Section 2 -

Chronic Fibrous Pleuritis Timothy Craig Allen The University of Texas Health Center at Tyler, Tyler, Texas

Chronic fibrous pleuritis has been described in the literature under a variety of names, including: organizing pleuritis, diffuse pleural fibrosis, fibrous pleurisy, organizing pleurisy, fibrous pleuritis, chronic pleuritis, fibrohyaline pleuritis, and fibrothorax. Chronic fibrous pleuritis is one of several types of pleural fibroses, including apical caps, pleural plaques, and rounded atelectasis. Chronic fibrous pleuritis is generally caused by the organization of a hemorrhagic or fibrinous pleural effusion or empyema. Specific etiologies include collagen vascular disease, asbestos exposure, TB-related empyema, and drug reactions, including amiodarone, methotrexate, and bleomycin, among others. Often there is a history of recurrent pleural effusions. Restrictive functional changes typically occur if pleural fibrosis is extensive. Grossly, continued effusions and ongoing pleuritis cause the development of a rind of organized collagenized tissue that ultimately obliterates the pleural space and encompasses the lung. Histologically, there may be active areas of overlying fibrinous pleuritis, with fibrin on the pleural surface and mixed with superficial underlying cells. The fibrinous component typically disappears with resolution of effusion. Zonation is often present, with more cellularity at surface, near the effusion, and progressively less cellularity and more fibrous component deeper, away from the effusion. Cells just beneath the effusion may be very atypical. Blood vessels in organizing pleuritis are often parallel to each other and perpendicular to the surface. Chronic areas contain scantly cellular fibrous tissue, sometimes in a "basketweave pattern." Organizing pleuritis may extend into subpleural fat, and occasionally into muscle. The primary, and often only, differential diagnosis of chronic fibrous pleuritis is the desmoplastic pattern of sarcomatous diffuse malignant mesothelioma (DMM). The desmoplastic pattern of sarcomatous DMM was first described in 1980 by Kannerstein and Churg, and described in detail in 1982 by Cantin and colleagues. Desmoplastic pattern sarcomatous DMM is uncommon, approximately 10% of all DMM. The desmoplastic pattern must make up >50% of tumor. Tumors are typically sarcomatous or biphasic; however, a few epithelial DMM have been characterized as having desmoplastic pattern. Its resemblance to chronic fibrous pleuritis makes it an extremely difficult histologic type of DMM to diagnose. The abundant hyalinized collagen may obscure the associated tumor cells and mimic chronic fibrous pleuritis. Further, fibrinous pleuritis and chronic fibrous pleuritis may occur in association with DMM. The desmoplastic pattern is characterized by the "patternless pattern" of Stout, with a scantly cellular fibrotic lesion, and a whorled, storiform arrangement of dense uniform collagen fibers. There are scant bland tumor spindle cells interspersed between bands of collagenous stroma. It may resemble a pleural plaque. A similar pattern may be identified in fibrous pleuritis. In 1998, Mangano and colleagues examined criteria for diagnosis of desmoplastic pattern sarcomatous DMM and its distinction from chronic fibrous pleuritis, and found that the diagnosis of desmoplastic pattern sarcomatous DMM depends upon identifying the "patternless pattern" of Stout, along with at least one of the following criteria: frankly sarcomatous areas, chest wall or lung invasion, bland necrosis, and distant metastases. Areas of frankly sarcomatous tumor show cells with marked nuclear pleomorphism and hyperchromasia. Random and abrupt transition from scant cellularity to more cellular spindle cell area is a feature often found in desmoplastic pattern sarcomatous DMM. Interpretation of areas as frankly sarcomatous must be done cautiously, because increased cellularity may occur in fibrous pleuritis. Mitoses are infrequent in both diagnoses. Spindle cell invasion within alveolar septa, or surrounding skeletal muscle or adipocytes is often obvious; however, low molecular weight cytokeratins can accentuate invading spindle cells when the finding is subtle. Interpretation of cytokeratin stains must be done carefully, because keratin-positive spindle cells within areas of thickened pleura are present in both sarcomatous DMM and fibrous pleuritis and positivity within those cells is valueless in determining invasion. Bland necrosis is a necrotic tumor focus with little or no associated inflammation, surrounded by viable tissue. Nuclear fragments are present focally. Distant metastases occur uncommonly, but may be the first clinical indication of tumor spread. Other nonspecific features may assist in distinguishing the two entities. Neither zonation nor parallel blood vessels distributed perpendicular to the pleural surface are features of desmoplastic pattern sarcomatous DMM. In order to best assure proper diagnosis, extensive sampling may be required. Core biopsies typically are inadequate, and small open biopsies may not be representative of the entire disease process. Wide sampling is generally required. The distinction between fibrous pleuritis and desmoplastic pattern sarcomatous DMM is a critical one because of their markedly different prognoses. Diagnosis should be conservative in order to avoid a false-positive DMM diagnosis with its attendant dismal prognosis. In summary, chronic fibrous pleuritis occurs from a variety of causes. Clinical history may be helpful. Distinction from desmoplastic pattern sarcomatous DMM is necessary because of their very different prognoses. Immunohistochemistry is of limited usefulness in making that distinction. Wide sampling and conservative diagnosis based on specific diagnostic criteria for the diagnosis of desmoplastic pattern sarcomatous DMM are required. References: Butnor KJ. My approach to the diagnosis of mesothelial lesions. J Clin Pathol. 2006;59:564-574. Cantin R, Al-Jabi M, McCaughey WTE. Desmoplastic diffuse mesothelioma. Am J Surg Pathol. 1982;6:215-222. Churg AM. Diseases of the Pleura. In: Churg AM, Myers JL, Tazelaar HD, Wright JL, eds. Thurlbeck's Pathology of the Lung, 3rd Ed. New York: Thieme; 2005. Churg A, Green FHS. Pathology of Occupational Lung Disease, 2nd Ed. New York:Williams & Wilkins;1998. Hammar SP. Pleural Disease. In: Dail DH, Hammar SP, eds. Pulmonary Pathology, 2nd Ed. New York:Springer-Verlag; pp.1463-1616. Kannerstein M, Churg J. Desmoplastic diffuse malignant mesothelioma. 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