Disseminated peritoneal tuberculosis mimicking advanced-stage endodermal sinus tumor: A case report

Metastatic ovarian cancer to the thoracic wall

303

Disseminated peritoneal tuberculosis mimicking advanced-stage endodermal sinus tumor: a case report ¨ CE* & A. AYHAN* P. DURSUN*, S. ERSOZy, M. GULTEKIN*, G. AKSAN*, K. YU *Department of Obstetrics and Gynecology, Faculty of Medicine, Hacettepe University, Ankara, Turkey; and yDepartment of Surgery, Faculty of Medicine, Ankara University, Ankara, Turkey

Abstract.

Dursun P, Ersoz S, Gultekin M, Aksan G, Yu¨ce K, Ayhan A. Disseminated peritoneal tuberculosis mimicking advanced-stage endodermal sinus tumor: a case report. Int J Gynecol Cancer 2006;16(Suppl. 1): 303–307. It is well known that peritoneal tuberculosis may mimic advanced-stage epithelial ovarian carcinoma because of similar clinical, radiologic, and laboratory findings. However, disseminated peritoneal tuberculosis mimicking advanced-stage endodermal sinus tumor (ESS) has not been reported previously. An 18-year-old nulliparous woman came with the complaint of pelvic pain and weight loss. Imaging studies demonstrated that she had multiple peritoneal implants and left adnexial mass. Also, laboratory studies showed elevated

Address correspondence and reprint requests to: Polat Dursun, MD, Department of Obstetrics and Gynecology, Faculty of Medicine, Hacettepe University, Ankara, 06100 Turkey. Email: pdursun@ttnet. net.tr #

2006 IGCS, International Journal of Gynecological Cancer 16 (Suppl. 1)

304 P. Dursun et al.

CA125 and alpha fetoprotein levels suggesting an initial diagnosis of ESS. However, intraoperative frozen section examination showed caseous necrosis, and she was diagnosed as having disseminated peritoneal tuberculosis. Two months after the initial exploration, the patient required liver transplantation because of hepatic failure due to widespread hepatic involvement of the tuberculosis. Concomitant peritoneal and hepatic involvement of tuberculosis may cause false elevation of multiple tumor markers of gynecological cancers and may lead to misdiagnosis and mismanagement of patients. Elevation of these markers should be carefully investigated especially in premenopausal women. To our knowledge, this is the first reported case of peritoneal tuberculosis misdiagnosed as endodermal sinus tumor. KEYWORDS:

adnexial mass, AFP, endodermal sinus tumor, extrapulmonary tuberculosis, germ cell tumor, ovarian cancer, peritoneal tuberculosis, tuberculosis.

Although tuberculosis is a rare infectious disease in Western countries, it is frequently seen in less developed countries. However, World Health Organization reported that tuberculosis was a global emergency in the early 1990s because of the increased number of HIV-infected patients, increasing number of immigrants to the industrialized countries from Third World countries, and various social problems such as poverty and homelessness(1). Here, we present a patient with primary peritoneal tuberculosis, which was misdiagnosed as endodermal sinus tumor (ESS) because of elevated serum CA125 and alpha fetoprotein (AFP) levels and similar radiologic findings to peritoneal carcinomatosis. Surprisingly, 2 months after the exploration, the patient required liver transplantation because of hepatic failure due to widespread hepatic involvement of the tuberculosis. To our knowledge, tuberculosis is an unusual cause of hepatic failure, which requires liver transplantation. Concomitant peritoneal and hepatic involvement of tuberculosis may cause false elevation of multiple tumor markers of gynecological cancers and may lead to misdiagnosis and mismanagement of patients.

Case history An 18-year-old nulliparous woman was referred to our hospital with the suspicion of ESS because of a left adnexial mass, mild ascites, and elevated AFP levels. Her presenting symptoms were abdominal pain and 7 kg weight loss in 3 months. Her previous medical and family history was unremarkable (eg, any familial liver diseases). She had no history of fever, chills, and night sweats. Systemic physical examinations were within normal limits except bilateral mild abdominal tenderness. Pelvic examination showed left adnexial #

2006 IGCS, International Journal of Gynecological Cancer 16 (Suppl. 1)

mass, cul-de-sac nodularity, and severe cervical motion tenderness. Blood cell count revealed microcytic anemia. Liver and renal function tests were within normal limits. Posteroanterior chest X-ray did not reveal any abnormalities. Eritrosit sedimentation rate (ESR) was extremely elevated (107 mm/h, range of 0–20 mm/h). Abdominopelvic ultrasonographic evaluation revealed a left adnexial mass, which contained solid and cystic areas and mild abdominal ascites. Serum CA125 and AFP were increased, 304 U/mL (range of 0–35 U/mL) and 41.9 U/mL (range of 0–5.8 IU/mL), respectively. Abdominopelvic computed tomography (CT) revealed multiple peritoneal tumor–like implants, enlarged retroperitoneal lymph nodes, and multiple liver implants in addition to the left adnexial mass. At the end of the initial laboratory investigation, exploratory laparotomy was performed through a midline incision, with the preliminary diagnosis of metastatic ESS. At laparotomy, the peritoneal cavity contained nearly 1 L of xanthochromic ascites. Also, a left adnexial mass, which was 6 3 7 cm in diameter, bilateral hydrosalpinx, and omental cake were seen intraoperatively. Omental cake was adherent to the bowel and uterus. There were multiple miliary deposits on both visceral and parietal peritoneum, pouch of Douglas, and liver. The uterus and both ovaries contained multiple miliary deposits. Multiple frozen section analysis from omentum, peritoneal surface, and left ovarian wedge biopsy showed welldeveloped epithelioid cell granulomas with caseous necrosis. These findings suggest that the patient had disseminated peritoneal tuberculosis. Following these results, the uterus and both ovaries were left intact. The final pathologic examination was reported that all specimens contained extensive caseous necrosis. ErlichZiehl-Neelson (EZN) stained positive for Mycobacterium tuberculosis. Polymerase chain reaction analysis and cultures from specimens, sputum, and urine were negative for M. tuberculosis.

Disseminated peritoneal tuberculosis

After the operation, we learned from the patient that one of her classmates had been diagnosed with lung tuberculosis. During the recovery period, we started quadruple antituberculosis therapy with 300 mg Isonizid per day, 1.5 g ethambutol per day, 600 mg rifampin per day, and morfozinamid 30 mg/kg/day. She was discharged home on the 10th postoperative day. Nearly 2 months after the initial exploratory laparotomy, the patient was readmitted to another hospital with the complaints of acute nausea, vomiting, jaundice, followed by deep coma. At the end of the initial laboratory investigation at this hospital, she was diagnosed as having fulminant hepatic failure, which required liver transplantation. Therefore, live donor liver transplantation (from her mother) was performed. Pathologic examination of total hepatectomy material showed hepatic necrosis plus caseating necrosis with epithelioid histiocytes and mononuclear infiltration and giant cells on the periphery of the granulomas. Eleven months following the liver transplantation, she remained well and has no complaint.

305

types of peritoneal tuberculosis have been described. The wet type with ascites or pockets of loculated fluids, a dry type with bulky mesenteric thickening and lymphadenopathy, and a third type with mass formation due to omental thickening. The wet type is seen in most of the patients, the other types being less common(6). Similar peritoneal appearance may occur with peritoneal carcinomatosis in all types of peritoneal tuberculosis(9). Common presenting symptoms of the peritoneal tuberculosis are abdominal pain, ascites, fever, weight loss, and anemia. The most common sign of abdominal tuberculosis is lymphadenopathy. It is well known that it may mimic a pelvic mass in imaging studies and also may increase CA125 levels(9,10). Also, peritoneal tuberculosis may produce massive ascites, and intraoperative gross appearance might be similar to the peritoneal carcinomatosis. Therefore, peritoneal tuberculosis is often confused with advanced-stage epithelial carcinoma because of similar clinical, radiologic, and laboratory findings and later intraoperative findings(9,10). Although CA125 is a useful marker for the treatment monitoring and relapse detection of epithelial ovarian carcinoma, it has a low sensitivity especially in premenopausal women. A pelvic mass with increased tumor markers is generally accepted to be part of a malignant process. However, elevated CA125 levels have been shown to be present in patients with nongynecological cancers and some benign pathologies including endometriosis, adenomyosis, uterine fibroids, and pelvic inflammatory disease. Therefore, increased CA125 levels should be evaluated carefully prior to aggressive surgical approach, especially in premenopausal women(11). On the other hand, AFP is well known as a tumor marker of ovarian ESS or embryonal carcinoma in gynecological malignancies. It is essential in the preoperative diagnosis and treatment monitoring of patients with ESS. In fact, many studies reported of elevated CA125 levels in patients with peritoneal tuberculosis(11–13). Surprisingly, AFP may increase without evidence of ovarian malignancy in patients with hepatic dysfunction and iatrogenic hypogonadism(14). However, we could not find any reports of elevated AFP and CA125 due to disseminated peritoneal and hepatic tuberculosis. Germa et al. reported false elevation of AFP without tumoral progression, recurrence, and residual tumor in nine patients with gonadal germ cell tumors. In this study, false elevation of AFP was attributed to liver damage secondary to drugs (chemotherapy, anesthetics, or antiepileptics), virus infection, or alcoholism(14). Although our patient may also have drug-induced

Discussion It is estimated that about 8 million new cases of tuberculosis infection occur each year worldwide, and 95% of these cases are in undeveloped country. Tuberculosis primarily affects the lungs, but about one third of the patients also have involvement of extrapulmonary organs such as the meninges, bone, skin, joints, genitourinary tract, and abdominal cavity(2). Extrapulmonary tuberculosis represents a progressively greater proportion of new cases in the developed countries, and this trend is still increasing(3). Genitourinary tuberculosis is the most common site of extrapulmonary tuberculosis and is most commonly seen in the fallopian tubes in the female genital tract. Peritoneal tuberculosis occurs in 4% of patients with pulmonary tuberculosis, and the peritoneum is the sixth most common extrapulmonary site(4,5). It is usually caused by ingestion of bacilli in infected sputum or contaminated food. Intestinal tuberculosis is followed by spread to the mesenteric lymph nodes, which may rupture, into the peritoneum, causing tuberculosis peritonitis. Hematogenous dissemination is another cause of peritoneal tuberculosis(6). On the other hand, tuberculosis very rarely affects the liver but may cause hepatic failure(7). Peritoneal tuberculosis is a rare situation in developed countries, but it has increased over the past decade because of the growing incidence of tuberculosis infection. It is frequently seen in association with gastrointestinal and hepatic tuberculosis(8). Three #

2006 IGCS, International Journal of Gynecological Cancer 16 (Suppl. 1)

306 P. Dursun et al.

hepatic failure due to the preoperative AFP elevation, we supposed her to have a tuberculosis-mediated hepatic failure primarily. Ultrasonographic findings of peritoneal tuberculosis consist of large volumes of ascites including septa and membranes, thickened ileal valve and bowel, mesenteric adhesions, and lymphadenopathy. Yapar et al. reported that septated ascites, particulate ascites, loculated fluid, thickened peritoneum, thickened omentum, adnexal mass, and adhesions are ultrasonographic findings of wet-type tuberculosis(15). Furthermore, adnexal masses, adhesions, and loculated fluid are associated with dry-type tuberculosis(5). Sonographic findings are not specific for the diagnosis of peritoneal tuberculosis, but when noted in the appropriate clinical situation, sonography would be useful in order to avoid clinical mismanagement and unnecessary surgical explorations in the peritoneal tuberculosis(15). On the other hand, sensitivity of the preoperative CT scan for predicting peritoneal tuberculosis was found as 69% by Ha et al.(16). At CT scan, one half of the patients with gastrointestinal tuberculosis show circumferential thickening of the cecum and terminal ileum, enlargement of the ileocecal valve, and mesenteric lymphadenopathy. Also, other findings such as asymmetry of the ileocecal valve, thickening of the medial cecal wall, exophytic extension and engulfment of the terminal ileum, and massive adenopathy are more suggestive of tuberculosis. Epstein and Mann reported that irregular softtissue densities in the omental area, low-density masses surrounded by thick solid rim, a disorganized appearance of soft-tissue densities, fluid, and bowel loops forming a poorly defined mass, low-density lymph nodes with a multilocular appearance after intravenous contrast administration, and high-density ascites are additional CT findings of peritoneal tuberculosis(17). As a result, preoperative imaging studies might be helpful in distinguishing peritoneal tuberculosis from peritoneal carcinomatosis by an experienced radiologist. A definitive diagnosis of tuberculosis depends on a positive mycobacterial culture from a diagnostic specimen, although most authorities today accept a diagnosis based on the standard histopathologic criteria of tissue biopsies(18). The gold standard for the diagnosis of peritoneal tuberculosis is the culture of ascitic fluid or peritoneum(19). Although there are some suggestive signs and appearance of peritoneal tuberculosis with ultrasonography and CT, these imaging studies have not enough sensitivity or specificity for the exact diagnosis of peritoneal tuberculosis. Imaging techniques may give valuable information for management of the patients with peritoneal tuberculosis, but sometimes, they may cause unnecessary extensive surgery. Voigt #

2006 IGCS, International Journal of Gynecological Cancer 16 (Suppl. 1)

et al. have shown that elevated adenosine deaminase enzyme activity is an excellent diagnostic test for peritoneal tuberculosis(20). Therefore, adenosine deaminase enzyme activity may be used in young patients with a pelvic mass to distinguish between peritoneal tuberculosis and peritoneal carcinomatosis, especially in endemic areas. This approach may reduce unnecessary extensive surgery and surgery-associated morbidity in patients with peritoneal tuberculosis.

Conclusion Tuberculosis is still a serious public health problem worldwide. Due to unspecific radiographic findings in extrapulmonary tuberculosis and lack of specific and sensitive tests, the preoperative diagnosis of peritoneal tuberculosis is often very difficult and it can be frequently confused with peritoneal carcinomatosis. False elevation of CA125 and AFP may be seen in abdominal tuberculosis, and it may be confused with ESS preoperatively. Also, an intraoperative frozen section is helpful in preventing extensive surgery.

References 1 Panoskaltsis TA, Moore DA, Haidopoulos DA, McIndoe AG. Tuberculous peritonitis: part of the differential diagnosis in ovarian cancer. Am J Obstet Gynecol 2000;182:740–2. 2 Zaidi SN, Conner M. Disseminated peritoneal tuberculosis mimicking metastatic ovarian cancer. South Med J 2001;94:1212–4. 3 Akhan O, Pringot J. Imaging of abdominal tuberculosis. Eur Radiol 2002;12:312–3. 4 Lenk S, Schroeder J. Genitourinary tuberculosis. Curr Opin Urol 2001;11:93–8. 5 Crowley JJ, Ramji FG, Amundson GM. Genital tract tuberculosis with peritoneal involvement: MR appearance. Abdom Imaging 1997;22:445–7. 6 Sinan T, Sheikh M, Ramadan S, Sahwney S, Behbehani A. Computed tomography (CT) features in abdominal tuberculosis: 20 years experience. BMC Med Imaging 2002;2:3. 7 Hussain W, Mutimer D, Harrison R, Hubscher S, Neuberger J. Fulminant hepatic failure caused by tuberculosis. Gut 1995;36:792–4. 8 Groutz A, Carmon E, Gat A. Peritoneal tuberculosis versus advanced ovarian cancer: a diagnostic dilemma. Obstet Gynecol 1998;91(5 Pt 2): 868. 9 Engin G, Acunas B, Acunas G, Tunaci M. Imaging of extrapulmonary tuberculosis. Radiographics 2000;20:471–88. 10 Bilgin T, Karabay A, Dolar E, Develioglu OH. Peritoneal tuberculosis with pelvic abdominal mass, ascites and elevated CA125 mimicking advanced ovarian carcinoma: a series of 10 cases. Int J Gynecol Cancer 2001;11:290–4. 11 Sheth SS. Elevated CA125 in advanced abdominal or pelvic tuberculosis. Int J Gynaecol Obstet 1996;52:167–71. 12 Simsek H, Savas MC, Kadayifci A, Tatar G. Elevated serum CA125 concentration in patients with tuberculous peritonitis: a case-control study. Am J Gastroenterol 1997;92:1174–6. 13 Straughn JM, Robertson MW, Partridge EE. A patient presenting with a pelvic mass, elevated CA-125, and fever. Gynecol Oncol 2000;77:471–2. 14 Germa JR, Llanos M, Tabernero JM, Mora J. False elevations of alpha-fetoprotein associated with liver dysfunction in germ cell tumors. Cancer 1993;72:2491–4. 15 Yapar EG, Ekici E, Karasahin E, Gokmen O. Sonographic features of tuberculous peritonitis with female genital tract tuberculosis. Ultrasound Obstet Gynecol 1995;6:121–5.

Disseminated peritoneal tuberculosis

307

19 Reddy KR, DiPrima RE, Raskin JB et al. Tuberculous peritonitis: laparoscopic diagnosis of an uncommon disease in the United States. Gastrointest Endosc 1988;34:422–6. 20 Voigt MD, Kalvaria I, Trey C, Berman P, Lombard C, Kirsch RE. Diagnostic value of ascites adenosine deaminase in tuberculous peritonitis. Lancet 1989;1:751–4.

16 Ha HK, Jung JI, Lee MS et al. CT differentiation of tuberculous peritonitis and peritoneal carcinomatosis. AJR Am J Roentgenol 1996; 167:743–8. 17 Epstein BM, Mann JH. CT of abdominal tuberculosis. AJR Am J Roentgenol 1982;139:861–6. 18 Namavar-Jahromi B, Parsanezhad ME, Ghane-Shirazi R. Female genital tuberculosis and infertility. Int J Gynaecol Obstet 2001;75: 269–72.

Accepted for publication October 18, 2004

#

2006 IGCS, International Journal of Gynecological Cancer 16 (Suppl. 1)