Gut 1995; 36: 303-305

303

Increased CA 125 in a patient with tuberculous peritonitis: case report and review of published works
D K O'Riordan, A Deery, A Dorman, 0 E Epstein

Abstract A case of a middle aged woman with weight loss, ascites, and a pleural effusion is presented where a clinical diagnosis of ovarian cancer was made. Her CA 125 was greatly increased at 873 IU/ml and the ascites was a lymphocytic exudate but cytology failed to show malignant cells. Operative biopsy showed numerous noncaseating granulomas in the omentum but no mycobacterial organisms were seen. Empiric antituberculous treatment was started before positive culture results were received and when treatment had ended both the ascites and pleural effusion had resolved and the CA 125 had fallen to 7 IU/ml. Review of published works showed several other examples of tuberculous peritionitis associated with increased CA 125 and the possible cause of raised CA 125 in this condition is

discussed.
(Gut 1995; 36: 303-305)
Keywords: peritonitis, tuberculosis, CA 125.

Case report A 55 year old Indian woman presented with a two month history of abdominal distension, shortness of breath, and right sided chest pain. She was anorexic and had noticed a 10 kg loss of weight. On examination she had signs of a right pleural effusion and considerable ascites. Tuberculosis seemed to be the most likely

Departments of Medicine D K O'Riordan 0 E Epstein Histopathology

A Dorman and Cytology A Deery

previously she had been referred with epigastric pain and weight loss. Duodenitis was diagnosed and she required maintenance treatment with H2 antagonists for six months. Her symptoms recurred when treatment ended. Endoscopy showed

diagnosis. Two years

oesophagitis and omeprazole had been prescribed. Full blood count was normal apart from mild lymphopaenia. Urea and electrolytes, liver function tests, and clotting were normal. Chest x ray confirmed a large right sided pleural effusion (not present on a film taken in 1989). Mantoux test at 1:10 000 and 1:1000 were negative. Computed tomography of abdomen and pelvis showed ascites. Pelvic ultrasound identified a small transonic area in the left ovary and fluid in the pouch of Douglas but no adnexal masses. Paracentesis showed a predominantly lymphocytic exudate. No malignant cells were seen and no organisms identified or grown from repeated taps. Pleural fluid analysis was similar to the peritoneal fluid. Serum tumour marker assays were CEA 7 ,ug/l (N<10), CA 19/9 13 U/ml (N<30), CA 125 873 U/ml (N<35). As a result of the extremely high concentration of CA 125 a diagnostic laparotomy was performed with the expectation of finding ovarian cancer. The omentum was adherent to the anterior abdominal wall and the peritoneal surfaces were covered with fine 'deposits'. The ovaries were normal and there were no palpable masses in the large or small bowel. The pancreas was normal. The caecum was thickened. An omental biopsy was taken for histological examination and culture. Macroscopically the specimen was mainly composed of fatty tissue (Figure). The cut surface was lobulated and covered by fine white deposits. On microscopy numerous non-caseating granulomas with Langhans' giant cells were seen but no acid fast bacilli were identified. The appearances were suggestive of tuberculosis with the lesser possibility of sarcoidosis. Repeat pleural tap and pleural biopsy were not

diagnostic.
At this stage we decided to treat empirically for tuberculosis and triple therapy was started with rifampicin, isoniazid (with pyridoxine), and pyrazinamide. Shortly after discharge mycobacterium tuberculosis was cultured from pleural fluid but not from ascites. Eight weeks after treatment had begun the ascites and pleural effusion had resolved. On completion of treatment CA 125 concentrations were normal. Cytospin preparations from the pleural and peritoneal fluids were retrospectively analysed immunocytochemically for the presence of CA 125 with a monoclonal antibody. Positive and negative controls were included composed of similar cytospins of ascitic fluid

Royal Free Hospital and Royal Free Hospital School of Medicine, London
Correspondence
to:

Dr D K O'Riordan, Department of Medicine, Royal Free Hospital, Pond Street, London NW3 2QG. Accepted for publication 27 May 1994

A single non-caseating granuloma in omental adipose tissue (haematoxylin and eosin, original magnification x 240).

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O'Riordan, Deery, Dorman, Epstein

Case reports of increased CA 125 with tuberculous peritonitis

immunocytochemically in either the granulomas from the biopsy material or in cytospin preparations of pleural and ascitic fluid with 1400 U/ml Imai et al 290 U/mI and 264 U/ml (2 cases) Ronay et al good positive controls in both cases. Therefore 1054 U/ml Okazaki et al we cannot confirm previous findings in this 369-5 U/ml and 402-6 U/ml (2 cases) Gurgan et al regard and the source of the CA 125 in this case remains to be found. The serum CA 125 incorporating ovarian carcinoma and without concentration, however, did return to normal primary antibody application respectively. No after antituberculous treatment. This case highlights the difficulty of diagnosstaining was identified in any of the lymphocytic, histiocytic or mesothelial populations ing abdominal tuberculosis in some instances. included in either the pleural or ascitic fluid. The onset is usually insidious although presentation as an acute abdomen has been described.'7 The commonest symptoms are abdominal swelling, weight loss, and Discussion Abdominal tuberculosis is rare in the abdominal pain. Acid fast bacilli are rarely developed world except among immigrants detected, though Singh et al reported 83% and cirrhotic patients. The most common form success when large volumes of ascitic fluid were is tuberculous peritonitis, which occurs in 0 1 cultured.'8 Chest x ray is abnormal in only to 0.70/ol of all cases of tuberculosis and in 2% 40-50/ of cases. Mantoux testing is positive of cases in the developing world. The most in 70% of patients. Adenosine deaminase is interesting aspect of our case was the consider- reported to be a useful marker for both periable increase in CA 125. This together with the toneal and pleural tuberculosis.'9 20 Definitive clinical presentation and negative Mantoux diagnosis still depends on finding caseating test led us to suspect overian cancer. CA 125 granulomas on biopsy. Laparoscopy seems is a soluble glycoprotein oncofetal antigen to to be the most effective way to obtain a diagwhich a monoclonal antibody has been raised. nosis.21 In our case the operative findings were This protein is increased in 82% of patients consistent with tuberculosis but the biopsy with ovarian cancer and in only 1% of showed non-caseating granulomas. This report controls.2 The upper limit of normal for shows that very high concentrations of CA 125 CA 125 is given as 32 U/ml although a value of can occur in conditions other than carcinoma of 65 U/ml has been suggested to give better the ovary and that tuberculosis needs to be specificity for ovarian cancer. Together with considered in the differential diagnosis of ascites pelvic ultrasound CA 125 is 99.8% specific for with raised tumour markers. This is especially ovarian cancer.3 CA 125 is, however, also important as tuberculosis is a curable disease, raised in some instances in endometriosis,4 which is becoming increasingly common and pelvic inflammatory disease, and pregnancy.5 more resistant to treatment.22 There are reports in cases of 'miliary tuberculosis and ascites' by two groups in 1 Vyravanathan S, Jeyarajah R. Tuberculous peritonitis: a review of thirty-five cases. Postgrad Med J 1980; 56: Germany6 7 and in further reports from 649-51. Japan8 9 and Turkey.'0 The Table lists the 2 Bast RC, Klug TL, St John E, Jenison E, NiloffJM, Lazarus H, et al. A radioimmunoassay using a monoclonal anticoncentrations of CA 125 in these cases. body to monitor the course of epithelial ovarian cancer. CA 125 may be increased in patients with NEnglJ Med 1983; 309: 883-7. tuberculous associated pleural effusions but 3 Jacobs I, Stabile I, Bridges J, Kempley P, Reynolds C, Grudzinkas J, et al. Multimodal approach to screening for the concentration falls significantly after one to ovarian cancer. Lancet 1988; i: 268-71. two months of antituberculous treatment.1' It 4 Barbieri RI, Niloff JM, Bast RC, Schaetzl E, Kistner RW, Knapp RC. Elevated serum concentrations of CA 125 in is also increased in tuberculous associated patients with advanced endometriosis. Fertil Steril 1986; 45: 630. pericarditis. 12 5 Halila H, Stenman U-K, Seppala M. Ovarian cancer CA 125 is raised in many diseases of antigen CA-1 25 levels in pelvic inflammatory disease and pregnancy. Cancer 1986; 57: 1327-9. the gastrointestinal tract. These have been Marczewski A, Rosen Beck A. High CA 125 comprehensively reviewed at a recent 6 Klein M, in miliary tuberculosisA,and ascites. Wien Klin values 101: 870-1. symposium.'3 The commonest occurrences of 7 Wochenschr 1989;Tulusan AH. Immunohistochemical and Ronay G, Jager W, raised CA 125 were in cirrhosis and peritonitis serological detection of CA-125 in patients with peritoneal tuberculosis and ascites. Geburtshilfe Frauenheilkd though it is also noted in tumours of the upper 61-3. 1989; and lower bowel, pancreatitis, hepatitis, and 8 Okazaki 49: Mizuno K, Katoh K, Hashimoto S, Fukuchi S. K, Tuberculous peritonitis with extraordinarily high serum inflammatory bowel disease. In cirrhosis the CA 125.JMed 1992; CA 125 value correlates with the degree of liver 9 Imai A, Itoh T, Niwa K, 23: 353-61. Elevated CA 125 levels Tamaya T. in a patient with tuberculous peritonitis. Arch Gynecol failure by Child's grade. The CA 125 value is Obstet 1991; 248: 157-9. higher in cirrhosis with ascites than without 10 Gurgan T, Zeyneloglu H, Urman B, Develioghu 0, Yarali H. Pelvic-peritoneal tuberculosis with elevated serum and and falls after paracentesis but not with peritoneal fluid CA 125 levels. Gynecol Obst Invest 1993; diuretic treatment suggesting the peritoneum 35: 60-1. 11 Nakanishi Y, Hiura K, Katoh 0, Yamaguchi T, Kuroki S, as the source of the antigen.'4 Aoki Y, et at. Clinical significance of serum CA 125 in Immunohistochemical staining detects patients with tuberculous pleurisy. Kekkaku 1991; 66: 525-30. CA 125 in carcinoma cells and in activated mesothelial cells.'5 The finding of CA 125 in 12 Cacoub P, Le Thi HD, Wechster B, Chapelon C, Auperin A, Gandjbakch I. Chronic constrictive pericarditis responsible for an increase of CA 125 levels. Two cases. Presse pleural mesothelial cells mirrors the finding in Med 1712-4. peritoneal lining cells and suggests that 13 Ruibal 1990; 19:A, Fernandez Llana B, Alvarez A, Allende Morrell MT. AnticancerRes 1993; 13: 1717-20. increased CA 125 may be partly a non-spe14 Molina R, Filella X, Jo J, Deulofeu R, Joseph J, Ballesta cific marker of inflammation or trauma. 16 AM. AnticancerRes 1993; 13: 1685-90. We could find no evidence of CA 125 15 Tomita Y. Clinical evaluation and tissue distribution of CA

Increased CA 125 in a patient with tuberculous peritonitis

125 in patients with pleural effusion. Igaku Kenkyu 1989; 59: 90-6. Redman CWE, Jones SR, Luesley DM, Nicholl SE, Kelly K, Buxton EH, et al. Peritoneal trauma releases CA 125? BrJ7 Cancer 1988; 58: 502-4. Khoury GA, Payne CA, Harvey DR. Tuberculosis of the peritoneal cavity. Br7 Surg 1978; 65: 808-11. Singh MM, Bhargava AN, Jain KP. Tuberculosis peritonitis. An evaluation of pathogenetic mechanisms, diagnostic procedures and theraputic measures. N EnglJ Med 1969; 281:1091-4. Martinez-Vasquez JM, Ocana I, Ribera E, Segura RM, Pasqual C. Adenosine deaminase activity in the diagnosis of tuberculosis peritonitis. Gut 1986; 27: 1049-53.

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20 Banales JL, Pineda PR, Fitzgerald JM, Rubio H, Selman M, Salazar-Lezama M, et al. Adenosine deaminase in the diagnosis of tuberculous pleural effusions. A report of 218 patients and review of the literature. Chest 1991; 99: 355-7. 21 Manohar A, Simjee AE, Haffejee AA, Pettengell KE. Symptoms and investigative findings in 145 patients with tuberculous peritonitis diagnosed by peritoneoscopy and biopsy over a five year period. Gut 1990; 31: 1130-2. 22 Frieden TR, Sterling T, Pablos-Mendez A, Kilburn JO, Cauthen GM, Dooley SW. The emergency of drug resistant tuberculosis in New York City. N Engl Jf Med 1993; 328: 521-6.

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