Is a 55-year-old lady with abdominal pain, ascitic fluid adenosine deaminase (ADA) level of 75, and empirical anti-tuberculosis treatment (ATT) started, but with a subsequent diagnosis of metastatic adenocarcinoma with signet ring cells on parietal pleura biopsy, suffering from both tuberculosis (TB) and malignancy, or just malignancy?

Diagnosis: Metastatic Adenocarcinoma Without Concurrent Active Tuberculosis

This patient has metastatic adenocarcinoma (confirmed by signet ring cells on pleural biopsy with IHC) and does not have active tuberculosis, despite the elevated ascitic fluid ADA of 75 U/L. The elevated ADA is a false positive in the setting of malignancy, and empirical anti-tuberculosis treatment should be discontinued.

Key Diagnostic Evidence Against Active TB

The definitive histopathological diagnosis of metastatic adenocarcinoma with signet ring cells on parietal pleura biopsy, combined with negative GeneXpert MTB testing and negative peritoneal deposit biopsy (showing only fibrous nodule), effectively rules out tuberculosis as the primary diagnosis. 1, 2

Critical Findings Supporting Malignancy Alone:

• Parietal pleura biopsy showing signet ring cells with IHC confirming metastatic adenocarcinoma - this is definitive tissue diagnosis 1
• Duodenal stricture on OGDscopy - highly suggestive of gastrointestinal primary malignancy with peritoneal carcinomatosis 1
• Peritoneal deposit biopsy showing fibrous nodule only - no granulomas or acid-fast bacilli 2, 3
• GeneXpert negative for MTB - has 100% specificity when positive, and negative result argues strongly against TB in this clinical context 1, 2
• Lack of response to empirical ATT - patient developed progressive disease with new pleural effusion despite treatment 1, 4

Understanding the Elevated ADA Level

ADA levels can be falsely elevated in malignancy, particularly lymphoma and adenocarcinoma with peritoneal involvement, making it an unreliable marker when malignancy is present. 1, 5, 4

Why ADA is Misleading Here:

• Non-Hodgkin lymphoma and other malignancies can produce ADA levels >65 U/L, mimicking TB peritonitis 4
• The specificity of ADA drops significantly in the presence of malignancy - one study showed specificity of only 70.4% when distinguishing TB from malignant effusions 5
• ADA should never be used as the sole diagnostic criterion without histopathological confirmation 1, 4
• In this case, the combination of high ADA with negative microbiological studies and positive malignancy histology indicates false-positive ADA 5, 4

Diagnostic Algorithm Applied to This Case

Stage 1: Initial Evaluation (Completed)

• Imaging showed peritoneal deposits and pleural effusion 1, 2
• Ascitic fluid ADA was elevated at 75 U/L 1, 3

Stage 2: Tissue Sampling (Completed - Definitive)

• Peritoneal deposit biopsy: fibrous nodule, no granulomas, GeneXpert negative 2, 3
• Parietal pleura biopsy: signet ring cells, IHC confirming metastatic adenocarcinoma 1
• This tissue diagnosis supersedes all biochemical markers 1, 2

Stage 3: Source Identification (In Progress)

• Duodenal stricture identified - biopsy pending 1
• Likely gastrointestinal primary (gastric or pancreatic adenocarcinoma) with peritoneal and pleural metastases 6, 7

Clinical Management Recommendations

Discontinue anti-tuberculosis treatment immediately and initiate oncology consultation for staging and chemotherapy planning. 1, 8, 7

Immediate Actions:

• Stop all ATT medications - no evidence of active TB and patient has not responded to empirical treatment 1, 4
• Await duodenal biopsy results to confirm primary site 1
• Complete staging with PET-CT (already done) and tumor markers (CEA, CA 19-9, CA 125) 1, 3
• Urgent oncology referral for treatment planning 7

Why TB Co-infection is Unlikely:

• Concurrent TB and malignancy occurs in only ~5% of cases with pleural disease 1
• All microbiological studies negative (GeneXpert, cultures, AFB staining) 1, 2, 3
• No granulomas on any tissue specimen 1, 2
• No response to ATT with disease progression 1, 4

Common Pitfall Avoided

The critical error would be continuing ATT based solely on elevated ADA without tissue confirmation of TB, delaying appropriate cancer treatment. 4 In regions with high TB prevalence, there is tendency to over-diagnose TB based on ADA alone, but tissue diagnosis always takes precedence over biochemical markers when they are discordant. 1, 2

In non-endemic areas (or when malignancy is proven), empirical ATT is not recommended when systematic investigation fails to yield TB diagnosis. 1