Pulmonary infections mimicking malignancy on bronchoscopy: A retrospective single‐center study in Japan

Abstract Background Pulmonary infections can imitate pulmonary neoplasms. Pulmonary tuberculosis (TB) is a typical example of an infection that mimics cancer and results in unexpected exposure of healthcare workers to TB. A large number of patients with suspected lung malignancy are referred to cancer centers, although the epidemiology of the final diagnosis is unclear in Japan. This study aimed to determine the frequency and nature of pulmonary infections that imitate malignancy among patients with presumed lung cancer that is subsequently diagnosed as a pulmonary infection based on bronchoscopy findings. We also aimed to identify the prevalence of formerly undiagnosed pulmonary tuberculosis that could pose an occupational risk to healthcare workers. Methods This single‐center retrospective cross‐sectional study included patients with suspected pulmonary malignancy who underwent bronchoscopy at a tertiary care cancer center in Japan between April 2017 and March 2020. Electronic medical records of the bronchoscopy database were reviewed to identify the final diagnoses recorded by physicians. Results Among the 460 patients enrolled in the present study, 362 (78.7%) and 8 (1.7%) had primary or metastatic pulmonary lesions and benign lesions, respectively. Sixty‐six patients (14.3%) had nonspecific findings or other pulmonary diseases. Infection was confirmed in 24 patients (5.2%). Mycobacterial infections (n = 16) were the most frequent infectious disease; four patients had TB and 12 had nontuberculous mycobacterial infections. Conclusions Despite the rare occurrence of TB in patients with suspected lung malignancy, healthcare workers should remain vigilant regarding the possibility of TB to prevent occupational exposure during invasive procedures such as routine bronchoscopy.


| INTRODUC TI ON
Pulmonary infections can imitate pulmonary neoplasms. In particular, pulmonary tuberculosis (TB) is a leading example of an infection that mimics cancer 1 and is well known as a diagnostic chameleon that can resemble a malignancy. TB and lung cancer present with similar clinical symptoms (fever, cough, sputum, hemoptysis, weight loss, anorexia, etc) and radiological findings. 2 The rate of incidence of newly notified TB cases in Japan was 12.3 per 100 000 population in 2018, 3  Association for Bronchology included a recommendation that healthcare workers should wear a fit-tested N95 particulate respirator to minimize exposure to airborne TB during bronchoscopy of patients with suspected pulmonary TB. 5 There are several reports from other countries with regard to lung infections that mimic cancer, although some of them are endemic fungal infections and the epidemiology differs from that in Japan. 6,7 Rolston et al reported pulmonary infections that mimic cancer at a US cancer center, wherein 46% of the infections were endemic fungal infections (eg, histoplasmosis, cryptococcosis, and coccidioidomycosis). 6 Similarly, Homrich et al reported lung infections that mimic cancer in a Brazilian university hospital, and approximately 20% of the infections were endemic mycoses. 7 In Japan, reports of these abovementioned infections are incredibly scarce. 8 Thus, this study was conducted to determine the frequency and nature of pulmonary infections that imitate malignancy among patients with presumed lung cancer that is subsequently diagnosed as a pulmonary infection based on findings from bronchoscopy. A secondary objective of our study was to identify the prevalence of formerly undiagnosed pulmonary tuberculosis that could pose an occupational risk to healthcare workers.

| PATIENTS AND ME THODS
This retrospective analysis covering a 3 year period enrolled patients who were referred to our Cancer Center Hospital, Japan-a 500-bed tertiary care hospital wherein approximately 11 000 patients are admitted per year. We extracted information from the bronchoscopy database for all adult patients (age ≥ 18 years) who underwent bronchoscopy between April 1, 2017, and March 31, 2020. The electronic medical records of the bronchoscopy database were reviewed, and the final diagnoses recorded by the physicians were identified and collated. Patients who underwent bronchoscopy for nondiagnostic purposes (treatment and observation only) and duplicate patients (patients who underwent more than two bronchoscopies) were excluded. This study was approved by the institutional ethics committee, and all patient information was anonymized before the analysis.
The need for consent was waived by the approving authority.

| Data collection
The following patient information was extracted from the medical records: age, gender, histologic diagnosis, symptoms of pulmonary infection, causative organisms, and indications for bronchoscopy.

| Statistical analysis
All data analyses were conducted using SPSS version 18 (SPSS Inc).

| RE SULTS
We screened 609 patients for inclusion and excluded 149 based on the prespecified study eligibility criteria ( Figure 1). The final analysis dataset included 460 patients (median age 70 years, interquartile range 63-76 years; males 63.3%). Among these 460 patients, 421 (91.5%) were outpatients and 39 (8.5%) were inpatients. Table 1 Table 2 presents the microbiological details at initial presentation for these 24 patients. Among these 24 patients, 12 (50.0%) were asymptomatic and the remaining 12 presented with various respiratory symptoms, with cough being the most common symptom (33.3%).

| D ISCUSS I ON
In cancer centers in Japan, such as this study center, many patients are referred for the evaluation of a presumptive diagnosis of lung cancer (most often, based on routine radiographic studies). However, it is important to clarify the frequency and nature of other diseases that imitate cancer. We found that among patients referred for the confirmation of suspected pulmonary malignancy, 24 (5.2%) patients were confirmed to have lung infections. Of these 24 patients, 4 (16.7%) were unexpectedly found to have pulmonary TB.

F I G U R E 2
Chest computed tomography (CT) scan of an 85-y-old male with intraductal papillary mucinous neoplasms (IPMN) of the pancreas showing a mass with a cavity and surrounding nodules in the right lower lobe, which was diagnosed as Mycobacterium tuberculosis

F I G U R E 3
Chest computed tomography (CT) scan of a 68-y-old female with postoperative left upper lobe lung cancer. A large lesion is seen in the right middle lobe, which was diagnosed as Mycobacterium avium using sputum that was collected by endotracheal suctioning The frequency of lung infections that mimic cancer was low, at 5.2%, in this study. The spectrum of these infections varies geographically and may be dependent on the regional prevalence of a particular infection. These findings suggested that pulmonary mycobacterial infections can mimic lung malignancies. Not only does pulmonary TB mimic lung malignancies 1,2 , but also NTM infections can imitate lung malignancy. 12  warranted to obtain more information on the epidemiology of pulmonary infections presenting as malignancies in Japan. However, this study's strength is that this is the first research to describe the epidemiology of infections that mimic cancer at Japanese cancer centers.
In conclusion, tuberculosis was diagnosed in 4 (0.9%) of the 460 patients who underwent bronchoscopy during a 3 year study period.
Healthcare workers should consider the use of higher-grade respiratory precautions, such as a fit-tested N95 particulate respirator, to prevent occupational exposure to TB during routine bronchoscopy.

CO N FLI C T O F I NTE R E S T
The authors have stated explicitly that there are no conflicts of interest in connection with this article.

AUTH O R ' S CO NTR I B UTI O N S
NI contributed to the study conception and design; NI and YM pre-

AUTH O R S H I P S TATEM ENT
All authors meet the ICMJE authorship criteria.

DATA AVA I L A B I L I T Y S TAT E M E N T
The dataset used and/or analyzed in this study are available in the Supporting Information.