Diffuse large B cell lymphoma with superimposed lung abscess: potential role for intracavitary fibrinolytic therapy through a percutaneous drain to facilitate lung abscess drainage

Abstract

This is a case of primary pulmonary lymphoma presenting concurrently with superimposed lung abscess, managed with the assistance of intracavitary fibrinolytic therapy. A 28-year-old man presented with 2 months of persistent cough. He had a large lung abscess involving almost the entire right upper lobe. The mass continued to progress in spite of appropriate antibiotic administration. Given the extent of involvement, he was not a surgical candidate. A bronchoscopy with bronchoalveolar lavage and transbronchial biopsies demonstrated diffuse large B cell lymphoma. Initial cultures were positive for Group G Streptococci. A CT-guided percutaneous drain was placed with initial purulent drainage that grew Prevotella and Streptococcus mitis; however, drainage quickly abated without adequate evacuation of the abscess cavity. To further optimise drainage in anticipation of chemotherapy administration, intracavitary fibrinolytic therapy including tissue plasminogen activator and deoxyribonuclease was attempted to better evacuate the infected space.

Background

A lung abscess is a circumscribed collection of pus formed from the necrosis of pulmonary parenchyma. Typically, lung abscesses can be managed successfully with antibiotics alone. Between 10% and 20% of cases fail medical therapy and require more invasive techniques, including surgical resection, percutaneous chest tube and endoscopic drainage.¹ Of those treated with percutaneous drainage and antibiotics, up to 30% fail.^{2 3} Fibrinolytic use for typical abscesses was described by Haaga in 1988.⁴ A more recent study by Haaga et al describes intracavitary use of urokinase, a plasminogen activator, for enhancement of extrathoracic percutaneous abscess drainage.⁵ Most of the data pertaining to intracavitary fibrinolytic therapy are with intra-abdominal abscesses. When drawing on experience from pleural space infections, fibrinolytics assist with cleaving intrapleural fibrinous septations and loculations. The Multicenter Intrapleural Sepsis Trial 2 demonstrated that the combination of tissue plasminogen activator (tPA) and deoxyribonuclease (DNase) improved efficacy of drainage for pleural space infections.³ We identify one case report using 10 mg of DNase diluted in 50 mL of normal saline through an endoscopically placed guide-sheath catheter for lung abscess drainage, which enhanced drainage.⁶ To our knowledge, this is the first reported case of administering intracavitary combined tPA and DNase via a percutaneous drain to enhance lung abscess drainage. In the following report, we describe a case of a 28-year-old man who presented with diffuse large B cell lymphoma (DLBCL) with superimposed lung abscess requiring percutaneous intracavitary drainage and fibrinolytic therapy to enhance treatment prior to chemotherapy.

Case presentation

A 28-year-old man was referred from an outside facility for evaluation and treatment of a progressive right upper lobe abscess accompanied by recurrent fevers as high as 103.9°F, cough, dyspnoea, night sweats and weight loss in spite of multiple courses of antibiotics. Chest X-ray demonstrated a right perihilar mass-like consolidation, with subsequent CT chest imaging demonstrating dense consolidation in the right upper and middle lobes with air bronchograms. HIV testing was negative. A bronchoscopy was performed prior to transfer, which demonstrated narrowed anterior, apical and posterior bronchopulmonary segments of the right upper lobe. Bronchial washings and transbronchial biopsies were obtained with cultures growing beta haemolytic Group G Streptococci, at which time antibiotics were broadened. The patient was transferred to our institution for further management of the presumed lung abscess. On arrival, induced sputum cultures further grew Stenotrophomonas maltophilia and Acinetobacter ursingii. Pathology results from the bronchoscopy returned positive for DLBCL, with features consistent with primary mediastinal large B-cell lymphoma. A subsequent bone marrow biopsy was negative for involvement by lymphoma. Positron emission tomography scan demonstrated a large fluid and gas filled mass in the right upper lobe with peripheral rim and adjacent mediastinal and right hilar hypermetabolic enhancement (figure 1). These findings were felt to represent DLBCL with superimposed infection and abscess formation. Thoracic surgical consultation was obtained; however, the patient was deemed a non-operative candidate due to the extent of the mass that included extensive mediastinal involvement. A 10 French percutaneous drain was placed by interventional radiology, initially with return of 400 cc of purulent material, from which cultures grew Prevotella sp and Streptococcus mitis. After the initial drainage, there was minimal output via the chest tube with a considerable amount of residual fluid within the necrotic abscess cavity. Initiation of chemotherapy was held due to the superimposed infection and persistent abscess. Given continued inadequate drainage, we elected to perform a 3-day trial of intracavitary tPA and DNase through the chest tube. A dose of tPA 5 mg followed by DNase 10 mg each in 30 cc of sterile saline were administered two times per day for 3 days. Between medication dosings, the drain was kept to −20 cmH₂O and a single additional 10 cc sterile saline flush was administered to maintain tube patency. After completion of the full six doses of tPA and DNase, a repeat CT chest was obtained, which demonstrated marked decrease in the volume of fluid within the central portion of the necrotic mass (figure 2).

Figure 1.

Positron emission tomography-CT demonstrating extension of the lymphoma into the mediastinum and chest wall.

Figure 2.

CT of the chest: (A) on presentation, (B) after 10 French pigtail chest tube placement, (C) after intracavitary tPA and DNase therapy through the indwelling chest tube. DNase, deoxyribonuclease; tPA, tissue plasminogen activator.

Outcome and follow-up

The diagnosis of DLBCL with concomitant polymicrobial lung abscess presented an extremely challenging clinical situation. Serial imaging demonstrated a highly aggressive malignancy and created a profound sense of urgency to initiate cytotoxic chemotherapy as soon as possible; however, this was encumbered by the concomitant, uncontrolled infection. Surgical resection was not considered an option given the extent of disease and expected duration of necessary recovery time. An attempt to drain the abscess percutaneously initially had a suboptimal result; however, this improved with the use of intracavitary tPA and DNase, such that the patient was able to initiate R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, prednisone) during the hospitalisation without infectious complication. Due to a persistent bronchopleural fistula, the percutaneous drain remained in place at the time of discharge. It was subsequently removed 25 days after discharge.

Discussion

Intracavitary fibrinolytics have been used historically to help break down loculations and enhance drainage of abscess cavities. Traditionally, they have been used to enhance drainage of the pleural space with empyema and intra-abdominal abscesses. This is the first reported case of administering intracavitary tPA and concomitant DNase via percutaneous chest tube to enhance lung abscess drainage. There has been one report describing two cases where intracavitary urokinase was used with similar effect.⁷

Potential complications with percutaneous catheter placement into a necrotic abscess cavity include bronchopulmonary or bronchopleural fistula.⁸ Bleeding is another concern with administration of fibrinolytics. Most of the studies involve intrapleural fibrinolytics and significant pleural bleeding, which was defined as a reduction in haematocrit requiring blood transfusion, is overall rare. In the MIST-2 trial, there were two intrapleural haemorrhages and one episode of haemoptysis in the tPA/DNase group (n=48).³ In the Piccolo et al longitudinal multicentre observational series, significant pleural bleeding occurred in two patients in the tPA/DNase group (n=107).⁹ These patients had underlying bleeding risks. Overall, contraindications with intrapleural fibrinolytics are not well defined, except those with high bleeding risk and bronchopleural fistula.¹⁰ When applied to intracavitary fibrinolytics, one should carefully assess underlying bleeding risks and discuss risks and benefits with the patient prior to proceeding.

Learning points.

• Consider alternative diagnoses, such as lymphoma or other malignancies, in a progressing lung abscess that is refractory to appropriate antibiotics.

• In non-operative cases, percutaneous drainage of refractory pulmonary abscesses may represent a reasonable treatment alternative.

• Consider using tissue plasminogen activator and deoxyribonuclease for pulmonary abscess to help facilitate drainage.