Manchen, Peter

E-cigarette or vaping-associated lung injury (EVALI) was initially recognized as a public health problem in 2019, but pathologic changes from vaping (if any) outside the context of EVALI remain unknown. We aimed to further characterize the pathology of EVALI and vaping-associated changes in otherwise healthy patients without EVALI, including those presenting with spontaneous pneumothorax. Archives were searched for lung specimens from these patient groups (2019 to 2025). Previously reported cases were excluded. Clinical history and pathology slides were reviewed. Sixty-three patients (43 men; mean age: 36.0±15.2 y) were enrolled, including 47 wedge resections, 15 transbronchial biopsies, and 1 core biopsy. All reported current or recent vaping, and 24 reported prior or concurrent cigarette smoking. Thirty-six met criteria for EVALI and showed characteristic histologic features; novel findings included 12 (35%) with coarse lipid vacuolization and 6 (18%) with grungy proteinosis-like deposits. Eleven patients with prior suspected EVALI had chronic respiratory symptoms with airway-centered macrophages and variable airway-centered fibrosis. The remaining 16 patients presented with spontaneous pneumothoraces without EVALI and had rare foamy or lightly pigmented macrophages in airspaces but no other abnormalities beyond secondary changes from the pneumothorax. To our knowledge, this is the largest pathologic study of EVALI and the first to review histologic findings in the lungs of otherwise healthy vapers. EVALI is less common than in 2019 but is still encountered. Outside the context of EVALI, patients who vape and develop spontaneous pneumothorax have minimal histologic changes. The role (if any) of vaping in the development of pneumothorax remains unknown.

Ameloblastomas are locally aggressive odontogenic tumors that most commonly arise in the mandible and maxilla and often harbor BRAF V600E mutations. While rare extragnathic ameloblastomas have been reported, primary pulmonary cases have not been documented. We identified 3 pulmonary neoplasms with features of ameloblastoma that were submitted for consultation between 2022 and 2025 at 3 academic institutions and performed detailed clinicopathologic and molecular analysis. The tumors presented as 5.4 to 7.3 cm peribronchial solitary lung masses. All resected tumors exhibited a predominant stellate reticulum-like component composed of loosely arranged p40-reactive bland squamoid-to-spindled cells with long intercellular bridges, and streaming and swirling architecture, surrounded by palisaded columnar cells with focal reverse nuclear polarity at the interface with myxoid stroma. All tumors were immunoreactive for BRAF V600E IHC, and BRAF V600E mutations were confirmed by molecular assays, including broad next-generation sequencing on 2 cases. Florid hyperplasia of entrapped pneumocytes initially suggested a biphasic neoplasm, but the absence of BRAF V600E IHC labeling confirmed pneumocyte entrapment. Occult gnathic primary tumors were excluded by subsequent clinical examination, including negative panoramic dental x-rays. No recurrences or metastases have been observed to date. This first series of primary pulmonary ameloblastomas highlights a distinctive tumor with histologic and molecular features identical to gnathic counterparts. We discuss the potential histogenesis of these unusual tumors.

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare precursor of neuroendocrine malignancy. Diagnosis is difficult as clinical and radiological findings can be non-specific. Histological confirmation is necessary, and surgical lung biopsy is still considered the gold standard technique to aid multidisciplinary discussion. There are increasing reports of using transbronchial lung cryobiopsy (TBLC) for tissue sampling, allowing a feasible and safe alternative to diagnosis. Here we present a case of cough, dyspnoea and hypoxia in a woman ultimately diagnosed with DIPNECH using TBLC.

AimsPolymyalgia rheumatica (PMR) is a chronic autoimmune disorder that mainly affects older adults. Pulmonary disease in PMR is rare but may be under‐recognized and pathological descriptions thereof are few. We aimed to characterize diffuse parenchymal lung disease (DPLD) in PMR.Methods and resultsInstitutional archives were searched for patients having PMR and DPLD with lung tissue sampling. After excluding cases with infection, concomitant rheumatoid arthritis, or smoking‐related DPLD only, 11 patients (9 women, median age 75 years) were enrolled. Clinical history and pathology slides were reviewed. One of the 11 patients (9%) had concomitant giant cell arteritis; the remaining patients had no other rheumatological diseases. All had been treated for PMR with immunosuppression, and most presented years later (median 6 years) with non‐specific respiratory symptoms. Radiographically, bilateral ground‐glass opacities and reticulation were typical and were usually lower lobe predominant. Histologically, fibrosis was seen in 8 of 11 (73%) patients and was unclassifiable in four; non‐specific interstitial pneumonia was encountered in three patients, and usual interstitial pneumonia was seen in only one case. Evidence of acute lung injury occurred in 9 (82%) patients, including three with acute lung injury only, usually manifesting as organizing pneumonia. Diffuse alveolar haemorrhage was seen in four cases (29%), including two patients with haemoptysis and capillaritis.ConclusionsOur data corroborate prior reports of clinically significant DPLD in some patients with PMR. Histopathological findings mirror other rheumatological disorders and include diffuse alveolar haemorrhage with capillaritis. Additional studies are warranted to clarify the association between PMR and DPLD.

Transbronchial cryobiopsies (CB) are increasingly replacing surgical biopsies (video-assisted thoracoscopic/VATS biopsies) for diagnosing diffuse parenchymal lung disease (interstitial lung disease, ILD), but there is very little guidance for pathologists on CB interpretation. Here we propose a fairly simple approach. First, if the diagnosis can be made on a traditional forceps biopsy, it can be made on a cryobiopsy. Many diseases with specific features will fall into this category (eg, sarcoidosis or Langerhans cell histiocytosis). More problematic are patterns such as usual interstitial pneumonia (UIP) or nonspecific interstitial pneumonia (NSIP), in which low-power architecture is the key to diagnosis. In this circumstance, an adequate sample is crucial to look for features such as fibroblast foci, because a combination of fibroblast foci plus any patchy old fibrosis, fibrotic architectural remodeling, or honeycombing, allows a diagnosis of a UIP pattern. However, in most instances, CB will not separate the UIP patterns seen in idiopathic pulmonary fibrosis, fibrotic hypersensitivity pneumonitis, or connective tissue disease-interstitial lung disease (CTD-ILD), although giant cells/granulomas (uncommon findings) in this setting favor fibrotic hypersensitivity pneumonitis. Fibroblast foci can be difficult to differentiate from organizing pneumonia (OP), but granulation tissue plugs clearly in airspaces favor OP. Absent fibroblast foci, patchy old fibrosis, architectural distortion, and honeycombing by themselves do not allow a specific diagnosis. NSIP in CB microscopically looks like NSIP in VATS biopsies, and the presence of an NSIP or an NSIP+OP pattern is typical of CTD-ILD. All the above diagnoses require correlation with clinical and radiologic findings.

Abstract Background: Diffuse pulmonary meningotheliomatosis (DPM) is a rare, benign proliferation of minute meningothelial-like nodules ranging from 100mm – 11mm.1 The condition presents primarily in women (9:1) in middle age.2 Discovered incidentally or with mild symptoms such as dyspnea and dry cough, the imaging findings can be concerning for miliary metastatic, atypical infectious, and immune mediated diffuse parenchymal lung disease thereby complicating the diagnostic process. Case Description: A 70-year-old female never smoker presented to our pulmonary clinic for evaluation of dyspnea and dry cough. She described evaluation roughly 20 years prior that had revealed innumerable small ground glass pulmonary nodules on CT imaging. Pulmonary function testing at that time was unremarkable, and laboratory studies had only revealed a weakly (+) SSA antibody. She was referred for a right mini-thoracotomy wedge resection, with pathology demonstrating small nodules partially involving the pleura, suspected to represent hypersensitivity pneumonitis (HP), as well as, several incidentally noted pulmonary “chemodectomas”. She was trialed on inhaled therapies, antibiotics, and even a two-year course of steroids for suspected HP without notable clinical or radiologic improvement. Interestingly, she was subsequently found to have an intracranial meningioma which was treated with external beam radiation. Upon presentation at our institution, a repeat high resolution chest CT showed mosaic attenuation with innumerable groundglass nodules and micronodules in a centrilobular and peri-lymphatic distribution. There was no significant change in appearance or distribution from prior imaging (Figure 1, A-B). Rigid bronchoscopy with transbronchial lung cryobiopsy was performed with pathology showing multiple meningothelial-like nodules (Figure 1, C). This pathologic finding, in conjunction with her clinical history, including past surgical biopsy, led to a diagnosis of DPM. Discussion: This case adds to about 50 cases of DPM and the clinical significance of diffuse perivenular and interstitial meningothelial-like cell proliferations in the lung without clear malignant potential. Additionally, it provides another case to a notable collection of cases with metachronous intracranial meningioma, suggesting possible shared pathogenesis or genetic predisposition.2 While the clinical course of DPM is generally indolent, it poses diagnostic challenges due to overlapping imaging characteristics with more aggressive pulmonary pathologies. The differential may include sarcoidosis, miliary infectious and malignant etiologies, DIPNECH, and follicular bronchiolitis. Conclusions: A systematic approach to this patient's ground-glass nodules with clinical re-evaluation given ineffective empiric treatment ultimately led to the correct diagnosis. It highlights the importance of biopsy for the diagnosis of pulmonary nodules of unclear etiology even with benign clinical progression.