To evaluate clinical utility of MUM-1 IHC to detect chronic endometritis due to genital tuberculosis

INTRODUCTION

World Health Organization (WHO) in 1993 declared tuberculosis (TB) as a “Global Emergency” considering its significant impact on individual's health and wider social and economic consequences.^[1] Mycobacterium tuberculosis is the etiological agent for TB. Female genital tract TB is a leading cause of infertility, especially in developing countries. Being silent in nature, it causes massive destruction of genital structures till it is diagnosed. It is usually secondary to a primary focus elsewhere in the body. The Fallopian tubes are involved in 90% to 100% of cases, endometrium is involved in 50% to 80% of cases, ovaries in 20% to 30%, and cervix is involved in 5% to 15% cases of genital tuberculosis (GTB).^[2] Incidence of GTB varies widely ranging from 1% in infertility clinics of USA to 1% to 19% in various parts of India.^[2,3,4]

Being paucibacillary in nature, diagnostic tests to evaluate GTB suffer from low detection rate. Culture methods are considered as the gold standard in the detection of GTB. Conventional media such as Löwenstein–Jensen medium requires 1000 bacilli/mL and takes up to 6 to 8 weeks to provide results. Liquid-based culture media such as BACTEC 460 provide results within 2 weeks and provide rapid assessment for drug sensitivity patterns.^[5] Polymerase chain reaction (PCR) is a rapid, sensitive, and specific method that can detect <10 bacilli/mL of the sample and results are available within 1 to 2 days,^[6] but it suffers from high false positive and false negative rates. Laparoscopy involves operative and anesthetic risks and risk of infection [Figure 1].

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Figure 1:

Sensitivity and Specificity of MUM1-IHC.

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CD 138 is widely used as an ancillary immunohistochemistry stain to identify plasma cells; however, it has a drawback of high background reaction. Multiple myeloma 1 transcription factor immunohistochemistry (MUM-1 IHC) has been shown to be a more sensitive stain than CD 138 in diagnosing chronic endometritis in addition to having clean background.^[7]

Since endometrium is involved in almost half of the cases of genital TB, we sought to evaluate MUM-1 as a marker of endometrial involvement and chronic endometritis due to GTB.

MATERIALS AND METHODS

RESULTS

Mean age of women was 32.24 ± 0.26 years. Sixty cases of GTB were diagnosed based on hysterolaparoscopic findings. Out of 60 patients, MUM-1 IHC was positive in 28 cases and negative in 32 cases [Table 1]. GeneXpert was negative in all 60 cases of laparoscopy-diagnosed GTB. Histopathology was positive in nine cases of GTB.

DISCUSSION

Diagnosis of GTB poses a great challenge owing to its paucibacillary nature and varied clinical features. Culture is considered as a gold standard but paucibacillary nature of GTB can lead to negative culture. In study by Sharma et al., adhesions were present in 88.8% women. Other findings were beading of tubes, presence of tubercles, caseation, and tubo-ovarian masses.^[9] The index TB guidelines on extrapulmonary TB in India guide for diagnosing GTB based on laparoscopic appearance typical for TB.^[10] In the present study, cases of GTB were diagnosed on laparoscopy.

Delay in treatment can cause significant morbidity and can have serious repercussions on the fertility of women. Endometrium is involved in almost half of the cases of GTB. Endometrial involvement can destroy endometrium causing Asherman syndrome. Therefore, there is a need to evaluate diagnostic modalities, which can diagnose endometrial involvement in GTB so treatment can be started at the earliest to prevent progression of the disease.

MUM-1 is a lymphocyte-specific transcriptional factor, a member of interferon regulatory factor (IRF) family. It contributes to the regulation of immunoglobin gene expression in the final step (late centrocyte) of B-cell differentiation within germinal center. MUM1 is not only a marker for plasma cells, but also highlights activated B and T cells; or only lymphoid cells in an activated state.^[11] Physiologically, B lymphocytes tend to aggregate in the basalis layer and constitute approximately 1% of the normal lymphoid population. In endometritis, the B cells increase in the endometrium aggregating in the functionalis rather than the basalis layer with no significant change in the T-cell population.^[12][13] Therefore, the presence of the MUM1-postive lymphoid B cells in the endometrial stroma may be a clue for the presence of active inflammation versus normal or physiological conditions.^[7] Recently, a new concept of impaired inflammatory state of endometrium has emerged instead of chronic endometritis, which considers both infectious factors (Streptococcus, Escherichia coli, Enterococcus, GTB, etc.) and noninfectious factors (endometriosis, adenomyosis, endometrial polyp, autoimmune, and hormonal disturbances) unlike chronic endometritis which only refers to infectious pathology.^[14]

To our knowledge, the present study is the first study to evaluate MUM-1 IHC as marker of endometrial involvement and chronic endometritis in GTB. Sensitivity and specificity of the test are 46.66% and 85.80% respectively. Sensitivity of histopatholgy is 15% and specificity is 100% in our study, whereas GeneXpert has 0% sensitivity and 99.3% specificity [Table 2]. Garg et al.^[15] did not find any patient positive with GeneXpert among 81 infertile women suspected of having GTB as a cause of infertility.^[15] MUM-1 has a good negative predictive value along with hysterolaparoscopy in ruling out endometrial involvement and chronic endometritis due to TB.

Limitations of the study include its being retrospective in nature which could have introduced bias in the study and small sample size.

CONCLUSION

MUM-1 IHC can be proven as a useful marker to rule out endometrial involvement in GTB owing to its high specificity and can be recommended in conditions in which histopathology and GeneXpert are negative; however, prospective studies are needed to confirm the findings of the present study.