{"paper_id":"dc774464-2134-4d51-9027-cd722fced01a","body_text":"289\nCASE REPORT\nCopyright© 2025 The Author. Published by Galenos Publishing House on behalf of University of Health Sciences Türkiye, Gülhane Faculty of Medicine. \nThis is an open access article under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 (CC BY-NC-ND) International License.\nGulhane Med J 2025;67(4):289-292\nDOI: 10.4274/gulhane.galenos.2025.89106\nIntroduction \nFemale genital tract tuberculosis (TB) is a variant of \nextrapulmonary tuberculosis (EPTB) (1). It causes a negative \nimpact on female fertility. TB’s effects on female hormone \nalterations and menstrual cycles are overlooked. TB outcomes \non hypothalamus, pituitary gland, and ovaries result in \ndisordered menstruation. Simultaneously change in hormone \nprofile and antigonadotrophic effects of Mycobacterium TB \nresults in hypogonadism which accounts for infertility and \nmenstrual irregularities. TB has been associated with lower \nserum oestrogen levels, and serum oestrogen levels are \nraised during TB treatment (2). It had been reported that in \nthe TB patients, there were reduction in female sex hormone \nwhich leads to diminished ovarian function (3). This leads to \nABSTRACT\nGenital tract tuberculosis (TB) occurring together with adenomyosis and leiomyoma is \nrarely observed. A 40-year-old nulligravida woman was clinically diagnosed with the \nfibroid uterus. Histopathological examination revealed leiomyoma with adenomyosis and \nTB. Immunohistochemistry for oestrogen and progesterone receptors was performed to \ndetermine their expression, which was found to be moderate, although it was expected \nto be strongly positive. This case is being reported because of its rare coexistence of \nthese conditions; moreover, it suggests that reduced hormone expression, particularly of \noestrogen, may enhance the severity of TB, ultimately resulting in adverse reproductive \noutcomes.\nDate submitted:\n22.10.2024\nDate accepted:\n24.08.2025\nPublication Date:\n11.12.2025\nCorresponding Author:\nSeema Dayal, Prof., Uttar Pradesh \nUniversity of Medical Sciences, \nDepartment of Pathology, Etawah, \nIndia\nseemadayal5@gmail.com\nORCID:  \norcid.org/0000-0001-8282-2507\nKeywords: Tuberculosis, leiomyoma, \nadenomyosis, histopathology, \nimmunohistochemistry, Ziehl-Neelsen \nstain\nCite this article as: Dayal S, Kumar A, Kumari K, Singh K, Sharma A. Significance of diminished hormone expression in nulligravida \nwoman presenting with triad of uterine pathologies. Gulhane Med J. 2025;67(4):289-292.\n Seema Dayal1,  Adesh Kumar2,  Kalpana Kumari3,  Kritika Singh1,  Abhishek Sharma1\n1Uttar Pradesh University of Medical Sciences, Department of Pathology, Etawah, India\n2Uttar Pradesh University of Medical Sciences, Department of Pulmonary Medicine, Etawah, India\n3Uttar Pradesh University of Medical Sciences, Department of Obstetrics and Gynecology, Etawah, India\nSignificance of diminished hormone expression in nulligravida \nwoman presenting with triad of uterine pathologies \n\nDayal et al. Significance of diminished hormone expression\n290\nspontaneous abortions, which result in infertility. Leiomyoma is \nbenign smooth muscle uterine tumour whereas adenomyosis is \nthe presence of ectopic endometrial tissue in the myometrium. \nBoth leiomyoma and adenomyosis are hormone-dependent \ntumors; that is, their size and activity increase with elevated of \noestrogen and progesterone levels (4,5). The coexistence of \ngenital TB with leiomyoma and adenomyosis is extremely rare. \nThey also exhibit antagonistic hormone effects. This case is \nbeing reported because of its rare occurrence and to highlight \nthe possible association between these pathologies.\nCase Presentation \nA 40-year-old nulligravida woman presented with complaints \nof pain and mass in the abdomen. She was also suffering \nfrom dysfunctional uterine bleeding, and her laboratory \ninvestigations revealed anemia, which represented her only \nclinical manifestation. Hormone levels could not be accessed \nearlier. A gynaecology examination was suggestive of fibroid \nuterus. The medications were not supportive in controlling \ndysfunctional uterine bleeding, so considering the dysfunctional \nuterine bleeding and the increased size of the fibroid uterus, \nhysterectomy was decided to be performed. Hysterectomy \nwith bilateral (B/L) salpingo-oophorectomy was sent for \nhistopathology examination. The specimen was measured \n14 x 9 x 6 cm. Fibroids obliterated the endometrial cavity. It \nmeasured 8 cm and 4 cm in its largest and smallest diameters, \nrespectively. On further sectioning, they were grey-white in \ncolour with whirling. \nThe right-sided ovary measured 3 x 2 x 1 cm and the left-\nsized ovary measured 6 x 3 x 2 cm. Cut section of B/L ovaries \nshowed solid and cystic areas.\nThe right-sided fallopian tube measured 3 cm in length, \nwhereas left-sided fallopian tube measured 4 cm.\nTissues were stained with hematoxylin and eosin. Ziehl-\nNeelsen (ZN) stain was applied to confirm TB (6), simultaneously \nimmunohistochemistry (IHC) for estrogen and progesterone \nwas also applied.\nHistopathology examination showed smooth muscle fibers \nwith elongated blunt-ended nucleus and eosinophilic cytoplasm \nrunning at various angles with whirling. These finding confirmed \nleiomyoma. \nPlenty of endometrial glands with stroma deep in myometrium \n(more than one low power field from endo myometrial junction) \nwere appreciated. This histomorphology microscopic findings \nwere suggestive of leiomyoma coexisting with adenomyosis and \ncaseous necrosis [Figure 1 (a)].\nThese findings were accompanied by multiple epithelioid \ngranulomas with caseous necrosis in myometrium [Figure 1 (b)]. \nZN stain was also applied to isolate tubercular bacilli but could \nnot be found contributory [Figure 1 (c)].\nBased on these morphologies, the present case was \nreported as leiomyoma with adenomyosis and extra pulmonary \nTB. Tubercular features were also reported in other sections of \nthe uterus. \nIHC was applied for estrogen and progesterone receptors \nexpression. Immunoreactive score (IRS) method was used. \nNuclear positivity was confirmed. It was calculated as follows: \nIRS=staining intensity (SI) x percentage of positive (PP) stained \ncells (PP), where SI was the optical SI (graded as 0=no, 1=weak, \n2=moderate, and 3=strong staining) and PP was the PP. The PP \nis mentioned as 0=no staining, 1=10%, 2=11-50%, 3=51-80% \nand 4=>80. The aggregation of these both finally result in IRS \nscore categorization into negative, mild, moderate and strong \nexpression. \nFigure 1. (a) H&E stained section showing adenomyosis (black arrow) leiomyoma (red) and caseous necrosis (blue). (b) H&E stained section showing \ncaseous necrosis. (c) ZN stained section showing non-contributory staining \nH&E: Hematoxylin and Eosin, ZN: Ziehl-Neelsen\na b c\n\n291Gulhane Med J 2025;67(4):289-292\nThe results showed moderate immunoexpression of \nestrogen [Figure 2 (a)] and progesterone [Figure 2 (b)]. \nInformed consent was obtained from participants.\nWritten informed consent was obtained from the patient for \npublication of this case report and accompanying images.\nDiscussion\nThis case presents a rare coexistence of leiomyoma, \nadenomyosis, and genital TB in a reproductive-age woman, \nhighlighting the complex interaction between hormonal and \ninfectious factors affecting the uterus. \nFemale genital tract TB causes adverse effect on \nreproduction. Tubercular bacilli infect the genital tract by four \nroutes–haematogenous, descending direct spread, lymphatic, \nand sexual transmission. It may cause damage to fallopian \ntube leading to blockage or adhesions, reduced endometrial \nreceptivity or ovarian damage. It is seen in patients of age range \nbetween 20 to 45 years. Clinically, it may be asymptomatic or \npresent with symptoms diversity of symptoms like infertility \nand chronic pelvic inflammatory disease, dysfunctional uterine \nbleeding, pelvic pain and abnormal vaginal discharge (1) .These \nclinical features are not specific to female genital tract TB and \nmay mimic other pathologies (6). \nIn current study, patient was 40-year-old nulligravida \nwoman who presented with pain, mass in the abdomen and \ndysfunctional uterine bleeding. \nThe diagnosis of female genital tract TB are made on basis \nof culture positive specimen, or positive histopathology or strong \nclinical evidence consistent with active EPTB. Chest X-ray, \ncomplete blood count, erythrocyte sedimentation rate, and \ntuberculin test should be applied to rule out systemic spread. The \ntwo imaging techniques hysterosalpingography and sonography \nare also useful, as hysterosalpingography evaluates internal \nstructure and tubal patency whereas ultrasonography carried \nout simultaneous evaluation of ovarian, uterine and extra pelvic \ninvolvement (1). \nRadiology investigations such as ultrasonography shows \nthickened fallopian tubes with or without endometrial thickening, \ntubo-ovarian masses or adhesion. It is often may be misleading \nand mimic other intra uterine pathologies like leiomyoma \nspecifically degenerated one, ovarian tumors etc (7). So, the \nawareness of sonographic changes associated with TB infection \nshould be specifically known which may improve diagnostic \naccuracy and avoid clinical mismanagement and surgical \nexplorations (8).\nIn the present case study, the ultrasonography findings were \nalso suggestive of leiomyoma uteri.\nOn histopathology examination, TB is characterized by the \npresence of epithelioid cell granulomas along with caseous \nnecrosis. The confirmation of TB is done by identification of \nMycobacterium TB with ZN stain (7), but is difficult to diagnose \nthe bacteria in the extrapulmonary sites because the organism \nare sparse in number at extra pulmonary locations (1).\nIn these cases, the ZN stain was also not contributory; \nhowever, the patient improved after antitubercular treatment.\nResearches had already reported that ovarian steroids, \noestradiol and progesterone promote leiomyoma growth (5). \nIntramural is the commonest variants (9). In present study, \nthere were two intramural leiomyoma visualized obliterating the \ncavity. The symptoms depend on location, size of tumour and \nhormonal effect. Here, the patient was presented with mass, \npain in abdomen and dysfunctional uterine bleed.\nLeiomyoma on histopathology is characterised by spindle-\nshaped tumor cells with an elongated, blunt-ended nuclei and \nFigure 2. (a) Figure showing moderate positive immunoreactivity for estrogen receptor (black-gland, blue-stroma). (b) Figure showing moderate \npositive immunoreactivity for progesterone receptor (black-gland, red-stroma)\na b\n\nDayal et al. Significance of diminished hormone expression\n292\neosinophilic cytoplasm forming bundles with whorls (9,10). We \nalso found these features. \nAdenomyosis is characterized by the presence of endometrial \nglands and stroma in the myometrium (11). We also observed these \nfindings in our case. \nAdenomyosis may coincide with leiomyoma, endometriosis, \nendometrial hyperplasia, endometrial polyp, and endometrial \ncarcinoma, which occur due to unopposed estrogen (9,11). The \npresent case consisted of adenomyosis with leiomyoma and \nmyometrial TB. \nEstrogen and progesterone receptors are the members \nof hormone receptor family of ligand dependent transcription \nfactors. Hormone expression rises in leiomyoma and \nadenomyosis (4,5). Rosenthal et al. (12) mentioned that a lack \nof estrogen results in wide dissemination of TB. Ukibe et al. \n(13) assessed the hormonal changes in women suffering from \nTB and reported that progesterone and estrogen were found \nsignificantly low. \nThe benefit of the IRS score is that it includes both epithelial \nand stromal elements for expression (14). In the current study, \nthe estrogen and progesterone receptor expression was found \nto be moderate.\nConclusion \nThe coexistence of leiomyoma with adenomyosis and TB is \nrare. Leiomyoma and adenomyosis depends on sex hormones \nfor proliferation, whereas TB is associated with lower hormone \nexpression. The reduced level of hormone expression, especially \nestrogen, increases the severity of TB and negatively affects \nreproduction. We emphasize that hormone receptor analysis \nshould be included as a supplementary investigation in young \nand nulliparous or gravida tubercular patients.\nEthics \nInformed Consent:  Informed consent was obtained from \nparticipants.\nFootnotes \nAuthorship Contributions\nSurgical and Medical Practices: A.K., K.K., Concept: S.D., \nDesign: S.D., Data Collection or Processing: K.S., Analysis or \nInterpretation: S.D., Literature Search: A.S., Writing: S.D.\nConflict of Interest:  The authors declared no conflict of \ninterest. \nFinancial Disclosure: The authors declared that this study \nreceived no financial support. \nReferences\n1. Sharma JB, Sharma E, Sharma S, Dharmendra S. \nFemale genital tuberculosis: revisited. Indian J Med Res.  \n2018;148(Suppl):S71-S83. \n2. Kleynhans L, Ruzive S, Ehlers L, Thiart L, Chegou NN, Conradie \nM, et al. Changes in host immune-endocrine relationships \nduring tuberculosis treatment in patients with cured and failed \ntreatment outcomes. Front Immunol. 2017;8:690.\n3. Magdy D, Azouz AM, El Zohne RA. Alteration of female sex \nhormones and menstrual pattern among women infected \nwith pulmonary tuberculosis. Egypt J Chest Dis Tuberc . \n2019;68(2):146-149.\n4. Sztachelska M, Ponikwicka-Tyszko D, Martínez-Rodrigo \nL, Bernaczyk P, Palak E, Półchłopek W, et al. Functional \nimplications of estrogen and progesterone receptors expression \nin adenomyosis, potential targets for endocrinological therapy. \nJ Clin Med. 2022;11(15):4407.\n5. Kawaguchi K, Fujii S, Konishi I, Iwai T, Nanbu Y, Nonogaki \nH, et al. Immunohistochemical analysis of oestrogen \nreceptors, progesterone receptors and Ki-67 in leiomyoma \nand myometrium during the menstrual cycle and pregnancy. \nVirchows Arch A Pathol Anat Histopathol.  1991;419(4):309-\n315.\n6. Tjahyadi D, Ropii B, Tjandraprawira KD, Parwati I, Djuwantono \nT, Permadi W, et al. Female genital tuberculosis: clinical \npresentation, current diagnosis, and treatment. Infect Dis \nObstet Gynecol. 2022;2022:3548190.\n7. Shirazi M, Shahbazi F, Pirzadeh L, Mohammadi SR, Ghaffari \nP, Eftekhar T. Tuberculosis endometritis presenting as a \nleiomyoma. Int J Fertil Steril. 2015;8(4):481-484. \n8. Yapar EG, Ekici E, Karasahin E, Gökmen O. Sonographic \nfeatures of tuberculous peritonitis with female genital tract \ntuberculosis. Ultrasound Obstet Gynecol. 1995;6(2):121-125. \n9. Rosai J. Female genital tract . Rosai and Ackerman’s Text \nbook surgical pathology. 9th ed. New Delhi,India: Elsevier; \n2004 pp. 1603-1608.\n10. Dayal S, Kumar A, Verma A. Clinicopathologic correlation \nof leiomyoma with clinical findings and secondary changes \nin a rural population of north India. Am J Clin Pathol.  \n2014;141(2):275-279. \n11. Dayal S, Nagrath A. Pattern and frequency of endometrial and \novarian pathologies with adenomyosis uteri in patients who \nattended the tertiary care hospital among rural population of \nNorth India. MAMC J Med Sci. 2015;1(3):147-150.\n12. Rosenthal AH, Rothfield LD, Chamorro Dauer L. Disseminated \ntuberculosis in a healthy adolescent female. Cureus. \n2019;11(6):e4967.\n13. Ukibe NR, Onyenekwe CC, Ahaneku JE, Ukibe SN, Meludu \nSC, Emelumadu  O, et al. Evaluation of hormonal changes \nin menstrual cycle of women infected with pulmonary \ntuberculosis in Nnewi, south eastern Nigeria. Indian J Tuberc. \n2014;61(2):152-158.\n14. Singh P, Singh P, Chaurasia A, Dhingra V, Misra V. Expression \nof ERα and PR in various morphological patterns of abnormal \nuterine bleeding-endometrial causes in reproductive age \ngroup. J Clin Diagn Res. 2016;10(8):EC06--EC09.","source_license":"CC0","license_restricted":false}