Primary Ovarian Tuberculosis: A Case Report with Unusual Clinical Presentation.

INTRODUCTION Tuberculosis (TB) is a significant global health issue, affecting around 10 million people in 2017 and causing approximately 1.5 million deaths.[1] The global incidence rate increased by 3.6% from 2020 to 2021, reversing a previous trend of about 2% annual reduction over the last two decades. India accounts for about 25% of the global TB burden, with an estimated incidence of 2.77 million cases in 2022. While TB primarily impacts the lungs, extrapulmonary cases are also common, particularly among younger patients, especially females, accounting for about 10%–15% of all TB infections. Genitourinary TB is the second most common extrapulmonary manifestation (40%), following lymphatic involvement (50%) and pleural effusions (24%). The fallopian tubes are the most frequently affected (90%–100%), followed by the uterus (70%), ovaries (30%), cervix (10%), and rarely, the vulva and vagina.[2,3] Genital TB (GTB) usually arises from lymphohematogeneous dissemination from pelvic lymph nodes, initially involving the outer surface of the ovaries. In cases of primary tuberculous infection, there is often no evidence of TB elsewhere in the body. Delayed diagnosis can lead to disease progression and irreversible tissue damage. Isolated primary ovarian TB is a very rare form of GTB. We present an unusual case of primary ovarian TB in a 41-year-old woman who presented with abdominal distension, with a clinical suspicion of ovarian carcinoma suggested by ultrasound findings. Inclusion criteria for the study required patients with confirmed primary ovarian TB, particularly those presenting with adnexal masses and symptoms mimicking ovarian cancer. It focused on women of reproductive age from high-prevalence TB areas to assess the impact on fertility. Exclusion criteria included patients with TB in other organs or those with preexisting fertility issues unrelated to TB. Cases lacking histopathological confirmation of TB were also excluded. In addition, patients who had already undergone TB treatment or those outside the reproductive age range were not included. CASE REPORT A 41-year-old multiparous woman presented to the surgical outpatient unit with abdominal and pelvic pain persisting for 1 year, accompanied by low-grade fever and weakness. She had no history of cough, breathlessness, or weight loss, and her family history was unremarkable. The patient had undergone tubectomy 2 years prior and had two previous cesarean sections. On examination, she appeared mildly anemic, with a distended abdomen and generalized tenderness, but no ascites were noted. Ultrasonography (USG) revealed a well-defined, heterogeneously hypoechoic lesion in the left ovary, characterized by multiple solid cystic areas and minimal vascularity, as well as minimal ascites. The right adnexa appeared normal. A diagnosis of a complex ovarian cyst and possible ovarian carcinoma was suspected. Laboratory tests indicated a hemoglobin level of 8.30 g/dL and an elevated erythrocyte sedimentation rate of 90 mm/h. She was seronegative for HIV, and her cancer antigen 125 (CA-125) level was elevated at 119 U/mL. The patient underwent laparotomy, which revealed a solid cystic mass in the left ovary covered with whitish, cheesy material. In addition, multiple whitish areas measuring 1–2 mm were observed in the omentum. A diagnosis of ovarian TB was suspected, while the left fallopian tube and right adnexa appeared normal. The surgical specimen from the left oophorectomy with omentum was submitted for histopathological examination. Grossly, it comprised a single piece of grayish-white tissue measuring 8 cm × 7.5 cm × 5 cm. The external surface of the ovary appeared congested with whitish areas, and multiple 1–2 mm whitish miliary tubercles were observed in the omentum. On cut section, solid cystic areas were noted, with the largest cyst measuring 0.6 cm × 0.9 cm. Amorphous to granular cheesy material was released upon cutting the specimen [Figure 1a]. Histological analysis showed extensive caseous necrosis surrounded by epithelioid histiocytes, Langhans giant cells, and multinucleated giant cells [Figures 1b and 2a]. Omental tissue revealed fibrofatty tissue with scattered epithelioid granulomas and caseous necrosis. Ziehl–Neelsen stain identified occasional acid-fast bacilli [Figure 2b], confirming a diagnosis of TB salpingitis. Chest X-ray and high-resolution computed tomography of the lungs showed no cavitary lesions or miliary tubercles. The patient is currently on close follow-up.

Female GTB (FGTB) is an uncommon cause of gynecological admissions and, despite being treatable, poses a significant global health challenge. The burden of FGTB remains unclear, as it is frequently underdiagnosed, even among women in high-burden TB settings. The perception that FGTB is a rare form of extrapulmonary TB (EPTB) stems from several challenges, including limited healthcare access for women, the often subtle or covert nature of its symptoms, and the paucibacillary nature of the disease, which complicates diagnosis. These factors contribute to the underreporting and misdiagnosis of FGTB, despite its potential prevalence.[4] The diagnostic challenge occurs when the disease presents with variable symptoms, making it essential for clinicians to maintain a high level of suspicion to accurately diagnose the condition.[5] It primarily affects women of reproductive age, especially those between 20 and 40 years. Genitourinary TB is the second most common form of EPTB, following lymph node involvement, with the endometrium and fallopian tubes frequently affected. Common symptoms of FGTB include infertility, pelvic pain, general malaise, and menstrual disturbances. Ovarian TB can be primary or secondary, with isolated cases being rare. In primary ovarian TB, no other TB evidence is present, while secondary infections typically arise from foci in the fallopian tubes, endometrium, or lungs. Possible routes of ovarian tuberculous infection include: Direct spread, hematogeneous spread which usually affects the outer surface of the ovaries, often linked to pulmonary infection, and lymphatic dissemination.[6,7] GTB is identified in approximately 1% of all patients diagnosed with TB. Rare instances of primary infection have been reported, occurring through sexual intercourse with an infected partner who has tuberculous lesions on the genitalia. The symptoms are typically mild and localized, which often leads to the disease being largely undiagnosed.[8,9] In our patient, imaging studies (USG and computed tomography) showed no abdominopelvic lymphadenopathy. Reports of primary ovarian TB without involvement of other organs are limited. The differential diagnosis for FGTB is broad, and it is often misdiagnosed as chronic pelvic inflammatory disease, both conditions presenting with elevated erythrocyte sedimentation rates. The genital tract becomes particularly susceptible to TB after puberty. Clinically, ovarian TB can mimic ovarian carcinoma, and it may be discovered incidentally during evaluations for malignancy. The clinical presentation of GTB varies depending on the affected area of the genital tract. Physical examinations can be unremarkable in up to 50% of FGTB cases, with little correlation between symptoms and physical findings. Abnormal findings typically include adnexal masses or signs of ascites. Laparoscopy represents a significant advancement in diagnosing TB, achieving over 97% accuracy while avoiding laparotomy.[10,11] However, it was not performed in our case due to a suspicion of ovarian carcinoma. During exploratory laparotomy, distinguishing between pelvic TB and extraovarian carcinomatosis can be challenging, as their macroscopic appearances may be similar. Intraoperative frozen sections can be valuable for ruling out pelvic TB in patients undergoing surgery for tubo-ovarian masses, especially in areas where TB is highly prevalent. Unfortunately, this was also not done in our case. Isolated ovarian TB is very rare and can mimic ovarian malignancy, presenting with an ovarian mass, ascites, and elevated CA-125 levels. In cases of ovarian TB, CA-125 levels rarely exceed 500 U/mL, as seen in this case with a level of 450 U/mL. Simsek et al. demonstrated that decreasing CA-125 levels correlate with the gradual resolution of the disease during antituberculous treatment, suggesting that serial measurements should be routinely used to assess treatment effectiveness. In addition, human epididymis protein 4 has shown greater specificity than CA-125 as a marker for benign conditions.[11,12] A diagnosis of pelvic TB should be kept in mind as a differential diagnosis, especially both in developing and underdeveloped countries where TB is more prevalent. The definitive diagnosis of pelvic Tb underlies in the demonstration of acid-fast bacilli in tissue sections. The World Health Organization recommends treating FGTB with an intensive phase of daily rifampicin (R), isoniazid (H), pyrazinamide (Z), and ethambutol (E) for 2 months, followed by a continuation phase of daily R and H for 4 months. An alternative regimen includes 2 months of RHZE, followed by alternate-day RH for 4 months. A thrice-weekly dosing option (2RHZE for 2 months and 4HR for 4 months) can be used under directly observed treatment, short-course (DOTS), ensuring each dose is directly observed.[12–14] Patients are categorized based on disease severity, with GTB classified as category 1 (serious extrapulmonary disease). Treatment is provided through DOTS centers with fixed drug combinations. Surgery is limited to cases unresponsive to medical therapy, including procedures like drainage of pyosalpinx and removal of large tubo-ovarian abscesses, followed by anti-TB treatment for better outcomes. Differential diagnosis of FGTB varies based on the site of involvement such as pelvic inflammatory disease, ectopic pregnancy, ovarian cyst, endometriosis, carcinoma of the colon and diverticulitis for tuberculous salpingitis; dysfunctional uterine bleeding and endometrial carcinoma in endometrial TB, ovarian malignancy in ovarian TB, carcinoma of the cervix in cervical TB, elephantiasis vulva in vulval TB.[15] The diagnosis and management of TB face several critical challenges that need to be urgently addressed. One major issue is the lack of a point-of-care test capable of reaching remote areas, despite numerous initiatives by the government and other partners. These advancements are not effectively reaching these regions, and diagnosing EPTB remains a significant hurdle due to difficulties in obtaining clinical samples from inaccessible sites and the low sensitivity of existing diagnostic tests. For instance, GeneXpert has a low detection rate in fluids like ascitic and pleural fluids, while liquid culture, though more reliable, takes 2–3 weeks for results. There is an urgent need for biomarkers to diagnose EPTB using alternative samples such as blood, serum, urine, or sweat. The lack of early diagnostic and prognostic markers, especially for distinguishing latent TB from active disease, is also a key concern. This is particularly important in patients co-infected with HIV, where alternative clinical samples for both pulmonary and EPTB require more research. In addition, the potency of anti-TB drugs, treatment compliance, and whether treatment should be adjusted based on mycobacterial burden are pressing issues. Experts suggest the development of novel triage tests, including biomarkers or handheld devices like X-rays or adhesive sensors. A promising new sensor technology, which changes color based on the presence of TB, is currently undergoing evaluation and could revolutionize TB screening.[16]

Primary ovarian TB is rare but can mimic ovarian tumors, presenting as an adnexal mass. It is crucial to consider it in evaluations of such masses. While TB is curable and preventable, GTB remains a significant infertility risk for women of reproductive age. Outcomes of the study This case highlights the importance of considering primary ovarian TB in the differential diagnosis of adnexal masses, as it can mimic ovarian cancer, with histopathological confirmation being key to accurate identification. The study underscores the effectiveness of anti-tubercular therapy in managing GTB and preventing complications like infertility, particularly in women of reproductive age in high-prevalence areas. Clinicians are reminded to maintain a high index of suspicion for TB in atypical cases, contributing to better diagnostic and therapeutic outcomes, while the documentation of this rare case adds valuable data to the literature and encourages further research. The study focuses on the rare occurrence of primary ovarian TB, which can be misdiagnosed as ovarian cancer, highlighting the need for accurate diagnosis to ensure appropriate treatment. It aims to raise awareness among clinicians, particularly in high-prevalence areas, to improve early detection and prevent complications like infertility. However, as a single case report, the findings are limited in generalizability. The lack of long-term follow-up on fertility and recurrence outcomes restricts insight into the therapy’s lasting effectiveness. In addition, the study’s reliance on histopathology may pose challenges in low-resource settings, limiting broader applicability. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initials will not be published and due efforts will be made to conceal her identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Extra pulmonary; ovary; primary; tuberculosis