The study focused on cats with pleural effusion and a cytologic or histopathologic diagnosis of pulmonary carcinoma, or metastatic epithelial cancer considered consistent with a pulmonary origin based on imaging and findings elsewhere. Fine-needle aspiration of a pulmonary mass confirmed carcinoma or malignant epithelial neoplasia in 12 of the 22 cats. For the remaining 10, the diagnosis was presumptive: malignant epithelial cells were demonstrated in pleural fluid, pleural or thoracic-wall lesions, or another metastatic site while imaging supported a primary pulmonary neoplasm. This distinction matters because an occult primary tumor outside the lung could not be completely excluded in every presumptive case, and the selected cohort likely represents cats with clinically apparent or advanced thoracic disease rather than all cats with lung cancer.

Ultrasonography was performed with linear probes reaching 18 MHz or microconvex probes reaching 9 MHz. Archived images from three ultrasound systems were reviewed in consensus by two board-certified veterinary radiologists and a veterinarian with 15 years of diagnostic imaging experience. The investigators recorded the location and distribution of pleural abnormalities, maximal thickness, shape, echogenicity relative to neighboring intercostal muscle, internal homogeneity, and whether invasion of the chest-wall musculature was suspected. Pleural effusion was probably central to this assessment: fluid can separate lung from the thoracic wall and create an acoustic window through which parietal and visceral pleural surfaces can be examined.

Based on the stored images, pleural thickening appeared diffuse in 12 cats, focal in six, and multifocal in four. The representative or measured abnormality was most often located in the cranial pleural region, ahead of the cardiac silhouette, appearing in 18 cats; it was in the middle region in three and the caudal region in one. These figures should not be interpreted as a complete map of pleural disease. The clinical protocol began with the cranial pleura and moved to the middle and caudal regions only when no cranial thickening was found, so the investigators could not determine the total number of lesions or their true anatomical distribution.

The maximal visible thickness of the pleural abnormalities averaged 5.6 millimeters, with a median of 4.9 millimeters and a range from 1.2 to 16.2 millimeters. Shape was smooth in nine cats, irregular in eight, and nodular in five. Most lesions, 15 of 22, were hypoechoic relative to adjacent intercostal muscle, although two were isoechoic and five had mixed echogenicity. Internal echoes were homogeneous in 14 cats and heterogeneous in eight. These overlapping appearances mean that a thickened pleura should not be considered malignant on ultrasound alone. Pleural thickening can also arise from inflammatory or reactive processes, and the study did not include cats with non-neoplastic pleural effusion for comparison.

One potentially important feature was an irregular or poorly defined interface between the thickened pleura and adjacent intercostal muscle, with apparent extension into the muscle or loss of the normal fascial plane. Such suspected intercostal muscle invasion was recorded in eight cats. All eight lesions were irregular or nodular, whereas none of the smooth lesions showed this feature. The median maximum thickness among these lesions was 7.1 millimeters, compared with 4.9 millimeters for the group as a whole. The appearance may help flag advanced local involvement, but the investigators did not have histological confirmation of muscle invasion in every cat, so it should be treated as an imaging suspicion rather than a validated sign of true invasion.

Pleural fluid cytology produced neoplastic cells in 15 of the 20 cats whose effusion was examined, but malignant cells were not detected in five. Within this selected group, therefore, a negative fluid cytology result did not exclude pulmonary carcinoma. The findings also identify a possible alternative route to diagnosis. Six cats underwent ultrasound-guided sampling of thickened pleura or an associated thoracic-wall lesion, and cytologic or histopathologic results supported carcinoma in all six. Five samples were interpreted as epithelial malignant neoplasia. In one cat, an initial fine-needle aspiration was suspicious for a non-epithelial malignant neoplasm, while subsequent biopsy of a thoracic-wall mass confirmed squamous cell carcinoma.

The sampled targets included four diffuse and two multifocal lesions; five were irregular and one was smooth. No focal or nodular lesion was sampled. These results support the feasibility of lesion-directed sampling when a safe acoustic window exists, especially if a primary pulmonary mass is central, surrounded by aerated lung, or otherwise difficult to reach directly. They do not establish that pleural sampling is safer, more accurate, or superior to aspirating the lung mass. Only six cats underwent the procedure, selection depended on clinical judgment and accessibility, and records inconsistently documented needle gauge, number of passes, and aspiration technique. The procedure’s diagnostic performance, safety profile, and comparative value therefore require prospective testing.

The study’s central clinical message is practical but cautious. In a cat with suspected pulmonary carcinoma and pleural effusion, the pleural surface deserves deliberate inspection rather than evaluation only for the presence of fluid. Ultrasound may show thickening that is smooth, irregular, or nodular; hypoechoic, isoechoic, or mixed; and variable in thickness and distribution. Such findings are suspicious in the presence of known or suspected carcinoma, particularly when malignant cells are present in the effusion, but imaging alone cannot distinguish neoplastic infiltration from reactive disease. Pleural fluid cytology remains an important test, yet the study shows that its negative result need not settle the question. Prospective studies using standardized whole-thorax scanning, comparison with computed tomography, cytologic or histopathologic reference standards, and controls with non-neoplastic effusion are needed to determine the true prevalence, diagnostic accuracy, staging value, and prognostic significance of these ultrasound findings in cats with pulmonary carcinoma.

Subject of Research: Ultrasonographic pleural changes and diagnostic sampling in cats with pulmonary carcinoma

Article Title: Ultrasonographic Features of Pleural Thickening in Cats With Pulmonary Carcinoma and Pleural Effusion: A Retrospective Descriptive Study

Article References: Toshima, A., Fulkerson, C. V., & Murakami, M. (2026). Ultrasonographic Features of Pleural Thickening in Cats With Pulmonary Carcinoma and Pleural Effusion: A Retrospective Descriptive Study. Veterinary Medicine and Science, 12(6), Article e71290. https://doi.org/10.1002/vms3.71290

Image Credits: AI Generated

DOI: 10.1002/vms3.71290

Keywords: feline pulmonary carcinoma, thoracic ultrasonography, pleural thickening, pleural effusion, fine-needle aspiration, veterinary oncology, thoracic imaging, intercostal invasion, cancer staging, Ultrasonographic, Features, Pleural

The central conceptual shift, according to the authors, is the explicit separation between the diagnostic and the quantitative uses of lung ultrasound. Both roles existed in 2012, but the new documents make clear that they demand different approaches and different techniques. Diagnosis answers a categorical question through a focused, pattern-based scan. Quantification translates findings into a reproducible measure through a standardized, multi-zone acquisition of the chest. The distinction matters because the two applications are easily conflated at the bedside, and the techniques that serve one do not automatically serve the other.

Quantification, the commentary stresses, does not concern aeration alone. Semi-quantitative techniques now extend to pulmonary congestion, pneumothorax volume and pleural effusion. In purely diagnostic applications, dividing the chest into zones and counting artifacts is usually unnecessary, with one exception: the differential diagnosis between diffuse and focal interstitial syndrome, assessed over the antero-lateral chest, where a criterion based on the number of positive zones provides a first orientation in the acutely ill patient. The quantitative techniques for aeration and congestion, by contrast, rest on zone division and apply semi-quantification to each scanned region.

The most substantial advance over 2012, the authors argue, is prognostic. A within-patient trajectory of repeated measurements enables monitoring, but it also underpins stratification that positions an individual patient’s risk relative to others. The commentary draws a careful line between two roles that are often blurred: as a prognostic tool, lung ultrasound predicts outcome, associating a measurement with a patient’s risk at a given moment; as a tool for treatment guidance, it informs a therapeutic decision and, through that decision, may alter the clinical course. The evidence base for the prognostic role, the authors note, is currently more robust than the evidence for treatment guidance.

A second structural novelty is the articulation of three diagnostic levels. The first concerns fundamental signs, for which the update refines nomenclature and definitions. The second, described as the genuine novelty, uses additional features to sharpen differential diagnosis between conditions that share the same elementary pattern: the distribution and quantity of B-lines, the characteristics of the pleural line, the correlation with clinical severity, the shape, margins, air bronchograms and size of consolidations, and the complexity of pleural effusion in relation to any associated consolidation. The third level is the final clinical interpretation, in which sonographic findings are integrated into a wider diagnostic puzzle where lung ultrasound may be decisive but should never be sufficient on its own.

The authors are explicit about why these levels need spelling out: they are too often collapsed in practice. A sign identified at the first level does not by itself deliver a diagnosis, and errors attributed to lung ultrasound frequently arise not in image acquisition but in the interpretation that follows. Competence in the technique and competence in clinical interpretation are distinct skills. The sonographic finding is a premise for reasoning, not a conclusion, and treating it as one is a recurring source of diagnostic misattribution.

Perhaps the most striking reframing concerns the power of exclusion. While confirming specific diagnoses, particularly in dedicated settings such as acute respiratory distress syndrome, is identified as one of the most promising future applications in intensive care, the commentary emphasizes the role of lung ultrasound in ruling conditions out and thereby narrowing the differential. This rule-out power rests on the high sensitivity, and therefore high negative predictive value, of the elementary signs: their absence renders the corresponding condition improbable even where a positive finding alone would not confirm it. Exclusion is typically achieved at the elementary-sign level, whereas confirmation requires the interpretive steps that follow.

The clinical applications where the new evidence bites hardest include heart failure and dialysis. In decompensated heart failure, the number of B-lines correlates with severity and predicts rehospitalization and death both at admission and at discharge, capturing residual, often subclinical congestion that clinical evaluation alone can miss. Because this prognostic value is independent of ejection fraction, it underscores the separation between cardiac function and cardiogenic congestion, and it extends to moderate-to-severe aortic stenosis, ST-elevation myocardial infarction and cardiogenic shock. In chronic heart failure, B-lines can also support therapeutic guidance: in one randomized trial, therapy titrated on sonographic monitoring reduced hospitalization for decompensation. In dialysis patients, sonographic congestion is often uncoupled from signs and symptoms, meaning an asymptomatic patient is not always euvolemic, and this occult overload predicts death and cardiac events. The authors caution, however, that there is not yet robust evidence that titrating fluid removal according to sonographic congestion during dialysis improves survival.

In mechanically ventilated patients, the lung aeration score monitors the effects of positive end-expiratory pressure, recruitment maneuvers and drugs, and carries prognostic weight, but it must be read alongside respiratory mechanics and gas exchange and is meaningful only when repeated acquisitions are rigorously standardized. The score provides no more than a coarse semi-quantification: it correlates with gold standards and with severity of lung involvement, yet it remains highly approximate because of the artifactual nature of the sonographic signs and the absence of a linear progression between score classes. A specific blind spot is overdistension, since overinflation of already aerated regions produces no change in the score; assessing reduced pleural sliding may eventually help close this gap. Lung ultrasound may also help select the ventilatory strategy itself: by distinguishing focal from non-focal lung morphology, it can guide a tailored approach assigning higher PEEP and recruitment maneuvers to non-focal ARDS and lower PEEP with prone positioning to focal ARDS, a strategy currently being compared with conventional ventilation in the ongoing PEGASUS trial.

The new guidelines also introduce, for the first time, an explicit distinction between aeration and congestion scores as separate techniques, validated in different populations against different gold standards and assessed over different chest regions, along with the concept of fluid tolerance: the absence of congestion signs defines a margin of safety for fluid administration. Fluid tolerance and fluid responsiveness are distinct questions, and lung ultrasound speaks to the former, functioning as a safety limit rather than a decision to give fluid, and is best complemented by focused cardiac ultrasound. Semi-quantification of pneumothorax, graded from the laterality of the lung point, and approximation of pleural effusion volume extend the same move from binary reading to graded measure, aiding decisions about drainage and enabling bedside monitoring without repeated radiographic exposure. The authors close with a caveat that doubles as a research agenda: prognostic weight is established, but validated numerical cut-offs for severity, characterization and prognosis in cardiogenic pulmonary edema, interstitial lung disease and ARDS are still missing, and that gap weighs most heavily on treatment guidance rather than prognosis.

Subject of Research: Updated evidence-based recommendations for diagnostic and quantitative point-of-care lung ultrasound in critical care

Article Title: What’s new in point-of-care lung ultrasound: reading the new recommendations

Article References: Volpicelli, G., Gargani, L., & Zieleskiewicz, L. (2026). What’s new in point-of-care lung ultrasound: reading the new recommendations. Intensive Care Medicine. https://doi.org/10.1007/s00134-026-08649-2

Image Credits: AI Generated

DOI: 10.1007/s00134-026-08649-2

Keywords: lung ultrasound, point-of-care ultrasound, intensive care, B-lines, ARDS, heart failure, aeration score, congestion, fluid tolerance, pneumothorax, pleural effusion, prognostication

The appeal of these compartments lies in basic physics and biology. Plasma-based liquid biopsy has transformed oncology by detecting circulating tumor DNA, or ctDNA, the fragments of tumor genome released into the bloodstream when cancer cells die through apoptosis or necrosis. But blood is a highly diluted medium, contaminated with abundant DNA from dying white blood cells, and the blood-brain barrier actively excludes tumor DNA shed by metastases in the brain or its protective membranes. Fluids that sit in direct contact with tumor deposits face neither problem. Ascites bathing peritoneal metastases, pleural fluid in contact with lung tumors, and cerebrospinal fluid surrounding the central nervous system all receive tumor-derived DNA at high local concentrations, with far less background genetic noise from peripheral blood cells. The result is a signal that is not only stronger but, in some cases, fundamentally different from what blood or a single needle biopsy of tissue can provide.

The research team, led by investigators including Aditya Shreenivas and Razelle Kurzrock, profiled fluid samples using a next-generation sequencing platform capable of detecting point mutations, copy number alterations, splice variants, indels, and gene fusions. The cohort of 45 patients, with a median age of 52, included 18 men and 27 women, and spanned lung cancer, breast cancer, ovarian cancer, pancreatic cancer, and a collection of rarer malignancies. Ascitic fluid accounted for 26 samples, pleural fluid 11, cerebrospinal fluid seven, and pericardial fluid one. The overall ctDNA detection rate was a striking 87 percent, with ascites performing best at 96 percent, pleural fluid at 72.7 percent, and cerebrospinal fluid at 71.4 percent. The single pericardial sample was also positive, though the authors caution that one case proves little. These rates, while descriptive rather than definitive performance estimates, underline how readily tumors seed their genetic material into the cavities they invade.

The mutational landscape the sequencing revealed was dominated by familiar oncogenic players. TP53, the guardian-of-the-genome gene whose loss is a hallmark of nearly all cancers, was altered in 49 percent of samples. EGFR and KRAS, two of the most clinically consequential oncogenes in lung and gastrointestinal malignancies, were each altered in 18 percent of patients, with co-existing EGFR amplifications detected in three cases that also carried sensitizing EGFR mutations. PIK3CA and FGFR3 each appeared in 9 percent of patients, GNAS and MYC in 7 percent, and CTNNB1 and the estrogen receptor gene ESR1 in 4 percent each. Amplifications were present in 20 percent of the cohort, most frequently affecting EGFR and MYC. No gene fusions or rearrangements were detected, a negative finding the authors report explicitly.

Perhaps the most clinically electrifying numbers came from the variant allele frequency analysis, a measure of what fraction of the cell-free DNA in a sample carries the mutation in question. Cerebrospinal fluid posted a median VAF of 23.2 percent, an order of magnitude higher than the 0.65 percent median typically achievable in plasma, reflecting the fluid’s remarkable purity and minimal contamination from blood-derived genomic DNA. Pleural fluid showed a median VAF of 6.5 percent and ascites 1.23 percent, while the lone pericardial sample harbored an EGFR mutation at a VAF of 70 percent. Such high fractions mean that even modest sequencing depth can reliably detect clinically relevant alterations in these fluids, potentially enabling the identification of low-frequency mutations and structural variants that current plasma-based platforms struggle to resolve.

To translate raw mutation lists into clinical meaning, the researchers classified every alteration using the ESCAT framework, the European Society for Medical Oncology’s scale for ranking the actionability of molecular targets. Roughly 31 percent of patients carried tier IA alterations, meaning mutations with approved targeted therapies for their specific tumor type, almost all of them in breast or lung cancer. Another 35.6 percent fell into tier IIIA, where drugs have proven benefit in the same molecular subtype but a different tumor type, and 53.3 percent carried tier IVA alterations supported only by preclinical evidence, highlighting unmet opportunities for clinical trial enrollment. The take-home message is that fluid profiling is not merely academic; the alterations it finds map directly onto therapies that already exist or are in development.

Even more provocative were the six patients whose fluids harbored therapeutically relevant alterations that were entirely absent from matched tissue and blood samples. One woman with breast cancer had an ERBB2 amplification detectable only in her ascites, a finding that opens the door to multiple FDA-approved HER2-directed drugs. Another breast cancer patient carried the ESR1 D538G resistance mutation, targetable with agents including elacestrant and fulvestrant, in her cerebrospinal fluid alone. A gastrointestinal stromal tumor patient had a KIT mutation in pleural fluid that imatinib can inhibit, and three patients, one with ovarian and two with pancreatic cancer, showed FGFR3 amplifications or KRAS G12V mutations exclusively in ascitic fluid. These discordances are the molecular fingerprint of spatial and temporal tumor heterogeneity: different metastatic sites evolve different resistance mechanisms, and local shedding enriches the adjacent fluid with clones that a single tissue biopsy or diluted plasma sample simply cannot see.

The concordance analysis quantified this incompleteness of conventional sampling. Among 16 patients with both fluid and blood profiling, only half shared at least one oncogenic alteration between the two sample types. Of 11 patients with matched tissue comparisons, seven showed overlapping alterations, and when all three sample types were compared simultaneously in seven patients, just three displayed fully concordant profiles. Cytology comparisons told a complementary story: of five cytology-negative fluid samples, four were positive for ctDNA, meaning molecular analysis flagged malignancy that the microscope had missed. The reverse also occurred, with three of twenty cytology-positive samples testing negative by sequencing, a pattern that reinforces the authors’ argument that the two approaches are complementary rather than competing. Fluid cytology retains formal staging importance, contributing, for example, to FIGO stage III classification in ovarian cancer, but ctDNA analysis catches cases cytology alone would miss.

The study is candid about its limitations. It was retrospective, exploratory, and descriptive, with a small and heterogeneous cohort, no formal statistical hypothesis testing, and representation of pericardial fluid limited to a single case. Matched samples were not available for every patient, timing differences between fluid, tissue, and plasma collection may have contributed to discordance through clonal evolution under therapeutic pressure, and platform differences in panel design and sequencing depth cannot be fully excluded as sources of the observed discrepancies. ESCAT tiers link drugs to mutations but do not demonstrate that any individual patient benefited from matching therapy. The authors explicitly frame their detection rates as preliminary observations that require prospective validation in larger, disease-specific cohorts with standardized sampling.

Even with those caveats, the implications are difficult to ignore. Effusions and cerebrospinal fluid are collected routinely from advanced cancer patients, often repeatedly, yet their genomic content has been largely discarded after the cytology slide is read. The new findings, consistent with prior reports of EGFR amplification found in ascites but not tissue, and with NCCN guidelines that already recommend considering CSF tumor DNA testing when leptomeningeal disease is suspected, suggest that these fluids deserve a formal place in precision oncology workflows. Body fluids sidestep the clonal hematopoiesis false positives that plague plasma sequencing, they can be sampled when tissue biopsy is unsafe or infeasible, and they capture the regional biology of metastatic sites that governs how each deposit will respond to treatment. If prospective trials confirm these descriptive signals, the cloudy fluid drained from a patient’s chest or abdomen may become as informative as any gene panel, transforming a routine byproduct of cancer care into a real-time map of the tumor’s evolving vulnerabilities.

Subject of Research: Circulating tumor DNA analysis of non-blood body fluids for cancer detection and molecular profiling

Article Title: Circulating tumor DNA in body fluids for molecular characterization of cancers beyond tissue and blood

Article References: Shreenivas, A., Limaye, S., Cristofanilli, M., Lechner, M., Gaya, A. M., Crook, T., Leite, P., Mokbel, K., Schaffrin-Nabe, D., Al-Shamsi, H. O., Patil, D., Datar, R., & Kurzrock, R. (2026). Circulating tumor DNA in body fluids for molecular characterization of cancers beyond tissue and blood. iScience, 29(11), Article 117893. https://doi.org/10.1016/j.isci.2026.117893

Image Credits: AI Generated

DOI: 10.1016/j.isci.2026.117893

Keywords: liquid biopsy, circulating tumor DNA, ascites, cerebrospinal fluid, pleural effusion, cytology, precision oncology, tumor heterogeneity, ESCAT, next-generation sequencing, EGFR, ERBB2

The research team, led by investigators at Al-Quds University in Jerusalem together with colleagues at St. Vincent’s University Hospital in Dublin, conducted a retrospective observational study of 113 consecutive cancer patients who underwent CTPA for suspected acute pulmonary embolism between January 2022 and January 2026. Their goal was straightforward but clinically important: to characterize the pleural and lung parenchymal abnormalities visible on these scans and determine which, if any, actually distinguish patients with confirmed embolism from those without. Pulmonary embolism remains one of the top three causes of cardiovascular death worldwide, and malignancy is among the most potent risk factors for developing one, so the stakes of accurate interpretation in this population are high.

What the team found first was sheer complexity. Pleural effusion — fluid around the lungs — was the single most common abnormality, present in 58.4 percent of all patients. Pulmonary nodules or masses appeared in 46.0 percent, atelectatic or collapse changes in 45.1 percent, consolidation in 38.1 percent, and ground-glass opacity in 30.1 percent. Interstitial or septal changes, infectious or inflammatory patterns, emphysema, bronchiectatic tree-in-bud changes, cavitary lesions, and infarct-like wedge-shaped opacities rounded out a long list of coexisting findings. In other words, the thorax of a cancer patient undergoing CTPA is almost never a clean canvas: it is a layered superimposition of tumor effects, treatment-related lung injury, infection, and chronic structural change, all of which can mimic or obscure the signature of an embolus.

Embolism itself was confirmed in 32 of the 113 patients, or 28.3 percent — a substantial yield that underscores the genuine thrombotic burden carried by oncology populations. The prevalence was highest among patients with gastrointestinal, gynecologic, and thoracic malignancies. The median age of the cohort was 59 years, and 42.5 percent were female. Notably, when the researchers examined where the clots actually sat, more than 71 percent of PE-positive patients had bilateral emboli, distributed across central, segmental, and mixed peripheral vascular territories. In this cohort, embolism was frequently not a small, isolated finding but an anatomically extensive thromboembolic process, a pattern that carries implications for how thoroughly radiologists must scrutinize the entire pulmonary arterial tree.

Against that noisy background, one finding stood out. Infarct-like wedge-shaped opacity — a peripheral, cone-shaped density classically associated with pulmonary infarction downstream of an occluded vessel — appeared in 12.5 percent of PE-positive patients compared with just 1.2 percent of those without embolism. That corresponds to an unadjusted odds ratio of 11.43, and in a deliberately parsimonious multivariable model restricted to three imaging predictors, the association held with an adjusted odds ratio of 11.72. From a pathophysiologic standpoint, the signal is biologically plausible: when a clot blocks a segmental pulmonary artery, the distal lung tissue can infarct, producing exactly this focal, peripheral wedge of damaged parenchyma on the scan.

But here is where the study’s statistical rigor matters. The researchers applied Benjamini–Hochberg false-discovery-rate correction across twelve imaging comparisons, and none of the associations — including the wedge-shaped opacity signal — survived that correction (q = 0.133 for the wedge finding). The confidence intervals were strikingly wide, stretching from 1.23 to 106.62, because only five patients in the entire cohort had this finding. The authors are appropriately candid: these results should be considered hypothesis-generating rather than confirmatory, and the wedge-shaped opacity should be viewed as a clue that heightens suspicion of embolic infarction when it appears, not as a standalone diagnostic predictor.

Equally interesting was what the data suggested in the opposite direction. Ground-glass opacity and interstitial or septal change were both less frequent in PE-positive patients — appearing in 15.6 percent versus 35.8 percent, and 3.1 percent versus 25.9 percent, respectively. The explanation likely lies in radiologic specificity. Acute pulmonary embolism produces focal, peripheral change reflecting segmental vascular occlusion, whereas ground-glass and interstitial abnormalities reflect diffuse processes affecting the alveolar-interstitial compartment: infection, pulmonary edema, lymphangitic tumor spread, drug-related pneumonitis, or radiation injury. Their relative predominance in PE-negative examinations suggests they should prompt careful consideration of non-embolic explanations for a patient’s breathlessness — though the authors caution that this inverse pattern may partly reflect referral behavior, and embolism must still be assessed on direct vascular findings regardless of the surrounding parenchyma.

Methodologically, the study has notable strengths. The team used consecutive sampling to minimize selection bias, extracted data from formal radiology reports produced by a consultant thoracic radiologist who had no knowledge of the research question, classified imaging terminology according to the Fleischner Society glossary, and followed STROBE reporting guidelines. The exploratory regression model was deliberately limited to three predictors to avoid overfitting given only 32 PE events, and it was internally validated with 2,000 bootstrap resamples, yielding an optimism-adjusted AUROC of 0.699 — only marginally below the apparent value of 0.707 — with acceptable calibration. Still, the authors acknowledge real limitations: a single-center retrospective design, modest event counts, missing data on chemotherapy, radiotherapy, anticoagulation, and infection, and the inability to definitively attribute individual findings to embolism rather than overlapping disease processes.

The practical message for clinicians is a dual-purpose reading of CTPA in oncology patients: first as a vascular study hunting for intravascular filling defects, and second as a comprehensive thoracic examination for alternative and coexisting causes of symptoms. The authors advocate a structured reporting approach that clearly separates direct vascular evidence of embolism, parenchymal findings plausibly related to embolic injury, and ancillary abnormalities pointing toward non-embolic disease. That kind of clarity, they argue, could reduce the over-attribution of nonspecific lung findings to embolism and improve communication between radiologists and treating oncologists.

Looking ahead, the team calls for larger, multicenter studies with prospective designs, blinded radiologic re-review, formal interobserver agreement analysis, and standardized severity scoring to confirm whether infarct-like wedge-shaped opacity truly is the most embolism-suggestive pattern in cancer patients. They also propose examining how cancer subtype, metastatic burden, recent chemotherapy or radiotherapy, and infectious status modify these imaging relationships — and correlating CT patterns with laboratory data, clot burden, and clinical outcomes to determine whether these findings are prognostically as well as diagnostically relevant. For now, the study delivers a nuanced verdict: in the imaging-dense world of cancer care, lung findings abound, most are nonspecific, and only careful, contextual interpretation — anchored in the direct visualization of the pulmonary arteries — can reliably separate clot from the many other culprits competing for attention on the scan.

Subject of Research: Pleuroparenchymal CT findings and their association with pulmonary embolism in cancer patients

Article Title: Pleuroparenchymal abnormalities in cancer patients undergoing CTPA for suspected pulmonary embolism

Article References: Allahham, M. F., Mustafa, H., Faroun, J., Amro, A. M., Allahham, F. M., Shrateh, O. N., & Murphy, D. (2026). Pleuroparenchymal abnormalities in cancer patients undergoing CTPA for suspected pulmonary embolism. Frontiers in Radiology, 6, Article 1901919. https://doi.org/10.3389/fradi.2026.1901919

Image Credits: AI Generated

DOI: 10.3389/fradi.2026.1901919

Keywords: pulmonary embolism, cancer, CT pulmonary angiography, radiology, pleuroparenchymal abnormalities, pulmonary infarction, ground-glass opacity, venous thromboembolism, oncology imaging, thoracic imaging, pleural effusion, diagnostic imaging

Fetal pleural effusion is an accumulation of fluid within the pleural space, the thin cavity that surrounds each lung. It is rare, affecting an estimated one in 10,000 to one in 15,000 pregnancies, and it can appear as an isolated primary condition or as a secondary feature of chromosomal abnormalities, genetic syndromes, congenital infections, heart defects, lymphatic disorders, or immune incompatibilities between mother and fetus. When the effusion is isolated, meaning no other structural or chromosomal anomaly is detected, its clinical course is notoriously unpredictable. Some effusions resolve spontaneously without any intervention. Others progress relentlessly, compressing the lungs, shifting the mediastinum, and setting in motion a cascade that can end in fetal death.

The mechanics of that cascade explain why the condition is so dangerous. As fluid fills the pleural space, it compresses the developing lung tissue, which can lead to pulmonary hypoplasia, a permanent underdevelopment of the lungs that makes survival after birth impossible or profoundly compromised. The pressure also squeezes the heart, reducing cardiac output and eventually triggering hydrops, a state of widespread fluid accumulation and impending heart failure that has long been recognized as the single most ominous prognostic sign. Meanwhile, the shift of chest structures can compress the esophagus, impairing the fetus’s ability to swallow amniotic fluid and producing polyhydramnios, an excess of fluid that itself raises the risk of preterm labor. Diagnosis is typically made in the second trimester by ultrasound, which reveals an anechoic fluid collection within one or both hemithoraces.

For decades, clinicians have sought ways to intervene before the damage becomes irreversible. The simplest option is thoracentesis, in which a 20-gauge needle is inserted into the pleural cavity under ultrasound guidance and the fluid is aspirated. The problem is that the fluid tends to reaccumulate rapidly, forcing repeated needle insertions, each of which carries its own risk of infection and of preterm premature rupture of membranes, or PPROM. The standard definitive treatment is therefore pleuro-amniotic shunting. In this procedure, a trocar with an outer diameter of three millimeters is introduced through the maternal abdomen and fetal chest wall under continuous ultrasound imaging. A double-coiled pigtail silicone catheter is then deployed to create a permanent channel between the pleural space and the amniotic cavity, allowing fluid to drain continuously out of the chest and be reabsorbed by the fetal membranes.

Despite the procedure’s long history, its safety and efficacy have remained uncertain, with individual centers reporting widely varying outcomes. The new analysis, led by Enzo Lofredo Amorim and colleagues at institutions in Brazil and Italy and registered prospectively with PROSPERO, set out to resolve that uncertainty. The team searched PubMed, Embase, Scopus, and the Cochrane Central Register, screening 847 records and ultimately including ten retrospective cohort studies published between 1988 and 2022. The studies spanned Europe, North America, South America, Asia, and Oceania, and collectively involved 587 fetuses, of whom 416 underwent shunting. The weighted mean gestational age at intervention was 28.1 weeks. Bilateral effusions predominated, accounting for 76.9 percent of cases, and nearly seven in ten of the treated fetuses were male.

The pooled results tell a story of meaningful benefit tempered by real cost. Of the 416 shunted fetuses, 272 survived to discharge, yielding an overall survival rate of 65.36 percent, with individual study estimates ranging from 46.34 to 75.44 percent and only low statistical heterogeneity. Among the four studies reporting hydrops outcomes, covering 151 fetuses, resolution occurred in 94 cases, a pooled rate of 62.25 percent with essentially perfect agreement across centers, as reflected by an I-squared value of zero percent. Catheter displacement, the most common device-related complication, was recorded 62 times across nine studies, corresponding to a prevalence of 17.13 percent. Chorioamnionitis, an infection of the fetal membranes, was rare, affecting just seven of 134 fetuses in three studies, a pooled prevalence of 5.22 percent.

The obstetric toll, however, was substantial. Across six studies involving 224 fetuses, there were 155 preterm births, a pooled prevalence of 69.67 percent, meaning that roughly seven in ten pregnancies ended before 37 weeks of gestation. PPROM occurred in 17.65 percent of cases, though this estimate carried high heterogeneity, driven largely by a single cohort that reported an incidence of 82.76 percent. The authors argue that these figures underscore a crucial clinical message: pleuro-amniotic shunting should never be viewed as an isolated surgical event. The procedure effectively converts the pregnancy into a high-risk one, demanding coordinated planning among fetal medicine specialists, anesthesiologists, neonatal intensive care teams, and support staff to manage early delivery and its consequences.

The analysis also sharpened understanding of prognosis. Hydrops at diagnosis remains the most powerful negative predictor, and the included data confirmed the dichotomy: one study cited in the review found survival of 93.3 percent among non-hydropic fetuses compared with 56.0 percent among those with hydrops. Yet the most striking finding concerns reversal. When shunting succeeds in decompressing the chest and reversing hydrops in utero, the prognosis transforms dramatically. Data from one included cohort showed that hydropic fetuses whose condition resolved after drainage achieved a survival rate of 67.3 percent, approaching the outcomes of fetuses that never developed hydrops at all. The zero heterogeneity in the hydrops resolution outcome suggests a highly consistent physiological response to mechanical decompression across different global centers, lending biological plausibility to the pooled estimate.

The authors are careful to frame the strength of the evidence honestly. Using the ROBINS-I tool for non-randomized studies, all ten included cohorts were judged to carry an overall moderate risk of bias, a classification driven entirely by the confounding domain inherent to retrospective designs. Every other domain, including participant selection, intervention classification, and outcome measurement, was rated as low risk. The rarity of isolated fetal pleural effusion makes large randomized controlled trials practically and ethically difficult, so retrospective cohorts remain the best available evidence. The authors also note that expectant management may still be appropriate for mild or stable effusions, while thoracentesis, though simpler, is limited by rapid fluid reaccumulation and the cumulative morbidity of repeated needle insertions.

The bottom line for clinicians and expectant parents is a quantified trade-off. For progressive or severe isolated fetal pleural effusion, pleuro-amniotic shunting offers sustained intrathoracic decompression and a realistic chance of survival in about two-thirds of cases, with most hydropic fetuses experiencing reversal of the condition. That benefit comes bundled with a high likelihood of preterm delivery and measurable rates of device displacement and membrane rupture, which is why the authors call for multidisciplinary perinatal management as an inseparable component of the therapy. They also emphasize the need for prospective multicenter studies to refine patient selection, standardize protocols, and clarify long-term neonatal trajectories. Until such trials exist, this meta-analysis provides the most reliable benchmark yet for counseling families facing one of fetal medicine’s most consequential decisions.

Subject of Research: Perinatal outcomes of pleuro-amniotic shunting for isolated fetal pleural effusion

Article Title: Perinatal Outcomes of Pleuro-Amniotic Shunting in Isolated Pleural Effusions: Systematic Review and Meta-analysis

Article References: Amorim, E. L., Araujo Júnior, E., da Silva Lourenço, M. C., de Sousa, D. G., Ferreira, F. M., dos Santos Lobo, M. F., Provinciatto, H., Nader, E. M., Braga, A., & Granese, R. (2026). Perinatal Outcomes of Pleuro-Amniotic Shunting in Isolated Pleural Effusions: Systematic Review and Meta-analysis. Advances in Therapy. https://doi.org/10.1007/s12325-026-03809-8

Image Credits: AI Generated

DOI: 10.1007/s12325-026-03809-8

Keywords: fetal therapy, pleural effusion, pleuro-amniotic shunting, fetal hydrops, preterm birth, PPROM, meta-analysis, perinatal outcomes, fetal medicine, pulmonary hypoplasia, neonatology, systematic review

Solitary fibrous tumours are spindle cell neoplasms of mesenchymal origin, meaning they arise from connective tissue cells rather than from the epithelial cells that give rise to the vast majority of lung cancers. Most solitary fibrous tumours of the chest originate from the pleura, the thin membrane enveloping the lungs, and they are typically slow-growing and benign. When they occur inside the lung parenchyma instead, they become a genuine clinical curiosity. Published analyses suggest these intrapulmonary tumours most often affect adults between 50 and 70 years of age, and a clinicopathological review of 52 cases found a mean age of onset of 52.7 years, with the left lower lobe being the most frequently affected pulmonary location. That detail matters here, because the tumour in this new case arose in precisely that region.

The patient’s story began seven months before her definitive diagnosis, when a left-sided pleural effusion, an accumulation of fluid around the lung, was discovered incidentally during a hospital admission for hypoglycaemia. She had a history of diabetes mellitus, passive exposure to tobacco smoke, and more than two decades of employment in a textile factory. Initial chest radiography showed a homogeneous opacity in the left lower lung field accompanied by the effusion. Because tuberculosis remains a leading cause of pleural disease in many parts of the world, her physicians administered an empirical two-month course of anti-tuberculosis treatment. It failed. The opacity did not budge, a signal that something other than infection was occupying her chest.

Contrast-enhanced computed tomography performed in July 2025 finally revealed the true scale of the problem: a large mass in the left lower lobe measuring 14.1 by 15.6 by 12.1 centimetres. The patient was then lost to follow-up for more than five months, and when she returned with worsening chest pain and shortness of breath, repeat imaging showed that the tumour had grown to 11 by 16.5 by 15.2 centimetres. The mass was displacing her heart toward the right side of her chest, causing collapse of portions of the surrounding lung, and was accompanied by both pericardial and pleural effusions. Most ominously, a 3.8-centimetre nodule had appeared in the liver, suspicious for metastasis. Under the standard tumour-node-metastasis framework, the findings were classified as T4N0M1b, indicating a locally advanced tumour with possible distant spread but no involved lymph nodes.

A core needle biopsy of the mass yielded the tissue that would settle the diagnosis. Under the microscope, pathologists saw a low-grade spindle cell neoplasm with only one to two mitoses per ten high-power fields, a measure of how actively the cells were dividing. The decisive evidence came from immunohistochemistry, the technique that uses antibodies to detect specific proteins in tissue sections. The tumour cells showed diffuse nuclear positivity for STAT6, partial positivity for CD34, and a Ki-67 proliferation index below 5 percent, while staining for CK7, desmin, smooth muscle actin and S100 was negative. Diffuse nuclear STAT6 expression is regarded as a highly sensitive and specific marker for solitary fibrous tumours, reflecting the characteristic NAB2-STAT6 gene fusion that drives these neoplasms, and it is particularly valuable for distinguishing them from the many other spindle cell tumours that can arise in the chest.

The size of this tumour alone sets it apart. Radiologically, pulmonary solitary fibrous tumours typically present as well-circumscribed soft-tissue masses, and the majority of reported tumours measure less than 10 centimetres. A comparable giant presentation was described in a 2025 case report, in which a mass measuring 14 by 12 by 23 centimetres caused compressive atelectasis and raised concern for hepatic and splenic metastases. The combination in the current patient of massive tumour burden, compressive effects on the heart and mediastinum, suspected pericardial involvement and possible distant spread represents an unusually aggressive-looking profile for a tumour whose microscopic features still looked comparatively indolent.

One intriguing thread in the case is the patient’s earlier episode of hypoglycaemia. Solitary fibrous tumours are among the rare neoplasms capable of secreting insulin-like growth factor 2, a hormone-like protein that can drive blood sugar to dangerously low levels. This paraneoplastic phenomenon is known as Doege-Potter syndrome, and fewer than 2,000 cases have been reported worldwide. The connection is more than a medical curiosity: in a patient with a known fibrous tumour, unexplained hypoglycaemia can be a clue to the tumour’s biology, and resection of the tumour typically abolishes the metabolic derangement. In this case, however, serum IGF-2 levels were never measured, so the physicians could not formally confirm that the earlier hypoglycaemic episode was tumour-driven, leaving the association suggestive but unproven.

Pathologists weigh several features when judging whether a solitary fibrous tumour is likely to behave badly. Size greater than 10 centimetres, necrosis, increased mitotic activity, hypercellularity and nuclear pleomorphism all raise concern for malignant behaviour. The present tumour sailed past the size threshold and had radiographic evidence of possible metastasis, yet its mitotic count and Ki-67 index pointed toward low-grade histology. This tension between benign-looking cells and clinically ominous behaviour is precisely what makes solitary fibrous tumours so difficult to manage, and it underscores why diagnosis cannot rest on any single test. The authors emphasise that integrating clinical findings, imaging, histopathology and immunohistochemistry is essential to reaching an accurate diagnosis and tailoring treatment to the individual patient.

For localized solitary fibrous tumours, complete surgical resection remains the treatment of choice, and long-term survival after clean excision is generally excellent. But in this patient, a multidisciplinary team concluded that the extent of disease and the suspicion of metastatic spread made upfront surgery too risky. Systemic therapy became the pragmatic alternative, even though the evidence base for chemotherapy in advanced solitary fibrous tumours remains thin. Anthracycline-based regimens are commonly employed in unresectable or metastatic cases, and targeted approaches, including combinations of temozolomide with bevacizumab and the kinase inhibitors pazopanib and sunitinib, have shown promising results in refractory disease. The patient received six cycles of a four-drug regimen combining doxorubicin, cisplatin, vincristine and cyclophosphamide.

Follow-up imaging after chemotherapy showed a persistent mass measuring 16.2 by 9.0 by 14.7 centimetres with suspected invasion of the pericardium, the sac surrounding the heart, but no mediastinal lymphadenopathy. Pulmonary function testing revealed mild impairment of the lung’s diffusing capacity, with a DLCO of 67 percent of predicted, while standard spirometry was preserved. Clinically, the patient remained stable. The case, reported by Desdiani Desdiani and colleagues, is a reminder that even in an era of sophisticated imaging and molecular diagnostics, the rarest tumours still test the limits of clinical intuition. A mass that mimics tuberculosis, grows to the size of a small melon, shifts the heart within the chest and seeds a suspicious lesion in the liver demands that physicians hold every diagnostic tool in view at once, and that pathologists, radiologists and oncologists work in close concert to chart a course through genuinely uncharted territory.

Subject of Research: A rare giant intrapulmonary solitary fibrous tumour with suspected liver metastasis

Article Title: Giant Intrapulmonary Solitary Fibrous Tumour With a Possible Liver Metastasis: A Rare Case

Article References: Desdiani, D., Siregar, N. C., Prawiro, A., & Syahbunan, K. K. C. (2026). Giant Intrapulmonary Solitary Fibrous Tumour With a Possible Liver Metastasis: A Rare Case. Respirology Case Reports, 14(10), Article e70754. https://doi.org/10.1002/rcr2.70754

Image Credits: AI Generated

DOI: 10.1002/rcr2.70754

Keywords: solitary fibrous tumour, intrapulmonary tumour, STAT6, lung cancer, Doege-Potter syndrome, metastasis, immunohistochemistry, chemotherapy, case report, rare disease, spindle cell neoplasm, pleural effusion

The clinical story began innocuously. After a hospital admission for severe community-acquired pneumonia, the man was referred to a London outpatient clinic for persistent shortness of breath on climbing stairs and unintentional weight loss. Follow-up chest radiographs arranged to confirm that his pneumonia had resolved revealed something unexpected: a persistent right-sided pleural effusion, an abnormal collection of fluid in the space surrounding the lung, accompanied by collapse of the underlying lung tissue. What might have been dismissed as a lingering complication of infection instead became the first clue to a far more serious process.

Computed tomography imaging escalated the concern. The scan demonstrated a moderate right-sided pleural effusion with circumferential nodular thickening of the pleura, the delicate membrane that envelops the lung, along with enlarged lymph nodes near the heart and in the right hilum. Fluorodeoxyglucose-positron emission tomography, a scanning technique that highlights metabolically active tissue, showed diffuse uptake across the pleura with moderate avidity, and identified an enlarged intercostal lymph node that was accessible for biopsy. Formal staging placed the tumour at T3N1M0, indicating locally advanced disease with regional lymph node involvement but no distant spread.

Fluid drawn from the chest under ultrasound guidance was a cloudy yellow exudate, with a protein level of 54 grams per litre, a fluid-to-serum protein ratio of 0.72, glucose of 3.8 millimoles per litre and lactate dehydrogenase of 490 units per litre. Cytology showed lymphocytosis but, crucially, no malignant cells. The diagnostic breakthrough came from the intercostal lymph node itself. Histopathology revealed morphology and an immunoprofile consistent with an epithelioid-type malignant mesothelioma with lymphovascular invasion, and adenocarcinoma markers were negative. The tumour cells expressed calretinin, WT-1 and D2-40 while testing negative for TTF-1, a marker profile that firmly pointed to mesothelioma rather than lung adenocarcinoma.

Immunohistochemistry demonstrated retained expression of BRCA-1 associated protein, known as BAP1, and germline testing for BAP1 tumour predisposition syndrome came back negative. This mattered because BAP1 loss is a hallmark of many mesotheliomas and because inherited mutations in BAP1 define a recognised cancer predisposition syndrome. Broader germline panel testing was not performed, however, leaving open the possibility of other inherited susceptibility genes. After discussion by the lung cancer multidisciplinary team and referral to the regional mesothelioma service, the tumour was deemed inoperable, and the patient began combination immunotherapy with nivolumab and ipilimumab, a checkpoint inhibitor regimen that has transformed outcomes for some patients with advanced disease.

The puzzle was the exposure history. The patient was born in Kandahar, Afghanistan, moved to Kabul at age three, relocated to Peshawar in Pakistan at thirteen, and immigrated to the United Kingdom at sixteen. He had no identifiable occupational exposure to asbestos, no para-occupational exposure through household contacts, and no memory of living near an asbestos mine. In Britain he worked as a hospital biochemist, an occupation far removed from the traditional asbestos trades. The reporting team, led by Sophie Mounouchos and colleagues writing in Respirology Case Reports, looked instead to his childhood environments, and what they found was a growing body of evidence linking environmental asbestos exposure in Afghanistan and Pakistan to mesothelioma and pleural disease.

In Afghanistan, pleural plaques, thickened patches on the pleura that serve as fingerprints of asbestos exposure, have been reported in a 51-year-old Kabul resident with no occupational exposure. The authors of that report proposed environmental exposure from the neighbouring Loghar region, where natural deposits of tremolite, an amphibole asbestos, have been documented. Kabul also used asbestos-containing materials during the 1970s, including asbestos-cement piping and sheeting. During the 1980s the city suffered repeated structural damage in the Soviet-Afghan conflict, and armed conflict may have mechanically disrupted those materials, releasing airborne fibres, although the researchers caution that the importance of this mechanism remains uncertain.

Pakistan may have added a second layer of exposure. Peshawar lies within Khyber Pakhtunkhwa province, which contains ninety percent of Pakistan’s naturally occurring asbestos deposits, and asbestos-containing construction materials remain widely used in the country. A case series has identified a heavy burden of malignant mesothelioma in the region, thought to be associated with the high concentration of asbestos deposits, and concern about rising diagnoses in younger people is reinforced by a 2011 report of a 26-year-old woman in northern Pakistan diagnosed with the disease despite no occupational exposure. The interval between the patient’s early childhood residence in Kabul and Peshawar and his diagnosis at age forty sits squarely within the recognised latency periods for mesothelioma, lending biological plausibility to the proposed pathway.

The case also illuminates the role of genetics. The environmental mesothelioma outbreak in Turkey linked to erionite, an asbestiform mineral, revealed familial clustering and indirectly led to the identification of the BAP1-associated tumour predisposition syndrome. In a United States cohort of 198 mesothelioma patients, twelve percent carried susceptible germline mutations, notably among younger patients, and BAP1 accounted for only a quarter of the pathogenic mutations found across thirteen cancer-susceptibility genes. Because broader germline testing was not performed in the London case, inherited susceptibility cannot be fully excluded. Together these threads suggest that mesothelioma in the young may represent a distinct entity, with environmental exposure and genetic predisposition interacting in ways that differ from the classic occupational disease of older men.

The implications reach well beyond a single patient. In the United Kingdom, the decline of heavy industry and progressively stricter exposure legislation have driven occupational mesothelioma deaths downward, bringing environmental exposures into sharper focus. While men bear the bulk of disease across all ages, reflecting their historically greater occupational exposure, the gender distribution among those diagnosed under forty is far more even, hinting that other causal factors dominate in the young. The authors argue that clinicians in high-income countries should consider earlier-life environmental and residential exposures acquired overseas, particularly in younger mesothelioma patients who lack conventional occupational histories. Migration to high-resource healthcare settings, they suggest, may be an important mechanism for recognising environmental mesothelioma that would otherwise go undiagnosed in lower-resource settings, and understanding the interplay between inherited susceptibility and environmental fibre exposure may prove essential to unravelling this rare and devastating cancer in the young.

Subject of Research: Environmental asbestos exposure and early-onset malignant pleural mesothelioma

Article Title: Environmental Asbestos Exposure as a Possible Pathway to Early‐Onset Pleural Mesothelioma: A Case From Afghanistan and Pakistan to London

Article References: Mounouchos, S., Aggarwal, A., Nafees, A. A., Johnson, E., Cullinan, P., & Reynolds, C. (2026). Environmental Asbestos Exposure as a Possible Pathway to Early‐Onset Pleural Mesothelioma: A Case From Afghanistan and Pakistan to London. Respirology Case Reports, 14(10), Article e70774. https://doi.org/10.1002/rcr2.70774

Image Credits: AI Generated

DOI: 10.1002/rcr2.70774

Keywords: mesothelioma, asbestos, environmental exposure, Afghanistan, Pakistan, pleural effusion, BAP1, genetic susceptibility, early-onset cancer, immunotherapy, tremolite, Khyber Pakhtunkhwa

The European Organisation for Research and Treatment of Cancer and the Mycoses Study Group, whose joint criteria have anchored invasive fungal disease research for decades, sort suspected cases into three tiers: possible, probable, and proven invasive aspergillosis. Host factors such as neutropenia, steroid exposure, and prior stem cell transplantation are weighed alongside mycological evidence, typically galactomannan antigen detection or culture, and clinical imaging features like the halo sign or air-crescent sign on computed tomography. In the Istanbul cohort, only a single patient, 0.6 percent, met the strictest proven category. Fifty-one patients, 31.9 percent, were classified as probable, while 87 patients, 54.4 percent, fell into the possible category. Critically, 21 patients, or 13.1 percent, could not be classified at all despite clinical suspicion strong enough that the investigators judged no alternative etiology could explain their findings.

That unclassified group is the study’s most provocative finding. These were patients whom experienced infectious diseases physicians believed had invasive pulmonary aspergillosis, yet they failed to satisfy the formal criteria, often because they lacked the canonical host factors or the characteristic radiological patterns. The authors argue that such cases indicate the EORTC/MSG criteria should be reviewed, particularly for patients outside the classical hematologic risk groups, because rigid application risks delaying clinical decision-making. In a disease where every day of delayed antifungal therapy can be fatal, a diagnostic framework that leaves more than one in ten clinically suspected cases in limbo is more than an academic inconvenience; it is a potential barrier to timely treatment.

The cohort itself reflected the changing face of the disease. Of the 160 patients, 97 were male and the mean age was 51.39 years, with a standard deviation of 14.27. Three quarters of the patients, 120 in total, had an underlying hematologic diagnosis, and within this group 38 had received allogeneic stem cell transplants while 25 had undergone autologous transplantation. Yet the remaining 40 patients had no hematologic condition at all, representing the non-classical populations, including critically ill and otherwise immunocompromised individuals, in whom aspergillosis is increasingly recognized. Graft-versus-host disease, the immunological complication of allogeneic transplantation in which donor immune cells attack recipient tissues, was significantly more frequent among patients classified as proven or probable, a statistically meaningful association with a p value of 0.042 that fits the biology, since graft-versus-host disease and its steroid treatment compound immunosuppression.

Imaging told its own nuanced story. Computed tomography findings consistent with the EORTC/MSG clinical criteria were present in 144 patients, 90 percent of the cohort, which on the surface suggests the radiological arm of the framework performs well. But the details mattered. Cavity formation, a late and destructive pattern of fungal invasion, was significantly more frequent among patients with mycological evidence of infection, with a p value of 0.037. More troubling was the finding that prolonged corticosteroid use was associated with non-criteria CT patterns, with a p value of 0.048. In other words, patients on long-term steroids, a growing population spanning transplant recipients, oncology patients, and those with autoimmune disease, often did not display the textbook halo signs and nodules the criteria expect. Their infections presented atypically, slipping through the radiological net.

Treatment patterns in the cohort also tracked with the diagnostic categories. Voriconazole, the triazole antifungal that guidelines favor as first-line therapy for invasive aspergillosis, was more often chosen as initial treatment in patients with clinical imaging evidence, a statistically significant association with a p value of 0.034. This suggests that clinicians anchor their therapeutic decisions on visible pulmonary lesions, which may explain why patients lacking criteria-consistent imaging face diagnostic and therapeutic delays. The authors also highlight a practical constraint: invasive diagnostic procedures such as bronchoscopy with bronchoalveolar lavage are often difficult or impossible in the sickest patients, underscoring the need for reliable non-invasive diagnostic methods that could confirm infection without subjecting fragile patients to risky procedures.

The mortality data are sobering. Six-week all-cause mortality stood at 21.2 percent and 12-week mortality at 31.9 percent, figures broadly consistent with published hematologic-malignancy cohorts, which typically report mortality in the range of 25 to 35 percent. But over the full follow-up period, 107 of the 160 patients died, a 66.9 percent overall mortality rate, with a median survival of 240 days. The authors note that this figure is higher than in hematologic cohorts but comparable to intensive care unit and non-hematologic populations, reinforcing the point that aspergillosis arising in atypical hosts carries a prognosis at least as grim as the classical one. The comparison also implies that deaths in this heterogeneous group were driven not only by the fungus itself but by the burden of underlying disease, a distinction with real consequences for how trials and outcome measures are designed.

Two predictors of death emerged from the analysis. Patients who died were significantly older than survivors, with a p value of 0.029, consistent with the accumulated vulnerabilities of advanced age. More intriguingly, pleural effusion, the accumulation of fluid in the space surrounding the lung, visible on chest CT, was associated with death, with an odds ratio of 2.326 and a 95 percent confidence interval of 1.156 to 4.681, yielding a p value of 0.018. However, the association lost significance when the analysis was restricted to the 6-week and 12-week timepoints. The authors interpret this pattern carefully: pleural effusion appears to signal a comorbidity-driven rather than IPA-specific prognostic risk, marking patients whose overall physiological reserve is compromised rather than those in whom the fungal infection itself is uniquely aggressive. It is a subtle but important distinction for clinicians weighing prognosis at the bedside.

The study’s design carries the usual caveats of retrospective cohort research. Classification depended on records assembled for clinical rather than research purposes, and the single-center design limits generalizability, even if the center is a major referral hospital. The authors received no external funding and declared no competing interests, and the work was approved by the Clinical Research Ethics Committee of Istanbul University Istanbul Faculty of Medicine. Still, the scale of the cohort, 160 patients with findings unexplained by any other etiology, gives the findings weight, and the message is consistent with a growing international conversation about whether diagnostic criteria built around neutropenic hematology patients can serve an era in which aspergillosis strikes influenza patients, COVID-19 survivors, steroid-treated transplant recipients, and the critically ill.

What emerges from Istanbul is a portrait of a disease outpacing its diagnostic tools. The EORTC/MSG criteria remain indispensable for standardizing clinical trials and enabling comparison across studies, but this real-world cohort shows their limits: most patients cluster in the weakest possible category, a substantial minority escape classification entirely, and the radiological signatures the criteria demand may be absent precisely in the growing population of corticosteroid-treated patients. With overall mortality approaching 67 percent and median survival measured in months, the stakes of closing that gap are high. The authors’ call is twofold: maintain vigilance and early diagnosis even when criteria are not met, and invest in non-invasive diagnostics that can confirm infection quickly in patients who cannot undergo invasive sampling. Until then, clinicians facing a suspicious lung lesion in an atypical host may need to trust their clinical judgment as much as the checklist.

Subject of Research: Real-world performance of EORTC/MSG diagnostic criteria and mortality predictors in invasive pulmonary aspergillosis

Article Title: Invasive pulmonary aspergillosis in a heterogeneous patient cohort: real-world performance of EORTC/MSG criteria and predictors of mortality

Article References: Alp, E., Bali, E. A., Evlice, O., Çağatay, A., Yavuz, S. Ş., & Eraksoy, H. (2026). Invasive pulmonary aspergillosis in a heterogeneous patient cohort: real-world performance of EORTC/MSG criteria and predictors of mortality. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14567-x

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14567-x

Keywords: invasive pulmonary aspergillosis, EORTC/MSG criteria, fungal infection, diagnostic criteria, mortality, pleural effusion, corticosteroids, computed tomography, voriconazole, stem cell transplantation, hematologic malignancy, survival analysis

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