Moderators: Dr. Kelly Butnor and Dr. Francoise Galateau-Salle
Section 2 -
Chronic Fibrous Pleuritis
Timothy Craig Allen
The University of Texas Health Center at Tyler,
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
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.
- Butnor KJ. My approach to the diagnosis of mesothelial lesions. J Clin
- 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. In: Ferioglio CM, Wolff M, eds.
Progress in Surgical Pathology. Vol II. New York:Masson Publishing;1980:19-29.
- Machin T, Mashiyama ET, Henderson JAM, et al. Bony metastases in desmoplastic pleural mesothelioma.
- Mangano WE, Cagle PT, Churg A, et al. The diagnosis of desmoplastic malignant mesothelioma and its
distinction from fibrous pleurisy. Am J Clin Pathol. 1998;110:191-199.
- Roggli VL, Sanfillippo F, Shelburne JD. Mesothelioma. In: Roggli VL, Greenberg SD, Pratt PC, eds.
Pathology of Asbestos-Associated Diseases. Boston: Little,
- Stout A. Biological effects of asbestosis. Ann NY Acad Sci.
- Travis WD, Brambilla E, Muller-Hermelink HK, Harris CC, eds. Pathology and
Genetics of Tumours of the Lung, Pleura, Thymus and Heart. Lyon, France:IARC Press;2004. World Health Organization
Classification of Tumours; vol. 10.