Organizing Pleuritis Presenting as Recurrent Lymphocyte Predominant, Exudative Effusion

Abstract

Long-standing pleural effusions may rarely progress to pleural fibrosis, and when no identifiable etiology is present, this entity is termed cryptogenic fibrosing pleuritis (also referred to as organizing pleuritis, fibrous pleurisy, or fibrosing pleurisy). This condition is characterized by persistent exudative effusions and progressive pleural thickening, often leading to diagnostic uncertainty and therapeutic challenges. Due to its rarity, only a limited number of cases have been described in the literature, and an evidence-based management strategy has yet to be established. Reported treatments have included glucocorticoids and surgical decortication, with variable success and unclear long-term benefits. The authors have presented the case of an older man with recurrent unilateral lymphocytic exudative pleural effusion, extensive occupational asbestos exposure, and imaging findings concerning for pleural disease, in whom repeated thoracenteses failed to provide durable resolution. Given concern for an underlying malignant process, medical thoracoscopy was pursued, allowing direct pleural visualization and diagnostic biopsy. Histopathology confirmed organizing pleuritis without malignancy. Rapid protocol pleurodesis and placement of a tunneled pleural catheter were performed simultaneously. This case highlighted the diagnostic value and therapeutic potential of thoracoscopy combined with pleural drainage strategies as a less invasive alternative to surgical decortication in carefully selected patients with cryptogenic fibrosing pleuritis.

Introduction

Pleural effusions affect up to 1.5 million patients annually, most commonly arising from heart failure, pneumonia, and malignancy. ¹ Diagnostic evaluation typically begins with thoracentesis, with pleural fluid analysis used to distinguish transudative from exudative effusions, thereby guiding etiologic assessment. The differential diagnosis for exudative pleural effusions is broad. However, a lymphocyte predominant profile most frequently suggests malignancy, tuberculosis, sarcoidosis, chylothorax, or rheumatoid disease. ¹ Management strategies for pleural effusions associated with these conditions include treatment of the underlying pathology, repeated thoracenteses, pleurodesis, or surgical intervention. ² In rare instances, persistent or long-standing pleural effusions may progress to pleural fibrosis. ³

When pleural fibrosis occurs in the absence of an identifiable cause, the condition is termed “cryptogenic fibrosing pleuritis,” also referred to as organizing pleuritis, fibrous pleurisy, or fibrosing pleurisy. ⁴ Known causes of pleural fibrosis include benign asbestos-related pleurisy, as well as malignant etiologies such as mesothelioma, osteosarcoma, and metastatic disease. ⁵ Notably, mesothelioma can closely mimic fibrous pleuritis and is strongly associated with asbestos exposure, underscoring the importance of accurate diagnosis and a thorough exposure history. ³ To date, only a limited number of cases of cryptogenic fibrosing pleuritis have been reported, and an optimal therapeutic strategy has yet to be clearly defined.

Herein, the authors have reported a case of recurrent unilateral exudative pleural effusion with lymphocytic predominance and persistently negative pleural fluid cytology. The authors have described a distinctive diagnostic and management approach to cryptogenic fibrosing pleuritis, contributing to the limited existing literature on this rare entity.

Case Patient Presentation

An 83-year-old man with a past medical history of substantial for liver cirrhosis, hypertension, and hyperlipidemia presented from an outside institution for evaluation of a recurrent right-sided pleural effusion despite 2 prior therapeutic thoracenteses, each yielding approximately 1.5 liters of fluid. He had a 30 pack per year smoking history and reported substantial occupational asbestos exposure during prior employment with both the US Navy and a municipal fire department. Initial evaluation revealed that prior pleural fluid analyses were consistent with an exudative effusion with lymphocytic predominance and negative cytology for malignancy.

Computed tomography imaging of the chest revealed an 8 mm calcified pleural plaque on the anterior pleura, with no parenchymal consolidation or nodules (Figure 1). A third thoracentesis was performed, revealing 82% lymphocytes, lactate dehydrogenase (LDH) 85 U/L, protein 4.5 g/dL, glucose 146 mg/dL, and cytology negative for malignancy. Postprocedural chest radiography demonstrated a reduction in the right-sided pleural effusion without pneumothorax and with appropriate lung reexpansion.

Figure 1:

(A) Anteroposterior chest x-ray following thoracentesis with residual dependant right-sided pleural effusion with no evidence of pneumothorax. (B) Chest computed tomography (CT) scan showing calcified pleural plaque.

Treatment Pathway

Given concern for an underlying malignant etiology, medical thoracoscopy was pursued to obtain pleural biopsies and to provide symptomatic management of the recurrent effusion. A rapid pleurodesis protocol was performed in conjunction with placement of a tunneled pleural catheter to facilitate daily outpatient drainage. Pleural manometry was not performed. However, prior thoracenteses demonstrated adequate lung reexpansion, suggesting the absence of a trapped lung and supporting the decision to proceed with pleurodesis. During medical thoracoscopy, a single thoracoscopic trocar was inserted, and a total of 2040 mL of pleural fluid was evacuated. Numerous pleural adhesions were encountered and dissected using a curved hemostat. Thoracoscopic inspection revealed diffusely white pleura with plaque-like changes (Figure 2). Multiple pleural biopsies were obtained using rigid forceps.

Figure 2:

(A) Gross appearance of the parietal pleura during thoracoscopy with evidence of diffuse white plaques. (B) Histopathology of the pleural biopsy. Image on the left demonstrates hematoxylin and eosin staining with thickened pleura with parallel fat-like spaces and decreasing cellularity away from the pleural cavity surface. Image on the right demonstrates keratin staining with keratin positive spindle cells. Both images are x16 magnification.

A tunneled pleural catheter was subsequently placed and positioned to facilitate drainage from the dependent posterior and diaphragmatic pleural surfaces. Four grams of aerosolized medical-grade talc were instilled under direct visualization. Following talc administration, a 24-French chest tube was inserted through the thoracoscopic port site and directed toward the lung apex. A 24-French chest tube was placed to facilitate immediate postprocedural drainage and optimize pleurodesis, while the tunneled pleural catheter was intended for ongoing outpatient management.

Pleural fluid analysis obtained during thoracoscopy demonstrated 80% lymphocytes, LDH of 131 U/L, and protein concentration of 4.5 g/dL. Corresponding serum studies showed an LDH level of 199 U/L (reference range: 122–222 U/L) and a protein level of 7.3 g/dL (reference range: 6.3–7.9 g/dL). Histopathologic examination of pleural biopsy specimens, including keratin immunostaining, confirmed a diagnosis of organizing pleuritis without evidence of malignancy (Figure 3). On postprocedure day 1, adjunctive iodine pleurodesis was performed using a solution composed of 80 mL of normal saline and 20 mL of 10% iodine, which was instilled into the pleural space and retained for 2 hours before removal. On postprocedure day 2, the 24-French chest tube was removed following confirmation of lung reexpansion, and the patient was discharged home on postprocedure day 3. At postprocedure day 14 follow-up, imaging demonstrated no reaccumulation of pleural fluid, and the tunneled pleural catheter was subsequently removed (Figure 3).

Figure 3:

Anteroposterior chest x-ray following medical thoracoscopy and removal of tunneled pleural catheter with reexpansion of the right lung and without reaccumulation of the right-sided effusion.

Outcomes

At 3 months postprocedure, the patient reported marked improvement in respiratory symptoms, including decreased dyspnea. Follow-up imaging demonstrated no reaccumulation of pleural fluid, indicating sustained resolution of the effusion and effective long-term symptomatic relief. A chest computed tomography performed 2 years postprocedure showed no evidence of disease progression, further supporting the diagnosis.

Discussion

The response of the pleural mesothelial cell to injury and inflammatory mediators is central to determining whether healing or pleural fibrosis occurs. Proinflammatory mediators such as tumor necrosis factor-α, vascular endothelial growth factor, and plasminogen activator inhibitor-1 contribute to pleural fibrosis. ^6,7 Although the acute pleural inflammation may resolve over several months, the persistence of pleural fibrosis may result in impaired pleural and pulmonary function via the formation of pleural thickening or fibrothorax, with associated restrictive lung disease and limitation of lung capacity, increasing morbidity for the patient. ⁷ Histologically, fibrotic pleural disease can be separated into 2 stages. ⁸ In the acute stage, fibrinous pleuritis will occur with dense areas of fibrin deposition along the pleural surface. ⁸ Gradually, fibrinous pleuritis is followed by fibrous pleuritis, demonstrating dense areas of fibrous tissue containing fibroblasts and loose stroma, along with capillaries and a variable mixed chronic inflammatory cell infiltrate, lining the pleural surface. ^7,8 As the acute condition begins to organize, fibrinous and fibrous pleuritis may occur together. Fibrous pleuritis may contain areas of mesothelial cell hyperplasia that may occasionally be so prominent as to mimic malignancy. ⁸

Reactive pleural lesions and organizing pleuritis must be distinguished from diffuse pleural mesothelioma (DPM) as certain histological subtypes demonstrate substantial overlap. ^8–11 DPM is a rare neoplasm. However, it is the most common primary pleural neoplasm, with approximately 2000 cases occurring in the United States each year. ⁸ The majority are due to prior occupational exposure to asbestos. Along with clinical and radiological correlation, histological examination is necessary for the accurate diagnosis of DPM. DPMs have 3 histological types: epithelioid, biphasic (or mixed), and sarcomatoid. ^5,8 The primary differential diagnosis for sarcomatoid DPM includes organizing pleuritis. ^5,8–11 Desmoplastic DPM is a subtype of sarcomatoid DPM composed predominantly of a fibrous neoplasm. ^5,8–11 The separation of desmoplastic malignant mesothelioma and organizing pleuritis is crucial to patient care, as desmoplastic mesotheliomas are highly aggressive tumors for which there is little effective therapy, whereas organizing pleuritis is a benign process that may leave the patient with pleural thickening but with usually no or minimal functional defects. ⁹

Cryptogenic fibrosing pleuritis was first described by Buchanan and colleagues, who reported 4 patients who developed progressive bilateral pleural fibrosis following exudative pleural effusions. ⁴ Histological examination demonstrated extensive fibrous thickening of both the parietal and visceral pleura, resulting in obliteration of the pleural space. Comprehensive evaluation failed to identify an underlying etiology, leading to the designation of cryptogenic fibrosing pleuritis. Three of the 4 patients underwent pleural decortication, which was initially successful. However, a single patient subsequently experienced disease recurrence on the contralateral side and demonstrated a rapid response to corticosteroid therapy. The fourth patient was treated initially with high-dose corticosteroids without decortication, with transient improvement followed by relapse. ⁴

Management strategies for cryptogenic fibrosing pleuritis remain limited, and no definitive treatment has been established. Therapeutic approaches have included glucocorticoid therapy and pleural decortication, although outcomes are variable. Emerging targeted therapies aimed at pleural organization and fibrosis are currently under investigation. ⁶ Most existing pharmacologic treatments focus on intrapleural fibrinolytic therapy during the acute phase, primarily addressing pleural loculation and impaired drainage. ⁶ However, these interventions do not adequately address the complex pathological tissue organization associated with organizing pleural injury. ⁴

In this case, the preprocedural differential diagnosis remained broad. Notably, prior thoracentesis resulted in both symptomatic improvement and lung reexpansion, reducing concern for lung entrapment and obviating the need for surgical decortication. Consequently, a less invasive diagnostic approach was selected in the form of medical thoracoscopy. This technique enabled direct visualization of the pleural surfaces, acquisition of pleural biopsies, and complete drainage of pleural fluid without the need for extensive surgical incision or prolonged recovery. Prior to the procedure, the patient was counseled regarding potential etiologies, including pleural malignancy and occult malignancy within the adjacent atelectatic lung. The patient was informed that performing rapid pleurodesis at the time of thoracoscopy could limit future therapeutic options should malignancy be identified, and he elected to proceed. Talc poudrage was performed during thoracoscopy, followed by placement of a tunneled pleural catheter to facilitate daily drainage and iodine pleurodesis on postprocedure day 1. The patient required a 3-day hospital admission, and the tunneled pleural catheter was removed on day 14. At 3-month follow-up, there was no evidence of pleural fluid reaccumulation, and the patient remained symptomatically improved. Although the patient had a history of asbestos exposure, there was no definitive radiologic or histopathologic evidence to attribute the pleural fibrosis to asbestos-related disease; thus, the etiology was considered cryptogenic. Although no malignancy was identified on thoracoscopic biopsy, longer-term follow-up would be valuable to definitively exclude an evolving malignant process.

Conclusion

This case described an alternative potential diagnostic and management option for cryptogenic fibrosing pleuritis. Patient selection is important, including identifying those with possible lung entrapment, and counseling on the possibility of malignancy is essential in all of these patients.

Relevancy Statement.

This case report contributed to practice change by highlighting a combined diagnostic and therapeutic strategy medical thoracoscopy with rapid pleurodesis and tunneled pleural catheter placement for the management of cryptogenic fibrosing pleuritis, a rare condition with limited established treatment guidance.