Continuing Education Activity

Solitary fibrous tumors of the pleura (SFTPs) are a quiet entity and grow to a great size and extent before manifesting signs or symptoms. Solitary pleural fibrous tumors represent a rare entity of primary neoplasms originating from mesenchymal cells in the submesothelial layer of the pleura. Solitary pleural fibrous tumors represent less than 5% of primary pleural neoplasms. They are mostly benign in nature. A histopathological workup is required in diagnosing these tumors. This activity reviews the evaluation and management of solitary fibrous tumors of the pleura and highlights the role of the interprofessional team in managing patients with the disease.

Objectives:

• Describe the clinical characteristics of solitary fibrous tumors of the pleura.

• Review the workup required for patients with solitary fibrous tumors of the pleura.

• Outline treatment modalities in patients with these tumors.

• Summarize recommendations for post-treatment surveillance.

Introduction

Solitary pleural fibrous tumors represent a rare entity of primary neoplasms originating from mesenchymal cells in the submesothelial layer of the pleura. Solitary pleural fibrous tumors represent less than 5% of primary pleural neoplasms.[1] These tumors are rarely malignant with indolent clinic course and asymptomatic presentation.[2] Solitary fibrous tumors of the pleura were first described in 1931 and historically referred to by different names, including benign mesothelioma, pleural fibroma, etc.[3][4] It is important to note that solitary fibrous tumors can potentially affect soft tissue, viscera, and other cavities, including the peritoneum and meninges. Due to their rarity, most of the existing knowledge on this is derived from case reports and retrospective studies.

Etiology

The causes of solitary pleural fibrous tumors are not known. Unlike other pleural malignancies like mesothelioma associated with asbestos exposure, the risk factors related to solitary pleural fibrous tumors are yet to be elucidated. No association with environmental exposure to radiation, tobacco, or other toxic agents has been found. There are no known genetic risk factors.

Epidemiology

Solitary fibrous tumors involving the pleura represent less than 5% of all pleural tumors.[1] The reported incidence of solitary pleural fibrous tumors is 2.8 per 100,000 people.[4] Solitary fibrous tumors of the pleura occur at equal frequencies in males and females. They predominantly affect older patients, usually in the 6th and 7th decade.[4][5] While solitary fibrous tumors of the pleura are mainly benign, about 20% are reportedly malignant.[6]

Pathophysiology

SFTPs arise from mesenchymal cells in the pleura. They usually originate from the visceral pleura, with one-third originating from the parietal pleura. The mid to lower zones of the chest are the most common predilection sites. The tumor usually has well-defined borders and may be pedunculated. The tumor may grow several centimeters in diameter, and its physical presence can result in clinical symptoms. SFTPs may produce insulin-like growth factor 2 (IGF-2), resulting in refractory hypoglycemia (Doege-potter syndrome). 

Due to the rarity of solitary fibrous tumors of the pleura, it is difficult to delineate between benign and malignant forms of the tumor. Characteristics typically felt to favor a diagnosis of malignancy include the following: high Ki67 proliferation index, p53 positivity, paraneoplastic syndrome, tumor diameter greater than 10 cm, pleural effusion, calcifications, tumor necrosis, and cellular dysmorphisms.[7][8][9]

Metastases are usually bloodborne, with common sites of metastases including the lungs, chest wall, and intrabdominal organs like the liver.[9]

Histopathology

Histologic evaluation of tissue samples is needed to diagnose solitary fibrous tumors of the pleura. The classic histologic phenotype of SFTP is hypocellular with stroma of thick collagen bands separating irregularly arranged fascicles which consist of spindle cells. The arrangement typically results in a “patternless pattern.” Capillaries are frequently present.

In the hypercellular presentation, the tumor consists of solid nests of tumor cells with scant or absent collagen fibers. The cells appear more ovoid rather than spindled. Very often, hemorrhage and necrosis can be seen in these tumors.

Histologic findings indicating malignancy include hypercellularity, high mitotic index (>4 mitoses per high-powered field), varying degrees of pleomorphism, hemorrhage, and necrosis.[10] While these features are useful in predicting malignant potential, solitary fibrous tumors often exhibit unpredictable histologic behaviors.[11]

History and Physical

Patients are usually asymptomatic, but some nonspecific pulmonary symptoms like dyspnea, chest pain, or dry cough have been reported by up to 40 to 60% of patients.[5][12][13][14] Hemoptysis can occur rarely. Other sequelae of the solitary fibrous tumors of the pleura include mechanical compression of the inferior vena cava resulting in lower extremity edema.[11] Occasionally, these malignancies may cause airway obstruction and result in obstructive pneumonitis.[5][15] Rarely do patients present with paraneoplastic syndromes such as Doege-potter syndrome and Pierre-Marie Bamberg syndrome.[16][17]

In Doege-Potter syndrome, patients may have symptoms of hypoglycemia since tumors produce IGF-II, which downregulates glucose production. Steroids may be considered in the treatment of IGF-2-induced hypoglycemia.

SFTPs may be associated with hypertrophic pulmonary osteoarthropathy (Pierre-Marie Bamberg syndrome), which manifests clinically as finger-clubbing, bilateral joint pain, and stiffness due to synovial effusions. The pathomechanism for this process is not fully elucidated but is thought to be related to increased hyaluronic acid synthesis. It occurs in <5% of tumors, and the rheumatologic signs and symptoms usually resolve within 2 to 5 months after the tumor is excised.

Malignant solitary fibrous tumors of the pleura are usually more symptomatic than benign SFTP. Larger-sized tumors are more likely to be symptomatic.[11][18][19]

Evaluation

Obtaining radiologic imaging is usually the first step in diagnosing these tumors. Cross-sectional imaging, such as computed tomography (CT) and magnetic resonance imaging (MRI), are the common imaging modalities used. No pathognomonic imaging characteristics are associated with solitary fibrous tumors of the pleura, and radiographic findings are like those found in other soft tissue tumors. A well-circumscribed, homogenous mass originating from the pleura is typically seen on CT.[20][21] Occasionally, the tumor may be lobulated. On CT with contrast, the mass usually appears enhanced, likely due to the vascularity of the tumor. Areas of cystic or myxoid degeneration look hypo-attenuated on enhanced CT.[20] 

The tumor usually arises from the pleural surface and frequently displaces or invades surrounding structures. SFTPs are usually pedunculated with associated changes in the position or shape of the tumor during respiration.[22] CT imaging may reveal associated pleural effusion.[18][19]

MRI helps differentiate the tumor from adjacent structures and determine the extent of vertebral involvement in massive posterior chest tumors.[13] MRI may be useful in showing necrosis, hemorrhage, and cystic changes if present. 

Some radiographic features like large size, pleural effusion, and necrosis are more characteristic of malignant SFTPs.[21] Calcifications have also been identified on CT imaging in some cases.[15][23]

The diagnosis of SFTP may be suspected based on imaging and clinical features. However, a definitive diagnosis requires histologic confirmation. Fine-needle aspiration biopsies rarely provide adequate tissue samples to make a diagnosis. Core biopsies may be sufficient to establish the diagnosis of SFT but are commonly limited in showing histologic features indicative of an aggressive tumor. Histological features are described in the “Histopathology” section.

Another useful tool in diagnosing solitary fibrous tumors of the pleura is immunohistochemistry. Immunohistochemistry can help distinguish solitary fibrous tumors from other entities like mesotheliomas.[11] The presence of CD34, Bcl-2, CD99, and vimentin in the absence of other markers like desmin, S100 protein, epithelial membrane antigen (EMA), and low molecular weight cytokeratins is characteristic of solitary fibrous tumors.[14] It is, however, important to note that these biomarkers are not consistently expressed by these tumors.

Treatment / Management

Complete surgical resection is the mainstay treatment and the most important prognostic determinant for both malignant and benign forms of solitary fibrous tumors of the pleura.[21] Ideally, negative surgical margins (R0) should be attained. The extent of the surgery depends on the gross morphology and origin of the tumor. For pedunculated tumors originating from the visceral pleura, wedge resection is typically sufficient to achieve negative margins.[13] A lobectomy, pneumonectomy, or chest wall resection may be required in cases where the tumors are large and/or sessile with extensive involvement.[10]

There is a lack of prospective data supporting neoadjuvant or adjuvant radiotherapy after surgical resection. The role of adjuvant radiation therapy is local control, especially in tumors at high risk for recurrence. Patients with tumors with high-risk histologic features and positive surgical margins are likely to benefit from adjuvant radiation therapy. In locally recurrent solitary fibrous tumors of the pleura, adjuvant radiation therapy may be employed after re-resection. Neoadjuvant radiotherapy may have a role as upfront therapy in patients with large-difficult-to- resect tumors. Radiation therapy can be offered for palliation in patients with metastatic disease.[24] Due to the lack of data on the use of radiotherapy, a highly individualized treatment plan should be made by a multidisciplinary team.

Chemotherapy has a limited role in the treatment of completely resected SFTPs. It may be offered in unresectable or metastatic disease but typically results in a poor partial response with progression-free survival in months.

Differential Diagnosis

Solitary fibrous tumors of the pleura may resemble other entities on imaging and histology. Tumors originating in an interlobar fissure may be hard to differentiate from an intraparenchymal mass. Rarely, a solitary fibrous tumor arising from the parietal pleura may appear inverted and resemble an intrapulmonary lesion.[21][25] Conversely, loculated pleural effusions and extra-pleural hematomas in the interlobar fissures may mimic pleural solitary fibrous tumors.[26]

Clinically, solitary fibrous tumors of the pleura may be mistaken for any of the following based on radiographic and histologic appearance:

• Pleural lipoma
• Posttraumatic thoracic splenosis
• Extrapleural hematoma
• Loculated pleural effusions
• Schwannoma
• Sarcomatoid mesothelioma
• Lymphoma
• Organized inflammation
• Solitary pleural metastasis
• Peripheral lung malignancy

Additional tests such as immunohistochemistry can help differentiate these entities from solitary fibrous tumors of the pleura.

Surgical Oncology

Complete surgical resection (R0) of solitary fibrous tumor of the pleura is the primary treatment modality with primary curative mode. Generally, pedunculated tumors arising from the visceral pleura can be removed safely by video-assisted thoracoscopy surgery (VATS). For the resection of larger tumors with sessile morphology attached to the parietal pleura, thoracotomy might be required.[21] Surgeons should attempt to preserve as much pulmonary tissue as possible.

Prognosis

The most important predictor of recurrence is the complete resection of the tumor.[21] Some case series have shown that 10 to 25% recurrence rate of SFTPs within ten years.[27][28] Benign tumors have an overall recurrence rate of approximately 5%, while malignant tumors have an estimated recurrence rate of about 60%.[11] Varying data on mortality in this disease entity exists. In general, a higher rate of mortality is associated with recurrent, unresectable, and metastatic tumors.

Complications

Complications can arise because of the tumor itself or the treatment used. Some of these complications include:

• Atelectasis
• Obstructive pneumonitis
• Pleural effusion
• Perioperative blood loss
• Mediastinal compression
• Radiation-related complications like pneumonitis

Postoperative and Rehabilitation Care

Patients may need rehabilitation after surgery. Proper nutrition is a necessity. It is encouraged to discontinue smoking to aid recovery. 

In addition, postoperative surveillance should be considered. Using National Comprehensive Cancer Network (NCCN) posttreatment surveillance guidelines for soft tissue sarcoma, CT or Chest X-ray can be done every six months for three years, followed by yearly surveillance through year 10 for low-risk patients. In intermediate and high-risk tumors, chest CT should be performed every three to four months for two years, then every six months for three years afterward, then yearly till year 20. 

To determine the risk of the tumor, risk stratification models described in several studies can be used.[28][29][30]

Consultations

• Cardiothoracic surgeon
• Medical oncologist
• Radiation oncologist
• Pulmonologist

Deterrence and Patient Education

• Solitary fibrous tumors of the pleura are usually benign and originate from the lining around the lungs called the pleura.

• The main treatment is surgery to remove the tumor. In some cases, part of the lung is removed during surgery if the tumor is near the lungs. 

• Symptoms will improve after surgical removal of the tumor.

• The tumor can reoccur after surgery.

• Most patients will need another surgery to remove the recurring tumor and, in some cases, radiation treatment. 

• Smoking has not been linked to solitary fibrous tumors, but it helps to discontinue smoking to reduce to risk of lung cancer and improve recovery after surgery.

Pearls and Other Issues

• Solitary fibrous tumors of the pleura are rare entities and are typically benign. About 20% of SFTPs are malignant.

• These tumors are frequently asymptomatic and usually manifest clinically when the tumors are large. The most common symptoms are atypical pulmonary symptoms like cough and dyspnea. Paraneoplastic syndromes such as Doege-Potter syndrome and Pierre-Marie Bamberg syndrome occur in approximately 5% of cases.

• Differentiating benign and malignant forms of SFTPs can be difficult. Some clinical and histological features indicative of malignancy include a high mitotic index, large tumor size ( diameter greater than 10cm), tumor necrosis, calcifications, cellular atypia, pleural effusion, and paraneoplastic syndromes.

• Histopathologic evaluation is needed for definitive diagnosis, and immunohistochemistry aids in differentiating SFTPs from other similar clinical entities, such as mesotheliomas.

• Complete resection of the tumor with negative surgical margins (R0) is the only treatment modality with curative intent. 

Enhancing Healthcare Team Outcomes

The most effective way to manage SFTPs is with a multidisciplinary team of healthcare professionals, including a thoracic surgeon, medical oncologist, radiation oncologist, and in some cases, pulmonologist. Ideally, cases should be discussed in a multidisciplinary tumor board with experienced sarcoma oncologists. Treatment at a high-volume center is recommended. Palliative measures can be considered in patients with advanced disease. Interprofessional care coordination is also necessary, using oncology-specialized nurses who can assist in patient surgical preparation and counseling. They will also be crucial in assisting during surgical resection and in post-operative care.