Ovarian carcinoma and peritoneal tuberculosis: A rare coexistence with challenging diagnosis,a case report and literature review

Abstract

Peritoneal tuberculosis is one of the most challenging forms of extrapulmonary tuberculosis to diagnose, especially, in women as it often mimics an advanced ovarian carcinoma. Many authors had documented cases where peritoneal tuberculosis was initially misdiagnosed as advanced ovarian carcinoma, but only four cases had reported the coexistence of both conditions. We present the fifth case in the literature of concurrent peritoneal tuberculosis and serous cystadenocarcinoma of the ovary. A 61-year-old female patient presented with diffuse abdominal tenderness. Physical examination revealed an abdominal distension. Computed tomography scan showed a heterogeneous, poorly defined right latero-uterine mass associated with ascites and nodular peritoneal infiltration. The level of cancer antigen 125 was elevated. Therefore, a diagnosis of advanced ovarian carcinoma was highly suspected. A diagnostic laparoscopy was performed. Peritoneal biopsy confirmed the diagnosis of peritoneal tuberculosis without any histological evidence of malignancy. The patient subsequently underwent a right adnexectomy, which revealed serous cystadenocarcinoma of the ovary. She received 6 months of antituberculosis treatment complicated with renal dysfunction. Computed tomography scan control showed no abnormalities. Tumor markers levels decreased to the normal range. The patient refused further surgery and chemotherapy was recommended. Female patients presenting with ascites, adnexal masses, and elevated levels of cancer antigen 125 are usually presumed to have advanced ovarian carcinoma. There are a few discriminating features that suggest the diagnosis of peritoneal tuberculosis rather than peritoneal carcinomatosis of an advanced ovarian carcinoma. Eventually, their coexistence should be considered as a differential diagnosis, particularly in developing countries where tuberculosis is still endemic as it is the case of Tunisia.

Introduction

Tuberculosis (TB) remains a major global health problem with significant morbidity and mortality, especially in developing countries. It ranks as the tenth leading cause of death worldwide. ¹

Peritoneal TB (PTB), although rarer than pulmonary TB, is a serious health concern in regions with high TB prevalence. ² It is a specific subtype of abdominal TB affecting the parietal and visceral peritoneum. ¹ The prevalence of PTB appears to be rising and is thought to be secondary to the increasing prevalence of immunocompromised states. It accounts for about 25%–50% of abdominal TB cases and ~1% of all TB cases. ² PTB most commonly affects those between the ages of 25 and 55 years with variable gender differences and has a strong correlation with lower socioeconomic status, malnutrition, poor hygiene, and overcrowding. ¹ Diagnosis of PTB in women is often challenging, as it frequently mimics advanced ovarian carcinoma (AOC). ³ Common indicators include pelvic pain or discomfort, abdominal distension, ascites, adnexal masses, and elevated levels of cancer antigen 125 (CA-125). ⁴ Laboratory tests are often of limited value, including elevated CA-125 serum levels, negative tuberculin skin tests, and difficulty in culturing Mycobacterium species. ⁵ Abdominal imaging of PTB frequently mimics malignancy and is reported to have limited diagnostic accuracy. ⁶ However, certain radiological features, when interpreted by an experienced radiologist, can help differentiate PTB from peritoneal carcinomatosis.^7,8 Conversely, abdominal ultrasound, when performed by a skilled radiologist, is an effective tool for diagnosing ovarian masses and differentiating between benign and malignant ovarian diseases, particularly in smaller-sized masses. ⁹

Treatment and prognosis of PTB differ significantly from those of AOC. PTB is managed medically with anti-TB drugs, and it is curable, whereas AOC requires debulking surgery followed or preceded by chemotherapy and typically has a poor prognosis. Therefore, it is important to differentiate between these two entities. In the literature, many cases of PTB, initially mistaken for AOC, had been reported, but only four cases presented the association between the two. We report the fifth case, which discusses the coexistence of PTB and serous cystadenocarcinoma of the ovary. This case report is reported according to the CARE criteria. ¹⁰

Case report

We report the case of a 61-year-old female patient with a history of hypertension and diabetes ongoing for 16 years, well-managed with good therapeutic compliance, who consulted for diffuse abdominal pain and progressive abdominal distension. There were no associated fever, night sweats, or weight loss. Upon questioning, there was no history of TB exposure or consumption of unpasteurized dairy products. Physical examination was notable for abdominal distention and diffuse tenderness. Furthermore, the gynecological exam was unremarkable. The biological assessment showed no abnormalities, notably no leukocytosis. A transabdominal ultrasound was performed by an experienced radiologist, showing a large effusion and echogenic pelvic nodular formations measuring 1–2 cm, associated with significant ascites. However, the pelvis could not be thoroughly evaluated due to the abundant ascites. The aspiration of the ascitic fluid showed a richly cellular fluid composed of numerous mesothelial cells with a dystrophic appearance, along with polymorphic inflammatory elements. Computed tomography (CT) scan of the abdomen and pelvis showed a heterogenous, poorly defined right latero-uterine mass, measuring 100 × 110 mm, largely necrotic, along with significant ascites, and nodular infiltration of the peritoneum. Tumor marker tests revealed elevated levels of CA-125 and carbohydrate antigen 19-9 (CA 19-9), respectively, at 4592 and 7267 U/ml, while the carcinoembryonic antigen level was normal at 18.79 U/ml. Esophagogastroduodenoscopy and colonoscopy were indicated but showed no significant abnormalities. Therefore, the diagnosis of AOC with peritoneal carcinomatosis was strongly suspected. A diagnostic laparoscopy was performed, revealing a right ovarian mass with diffuse peritoneal nodules (Figure 1). A peritoneal biopsy was carried out. Histopathological examination, revealed an inflammatory infiltrate rich in lymphocytes containing epithelioid and giant-cell granulomas without caseous necrosis, suspecting PTB with no histological evidence of malignancy. A search of Mycobacterium tuberculosis in sputum and a tuberculin skin test were negative. The patient was reoperated. Abdominal exploration showed extensive disseminated peritoneal granulations of regular size (2–5 mm), confluenting to larger friable nodules in some areas, associated with a right ovarian mass. This mass was fibrocystic, without external vegetation, and measuring 10 cm. The contralateral ovary, uterus, and liver were normal. There were no pelvic or lombo-aortic lymph nodes. Based on these intraoperative findings, cytological sample with second peritoneal biopsy and right adnexectomy were performed (Figure 2).

Figure 1.

Intraoperative image showing peritoneal nodules.

Figure 2.

Right adnexectomy specimen.

Pathological examination of the right adnexectomy specimen concluded the diagnosis of ovarian serous cystadenocarcinoma of high grade, presenting only intracystic vegetations. Peritoneal biopsy confirmed the diagnosis of PTB, whereas the cytologic sample was inconclusive.

The case was presented at a multidisciplinary consultation meeting, and the decision was to initiate antituberculous treatment before proceeding with ovarian staging surgery. The patient received 2 months of treatment with isoniazid at 5 mg/kg/J, rifampin at 10 mg/kg/J, pyrazinamide at 25 mg/kg/J, and ethambutol at 15 mg/kg/J. Then, she passed over her second multidisciplinary consultation meeting but continued her anti-TB treatment with 4 months of isoniazid and rifampin. She developed an acute renal insufficiency characterized by an increase in creatinine levels. Renal recovery was obtained with proper hydration and adjustment of hypertension and diabetes drugs without any dose modifications in anti-TB treatment. After 6 months of follow-up, the CT scan showed no abnormalities, with CA-125 and CA-19-9 levels reassessed at 23 and 48 U/ml, respectively. CA-19-9 level continued to decrease, and a normal level was obtained a month later. As a consequence of favorable clinical evolution and a history of renal dysfunction, the patient refused to undergo a complete staging surgery. Therefore, chemotherapy based on paclitaxel and carboplatin was recommended.

Discussion

TB, caused by a Mycobacterium of the TB complex, is a contagious disease that continues to pose a public health challenge in developing countries. ¹¹ Despite ongoing efforts by the National Tuberculosis Control Program, Tunisia remains a country with an intermediate level of TB endemicity, with an increasing trend in extrapulmonary localizations. ¹²

This increasing prevalence of PTB is thought to be associated with immunocompromised states that include liver cirrhosis, renal failure requiring peritoneal dialysis, diabetes mellitus, malignancies, AIDS, and the administration of systemic corticosteroids. ¹ However, about 12% of patients with PTB have no identifiable risk factors, making diagnosis even more difficult. ⁵

The peritoneum can be implicated during TB infection by different mechanisms that include ¹ :

• Reactivated latent tuberculous foci in the peritoneum, acquired by hematogenous spread from a primary lung focus.

• Hematogeneous spread from active pulmonary, miliary TB, or silent bacteremia during the primary phase of TB.

• Direct spread from infected organs such as the intestine and fallopian tubes and rupture of a tuberculous intra-abdominal lymph node.

• Through lymph channels from infected abdominal lymph nodes. Indeed, abdominal lymph nodal TB and PTB may occur without gastrointestinal involvement.

Clinically, PTB often presents with nonspecific symptoms such as an insidious progression of abdominal pain (50%–100%) and distention due to ascites (40%–73%). General symptoms including weight loss, fever, and night sweats may also be reported. ¹³ In female patients, PTB may manifest with pelvic pain, abdominal distension, elevation of serum CA-125 levels, or adnexal mass, which may resemble AOC. ⁶ In our case, the clinical presentation alone was unlikely to suggest PTB, except for the epidemiological context of Tunisia, a region where TB remains prevalent.

However, clinical findings cannot establish or exclude the diagnosis of PTB and there are still no tools for the rapid and accurate diagnosis of PTB. Laboratory tests often prove unhelpful, as confirmed in this report. Examples include elevated CA-125 serum levels, negative tuberculin skin tests, and the culture growth of Mycobacterium species. ⁵

Elevated serum CA-125 levels are generally considered indicative of epithelial ovarian malignancies, particularly in postmenopausal women. However, CA-125 is a nonspecific marker that may also be elevated in various benign gynecological and non-gynecological conditions. CA-125 is a glycoprotein expressed by cells lining the uterine endometrium, and its levels can rise in conditions such as ovarian malignancies, endometriosis, and pelvic inflammatory disease. Additionally, CA-125 is expressed by cells lining the pleura, pericardium, and peritoneum, leading to elevated serum levels in cases of PT, intestinal malignancies, and postoperative states. ¹⁴ While an elevated CA-125 level is not useful in the differential diagnosis of PT, it may serve as a marker for monitoring the efficacy of anti-tuberculous treatment. ⁵ In our case, involving the coexistence of ovarian serous cystadenocarcinoma and PT, an initial CA-125 level of 4592 U/ml significantly decreased to 23 U/ml following adnexectomy and antituberculous treatment.

Direct analysis of ascitic fluid in PTB, revealing lymphocyte dominance without malignant cells, can provide a diagnostic clue. The culture growth of Mycobacterium species from ascitic fluid can aid in diagnosing PT; however, the 4–6 week delay in obtaining culture results poses a significant risk of increased mortality. ⁵ Several studies highlight the diagnostic value of adenosine deaminase levels in biological fluids. ¹⁵

Abdominal imaging in PTB often resembles malignancy and has been reported to have limited diagnostic accuracy. Features such as ascites, peritoneal and omental disease, pelvic masses, and enlarged retroperitoneal lymph nodes are common to both TB and advanced malignancy. ¹⁶ However, specific radiological findings may help differentiate tubercular pathology from malignancy, particularly when interpreted by an experienced radiologist. On abdominal ultrasound, ascites with fine fibrous strands and lymphadenopathy with hypoechoic cores indicative of caseation are more suggestive of TB. ⁶ Conversely, abdominal ultrasound can effectively diagnose ovarian masses and distinguish between benign and malignant ovarian diseases when performed by an experienced radiologist.^7,8 In our patient’s case, however, the abundant ascites hindered the visualization of the ovarian mass on abdominal ultrasound. An abdominal contrast-enhanced CT scan can provide further diagnostic clarity. Findings, such as septate or particulate ascites, omental fat stranding, ill-defined adnexal masses, smooth and strongly enhancing peritoneal thickening, and caseous lymph nodes, suggest TB. In contrast, well-defined, heterogeneous adnexal masses, nodular peritoneal thickening, and a nodular or caked omentum are more indicative of malignancy. ⁶ Furthermore, heterogeneous parenchymal hyperattenuation and capsular change of the ovary were more frequently seen in cases of peritoneal carcinomatosis than in cases of female PTB. ¹⁷ In our case, the CT scan revealed a heterogeneous right ovarian mass accompanied by a large volume of ascites and nodular peritoneal infiltration, findings highly suggestive of ovarian cancer with peritoneal carcinomatosis.

The peritoneal biopsy is the most sensitive and specific diagnostic procedure for PTB. It can be obtained by different procedures including CT-guided peritoneal biopsy and laparotomy or laparoscopic biopsy. ¹³ Laparoscopy with directed biopsy has a better diagnostic value. It is safer, provides better inspection, and allows a shorter hospital stay, rapid postoperative recovery, and quick return to social activities. Characteristic laparoscopic findings include free ascites, multiple yellowish-white nodules or tubercles on the visceral and parietal peritoneum, peritoneal or visceral adhesion, and occasionally inflamed hemorrhagic areas on the peritoneum. ¹ However, while laparoscopy is crucial for diagnosing PTB, its visual appearance can be misleading even for experienced clinicians since the features of TB can resemble those of disseminated abdominal malignancies, such as ovarian cancer. ¹⁸ A diagnostic laparoscopy of our patient revealed a right ovarian mass with diffuse peritoneal granulations and nodules. Only a peritoneal biopsy was performed as AOC was strongly suspected. Therefore, a subsequent surgical procedure for an adnexectomy was necessary to confirm a serous ovarian cystadenocarcinoma associated with the previously diagnosed PTB.

Biopsy specimens should be sent for microbiological and histopathological evaluation. The sensitivity of acid-fast bacilli smears and mycobacterial cultures for biopsies is low (<50%). Polymerase chain reaction is more sensitive and specific for diagnosing TB. ¹⁹ Microscopically, PTB is characterized by numerous large and confluent granulomas of epitheloid cells, with a peripheral zone of lymphocytes and Langhans giant cells, often accompanied by central caseous necrosis. ²⁰ Histological examination may reveal only epitheloid necrotizing gigantocellular granulomas, indicative of TB but not pathognomonic. ¹⁹

In the literature, many authors had documented cases of PTB initially mistaken for AOC, but only five cases, including our patient, had reported the association between the two conditions. All cases are summarized in Table 1.

Table 1.

Reported cases of association between PTB and ovarian cancer.

Case	Author, year	Age (years)	Symptoms and examination findings	Tumor markers	Ascitic fluid	PTB diagnosis	Type of surgery	Ovarian cancer stage (FIGO	Ovarian cancer histological type
1	Nagashima 21 (2013)	47	ND	ND	ND	Peritoneal biopsy	Hysterectomy + bilateral salpingo-oophorectomy + omentectomy + pelvic and para-aortic lymphadenectomy	IIIC	Papillary serous carcinoma
2	Shukla 22 (2019)	50	Postmenopausal bleed + abdominal distension + loss of weight and appetite + fever Examination: abdominal distension + ascites	CA-125: 529 U/ml	ADA: 47.78 U/ml Microscopic examination: mesothelial cells, lymphocytes, clusters of atypical cells	Endometrial biopsy	Non-operated	ND	Papillary serous carcinoma
3	Saini 23 (2020)	21	Asymptomatic examination: abdominopelvic mass	CA-125: 229 U/ml LDH: 5454 U/L	ND	Peritoneal biopsy	Right salpingo-oophorectomy + omentectomy + pelvic and para-aortic lymphadenectomy	IC2	Dysgerminoma
4	Yamamura 24 (2024)	68	Abdominal mass + fever Examination: abdominal mass	ND	ND	Peritoneal biopsy	Hysterectomy + bilateral salpingo-oophorectomy + omentectomy	IC1	Endometrioid carcinoma grade 3
Present case		61	Diffuse abdominal pain + abdominal distensionExamination: abdominal distension + ascites	CA-125: 4592 U/mlCA-19-9: 7267 U/ml	Microscopic examination: mesothelial cells with a dystrophic appearance, polymorphic inflammatory elements	Peritoneal biopsy	Adnexectomy	a	Serous cystadenocarcinoma

ADA: adenosine deaminase; CA-19-9: carbohydrate antigen 19-9; CA-125: cancer antigen 125; ND: no data; PTB: peritoneal tuberculosis.

a

In our case, no complete stagging surgery was performed to assess the FIGO stage.

Treatment and prognosis of PTB differ significantly from those of AOC. Therefore, it is important to differentiate between these two entities. Treatment of extrapulmonary TB consists of a 6-month regimen based on isoniazid, rifampicin, pyrazinamide, and ethambutol, which is effective for patients with abdominal TB, including PTB. ²⁵ Although the disease is usually sensitive to this standard treatment, the optimal duration of therapy is debatable and can be extended to 9–12 months by some physicians without any scientific proof. ¹ AOC requires debulking surgery preceded or followed by chemotherapy and typically has a poor prognosis. In our case, initiation of anti-TB treatment before reoperating our patients was discussed due to the extensive nodular infiltration and hyperemia of the peritoneum and the extended surgery needed for staging ovarian cancer, which would increase perioperative complications.

Conclusion

Diagnosing PTB is challenging due to its insidious nature, the variability of clinical presentation, and the limitations of accurate diagnostic tools.

Among the many diseases that need to be differentiated from PTB, AOC with peritoneal carcinomatosis remains the most challenging, due to their similar clinical and imaging findings. Therefore, It is important to distinguish between these two conditions, as their treatment differs drastically. Laparoscopy with guided biopsies is valuable for establishing an accurate diagnosis.

Furthermore, The coexistence of PTB and AOC should be considered as a differential diagnosis, particularly in developing countries where TB is still endemic. The prognosis of this association remains uncertain as only five cases were reported in the literature.

Supplemental Material

sj-pdf-1-whe-10.1177_17455057251342358 – Supplemental material for Ovarian carcinoma and peritoneal tuberculosis: A rare coexistence with challenging diagnosis, a case report and literature review

Supplemental material, sj-pdf-1-whe-10.1177_17455057251342358 for Ovarian carcinoma and peritoneal tuberculosis: A rare coexistence with challenging diagnosis, a case report and literature review by Sabrine Boukhris, Eya Rahmouni, Racha Ben Romdhane, Houyem Mansouri, Samia Ben Hssine, Najet Mahjoub, Ines Zemni and Leila Achouri in Women's Health