Abnormal Shadow on Chest Radiograph

An 87-year-old man presents to Okinawa National Hospital in Japan following referral for evaluation of an abnormal shadow on the left lower lobe of his lung. This was detected in December 2016, during a routine chest x-ray performed for lung cancer screening.

The patient says he has been healthy and had no symptoms. He is a non-smoker, with an unremarkable medical and family history. Physical examination finds no evidence of swelling in the cervical, axillary, and inguinal regions that would suggest lymphadenopathy. Auscultation of the chest notes normal breath sounds.

Laboratory test results include a total leukocyte count of 4,610 cells/mm³ and C-reactive protein level of 0.07 mg/dL (normal range: 0.0-0.3 mg/dL). Tests also reveal normal-range levels of serum tumor markers such as carcinoembryonic antigen and CYFLA.

Clinicians perform a contrast-enhanced computed tomography (CT) scan, which identifies a cavitating mass with a thick ring-enhancing irregular wall in the left lower lobe. Other lobes show no sign of bronchiectasis or consolidation.

The mass is 20×40 mm, with poorly defined margins. There is no evidence of gas collection or calcification, and no enlargement of lymph nodes in the mediastinum. A positron emission tomography (PET)/CT scan of the lesion reveals a high uptake, with a maximum standardized uptake value (SUV) of 10.1. Based on imaging results, clinicians suspect lung cancer. However, this possibility is dismissed given the absence of any signs of distant metastasis.

Clinicians perform a transbronchial lung biopsy (TBLB) of the lesion, and find no evidence of malignant cells or sputum; however, bronchial lavage fluid examinations for acid-fast bacilli are positive.

These findings -- combined with negative findings on a Mycobacterium tuberculosis polymerase chain reaction test -- suggest non-tuberculous mycobacterium (NTM) infection rather than lung cancer.

A Diagnostic Challenge

Nevertheless, differentiation of NTM infection from lung cancer can be challenging. Given the absence of other lung lesions in the pulmonary parenchyma to help confirm the provisional diagnosis of NTM pulmonary disease, the clinicians handling the case decide to perform surgery.

Examination of the frozen section biopsy of the mass results in a diagnosis of lung cancer being confirmed. A left lower lobectomy is performed, with no intraoperative complications. Final pathological examination of the mass shows a stage 1B adenocarcinoma (pT2aN0M0) with Mycobacterium avium complex (MAC) detected in the cancer tissue culture. The patient recovers without incident.

Discussion

Clinicians reporting this case¹ of lung cancer and NTM infection found in a single lung mass note that their coexistence in one solitary mass is very rare.^2-4

NTM pulmonary disease can manifest as a solitary pulmonary nodule or mass that mimics lung cancer on a CT scan, making it crucial to distinguish one from the other. A positive culture finding for sputum or bronchial lavage fluid does not exclude the possibility of concomitant lung cancer⁴; thus, the case authors urge a high degree of suspicion in such patients.

Pulmonary NTM infections have been found in 2.0-8.5% of lung cancer patients,^2,3,5,6 often in the setting of a preexisting lung disease such as chronic obstructive pulmonary disease, bronchiectasis, and previous tuberculosis.^3,4

Based on radiologic patterns, NTM pulmonary diseases are classified as fibrocavitary disease, characterized by heterogeneous nodular and cavitary opacities, or as nodular bronchiectatic disease, marked by bronchiectasis and branching centrilobular nodules.^4,7

A study⁴ of NTM pulmonary disease that presents as a solitary mass like lung cancer noted that like many benign lesions, they demonstrated poor contrast-enhancement (in 75% of the cases) and internal calcification in 43%

As well, there were CT features that mimicked those of primary lung cancer, such as a lobulated border (71% of cases) and pleural retraction in 28%.

These NTM lesions also demonstrated strong fluorodeoxyglucose uptake, thus simulating the effects of malignant lesions on PET/CT imaging. The case authors noted that traditionally an SUV of 2.5 or greater has been associated with malignant pulmonary nodules.⁷ Nevertheless, the authors caution that PET/CT imaging may not provide sufficient additional information to differentiate benign tumors from lung cancer.⁴

Given the difficulties of accurately distinguishing lung cancer from NTM pulmonary disease in a solitary mass based on imaging, microbiologic procedures such as TBLB and brushing, or lavage during bronchoscopy, are important for diagnosis.

In this case, while the patient's microbiological findings suggested NTM infection, the absence of lung lesions suggestive of NTM pulmonary disease in the pulmonary parenchyma (i.e., consolidation or bronchiectasis) led clinicians to suspect the mass was actually a malignancy.

Based on their case, the authors concluded that a positive culture result for sputum or bronchial lavage fluid does not exclude the possibility of concomitant lung cancer,⁴ even if no malignant cells are seen in a TBLB.

The authors note that although it is not well recognized, chronic NTM-related pulmonary inflammation has been linked to the development of lung cancer,^5,8 and while this patient developed an adenocarcinoma, other data^2,3 suggest a higher proportion of the squamous cell carcinoma subtype in the context of NTM.

In addition, the case report authors note, it is possible that this patient's cancer subtype might reflect the recent increase in the proportions of adenocarcinoma in lung cancer patients.^4,9 The link between histological subtype and NTM infection requires further scientific documentation, the authors stated, adding that further research is needed to clarify the role of postoperative medical therapy in patients who have had resection of an isolated solitary mass for NTM pulmonary disease.¹⁰

In conclusion, the authors said, physicians should suspect the coexistence of lung cancer and NTM infection in patients with a solitary lung mass and a positive culture result for sputum or bronchial lavage fluid.

References

1. Taira N, et al: The Presence of Coexisting Lung Cancer and Non-Tuberculous Mycobacterium in a Solitary Mass. Am J Case Rep 2018; 19: 748-751

2. Tamura A, et al: Pulmonary nontuberculous mycobacteriosis in patients with lung cancer. Kekkaku 2004; 79(6): 367–373

3. Lande L, et al: Association between pulmonary Mycobacterium avium complex infection and lung cancer. J Thorac Oncol 2012; 7(9): 1345–1351

4. Hong SJ, et al: Nontuberculous mycobacterial pulmonary disease mimicking lung cancer. Medicine (Baltimore) 2016; 95(26): e3978

5. Winthrop KL, et al: Pulmonary nontuberculous mycobacterial disease prevalence and clinical features. Am J Respir Crit Care Med 2010; 182: 977–982

6. Tamura A, et al: Relationship between lung cancer and Mycobacterium avium complex isolated using bronchoscopy. Open Respir Med J 2016; 10: 20–28

7. Lowe VJ, et al: Semiquantitative and visual analysis of FDG-PET images in pulmonary abnormalities. J Nucl Med 1994; 35: 1771–1776

8. Daley CL, Iseman M: Mycobacterium avium complex and lung cancer: Chicken or egg? Both? J Thorac Oncol 2012; 7(9): 1329–1330

9. Hosoda C, et al: Clinical characteristics of pulmonary Mycobacterium avium complex infection complicated with lung cancer. Kekkaku 2014; 89(8): 691–695

10. Johnson MM, Odell JA: Nontuberculous mycobacterial pulmonary infections. J Thorac Dis 2014; 6(3): 210–220

Comment