Usefulness of PET/CT in distinguishing non-tuberculous mycobacterium infection and lung adenocarcinoma: An elderly case

Case Reprot

Yuki Kaji1, Esuteru Hirokawa1, *Hiroaki Satoh2
1Division of General Medicine, Mito Medical Center, University of Tsukuba-Mito Kyodo General Hospital, Japan
2Division of Respiratory Medicine, Mito Medical Center, University of Tsukuba-Mito Kyodo General Hospital, Japan
DOI: http://dx.doi.org/10.24816/jcgg.2018.v9i3.07

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Abstract

Development of lung cancer may develop in patients with pulmonary non-tuberculous mycobacterial (NTM) infection. Pulmonary NTM infection may present as mass-like consolidations mimicking lung cancer. Recent improvement in imaging modalities may enable correct diagnosis of lung cancer in these patients. We show herein an elderly patient developed in his clinical course of pulmonary NTM. Two sputum cultures were positive for acid-fast bacilli and the result polymerase chain reaction of his sputum showed a positive for Mycobacterium intracellulare. Lung cancer was detected in a follow-up chest computed tomography (CT) scan and PET/CT scan demonstrated significantly high the maximum standardized uptake values (SUVmax) of 34.5, and pulmonary NTM lesions showed SUVmax up to 4.9. The patient developed carcinomatous pleuritis, and cytological examination using the specimen obtained from pleural fluid proved to be adenocarcinoma. Although very rare, chest physicians and thoracic surgeons would be alert to the possibility of development of lung cancer in patients with pulmonary NTM infection. FDG-PET/CT scanning and a pathological approach provide important information to clarify the possibility of such a rare condition.

Keywords:

lung adenocarcinoma, non-tuberculous mycobacterial infection: FDG-PET/CT

Article Outline

  1. Introduction
  2. Case presentation
  3. Discussion
  4. Conflicts of interest statement
  5. References

Abstract

Development of lung cancer may develop in patients with pulmonary non-tuberculous mycobacterial (NTM) infection. Pulmonary NTM infection may present as mass-like consolidations mimicking lung cancer. Recent improvement in imaging modalities may enable correct diagnosis of lung cancer in these patients. We show herein an elderly patient developed in his clinical course of pulmonary NTM. Two sputum cultures were positive for acid-fast bacilli and the result polymerase chain reaction of his sputum showed a positive for Mycobacterium intracellulare. Lung cancer was detected in a follow-up chest computed tomography (CT) scan and PET/CT scan demonstrated significantly high the maximum standardized uptake values (SUVmax) of 34.5, and pulmonary NTM lesions showed SUVmax up to 4.9. The patient developed carcinomatous pleuritis, and cytological examination using the specimen obtained from pleural fluid proved to be adenocarcinoma. Although very rare, chest physicians and thoracic surgeons would be alert to the possibility of development of lung cancer in patients with pulmonary NTM infection. FDG-PET/CT scanning and a pathological approach provide important information to clarify the possibility of such a rare condition.

Keywords:

lung adenocarcinoma, non-tuberculous mycobacterial infection: FDG-PET/CT

1. Introduction

The increase in non-tuberculous mycobacterial (NTM) infections in recent years is remarkable especially in people over 50 years of age. Pulmonary NTM infection may present as a solitary nodule, mass, or mass-like consolidation mimicking lung cancer.1 Therefore, it may sometimes be difficult to diagnose development of lung cancer in patients with pulmonary NTM. To correct diagnosis in these patients, pathological and bacteriological confirmation of both diseases must be required. Especially in the elderly patients, obtaining adequate specimens for the confirmation can be a physical burden.

We show herein an elderly NTM patient who developed lung adenocarcinoma. In this case, fluorodeoxyglucose positron emission tomography (FDG-PET)/CT scan and cytological evaluation of the specimen from pleural fluid provided important information to establish a correct diagnosis.

2. Case presentation

An 88-year-old man presented with the incidental detection of a mass 30 mm in diameter in the left lung on chest computed tomography (CT), at the Mito Medical Center of the University of Tsukuba (Mito, Japan). At the age of 84, he was diagnosed as having NTM lung disease based on ATS/IDSA criteria for the disease2 as two sputum cultures were positive for acid-fast bacilli. Sputum smear examination stained positive for acid-fast bacilli and the result polymerase chain reaction of his sputum showed a positive result for Mycobacterium intracellulare. On chest CT scan at that time, the patient had radiographic findings consistent with NTM lung disease such as bronchiectasis, tree-in- bud opacities (bronchiolitis), and nodules with or without cavities in both lungs (Figure 1-A). Chest CT scan taken at the time of presentation revealed the appearance of a well-circumscribed mass in the left lower lobe of the lung that measured 30×27×18 mm with direct pleural invasion (Figure 2-B), which was not found in the CT scan taken at the first visit (Figure 2-A). Radiographic features that are consistent with NTM lung disease were also observed in this CT scan (Figure 1-B). The patient was asymptomatic except for cough and sputum and had been in good health since then. At this presentation, the physical examination was unremarkable. The routine laboratory tests were normal, as were tumor markers including carcinoembryonic antigen. Sputum smear examination stained positive for acid- fast bacilli and polymerase chain reaction of his sputum revealed Mycobacterium intracellulare. Cytological examinations of the sputa failed to demonstrate malignant cells. In the chest CT conducted at the time of 5 months after this presentation, FDG-PET/CT confirmed significantly high uptake with the maximum standardized uptake values (SUVmax) 34.5 in the mass in the lower lobe of the left lung (Figure 3). On the other hand, there was mild uptake with the SUVmax up to 4.9 in other pulmonary NTM lesions (Figure 4). Appearance of small amount of left pleural fluid was observed in the CT scan (Figure 2-C). The mass was strongly suspected lung cancer, but the patient refused to receive additional examination at that time. Seven months after the PET/CT scan, the patient had exertional dyspnea. Chest radiograph showed enlargement of the mass in the left lower lobe of the lung and massive pleural fluid (Figure 5-A). Cytological examination of the specimens obtained from pleural fluid showed adenocarcinoma cells with high nuclear-cytoplasmic ratio and abundant cytoplasm (Figure 5-B). The patient was diagnosed with pulmonary adenocarcinoma on the basis of cytological examination of specimens from pleural fluid. Thereafter, the patient did not hope to receive chemotherapy and had supportive care.

Figure 1. Chest CT scan taken at the age of 84 (A) and follow up CT scan taken at the age of 87 (B). In both CT scans, there were bronchiectasis (arrows), tree-in-bud opacities (arrow heads), and nodules with or without cavities (stars) in both lungs

Figure 2. Chest CT scan taken at the age of 84 (A), CT scan taken at the time of first presentation (B), and CT scan taken 5 months after the presentation (C). A well-circumscribed mass in the left lower lobe of the lung that measured 30×27×18 mm with direct pleural invasion was found in CT scan at the time of presentation (B), which was not found in the CT scan taken at the age of 84 (A).Enlargement of the mass and appearance of small amount of left pleural fluid (arrows) was observed in the CT scan (C)

3. Discussion

Pulmonary NTM infection can be found in any lobe or any

Figure 3. 18F-fluorodeoxyglucose positron emission tomography/ CT scan confirming uptake the maximum standardized uptake values (SUVmax) 34.5 in the mass in the lower lobe of the left lung

Figure 4. 18F-fluorodeoxyglucose positron emission tomography/ CT scan shows mild uptake with the maximum standardized uptake values (SUVmax) up to 4.9 in other pulmonary NTM lesions

Figure 5. Chest radiograph showed enlargement of the mass in the left lower lobe of the lung (arrows) and massive pleural fluid (A). Cytological examination of the specimens obtained from pleural fluid showed adenocarcinoma cells with high nuclear-cytoplasmic ratio and abundant cytoplasm (B)

segment, although the right middle lobe and the lingual are the most frequently affected. Centrilobular small nodules, tree-in-bud opacities, and consolidation are the most common findings. Diffuse ground-glass attenuation, bronchiectasis and bronchiolectasis, and large nodules are also noted in NTM.3 In addition, pulmonary NTM infection may present as a solitary nodule, mass, or mass- like consolidation mimicking lung cancer, and some authors described NTM patients complicated with development of lung cancer.3,4,5,6,7 These patients were middle age and the elderly, male dependent, and adenocarcinoma were common and all of them had Mycobacterium avium complex.4,5,6,7,8 From the viewpoint of prognostic factors, it seems that smoking and COPD are risk factors for both NTM lung disease and lung cancer.9 Due to the scarcity of the coexistence of the diseases, it has not been clarified whether the co-occurrence of NTM lung disease and lung cancer could merely be a coincident event due to random events vs. having similar risk factors. Additionally, it is not clear whether there could possibly be a cause-and-effect wherein NTM lung disease predisposes to lung cancer, lung cancer predisposes to NTM lung disease, or both. The accumulation of cases in the future will bring answers to this question.

Recently, a usefulness of FDG- PET/CT scan to differentiate between NTM and lung cancer has been reported.1,10,11 Regarding PET/CT scan, it is necessary to note that some lung cancer such as bronchoalveolar cell carcinoma and adenocarcinoma-in-situ have low SUV so a negative PET/CT scan does not rule out cancer.12,13,14 However, it is well known fact that the SUVmax value of lung cancer usually shows high values, although the SUVmax value of lung adenocarcinoma may differ depending on characteristics of the tumor such as size, histological features, and EGFR mutation.15,16,17,18 Two recent studies have reported that mean value of SUVmax was 16.7, 10.9 in lung adenocarcinoma in patients with EGFR mutation, and 13.8, 9.9 in those without17,18(Table 1). Whereas, the SUVmax value of NTM does not usually show a high value because it is an inflammatory lesion1,10,19,20,21,22,23 As shown in Table 1, some previous researchers evaluated SUVmax in pulmonary nodule in patients with NTM1,10,19,20,21,22,23 For example, Kawate et al reported two patients with a solitary pulmonary nodule due to infection with non-tuberculous mycobacteria.22 In each case, the nodule showed a high FDG uptake with the SUVmax of 13.2 and 4.8, respectively. Both cases required partial lung resection for confirmation of the histological diagnosis.22 In their review of six reported patients with solitary pulmonary nodule due to NTM infections showed that the SUV of FDG was more than 4.0 in the nodules of all these patients.22 On the other hand, however, Del Giudice et al evaluated the role of FDG PET/CT in the assessment of lung involvement in 26 NTM patients.20 According to them, NTM exhibited different radiological lung patterns with an average SUV max value at PET/CT scan of 3.59 ± 2.32 (range 1.14 to 9.01) on pulmonary lesions.20 Positive results on FDG-PET should be interpreted cautiously when evaluating solitary pulmonary nodule, especially in patients with NTM infections, however, these previous data suggested that the SUVmax in pulmonary NTM could be up to 15.0, and if the SUVmax are 15.0 or more, as shown in our patient, the lesion can be lung cancer.

In the present case, PET/CT scan demonstrated significantly high metabolic pulmonary lesions with the SUV of 34.5, consistent with lung cancer. FDG-PET/ CT scanning and a pathological approach might play an important role to clarify the possibility of development of lung cancer in patients with pulmonary TNM infection.

Table 1. The maximum standardized uptake values (SUVmax) in pulmonary nodule in patients with lung adenocarcinoma and non-tuberculous mycobacterial infection

Conflicts of interest statement

None declared.

References

  1. Hong SJ, Kim TJ, Lee JH, Park JS. Nontuberculous mycobacterial pulmonary disease mimicking lung cancer: Clinicoradiologic features and diagnostic implications. Medicine (Baltimore) 2016;95:e3978.
  2. Griffith DE, Aksamit T, Brown-Elliott BA, Catanzaro A, Daley C, Gordin F, et ATS Mycobacterial Diseases Subcommittee American Thoracic Society Infectious Disease Society of America An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases Am J Respir Crit Care Med. 2007;175:367-416.
  3. Mori S, Tokuda H, Sakai F, Johkoh T, Mimori A, Nishimoto N, et Radiological features and therapeutic responses of pulmonary nontuberculous mycobacterial disease in rheumatoid arthritis patients receiving biological agents: a retrospective multicenter study in Japan. Mod Rheumatol. 2012;22:727-37.
  4. Suehisa H, Matsuda F, Kawamoto H, Ueno T, Sawada S, Yamashita M, et Pulmonary non-tuberculous mycobacteriosis complicated with lung cancer. ftyobu Geka. 2014;67:549-52.
  5. Fujita Y, Ishii S, Hirano S, Takeda Y, Sugiyama H, Kobayashi A case of lung cancer complicated with active non-tuberculous mycobacterium (NTM) infection successfully treated with anti-cancer agents and anti-NTM agents. Nihon ftokyuki Gakkai Zasshi. 2011;49: 855- 60.
  6. Koga T, Sato R, Kamimura T, Nishimura M, Kage M, Matsuo Concurrent lung cancer in non-tuberculous mycobacteriosis: case report. fturume Med J. 2011;58:87-90.
  7. Matsumoto A, Enomoto T, Muroya Y, Sugisaki M, Shingu A, Saitoh H, et al. Pulmonary non-tuberculous mycobacteriosis (Mycobacterium intracellulare) with cavities developing in a non-small cell lung cancer patient during Nihon ftokyuki Gakkai Zasshi. 2010;48:609-13.
  8. Kobayashi K, Yano S, Kato K, Yajima H, Saito S, Watanabe M, et A case of M. avium lung disease complicated with adenocarcinoma. Nihon ftokyuki Gakkai Zasshi. 2003;41:177-80.
  9. Gitti Z, Mantadakis E, Maraki S, Samonis Clinical significance and antibiotic susceptibilities of nontuberculous mycobacteria from patients in Crete, Greece. Future Microbiol. 2011;6:1099-109.
  10. Min Z, Amlani Pulmonary Mycobacterium kansasii Infection Mimicking Malignancy on the (18)F-FDG PET Scan in a Patient Receiving Etanercept: A Case Report and Literature Review. Case Rep Pulmonol. 2014;2014:973573.
  11. Drijkoningen J, van der Pol H, de Vries PET scanning used for monitoring treatment response in Mycobacterium avium complex infection mimicking malignancy. Clin Nucl Med. 2009;34:818-20.
  12. Skoura E, Datseris IE, Exarhos D, Chatziioannou S, Oikonomopoulos G, Samartzis A, et Clinical importance of [18F]fluorodeoxyglucose positron emission tomography/computed tomography in the management of patients with bronchoalveolar carcinoma: Role in the detection of recurrence. Oncol Lett 2013;5:1687-93.
  13. Bryant AS, Cerfolio The maximum standardized uptake values on integrated FDG-PET/CT is useful in differentiating benign from malignant pulmonary nodules. Ann Thorac Surg. 2006;82:1016-20.
  14. Park EA, Lee HJ, Kim YT, Kang CH, Kang KW, Jeon YK, et EGFR gene copy number in adenocarcinoma of the lung by FISH analysis: investigation of significantly related factors on CT, FDG-PET, and histopathology. Lung Cancer. 2009;64:179-86.
  15. Farid K, Poullias X, Alifano M, Regnard JF, Servois V, Caillat-Vigneron N, et Respiratory-gated imaging in metabolic evaluation of small solitary pulmonary nodules: 18F-FDG PET/CT and correlation with histology. Nucl Med Commun. 2015;36:722-7.
  16. Nomori H, Cong Y, Sugimura H, Kato Comparing diffusion- weighted imaging and positron emission tomography for pulmonary nodules measuring from 1 to 3 cm in size. Surg Today. 2015;45:1535-41.
  17. Putora PM, Früh M, Müller FDG-PET SUV-max values do not correlate with epidermal growth factor receptor mutation status in lung adenocarcinoma. Respirology. 2013;18:734-5.
  18. Kanmaz ZD, Aras G, Tuncay E, Bahadır A, Kocatürk C, Yaşar ZA, et Contribution of ¹⁸Fluorodeoxyglucose positron emission tomography uptake and TTF-1 expression in the evaluation of the EGFR mutation in patients with lung adenocarcinoma. Cancer Biomark. 2016;16:489-98.
  19. Schmeeckle KD, Yankelevitz D, Kim JW, Sartor Increased uptake of 18F-fluorodeoxyglucose due to Mycobacterium avium complex in a solitary pulmonary nodule. J La State Med Soc. 2008;160:150-2.
  20. Del Giudice G, Bianco A, Cennamo A, Santoro G, Bifulco M, et Mazzarella G. Lung and Nodal Involvement in Nontuberculous Mycobacte rial Diseas e : PET/CT Role. Biomed Res Int. 2015;2015:353202.
  21. Fiogbe AA, Liistro G, Hoton D, Pieters Mycobacterium avium tumoral infection mimicking a lung adenocarcinoma: A potential diagnostic pitfall. Rev Pneumol Clin. 2016;72:147-51.
  22. Kawate E, Yamazaki M, Kohno T, Fujimori S, Takahashi Two cases with solitary pulmonary nodule due to non-tuberculous mycobacterial infection showing intense 18F-fluorodeoxyglucose uptake on positron emission tomography scan. Geriatr Gerontol Int. 2010;10:251-4.
  23. Kaira A case with nodular lesions with non-tuberculous mycobacterial infection and lung cancer. Nihon ftokyuki Gakkai Zasshi. 2009;47:969.

Figure 1. Chest CT scan taken at the age of 84 (A) and follow up CT scan taken at the age of 87 (B). In both CT scans, there were bronchiectasis (arrows), tree-in-bud opacities (arrow heads), and nodules with or without cavities (stars) in both lungs

Figure 2. Chest CT scan taken at the age of 84 (A), CT scan taken at the time of first presentation (B), and CT scan taken 5 months after the presentation (C). A well-circumscribed mass in the left lower lobe of the lung that measured 30×27×18 mm with direct pleural invasion was found in CT scan at the time of presentation (B), which was not found in the CT scan taken at the age of 84 (A).Enlargement of the mass and appearance of small amount of left pleural fluid (arrows) was observed in the CT scan (C)

Figure 3. 18F-fluorodeoxyglucose positron emission tomography/ CT scan confirming uptake the maximum standardized uptake values (SUVmax) 34.5 in the mass in the lower lobe of the left lung

Figure 4. 18F-fluorodeoxyglucose positron emission tomography/ CT scan shows mild uptake with the maximum standardized uptake values (SUVmax) up to 4.9 in other pulmonary NTM lesions

Figure 5. Chest radiograph showed enlargement of the mass in the left lower lobe of the lung (arrows) and massive pleural fluid (A). Cytological examination of the specimens obtained from pleural fluid showed adenocarcinoma cells with high nuclear-cytoplasmic ratio and abundant cytoplasm (B)

References

  1. Hong SJ, Kim TJ, Lee JH, Park JS. Nontuberculous mycobacterial pulmonary disease mimicking lung cancer: Clinicoradiologic features and diagnostic implications. Medicine (Baltimore) 2016;95:e3978.

  2. Griffith DE, Aksamit T, Brown-Elliott BA, Catanzaro A, Daley C, Gordin F, et ATS Mycobacterial Diseases Subcommittee American Thoracic Society Infectious Disease Society of America An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases Am J Respir Crit Care Med. 2007;175:367-416.


  3. Mori S, Tokuda H, Sakai F, Johkoh T, Mimori A, Nishimoto N, et Radiological features and therapeutic responses of pulmonary nontuberculous mycobacterial disease in rheumatoid arthritis patients receiving biological agents: a retrospective multicenter study in Japan. Mod Rheumatol. 2012;22:727-37.


  4. Suehisa H, Matsuda F, Kawamoto H, Ueno T, Sawada S, Yamashita M, et Pulmonary non-tuberculous mycobacteriosis complicated with lung cancer. ftyobu Geka. 2014;67:549-52.


  5. Fujita Y, Ishii S, Hirano S, Takeda Y, Sugiyama H, Kobayashi A case of lung cancer complicated with active non-tuberculous mycobacterium (NTM) infection successfully treated with anti-cancer agents and anti-NTM agents. Nihon ftokyuki Gakkai Zasshi. 2011;49: 855- 60.


  6. Koga T, Sato R, Kamimura T, Nishimura M, Kage M, Matsuo Concurrent lung cancer in non-tuberculous mycobacteriosis: case report. fturume Med J. 2011;58:87-90.


  7. Matsumoto A, Enomoto T, Muroya Y, Sugisaki M, Shingu A, Saitoh H, et al. Pulmonary non-tuberculous mycobacteriosis (Mycobacterium intracellulare) with cavities developing in a non-small cell lung cancer patient during Nihon ftokyuki Gakkai Zasshi. 2010;48:609-13.


  8. Kobayashi K, Yano S, Kato K, Yajima H, Saito S, Watanabe M, et A case of M. avium lung disease complicated with adenocarcinoma. Nihon ftokyuki Gakkai Zasshi. 2003;41:177-80.


  9. Gitti Z, Mantadakis E, Maraki S, Samonis Clinical significance and antibiotic susceptibilities of nontuberculous mycobacteria from patients in Crete, Greece. Future Microbiol. 2011;6:1099-109.


  10. Min Z, Amlani Pulmonary Mycobacterium kansasii Infection Mimicking Malignancy on the (18)F-FDG PET Scan in a Patient Receiving Etanercept: A Case Report and Literature Review. Case Rep Pulmonol. 2014;2014:973573.


  11. Drijkoningen J, van der Pol H, de Vries PET scanning used for monitoring treatment response in Mycobacterium avium complex infection mimicking malignancy. Clin Nucl Med. 2009;34:818-20.


  12. Skoura E, Datseris IE, Exarhos D, Chatziioannou S, Oikonomopoulos G, Samartzis A, et Clinical importance of [18F]fluorodeoxyglucose positron emission tomography/computed tomography in the management of patients with bronchoalveolar carcinoma: Role in the detection of recurrence. Oncol Lett 2013;5:1687-93.


  13. Bryant AS, Cerfolio The maximum standardized uptake values on integrated FDG-PET/CT is useful in differentiating benign from malignant pulmonary nodules. Ann Thorac Surg. 2006;82:1016-20.


  14. Park EA, Lee HJ, Kim YT, Kang CH, Kang KW, Jeon YK, et EGFR gene copy number in adenocarcinoma of the lung by FISH analysis: investigation of significantly related factors on CT, FDG-PET, and histopathology. Lung Cancer. 2009;64:179-86.


  15. Farid K, Poullias X, Alifano M, Regnard JF, Servois V, Caillat-Vigneron N, et Respiratory-gated imaging in metabolic evaluation of small solitary pulmonary nodules: 18F-FDG PET/CT and correlation with histology. Nucl Med Commun. 2015;36:722-7.


  16. Nomori H, Cong Y, Sugimura H, Kato Comparing diffusion- weighted imaging and positron emission tomography for pulmonary nodules measuring from 1 to 3 cm in size. Surg Today. 2015;45:1535-41.


  17. Putora PM, Früh M, Müller FDG-PET SUV-max values do not correlate with epidermal growth factor receptor mutation status in lung adenocarcinoma. Respirology. 2013;18:734-5.


  18. Kanmaz ZD, Aras G, Tuncay E, Bahadır A, Kocatürk C, Yaşar ZA, et Contribution of ¹⁸Fluorodeoxyglucose positron emission tomography uptake and TTF-1 expression in the evaluation of the EGFR mutation in patients with lung adenocarcinoma. Cancer Biomark. 2016;16:489-98.


  19. Schmeeckle KD, Yankelevitz D, Kim JW, Sartor Increased uptake of 18F-fluorodeoxyglucose due to Mycobacterium avium complex in a solitary pulmonary nodule. J La State Med Soc. 2008;160:150-2.


  20. Del Giudice G, Bianco A, Cennamo A, Santoro G, Bifulco M, et Mazzarella G. Lung and Nodal Involvement in Nontuberculous Mycobacte rial Diseas e : PET/CT Role. Biomed Res Int. 2015;2015:353202.


  21. Fiogbe AA, Liistro G, Hoton D, Pieters Mycobacterium avium tumoral infection mimicking a lung adenocarcinoma: A potential diagnostic pitfall. Rev Pneumol Clin. 2016;72:147-51.


  22. Kawate E, Yamazaki M, Kohno T, Fujimori S, Takahashi Two cases with solitary pulmonary nodule due to non-tuberculous mycobacterial infection showing intense 18F-fluorodeoxyglucose uptake on positron emission tomography scan. Geriatr Gerontol Int. 2010;10:251-4.


  23. Kaira A case with nodular lesions with non-tuberculous mycobacterial infection and lung cancer. Nihon ftokyuki Gakkai Zasshi. 2009;47:969.