Disseminated peritoneal tuberculosis mimicking metastatic ovarian cancer. (Case Histories).

ABSTRACT: A 41-year-old woman had a 2-week history of low-grade fever, associated with gradually increasing abdominal pain and girth. Ultrasonography showed a complex cystic right adnexal mass. Diffuse nodules (0.1 to 0.5 cm) were found at exploratory laparotomy involving the serosal surfaces of the uterus, fallopian tubes, and ovaries. She had a total abdominal hysterectomy, with bilateral salpingo-oophorectomy and omentectomy for presumed stage IIIC ovarian carcinoma. Histopathologic examination showed chronic granulomatous inflammation with no evidence of neoplasm. Special stains on tissue sections and ascitic fluid were negative for fungi and mycobacteria. Additional history indicated a recently positive PPD skin test (within 6 months), followed by isoniazid therapy for 4 months. Polymerase chain reaction (PCR) done on paraffin-embedded tissues produced evidence of Mycobacterium tuberculosis. Ascitic fluid cultures became positive for M tuberculosis at 6 weeks. The patient was placed on four-drug antitube rculous therapy and had a complete recovery.

IT IS ESTIMATED that about 8 million new cases of Mycobacterium tuberculosis infection occur each year worldwide, and 95% of these are in underdeveloped nations. About 3 million people die of this disease each year. If left untreated, about 50% would die within 5 years. (1-3)

The developed world (including the United States) had a dramatic reduction in the incidence of M tuberculosis infection after the early 1950s, mainly due to reduction in overcrowding and availability of effective antibiotics. Since 1986, however, the incidence of M tuberculosis infection in the United States has been rising, largely because of the increase of persons infected with the human immunodeficiency virus (HIV), immigration of infected individuals from endemic areas, and social problems such as poverty, homelessness, and drug abuse. The disease mainly affects the lung, but about one third of patients also have involvement of other organs, such as meninges, bone, joints, genitourinary tract, and abdominal cavity. (1-3)

Peritoneal/abdominal tuberculosis is still common in underdeveloped countries. Its incidence is low in developed countries (sixth most common extrapulmonary site), but an increasing number of cases have been identified with the recent rise in the incidence of M tuberculosis infection. (4-7) Peritoneal infection is commonly manifested by abdominal pain, ascites, diarrhea, fever, weight loss, and anemia. The clinical, radiologic, and laboratory (elevated CA-125 levels) presentation is often confused with peritoneal carcinomatosis. (5-8) Laparoscopically directed biopsy and histologic and PCR tests provide a rapid and definitive diagnosis. (8,9) When promptly diagnosed, it is one of the few diffuse peritoneal processes for which there is effective therapy, with an excellent prognosis.

CASE REPORT

A 41-year-old woman (gravida 2, para 2) was admitted for evaluation of a right pelvic mass and ascites. The patient was in good health until 2 weeks before admission, when diffuse abdominal pain developed. Over the next 2 weeks, the pain intensified and was accompanied by a sensation of increasing abdominal girth. She denied nausea, vomiting, fever, or chills. Pelvic ultrasonography showed a complex right adnexal mass and a large amount of ascites (Fig 1). Her medical history included hypothyroidism, hypertension, cesarean section (x 2), and bilateral tubal ligation. The patient's half sister had died of ovarian cancer.

Physical examination showed a distended abdomen with a palpable right adnexal mass, shifting dullness, mild tenderness in the right lower quadrant, and normal bowel sounds. The right adnexal mass was also confirmed on bimanual examination. Chest was clear to auscultation bilaterally. Except for body temperature of 101.2[degrees]F, all other vital signs and organ systems were within normal limits.

The patient continued to have abdominal pain and low-grade fever (100[degrees] to 102[degrees]F). Workup included multiple blood cultures that remained sterile. The hematocrit value fell from 28% to 23% within 2 days, necessitating transfusion of 10 units of packed red blood cells in anticipation of exploratory laparotomy. Operative findings included a small right tubo-ovarian mass and a diffuse peritoneal and mesenteric fine nodularity. Surgery included debulking with total abdominal hysterectomy, bilateral salpingo-oophorectomy, and omentectomy. In addition, 8 L of yellow ascitic fluid were removed. Postoperative diagnosis was stage IIIC ovarian carcinoma. Postoperatively, the patient had a rapid recovery but continued to spike fevers of up to 102[degrees]F despite empiric antibiotic therapy.

The surgical specimen consisted of uterus, bilateral adnexae, and omentum. The serosal surfaces of the uterus, cervix, adnexae, and omentum were studded with numerous small (0.1 to 0.5 cm), pale tan, focally hemorrhagic nodules. The right and left ovaries measured 3.5 and 3.1 cm in maximum dimensions, respectively. The right ovary revealed a single smooth wall cyst measuring 1.5 cm and two small hemorrhagic corpus luteal cysts. The left ovary, both fallopian tubes, endometrial cavity, and cervix were within normal limits. Several small (0.3 to 0.5 cm) intramural leiomyomas were identified in the uterus. On microscopic examination, the grossly described serosal surface nodules were characterized by chronic granulomatous inflammation (Fig 2). The granulomas were composed of epithelioid histiocytes admixed with occasional multinucleated giant cells. A few granulomas showed evidence of caseous necrosis. Special stains for acid-fast bacilli and fungi were negative with adequate controls. Both ovaries were benign, showing no evidence of malignancy. The endometrium was proliferative, without evidence of hyperplasia or malignancy. A few benign leiomyomas and adenomyosis were identified within the myometrium.

On further questioning, the patient revealed that a PPD test had converted to positive 6 months previously and she had taken isoniazid for 4 months. Treatment was started with four antituberculous drugs (isoniazid, rifampin, pyrazinamide, and ethambutol). The paraffin embedded tissue was sent for PCR analysis, which showed evidence of M tuberculosis. At the same time, additional ascitic fluid was obtained for culture and 6 weeks later was reported to be positive for M tuberculosis. The patient continued taking the four antituherculous drugs for the next 9 months and completely recovered.

DISCUSSION

The incidence of tuberculosis is rising in the developed world. Occasionally, cases of tuberculosis have atypical extrapulmonary presentation, as exemplified by the present case.

An infected person most likely transmits M tuberculosis by droplet infection associated with coughing, sneezing, or talking. The probability of infection increases with the intimacy and duration of contact and the degree of infectiousness (ie, positive tests of sputum for acid-fast bacilli). The risk of tuberculosis developing after exposure depends largely on endogenous factors, including coinfection with HIV immunosuppressive states such as organ transplantation and malignancies, uncontrolled diabetes, and chronic renal failure. It is estimated that active tuberculosis will develop in about 10% of infected individuals. (1) Health care workers are at greater risk than the general population for acquiring tuberculosis because of their higher exposure rates. (1-3)

In summary, peritoneal tuberculosis may occasionally be misdiagnosed as peritoneal carcinomatosis, as shown by our case and by previous reports. (47) The patient need not be immunocompromised. Serum CA-125 determinations are not diagnostically significant in peritoneal M tuberculosis infections. (7,8) Peritoneal tuberculosis should be considered in the differential diagnosis in patients with abdominal pain, fever, and weight loss. A clinical awareness of peritoneal tuberculosis might result in appropriate procedures (laparoscopic biopsy and/or PCR or intraoperative frozen section examination) for detecting this rapidly fatal but curable disease.

In our case, the acid-fast stain for mycobacteria was negative. However, the history of a recent positive conversion of PPD test results within the previous 6 months led to PCR analysis on paraffin embedded tissue. Cultures of peritoneal fluid eventually grew M tuberculosis, but the positive results with PCR analysis allowed appropriate therapy to be instituted earlier. Thus, PCR analysis is helpful in cases with a history suggestive of possible M tuberculosis infection but with negative special stains for acid-fast bacilli on tissue sections.

References

(1.) Raviglione MC, Obrien RJ: Mycobacterial diseases: tuberculosis. Harrison's Principles of Internal Medicine. New York, McGraw-Hill, 14th Ed, 1998, pp 1004-1014

(2.) Centers for Disease Control and Prevention: Core curriculum on tuberculosis: what clinicians should know. Atlanta, US Department of Health and Human Services, 3rd Ed, 1994

(3.) Fatkenheuer G, Taelman H, Lepage P, et al: The return of tuberculosis. Diagn Microbiol Infect Dis 1999; 34:139--146

(4.) Lisehora GB, Peters CC, Lee YTM, et al: Tuberculous peritonitis. do not miss it. Dis Colon Rectum 1996; 39:394--399

(5.) Groutz A, Carmon E, Gat A: Peritoneal tuberculosis and advanced ovarian cancer: a diagnostic dilemma. Obstet Gynecol 1998; 91:868

(6.) Rodriguez E, Pombo F: Peritoneal tuberculosis versus peritoneal carcinomatosis: distinction based on CT findings. J Comput Assist Tomogr 1996; 20:269--272

(7.) de Paz FN, Fernandez BH, Simon RP, et al: Pelvic-pentoneal tuberculosis simulating ovarian carcinoma: report of three cases with elevation of CA 125. Am J Gynecol 1996; 91:1660-1661

(8.) Mclaughlin S, Jones T, Pitcher M, et al: Laparoscopic diagnosis of abdominal tuberculosis. Aust N Z J Surg 1998; 68:599-601

(9.) Apaydin B, Paksoy M, Billir M, et al: Value of diagnostic laparoscopy in tuberculous peritonitis. Eur J Surg 1999; 165:158-163

RELATED ARTICLE: KEY POINTS

* Eight million new cases of Mycobacterium tuberculosis infections occur each year worldwide, and 95% of these are in underdeveloped nations.

* About 3 million people die of this disease each year. If left untreated, about 50% would die within 5 years.

* Peritoneal tuberculosis may occasionally be misdiagnosed as peritoneal carcinomatosis and is demonstrated in this case.

* Peritoneal tuberculosis should be considered in the differential diagnosis in patients with abdominal pain, fever, and weight loss.

* Polymerase chain reaction analysis is helpful in cases with a history suggestive of possible M tuberculosis infection, but with negative special stains for acid-fast bacilli on tissue sections.