sclerosing pattern.1 Surgical resection of solitary fibrous tumor, which is usually a benign tumor, is the treatment of choice. However, locally aggressive clinical behavior, including recurrence, malignant transformation, metastasis, and death from this disease, are possible.2 

In June 2002, an 85-year-old white woman was admitted for a recurring mass in her left chest wall. The patient had undergone prior surgical resection of this recurrent mass at 2, 5, and 9 years prior to the current presentation. The findings from physical examinations and laboratory tests were otherwise noncontributory. The patient underwent surgical removal of the mass, and except for a difficult intubation, the surgery and the postoperative period were uneventful.

The patient's original chest wall tumor was diagnosed 5 and 9 years prior to the current presentation. However, at the last local recurrence, the lesion was reclassified as solitary fibrous tumor of the pleura with the aid of immunohistochemical and ultrastructural ancillary studies. In light of these observations, we reexamined the current specimen with the previously used immunohistochemical panel of S100 (Dako, Mississauga, Ontario), low-molecular-weight keratin (Becton Dickinson, Mississauga, Ontario), smooth muscle actin (Sigma, Oakville, Ontario), and CD34 (Dako). All immunostains were negative in the current resected tumor. This included CD34 immunostaining, which was strongly positive in the specimen resected 2 years earlier (Figure 1). The histomorphologic appearances of routine hematoxylin-eosin–stained slides showed features that were similar to those of all the previous lesions, which were reviewed for this recurrence (Figure 2). However, there was a perceptible increase in the number of mitotic figures, which reached 10 per 10 high-power fields (HPF) in the current specimen (Figure 3, a), in contrast to 1 to 2 per 10 HPF in the previous tumor resections. This change was also supported by an increased overexpression of Ki-67 (Dako) in 30% of the lesional cells in the current lesion (Figure 3, b), in comparison to less than 10% in the previous tumor sections, indicating increased proliferative activity of the current lesion. Supporting evidence for malignant transformation included high cellularity, increased mitotic activity, cellular pleomorphism, hemorrhage, and necrosis (Figure 3, a through c). A fibrous pseudocapsule generally surrounded these recurrent tumor nodules, although the tumor protruded through the capsule in some areas (Figure 3, d). The presumptive working diagnosis was recurrent sarcoma prior to review of all previous material; following review, the current tumor was classified as malignant solitary fibrous tumor of the pleura.

Solitary fibrous tumor is a rare tumor of the pleura that usually occurs in the elderly. Respiratory symptoms, which can be present in one third of patients, include cough, dyspnea, pleuritic pain, and hemoptysis. Extrathoracic manifestations of solitary fibrous tumor, which are more often associated with larger tumors, include osteoarthropathy, clubbing, and less frequently, hypoglycemia. Hypoglycemia occurs due to tumor secretion of an insulin-like growth factor.1,3 

Solitary fibrous tumor has also been reported in extrapleural sites, such as thyroid, salivary glands, orbit, liver, breast, upper and lower respiratory tract, soft tissues, peritoneal cavity, retroperitoneum, meninges, and heart. Clinically, malignant mesothelioma and metastatic pulmonary carcinomas are the most important entities in the differential diagnoses of this lesion. Histopathologically, mesothelioma, synovial sarcoma, sarcomatoid carcinoma, malignant peripheral nerve sheath tumor, hemangiopericytoma, and fibrosarcoma are diagnostic considerations. Solitary fibrous tumor of the pleura is usually a benign neoplasm, and surgical resection is curative and remains the treatment of choice. However, locally aggressive behavior with repeated recurrences and distant metastasis has been observed in some cases.4,5 

Criteria used by England et al6 for evaluation of malignancy included high cellularity, increased mitotic activity (>4 mitotic figures per 10 HPF), pleomorphism, hemorrhage, and necrosis. However, histologic evidence of malignancy alone does not always forecast an unfavorable clinical course. The most important single indicator of clinical outcome is whether the tumor is completely excised at primary presentation.6 

Solitary fibrous tumor is a neoplasm that, in the pleura, seems to originate from the submesothelial connective tissue. Immunohistochemical staining and ultrastructural studies show the nonmesothelial origin of the tumor. Immunoreactivity with S100 is typical of nerve sheath tumors and is not evident in any solitary fibrous tumor of the pleura. Cytokeratin is expressed in mesothelioma and is usually negative in solitary fibrous tumors of the pleura. CD34, a myeloid progenitor cell antigen that is also present in normal and neoplastic endothelial cells, including subsets of fibroblasts, is strongly positive in most cases of solitary fibrous tumor.5 CD34 is, however, widely expressed in mesenchymal neoplasms and is therefore not specific for solitary fibrous tumors. Nevertheless, in the proper histologic context of a pleura-based lesion, CD34 expression is extremely useful, as it is consistently positive in solitary fibrous tumor but absent in malignant mesothelioma. Careful selection of a panel of such markers, including cytokeratin and calretinin, helps in the diagnostic workup of malignant mesothelioma. Definite diagnosis of solitary fibrous tumor without these immunohistochemical staining patterns remains a diagnostic challenge, and we assume that it had affected our case when first diagnosed as a malignant mesothelioma; however, one should bear in mind that although CD34 is a useful marker in the diagnosis of solitary fibrous tumor, its expression can be lost in high-grade tumors or with repeated recurrences. Conversion of a CD34-positive solitary fibrous tumor to a CD34-negative lesion is associated with malignant transformation. In our case, loss of such expression was also accompanied by malignant criteria in the histomorphologic appearance.5 

Distinction of malignant solitary fibrous tumor from diffuse malignant mesothelioma is important because the treatment modalities and prognoses for the 2 lesions are different. Malignant solitary fibrous tumor, even when high grade, may be cured by wide local resection of tumor, whereas pneumonectomy with decortication of total parietal pleura is the recommended procedure in the surgical management of resectable malignant mesotheliomas. CD34 and keratin immunostaining in addition to gross and histologic findings is usually effective in distinguishing most of the malignant pleural spindle tumors. However, CD34 immunostaining is negative in solitary fibrous tumors, like the tumor in our case, and keratin immunostain–negative malignant mesotheliomas do exist and can cause diagnostic confusion.2 

The main method of treatment for solitary fibrous tumors remains wide local excision of the tumor. Postoperative adjuvant therapy with chemotherapy and/or radiotherapy has been used sporadically, but the benefit of these adjuvant therapies remains unproven. Recurrence after complete resection does occur in both the benign and malignant forms; therefore, long-term clinical follow-up is highly recommended.3,7 

Histopathologic recognition of solitary fibrous tumor of the pleura without immunohistochemical staining is quite challenging as it is a rare disease. Accurate diasnosis is important because life-long follow-up is recommended in these rare cases, owing to the possibility of repeated recurrences with or without malignant transformation.

We thank Todd Reichert and Michelle Hesson for their help in the production of the illustrations for this article.