Tuberculosis and childhood cancer - A review of literature.

Tuberculosis and malignancy are major public health problems in developing countries like India and causes significant morbidity and mortality. Mycobacterium tuberculosis is an aerobic acid-fast bacilli which is an important pathogen especially complicating clinical status of paediatric oncology patients and treatment of infection with this bacilli is challenging in this subpopulation of patients because of ongoing immunosuppression and relative lack of published guidelines. Atypical presentations of tuberculosis in children also complicate the diagnosis and management. All the more, in tuberculosis endemic area lung cancer may be mistakenly diagnosed as tuberculosis or vice versa and this wrong diagnosis increases the burden on country's health status. It is noted that tuberculosis prevalence is high in children with haematological malignancy and head and neck tumours compared to other solid organ tumours. Moreover, it is found that morbidity and mortality from tuberculosis is more in children from WHO listed high TB burden countries who undergo hematopoietic stem cell and solid organ transplantation. Use of immune checkpoint inhibitors as novel therapy in treatment of childhood malignancies has led to modification of the body's immunological response and has resulted in increased latent tuberculosis infection reactivation as one immune-related infectious consequence. Latent TB infection screening is important concept in management of paediatric oncology patients. Currently, the tests employed as screening diagnostics for LTBI are interferon-gamma release assay (IGRA) blood test and the tuberculin skin test (TST). Various regimens have been suggested for the treatment of LTBI. But, after a positive IGRA or TST and prior to latent TB treatment, active tuberculosis should be ruled out by detailed history taking, examination and appropriate investigations so as to minimize the risk of drug resistance with anti-tuberculosis monotherapy used in LTBI treatment. To add on to literature, Non tuberculous mycobacteria are universally present environmental organisms. However, in immunocompromised children especially in subpopulation of malignancy, NTM is known to cause infections which needs protocol based management. Also importance has to given to implementation of adequate preventive and corrective measures to prevent such opportunistic infection in paediatric oncology subpopulation. In this review, we provide an overview of tuberculosis in paediatric oncology patients and summarize the expansive body of literature on the tuberculosis mimicking carcinoma, tuberculosis burden in transplantation patients and those receiving immune check point inhibitors, latent TB infection screening and management, and NTM infection in children with malignancy.

Microsatellite instability, promoter methylation and protein expression of the DNA mismatch repair genes in epithelial ovarian cancer.

The role of defective mismatch repair (MMR) system in ovarian carcinoma is not well defined. The purpose of the study was to determine the relationship between microsatellite instability (MSI), promoter methylation and protein expression of MMR genes in epithelial ovarian carcinoma (EOC). MSI and promoter methylation of MLH1, MSH2 and PMS2 genes were studied using PCR methods in the study cohort. A small subset of samples was used to analyze the protein expression by immunohistochemistry (IHC). MSI was observed in >60% of tumor samples and 47% of normal ovaries. MLH1 was methylated in 37.5% and 64.3% EOCs and LMP tumors. The loss of immunoexpression of MMR genes was not seen in ovarian tumors. There was no correlation between MSI, promoter methylation and protein expression of the MMR genes suggesting that each may function independently. MSI is a common event in ovarian carcinoma and may increase the clinical awareness of the subset of tumors.