Each pleural membrane is composed of five separate layers: the mesothelial layer; a thin submesothelial connective tissue layer; a superficial elastic tissue layer; a loose subpleural connective tissue layer, in which run lymphatics, nerves, arteries, and veins; and a fibroelastic layer that is adherent to the underlying structures (i.e., lung, mediastinum, diaphragm, chest wall)¹ (Fig. 109-1).

Benign tumors of the pleura constitute less than 5% of all pleural tumors. Metastatic cancers or diffuse malignant mesotheliomas are more common pleural tumors yet still very rare. They share common properties with benign pleural tumors in that they originate from or metastasize to mesothelial or submesothelial surfaces, they may recur after surgical removal, and there may be difficulty in establishing a diagnosis with small biopsy specimens.

The importance of distinguishing benign pleural tumors from the two other more common malignant tumors resides in the excellent survival potential they confer, the fact that some benign tumors can recur or metastasize, and the difficulty in establishing the diagnosis with small biopsy specimens because of the heterogeneous patterns of cellularity in these tumors.²

From a clinical perspective, primary pleural tumors span a pathologic spectrum from benign tumors to benign tumors with some malignant features to frankly malignant tumors. The most common pleural tumor (i.e., solitary fibrous tumor of the pleura) can occur in either a benign or a malignant form. Likewise, these tumors may recur in either a benign or a malignant form.^2,3

Benign tumors of the pleura are recognized by a radiographic appearance of a thickened parietal layer with underlying lung compression (Figs. 109-2 and 109-3). Occasionally, they may present with the appearance of invasion of lung (particularly if they are based in the visceral pleura), as in the inverted fibroma form of solitary fibrous tumors. These pleural abnormalities are identified by a variable thickening of either the visceral or parietal pleura. They impose a diagnostic dilemma on the clinician owing to the multiple possible etiologies for pleural masses. Furthermore, fine-needle aspirates of these abnormalities are often unreliable for confirming the diagnosis of benign pleural tumor.^4–7

BENIGN PLEURAL ABNORMALITIES

Pleural thickening can be attributable to multiple causes, ranging from benign inflammation to malignancy, as listed in Table 109-1. Benign pleural abnormalities can be distinguished by several specific features.

Inflammatory Pleural Lesions

A reactive pleural response can be elicited by numerous intrinsic and extrinsic assaults, such as exposure to radiation therapy, systemic immune diseases, and occupational exposures to environmental hazards, to name a few. The complete spectrum is detailed in Table 109-2.^5–8 In response to injury, the mesothelial cell releases mediators (e.g., cytokines, chemokines, oxidants, and proteases), which, in turn, induce an exudative pleural reaction that gives rise to a proliferative hyperplasia of the mesothelial and submesothelial layer^1,9 (see Fig. 109-1).

Benign reactive hyperplasia has specific histologic features that mimic malignancy, such as high cellularity, cytologic mitoses, necrosis, papillary excrescences, and entrapment of mesothelial cells in organizing pleuritis. Immunohistochemistry may be of limited help in differentiating benign from malignant pleural pathologies. Its primary value may be in simply demonstrating invasion by immunostaining of invasive cells. Invasion becomes a key marker for malignancy and must be differentiated from entrapment, pseudoinvasion, or sequestration.^5,8

Indeterminate lesions may be found in a pleural biopsy that reveals a proliferation of atypical mesothelial cells either as a monolayer or piled up with cellular accumulations. These lesions may demonstrate increased cytologic atypia without evidence of true invasion. Furthermore, they may remain benign or degenerate into malignancy.^8,10

Nodular Pleural Plaques

These are acellular deposits on the parietal pleura that often calcify and usually are associated with asbestos exposure.^11,12 These benign lesions are often multiple and bilateral; their presence raises the possibility of mesothelioma or lung cancer—either on presentation or in the future.

BENIGN PLEURAL TUMORS

Solitary Fibrous Tumor

The solitary fibrous tumor is the most common benign pleural tumor, and it is rare (by 2002, there were only 800 reported cases² ). In contrast, there are 3000 new cases of diffuse mesothelioma yearly in the United States.¹³ The solitary fibrous tumor arises from the submesothelial layer, and it is usually solitary, although it may occur in multiple sites.^14,15 It is associated with hypertrophic pulmonary osteoarthropathy in up to 22% of patients and with severe hypoglycemia in 3–4% of patients.¹⁶ This syndrome (i.e., Doege-Potter syndrome) is attributable to tumor-derived growth factor (i.e., insulin-like growth factor II).¹⁷

These tumors are often attached to the visceral pleura (>80%) and often pedunculated (80%). They originate from the parietal pleura on the diaphragmatic or mediastinal surface in the remaining 20% of patients. Parietal-based tumors are more likely to be sessile than pedunculated.¹⁵ Pedunculated tumors have a 2% recurrence rate, whereas sessile tumors have an 8% recurrence rate.¹

Solitary fibrous tumors may be removed by means of video-assisted thoracic surgery (VATS) resection, particularly if they are pedunculated.¹⁵ However, sessile lesions larger than 5 cm probably should be removed by thoracotomy to prevent recurrences.⁶ These tumors also may appear to have lung invasion owing to apparent visceral growth (inverted fibroma), which may require a formal lung resection. Peritumoral adhesions, in which microscopic tumor deposits may hide, are common (60%) and make wide resection necessary. This resection can encompass lung, diaphragm, chest wall, and pericardium, with frozen-section determination that all margins are free of tumor at resection.⁶ Recurrent tumors may be multifocal, and they may undergo malignant transformation.³ Histologic characteristics do not always predict the potential for recurrence, necessitating long-term follow-up.

Lipomas and Lipoblastomas

Chest wall lipomas are common incidental findings occurring in 0.1% of all CT scans of the chest.¹⁸ Lipoblastoma is a tumor of embryonic white fat that typically occurs in infancy or early childhood.¹⁹ Both lipomas and lipoblastomas are benign and are best treated by surgical excision of the involved area.

Adenomatoid Tumors

These tumors are very rare incidental findings, appearing as solitary circumscribed lesions on either the parietal or visceral pleura. They are usually identified at the time of pulmonary resection for unrelated pathology. They occur more commonly in other sites (e.g., the genital tract), and resection is performed to discriminate them from other malignant pleural tumors.²⁰

Calcifying Fibrous Tumors

Calcifying fibrous tumors are rare. They are characterized by dense collagenous tissue with psammoma bodies that contain dystrophic calcifications. These tumors commonly occur within subcutaneous tissue or in deep soft tissue; they rarely occur in the pleura (there have been nine reports of this tumor since it was reported initially in 1996). These tumors can occur as solitary lesions or in multiple sites; calcifications typically are not seen on chest x-ray but are visualized on CT scans.^21–28

Simple Mesothelial Cysts

The pleura is an uncommon site for mesothelial cyst development, which is thought to arise from persistence of the ventral pericardial recess after embryonic development. These lesions often occur in the anterior right cardiophrenic angle. Cysts that retain a connection to the pericardium are called pleuropericardial cysts, and if the neck to the pericardium is pinched off, they become mesothelial cysts. These can be treated with surveillance unless symptoms develop; then they can be treated by either aspiration or excision by VATS.^29,30

Multicystic Mesothelial Cysts

Multicystic inclusion cysts (i.e., multicystic mesothelioma or multilocular inclusion cysts) appear as multilocular fluid-filled cysts that spread along the serosal surface of the pleura. They are extremely rare abnormalities occurring in asymptomatic individuals, and their removal to exclude other pathologies can be accomplished by VATS.³¹

Schwannoma

These are peripheral nerve sheath tumors that may occur spontaneously or following radiotherapy.³² They occur in paraspinal intrathoracic locations and may mimic loculated fibrous deposits or localized pleural tumors. The key to the removal of this tumor is to exclude the possibility of spinal extension to prevent paraplegia from compressive spinal cord hematoma formation owing to bleeding into the peritumoral area.

PLEURAL TUMORS WITH LOW MALIGNANT POTENTIAL

Well-Differentiated Papillary Mesothelioma

This tumor typically occurs with a diffuse nodular growth over the mesothelial surface, although there is only superficial invasion without deep invasion, except in recurrent or long-standing lesions. The difficulty with diagnosis of this lesion is the differentiation of this tumor from invasive mesothelioma (i.e., diffuse malignant mesothelioma) on small biopsy specimens. These lesions have an indolent course in the absence of invasive features, and in most instances, they do not shorten life expectancy.³³

Desmoid Tumors

These tumors, usually arising from facial or musculoaponeurotic structures, commonly arise from the chest wall with visceral invasion, although there is documentation of pleural desmoid tumors.^34,35 The treatment of these tumors requires complete resection with negative margins.^34–36 Recurrence may be seen with negative margins,³⁵ but surgical resection of recurrences has excellent potential for long-term cure.³⁶

Pleural Thymoma

These tumors, which may arise from the pleura, can appear in either a localized or diffuse form. They probably arise from ectopic thymic tissue in the pleura, although this occurrence is rare (only 15 cases reported by 2002³⁷ ). The localized form can be surgically removed for cure; the diffuse form may require radiotherapy.^33,38

TECHNIQUES OF SURGICAL RESECTION OF SOLITARY FIBROUS TUMORS OF THE PLEURA

Solitary fibrous tumor, although uncommon, is the major benign pleural tumor. This lesion is often pedunculated and thus amenable to VATS resection. However, resection should be complete and without tumor disruption to prevent tumor recurrence. It is important to remove not only the tumor but also the stalk with a 1-cm base of underlying lung. If the tumor is too large for VATS resection, a thoracotomy may be required.^2,6 Tumors originating from the parietal pleura minimally require a partial pleurectomy with the tumor resection. Occasionally, a chest wall resection with tumor removal is required if there is concern about recurrence or invasion from possible malignant transformation of this tumor.

EDITOR'S COMMENT

Benign pleural tumors are the exception, along with some breast and uterine tumors, to the general notion that large tumors are malignant. Large smooth-walled tumors in the pleura may only require complete excision to prevent recurrence. Pleural tumors also challenge the notion of what constitutes a "benign" tumor. Although the genetic signature of tumors is likely to be more useful in the future, we are currently limited to counting mitoses to estimate the likelihood of local or distant recurrence.

–SJM

REFERENCES