Malignant pleural mesothelioma mimics thoracic empyema: A case report

Abstract

BACKGROUND

Thoracic empyema and malignant pleural mesothelioma (MPM) are distinct medical conditions with similar symptoms, including cough, chest pain, and breathing difficulty. We present a rare MPM case mimicking thoracic empyema. Physicians must consider MPM risks for patients exposed to building material who exhibit lobulated pleural effusions, indicating thoracic empyema.

CASE SUMMARY

A 68-year-old retired male construction worker suffered from shortness of breath and chest tightness over 10 d, particularly during physical activity. A poor appetite and 4 kg weight loss over the past 3 wk were also reported. Chest images and laboratory data concluded a tentative impression of empyema thoracis (right). Video-assisted thoracic surgery with decortication and delobulation (right) was conducted. The pathological report yielded an MPM diagnosis. Refractory pleural bilateral effusions and respiratory failure developed postoperatively, and the patient died three weeks after the operation.

CONCLUSION

Thoracic empyema and MPM are distinct medical conditions that can present similar symptoms, and video-assisted thoracic surgery facilitates an accurate diagnosis. Empyema-mimicking presentations and postoperative refractory pleural effusion may indicate a poor MPM outcome.

Key Words: Thoracic empyema; Malignant pleural mesothelioma; Video-assisted thoracic surgery; Case report

Core Tip: Malignant pleural mesothelioma (MPM) shows similar clinical symptoms and imaging features to thoracic empyema. In the present case, the final diagnosis was confirmed by the thoracoscopic surgery. This article could offer clinicians a hint to consider a diagnosis of MPM when treating thoracic empyema and consider thoracoscopic surgery for accurate diagnosis.

INTRODUCTION

Malignant pleural mesothelioma (MPM) is a rare pleural disease associated with environmental or occupational asbestos exposure and maintains one of the poorest prognoses among respiratory diseases[1,2]. Past studies have primarily linked MPM to asbestos exposure, theorizing that inhaling asbestos prompts repeated pleural inflammation, proto-oncogene activation, and free radical production[2].

Image studies [i.e., chest computed tomography (CT) with intravenous contrast] and invasive procedures (i.e., thoracoscopic pleural biopsy and thoracentesis of pleural effusion with cytologic analysis) are often required to diagnose MPM[3,4]. However, not all patients with pleural effusion receive invasive procedures, such as pleural biopsy. Clinically, MPM has a nonspecific presentation and can be misdiagnosed as other conditions, such as pulmonary empyema or metastatic pleural lung cancer, without a thorough patient history[5].

Hence, we present the case of a patient initially suspected to have lobulated pleural effusion on his right side due to empyema or tumor. However, the biopsy performed during video-assisted thoracic surgery revealed poorly differentiated pleural mesothelioma (Table 1).

Table 1 Timeline.

Time	Events
January 13, 2023	Visited emergent department; tube thoracostomy, right and admission
January 16, 2023	Video-assisted thoracoscopic decortication and pleural biopsy, right
January 31, 2023	Acute respiratory failure; endotracheal intubation
February 1, 2023	Thoracic tumor board conference discussion; chemoport implantation
February 2, 2023	Cisplatin based chemotherapy
February 17, 2023	Percutaneous tracheostomy
February 22, 2023	Ventilator-associated pneumonia, bilateral with severe acute respiratory distress syndrome, and septic shock
February 23, 2023	Expired

CASE PRESENTATION

Chief complaints

A 68-year-old retired male construction worker suffered from shortness of breath and chest tightness, particularly during physical activity, for 10 d. A recent appetite loss, resulting in a 4 kg weight loss over the past 3 wk, was also reported.

History of present illness

The patient entered the emergency department after 10 d of shortness of breath and chest tightness, particularly during physical activity. He also reported a recent appetite loss, resulting in a 4 kg weight loss over the past 3 wk.

History of past illness

The patient had a past coronary artery disease medical history managed by percutaneous coronary artery intervention with one stent implantation. He also experienced an abdominal aortic aneurysm, which was treated by endovascular aneurysm repair.

Personal and family history

The patient, a non-smoker, denied any family cancer history.

Physical examination

The breathing sound was decreased in the right side chest.

Laboratory examinations

The patient's blood examination revealed an elevated leukocyte count of 24020/µL, with 92.5% neutrophils, a low hemoglobin level at 8.9 g/dL, and a high C-reactive protein level at 27.08 mg/dL. As a result, a tube thoracostomy was performed on the right side, and the pleural effusion was collected for analysis. The subsequent analysis indicated a total cell count of 154686, red blood cell count of 154000/μL, total protein level at 4.2 g/dL, lactate dehydrogenase fluid level at 1801 U/L, polymorphonuclear leukocyte percentage of 76%, and morphonuclear leukocyte percentage of 24%. No pathogens were cultured from the pleural effusion, but the Rivalta test was positive, confirming the exudate and raising suspicion of empyema. Influenza A and B virus antigen detection was arranged, but all tests were negative.

Imaging examinations

The chest plain film (Figure 1A) and CT (Figure 1B and C) confirmed multiple lobulated pleural effusions with the reverse D sign, raising suspicion of thoracic empyema on the right side.

Figure 1 Initial chest images suggesting an impression of thoracic empyema. A: At the initial visit, chest radiography revealed a large pleural effusion in the right thorax (orange arrows) with almost complete opacification of the right lung field; B: Coronal view of chest contrast-enhanced computed tomography confirmed multiple right-side lobulated pleural effusions (orange arrows); C: Axial view of chest contrast-enhanced computed tomography confirmed multiple right-side lobulated pleural effusions (orange arrows).

MULTIDISCIPLINARY EXPERT CONSULTATION

The thoracic tumor board conference at the Tri-Service General Hospital suggested that the impression of postoperative tumor-related leukocytosis was considered rather than postoperative empyema. Cisplatin based chemotherapy was suggested for the patient.

FINAL DIAGNOSIS

Malignant pleura mesothelioma with bilateral malignant pleural effusion, epithelioid subtype (AJCC Cancer Staging Manual, 8^th Edition), clinical stage T4N0M0, stage IIIB.

TREATMENT

Due to symptom persistence and the lobulated pleural effusion in the right-side pleural cavity, which was suspected to be caused by the tentative impression of thoracic empyema, the patient underwent video-assisted thoracic surgery with decortication and delobulation. After entering the right pleural cavity, multiple lobulated bloody pleural effusions were observed (Figure 2A). In addition, several tiny pleural nodules were observed during thoracoscopic surgery (Figure 2B), and intra-operative frozen sections from the pleural biopsy displayed positive malignancy.

Figure 2 Operative findings during video-assisted thoracoscopic surgery. A: Video-assisted thoracoscopic surgery indicated massive bloody pleura effusion (white arrow). Adhesion bands and peels are shown (blue arrow); B: Multiple pleural nodules were found after removing the bloody pleural effusion and pneumolysis (white arrows). Peel-coating over the visceral pleura of the right lung was observed (blue arrow). Then pulmonary docortication was performed.

The chest plain film on the fifth postoperative day showed a massive pleural effusion on the left side, and a pig-tail drainage tube was inserted into the left pleural cavity. The left-side pleural effusion also exhibited bloody fluid, and the cytology analysis suggested malignancy. The pleural nodule pathological report (Figure 3) revealed poorly differentiated carcinoma compatible with MPM. The diagnosis of MPM with bilateral malignant pleural effusion, epithelioid subtype (AJCC Cancer Staging Manual, 8^th Edition), clinical stage T4N0M0, stage IIIB was determined after the series of examinations, including blood tests, abdominal CT, brain magnetic resonance imaging (MRI), and a bone scan.

Figure 3 Histological and immunohistochemistry staining of pleural tumors yielded a diagnosis of epithelioid subtype of malignant mesothelioma. A: Hematoxylin & eosin staining showed poorly differentiated carcinoma characterized by nested tumor growth pattern composed of tumor cells with epithelioid cytoplasm, high nuclear/cytoplasmic ratio, enlarged nuclei, and marked nucleoli infiltrating in the stromal of the pleural peel tissue; B: Immunohistochemistry staining of pleural tumors showed negative immunoreactivity to calretinin; C: Immunohistochemistry staining of pleural tumors showed immunoreactivity to the WT1, determining a diagnosis of malignant pleural mesothelioma of epithelioid subtype.

In addition, follow-up chest plain films indicated no remission of the right-side pleural effusion. The refractory bilateral massive pleural effusion was observed following the postoperative course. Intravenous diuretics, frequent bilateral thoracentesis, and pleural catheter insertion were conducted during this period. Then, an acute hypoxemic respiratory failure developed on the tenth postoperative day. Emergent endotracheal intubation was performed, and the patient was transferred to the intensive care unit. The laboratory data revealed persistent leukocytosis with leukocyte counts of 20000/µL to 26000/µL and mildly elevated serum C reactive protein levels of 2 mg/dL to 4 mg/dL post operation. However, no definitive toxic signs, such as fever, were evident, and tachycardia was observed clinically.

Following the thoracic tumor board conference discussion at our hospital, tumor-related leukocytosis was considered rather than postoperative empyema.

OUTCOME AND FOLLOW-UP

A chemo port was implemented on the 14^th postoperative day (Figure 4). On the 15^th postoperative day, a first course of cisplatin-based chemotherapy was performed. After the first chemotherapy course, ventilator-associated pneumonia, bilateral with severe acute respiratory distress syndrome, and septic shock developed. The patient died on the 21^st postoperative day.

Figure 4 Postoperative chest plain films showing refractory bilateral pleural effusion and disease severity. A: Postoperative chest plain film exhibiting improved expansion of the right lung. Minimal bilateral pleural effusions (orange arrows) and two chest tubes in the right pleural cavity (black arrow) were observed; B: Chest plain film on the 14^th POD revealing bilateral pleural effusion after bilateral pleural catheter drainage (black arrows). A tracheostomy was performed due to respiratory failure (orange arrow).

DISCUSSION

Thoracic empyema and MPM are distinct medical conditions with similar symptoms, such as cough, chest pain, and breathing difficulty. Thoracic empyema occurs when pus collects in the pleural cavity, the space between the lungs and the chest wall. Bacterial infection or other underlying conditions, such as pneumonia, lung abscess, or tuberculosis, can beget this condition. In contrast, MPM is a type of cancer that affects the lining of the lungs, chest wall, or abdomen, often caused by asbestos exposure and can take decades to develop.

Although thoracic empyema and MPM symptoms can be similar, their underlying causes and treatment options vary. Thoracic empyema is typically treated with antibiotics and pus drainage, whereas mesothelioma may require surgery, chemotherapy, or radiation therapy. MPM is usually diagnosed through needle biopsy rather than surgery. Diagnostic imaging methods for pleural mesothelioma include standard X-rays, CT scans, MRI, and positron emission tomography scans[6-8]. However, the chest CT scan for our patient revealed no bilateral pleura thickening but a typical lobulated pleural effusion appearance on his right side. Still, deciding the optimal site for CT-guided core biopsy is challenging.

Finally, the pathological diagnosis was determined with video-assisted thoracoscopic surgery (VATS). VATS may be the most reliable method for a final tissue diagnosis[9-11] and could also serve as a curative treatment method. We conclude that VATS has unique diagnostic value for empyema-mimicking pleural mesothelioma than the CT-guided core biopsy. Based on NCCN guidelines and Zhou et al's study (2022) concerning MPM management, pleurectomy/decortication (PDC) and extrapleural pneumonectomy (EPP) have comparable long-term oncologic outcomes, but PDC has much lower perioperative mortality[12].

Our patient underwent a PDC-like surgery. However, further surgical intervention, such as EPP, was not considered due to his poor postoperative conditions. Zhou et al[12] reported that the surgical cytoreduction goal for pleural mesothelioma should be to achieve macroscopic complete resection with the safest operation that the patient can tolerate. In addition, our patient suffered from bilateral refractory pleural effusion caused by MPM following the VATS procedure. Maione et al[13] discussed that chemical pleurodesis and pleural catheter insertion may be an ideal option for patients like ours. However, the patient later became unfit for surgery due to deteriorating health conditions before this attempt could be made.

In this case, we faced a dilemma in distinguishing empyema-related leukocytosis from tumor-related leukocytosis during the postoperative course. Tumor-related leukocytosis is a paraneoplastic syndrome that was reported as a poor negative prognostic factor in the clinical course of patients with lung cancer[13,14]. Thus, chemotherapy was performed under the curative intent after the thoracic tumor board conference discussion.

Matsuoka et al[15] described a patient initially diagnosed with acute empyema and severe leukocytosis but ultimately diagnosed with MPM and opted for palliative care. Our patient had a similar poor outcome and died on the 21^st postoperative day. We theorize that empyema-mimicking presentations and postoperative refractory pleural effusion indicate a poor outcome.

A recent study by Lapidot et al[16] published in the Annals of Thoracic Surgery reported postoperative empyema rates after PDC for MPM up to 10% and identified several risk factors, including prolonged air leak, diabetes, and previous radiation therapy. Although the study focused on postoperative empyema following PDC, its findings highlight the necessity for developing novel strategies to prevent empyema in MPM patients who have undergone other treatments, such as chemotherapy.

In the Journal of Clinical Oncology, Javidfar et al[17] revealed a different treatment option: Repeated ambulatory intrapleural chemotherapy for patients with MPM who are not eligible for surgery or unresponsive to prior treatments. The procedure involves placing a catheter into the pleural cavity and infusing chemotherapy drugs directly into the affected area on an outpatient basis. Several studies have demonstrated that this approach can effectively control pleural effusions, extend survival, and improve patients' quality of life, as measured by various scales and questionnaires[18,19]. However, this treatment is not without risks and potential complications. Some patients may experience pain or discomfort during the procedure, while others may develop infections or other adverse events, as in our case. Furthermore, there is limited data on the long-term safety and efficacy of repeated intrapleural chemotherapy, and further research is needed to evaluate its comprehensive benefits and risks.

Considering these studies, combining induction chemotherapy, EPP, and adjuvant radiotherapy has emerged as a treatment option for select patients with resectable diseases. In a retrospective analysis, Guy and St. Thomas Hospital researchers chronicled their experience with this tri-modality approach in 36 patients with MPM[20]. All patients received induction chemotherapy with cisplatin and pemetrexed, followed by EPP and adjuvant hemi-thoracic radiotherapy. The median overall survival was 20.2 mo, with a 43% 2-year survival rate. However, the high morbidity associated with EPP and adjuvant radiotherapy should be considered when contemplating this treatment strategy.

In summary, clinicians should have a high level of suspicion for MPM risks in patients with thoracic empyema or pleural effusions. MPM can mimic empyema, delaying diagnosis and resulting in missed treatment opportunities and poor outcomes. Thoracoscopic surgery may be crucial for pathological diagnosis.

CONCLUSION

Although thoracic empyema and MPM are distinct medical conditions exhibiting similar symptoms, VATS can offer an accurate diagnosis. In addition, empyema-mimicking presentations and postoperative refractory pleural effusion may signal poor outcomes for MPM.