The mass was ultimately identified as a T-lymphoblastic lymphoma, an aggressive cancer of immature T-cell lymphocytes that often announces itself as a rapidly enlarging mediastinal tumor. Lymphomas of this type are notorious among diagnosticians because they demand not just a sample of tissue but a well-preserved one. Pathologists need to see the architecture of the tissue, the shape of the cells, and the results of an entire panel of immunohistochemical stains, each of which reveals whether the malignant cells carry particular protein markers. A crushed or blood-soaked fragment of tumor can render all of that analysis impossible, forcing patients into more invasive surgery or delaying treatment of a fast-moving disease.

For decades, the gold standard for sampling mediastinal tumors was mediastinoscopy, a surgical procedure in which a camera is inserted through an incision above the breastbone to reach the space between the lungs. It provides generous tissue samples, but it requires general anesthesia in a operating room, leaves a scar, and carries the risks of any surgical approach to a crowded anatomical neighborhood. Endobronchial ultrasound-guided transbronchial needle aspiration, known as EBUS-TBNA, changed that calculus. In this minimally invasive technique, a bronchoscope equipped with an ultrasound probe at its tip is passed through the windpipe, allowing the physician to see lymph nodes and masses through the airway wall and to pierce them with a fine needle. EBUS-TBNA has become the standard first-line tool for staging lung cancer and sampling mediastinal lesions, with high accuracy for detecting metastatic disease in lymph nodes.

But lymphoma is where the needle technique hits its limits. The tiny cores of tissue obtained through a 22-gauge needle are often fragmented and distorted by crush artefact, the mechanical damage inflicted as the needle cuts through delicate lymphoid cells. Add blood contamination, and the pathologist may receive a specimen too poor to distinguish between the many subtypes of lymphoma or to rule out other malignancies. That is precisely what happened in this case. When the medical team performed EBUS-TBNA three times at the same site using a 22-gauge needle, the resulting specimen failed to yield definitive findings. The tissue was crushed and blood-stained, and the diagnosis remained out of reach.

The team then turned to a newer approach that has been generating enthusiasm in interventional pulmonology: endobronchial ultrasound-guided transbronchial mediastinal cryobiopsy, or EBUS-Cryo. Cryobiopsy exploits one of the simplest physical effects in medicine, the fact that moisture instantly freezes and bonds to a very cold metal surface. Instead of cutting tissue with a blade or tearing it with forceps, the physician touches a cryoprobe cooled to extreme subzero temperatures against the target tissue for a few seconds. The tissue freezes onto the probe and is pulled away en bloc, retaining its cellular architecture far better than tissue harvested by cutting instruments. The technique has already shown promise in diagnosing pulmonary lymphomas and other lymphoproliferative disorders, and its extension into mediastinal sampling through the EBUS working channel represents a significant technical advance.

In this case, the procedure was performed under endotracheal intubation with an 8.5-millimeter tube, which secured the airway throughout. First, the EBUS-TBNA needle was used to create a tract through the airway wall into the mass. Then a 1.1-millimeter cryoprobe was threaded through that same tract and advanced under EBUS guidance into the tumor. The probe tip was frozen for seven seconds, after which the cryoprobe was withdrawn together with the bronchoscope as a single unit, bringing the frozen specimen with it. This maneuver was repeated until six cryobiopsy specimens had been collected. Notably, rapid on-site cytologic evaluation was not used, yet the samples proved diagnostically decisive. The entire examination proceeded without hypoxemia, bleeding, or any other adverse event, and the patient went home the very next day.

The pathological comparison between the two sampling methods was striking. The needle aspiration specimens were non-diagnostic, whereas the cryobiopsy material showed beautifully preserved tissue structure, with diffuse proliferation of atypical lymphocytes bearing round nuclei and a high nucleus-to-cytoplasm ratio. Immunohistochemical staining then told the full story. The atypical cells were positive for CD3, CD2, CD7, and CD99, a profile pointing firmly toward a T-cell lineage. They were negative for CD20, which argued against a B-cell lymphoma, and negative for AE1/AE3, which excluded an epithelial cancer such as thymoma or carcinoma. Markers including CD4, CD5, CD8, CD1a, CD34, c-kit, and SALL4 were also absent, narrowing the differential diagnosis further. Terminal deoxynucleotidyl transferase, or TdT, a hallmark of immature lymphoblasts, was expressed in only a small subset of cells, an atypical feature for T-lymphoblastic lymphoma. Weighing the full histopathological and immunophenotypic picture alongside the patient’s young age and the anterior mediastinal location of the tumor, the team arrived at a definitive diagnosis of T-lymphoblastic lymphoma, and she was referred promptly to hematology for systemic chemotherapy.

Safety deserves particular emphasis, because this case involved an unusually hazardous starting point. Mediastinal cryobiopsy, while generally considered relatively safe, carries recognized complications including bleeding, pneumomediastinum, and mediastinal infection. In a patient whose trachea was already markedly narrowed by extrinsic compression, even modest bleeding into the airway could have precipitated life-threatening obstruction. The authors note that the small 1.1-millimeter cryoprobe requires only a tiny puncture tract, which may theoretically reduce procedural risks compared with larger devices such as forceps or electrocautery instruments. The successful completion of the procedure, with discharge the following day and no airway compromise, suggests that in carefully selected patients, substantial airway compression need not disqualify a patient from this minimally invasive route to diagnosis.

The broader lesson of this case report, published in Respirology Case Reports, is that sampling technique can be the deciding variable in cancer diagnosis. EBUS-TBNA remains an outstanding tool for many mediastinal questions, particularly lung cancer staging, but when a suspected lymphoma demands assessment of tissue architecture and an extensive immunophenotypic workup, larger and better-preserved specimens can make the difference between an inconclusive result and an actionable answer. Cryobiopsy through the EBUS tract offers exactly that, using physical freezing rather than mechanical cutting to preserve the fragile cellular detail that immunohistochemistry depends upon. For patients with mediastinal masses, especially those compressing the airway, the prospect of a definitive diagnosis without open surgery, delivered through a probe thinner than a pencil lead and often within a single hospital day, represents a meaningful step forward in interventional pulmonology. As experience with EBUS-Cryo accumulates, this frozen needle may become a standard complement to conventional needle aspiration, ensuring that tumors like the one discovered on this young woman’s routine X-ray can be named, classified, and treated without delay.

Subject of Research: Diagnosis of primary mediastinal T-lymphoblastic lymphoma using endobronchial ultrasound-guided transbronchial mediastinal cryobiopsy

Article Title: Primary Mediastinal T‐Lymphoblastic Lymphoma With Airway Stenosis Diagnosed Using Endobronchial Ultrasound‐Guided Transbronchial Mediastinal Cryobiopsy: A Case Report

Article References: Nagamine, H., Bungo, M., Nagaki, Y., Todoriki, A., Niina, K., Enomoto, K., Kakuno, S., Nakai, T., Yamada, K., Watanabe, T., Asai, K., Mukai, D., Nagasaki, J., Nakamae, H., & Kawaguchi, T. (2026). Primary Mediastinal T‐Lymphoblastic Lymphoma With Airway Stenosis Diagnosed Using Endobronchial Ultrasound‐Guided Transbronchial Mediastinal Cryobiopsy: A Case Report. Respirology Case Reports, 14(9), Article e70756. https://doi.org/10.1002/rcr2.70756

Image Credits: AI Generated

DOI: 10.1002/rcr2.70756

Keywords: T-lymphoblastic lymphoma, EBUS-Cryo, cryobiopsy, mediastinal mass, airway stenosis, EBUS-TBNA, interventional pulmonology, immunohistochemistry, bronchoscopy, lymphoma diagnosis, case report, Respirology Case Reports

Ulcerative colitis is well known for the symptoms it causes in the large intestine, but it belongs to a family of conditions whose influence is systemic. Extraintestinal manifestations affect up to 27 percent of patients, and among these, lung disease has been increasingly appreciated. One large cohort study of 563 patients with ulcerative colitis identified lung involvement in 5 percent, with organising pneumonia accounting for 1.8 percent. Yet that same study attributed nine of the ten organising pneumonia cases to drug-induced mechanisms, leaving open a fundamental question: can organising pneumonia arise as a primary, disease-intrinsic feature of ulcerative colitis itself, independent of any medication?

The new case suggests that it can. The 2025 update to the international multidisciplinary classification of the interstitial pneumonias, issued jointly by the European Respiratory Society and the American Thoracic Society, now explicitly lists ulcerative colitis among the secondary causes of cicatricial organising pneumonia, a histologically distinct entity. That formal recognition matters, because it provides a framework for attributing lung disease to the underlying bowel condition rather than defaulting to a drug reaction—a distinction with direct consequences for how patients are treated.

The patient at the centre of the report was a lifelong never-smoker with a ten-year history of ulcerative colitis pancolitis, maintained on a stable dose of mesalamine at 2.4 grams daily. She carried a concurrent diagnosis of rheumatoid arthritis, made five years after her colitis began, based on bilateral symmetric polyarthritis affecting fifteen small joints with finger nodules. Two biologic drugs, adalimumab and certolizumab, had been trialled and discontinued for lack of efficacy. Three months before admission, her pulmonary function tests had been entirely normal. Then she developed progressive shortness of breath over the course of a single month.

On admission, she required low-flow oxygen, and examination revealed crackles in both lungs. Crucially, a faecal calprotectin measurement obtained one month earlier stood at 62 micrograms per gram, below the 80 micrograms per gram threshold that identifies histological bowel activity—a biomarker-confirmed remission. Her systemic inflammatory markers, however, told a different story: C-reactive protein, erythrocyte sedimentation rate and white cell count were all elevated. High-resolution computed tomography of the chest showed bilateral interstitial haziness, predominantly in the mid and lower lung fields, representing clear progression from prior imaging that had shown only mild scattered scarring.

Diagnostic workup proceeded along two tracks. Bronchoalveolar lavage fluid revealed a differential cell count of 42 percent neutrophils and only 3 percent lymphocytes—a profile that would later prove important. A transbronchial cryobiopsy of the right lower lobe was performed, and the initial histopathological interpretation locally was fibrotic non-specific interstitial pneumonia, a diagnosis that prompted plans for antifibrotic therapy with mycophenolate and nintedanib. But when the slides were reviewed by expert pulmonary pathologists, the interpretation changed fundamentally. The expert consultation identified organising pneumonia, characterised by polypoid fibroblast plugs known as Masson bodies within the airspaces, with only mild background fibrosis and an absence of honeycomb change or fibroblast foci—the hallmarks that would have supported a diagnosis of usual interstitial pneumonia or fibrotic non-specific interstitial pneumonia.

That diagnostic reversal was directly consequential. The planned antifibrotic regimen was abandoned in favour of corticosteroid therapy, the standard treatment for organising pneumonia, which carries a five-year survival exceeding 90 percent when treated appropriately. The patient received three days of intravenous pulse methylprednisolone followed by oral prednisone with a planned six-month taper. Mesalamine was held as a precaution, but withholding the drug produced no clinical improvement on its own—further evidence against a drug-induced mechanism. Follow-up imaging at two months showed partial resolution of the bilateral infiltrates, with residual changes consistent with her pre-existing baseline scarring, and azathioprine was added as a steroid-sparing agent with the additional benefit of maintaining her colitis.

The authors lay out a careful argument for why this organising pneumonia was disease-intrinsic rather than drug-induced. First, mesalamine exposure had been stable for a decade; drug-induced pneumonitis typically appears within weeks to months of initiation or dose change. Second, discontinuation of the drug during hospitalisation brought no improvement, whereas corticosteroids were required for a response—inconsistent with the natural history of a drug reaction. Third, the 2025 classification now formally recognises ulcerative colitis as a secondary cause of cicatricial organising pneumonia. The case also extends the sole prior published report of organising pneumonia occurring after histologically confirmed ulcerative colitis remission, adding biomarker-confirmed remission, systematic drug exclusion, detailed lavage data and a complete autoimmune workup that reclassified the patient’s joint disease as ulcerative colitis-associated spondyloarthropathy rather than rheumatoid arthritis, removing rheumatoid-associated lung disease from the differential.

Perhaps the most scientifically intriguing observation is the lavage profile. Classic cryptogenic organising pneumonia typically shows lymphocytic predominance in bronchoalveolar lavage, with lymphocyte counts of 20 to 40 percent and only mild neutrophil elevation. This patient showed the reverse: 42 percent neutrophils and a mere 3 percent lymphocytes. Prior research has shown that secondary organising pneumonia carries lower lymphocyte counts than the cryptogenic form, and the authors hypothesise that ulcerative colitis-associated disease may carry a distinctly neutrophil-predominant signature reflecting immune cell trafficking along the gut-lung axis. Mouse studies lend plausibility to this idea: colitis has been shown to induce pulmonary neutrophil infiltration through interleukin-17 elevation and microbial translocation, and interleukin-6-driven, neutrophil-mediated pulmonary inflammation has been documented in murine models of colitis with bacteremia.

The case is also a cautionary tale about diagnostic uncertainty in interstitial lung disease. The discordance between the local reading of fibrotic non-specific interstitial pneumonia and the expert reading of organising pneumonia mirrors a documented pitfall of cryobiopsy interpretation: intraluminal Masson bodies within airspaces favour organising pneumonia, whereas interstitial fibroblast foci within the alveolar wall characterise the fibrotic pneumonias. The CAN-ICE trial found only fair between-center agreement for cryobiopsy-based diagnoses, with a kappa of 0.29. In this instance, expert pathology review changed the entire treatment trajectory, and the authors argue that such review should be considered routine whenever cryobiopsy-based diagnoses drive major therapeutic decisions. Two cases over thirteen years may reflect genuine rarity, the authors concede, but under-recognition is equally plausible, given that prior cohorts attributed drug causation without systematic exclusion criteria. For clinicians, the message is twofold: organising pneumonia can flare during biomarker-confirmed bowel remission, and drug-induced causes must be rigorously excluded before the lung disease is attributed to the bowel condition—because the correct diagnosis determines whether a patient receives antifibrotics or steroids, a fork in the road with very different prognoses.

Subject of Research: A case of disease-intrinsic organising pneumonia occurring during biomarker-confirmed ulcerative colitis remission

Article Title: Disease‐Intrinsic Organising Pneumonia During Biomarker‐Confirmed Ulcerative Colitis Remission

Article References: Disease‐Intrinsic Organising Pneumonia During Biomarker‐Confirmed Ulcerative Colitis Remission. (n.d.). https://doi.org/10.1002/rcr2.70702

Image Credits: AI Generated

DOI: 10.1002/rcr2.70702

Keywords: ulcerative colitis, organising pneumonia, extraintestinal manifestations, gut-lung axis, cryobiopsy, interstitial lung disease, bronchoalveolar lavage, corticosteroids, ERS/ATS classification, mesalamine, inflammatory bowel disease, Masson bodies