What happened next transformed this routine infection into a diagnostic puzzle that physicians rarely encounter. By hospital day 11, imaging showed that the right upper lobe infiltrate had resolved, but new bilateral pleural effusions had appeared in its place. Thoracentesis was performed on both sides of the chest, and both effusions were grossly bloody and exudative. Yet beneath that identical bloody appearance lay a startling discordance: the right-sided fluid was dominated by neutrophils, at 85 percent, while the left-sided fluid was dominated by lymphocytes, at 90 percent. Cytology was negative for malignancy in both samples, and cultures grew no organisms. A single systemic process, such as heart failure or carcinomatosis, could not plausibly produce two fluids with such different cellular signatures. Instead, the findings pointed toward two entirely independent diseases developing simultaneously in the same chest.

The right effusion was straightforward to explain. Parapneumonic effusions are a well-recognised complication of bacterial pneumonia, particularly pneumococcal infection, in which parenchymal inflammation extends to the pleural space and generates a protein-rich, neutrophil-dominant exudate driven by acute inflammation. The antibiotic therapy was working against the pneumonia itself, but the severe initial inflammatory burden likely led to a delayed manifestation of pleurisy, with effusions emerging even as the lung infiltrate retreated. That mechanism accounted for the right hemithorax. The left effusion, with its lymphocyte predominance and later behaviour, was a far more elusive entity that would take months to reveal its full character.

The bloody appearance of both effusions added another layer of complexity. The patient’s antithrombotic regimen included edoxaban, a direct oral anticoagulant, along with aspirin, prescribed after coronary artery bypass grafting approximately 12 months earlier for acute coronary syndrome. Direct oral anticoagulants have been reported to induce spontaneous pleural bleeding, and the clinicians hypothesised that the combination of anticoagulant and antiplatelet therapy exacerbated microvascular oozing within inflamed pleura. Notably, however, the red blood cell counts in the effusions were relatively modest, yielding calculated pleural fluid haematocrits of only 0.18 percent on the right and 0.44 percent on the left, far below the diagnostic threshold for haemothorax. In other words, the bleeding tendency likely painted the exudates red without fundamentally changing their underlying inflammatory nature.

Management reflected the uncertainty. Given the bloody effusions, the team discontinued only the edoxaban and administered haemostatic agents, while continuing aspirin after consultation with the cardiovascular surgery team. Follow-up chest CT on May 21 showed partial resolution of the effusions, and with fever and hypoxaemia resolved, the patient was discharged on May 23. He remained stable as an outpatient for three months. Then, in late August, the left effusion worsened, and a concurrent chest CT revealed a small pericardial effusion that was too small for pericardiocentesis. A repeat left thoracentesis again yielded bloody, lymphocyte-dominant fluid, and C-reactive protein, which had normalised after discharge, had crept back above the institutional upper limit of normal. Echocardiography demonstrated preserved left ventricular function, arguing against heart failure as the cause.

This late recurrence allowed the clinicians to apply formal diagnostic criteria. The 2015 European Society of Cardiology guidelines for pericardial diseases require at least two of five criteria for a diagnosis of post-cardiac injury syndrome, the category that encompasses Dressler syndrome. The patient fulfilled two: pericardial effusion on CT and pleural effusion with elevated inflammatory markers. Fever, pericarditic or pleuritic chest pain, and audible rubs were all absent, making the presentation distinctly indolent. Late-onset Dressler syndrome was suspected, and the team initiated diagnostic therapy with ibuprofen at 600 mg per day, the maximum dose covered by Japanese medical insurance. Follow-up imaging confirmed significant improvement of both the left pleural and pericardial effusions, and no recurrence occurred during 10 months of follow-up after the anti-inflammatory treatment began.

Dressler syndrome is an immune-mediated pleuropericarditis that classically appears within weeks to a few months of cardiac injury, most often after cardiac surgery such as coronary artery bypass grafting. The prevailing pathophysiological model holds that cardiac injury releases sequestered cardiac antigens, triggering the formation of anti-heart autoantibodies. The time required for this immunological sensitisation inherently creates a latent period between injury and clinical onset. The reported profile of post-cardiac injury syndrome effusions fits this patient’s left-sided fluid almost exactly: such effusions are unilateral in about two thirds of cases and left-sided in the large majority, with no Dressler syndrome patients in one published series showing right-sided unilateral effusions; nearly all are exudates, and roughly three quarters are lymphocyte-predominant.

The timing, however, was extraordinary. Onset occurred approximately 12 months after bypass surgery, exceeding not only the usual latent window but also the nine-month interval described in one of the longest previously reported cases. The authors propose a two-hit hypothesis: the patient developed long-standing latent immune sensitisation following his cardiac surgery, and the intense systemic inflammatory response generated by severe pneumococcal pneumonia acted as a necessary catalyst, reactivating the dormant autoreactive process and culminating in the delayed manifestation of Dressler syndrome. In this framing, the pneumonia did not merely coexist with the immune syndrome; it may have ignited it. The two mechanisms are not mutually exclusive, and an immune-mediated predisposition related to prior cardiac injury may have been unmasked by systemic inflammation from the contralateral infection.

The authors are careful to acknowledge residual diagnostic uncertainty, since a response to non-steroidal anti-inflammatory drugs is common in pleuropericarditis of virtually any cause. A reactive post-infectious serositis following the pneumonia remains a plausible alternative, as autoimmune pleuropericarditis has been reported after community-acquired pneumonia, including Chlamydia pneumoniae-associated cases. Furthermore, no pericardial effusion was present at the time of the initial thoracenteses, and the left effusion was attributed to a post-cardiac injury process only retrospectively, once the August recurrence fulfilled the formal criteria. The lymphocyte-predominant profile and prompt ibuprofen response support an immune-mediated process, but they do not definitively tie it to the prior surgery rather than the preceding infection. Late-onset Dressler syndrome is therefore presented as the most likely clinical diagnosis rather than a certain one.

The broader lesson reaches well beyond this single patient. Clinicians frequently assume that bilateral pleural effusions stem from a single systemic aetiology such as heart failure, renal failure or malignancy, and this assumption can obscure independent localised pathologies that demand separate therapeutic strategies. In this case, the two sides of the chest required targeted antibiotic therapy on the right and anti-inflammatory treatment on the left, and neither intervention alone would have addressed both conditions. The definitive clue was not the grossly bloody appearance, which was identical on both sides and heavily influenced by antithrombotic medications, but the rare and striking discordance of pleural fluid cellular profiles between hemithoraces. For patients with bilateral effusions whose clinical or radiological presentation is atypical, the case argues strongly for bilateral thoracentesis with detailed cellular analysis, a practice this team believes should be adopted far more widely. To their knowledge, a PubMed search identified no previous report of parapneumonic effusion and Dressler syndrome presenting concurrently, and the combination is classically described under the label of Contarini syndrome, in which each side of the chest harbours a different cause.

Subject of Research: A rare case of bilateral bloody pleural effusions arising from two independent causes, concurrent parapneumonic effusion and suspected late-onset Dressler syndrome, distinguished by discordant pleural fluid cellular profiles.

Article Title: Bilateral Bloody Pleural Effusions With Discordant Cellular Patterns: A Case of Concurrent Parapneumonic Effusion and Dressler Syndrome

Article References: Narumi, Y., Hoshino, S., Yamakawa, M., & Amano, Y. (2026). Bilateral Bloody Pleural Effusions With Discordant Cellular Patterns: A Case of Concurrent Parapneumonic Effusion and Dressler Syndrome. Respirology Case Reports, 14(9), Article e70764. https://doi.org/10.1002/rcr2.70764

Image Credits: AI Generated

DOI: 10.1002/rcr2.70764

Keywords: pleural effusion, Dressler syndrome, post-cardiac injury syndrome, parapneumonic effusion, Streptococcus pneumoniae, thoracentesis, coronary artery bypass grafting, edoxaban, lymphocyte-dominant exudate, Contarini syndrome, pericardial effusion, ibuprofen

The case, reported in the journal Respirology Case Reports, describes how a lethal cancer called sarcomatoid malignant pleural mesothelioma hid behind a convincing facade of infection. When thoracoscopy under local anesthesia revealed a purulent, pus-filled effusion with fibrin deposited across the pleural cavity, the medical team could not even obtain an adequate pleural biopsy because inflammation obscured the tissue. Acting on a clinically suspected diagnosis of tuberculosis pleurisy, physicians in January 2025 began empiric anti-tuberculosis therapy with the standard four-drug regimen of isoniazid, rifampicin, ethambutol, and pyrazinamide. The patient had a smoking history of 10 pack-years and had worked in administrative roles at construction sites, an occupation that can involve asbestos exposure, the primary known cause of mesothelioma. His history also included colon cancer, surgically treated at stage IIIA, adding another layer of complexity to the clinical picture.

For four months the treatment failed. The pleural effusion persisted, and a positron emission tomography scan fused with computed tomography, which uses a radioactive glucose analog to light up metabolically active tumors, showed no abnormal accumulation to suggest malignancy. By April 2025 the patient was referred to a second hospital, where surgeons performed a thoracoscopic biopsy at the site of pleural thickening identified on preoperative imaging. The histopathology was frustratingly non-specific: fibrous pleural thickening without any granulomatous inflammation, the clustered immune structures characteristic of tuberculosis, and no acid-fast bacilli visible under Ziehl-Neelsen staining. Cultures of the tissue for mycobacteria and ordinary bacteria were all negative. The biopsy, in other words, proved the absence of infection but could not name what was actually there.

What happened next provides the dramatic core of the report. Two months after the surgical biopsy, a routine follow-up CT scan in August 2025 revealed a new mass in the posterior right eighth rib, invading bone, and the patient had begun to feel pain at the site. A CT-guided percutaneous biopsy of that rapidly growing mass delivered tissue that was still ambiguous under the microscope. The specimen showed fibrosis mingled with a proliferation of atypical spindle cells, elongated cells with enlarged and irregular nuclei that could belong to either an aggressive cancer or a benign scarring process called fibrosing pleuritis. Even experienced pathologists cannot reliably separate these two entities on routine hematoxylin and eosin stained sections, and this case proved no exception.

The diagnostic breakthrough came from molecular testing rather than conventional histology. Immunohistochemistry showed that the spindle cells stained diffusely positive for CAM5.2, a cytokeratin marker that hints at epithelial origin and supports a mesothelial lineage, but the definitive answer required fluorescence in situ hybridization, or FISH. This technique uses fluorescently labeled DNA probes to examine tumor cells at the level of individual genes. In this patient, FISH revealed a homozygous deletion of the CDKN2A gene, also known as p16, meaning both copies of this critical tumor suppressor had been lost. The deletion of a gene whose normal function is to halt the cell cycle when DNA damage is detected is a hallmark of malignant transformation. Because homozygous CDKN2A loss is frequently found in sarcomatoid mesothelioma but is absent in benign fibrosing pleuritis, its detection confirmed the diagnosis of sarcomatoid mesothelioma. The disease had been masquerading as infection and inflammation for months, and molecular pathology finally unmasked it.

The clinical course then moved with brutal speed. Just two months after the definitive diagnosis, the patient died under best supportive care. That trajectory is characteristic of sarcomatoid mesothelioma, which carries a poorer prognosis and progresses more rapidly than the epithelioid and biphasic subtypes of the disease. Within the sarcomatoid family, the case authors note, lies an even more deceptive variant called desmoplastic mesothelioma, whose early lesions are pathologically indistinguishable from benign fibrous pleuritis. In this patient, retrospective analysis of the original surgical biopsy proved revelatory: when researchers later stained that older sample, scattered spindle cells turned out to be positive for CAM5.2, and FISH on the same archival tissue also detected the CDKN2A deletion. The cancer had been present all along, hiding in plain sight within a fibrotic pleura, in an occult phase where the tumor burden was too small and too metabolically quiet to register on FDG-PET or to catch the pathologist’s eye.

Why was tuberculosis such a plausible impostor? The report contextualizes the difficulty with sobering numbers. The sensitivity of pleural fluid smears for acid-fast bacilli in tuberculous pleurisy is below 10 percent, and cultures are positive in fewer than 30 percent of cases, meaning that a negative smear or culture never truly excludes the disease. Adenosine deaminase, while useful, has limited specificity, and in regions where tuberculosis remains common, clinicians are often justified in starting empiric therapy when the clinical constellation fits. Here, a positive interferon-gamma release assay combined with a lymphocyte-predominant exudate created a strong circumstantial case. Yet previous studies indicate that among patients who receive a diagnosis of non-specific pleuritis after invasive biopsy, between 5 and 15 percent are eventually found to have malignancy, particularly mesothelioma. That statistic transforms an initially reassuring non-specific biopsy result into a warning sign demanding surveillance rather than closure.

The British Thoracic Society guidelines recommend approximately 12 months of follow-up for patients whose pleural biopsies yield non-specific results, and this case illustrates precisely why such vigilance matters. When the effusion failed to resolve despite four months of antituberculosis drugs, the appropriate response was prompt, repeated pleural biopsy rather than continued ineffective treatment. The report argues that clinicians facing presumed tuberculous pleurisy that responds poorly to therapy must actively hunt for malignant mesothelioma. It also highlights a structural gap in clinical practice: FISH testing for CDKN2A deletion remains limited in availability and prevalence in general clinical settings, and restricted access to this powerful tool can delay mesothelioma diagnoses, sometimes fatally. Expanding access to molecular diagnostics for pleural disease emerges as an urgent unmet need.

Beyond its immediate clinical lessons, the case offers a window into how modern oncology resolves diagnostic uncertainty. A single molecular event, the loss of both copies of a tumor suppressor gene, served as the fingerprint that distinguished a rapidly lethal cancer from benign scar tissue that looked nearly identical under the microscope. The trajectory of this patient’s illness, from an occult phase invisible to imaging and pathology, through an explosive two-month emergence of a bone-invading chest wall mass, to death within weeks of diagnosis, underscores the aggressive biology of the sarcomatoid subtype. For physicians, the message is layered: treat the statistics with humility, because negative cultures and smears cannot exclude tuberculosis, and non-specific biopsies cannot exclude mesothelioma. For patients with unexplained pleural effusions that defy treatment, repeated biopsies and multidisciplinary discussion, combined with molecular tools capable of interrogating the genome rather than only the architecture of tissue, may be the difference between catching a cancer in time and discovering it only after it has claimed the advantage. This single case, reported with full clinical detail, adds a compelling data point to the growing argument that the future of pleural disease diagnosis lies as much in molecular pathology as in the pathologist’s optical microscope.

Subject of Research: A case report of sarcomatoid malignant pleural mesothelioma initially misdiagnosed and treated as tuberculous pleurisy

Article Title: Sarcomatoid Mesothelioma Revealed After Treatment for Tuberculous Pleurisy: A Case Report

Article References: Nagayama, D., Yokoo, K., Yabushita, Y., Sekikawa, M., Abe, M., Kato, H., Takayanagi, A., Takahashi, B., Kato‐Shinomiya, M., Ota, S., Yamada, G., Hiroshima, K., & Chiba, H. (2026). Sarcomatoid Mesothelioma Revealed After Treatment for Tuberculous Pleurisy: A Case Report. Respirology Case Reports, 14(9), Article e70734. https://doi.org/10.1002/rcr2.70734

Image Credits: AI Generated

DOI: 10.1002/rcr2.70734

Keywords: sarcomatoid mesothelioma, tuberculous pleurisy, pleural effusion, CDKN2A deletion, FISH testing, pleural biopsy, interferon-gamma release assay, adenosine deaminase, fibrosing pleuritis, immunohistochemistry, PET-CT, case report