Granulomatous Endometritis: Causes
Granulomatous endometritis is caused by tuberculosis (most common globally), nontuberculous mycobacteria, sarcoidosis, foreign body reactions (particularly post-procedural), and rarely CMV or fungal infections.
Infectious Causes
Mycobacterial Infections
Tuberculosis remains the most important infectious cause of granulomatous endometritis worldwide, though it is rare in developed countries 1. The infection typically reaches the endometrium through hematogenous spread from pulmonary or other sites. Diagnosis requires culture of Mycobacterium tuberculosis from endometrial tissue, though histopathology showing caseating granulomas provides strong presumptive evidence 2.
Nontuberculous mycobacteria (NTM) can cause chronic granulomatous endometrial infections, particularly M. marinum and MAC (Mycobacterium avium complex), though virtually all NTM species have been implicated in tissue infections 2. These infections typically occur after direct inoculation through procedures or trauma.
Viral Infections
Cytomegalovirus (CMV) can cause granulomatous endometritis, even in immunocompetent patients 3. The diagnosis may be challenging as CMV inclusions can be histologically occult, requiring polymerase chain reaction (PCR) for detection in paraffin-embedded tissue. While CMV endometritis is classically associated with immunosuppression 4, case reports demonstrate it should be considered in the differential diagnosis of granulomatous endometritis in otherwise healthy patients 3.
Fungal Infections
Aspergillosis represents a rare but documented cause of endometrial infection, with recent identification of Aspergillus quadrilineatus in an immunocompetent woman 5. Fungal infections are often overlooked in the evaluation of abnormal uterine bleeding and endometritis.
Non-Infectious Causes
Iatrogenic/Procedural
Post-procedural granulomas are an important and increasingly recognized cause. Endometrial resection can lead to granulomatous reactions 6. After curettage or endometrial biopsy, eosinophilic xanthogranulomatous or granulomatous endometritis and foreign body granuloma reactions can occur 4. Xanthogranulomatous endometritis (XGE) is extremely rare, characterized by replacement of endometrial tissue with foamy histiocytes, giant cells, lymphocytes, and plasma cells 7.
Systemic Inflammatory Conditions
Sarcoidosis rarely affects the female genital tract but can present as endometrial involvement with noncaseating granulomas containing sarcoid-type asteroid bodies 8. This can manifest as postmenopausal bleeding and should be considered when other causes are excluded.
Clinical Approach
When evaluating granulomatous endometritis:
- Obtain endometrial biopsy for histopathology showing granulomas (caseating vs. non-caseating)
- Send tissue for mycobacterial culture with specific notification to the laboratory to hold cultures ≥5 days for slow-growing organisms 9
- Consider PCR testing for CMV if granulomas are present but no organisms identified 3
- Review procedural history for recent intrauterine interventions that could cause foreign body reactions 4, 6
- Evaluate for systemic sarcoidosis if non-caseating granulomas are found 8
- Consider fungal cultures in refractory cases, particularly with abnormal uterine bleeding 5
The key pitfall is assuming all granulomatous endometritis is tuberculous without appropriate microbiological confirmation, as this leads to unnecessary prolonged anti-tuberculous therapy when the cause may be iatrogenic, sarcoidosis, or another treatable condition.