Journal of Obstetrics and Gynaecology, 2014; 34: 268–271 © 2014 Informa UK, Ltd. ISSN 0144-3615 print/ISSN 1364-6893 online DOI: 10.3109/01443615.2013.870140
GYNAECOLOGY
Disseminated peritoneal tuberculosis mimicking advanced ovarian cancer I. Lataifeh1,4, I. Matalka2, W. Hayajneh3, B. Obeidat1, H. Al Zou’bi2 & G. Abdeen5
J Obstet Gynaecol Downloaded from informahealthcare.com by University of Washington on 02/11/15 For personal use only.
Departments of 1Obstetrics and Gynecology, 2Pathology and 3Pediatrics, Jordan University of Science and Technology, Irbid, 4Surgery and 5Medicine, King Hussein Cancer Center, Amman, Jordan
The objective was to evaluate the clinical and radiological features of peritoneal tuberculosis (PTB) that resembled advanced ovarian malignancy. A retrospective review of all patients diagnosed with PTB over a period of 10 years was made. The data included: age, presenting symptom(s), CA125 level, microbiological, histological and cytological studies of the surgical specimens. The radiological and operative findings were also reviewed. A total of 16 patients were identified. The median age was 29.5 years (range 13–65 years). The median CA125 level was 319 U/ml (range 45–1,072 U/ml). The most common symptoms were abdominal distention and pain in 13 patients. Imaging studies showed ascites in all patients. Six patients had laparotomy and 10 had laparoscopy procedure. All patients received anti-tuberculosis treatment and had complete cure. A high index of suspicion of PTB is important to avoid unnecessary extended surgery in relatively young patients with nonspecific clinical features. Keywords: Ascites, CA125, laparoscopy, laparotomy, ovarian cancer, peritoneal tuberculosis
Introduction Peritoneal tuberculosis (TB) is a form of abdominal TB that predominantly involves the omentum, intestinal tract, liver surface, spleen or the female genital tract in addition to the parietal and visceral peritoneum (Hopewell 1994). It occurs in 1–4% of patients with pulmonary TB and results from reactivation of latent tuberculous foci in the peritoneum or from haematogenous spread from a primary disease in the lungs (Hopewell 1994; Sinan et al. 2002; Koc et al. 2006). Many women with peritoneal TB lack typical symptoms and laboratory data, therefore, peritoneal TB is usually difficult to diagnose in women and often mimics advanced stage epithelial ovarian carcinoma or primary peritoneal carcinoma (Ibrahim et al. 1999; Tan et al. 1999). Pelvic pain or discomfort and mass, ascites and elevated serum CA125 levels are common markers (Engin et al. 2000; Bilgin et al. 2001). The treatment and outcome of peritoneal TB and that of advanced ovarian carcinoma differ markedly. Peritoneal TB is treated medically with anti-tuberculosis drugs and is a curable disease, while advanced ovarian carcinoma is treated by debulking surgery followed by cytotoxic drugs and has a poor outcome. Reports of peritoneal TB in the literature have been limited to small series and sporadic case studies, which were often
misdiagnosed as carcinomatous peritonitis (Demir et al. 2001; Wu et al. 2003). In this retrospective study, we evaluated the clinical, laboratory and radiological features in patients with peritoneal TB.
Materials and methods We retrospectively reviewed the medical records of all patients diagnosed with peritoneal TB at King Abdullah University Hospital (KAUH) and King Hussein Cancer Center (KHCC) in Jordan, over a period of 10 years between July 2002 and June 2012. The following data were collected for each patient – clinical data including: age, parity, presenting symptom(s) and its duration and presence or absence of ascites; laboratory data including: preoperative CA125 levels (U/ml) and microbiological, chemical and cytological studies of ascites. Frozen section and final pathology results of the biopsy(ies) and specimens of peritoneal or omental nodules and ovarian masses were also collected. The radiological studies included: chest radiographic findings; imaging studies, such as abdomen and pelvis ultrasound scan (USS); computed tomography (CT); magnetic resonance imaging (MRI) and upper and lower gastrointestinal (GI) endoscopy. The operative findings of exploration laparotomy or laparoscopy were also collected. The diagnosis of TB was established on the basis of at least one of the following criteria (as advocated by Pauslian et al. 1964): (1) histological evidence of caseating granulomatous inflammation; (2) acid-fast bacilli identified in tissue specimens or ascitic fluid; (3) tissue or ascitic fluid culture yielding M. tuberculosis; (4) positive polymerase chain reaction (PCR) analysis for M. tuberculosis DNA on tissue specimens or ascitic fluid; or (5) a good therapeutic response to anti-TB agents in patients with clinical evidence of peritoneal TB. The data was analysed using Microsoft Excel 2007 program. Descriptive statistics was performed. The median, minimum and maximum values for age, and serum CA125 levels were calculated. The study was approved by the local IRB of both institutions.
Results During the study period, a total of 16 patients with a documented diagnosis of peritoneal TB were identified at the two centres. The distribution by centre was 13 patients (81.3%) at KAUH
Correspondence: I. Lataifeh, Department of Obstetrics and Gynecology, Jordan University of Science and Technology, PO Box 3030, Irbid 22110, Jordan. E-mail: [email protected]
J Obstet Gynaecol Downloaded from informahealthcare.com by University of Washington on 02/11/15 For personal use only.
Peritoneal TB mimicking advanced ovarian cancer 269 and three patients (18.7%) at KHCC. Clinical and radiological characteristics of the patients are shown in Table I. The median age of the patients was 29.5 years (range 13–65 years). A total of 12 patients (75%) were premenopausal and four patients (25%) were postmenopausal. Preoperative serum CA125 levels were elevated in all patients, with a median serum level of CA125 of 319 U/ml (range 45–1,072 U/ml). The serum level of CA125 was lower than 100 U/ml in three patients, between 101 and 1,000 U/ml in 12 patients and higher than 1,000 U/ml in one patient. The most common symptoms reported were abdominal distention and pain; they were reported in 13 patients (81.3%). Six patients (37.5%) had fever, and none of them presented with abdominal masses. The duration of the symptoms varied from 1 week to 12 months. One patient had a family history of TB. None of the patients was receiving immune suppressive therapy. Preoperative radiological studies showed ascites in all patients. Omental and peritoneal thickening was noted in eight patients (50%); omental nodule(s) in four patients (25%). Heterogeneous pelvic mass was noted in six patients (37.5%) and pleural effusion was noted in four patients (25%). Paracentesis was done in three patients (18.8%) but it was not helpful to predict peritoneal TB. Peritoneal TB was suspected at presentation in only three of the patients, and was confirmed by diagnostic laparoscopy and tissue biopsy. The remaining 13 patients underwent diagnostic procedures, with a provisional diagnosis of advanced ovarian cancer or primary peritoneal carcinoma. The diagnostic procedures, pathology, and peritoneal fluid analysis findings are shown in Table II. Six patients (37.5%) had laparotomy, while 10 patients (62.5%) had diagnostic laparoscopy. On the laparotomy group, two patients who were postmenopausal underwent extended surgery, including a total hysterectomy, bilateral salpingo-oophorectomy and omentectomy (owing to the co-existing uterine fibroid in one patient and to the suspicion of advanced ovarian malignancy in the other patient). The other four patients had limited surgical procedure. Table I. Clinical and radiological characteristics of the patients. Findings Age (years) (median, range) Menopausal status Premenopausal Postmenopausal CA125 level (U/ml) (median, range) Clinical symptoms Abdominal distention Abdominal pain Fever Anorexia Weight loss Nausea and vomiting Cough Night sweat Abdominal mass USS/CT scan/MRI Ascites Omental and peritoneal thickening Omental nodule(s) Pelvic mass Peritoneal thickening/carcinomatosis Pleural effusion
n
(%) 29.5 (13–65)
12 4
75 25 319 (45–1,072)
13 13 6 4 3 3 2 1 0
81.3 81.3 37.5 25.0 18.8 18.8 12.5 6.3 0
16 8 4 6 1 4
100 50.0 25.0 37.5 6.3 25.0
CA125, carcinogenic antigen; CT, computed tomography; GIS, gastrointestinal system. MRI, magnetic resonance imaging; USS, ultrasound scans.
Table II. Diagnostic procedures, pathology and peritoneal fluid analysis. Parameter Diagnostic approach Laparotomy Peritoneal, omental biopsy Omental biopsy, OC Omental biopsy, Ov. cystectomy Omentectomy, TAH, BSO Laparoscopy Peritoneal and omental biopsy Omental biopsy, USO Frozen section CGR Inflammation only Final pathology CGR with caseation suggesting TB Acid-fast bacilli on ascites Positive Negative Culture for Mycobacterium TB Positive Negative PCR assays for Mycobacterium TB Positive Negative
n
(%)
(6) 2 1 1 2 (10) 7 3 11 7 4
(37.5)
16 7 1 6 8 2 6 3 2 1
(100) (43.8)
(62.5)
(68.8)
(50.0)
(18.8)
CGR, chronic granulomatous reaction; CT, computed tomography; TAH, total abdominal hysterectomy; B(U)SO, bilateral/unilateral salpingo-oophorectomy; PCR, polymerase chain reaction; TB, tuberculosis; OC, ovarian cystectomy.
In the laparoscopy group, three patients who were below the age of 40 years, underwent unilateral salpingo-oophorectomy, omentectomy and multiple peritoneal biopsies (because the frozen-section facility was not available and the appearance of the lesions resembled ovarian carcinoma in all of them). The other seven patients underwent limited surgery. Frozen section examination of peritoneal and or omental biopsies was performed in four patients of the laparotomy group and in seven patients during diagnostic laparoscopy. The common findings encountered at the time of surgery were ascites, multiple white coloured tubercles, peritoneal and omental thickening and adhesions throughout the peritoneal cavity. Ascitic fluid was obtained from all patients and showed clear exudative fluid with benign lymphocytic cells being predominant. Staining for acid-fast bacilli (Ziehl–Neelsen) of the ascitic fluid was performed in seven cases (43.8%) and it was positive in only one case (14.3%). Culture of the ascitic fluid and tissue specimens for Mycobacterium TB was performed in eight cases (50%), and revealed positive results in two cases (25%) only. Polymerase chain reaction assays of the tissue specimens for Mycobacterium TB DNA were performed in three cases, and revealed a positive result in two of them (66.7%). The frozen-section reports of 11 patients who underwent surgery revealed granulomatous inflammatory changes in seven patients and inflammatory changes in four patients. The final pathological examination revealed chronic granulomatous inflammation suggestive of TB in all patients. There were no complications related to the surgical procedures. Once these patients were diagnosed with peritoneal TB, the infection control team was involved in their management. These patients had a chest CT scan to find out if they had pulmonary TB. Two patients were diagnosed with pulmonary TB. All patients received anti-tuberculosis treatment. Once the patients had completed the treatment, their clinical condition and CA125 values returned to normal levels.
270
I. Lataifeh et al.
J Obstet Gynaecol Downloaded from informahealthcare.com by University of Washington on 02/11/15 For personal use only.
Discussion Peritoneal TB may present with nonspecific clinical features such as abdominal fullness, ascites, pelvic discomfort or pain, weight loss, anaemia, increase level of serum CA125 and/or pelvic mass (Koc et al. 2006; Sharma et al. 2010). Peritoneal TB in female patients may mimic advanced ovarian cancer or primary peritoneal carcinoma. Therefore, this disease should be included in the differential diagnosis of advanced ovarian cancer, especially in developing countries, where it remains endemic. Ovarian cancer peaks at age 65–75 years, and is rare before the age of 40 years, but peritoneal TB often occurs in patients between the age of 20 and 40 years (Panoskaltsis et al. 2000). In our study, the median age of the patients was 29.5 years (range 13–65 years) and the majority of them (75%) were premenopausal. The CA125 elevation is a common finding in both advanced ovarian cancer and peritoneal TB. In this study, serum CA125 levels were elevated in all patients. Elevated serum CA125 levels are well reported in patients with peritoneal TB (Simsek et al. 1997; Thakur et al. 2001). The CA125 levels are elevated in more than 80% of patients with advanced ovarian cancer, and are reported to be higher in patients with ascites (Panoskaltsis et al. 2000). The sensitivity and specificity of the serum CA125 declines in premenopausal women because of the high incidence of benign pathology, including endometriosis, uterine fibroids and pelvic inflammatory disease, that can cause an elevation of this marker (Penna et al. 1993). For this reason, in young patients with elevated serum CA125 levels, peritoneal TB should be included in the differential diagnosis, especially in areas where TB is endemic (Penna et al. 1993; Panoskaltsis et al. 2000). Imaging techniques such as USS, CT scan and MRI have been used in the diagnoses of peritoneal TB but have limited efficacy due to the diffuse nature of the disease and small implants (Akhan and Pringot 2002; Sharma et al. 2010). An abdominal CT scan in patients with peritoneal TB may illustrate: septated or particulate ascites; strands of omentum; ill-defined or no apparent adnexal mass; thickened peritoneum with pronounced enhancement suggestive of peritoneal TB; nodular implants with irregular peritoneal thickening suggestive of peritoneal carcinomatosis (Rodriguez and Pombo 1996). The majority of our patients
had some or all of these findings illustrated in the abdominal CT scan. The gross appearance of peritoneal TB at laparoscopy or laparotomy may be deceptive (Mimica et al. 1992). It may resemble advanced ovarian carcinoma, and lack of awareness of peritoneal TB by the gynaecologist may lead to unnecessary extended surgery. Therefore, frozen sections are necessary to differentiate the two conditions. This has been identified in the results of similar studies that addressed the diagnosis of peritoneal TB (Table III). In this study, frozen section was performed in 11 patients and revealed granulomatous reaction and inflammation with caseation necrosis. Although a histological diagnosis of TB could not be made on frozen sections of multiple peritoneal biopsies, it was possible to exclude ovarian or primary peritoneal carcinoma. In the other five patients, where frozen section determination was not available, two patients in the laparotomy group had unnecessary extended surgery, and three patients in the laparoscopy group had unilateral salpingo-oophorectomy. Polymerase chain reaction in the present series was performed in only three patients; two of them were found positive for Mycobacterium TB complex. Peritoneal TB should be considered in the differential diagnosis in young patients with abdominal pain, fever, ascites, weight loss and elevated serum CA125 levels. A clinical awareness of peritoneal TB might result in minimal invasive procedures (laparoscopic biopsy and/or PCR or intraoperative frozen section examination) for detecting this serious but curable disease. Laparoscopy seems to be a good sufficient and safe procedure to obtain tissue samples for histological and bacteriological diagnosis of tuberculous infection (Panoskaltsis et al. 2000). The strength of the present study is reporting data from two referral oncology institutions. The main limitations of our study include its retrospective nature, and its small sample size. In conclusion, the results of this study emphasise that a high index of suspicion for peritoneal TB is of paramount importance to increase the rate of detection and avoid unnecessary extended surgery in relatively young patients with nonspecific clinical features.
Table III. The results of similar studies that addressed the diagnosis of peritoneal TB. Publication
CA125 level above normal range
Frozen section rate
Patients (n)
Age (years)
Koc et al. 2006
22
36.9
Bilgin et al. 2001
10
40.6 ⫾ 6.1
10 (100%)
–
Demir et al. 2001
26
34.8 ⫾ 3.4
–
–
Xi et al. 2010
20
28.9 ⫾ 10.8
18/20 (90%)
10 cases (50%)
Oge et al. 2012
20
37.5 ⫾ 17.3
16/20 (80%)
8/13 (72%)
Wu et al. 2011
17
38
16/17 (94%)
20 (90.91%)
15/20 (75%)
16/17 cases
Operative rate (laparotomy vs laparoscopy) 11 laparotomy 9 laparoscopy 3 extended surgery All had laparotomy
24 of the 25 patients underwent laparoscopy
17 laparotomy 1 laparoscopy 11 laparotomy 2 laparoscopy 13 laparotomy (76%) 3 laparoscopy (18%)
Cultures and cytology positive rate for mycobacterium –
Mycobacteria could not be demonstrated on direct preparations in five patients The ascitic fluid of one patient (3.8%) was positive for acid-resistant bacilli, and culture was positive in two patients (7.7%) 10 cases, all negative None Seven cases had paracentesis; no malignancy. Negative for organism
Peritoneal TB mimicking advanced ovarian cancer 271 Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
J Obstet Gynaecol Downloaded from informahealthcare.com by University of Washington on 02/11/15 For personal use only.
References Akhan O, Pringot J. 2002. Imaging of abdominal tuberculosis. European Radiology 12:312–323. Bilgin T, Karabay A, Dolar E, Develioğlu OH. 2001. Peritoneal tuberculosis with pelvic abdominal mass, ascites and elevated CA 125 mimicking advanced ovarian carcinoma: a series of 10 cases. International Journal of Gynecological Cancer 11:290–294. Demir K, Okten A, Kaymakoglu S, Dincer D, Besisik F, Cevikbas U et al. 2001. Tuberculous peritonitis – reports of 26 cases, detailing diagnostic and therapeutic problems. European Journal of Gastroenterology and Hepatology 13:581–585. Engin G, Acunaş B, Acunaş G, Tunaci M. 2000. Imaging of extra pulmonary tuberculosis. Radiographics 20:471–488. Hopewell PC. 1994. Overview of clinical tuberculosis. In: Bloom BR, editor. Tuberculosis, pathogenesis, protection and control. 1st ed. Washington, DC: American Society for Microbiology. p 25–46. Ibrahim G, Gelzayd B, DeMatia F, Maas L. 1999. CA-125 tumor –associated antigen in a patient with tuberculous peritonitis. Southern Medical Journal 92:1103–1104. Koc S, Beydilli G, Tulunay G, Ocalan R, Boran N, Ozgul N et al. 2006. Peritoneal tuberculosis mimicking advanced ovarian cancer: a retrospective review of 22 cases. Gynecologic Oncology 103:565–569. Mimica M. 1992. Usefulness and limitations of laparoscopy in the diagnosis of tuberculous peritonitis. Endoscopy 24:588–591. Oge T, Ozalp SS, Yalcin OT, Kabukcuoglu S, Kebapci M, Arik D et al. 2012. Peritoneal tuberculosis mimicking ovarian cancer. European Journal of Obstetrics, Gynecology, and Reproductive Biology 162:105–108. Panoskaltsis TA, Moore DA, Haidopoulos DA, McIndoe AG. 2000. Tuberculous peritonitis: part of the differential diagnosis in ovarian cancer. American Journal of Obstetrics and Gynecology 182:740–742.
Pauslian FF. 1964. Tuberculosis of the intestine. In: Bockus HL, editor. Gastroenterology. 2nd ed. Vol. 11. Philadelphia: Saunders. p 31. Penna L, Manyonda I, Amias A. 1993. Intra-abdominal miliary tuberculosis presenting as disseminated ovarian carcinoma with ascites and raised CA 125. British Journal of Obstetrics and Gynaecology 100: 1051–1053. Rodriguez Z, Pombo F. 1996. Peritoneal tuberculosis versus peritoneal carcinomatosis: distinction based on CT findings. Journal of Computer Assisted Tomography 20:269–272. Sharma JB, Jain SK, Pushparaj M, Roy KK, Malhotra N, Zutshi V et al. 2010. Abdomino-peritoneal tuberculosis masquerading as ovarian cancer: a retrospective study of 26 cases. Archives of Gynecology and Obstetrics 282:643–648. Simsek H, Savas MC, Kadayifci A, Tatar G. 1997. Elevated serum CA 125 concentration in patients with tuberculous peritonitis: a case-control study. American Journal of Gastroenterology 92:1174–1176. Sinan T, Sheikh M, Ramadan S, Sahwney S, Behbehani A. 2002. CT features in abdominal tuberculosis: 20 years’ experience. BMC Med Imaging 2:3. Tan O, Luchansky E, Roseenman S, Pua T, Azodi M. 1999. Peritoneal tuberculosis with elevated serum Ca-125 level mimicking advanced ovarian cancer: a case report. Archives of Gynecology and Obstetrics 280:333–335. Thakur V, Mukherjee U, Kumar K. 2001. Elevated serum cancer antigen 125 levels in advanced abdominal tuberculosis. Medical Oncology 18:289–291. Wu CH, Changchien CC, Tseng CW, Chang HY, Ou YC, Lin H. 2011. Disseminated peritoneal tuberculosis simulating advanced ovarian cancer: A retrospective study of 17 cases. Taiwanese Journal of Obstetrics and Gynecology 50:292–296. Wu JF, Li HJ, Lee PI, Ni YH, Yu SC, Chang MH. 2003. Tuberculous peritonitis mimicking peritonitis carcinomatosis: a case report. European Journal of Pediatrics 162:853–855. Xi X, Shuang L, Dan W, Ting H, Han MY, Ying C et al. 2010. Diagnostic dilemma of abdominopelvic tuberculosis: a series of 20 cases. Journal of Cancer Research and Clinical Oncology 136:1839–1844.
GYNAECOLOGY
Disseminated peritoneal tuberculosis mimicking advanced ovarian cancer I. Lataifeh1,4, I. Matalka2, W. Hayajneh3, B. Obeidat1, H. Al Zou’bi2 & G. Abdeen5
J Obstet Gynaecol Downloaded from informahealthcare.com by University of Washington on 02/11/15 For personal use only.
Departments of 1Obstetrics and Gynecology, 2Pathology and 3Pediatrics, Jordan University of Science and Technology, Irbid, 4Surgery and 5Medicine, King Hussein Cancer Center, Amman, Jordan
The objective was to evaluate the clinical and radiological features of peritoneal tuberculosis (PTB) that resembled advanced ovarian malignancy. A retrospective review of all patients diagnosed with PTB over a period of 10 years was made. The data included: age, presenting symptom(s), CA125 level, microbiological, histological and cytological studies of the surgical specimens. The radiological and operative findings were also reviewed. A total of 16 patients were identified. The median age was 29.5 years (range 13–65 years). The median CA125 level was 319 U/ml (range 45–1,072 U/ml). The most common symptoms were abdominal distention and pain in 13 patients. Imaging studies showed ascites in all patients. Six patients had laparotomy and 10 had laparoscopy procedure. All patients received anti-tuberculosis treatment and had complete cure. A high index of suspicion of PTB is important to avoid unnecessary extended surgery in relatively young patients with nonspecific clinical features. Keywords: Ascites, CA125, laparoscopy, laparotomy, ovarian cancer, peritoneal tuberculosis
Introduction Peritoneal tuberculosis (TB) is a form of abdominal TB that predominantly involves the omentum, intestinal tract, liver surface, spleen or the female genital tract in addition to the parietal and visceral peritoneum (Hopewell 1994). It occurs in 1–4% of patients with pulmonary TB and results from reactivation of latent tuberculous foci in the peritoneum or from haematogenous spread from a primary disease in the lungs (Hopewell 1994; Sinan et al. 2002; Koc et al. 2006). Many women with peritoneal TB lack typical symptoms and laboratory data, therefore, peritoneal TB is usually difficult to diagnose in women and often mimics advanced stage epithelial ovarian carcinoma or primary peritoneal carcinoma (Ibrahim et al. 1999; Tan et al. 1999). Pelvic pain or discomfort and mass, ascites and elevated serum CA125 levels are common markers (Engin et al. 2000; Bilgin et al. 2001). The treatment and outcome of peritoneal TB and that of advanced ovarian carcinoma differ markedly. Peritoneal TB is treated medically with anti-tuberculosis drugs and is a curable disease, while advanced ovarian carcinoma is treated by debulking surgery followed by cytotoxic drugs and has a poor outcome. Reports of peritoneal TB in the literature have been limited to small series and sporadic case studies, which were often
misdiagnosed as carcinomatous peritonitis (Demir et al. 2001; Wu et al. 2003). In this retrospective study, we evaluated the clinical, laboratory and radiological features in patients with peritoneal TB.
Materials and methods We retrospectively reviewed the medical records of all patients diagnosed with peritoneal TB at King Abdullah University Hospital (KAUH) and King Hussein Cancer Center (KHCC) in Jordan, over a period of 10 years between July 2002 and June 2012. The following data were collected for each patient – clinical data including: age, parity, presenting symptom(s) and its duration and presence or absence of ascites; laboratory data including: preoperative CA125 levels (U/ml) and microbiological, chemical and cytological studies of ascites. Frozen section and final pathology results of the biopsy(ies) and specimens of peritoneal or omental nodules and ovarian masses were also collected. The radiological studies included: chest radiographic findings; imaging studies, such as abdomen and pelvis ultrasound scan (USS); computed tomography (CT); magnetic resonance imaging (MRI) and upper and lower gastrointestinal (GI) endoscopy. The operative findings of exploration laparotomy or laparoscopy were also collected. The diagnosis of TB was established on the basis of at least one of the following criteria (as advocated by Pauslian et al. 1964): (1) histological evidence of caseating granulomatous inflammation; (2) acid-fast bacilli identified in tissue specimens or ascitic fluid; (3) tissue or ascitic fluid culture yielding M. tuberculosis; (4) positive polymerase chain reaction (PCR) analysis for M. tuberculosis DNA on tissue specimens or ascitic fluid; or (5) a good therapeutic response to anti-TB agents in patients with clinical evidence of peritoneal TB. The data was analysed using Microsoft Excel 2007 program. Descriptive statistics was performed. The median, minimum and maximum values for age, and serum CA125 levels were calculated. The study was approved by the local IRB of both institutions.
Results During the study period, a total of 16 patients with a documented diagnosis of peritoneal TB were identified at the two centres. The distribution by centre was 13 patients (81.3%) at KAUH
Correspondence: I. Lataifeh, Department of Obstetrics and Gynecology, Jordan University of Science and Technology, PO Box 3030, Irbid 22110, Jordan. E-mail: [email protected]
J Obstet Gynaecol Downloaded from informahealthcare.com by University of Washington on 02/11/15 For personal use only.
Peritoneal TB mimicking advanced ovarian cancer 269 and three patients (18.7%) at KHCC. Clinical and radiological characteristics of the patients are shown in Table I. The median age of the patients was 29.5 years (range 13–65 years). A total of 12 patients (75%) were premenopausal and four patients (25%) were postmenopausal. Preoperative serum CA125 levels were elevated in all patients, with a median serum level of CA125 of 319 U/ml (range 45–1,072 U/ml). The serum level of CA125 was lower than 100 U/ml in three patients, between 101 and 1,000 U/ml in 12 patients and higher than 1,000 U/ml in one patient. The most common symptoms reported were abdominal distention and pain; they were reported in 13 patients (81.3%). Six patients (37.5%) had fever, and none of them presented with abdominal masses. The duration of the symptoms varied from 1 week to 12 months. One patient had a family history of TB. None of the patients was receiving immune suppressive therapy. Preoperative radiological studies showed ascites in all patients. Omental and peritoneal thickening was noted in eight patients (50%); omental nodule(s) in four patients (25%). Heterogeneous pelvic mass was noted in six patients (37.5%) and pleural effusion was noted in four patients (25%). Paracentesis was done in three patients (18.8%) but it was not helpful to predict peritoneal TB. Peritoneal TB was suspected at presentation in only three of the patients, and was confirmed by diagnostic laparoscopy and tissue biopsy. The remaining 13 patients underwent diagnostic procedures, with a provisional diagnosis of advanced ovarian cancer or primary peritoneal carcinoma. The diagnostic procedures, pathology, and peritoneal fluid analysis findings are shown in Table II. Six patients (37.5%) had laparotomy, while 10 patients (62.5%) had diagnostic laparoscopy. On the laparotomy group, two patients who were postmenopausal underwent extended surgery, including a total hysterectomy, bilateral salpingo-oophorectomy and omentectomy (owing to the co-existing uterine fibroid in one patient and to the suspicion of advanced ovarian malignancy in the other patient). The other four patients had limited surgical procedure. Table I. Clinical and radiological characteristics of the patients. Findings Age (years) (median, range) Menopausal status Premenopausal Postmenopausal CA125 level (U/ml) (median, range) Clinical symptoms Abdominal distention Abdominal pain Fever Anorexia Weight loss Nausea and vomiting Cough Night sweat Abdominal mass USS/CT scan/MRI Ascites Omental and peritoneal thickening Omental nodule(s) Pelvic mass Peritoneal thickening/carcinomatosis Pleural effusion
n
(%) 29.5 (13–65)
12 4
75 25 319 (45–1,072)
13 13 6 4 3 3 2 1 0
81.3 81.3 37.5 25.0 18.8 18.8 12.5 6.3 0
16 8 4 6 1 4
100 50.0 25.0 37.5 6.3 25.0
CA125, carcinogenic antigen; CT, computed tomography; GIS, gastrointestinal system. MRI, magnetic resonance imaging; USS, ultrasound scans.
Table II. Diagnostic procedures, pathology and peritoneal fluid analysis. Parameter Diagnostic approach Laparotomy Peritoneal, omental biopsy Omental biopsy, OC Omental biopsy, Ov. cystectomy Omentectomy, TAH, BSO Laparoscopy Peritoneal and omental biopsy Omental biopsy, USO Frozen section CGR Inflammation only Final pathology CGR with caseation suggesting TB Acid-fast bacilli on ascites Positive Negative Culture for Mycobacterium TB Positive Negative PCR assays for Mycobacterium TB Positive Negative
n
(%)
(6) 2 1 1 2 (10) 7 3 11 7 4
(37.5)
16 7 1 6 8 2 6 3 2 1
(100) (43.8)
(62.5)
(68.8)
(50.0)
(18.8)
CGR, chronic granulomatous reaction; CT, computed tomography; TAH, total abdominal hysterectomy; B(U)SO, bilateral/unilateral salpingo-oophorectomy; PCR, polymerase chain reaction; TB, tuberculosis; OC, ovarian cystectomy.
In the laparoscopy group, three patients who were below the age of 40 years, underwent unilateral salpingo-oophorectomy, omentectomy and multiple peritoneal biopsies (because the frozen-section facility was not available and the appearance of the lesions resembled ovarian carcinoma in all of them). The other seven patients underwent limited surgery. Frozen section examination of peritoneal and or omental biopsies was performed in four patients of the laparotomy group and in seven patients during diagnostic laparoscopy. The common findings encountered at the time of surgery were ascites, multiple white coloured tubercles, peritoneal and omental thickening and adhesions throughout the peritoneal cavity. Ascitic fluid was obtained from all patients and showed clear exudative fluid with benign lymphocytic cells being predominant. Staining for acid-fast bacilli (Ziehl–Neelsen) of the ascitic fluid was performed in seven cases (43.8%) and it was positive in only one case (14.3%). Culture of the ascitic fluid and tissue specimens for Mycobacterium TB was performed in eight cases (50%), and revealed positive results in two cases (25%) only. Polymerase chain reaction assays of the tissue specimens for Mycobacterium TB DNA were performed in three cases, and revealed a positive result in two of them (66.7%). The frozen-section reports of 11 patients who underwent surgery revealed granulomatous inflammatory changes in seven patients and inflammatory changes in four patients. The final pathological examination revealed chronic granulomatous inflammation suggestive of TB in all patients. There were no complications related to the surgical procedures. Once these patients were diagnosed with peritoneal TB, the infection control team was involved in their management. These patients had a chest CT scan to find out if they had pulmonary TB. Two patients were diagnosed with pulmonary TB. All patients received anti-tuberculosis treatment. Once the patients had completed the treatment, their clinical condition and CA125 values returned to normal levels.
270
I. Lataifeh et al.
J Obstet Gynaecol Downloaded from informahealthcare.com by University of Washington on 02/11/15 For personal use only.
Discussion Peritoneal TB may present with nonspecific clinical features such as abdominal fullness, ascites, pelvic discomfort or pain, weight loss, anaemia, increase level of serum CA125 and/or pelvic mass (Koc et al. 2006; Sharma et al. 2010). Peritoneal TB in female patients may mimic advanced ovarian cancer or primary peritoneal carcinoma. Therefore, this disease should be included in the differential diagnosis of advanced ovarian cancer, especially in developing countries, where it remains endemic. Ovarian cancer peaks at age 65–75 years, and is rare before the age of 40 years, but peritoneal TB often occurs in patients between the age of 20 and 40 years (Panoskaltsis et al. 2000). In our study, the median age of the patients was 29.5 years (range 13–65 years) and the majority of them (75%) were premenopausal. The CA125 elevation is a common finding in both advanced ovarian cancer and peritoneal TB. In this study, serum CA125 levels were elevated in all patients. Elevated serum CA125 levels are well reported in patients with peritoneal TB (Simsek et al. 1997; Thakur et al. 2001). The CA125 levels are elevated in more than 80% of patients with advanced ovarian cancer, and are reported to be higher in patients with ascites (Panoskaltsis et al. 2000). The sensitivity and specificity of the serum CA125 declines in premenopausal women because of the high incidence of benign pathology, including endometriosis, uterine fibroids and pelvic inflammatory disease, that can cause an elevation of this marker (Penna et al. 1993). For this reason, in young patients with elevated serum CA125 levels, peritoneal TB should be included in the differential diagnosis, especially in areas where TB is endemic (Penna et al. 1993; Panoskaltsis et al. 2000). Imaging techniques such as USS, CT scan and MRI have been used in the diagnoses of peritoneal TB but have limited efficacy due to the diffuse nature of the disease and small implants (Akhan and Pringot 2002; Sharma et al. 2010). An abdominal CT scan in patients with peritoneal TB may illustrate: septated or particulate ascites; strands of omentum; ill-defined or no apparent adnexal mass; thickened peritoneum with pronounced enhancement suggestive of peritoneal TB; nodular implants with irregular peritoneal thickening suggestive of peritoneal carcinomatosis (Rodriguez and Pombo 1996). The majority of our patients
had some or all of these findings illustrated in the abdominal CT scan. The gross appearance of peritoneal TB at laparoscopy or laparotomy may be deceptive (Mimica et al. 1992). It may resemble advanced ovarian carcinoma, and lack of awareness of peritoneal TB by the gynaecologist may lead to unnecessary extended surgery. Therefore, frozen sections are necessary to differentiate the two conditions. This has been identified in the results of similar studies that addressed the diagnosis of peritoneal TB (Table III). In this study, frozen section was performed in 11 patients and revealed granulomatous reaction and inflammation with caseation necrosis. Although a histological diagnosis of TB could not be made on frozen sections of multiple peritoneal biopsies, it was possible to exclude ovarian or primary peritoneal carcinoma. In the other five patients, where frozen section determination was not available, two patients in the laparotomy group had unnecessary extended surgery, and three patients in the laparoscopy group had unilateral salpingo-oophorectomy. Polymerase chain reaction in the present series was performed in only three patients; two of them were found positive for Mycobacterium TB complex. Peritoneal TB should be considered in the differential diagnosis in young patients with abdominal pain, fever, ascites, weight loss and elevated serum CA125 levels. A clinical awareness of peritoneal TB might result in minimal invasive procedures (laparoscopic biopsy and/or PCR or intraoperative frozen section examination) for detecting this serious but curable disease. Laparoscopy seems to be a good sufficient and safe procedure to obtain tissue samples for histological and bacteriological diagnosis of tuberculous infection (Panoskaltsis et al. 2000). The strength of the present study is reporting data from two referral oncology institutions. The main limitations of our study include its retrospective nature, and its small sample size. In conclusion, the results of this study emphasise that a high index of suspicion for peritoneal TB is of paramount importance to increase the rate of detection and avoid unnecessary extended surgery in relatively young patients with nonspecific clinical features.
Table III. The results of similar studies that addressed the diagnosis of peritoneal TB. Publication
CA125 level above normal range
Frozen section rate
Patients (n)
Age (years)
Koc et al. 2006
22
36.9
Bilgin et al. 2001
10
40.6 ⫾ 6.1
10 (100%)
–
Demir et al. 2001
26
34.8 ⫾ 3.4
–
–
Xi et al. 2010
20
28.9 ⫾ 10.8
18/20 (90%)
10 cases (50%)
Oge et al. 2012
20
37.5 ⫾ 17.3
16/20 (80%)
8/13 (72%)
Wu et al. 2011
17
38
16/17 (94%)
20 (90.91%)
15/20 (75%)
16/17 cases
Operative rate (laparotomy vs laparoscopy) 11 laparotomy 9 laparoscopy 3 extended surgery All had laparotomy
24 of the 25 patients underwent laparoscopy
17 laparotomy 1 laparoscopy 11 laparotomy 2 laparoscopy 13 laparotomy (76%) 3 laparoscopy (18%)
Cultures and cytology positive rate for mycobacterium –
Mycobacteria could not be demonstrated on direct preparations in five patients The ascitic fluid of one patient (3.8%) was positive for acid-resistant bacilli, and culture was positive in two patients (7.7%) 10 cases, all negative None Seven cases had paracentesis; no malignancy. Negative for organism
Peritoneal TB mimicking advanced ovarian cancer 271 Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
J Obstet Gynaecol Downloaded from informahealthcare.com by University of Washington on 02/11/15 For personal use only.
References Akhan O, Pringot J. 2002. Imaging of abdominal tuberculosis. European Radiology 12:312–323. Bilgin T, Karabay A, Dolar E, Develioğlu OH. 2001. Peritoneal tuberculosis with pelvic abdominal mass, ascites and elevated CA 125 mimicking advanced ovarian carcinoma: a series of 10 cases. International Journal of Gynecological Cancer 11:290–294. Demir K, Okten A, Kaymakoglu S, Dincer D, Besisik F, Cevikbas U et al. 2001. Tuberculous peritonitis – reports of 26 cases, detailing diagnostic and therapeutic problems. European Journal of Gastroenterology and Hepatology 13:581–585. Engin G, Acunaş B, Acunaş G, Tunaci M. 2000. Imaging of extra pulmonary tuberculosis. Radiographics 20:471–488. Hopewell PC. 1994. Overview of clinical tuberculosis. In: Bloom BR, editor. Tuberculosis, pathogenesis, protection and control. 1st ed. Washington, DC: American Society for Microbiology. p 25–46. Ibrahim G, Gelzayd B, DeMatia F, Maas L. 1999. CA-125 tumor –associated antigen in a patient with tuberculous peritonitis. Southern Medical Journal 92:1103–1104. Koc S, Beydilli G, Tulunay G, Ocalan R, Boran N, Ozgul N et al. 2006. Peritoneal tuberculosis mimicking advanced ovarian cancer: a retrospective review of 22 cases. Gynecologic Oncology 103:565–569. Mimica M. 1992. Usefulness and limitations of laparoscopy in the diagnosis of tuberculous peritonitis. Endoscopy 24:588–591. Oge T, Ozalp SS, Yalcin OT, Kabukcuoglu S, Kebapci M, Arik D et al. 2012. Peritoneal tuberculosis mimicking ovarian cancer. European Journal of Obstetrics, Gynecology, and Reproductive Biology 162:105–108. Panoskaltsis TA, Moore DA, Haidopoulos DA, McIndoe AG. 2000. Tuberculous peritonitis: part of the differential diagnosis in ovarian cancer. American Journal of Obstetrics and Gynecology 182:740–742.
Pauslian FF. 1964. Tuberculosis of the intestine. In: Bockus HL, editor. Gastroenterology. 2nd ed. Vol. 11. Philadelphia: Saunders. p 31. Penna L, Manyonda I, Amias A. 1993. Intra-abdominal miliary tuberculosis presenting as disseminated ovarian carcinoma with ascites and raised CA 125. British Journal of Obstetrics and Gynaecology 100: 1051–1053. Rodriguez Z, Pombo F. 1996. Peritoneal tuberculosis versus peritoneal carcinomatosis: distinction based on CT findings. Journal of Computer Assisted Tomography 20:269–272. Sharma JB, Jain SK, Pushparaj M, Roy KK, Malhotra N, Zutshi V et al. 2010. Abdomino-peritoneal tuberculosis masquerading as ovarian cancer: a retrospective study of 26 cases. Archives of Gynecology and Obstetrics 282:643–648. Simsek H, Savas MC, Kadayifci A, Tatar G. 1997. Elevated serum CA 125 concentration in patients with tuberculous peritonitis: a case-control study. American Journal of Gastroenterology 92:1174–1176. Sinan T, Sheikh M, Ramadan S, Sahwney S, Behbehani A. 2002. CT features in abdominal tuberculosis: 20 years’ experience. BMC Med Imaging 2:3. Tan O, Luchansky E, Roseenman S, Pua T, Azodi M. 1999. Peritoneal tuberculosis with elevated serum Ca-125 level mimicking advanced ovarian cancer: a case report. Archives of Gynecology and Obstetrics 280:333–335. Thakur V, Mukherjee U, Kumar K. 2001. Elevated serum cancer antigen 125 levels in advanced abdominal tuberculosis. Medical Oncology 18:289–291. Wu CH, Changchien CC, Tseng CW, Chang HY, Ou YC, Lin H. 2011. Disseminated peritoneal tuberculosis simulating advanced ovarian cancer: A retrospective study of 17 cases. Taiwanese Journal of Obstetrics and Gynecology 50:292–296. Wu JF, Li HJ, Lee PI, Ni YH, Yu SC, Chang MH. 2003. Tuberculous peritonitis mimicking peritonitis carcinomatosis: a case report. European Journal of Pediatrics 162:853–855. Xi X, Shuang L, Dan W, Ting H, Han MY, Ying C et al. 2010. Diagnostic dilemma of abdominopelvic tuberculosis: a series of 20 cases. Journal of Cancer Research and Clinical Oncology 136:1839–1844.
