An old enemy not to be forgotten during PET CT scanning of cancer patients: tuberculosis

Introduction

One of the most important issues in patients diagnosed with cancer is the staging after pathological diagnosis. Appropriate staging at the time of diagnosis is one of the most important factors determining the follow up and treatment process, and also the prognosis of the disease [1]. Moreover, rebiopsy of suspected lesions according to positron emission tomography–computed tomography (PET CT) scanning to determine the nature of the lesion in cancer patients during treatment or follow up periods is the recommended method for rational patient management. Imaging methods (CT, magnetic resonance imaging – MRI) have commonly been used for staging and follow up, and PET CT scanning, which has extensively been used in the clinical setting in the last decade, aroused high expectations because of its high sensitivity and specificity, but later it was realised that this examination method should be used more carefully due to its potential for false positivity and negativity [2]. False positivity conditions are physiological involvements, infections (specific infections), inflammations (soft tissue trauma, collagen tissue diseases) and granulomatous infections (sarcoidosis, tuberculosis) [3–7]. Although tuberculosis, a chronic problem as old as human history, was once a problem mainly for low socioeconomic populations, it has evolved into a rising problem in developed countries because of acquired immunosuppression conditions (AIDS, haematological and solid organ cancers, medical conditions requiring immunosuppressive treatments). In this present study we presented data from cancer patients who were followed at our clinic and suspected of having tuberculosis during PET CT scanning. After the biopsy, they were diagnosed with concomitant tuberculosis.

Material and methods

A total of 14 patients, who applied to our clinic and were followed up due to cancer, and had PET CT scanning for the preliminary staging or further evaluation, were included in this present study. The patients were diagnosed with metastatic or recurrent disease, and their biopsy results revealed tuberculosis. Fine needle aspiration technique was used to perform lymph node biopsies from patients suspected of having tuberculosis. Pathological cancer diagnoses had already been made in all enrolled patients. Demographic, laboratory, pathological and nuclear imaging results of all patients were recorded. Statistical analysis was performed by using the SPSS for Windows 15.0 (Statistical Package for Social Sciences) package program. Both descriptive and analytical statistics were used.

PET/CT technique

The patients were imaged using a dedicated PET/CT system (Discovery-STE 8; General Electric Medical System, Milwaukee, WI). The patients fasted for at least 6 hours before intravenous administration of 370 to 555 MBq (10–15 mCi) 18F-FDG. Pre-injection blood glucose levels were measured to ensure that they were below 150 mg/dl. During the distribution phase, the patients lay supine in a quiet room. Combined image acquisition began 55–65 minutes after FDG injection. First, an unenhanced CT scan (5-mm slice thickness) from the vertex of the skull to the inferior border of the pelvis was acquired using a standardised protocol (140 kV and 80 mA). The subsequent PET scan was acquired in the 3-dimensional mode (3 minutes per bed position) without repositioning the patient on the table. Computed tomographic and PET images were acquired with the patient breathing shallowly. Attenuation was corrected using the CT images.

Results

A total of 14 patients were included in the study. Clinical and demographic characteristics of patients are shown in Table 1. The mean age was 57.8 (SD 13.1) years. Of the included patients, 11 (78.6%) were females and 3 (21.4%) were males. None of the patients had tuberculosis in their personal history (0%). When tuberculosis in the family history was asked about, the history was positive in 3 (21.4%) of the patients. The distribution of cancer diagnosis was gastric cancer in 3 (21.4%) patients, endometrium cancer in 2 (14.3%) patients, rectum cancer in 2 (14.3%) patients, cervical cancer in 2 (%14.3) patients and hepatocellular carcinoma, hodgkin’s lymphoma and breast, pancreas and prostate cancers in 1 patient (for each) (7.1%). Among the patients, 5 (35.7%) were diagnosed with tuberculosis during the preliminary staging, whereas 9 (64.3%) were diagnosed during the follow-up after the treatment. Mediastinal lymph nodes were affected lymph nodes in patients at preliminary staging. The median time to tuberculosis diagnosis was 11 months (min-max: 3-24 months) after the treatment. The most commonly involved lymph nodes during PET CT scanning were mediastinal in 8 (64.3%), axillary in 3 (21.4%) and para-aortic in 3 (21.4%) patients. Mean values for erythrocyte sedimentation, C-reactive protein and SUV max at involved lymph nodes detected by PET CT scanning were defined as 41.8 (SD 22.4), 14.4 (SD 5.4) and 8.5 (SD 2.6), in reciprocal order. Laboratory and PET CT findings of patients are shown in Table 2. PET CT coronal and transverse section images of two patients with involvement are shown in Figs. 1–4.

Discussion

Tuberculosis, which may mimic signs of metastatic malignancies, should always be considered by clinicians during differential diagnosis when evaluating patients with cancer. This condition may be encountered either as an accompanying tuberculosis infection in a patient with a malignancy, or as an infection mimicking recurrence signs during the patient follow-up. If it is not detected early in both conditions, it may be fatal for the patient. However, two of our cases (one with cervical cancer and the other with gastric cancer) had mediastinal multiple lymph nodes with high SUV max values in their follow-up PET CT scans performed after the adjuvant treatment. Initially, they were considered as recurrence cases, so they received chemotherapy. As their clinical performances deteriorated during chemotherapy, lymph node biopsy was performed and then they were diagnosed with tuberculosis. In such conditions, tuberculosis diagnosis is made mainly by microbiological and histological examinations, because none of the available imaging methods is specific for tuberculosis [8–10]. Although it is suggested that nodular FDG involvement above 2.5 should lead to malignancy with 80% sensitivity and 70% specificity in PET CT examinations, the SUV max values of involved lymph nodes were above 2.5 in all of our patients [4, 9–13]. Moreover, SUV max values relating to tuberculosis in PET CT examinations were reported as high in some studies but low in some others, published in the literature [14, 15]. Chao-Jung Chen et al. diagnosed tuberculosis in a patient who presented with high Ca 125 and multiple peritoneal implants resembling metastatic ovarian cancer during PET CT scan, and they showed that all signs were recovered completely after antituberculous treatment [16]. Jin Mo Goo et al. reported a 10-case series with pulmonary nodules and positive PET CT results. After the biopsy, they diagnosed tuberculosis, and they underline that tuberculosis should always be considered in endemic regions during PET CT scan evaluations [17]. Geng Tian et al. reported 3 patients with abdominal tuberculosis, who had signs similar to peritoneal malignancy in PET CT scan, and they concluded that PET CT examination was not helpful to resolve the problem in such circumstances, so tissue sampling should be performed for the diagnosis [18]. In our series, tuberculosis diagnosis was made in 5 patients during the preliminary staging and in 9 patients during the follow-up, by biopsy results collected from regions suspected for malignancy in PET CT examinations. The treatment plan and follow-up were completely changed in those patients. If the number of patients reported from a single centre were projected to the general population of the country, then the size of the issue would have been quite significant. In this global world, tuberculosis is still a public health problem both for developing and developed countries. Therefore, as medical oncology specialists, we should definitely consider tuberculosis in differential diagnosis of PET CT results
In conclusion, as in most medical conditions, the physician’s suspicion retains its specific and sensitive value in evaluating PET CT results so as not to miss the old enemy, tuberculosis, in patients with malignancies, despite all the improvements that have been seen in modern medicine. The authors declare no conflicts of interest.

References

1. DeVita VT Jr, Lawrence TS, Rosenberg SA. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 9th edition. Lippincott Williams & Wilkins, Philadelphia 2011.
2. Li Y, Su M, Li F, Kuang A, Tian R. The value of (18)F-FDG-PET/CT in the differential diagnosis of solitary pulmonary nodules in areas with a high incidence of tuberculosis. Ann Nucl Med 2011; 25: 804-11.
3. Patz EF Jr, Lowe VJ, Hoffman JM, Paine SS, Burrowes P, Coleman RE, Goodman PC. Focal pulmonary abnormalities: evaluation with F-18 fluorodeoxyglucose PET scanning. Radiology 1993; 188: 487-90.
4. Knight SB, Delbeke D, Stewart JR, Sandler MP. Evaluation of pulmonary lesions with FDG-PET: comparison of findings in patients with and without a history of prior malignancy. Chest 1996; 109: 982-8.
5. Gupta NC, Maloof J, Gunel E. Probability of malignancy in solitary pulmonary nodules using fluorine-18-FDG and PET. J Nucl Med 1996; 37: 943-8.
6. Liu BJ, Dong JC, Xu CQ, et al. Accuracy of 18F-FDG PET/CT for lymph node staging in non-small-cell lung cancers. Chin Med J (Engl) 2009;122: 1749-54.
7. Lewis PJ, Salama A. Uptake of fluorine-18-fluorodeoxyglucose in sarcoidosis. J Nucl Med 1994; 35: 1647-9.
8. Som P, Atkins HL, Bandoypadhyay D, et al. A fluorinated glucose analog, 2-fluoro-2-deoxy-D-glucose [18F]: nontoxic tracerfor rapid tumor detection. J Nucl Med 1980; 21: 670-5.
9. Gallagher BM, Fowler JS, Gutterson NI, MacGregor RR, Wan CN, Wolf AP. Metabolic trapping as a principle of radiopharmaceutical design: some factors responsible for the biodistribution of [18F] 2-deoxy-2-fluoro-D-glucose. J Nucl Med 1978; 19: 1154-61.
10. Gupta NC, Frank AR, Dewan NA, et al. Solitary pulmonary nodules: detection of malignancy with PET with 2[F-18]-fluoro-2-deoxy-D-glucose. Radiology 1992; 184: 441-4.
11. Dewan NA, Gupta NC, Redepenning LS, Phalen JJ, Frick MP. Diagnostic efficacy of PET-FDG imaging in solitary pulmonary nodules: potential role in evaluation and management. Chest 1993; 104: 997-1002.
12. Kubota K, Matsuzawa T, Fujiwara T, Ito M, Hatazawa J, Ishiwata K, Iwata R, Ido T. Differential diagnosis of lung cancer with positron emission tomography: a prospective study. J Nucl Med 1990; 31: 1927-33.
13. Duhaylongsod FG, Lowe VJ, Patz EF Jr, Vaughn AL, Coleman RE, Wolfe WG. Detection of primary and recurrent lung cancer by means of F-18 fluorodeoxyglucose positron emission tomography (FDG PET). J Thorac Cardiovasc Surg 1995; 110: 130-9.
14. Hu ML, Lee CH, Kuo CM, Huang CC, Tai WC, Chang KC, Lee CM, Chuah SK. Abdominal tuberculosis: analysis of clinical features and outcome of adult patients in southern Taiwan. Chang Gung Med J 2009; 32: 509-16.
15. Makino I, Yamaguchi T, Sato N, Yasui T, Kita I. Xanthogranulomatous cholecystitis mimicking gallbladder carcinoma with a false-positive result on fluorodeoxyglucose PET. World J Gastroenterol 2009; 15: 3691-3.
16. Chen CJ, Yao WJ, Chou CY, Chiu NT, Lee BF, Wu PS.Peritoneal tuberculosis with elevated serum CA125 mimicking peritoneal carcinomatosis on F-18 FDG-PET/CT. Ann Nucl Med 2008; 22: 525-527.
17. Goo JM, Im JG, Do KH, Yeo JS, Seo JB, Kim HY, Chung JK. Pulmonary tuberculoma evaluated by means of FDG PET: findings in 10 cases. Radiology 2000; 216: 117-21.
18. Tian G, Xiao Y, Chen B, Guan H, Deng QY. Multi-site abdominal tuberculosis mimics malignancy on 18F-FDG PET/CT: report of three cases. World J Gastroenterol 2010; 16: 4237-42.

Address for correspondence
Ahmet Taner Sümbül
Department of Medical Oncology
Medical Faculty
Mustafa Kemal University
Serinyol, Hatay, Turkey
31000
tel. +905056166338
e-mail: drtanersu@yahoo.com

Submitted: 18.02.2014
Accepted: 11.04.2014