Asymptomatic primary tuberculous pleurisy with intense 18-fluorodeoxyglucose uptake mimicking malignant mesothelioma
© Shinohara et al.; licensee BioMed Central Ltd. 2013
Received: 17 September 2012
Accepted: 11 January 2013
Published: 14 January 2013
The pathogenesis of primary tuberculous pleurisy is a delayed-type hypersensitivity immunogenic reaction to a few mycobacterial antigens entering the pleural space rather than direct tissue destruction by mycobacterial proliferation. Although it has been shown that pulmonary tuberculosis induces 18-fluorodeoxyglucose (FDG) uptake in active lesions, little is known about the application of FDG positron emission/computed tomography (FDG PET/CT) to the management of primary tuberculous pleurisy.
We report a case of asymptomatic primary tuberculous pleurisy presenting with diffuse nodular pleural thickening without distinct pleural effusion and parenchymal lung lesions mimicking malignant mesothelioma. An initial FDG PET/CT scan demonstrated multiple lesions of intense FDG uptake in the right pleura and thoracoscopic biopsy of pleural tissue revealed caseous granulomatous inflammation. The patient received antituberculous therapy for 6 months, with clearly decreased positive signals on a repeated FDG PET/CT scan.
FDG PET/CT imaging may be useful for evaluating disease activity in tuberculous pleurisy patients with an unknown time of onset.
KeywordsPrimary tuberculous pleurisy Fluorodeoxyglucose Positron emission tomography
18-fluorodeoxyglucose positron emission/computed tomography (FDG PET/CT) is a noninvasive imaging technique that visualizes glucose metabolism and has been regarded as useful for differentiating between benign and malignant diseases [1, 2]. However, it has been shown that inflammatory disorders, especially pulmonary tuberculosis, also induce FDG uptake in active lesions, which suggests that FDG PET results should be interpreted with caution [3–5]. Conventional or dual phase FDG PET can not effectively distinguish malignant disease from mycobacterium infections. Multi-tracer PET, a novel promising technology utilizing differences in tracer kinetics and decay, has been providing additional and complementary information to improve pulmonary nodule characterization .
The usefulness of FDG PET in the detection of mycobacterium infection sites has been shown in patients with miscellaneous infectious lesions or human immunodeficiency virus-associated fever of unknown origin [6, 7]. Moreover, it has been reported that FDG PET/CT is helpful not only for evaluating disease activity, but also for monitoring therapeutic responses in pulmonary tuberculosis, tuberculous lymphadenitis, and skeletal tuberculosis, particularly in smear-negative patients [5, 8–10]. Via et al. demonstrated that FDG-PET uptake in tuberculous pulmonary lesions was significantly reduced with as little as 1 week of treatment prior to changes in the volume and density of lesions in a rabbit model . The absence of reduced FDG PET uptake in the early phase of treatment may suggest active tuberculosis due to a lack of adherence, drug resistance, or misdiagnosis .
The pathogenesis of primary tuberculous pleurisy is a delayed-type hypersensitivity immunogenic reaction to a few mycobacterial antigens entering the pleural space rather than direct tissue destruction by mycobacterial proliferation . However, little is known about the application of FDG PET/CT imaging to the management of primary tuberculous pleurisy. We report here a case of asymptomatic primary tuberculous pleurisy with intense FDG uptake mimicking malignant mesothelioma.
Although no positive culture was obtained, other clinical data suggested that a diagnosis of tuberculous pleurisy was highly likely in this case and the patient received antituberculous therapy for 6 months (2HREZ/4HRE) without any side effects. Just after chemotherapy, a repeated FDG PET/CT scan revealed clearly decreased positive signals (SUVmax = 5.7) with marked improvements in pleural thickening (Figure 2B and Figure 3B). Six months after the completion of chemotherapy, a chest radiograph showed further improvements in pleural based opacities relative to that taken just after chemotherapy (Figure 1B and C).
Pleural inflammation caused by bacteria, mycobacterium, or autoimmune disease is usually characterized by effusion, fever, malaise, chest pain, nonproductive cough, and dyspnea in the acute phage , or diffuse thickening of the pleura, with or without calcification, in the chronic phase. Therefore, pleural thickening with no subjective symptoms generally implies non-active inflammatory pleural diseases, so-called “residual pleural thickness”, or neoplasm of the pleura. Interestingly, the asymptomatic diffuse pleural thickening in our case showed intense FDG uptake and proved to be caseous granulomatous inflammation.
Duysinx et al. suggested that FDG PET/CT is an effective tool for differentiating between benign and malignant pleural diseases. The uptake of FDG was intense in all cases of mesothelioma and neoplastic pleurisy associated with primary lung cancer. In contrast, FDG PET/CT imaging revealed an absence of FDG uptake within the pleura of 2 of 3 patients with tuberculous pleurisy and the rest showed moderate uptake, although detailed clinical data of these patients were not described . Kramer et al. also evaluated the feasibility of PET in the diagnosis of pleural thickening on CT. They concluded that qualitative assessment with PET discriminates between malignant and benign pleural thickening with high accuracy and a high negative predictive value. However, there has been no description of tuberculous pleurisy . To the best of our knowledge, this is the first reported case of tuberculous pleurisy with intense FDP uptake.
The pathogenesis of primary tuberculous pleurisy is a delayed-type hypersensitivity immunogenic reaction to a few mycobacterial antigens entering the pleural space rather than direct tissue destruction by uncontrolled mycobacterial proliferation . This appears to be the reason for the low rate of positive results in acid-fast staining of pleural fluid and tissue, as seen in this case . Recent findings suggest that the immunogenic reaction in tuberculous pleurisy involves lymphocytes (including CD3, CD4, CCR4, and Th17 cells), neutrophils, mesothelial cells, and various cytokines such as interferon-γ, interleukin (IL)-8, IL-12, and monocyte chemoattractant protein-1 [17, 18]. However, the complex mechanisms that induce high glucose metabolism and show high uptake of FDG in pleural thickening is unclear at this time.
About half of untreated cases of primary tuberculous pleurisy relapse with more severe forms of active pulmonary or extra-pulmonary tuberculosis, which may result in severe disability or death [19, 20]. However, in general, many cases of pleural thickening suspiciously caused by primary tuberculous pleurisy with no subjective symptoms have not received antituberculous chemotherapy. FDG uptake in the pleura with positive QuantiFERON-TB may support the use of antituberculous treatment in such cases.
Active tuberculosis should be considered in the differential diagnosis of diffuse pleural thickening even when there are no subjective symptoms. Moreover, FDG PET/CT imaging may be useful for evaluating disease activity and monitoring therapeutic responses in tuberculous pleurisy patients with an unknown time of onset.
Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
Positron emission tomography
Maximal standard uptake value
QuantiFERON-TB second generation
- Strauss LG: Positron emission tomography: current role for diagnosis and therapy monitoring in oncology. Oncologist. 1997, 2: 381-388.PubMedGoogle Scholar
- Gould MK, Maclean CC, Kuschner WG, Rydzak CE, Owens DK: Accuracy of positron emission tomography for diagnosis of pulmonary nodules and mass lesions: a meta-analysis. JAMA. 2001, 285: 914-924. 10.1001/jama.285.7.914.View ArticlePubMedGoogle Scholar
- Zheng Z, Pan Y, Guo F, Wei H, Wu S, Pan T, Li J: Multimodality FDG PET/CT appearance of pulmonary tuberculoma mimicking lung cancer and pathologic correlation in a tuberculosis-endemic country. South Med J. 2011, 104: 440-445. 10.1097/SMJ.0b013e318218700a.View ArticlePubMedGoogle Scholar
- Soussan M, Brillet PY, Mekinian A, Khafagy A, Nicolas P, Vessieres A, Brauner M: Patterns of pulmonary tuberculosis on FDG-PET/CT. Eur J Radiol. 2012, 81: 2872-2876. 10.1016/j.ejrad.2011.09.002.View ArticlePubMedGoogle Scholar
- Treglia G, Taralli S, Calcagni ML, Maggi F, Giordano A, Bonomo L: Is there a role for fluorine 18 fluorodeoxyglucose-positron emission tomography and positron emission tomography/computed tomography in evaluating patients with mycobacteriosis? A systematic review. J Comput Assist Tomogr. 2011, 35: 387-393. 10.1097/RCT.0b013e318219f810.View ArticlePubMedGoogle Scholar
- Ichiya Y, Kuwabara Y, Sasaki M, Yoshida T, Akashi Y, Murayama S, Nakamura K, Fukumura T, Masuda K: FDG-PET in infectious lesions: The detection and assessment of lesion activity. Ann Nucl Med. 1996, 10: 185-191. 10.1007/BF03165391.View ArticlePubMedGoogle Scholar
- Castaigne C, Tondeur M, de Wit S, Hildebrand M, Clumeck N, Dusart M: Clinical value of FDG-PET/CT for the diagnosis of human immunodeficiency virus-associated fever of unknown origin: a retrospective study. Nucl Med Commun. 2009, 30: 41-47. 10.1097/MNM.0b013e328310b38d.View ArticlePubMedGoogle Scholar
- Park IN, Ryu JS, Shim TS: Evaluation of therapeutic response of tuberculoma using F-18 FDG positron emission tomography. Clin Nucl Med. 2008, 33: 1-3. 10.1097/RLU.0b013e31815c5128.View ArticlePubMedGoogle Scholar
- Martinez V, Castilla-Lievre MA, Guillet-Caruba C, Grenier G, Fior R, Desarnaud S, Doucet-Populaire F, Boué F: 18F-FDG PET/CT in tuberculosis: an early non-invasive marker of therapeutic response. Int J Tuberc Lung Dis. 2012, 16: 1180-1185. 10.5588/ijtld.12.0010.View ArticlePubMedGoogle Scholar
- Go SW, Lee HY, Lim CH, Jee WH, Wang YP, Yoo IR, Kang JY: Atypical disseminated skeletal tuberculosis mimicking metastasis on PET-CT and MRI. Intern Med. 2012, 51: 2961-2965. 10.2169/internalmedicine.51.8347.View ArticlePubMedGoogle Scholar
- Via LE, Schimel D, Weiner DM, Dartois V, Dayao E, Cai Y, Yoon YS, Dreher MR, Kastenmayer RJ, Laymon CM, Carny JE, Flynn JL, Herscovitch P, Barry CE: Infection dynamics and response to chemotherapy in a rabbit model of tuberculosis using [18F]2-fluoro-deoxy-D-glucose positron emission tomography and computed tomography. Antimicrob Agents Chemother. 2012, 56: 4391-4402. 10.1128/AAC.00531-12.View ArticlePubMedPubMed CentralGoogle Scholar
- Barnes PF, Mistry SD, Cooper CL, Pirmez C, Rea TH, Modlin RL: Compartmentalization of a CD4+ T lymphocyte subpopulation in tuberculous pleuritis. J Immunol. 1989, 142: 1114-1119.PubMedGoogle Scholar
- Levine H, Szanto PB, Cugell DW: Tuberculous pleurisy. An acute illness. Arch Intern Med. 1968, 122: 329-332. 10.1001/archinte.1968.00300090039009.View ArticlePubMedGoogle Scholar
- Duysinx B, Nguyen D, Louis R, Cataldo D, Belhocine T, Bartsch P, Bury TJ: Evaluation of pleural disease with 18-fluorodeoxyglucose positron emission tomography imaging. Chest. 2004, 125: 489-493. 10.1378/chest.125.2.489.View ArticlePubMedGoogle Scholar
- Kramer H, Pieterman RM, Slebos DJ, Timens W, Vaalburg W, Koëter GH, Groen HJ: PET for the evaluation of pleural thickening observed on CT. J Nucl Med. 2004, 45: 995-998.PubMedGoogle Scholar
- Gopi A, Madhavan SM, Sharma SK, Sahn SA: Diagnosis and treatment of tuberculous pleural effusion in 2006. Chest. 2007, 131: 880-889. 10.1378/chest.06-2063.View ArticlePubMedGoogle Scholar
- Ferrer Sancho J: Pleural tuberculosis: incidence, pathogenesis, diagnosis, and treatment. Curr Opin Pulm Med. 1996, 2: 327-334.PubMedGoogle Scholar
- Caramori G, Lasagna L, Casalini AG, Adcock IM, Casolari P, Contoli M, Tafuro F, Padovani A, Chung KF, Barnes PJ, Papi A, Rindi G, Bertorelli G: Immune response to Mycobacterium tuberculosis infection in the parietal pleura of patients with tuberculous pleurisy. PLoS One. 2011, 6: e22637-10.1371/journal.pone.0022637.View ArticlePubMedPubMed CentralGoogle Scholar
- Patiala J: Initial tuberculous pleuritis in the Finnish armed forces in 1939–1945 with special reference to eventual postpleuritic tuberculosis. Acta Tuberc Scand. 1954, 36 (Suppl): 1-57.Google Scholar
- Roper WH, Waring JJ: Primary serofibrinous pleural effusion in military personnel. Am Rev Tuberc. 1955, 71: 616-634.PubMedGoogle Scholar
- The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2334/13/12/prepub
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