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Chest Pain and a Cavitary Lung Mass in a Woman With Diabetes


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Chest Pain and a Cavitary Lung Mass in a Woman With Diabetes

Alan Koff, MBBS; Maricar Malinis, MD

A 55-year-old womanfrom the Southeastern US with a history of smoking, poorly con- trolled type 2 diabetes mellitus (hemoglobin A1clevel, 15.5%), and chronic pain from osteo- arthritis treated with inhalational medical marijuana presented with 4 months of produc- tive cough, 22.7-kg (50-lb) weight loss, subjective fevers, and 3 days of worsening chest pain.

Chest computed tomography (CT) showed a large right upper lobe cavitary mass.

She was treated empirically with intravenous vancomycin and piperacillin-tazobactam.

Bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial biopsy was per- formed. Lung tissue was sent for bacterial, fungal, mycobacterial, and Nocardia cultures and for histopathology. BAL cultures grew 100 colony-forming units (CFUs)/mL of group B strep- tococci and 1 CFU/mL of Aspergillus niger. Results of acid-fast bacilli (AFB) smear and GeneXpert MTB/RIF testing were negative. Voriconazole was added to her treatment. Trans- bronchial biopsy histopathology showed acute and chronic inflammation, granulation tis- sue and necrosis, and negative fungal and AFB stains.

Two weeks later, the patient reported worsening right-sided chest pain provoked by pal- pation, right arm movement, and deep inspiration. Repeat chest CT demonstrated cavitary mass enlargement with possible pleural invasion (Figure 1, left). She developed hypoxemia and required intubation. A right-sided tension pneumothorax developed and required emer- gency chest tube placement, which yielded charcoal-colored pleural fluid (Figure 1, right).

Diagnosis Fungal empyema

What to Do Next

D.Perform right upper lobe resection

The key to the correct diagnosis was recognizing that the tension pneumothorax after intubation suggested rupture of the right-sided cavitary lesion into the pleural space. The charcoal-colored pleural fluid is characteristic of the melanin-producing Aspergillus niger.

A change in antimicrobial therapy would not be sufficient to manage this complication. Voriconazole is favored over amphotericin B for Aspergillus spp. Without malignancy, radiation therapy is not indicated.


The differential diagnosis of a cavitary lung mass includes infection, malignancy, or autoimmune disease. In patients with immunosup-

pression from diabetes, infection should be considered. Fevers, weight loss, and chronic productive cough are consistent with Mycobacterium tuberculosis or nontuberculous mycobacteria, but negative AFB smears and Xpert MTB/RIF results (for Mycobacte- rium tuberculosis) from the BAL makes this less likely. Prior resi- dence in the Southeastern US is associated with cavitary histoplas- mosis or blastomycosis, showing small intracellular yeast or broad- based budding yeast on histopathology, respectively. The lungs may be the primary site of mold infections (eg, Aspergillus or Mucorales spp), which cause significant morbidity and mortality.

Mold in the sputum may be considered a contaminant but should be further evaluated in patients with a cavitary lung lesion or underlying risk factors. Pulmonary cavitation may be caused by a necrotizing bacterial infection (eg, Staphylococcus aureus, Klebsiella pneumoniae, anaerobes) or bacterial superinfection of existing cavities. Noninfectious causes of cavitary lung disease Figure 1. Left, Computed tomography scan of the chest demonstrating large right upper lobe cavitary lesion, layering debris, and bronchial wall thickening.

Right, Charcoal-black appearance of the pleural fluid seen in the atrium of the patient’s right-side chest tube placed for tension pneumothorax.


A.Change antimicrobial therapy to meropenem and vancomycin

B.Change voriconazole to liposomal amphotericin B

C.Consult radiation oncology immediately

D.Perform right upper lobe resection

Clinical Review & Education

JAMA Clinical Challenge

jama.com (Reprinted) JAMA Published online May 22, 2020 E1

© 2020 American Medical Association. All rights reserved.

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include malignancy (eg, primary lung cancer, metastatic squamous cell carcinoma), granulomatosis with polyangiitis, or thromboem- bolism with pulmonary infarction.

Pulmonary aspergillosis is more common in the setting of pro- longed neutropenia, high-dose corticosteroids, or lung transplan- tation but should also be considered in patients with chronic lung disease due to cigarette smoking, inhaled marijuana use, malnutri- tion, alcohol abuse, or poorly controlled diabetes. This patient de- veloped subacute invasive pulmonary aspergillosis (SIPA) due to Aspergillus niger. Diagnosing SIPA requires at least 3 months of symp- toms (eg, productive cough, weight loss, fevers), a cavitary lung le- sion with or without a fungus ball (intracavitary rounded consolida- tion), and microbiologic evidence such as an elevated serum Aspergillus IgG level, positive respiratory cultures, or lung histopa- thology demonstrating fungal hyphae. Historically, itraconazole was the drug of choice, but voriconazole has more predictable drug levels and an improved safety profile.2,3These drugs inhibit P450 enzymes and are also metabolized by P450 enzymes. Therefore, po- tential drug interactions must be considered. Monitoring serum drug concentrations is recommended to help ensure that levels remain in the therapeutic window.2Newer triazole antifungals such as posaconazole and isavuconazole are increasingly prescribed for in- vasive aspergillosis, although data for treating SIPA are limited.

Amphotericin B or the echinocandins (eg, anidulafungin) may be con- sidered for resistant or refractory infection.2,3Treatment duration

is often greater than 6 months—sometimes years. Optimal dura- tion varies depending on the rate of clinical improvement and sur- gical intervention.3Clinical monitoring of symptoms and serial imaging alone may be reasonable for asymptomatic patients with- out significant respiratory impairment.3While surgery may be cu- rative when infection is completely resected, relapse is common.4 Because of risks associated with operative treatment, resection is typically reserved for those with treatment intolerance, refractory disease, refractory hemoptysis, or local complications such as rup- ture into the pleural space.3,4

Patient Outcome

Due to her rapid decline and concern for empyema, the patient underwent emergent right upper lobe resection (Figure 2A).

Pathology showed acute necrotizing pneumonia and invasive fun- gal hyphae (Figure 2B), with calcium oxalate crystals consistent with Aspergillus niger (Figure 2C). Morphologic appearance on Sabouraud dextrose media was diagnostic of Aspergillus niger (Figure 2D). Serum (1-3)-β-D-glucan and galactomannan were undetectable. BAL galactomannan index was 5.27 (normal, <0.5).

Citrobacter freundii and Klebsiella oxytoca were isolated from the pleural fluid, suggesting possible superinfection. For fungal empy- ema, she was treated with voriconazole and anidulafungin for 2 weeks and discharged to a skilled nursing facility for rehabilitation and continued receipt of voriconazole.


Author Affiliations: Yale School of Medicine, Section of Infectious Diseases, Department of Medicine, New Haven, Connecticut.

Corresponding Author: Maricar Malinis, MD, Yale School of Medicine, PO Box 208022, New Haven, CT 06520-8022 (maricar.malinis@yale.edu).

Section Editor: Mary McGrae McDermott, MD, Deputy Editor.

Published Online: May 22, 2020.


Conflict of Interest Disclosures: None reported.

Additional Contributions: We thank Santiago Delgado, MD (Department of Pathology and Laboratory Medicine, Yale University) for providing

slides and thank the patient for providing permission to share her information. Dr Delgado received no compensation for his contributions.

Submissions: We encourage authors to submit papers for consideration as a JAMA Clinical Challenge. Please contact Dr McDermott at mdm608@northwestern.edu.


1. Nam HS, Jeon K, Um SW, et al. Clinical characteristics and treatment outcomes of chronic necrotizing pulmonary aspergillosis: a review of 43 cases.Int J Infect Dis. 2010;14(6):e479-e482.

2. Denning DW, Cadranel J, Beigelman-Aubry C, et al; European Society for Clinical Microbiology and

Infectious Diseases and European Respiratory Society. Chronic pulmonary aspergillosis: rationale and clinical guidelines for diagnosis and management.Eur Respir J. 2016;47(1):45-68.

3. Patterson TF, Thompson GR III, Denning DW, et al. Practice guidelines for the diagnosis and management of aspergillosis. Clin Infect Dis. 2016;

63(4):e1-e60. doi:10.1093/cid/ciw326 4. Endo S, Sohara Y, Murayama F, et al. Surgical outcome of pulmonary resection in chronic necrotizing pulmonary aspergillosis. Ann Thorac Surg.

2001;72(3):889-893. doi:10.1016/S0003-4975(01) 02884-3


Figure 2. A, Right upper lobe resection with cavity hyperpigmented lung mass.

B, Fungal hyphae on surgical pathology (Gomori methanamine silver, original

magnification ×40). C, Calcium oxalate crystal produced by Aspergillus niger.

D, Growth of melanin-pigmented Aspergillus niger on Sabouraud dextrose media.

Clinical Review & Education JAMA Clinical Challenge

E2 JAMA Published online May 22, 2020 (Reprinted) jama.com

© 2020 American Medical Association. All rights reserved.

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