December 2022 – Pulmonary

A 65-year-old woman presents with a history of bronchiectasis, asthma, previous fungal and non-tuberculous mycobacteria infection, and psoriatic arthritis status post methotrexate and other immunosuppressive treatment. A recent CT showed soft tissue masses concerning for malignancy in the left upper and lower lobes, but no associated activity on PET/CT is seen. Bronchoscopy showed white friable endobronchial masses corresponding to the CT masses, sampled by endobronchial biopsy.

Figure 1: Intraluminal material (20x, H&E)
Figure 2: Intraluminal material (40x, H&E)
Figure 3: Intraluminal material (40x, H&E)
Figure 4: Airway wall (20x, H&E)

Based on the H&E morphology, what is the most common causative agent for this condition?

  • Fusarium vasinfectum
  • Mycobacteria abscessus
  • Aspergillus fumigatus
  • Histoplasma capsulatum
  • Candida albicans

The correct answer is ...

Aspergillus fumigatus.

Biopsies of the mass demonstrate large amounts of mucin and proteinaceous exudates containing Charcot-Leyden crystals and numerous (often necrotic) eosinophils, arranged in a lamellar configuration, consistent with allergic mucin. 

There are also fragments of benign airway mucosa with increased submucosal eosinophils, focal mucus cell hyperplasia, basement membrane thickening, and Charcot-Leyden crystals. No granuloma or malignancy are identified. The airway changes are compatible with asthma.

Grocott Methenamine Silver and Ziehl-Neelsen stains were negative for fungal and mycobacterial organisms, respectively. 

The presence of allergic mucin with background asthma-like airway changes, and a clinical history of asthma, is highly suggestive of allergic bronchopulmonary aspergillosis (ABPA). A positive GMS stain, typically showing scattered fragmented fungal hyphae, would have been diagnostic of ABPA.1 However, as in this case, fungi are not always identified on GMS in cases of ABPA. Thus additional clinical work-up will be necessary to confirm the diagnosis. In this patient, the masses seen on imaging likely  correspond to impacted mucus. 

ABPA is caused by hypersensitivity to fungi, usually to Aspergillus species, particularly A. fumigatus, but may be caused by other fungi as well (e.g., Candida albicans, Fusarium vasinfectum, Curvularia lunata, Helminthosporium, etc.). Hence it is also known as allergic bronchopulmonary fungal disease.1

Clinically, ABPA is seen mostly in patients with asthma, and occasionally those with cystic fibrosis.2 However, rare cases of ABPA without asthma or cystic fibrosis have been reported.As such, ABPA often presents as poorly controlled asthma and/or acute pneumonia secondary to bronchial obstruction. Expectoration of brownish mucus plugs is a characteristic symptom, but is seen only in a third of the patients. Some patients are asymptomatic.1,2

On CT imaging, mucus impaction and upper-lobe bronchiectasis are typical findings. Although impacted mucus is commonly hypodense, the presence of high-attenuation mucus (denser than paraspinal skeletal muscle) indicates severe disease, and is considered pathognomonic for ABPA.The impacted mucus may also present radiographically as V- or Y-shaped densities or a “cluster of grapes” in the proximal bronchi, with associated distal collapse or consolidation. Rounded densities are a rare imaging finding in ABPA, and may cause confusion with neoplasms.1

Pathologically, ABPA manifests most often as mucoid impaction of bronchi (MIB), frequently accompanied by eosinophilic pneumonia and/or bronchocentric granulomatosis. The histologic hallmark of MIB is the presence of allergic mucin, which is inspissated mucin with a characteristic lamellar appearance caused by alternating layers of degenerating cells (mostly eosinophils) and blue-gray to eosinophilic mucin, as seen in this case. Charcot-Leyden crystals — considered to be eosinophil breakdown products — are always present in allergic mucin. These crystals are greatly variable in size, and appear bipyramidal in longitudinal section, but hexagonal in cross section. Neutrophils are never numerous. GMS stains may highlight scattered, fragmented fungal hyphae in the mucin. Given the importance of allergic mucin for the diagnosis, intraluminal mucinous material in bronchiectasis should be sampled, and not washed out and discarded.1,2

Further to MIB, lung parenchyma adjacent to ABPA often shows eosinophilic pneumonia, featuring alveolar filling by eosinophils and macrophages. In airways distal to MIB, bronchocentric granulomatosis is often also present, showing airway-centric necrotizing granulomas that may destroy bronchioles. However, as bronchocentric granulomas may also appear in the settings of other infections, rheumatoid arthritis, and granulomatosis with polyangiitis, careful histologic assessment and clinical correlation is necessary, especially in patients without a known asthmatic history.1,2,4

ABPA is typically diagnosed clinically, by combining clinical, immunologic/microbiological, and imaging findings. Diagnostic criteria generally include a history of asthma or cystic fibrosis, peripheral blood eosinophilia, elevated serum IgE (total and aspergillus-specific), bronchiectasis on CT, and immediate cutaneous reactivity to aspergillus antigens. However, a widely accepted diagnostic criteria has yet to be established.1,2,5

Treatment for ABPA involves corticosteroids and sometimes antifungal agents. Anti-IgE agents such as omalizumab are sometimes used as second-line treatment. Early diagnosis and treatment of ABPA is important, especially in cases without clinical suspicion, as recurrences are common in untreated cases and may lead to irreversible fibrosis.1,2


  1. Katzenstein, AL., Diagnostic Atlas of Non-Neoplastic Lung Disease : A Practical Guide for Surgical Pathologists. 2016: Demos Medical.
  2. Agarwal R, Muthu V, Sehgal IS, Dhooria S, Prasad KT, Aggarwal AN. Allergic bronchopulmonary aspergillosis. Clin Chest Med. 2022 Mar;43(1):99-125. doi:10.1016/j.ccm.2021.12.002. PMID: 35236565.
  3. Kaur P, Kumar P, Randev S, Guglani V. Allergic bronchopulmonary aspergillosis without asthma or cystic fibrosis. Paediatr Int Child Health. 2020 Aug;40(3):199-201. doi:10.1080/20469047.2020.1744872. Epub 2020 Apr 2. PMID: 32238049.
  4. Rosen Y. Pathology of Granulomatous Pulmonary Diseases. Arch Pathol Lab Med. 2022 Jan 2;146(2):233-251. doi:10.5858/arpa.2020-0543-RA. PMID: 33905479.
  5. Saxena P, Choudhary H, Muthu V, et al. Which are the optimal criteria for the diagnosis of allergic bronchopulmonary aspergillosis? A latent class analysis. J Allergy Clin Immunol Pract. 2021 Jan;9(1):328-335.e1. doi:10.1016/j.jaip.2020.08.043. 

Cheuk Ki (Jackie) Chan, M.D.

Fellow, Pulmonary Pathology
Mayo Clinic

Marie-Christine Aubry, M.D.

Consultant, Anatomic Pathology 
Mayo Clinic
Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science

MCL Education

This post was developed by our Education and Technical Publications Team.