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Published in: BMC Infectious Diseases 1/2018

Open Access 01-12-2018 | Research article

Outcome of untreated lung nodules with histological but no microbiological evidence of tuberculosis

Authors: Che-Liang Chung, Yen-Fu Chen, Yen-Ting Lin, Jann-Yuan Wang, Shuenn-Wen Kuo, Jin-Shing Chen

Published in: BMC Infectious Diseases | Issue 1/2018

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Abstract

Background

The outcome of lung nodule(s) with histopathological findings suggestive of tuberculosis (TB) but lack of microbiologic confirmation remains unclear. Whether these patients require anti-TB treatment remains unknown. The aim of the study was to compare the risk of active TB within 4 years in untreated patients with histological findings but no microbiological evidences suggestive of TB.

Methods

From January 2008 to June 2013, patients with either solitary or multiple lung nodules having histological findings but no microbiological evidences suggestive of TB were identified from a medical center in Taiwan and were followed for 4 years unless they died or developed active TB.

Results

A total of 107 patients were identified. Among them, 54 (51%) were clinical asymptomatic. Biopsy histology showed granulomatous inflammation in 106 (99%), and caseous necrosis was present in 55 (51%) cases. Forty (37%) patients received anti-TB treatment, and 21 (53%) of them had adverse events, including 13 initially asymptomatic patients. Anti-TB treatment was favored in patients with caseous necrosis, whereas observation was preferred in subjects whose nodules were surgically removed. Only 1 case in the untreated group developed culture-confirmed active pulmonary TB during 4-year follow-up (1 case per 251.2 patient-years). None of the 16 cases having co-existing histologic finding of malignancy became incident TB case within a follow-up of 56.7 patient-years.

Conclusions

In patients having lung nodules with only histologic features suggestive of TB, the incidence rate of developing active TB was low. Risk of adverse events and benefit from immediate treatment should be carefully considered.
Literature
1.
go back to reference Centers for Disease Control, Minitry of Health and Welfare, Taiwan: Taiwan Tuberculosis Control Report 2013. 2014. Centers for Disease Control, Minitry of Health and Welfare, Taiwan: Taiwan Tuberculosis Control Report 2013. 2014.
2.
go back to reference Sihoe A, Yew W. Role of surgery in the diagnosis and Management of Tuberculosis. In: Schlossberg D, editor. Tuberculosis and nontuberculous mycobacterial infections. 6th ed. Washington, DC: ASM Press; 2011. p. 141–61. Sihoe A, Yew W. Role of surgery in the diagnosis and Management of Tuberculosis. In: Schlossberg D, editor. Tuberculosis and nontuberculous mycobacterial infections. 6th ed. Washington, DC: ASM Press; 2011. p. 141–61.
3.
go back to reference Zumla A, James DG. Granulomatous infections- etiology and classification. Clin Infect Dis. 1996;23(7):146–58.CrossRef Zumla A, James DG. Granulomatous infections- etiology and classification. Clin Infect Dis. 1996;23(7):146–58.CrossRef
4.
go back to reference Selman M, Pardo A, King TE Jr. Hypersensitivity pneumonitis: insights in diagnosis and pathobiology. Am J Respir Crit Care Med. 2012;186(4):314–24.CrossRef Selman M, Pardo A, King TE Jr. Hypersensitivity pneumonitis: insights in diagnosis and pathobiology. Am J Respir Crit Care Med. 2012;186(4):314–24.CrossRef
5.
go back to reference Ma Y, Gal A, Koss MN. The pathology of pulmonary sarcoidosis: update. Semin Diagn Pathol. 2007;24(3):150–61.CrossRef Ma Y, Gal A, Koss MN. The pathology of pulmonary sarcoidosis: update. Semin Diagn Pathol. 2007;24(3):150–61.CrossRef
6.
go back to reference Centers for Disease Control, Minitry of Health and Welfare, Taiwan. Taiwan Guidelines for TB Diagnosis & Treatment (6E). 6th ed. Taiwan: Centers for Disease Control, Ministry of Health and Welfare, R.O.C.(Taiwan); 2017. Centers for Disease Control, Minitry of Health and Welfare, Taiwan. Taiwan Guidelines for TB Diagnosis & Treatment (6E). 6th ed. Taiwan: Centers for Disease Control, Ministry of Health and Welfare, R.O.C.(Taiwan); 2017.
7.
go back to reference WHO. Treatment of tuberculosis: guidelines for national programmes. 4th ed; 2010. WHO. Treatment of tuberculosis: guidelines for national programmes. 4th ed; 2010.
8.
go back to reference Ko JM, Park HJ, Kim CH, Song SW. The relation between CT findings and sputum microbiology studies in active pulmonary tuberculosis. Eur J Radiol. 2015;84(11):2339–44.CrossRef Ko JM, Park HJ, Kim CH, Song SW. The relation between CT findings and sputum microbiology studies in active pulmonary tuberculosis. Eur J Radiol. 2015;84(11):2339–44.CrossRef
9.
go back to reference Wang JY, Shu CC, Lee CH, Yu CJ, Lee LN, Yang PC. Interferon-gamma release assay and rifampicin therapy for household contacts of tuberculosis. J Inf Secur. 2012;64(3):291–8. Wang JY, Shu CC, Lee CH, Yu CJ, Lee LN, Yang PC. Interferon-gamma release assay and rifampicin therapy for household contacts of tuberculosis. J Inf Secur. 2012;64(3):291–8.
10.
go back to reference Nahid P, Dorman SE, Alipanah N, Barry PM, Brozek JL, Cattamanchi A, Chaisson LH, Chaisson RE, Daley CL, Grzemska M, et al. Official American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America clinical practice guidelines: treatment of drug-susceptible tuberculosis. Clin Infect Dis. 2016;63(7):e147–95.CrossRef Nahid P, Dorman SE, Alipanah N, Barry PM, Brozek JL, Cattamanchi A, Chaisson LH, Chaisson RE, Daley CL, Grzemska M, et al. Official American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America clinical practice guidelines: treatment of drug-susceptible tuberculosis. Clin Infect Dis. 2016;63(7):e147–95.CrossRef
11.
go back to reference Lee HS, Oh JY, Lee JH, Yoo CG, Lee CT, Kim YW, Han SK, Shim YS, Yim JJ. Response of pulmonary tuberculomas to anti-tuberculous treatment. Eur Respir J. 2004;23(3):452–5.CrossRef Lee HS, Oh JY, Lee JH, Yoo CG, Lee CT, Kim YW, Han SK, Shim YS, Yim JJ. Response of pulmonary tuberculomas to anti-tuberculous treatment. Eur Respir J. 2004;23(3):452–5.CrossRef
12.
go back to reference Grenville-Mathers R. The Natural History of so-called tuberculoma. J Thorac Surg. 1952;23(3):251–2.PubMed Grenville-Mathers R. The Natural History of so-called tuberculoma. J Thorac Surg. 1952;23(3):251–2.PubMed
13.
go back to reference Subotic D, Yablonskiy P, Sulis G, Cordos I, Petrov D, Centis R, D'Ambrosio L, Sotgiu G, Migliori GB. Surgery and pleuro-pulmonary tuberculosis: a scientific literature review. J Thorac Dis. 2016;8(7):E474–85.CrossRef Subotic D, Yablonskiy P, Sulis G, Cordos I, Petrov D, Centis R, D'Ambrosio L, Sotgiu G, Migliori GB. Surgery and pleuro-pulmonary tuberculosis: a scientific literature review. J Thorac Dis. 2016;8(7):E474–85.CrossRef
14.
go back to reference Prytz S, Hansen JL. Surgical treatment of “Tuberculoma”. Scand J Thorac Cardiovasc Surg. 1976;10(2):179–82.CrossRef Prytz S, Hansen JL. Surgical treatment of “Tuberculoma”. Scand J Thorac Cardiovasc Surg. 1976;10(2):179–82.CrossRef
16.
go back to reference Fukunaga H, Murakami T, Gondo T, Sugi K, Ishihara T. Sensitivity of acid-fast staining forMycobacterium tuberculosisin formalin-fixed tissue. Am J Respir Crit Care Med. 2002;166(7):994–7.CrossRef Fukunaga H, Murakami T, Gondo T, Sugi K, Ishihara T. Sensitivity of acid-fast staining forMycobacterium tuberculosisin formalin-fixed tissue. Am J Respir Crit Care Med. 2002;166(7):994–7.CrossRef
17.
go back to reference Kradin RL, Mark EJ. Pulmonary infections. In: Kradin R, editor. Diagnostic pathology of infectious disease. 1st ed; 2010. p. 125–88.CrossRef Kradin RL, Mark EJ. Pulmonary infections. In: Kradin R, editor. Diagnostic pathology of infectious disease. 1st ed; 2010. p. 125–88.CrossRef
18.
go back to reference Hernández-Pando R, Jeyanathan M, Mengistu G, Aguilar D, Orozco H, Harboe M, Rook GAW, Bjune G. Persistence of DNA from Mycobacterium tuberculosis in superficially normal lung tissue during latent infection. Lancet. 2000;356(9248):2133–8.CrossRef Hernández-Pando R, Jeyanathan M, Mengistu G, Aguilar D, Orozco H, Harboe M, Rook GAW, Bjune G. Persistence of DNA from Mycobacterium tuberculosis in superficially normal lung tissue during latent infection. Lancet. 2000;356(9248):2133–8.CrossRef
19.
go back to reference Doucette K, Cooper R. Tuberculosis. In: Grippi MA, Elias JA, Fishman JA, Kotloff RM, Pack AI, Senior RM, Siegel MD, editors. Fishman’s pulmonary diseases and disorders. 5th ed. New York: McGraw-Hill Education; 2015. Doucette K, Cooper R. Tuberculosis. In: Grippi MA, Elias JA, Fishman JA, Kotloff RM, Pack AI, Senior RM, Siegel MD, editors. Fishman’s pulmonary diseases and disorders. 5th ed. New York: McGraw-Hill Education; 2015.
20.
go back to reference Kendall BA, Varley CD, Choi D, Cassidy PM, Hedberg K, Ware MA, Winthrop KL. Distinguishing tuberculosis from nontuberculous mycobacteria lung disease, Oregon, USA. Emerg Infect Dis. 2011;17(3):506–9.CrossRef Kendall BA, Varley CD, Choi D, Cassidy PM, Hedberg K, Ware MA, Winthrop KL. Distinguishing tuberculosis from nontuberculous mycobacteria lung disease, Oregon, USA. Emerg Infect Dis. 2011;17(3):506–9.CrossRef
21.
go back to reference Grubek-Jaworska H, Walkiewicz R, Safianowska A, Nowacka-Mazurek M, Krenke R, Przybylowski T, Chazan R. Nontuberculous mycobacterial infections among patients suspected of pulmonary tuberculosis. Eur J Clin Microbiol Infect Dis. 2009;28(7):739–44.CrossRef Grubek-Jaworska H, Walkiewicz R, Safianowska A, Nowacka-Mazurek M, Krenke R, Przybylowski T, Chazan R. Nontuberculous mycobacterial infections among patients suspected of pulmonary tuberculosis. Eur J Clin Microbiol Infect Dis. 2009;28(7):739–44.CrossRef
22.
go back to reference Koh WJ, Yu CM, Suh GY, Chung MP, Kim H, Kwon OJ, Lee NY, Chung MJ, Lee KS. Pulmonary TB and NTM lung disease- comparison of characteristics in patients with AFB smear-positive sputum. Int J Tuberc Lung Dis. 2006;10(9):1001–7.PubMed Koh WJ, Yu CM, Suh GY, Chung MP, Kim H, Kwon OJ, Lee NY, Chung MJ, Lee KS. Pulmonary TB and NTM lung disease- comparison of characteristics in patients with AFB smear-positive sputum. Int J Tuberc Lung Dis. 2006;10(9):1001–7.PubMed
23.
go back to reference Tang YW, Procop GW, Zheng X, Myers JL, Roberts GD. Histologic parameters predictive of mycobacterial infection. Am J Clin Pathol. 1998;109(3):331.CrossRef Tang YW, Procop GW, Zheng X, Myers JL, Roberts GD. Histologic parameters predictive of mycobacterial infection. Am J Clin Pathol. 1998;109(3):331.CrossRef
24.
go back to reference Marchevsky A, Damsker B, Gribetz A, Tepper S, Geller SA. The Spectrum of pathology of nontuberculous mycobacterial infections in open-lung biopsy specimens. Am J Clin Pathol. 1982;78(5):695.CrossRef Marchevsky A, Damsker B, Gribetz A, Tepper S, Geller SA. The Spectrum of pathology of nontuberculous mycobacterial infections in open-lung biopsy specimens. Am J Clin Pathol. 1982;78(5):695.CrossRef
25.
go back to reference Aubry MC. Necrotizing granulomatous inflammation: what does it mean if your special stains are negative? Mod Pathol. 2012;25(Suppl 1):S31–8.CrossRef Aubry MC. Necrotizing granulomatous inflammation: what does it mean if your special stains are negative? Mod Pathol. 2012;25(Suppl 1):S31–8.CrossRef
26.
go back to reference Ulbright TM, Katzenstein AL. Solitary necrotizing granulomas of the lung: differentiating features and etiology. Am J Surg Pathol. 1980;4(1):13–28.CrossRef Ulbright TM, Katzenstein AL. Solitary necrotizing granulomas of the lung: differentiating features and etiology. Am J Surg Pathol. 1980;4(1):13–28.CrossRef
27.
go back to reference Rui Y, Han M, Zhou W, He Q, Li H, Li P, Zhang F, Shi Y, Su X. Non-malignant pathological results on transthoracic CT guided core-needle biopsy: when is benign really benign? Clin Radiol. 2018;73(8):757.e751–7.CrossRef Rui Y, Han M, Zhou W, He Q, Li H, Li P, Zhang F, Shi Y, Su X. Non-malignant pathological results on transthoracic CT guided core-needle biopsy: when is benign really benign? Clin Radiol. 2018;73(8):757.e751–7.CrossRef
28.
go back to reference Kim JI, Park CM, Kim H, Lee JH, Goo JM. Non-specific benign pathological results on transthoracic core-needle biopsy: how to differentiate false-negatives? Eur Radiol. 2017;27(9):3888–95.CrossRef Kim JI, Park CM, Kim H, Lee JH, Goo JM. Non-specific benign pathological results on transthoracic core-needle biopsy: how to differentiate false-negatives? Eur Radiol. 2017;27(9):3888–95.CrossRef
29.
go back to reference Mukhopadhyay S, Farver CF, Vaszar LT, Dempsey OJ, Popper HH, Mani H, Capelozzi VL, Fukuoka J, Kerr KM, Zeren EH, et al. Causes of pulmonary granulomas: a retrospective study of 500 cases from seven countries. J Clin Pathol. 2012;65(1):51–7.CrossRef Mukhopadhyay S, Farver CF, Vaszar LT, Dempsey OJ, Popper HH, Mani H, Capelozzi VL, Fukuoka J, Kerr KM, Zeren EH, et al. Causes of pulmonary granulomas: a retrospective study of 500 cases from seven countries. J Clin Pathol. 2012;65(1):51–7.CrossRef
30.
go back to reference Fox GJ, Mitnick CD, Benedetti A, Chan ED, Becerra M, Chiang CY, Keshavjee S, Koh WJ, Shiraishi Y, Viiklepp P, et al. Surgery as an adjunctive treatment for multidrug-resistant tuberculosis: an individual patient data Metaanalysis. Clin Infect Dis. 2016;62(7):887–95.CrossRef Fox GJ, Mitnick CD, Benedetti A, Chan ED, Becerra M, Chiang CY, Keshavjee S, Koh WJ, Shiraishi Y, Viiklepp P, et al. Surgery as an adjunctive treatment for multidrug-resistant tuberculosis: an individual patient data Metaanalysis. Clin Infect Dis. 2016;62(7):887–95.CrossRef
31.
go back to reference FurÁk J, TrojÁn I, Szöke T, Tiszlavicz L, Morvay Z, Csada E, Balogh Á. Surgical intervention for pulmonary tuberculosis: analysis of indications and perioperative data relating to diagnostic and therapeutic resections. Eur J Cardiothorac Surg. 2001;20(4):722–7.CrossRef FurÁk J, TrojÁn I, Szöke T, Tiszlavicz L, Morvay Z, Csada E, Balogh Á. Surgical intervention for pulmonary tuberculosis: analysis of indications and perioperative data relating to diagnostic and therapeutic resections. Eur J Cardiothorac Surg. 2001;20(4):722–7.CrossRef
33.
go back to reference Getahun H, Matteelli A, Chaisson RE, Raviglione M. Latent Mycobacterium tuberculosis infection. N Engl J Med. 2015;372(22):2127–35.CrossRef Getahun H, Matteelli A, Chaisson RE, Raviglione M. Latent Mycobacterium tuberculosis infection. N Engl J Med. 2015;372(22):2127–35.CrossRef
34.
go back to reference Gould MK, Tang T, Liu IL, Lee J, Zheng C, Danforth KN, Kosco AE, Di Fiore JL, Suh DE. Recent trends in the identification of incidental pulmonary nodules. Am J Respir Crit Care Med. 2015;192(10):1208–14.CrossRef Gould MK, Tang T, Liu IL, Lee J, Zheng C, Danforth KN, Kosco AE, Di Fiore JL, Suh DE. Recent trends in the identification of incidental pulmonary nodules. Am J Respir Crit Care Med. 2015;192(10):1208–14.CrossRef
35.
go back to reference Yee D, Valiquette C, Pelletier M, Parisien I, Rocher I, Menzies D. Incidence of serious side effects from first-line Antituberculosis drugs among patients treated for active tuberculosis. Am J Respir Crit Care Med. 2003;167(11):1472–7.CrossRef Yee D, Valiquette C, Pelletier M, Parisien I, Rocher I, Menzies D. Incidence of serious side effects from first-line Antituberculosis drugs among patients treated for active tuberculosis. Am J Respir Crit Care Med. 2003;167(11):1472–7.CrossRef
36.
go back to reference Singla R, Sharma S, Mohan A, Makharia G, Sreenivas V, Jha B, Kumar S, Sarda P, Singh S. Evaluation of risk factors for antituberculosis treatment induced hepatotoxicity. Indian J Med Res. 2010;132(1):81–6.PubMed Singla R, Sharma S, Mohan A, Makharia G, Sreenivas V, Jha B, Kumar S, Sarda P, Singh S. Evaluation of risk factors for antituberculosis treatment induced hepatotoxicity. Indian J Med Res. 2010;132(1):81–6.PubMed
37.
go back to reference Yew WW, Leung CC. Antituberculosis drugs and hepatotoxicity. Respirology. 2006;11(6):699–707.CrossRef Yew WW, Leung CC. Antituberculosis drugs and hepatotoxicity. Respirology. 2006;11(6):699–707.CrossRef
38.
go back to reference Raslan WF, Rabaan A, Al-Tawfiq JA. The predictive value of gen-Probe’s amplified Mycobacterium tuberculosis direct test compared with culturing in paraffin-embedded lymph node tissue exhibiting granulomatous inflammation and negative acid fast stain. J Infect Public Health. 2014;7(4):251–6.CrossRef Raslan WF, Rabaan A, Al-Tawfiq JA. The predictive value of gen-Probe’s amplified Mycobacterium tuberculosis direct test compared with culturing in paraffin-embedded lymph node tissue exhibiting granulomatous inflammation and negative acid fast stain. J Infect Public Health. 2014;7(4):251–6.CrossRef
39.
go back to reference Ulrichs T, Lefmann M, Reich M, Morawietz L, Roth A, Brinkmann V, Kosmiadi GA, Seiler P, Aichele P, Hahn H, et al. Modified immunohistological staining allows detection of Ziehl–Neelsen-negative Mycobacterium tuberculosis organisms and their precise localization in human tissue. J Pathol. 2005;205(5):633–40.CrossRef Ulrichs T, Lefmann M, Reich M, Morawietz L, Roth A, Brinkmann V, Kosmiadi GA, Seiler P, Aichele P, Hahn H, et al. Modified immunohistological staining allows detection of Ziehl–Neelsen-negative Mycobacterium tuberculosis organisms and their precise localization in human tissue. J Pathol. 2005;205(5):633–40.CrossRef
Metadata
Title
Outcome of untreated lung nodules with histological but no microbiological evidence of tuberculosis
Authors
Che-Liang Chung
Yen-Fu Chen
Yen-Ting Lin
Jann-Yuan Wang
Shuenn-Wen Kuo
Jin-Shing Chen
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2018
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-018-3442-9

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