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

The patient’s blood counts told the first part of the story. He was severely anemic and profoundly neutropenic, with an absolute neutrophil count of just 150 cells per microliter—far below the threshold of 500 cells per microliter that clinicians regard as a major risk factor for invasive aspergillosis. Neutrophils are the body’s first line of defense against filamentous fungi, engulfing and destroying inhaled spores before they can germinate into invasive hyphae. When chemotherapy strips that defense away, ubiquitous environmental molds that most people breathe in daily without consequence can colonize and invade tissue with alarming speed. Prolonged neutropenia lasting more than 20 days is among the strongest known predisposing factors, and the cumulative risk of invasive aspergillosis climbs to roughly 70 percent after 34 days of persistent neutropenia in vulnerable patients.

What happened next is what makes this case remarkable. A chest computed tomography scan revealed a mass-like lesion along the posterior wall of the trachea, just below the suprasternal notch. Critically, the scan showed no evidence of involvement of the lung parenchyma itself—the tissue where pulmonary aspergillosis almost always announces itself. Invasive pulmonary aspergillosis, the most feared form of the disease, typically produces nodules, halos of hemorrhage, or cavitary lesions within the lung tissue, and radiologists use these patterns to guide early treatment. Here, the lungs appeared spared. The infection had instead declared itself as a solitary, obstructing lesion inside the central airway, a pattern that mimics an endobronchial tumor or an aspirated foreign body far more than a fungal infection.

Flexible bronchoscopy settled the question of what was occupying the trachea, though not before revealing how dangerous the situation had become. The scope encountered a whitish, irregular endoluminal mass with elongated, intertwined projections and a pseudomembranous appearance—classic visual features of fungal growth—situated in the mid-trachea. The lesion was obstructing enough that the bronchoscope could not be advanced beyond it, meaning the medical team could not visually assess the distal airways for further disease, mucus impaction, or more extensive tracheobronchial involvement. Notably, the visible mucosa showed no overt invasion, necrosis, or active bleeding, and biopsies were taken without complication.

Laboratory analysis of the sampled tissue provided the definitive answer. Microscopy demonstrated septate hyphae branching at acute angles of approximately 45 degrees—the morphological signature of Aspergillus species—and polymerase chain reaction testing confirmed Aspergillus fumigatus as the causative organism. That identification is hardly surprising from an epidemiological standpoint: A. fumigatus accounts for more than 90 percent of human aspergillosis cases. The fungus is found everywhere—soil, decaying vegetation, water, food, and air—and infects hosts almost exclusively through inhalation of airborne spores, which helps explain why the respiratory tract bears the brunt of disease. Research also suggests A. fumigatus adheres to airway epithelium more effectively than related species such as A. flavus or A. niger, potentially giving it a particular advantage in colonizing the tracheobronchial tree.

Treatment was initiated promptly with amphotericin B and voriconazole, the workhorse antifungals for invasive aspergillosis. It did not matter. The patient deteriorated rapidly and died of respiratory failure within 36 hours of diagnosis. The authors of the report acknowledge that the precise mechanism of this fulminant collapse remains uncertain. The obstructing tracheal lesion itself likely played a central role—endobronchial fungal proliferation can critically narrow the airway lumen and precipitate respiratory failure—but the inability to examine beyond the obstruction means distal airway spread could not be excluded. In a patient with essentially no neutrophil defense, the authors note, multiple converging factors may have driven the fatal outcome.

The rarity of this presentation underscores its diagnostic difficulty. Endobronchial aspergillosis, defined by endoluminal fungal growth within the tracheobronchial tree, is an uncommon manifestation of Aspergillus disease. A 2019 review by Ngu and colleagues identified only 28 documented cases worldwide, most occurring in Asian males with a mean age of 58 years, and a separate series described by Huang and colleagues found 17 cases with similar demographics. The condition is frequently discovered incidentally during bronchoscopy performed for other reasons, such as evaluating hemoptysis. Symptoms—fever, breathlessness, chest pain, cough, and bleeding—are nonspecific, and risk factors include any form of immunosuppression as well as underlying lung disease. In a 2011 series of ten patients reported by Ma and colleagues, all had identifiable predisposing conditions such as tuberculosis, lung cancer, or foreign body aspiration, and only two had concurrent parenchymal lung involvement, a pattern echoed by the present case.

The stakes of missing or delaying diagnosis are stark. Among patients with severe airway aspergillosis who require mechanical ventilation, mortality reaches 94 percent, compared with 25 percent among those who do not—a difference that reflects both advanced disease at presentation and the mechanical consequences of airway obstruction. Diagnosis itself is far from straightforward. The traditional gold standard, fungal culture, is limited by the difficulty of obtaining adequate samples from hemodynamically unstable patients, by coagulopathies such as thrombocytopenia that make biopsy risky, and by false-negative results in patients already receiving antifungal therapy. Indirect methods fill some of the gap: galactomannan detection in serum or bronchoalveolar lavage fluid shows reasonable reliability in hematologic malignancy, though its sensitivity ranges widely from 44 to 90 percent, and false positives occur with certain antibiotics and with dimorphic fungal infections. Beta-D-glucan testing, meanwhile, lacks specificity for aspergillosis altogether.

Treatment of endobronchial aspergillosis remains unstandardized, with management individualized case by case. Most clinicians favor combining systemic antifungal therapy with interventional bronchoscopy to debulk obstructing lesions, and favorable outcomes have been reported with bronchoscopically guided resection combined with drug therapy. Some experts have argued for conservative approaches, noting that systemic agents may penetrate airway lesions poorly, while intolerance or resistance to azoles, or competing infections, can push clinicians toward surgical resection. The pharmacology is also evolving: liposomal amphotericin B carries less nephrotoxicity than the deoxycholate formulation, but adverse effects including renal tubular acidosis, hypomagnesemia, and hypokalemia have shifted general clinical preference toward azoles and echinocandins for pulmonary disease.

The authors are candid about the limits of their own report. Histopathological assessment was confined to the obstructing endoluminal lesion; because of the patient’s critical condition and the risk of procedure-related complications, no biopsies were taken from the tracheal wall or cartilage. That means direct evidence of mucosal, submucosal, or cartilaginous invasion was never obtained, and the lesion could not be definitively classified as invasive or necrotizing tracheobronchitis rather than more superficial endobronchial disease. The pseudomembranous bronchoscopic appearance, the profound neutropenia, and the explosively fatal course all hint at a more aggressive process, but certainty was impossible. What the case establishes beyond doubt is the clinical lesson the authors emphasize: endobronchial Aspergillus infection belongs on the differential for any immunocompromised patient with airway obstruction, even when chest imaging shows the lungs themselves are clear. In this patient, an isolated tracheal lesion—invisible to the usual radiologic playbook—was enough to kill within two days of identification, a reminder that in the profoundly neutropenic host, the absence of parenchymal disease offers no reassurance at all.

Subject of Research: A fatal case of isolated endobronchial Aspergillus fumigatus infection in a neutropenic lymphoma patient without lung parenchymal involvement

Article Title: Endobronchial Aspergillosis Presenting as an Isolated Airway Lesion in an Immunocompromised Patient

Article References: Sadeghi, M., Sadat Hosseini Khajouei, F., GhanbarAliAkhavan, H., & Soleimani, A. M. (2026). Endobronchial Aspergillosis Presenting as an Isolated Airway Lesion in an Immunocompromised Patient. Respirology Case Reports, 14(9), Article e70701. https://doi.org/10.1002/rcr2.70701

Image Credits: AI Generated

DOI: 10.1002/rcr2.70701

Keywords: aspergillosis, Aspergillus fumigatus, endobronchial aspergillosis, neutropenia, immunocompromised, bronchoscopy, tracheal obstruction, invasive fungal infection, lymphoma, chemotherapy, respiratory failure, case report