Does tuberculosis (TB) increase the risk of cancer?

Ample reports in the literature suggest that TB is associated with the development of certain cancers, including lung cancer, lymphoma and urothelial cancers of the genitourinary tract. 1-5

A 2010 literature review including 9 retrospective studies found that several (not all) studies reported a significant association between prior history of TB and lung cancer, with odds ratios as high as 20.5 ( C.I. 8.1-51.8) at 1-5 years following TB.1 One study involving non-smoking women found a lung cancer (mostly adenocarcinoma) prevalence of 18% among those with prior history of TB (O.R. 5.9, CI 1.3-25.9).5 Cases of “pyothorax-associated lymphoma” of the pleural cavity have also been attributed to TB diagnosed as remote as 40 years or greater before the diagnosis of cancer.1

Urinary tuberculosis was associated with the development of urothelial carcinoma (including bladder, ureteral, renal pelvic transitional cell carcinoma) but not renal cell carcinoma in a nationwide cohort study from Taiwan (hazard ratio 3.4, C.I. 2.0-5.7). 2 The mean interval between the index date of TB and the diagnosis of urinary tract cancer was about 5 years in this study.

Several potential mechanisms for TB predisposing to malignancy have been proposed.1,6 Chronic inflammation associated with higher rate of cell turnover may increase the risk of genetic mutation and subsequent malignancy, as observed in other conditions such as gastroesophageal reflux disease and esophageal cancer and inflammatory bowel disease and colon cancer. The ability of Mycobacterium tuberculosis to induce DNA damage, inhibit apoptosis and augment concentrations of leukotrienes, prostaglandins and vascular endothelial growth factors have also been implicated.

And don’t forget that active TB may not only coexist with but may also mimic malignancy (see related pearl on P4P).

 

Bonus Pearl: Did you know that the association of TB with cancer was first described in 1810 by Gaspard Laurent Bayle, a French physician who considered “cavitation cancereuse” as a distinct TB category? 1

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 References

  1. Falagas ME, Kouranos VD, Athanassa Z, et al. Tuberculosis and malignancy. Q J Med 2010;103: 461-87. Doi:10.1093/qjmed/hcq068 https://pubmed.ncbi.nlm.nih.gov/20504861/
  2. Lien YC, Wang JY, Lee MC, et al. Urinary tuberculosis is associated with the development of urothelial carcinoma but not renal cell carcinoma: a nationwide cohort study in Taiwan. B J Cancer 2013;109:2933-2940. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3844900/
  3. Chin SN, Foster T, Char G, et al. Concomitant urothelial cancer and renal tuberculosis. Case Reports in Urology. Volume 2014, Aricle ID 625153. https://www.hindawi.com/journals/criu/2014/625153/
  4. Dobler CC, Cheung K, Nguyen J, et al. Risk of tuberculosis in patients with solid cancers and haematological malignancies: a systematic review and meta-analysis. Eur Respir J 2017;50:1700157. https://doi.org/10.1183/13993003.00157-2017.
  5. Ko YC, Lee CH, Chen MJ, et al. Risk factors for primary lung cancer amng non-smoking women in Taiwan. Int J Epidemiol 1997;26:24-31. https://pubmed.ncbi.nlm.nih.gov/9126500/
  6. Ling S, Chang X, Schultz L, et al. An EGFR-ERK-SOX9 signaling cascade links urothelial development and regeneration to cancer. Cancer Res 2011;71:3812-21. https://pubmed.ncbi.nlm.nih.gov/21512138/ 

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Massachusetts General Hospital, Harvard Catalyst, Harvard University, its affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

Does tuberculosis (TB) increase the risk of cancer?

The chest CT of my patient with “B” symptoms shows hilar mass and mediastinal lymphadenopathy, highly suspicious for lymphoma or malignancy per radiology report. Should I still consider tuberculosis (TB) as a possibility?

Absolutely! TB often mimics malignancy, particularly lymphoma, both clinically and radiographically, even when sophisticated imaging techniques are used.1  

There are ample reports of TB being confused with mediastinal lymphoma, 1-6 with several reports also stressing abdominal TB mimicking malignancy. 7-10 As early as  1949, a  NEJM autopsy study emphasized “the difficulty in differentiating primary progressive TB and some types of lymphoma” and metastatic neoplasms, clinically and radiographically.  Over half-century later, despite major advancement in imaging techniques, TB is often confused for lymphoma or malignancy.

One reason for confusing TB with lymphoma is that primary TB can involve any pulmonary lobe or segment and is often associated with hilar and mediastinal adenopathy. 1 TB may also be overlooked in the differential diagnosis of mediastinal mass that often highlights neoplasms such as lymphoma, thymoma and germ cell tumors. 3 Lack of concurrent pulmonary infiltrates in the presence of mediastinal adenopathy may also veer clinicians away from TB diagnosis. 2,3,6 Unfortunately, even more sophisticated PET/CT scans may not be able to differentiate TB from lymphoma.5,6,9

Besides chest and abdomen, TB can also mimic malignancy in cervical nodes, bones (particularly the spine), bowels, and brain.1,2,6,8,9  To make matters worse, splenomegaly 2,10 and elevated LDH 3 may also be seen with TB and TB may coexist with lymphoma and other malignancies. 7,9,11

One of the best advices I ever received from a radiologist was “Think of TB anytime you think of lymphoma.”

Bonus Pearl: Did you know that TB lymphadenitis is the most common form of extrapulmonary TB with the majority involving the mediastinum? 4

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References

  1. Tan CH, Kontoyiannis DP, Viswanathan C, et al. Tuberculosis: A benign impostor. AJR 2010;194:555-61. https://www.researchgate.net/publication/41509877_Tuberculosis_A_Benign_Impostor
  2. Smith DT. Progressive primary tuberculosis in the adult and its differentiation from lymphomas and mycotic infections. N Engl J Med 1949;241:198-202. https://www.ncbi.nlm.nih.gov/pubmed/18137399
  3. Maguire S, Chotirmall SH, Parihar V, et al. Isolated anterior mediastinal tuberculosis in an immunocompetent patient. BMC Pulm Med 2016;16:24. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4739107/
  4. Tang SS, Yang ZG, Deng W, et al. Differentiation between tuberculosis and lymphoma in mediastinal lymph nodes: evaluation with contrast-enhanced MDCT. Clin Radiol 2012;67:877-83. https://www.sciencedirect.com/science/article/abs/pii/S0009926012001079
  5. Hou S, Shen J, Tan J. Case report: Multiple systemic disseminated tuberculosis mimicking lymphoma on 18F-FDG PET/CT. Medicine 2017;96:29(e7248). https://journals.lww.com/md-journal/Pages/ArticleViewer.aspx?year=2017&issue=07210&article=00005&type=Fulltext
  6. Tian G, Xiao Y, Chen B, et al. Multi-site abdominal tuberculosis mimics malignancy on 18F-FDG PET/CT: Report of three cases. World J Gastroenterol 2010;16:4237-4242. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2932932/
  7. Dres M, Demoule A, Schmidt M, et al. Tuberculosis hiding a non-Hodgkin lymphoma “there may be more to this than meets the eye”. Resp Med Case Rep 2012;7:15-16. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3920344/
  8. Banerjee Ak, Coltart DJ. Abdominal tuberculosis mimicking lymphoma in a patient with sickle cell anemia. Br J Clin Pract 1990;44:660-61. https://www.ncbi.nlm.nih.gov/pubmed/2102179?dopt=Abstract
  9. Gong Y, Li S, Rong R, et al. Isolated gastric varices secondary to abdominal tuberculosis mimicking lymphoma: a case report. Gastroenterology 109;19:78. https://www.ncbi.nlm.nih.gov/pubmed/31138138
  10. Uy AB, Garcia Am Manguba A, et al. Tuberculosis: the great lymphoma pretender. Int J Cancer Res Mol Mech 2016; 2(1):doi http://dx.doi.org/10.16966/2381-3318.123
  11. Nayanagari K, Rani R, Bakka S, et al. Pulmonary tuberculosis with mediastinal lymphadenopathy and superior veno caval obstruction, mimicking lung malignancy: a case report. Int J Sci Study 2015;2:211-14. https://www.ncbi.nlm.nih.gov/pubmed/31138138
The chest CT of my patient with “B” symptoms shows hilar mass and mediastinal lymphadenopathy, highly suspicious for lymphoma or malignancy per radiology report. Should I still consider tuberculosis (TB) as a possibility?

My middle-aged patient with a history of mediastinal irradiation for Hodgkin’s lymphoma in his 20s now has moderate aortic regurgitation. Could his valvular disease be related to the radiation he received over 20 years ago?

Absolutely! Mediastinal irradiation is associated with several cardiac complications, including coronary artery disease, pericarditis, systolic or diastolic dysfunction and valvular disease. Valvular disease may occur in 2-37% of patients after mediastinal irradiation, is dose-dependent, and generally does not manifest until 10-20 years after the radiation exposure.1 Since mediastinal irradiation is common in young adults diagnosed with Hodgkin’s lymphoma, these complications may be seen in early middle-age or later.

Valvular retraction is usually the first radiation-induced valvular change, and most commonly leads to mitral and aortic valve regurgitation.2 This retraction tends to occur within 10 years of the radiation therapy, followed by fibrosis and calcification of the valves after 20 years.

Although the pathophysiology of radiation-induced valvular disease is not entirely understood, activation of fibrogenic growth factors (eg, tissue growth factor β1 and myofibroblasts) which promote the synthesis of collagen has been postulated.1 Additionally, irradiation of aortic interstitial cells has been shown to cause transformation to an osteogenic phenotype that produces bone morphogenic protein 2, osteopontin and alkaline phosphatase, all important factors in bone formation and possibly valvular calcification.3

Since radiation-induced heart disease is the most common cause of non-malignant morbidity and mortality in patients who have undergone mediastinal irradiation, some have recommended screening of asymptomatic patients for valvular disease every 5 years by echocardiography beginning 10 years after radiation therapy. 2  If an abnormality is found, the screening frequency should increase to every 2-3  years,  if the valvular abnormality is mild, or annually if the abnormality is moderate. For severe valvular abnormalities, the patients should be considered for valve replacement.

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References

    1. Gujral DM, Lloyd G, Bhattacharyya S. Radiation-induced valvular heart disease. Heart 2016;102:269–276. https://heart.bmj.com/content/heartjnl/102/4/269.full.pdf
    2. Cuomo JR, Sharma GK, Conger PD, Weintraub NL. Novel concepts in radiation-induced cardiovascular disease. World J Cardiol. 2016; 8 (9):504-519. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5039353/
    3. Nadlonek NA, Weyant MJ, Yu JA, et al. Radiation induces osteogenesis in human aortic valve interstitial cells. J Thorac Cardiovasc Surg 2012;144:1466–70. doi:10.1016/j.jtcvs.2012.08.041 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3665422/

Contributed by Rachel Wallwork, MD, Mass General Hospital, Boston, MA

 

My middle-aged patient with a history of mediastinal irradiation for Hodgkin’s lymphoma in his 20s now has moderate aortic regurgitation. Could his valvular disease be related to the radiation he received over 20 years ago?