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