Can lymphoma cause caseating granuloma?

Can Lymphoma Cause Caseating Granuloma?

Yes, lymphoma can cause caseating granulomas, although this is relatively uncommon and can create diagnostic challenges as it may mimic tuberculosis or other granulomatous diseases.

Relationship Between Lymphoma and Granulomas

Types of Granulomas

Granulomas are classified into several types based on their microscopic appearance:

• Non-necrotizing (non-caseating) granulomas: Typically seen in sarcoidosis 1
• Necrotizing (caseating) granulomas: Classically associated with tuberculosis and fungal infections 1
• Suppurative granulomas: Seen in cat scratch disease and certain fungal infections 2
• Foreign body granulomas: Form in response to inert foreign material 2

Lymphoma and Granulomatous Reactions

Lymphomas, particularly Hodgkin lymphoma and certain non-Hodgkin lymphomas, can be associated with granulomatous reactions of various types:

1. Sarcoid-type (non-caseating) granulomas:

   • More commonly reported in association with lymphomas 3
   • May occur in both involved and uninvolved organs

2. Caseating granulomas:

   • Less commonly associated with lymphoma but documented in the literature
   • Can be found in lymph nodes, liver, and other organs affected by lymphoma 4
   • May contain central necrosis that mimics tuberculosis

Evidence for Lymphoma Causing Caseating Granulomas

Several case reports and studies document the association between lymphoma and caseating granulomas:

• A case of Hodgkin's lymphoma with caseating hepatic granulomas has been reported, where the patient responded to lymphoma treatment without antituberculous therapy 4

• A case of gastric T-cell lymphoma presented with epithelioid granulomas with caseous necrosis in regional lymph nodes, strongly mimicking tuberculosis. Anti-tuberculous treatment was ineffective, and the diagnosis of lymphoma was eventually established 5

• Diffuse large B-cell lymphoma has been reported with chronic granulomatous inflammation, where the granulomas can obscure the underlying tumor cells, leading to diagnostic delay 6

Diagnostic Challenges

The presence of caseating granulomas in lymphoma creates significant diagnostic challenges:

1. Misdiagnosis risk: Patients with lymphoma-associated granulomas may be misdiagnosed with tuberculosis or other infectious diseases 7, 5

2. Masked malignancy: Granulomatous reactions can mask the underlying lymphoma cells, leading to delayed diagnosis and treatment 6

3. Differential diagnosis complexity: When caseating granulomas are found, the differential diagnosis should include:

   • Mycobacterial infections (tuberculosis and non-tuberculous mycobacteria) 1
   • Fungal infections 1
   • Granulomatosis with polyangiitis (GPA) 1
   • Lymphoma 7, 4

Clinical Approach to Granulomas with Suspected Lymphoma

When encountering caseating granulomas in clinical practice:

1. Thorough histopathological examination:

   • Look carefully for atypical lymphoid cells within or adjacent to granulomas 6
   • Perform immunohistochemistry to identify potential lymphoma cells 7

2. Microbiological studies:

   • Culture for mycobacteria and fungi 1
   • Molecular diagnostic tools (PCR) to detect mycobacterial or fungal DNA 1

3. Additional biopsies:

   • If initial biopsy shows only granulomas but lymphoma is suspected, consider repeat or excisional biopsy 6
   • Sampling from multiple sites may be necessary 7

4. Clinical correlation:

   • Response to therapy can be diagnostic (lack of response to anti-TB treatment may suggest alternative diagnosis) 5
   • Monitor for systemic symptoms of lymphoma even when initial pathology suggests only granulomatous disease 3

Conclusion

While non-caseating granulomas are more commonly associated with lymphomas, caseating granulomas can indeed occur in both Hodgkin and non-Hodgkin lymphomas. The presence of caseating granulomas should not exclude lymphoma from the differential diagnosis, particularly when there is no response to antimicrobial therapy or when clinical features suggest malignancy.