Peritoneal Tuberculosis Mimicking Cancerous Peritonitis With Elevated Serum Cancer Antigen 125 and Carbohydrate Antigen 19-9 Levels: A Case Report.

A 75‐year‐old Japanese female patient with rheumatoid arthritis had been receiving certolizumab for 5 months and had experienced fatigue, low‐grade fever, and abdominal pain for 1 month. Abdominal computed tomography (CT) revealed massive ascites and peritoneal thickening, and she was referred to our hospital for further evaluation. Upon admission, her physical examination revealed the following: height, 162 cm; body weight, 53 kg (body mass index of 20.2 kg/m 2 ); body temperature, 37.4°C; heart rate, 111 bpm; blood pressure, 136/79 mmHg; and oxygen saturation, 95% (room air, at rest), and her European Cooperative Oncology Group performance status was 1. Laboratory results revealed abnormal results including high serum CA125 (332.0 U/mL) and CA19‐9 (213.0 U/mL) levels (Table  1 ). High‐resolution contrast‐enhancement CT showed centrilobular nodular opacities in bilateral lungs, massive ascites, and localised peritoneal thickening with contrast‐enhancement (Figure  1A,B ). Laboratory data on admission. Abbreviations: ADA, adenosine deaminase; Alb, albumin; ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BUN, blood urea nitrogen; CA125, cancer antigen 125; CA19‐9, cancer antigen 19‐9; CEA, carcinoembryonic antigen; CRP, C‐reactive protein; Hb, haemoglobin; Ht, haematocrit; LDH, lactate dehydrogenase; RBC, red blood cell; T‐bil, total bilirubin; TP, total protein; WBC, white blood cell; γ‐GTP, gamma‐glutamyl transferase. Computed tomography (CT) and laparoscopic findings. CT on admission reveals centrilobular nodular opacities in the lungs (A), massive ascites, and localised peritoneal thickening with enhancement (yellow arrow) (B). Laparoscopic findings. Numerous miliary yellow‐white nodules are observed in the parietal peritoneum, with some coalescing into larger lesions (C and D). To differentiate from gastrointestinal carcinomatous peritonitis, we performed upper and lower gastrointestinal endoscopies, which revealed no evidence of malignancy. The interferon‐gamma release assay yielded an indeterminate result, with a mitogen control value of 0.20 IU/mL, which was presumed to be related to methotrexate treatment [ 2 ]. Paracentesis revealed straw‐coloured ascitic fluid with elevated levels of adenosine deaminase (ADA) (108 U/L), whereas cytology revealed no malignant cells. Culture for acid‐fast bacilli and PCR for Mycobacterium tuberculosis tested negative. Laparoscopy on the 2nd day revealed numerous miliary yellow‐white nodules in the parietal peritoneum, some of which coalesced into larger lesions (Figure  1C,D ). Peritoneal biopsy revealed epithelioid cell granulomas and Langhans giant cells, with bacilli positive for Ziehl‐Neelsen stain. Additionally, sputum acid‐fast bacilli culture and PCR for M. tuberculosis were both positive and M. tuberculosis was subsequently isolated from mycobacterial culture. The patient was diagnosed with pulmonary and peritoneal tuberculosis, and treatment with three anti‐tuberculous medications (rifampicin 9 mg/kg, isoniazid 5 mg/kg, and ethambutol 15 mg/kg) was initiated. However, owing to cholestatic liver injury, treatment was temporarily discontinued. After liver dysfunction improvement, treatment was changed to ethambutol (15 mg/kg) and levofloxacin (500 mg/body), and isoniazid (5 mg/kg) and pyrazinamide (25 mg/kg) were added subsequently (Figure  2 ). Three months after initiating anti‐tuberculous treatment, serum levels of CA125 (8.92 U/mL) and CA19‐9 (216.9 U/mL) had decreased (Figure  2 ). Clinical course of the patient: The patient was diagnosed with pulmonary and peritoneal tuberculosis (PTB), and treatment with three anti‐tuberculosis medications (rifampicin, isoniazid, ethambutol) was initiated, but these treatments were temporarily discontinued due to cholestatic liver injury. After liver function improvement, treatment was changed to ethambutol and levofloxacin, and subsequently isoniazid and pyrazinamide. Three months after initiating anti‐tuberculous treatment, serum CA125 and CA19‐9 levels decreased with anti‐tuberculous medication.

All the authors met the ICMJE authorship criteria. Toshiki Morimoto drafted the study. Kei Yamasaki supervised the writing of the manuscript and was responsible for clinical data. Rumiko Fujimasa and Atsushi Tohyama performed the laparoscopy. Maika Meguro, Hiroaki Degawa, Riho Hirosawa, Hiroaki Ikegami, Masahiro Tahara and Takanobu Jotatsu critically reviewed the manuscript. Kazuhiro Yatera organized and contributed to the management of this case report. All authors contributed to the writing of the final manuscript.

The authors state that written informed consent for the publication of this manuscript and the accompanying images was obtained using the consent form provided by the Journal.

Here, we present a rare case of PTB mimicking peritoneal carcinomatosis characterised by elevated serum CA125 and CA19‐9 levels, both of which decreased after anti‐tuberculous treatment. PTB is a rare entity with nonspecific clinical features that hinder its differentiation from malignancies and other conditions. It comprises approximately 0.1%–0.7% of tuberculosis cases globally [ 1 ]. Although Japan has maintained a relatively low tuberculosis incidence rate of 9.2 per 100,000 population since 2021 [ 3 ], this rate remains higher than that of most European countries and the United States. Therefore, physicians in Japan frequently encounter and manage tuberculosis patients and may also have opportunities to diagnose PTB. Serum CA19‐9 is synthesised by pancreatic and biliary ductal cells, as well as by the epithelium of the stomach, colon, and endometrium. Elevated serum CA19‐9 levels are typically observed in conditions such as obstructive jaundice [ 4 ], particularly in association with lesions in the pancreatic head. Although rare, a few cases of PTB presenting with elevated CA19‐9 have been reported, including our own, bringing the total to just two known cases to date [ 5 ]. In contrast, serum CA125 levels are more frequently elevated in patients with PTB. CA125 can also be elevated in various benign conditions, including endometriosis, uterine fibroids, peritoneal inflammation of any aetiology, menstruation, pregnancy, obesity, heart failure, and liver cirrhosis. Clinically, CA125 is primarily used as a tumour marker in patients with ovarian cancer complicated by peritoneal carcinomatosis, but elevated levels have also been reported in PTB [ 6 ]. Tumour marker elevation patterns vary depending on the form of tuberculosis and may be explained by different underlying mechanisms. CA125 elevation has been reported in both tuberculous peritonitis and pleurisy, likely due to mesothelial inflammation. Previous studies have proposed that a specific tumour marker profile—elevated serum CA125 (> 35 U/mL) with normal serum CA19‐9 (< 37 U/mL) and CEA (< 5 ng/mL)—can help differentiate PTB from peritoneal carcinomatosis. When combined with fever, this diagnostic pattern demonstrated a sensitivity of 88.2% and specificity of 100% for PTB diagnosis [ 7 ]. In contrast, elevated CA19‐9 has been observed in cases of pulmonary tuberculosis [ 8 ]. Therefore, in the present patient, the pulmonary tuberculosis lesions identified may have contributed to the observed increase in serum CA19‐9, in addition to peritoneal involvement. In the present case, both serum CA125 and CA19‐9 levels were elevated. However, no malignant findings were identified on upper or lower gastrointestinal endoscopy or CT imaging. Following anti‐tuberculous therapy alone, both markers decreased significantly, suggesting that the elevation of CA125 and CA19‐9 was attributable to PTB rather than malignancy. In conclusion, even in patients with ascites accompanied by elevated levels of serum tumour markers such as CA125 and CA19‐9, who are likely to have malignant peritonitis, PTB should be considered in appropriate clinical contexts such as in patients receiving biological agents and when chest CT reveals findings suggestive of pulmonary tuberculosis, such as centrilobular nodular opacities. As serum CA125 and CA19‐9 levels may also be elevated in PTB, serial monitoring of these markers may help in evaluating treatment response of tuberculosis.

Peritoneal tuberculosis (PTB) is a rare manifestation of extrapulmonary tuberculosis. The primary mechanism of PTB is the reactivation of latent tuberculosis through lymphohematogenous or hematogenous spread from a previous pulmonary focus of infection. The diagnosis of PTB is occasionally challenging, as PTB mimics carcinomatous peritonitis with very similar radiographic characteristics and clinical symptoms [ 1 ]. In most PTB cases, abdominal radiological images may initially indicate malignant peritonitis and an unexpectedly diagnosed PTB only after typical laparoscopic findings with peritoneal biopsy results [ 1 ]. Physicians should be aware of PTB when managing patients with ascites with gynaecological and gastrointestinal malignancies. We herein present a patient with massive ascites with elevated serum cancer antigens 125 (CA125) and carbohydrate antigen 19‐9 (CA19‐9) levels who was diagnosed with PTB by laparoscopic findings and peritoneal biopsy, and was successfully treated with anti‐tuberculous agents with a decrease of serum CA125 and CA19‐9.

The authors declare no conflicts of interest.