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American Board of Abdominal Surgery


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ABDOMINAL SURGERY

Official Journal of the American Society of Abdominal Surgeons, Inc.

This article originally appeared in the Winter 2013 / Spring 2014 issue of the Journal.

Primary Peritoneal Tuberculosis with Ascites and Elevated CA 125 Mimicking Advanced Ovarian Carcinoma: Case Report.

Dr. Zlatko Hrgovic
Tomislav Kulas
Danijel Bursac
Gordana Planinic Rados
Katarina Bojanic

Address for correspondence:
Dr. Zlatko Hrgovic
Frankfurt, Germany
Tel: +4969293000
Email: info@hrgovic


CASE REPORT

We present the case of a 37-year-old woman (G3, P2), who presented with stress urinary incontinence (SUI). The patient is of Bulgarian descent, obese (BMI 30). Her medical history was uneventful. There was no evidence of personal exposure or family history to tuberculosis. Diagnostic work-up revealed SUI grade 3. Following a two month reduction diet, SUI was surgically corrected with GYNECARE TVT Obturator System Tension-free Support for Incontinence. Surgery follow-up 12 days later showed the tape in place, no symptoms of SUI, a normal urodynamic exam but the ultrasound exam showed ascites. Ovarian cancer was suspected. Chest X-ray, CT scan of the abdomen and bone scintigraphy was normal. Laboratory findings showed a mild secondary anemia and CA 125 value of 582 U/ml. Other tumor marker values were: CEA 0,8 μg/l (<5), Ca 15-3 33,3 U/ml (<25), Ca 19-9 8,6 U/ml (<37) and Ca 72-1 1,3 U/ml (<8,2). MRI of the abdomen showed cystic ovaries bilaterally. Fractional curettage and diagnostic laparoscopy were done. Pathohistology of the material from fractional curettage showed normal results and 35 ml ascites obtained during laparoscopy showed no signs of peritoneal carcinomatosis or malignant cells, but pseudo-papular nodules, sporadic thickening of the peritoneum and adhesions were found. Tumor makers obtained from the ascites were: Ca 125 1156 U/l, CEA 0,6 μg/l, Ca 15-3 44,2 U/l, Ca 19-9 9,0 U/l. Contact allergy to Polypropylen (from which the TVT™ Obturator tape) was suspected but excluded. The Ca 125 was now at 2000 U/l. Advanced-stage epithelial ovarian carcinoma and primary peritoneal carcinomatosis were still the main suspected diagnosis. Twelve days following diagnostic laparoscopy, explorative laparatomy was done with cytoreductive surgery. During surgery ascites and multiple peritoneal implants covering the parietal peritoneum, omentum, small intestines, liver and adnexa were confirmed.

Adnexectomy was done. Intraoperative pathohistology of the left ovary and parietal peritoneum ruled out malignancy, but the granulomatous inflammatory lesions found were highly suspicious for tuberculosis. The pathology report stated: serous papillary deposits on the peritoneum with atypical proliferative cells could be features of ovarian borderline carcinoma. Granulomatous salpingitis with abnormal, probably reactive changes of the cylindrical epithelium (Figure 1, 2 – histology). A QuantiFERON-TB Gold test was performed and determined to be positive. Culture isolation and definitive diagnosis of Mycobacterium tuberculosis was made from biopsy of the omentum. Following surgery our patient was started on tuberculosis therapy: Ethambutol (1200+0+0 mg), Pyrafat (2+0+0+0 g), Rifampicin (600+0+0+0 mg) and Isoniazid. The outcome of the tuberculosis treatment was successful.

Figure 1
Thickened wall of Fallopian tube (HE).

click to enlarge

DISCUSSION

Tuberculosis (TBC) is an infectious disease caused by various strains of mycobacteria usually Mycobacterium tuberculosis. One third of the world’s population is thought to have been infected. Twenty percent of infected individuals do not develop active disease but have a latent form of tuberculosis without any clinical symptoms. Tuberculosis may infect any part of the body, most commonly the lungs, but can also infect the central nervous system, lymphatic system, genitourinary system, bones, pelvis and joints. A more serious disseminated form of the disease is commonly known as milliary tuberculosis.1

There are an increasing number of new cases with an increasing number of atypical forms of tuberculosis in the world. Because of this trend gynecologists should be aware of atypically presenting forms of tuberculosis in the female genital tract and pelvis mimicking gynecologic malignancies, diseases and causes of infertility. In developing countries pelvic tuberculosis is common and mostly occurs in young and fertile women between the ages of 15 and 25, while in developed countries postmenopausal women (62%) are more frequently affected.2 Disseminated pelvic tuberculosis comprises 1-3% of all forms of tuberculosis.3 Pelvic tuberculosis is almost always secondary to tuberculosis elsewhere in the body, such as lungs, abdomen, lymph nodes etc. Direct sexual transmission and spread from other intraperitoneal organs is reported but very rare.4We present a in our case of primary peritoneal tuberculosis.

The primary focuses of pelvic tuberculosis are fallopian tubes, which are almost always infected. Clinical manifestations are pelvic pain, infertility or menstrual problems. Less common clinical manifestations are adnexal masses, ascites or both with an elevated level of CA-125. The clinical signs are difficult to differentiate from advanced adnexal malignancies.5, 6

History of primary tuberculosis infection or contact with an infected individual is important in making the diagnosis. Pelvic tuberculosis should be suspected in infertility cases of unknown cause, pelvic infections resistant to antibiotic therapy, adnexal masses with ascites in virgo patients.

Pelvic tuberculosis can be a sign of Ashermanov’s syndrome, fallopian tube obstruction, pelvic, abdominal and perihepatic adhesions (Fitz- Hugh-Curtis syndrome).7, 8, 9

Figure 2
Round form granulomas in outer wall of Fallopian tubes.

click to enlarge

Pelvic tuberculosis is rare and difficult to diagnose because of atypical and nonspecific clinical manifestations. Commonly it is mistaken for adnexal tumors, especially if ascites is present. Tumor marker CA 125 is a nonspecific marker of ovarian cancer. It is also elevated in other conditions and diseases (endometriosis, Meigsov syndrome, menstruation, ovarian hyperstimulation, active hepatitis, acute pancreatitis, pericarditis). Commonly it is elevated in pelvic tuberculosis, which makes the diagnosis even more difficult.

The gold standard in diagnosing tuberculosis is characteristic histology showing granulomas, and/or acidfast bacili (Ziehl-Neelsen stains) and/or positive culture for mycobacterium on Lowenstein-Jensen agar. These methods are time-consuming and have low specificity and sensitivity. PCR detection of DNA Mycobacterium tuberculosis is the most commonly used method today, it is superior in speed, sensitivity and specificity.10

As mentioned earlier, tuberculosis being a worldwide problem with its incidence increasing, it is endemic in some parts of the world and rare in others. Incorrect diagnosis is often made, therapy choices, often with mutilating surgical treatments, are unfortunately consequently applied. The diagnosis is often made following pathohistology analysis and exclusion of malignancies retrospectively.

In our case the diagnosis was made following unilateral adnexectomy and malignancy exclusion.

There are no reported algorithms for diagnosing pelvic tuberculosis but different laboratory, surgical and imaging techniques are used.

Pelvic US, CT and hysterosalpingography are imaging methods used in making the diagnosis, but can commonly take us on the wrong path.

Diagnostic laparoscopy is now the most important method for making the diagnosis.11 We can analyze the changes macroscopically (peritoneal carcinosis like lesions) and microscopically. Targeted biopsy and access to the peritoneal contents (body fluids, ascites) helps in further laboratory testing and pathology diagnosis which was not done initially in our case.12 Diagnostic laparoscopy with target biopsy and PCR is one of the fundamental diagnostic methods in making the right diagnosis. The most common therapy includes Isoniazide and Rifampin for 6 months duration, in combination with Pyrazinamid and Ethamutol for the first 2 months. Prognosis is excellent. Most women are cured with this therapy but permanent sterility can be a complication.13

CONCLUSION

With a globalised world today, there is free movement and migration, making tuberculosis once again a worldwide problem. Pelvic tuberculosis should therefore be taken into account as differential diagnosis when treating sterility of unknown cause, pelvic inflammatory diseases unresponsive to therapy, or adnexal malignancies. In our case, the clinical presentation directed us towards adnexal malignancy. Following patient history, laboratory and clinical workup we did not suspect pelvic tuberculosis and the diagnosis was made following intraoperative exclusion of malignancy. Biopsy taken during diagnostic laparoscopy and culture of ascites would have given us the right diagnosis preventing unnecessary surgery, but was not done in our case.

This shows how challenging the differential and definitive diagnosis of pelvic tuberculosis can be even though detailed diagnostics were done prior to exclusion of malignancy.

Because of nonspecific and often mimicking clinical presentations, regardless of its geographical and population specifics, we must take pelvic tuberculosis into account when making our differential diagnosis of the above clinical presentations.

REFERENCES

1.“Tuberculosis Fact sheet N°104”. World Health Organization. November 2010. http://www.who.int/ mediacentre/factsheets/fs104/en/index.html

2. Marcus SF, Rizk B, Fountain S, Brinsden P. Tuberculous infertility and in vitro fertilization. Am J Obstet Gynecol. 1994 Dec;171(6):1593-6.

3. Lantheaume S, Soler S, Issartel B, Isch JF, Lacassin F, Rougier Y, Tabaste JL. Peritoneal tuberculosis simulating advanced ovarian carcinoma: a case report. Gynecol Obstet Fertil. 2003 Jul-Aug;31(7-8):624-6.

4. Hassoun A, Jacquette G, Huang A, Anderson A, Smith MA. Female genital tuberculosis: uncommon presentation of tuberculosis in the United States. Am J Med. 2005 Nov;118(11):1295-6.

5. Chavhan GB, Hira P, Rathod K, Zacharia TT, Chawla A, Badhe P, Parmar H. Female genital tuberculosis: hysterosalpingographic appearances. Br J Radiol. 2004 Feb;77(914):164-9.

6. Sinha P, Johnson AN, Chidamberan-Pillai S. Pelvic tuberculosis: an uncommon gynaecological problem presenting as ovarian mass. BJOG. 2000 Jan;107(1):139-40.

7. Gupta N, Sharma JB, Mittal S, Singh N, Misra R, Kukreja M. Genital tuberculosis in Indian infertility patients. Int J Gynaecol Obstet. 2007 May;97(2):135-8.

8. Sharma JB, Roy KK, Gupta N, Jain SK, Malhotra N, Mittal S. High prevalence of Fitz-Hugh-Curtis Syndrome in genital tuberculosis. Int J Gynaecol Obstet. 2007 Oct;99(1):62-3.

9. Sharma JB, Roy KK, Pushparaj M, Gupta N, Jain SK, Malhotra N, Mittal S. Genital tuberculosis: an important cause of Asherman’s syndrome in India. Arch Gynecol Obstet. 2008 Jan;277(1):37-41.

10. Poyrazoglu OK, Timurkaan M, Yalniz M, Ataseven H, Dogukan M, Bahcecioglu IH. Clinical review of 23 patients with tuberculous peritonitis: presenting features and diagnosis. J Dig Dis. 2008 Aug;9(3):170-4.

11. Sharma JB, Roy KK, Pushparaj M, Kumar S, Malhotra N, Mittal S. Laparoscopic findings in female genital tuberculosis. Arch Gynecol Obstet. 2008 Oct;278(4):359-64.doi: 10.1007/s00404-008-0586-7.

12. Crochet JR, Hawkins KC, Holland DP, Copland SD. Diagnosis of pelvic tuberculosis in a patient with tubal infertility. Fertil Steril. 2011 Jan;95(1):289.e17-20. doi: 10.1016/j.fertnstert.2010.06.012.

13. Ainbinder SW, Ramin SM. Sexually transmitted disease & pelvic infections. In: DeCheney AH, Nathan L, eds. Current obstetric & treatment. New York: McGraw Hill, 2003:742-3.



Journal CoverOFFICIAL PUBLICATION OF:
The American Board of Abdominal Surgery
The American Society of Abdominal Surgeons, Inc.
Foundation for Abdominal Surgery

Louis F. Alfano, Jr., M.D., Editor-in-Chief
Diane M. Pothier, Executive Editor and
Director of Continuing Medical Education


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Figure 1:

Thickened wall of Fallopian tube (HE).

Figure 2:

Round form granulomas in outer wall of Fallopian tubes.