Can Mycobacterium avium complex involve the bone marrow in patients with advanced HIV infection or other severe immunosuppression?

Can MAC Involve the Bone Marrow?

Yes, Mycobacterium avium complex (MAC) routinely involves the bone marrow in disseminated disease, particularly in patients with advanced HIV infection (CD4 <50 cells/µL), and bone marrow examination can be diagnostically valuable when blood cultures are negative or rapid diagnosis is needed. 1

Bone Marrow Involvement in Disseminated MAC

Pathophysiology and Frequency

• Disseminated MAC is a multi-organ infection that characteristically involves most internal organs, including bone marrow, in patients with severe immunosuppression. 1, 2

• Autopsy series demonstrate widespread organ involvement even when localizing symptoms are absent, confirming that bone marrow is routinely affected in disseminated disease. 2

• The infection occurs almost exclusively when CD4 counts fall below 50 cells/µL, with median presentation at CD4 <25 cells/µL. 2

Clinical Manifestations of Bone Marrow Involvement

• Hematologic abnormalities are hallmark features of disseminated MAC and reflect bone marrow involvement: 1

  • Anemia (present in all patients, often severe with hematocrit <25%) 3, 4
  • Leukopenia (73% of cases) 3
  • Thrombocytopenia (45% of cases) 3
  • Pancytopenia (45% of cases) 3

• The anemia associated with disseminated MAC is often "out of proportion to that expected for the stage of HIV disease," serving as a clinical clue to MAC involvement. 1

Diagnostic Utility of Bone Marrow Examination

When to Consider Bone Marrow Biopsy

Bone marrow aspiration, biopsy, and culture should be performed when: 4

• Blood cultures are negative in symptomatic patients with suspected disseminated MAC
• Rapid diagnosis is needed to initiate therapy promptly
• Clinical features suggest MAC but microbiologic confirmation is lacking

High-yield clinical predictors for positive bone marrow findings include: 4

• High fever
• Prolonged duration of fever prior to examination
• Elevated direct bilirubin

Diagnostic Yield

• Blood cultures remain the gold standard, detecting >90% of disseminated MAC cases with a single positive culture. 2

• Bone marrow culture sensitivity (63%) equals that of blood cultures, but does not exceed it. 4

• Histopathologic examination of bone marrow provides unique diagnostic value: 4, 5

  • Identifies infection in approximately one-third of patients (34%) through visualization of granulomas and/or organisms 4
  • Detects infection in some culture-negative patients 4
  • Provides rapid diagnosis (mean 1.1 days) compared to culture (16-19 days) 5
  • Allows prompt initiation of therapy in one-third of patients 5

Histopathologic Patterns

Bone marrow specimens in disseminated MAC show characteristic but variable findings: 3, 6

• Granulomas are present in 52% of cases, ranging from: 3

  • Small, subtle lymphohistiocytic aggregates (often initially missed)
  • Larger lymphohistiocytic lesions
  • Clusters of epithelioid histiocytes

• Acid-fast bacilli (AFB) are rarely visualized on routine staining (seen in only one case in one series), despite positive cultures in 53% of specimens. 3

• Immunohistochemical staining significantly improves organism detection: 6

  • Anti-M. duvalii antibodies: 91% sensitivity
  • Anti-BCG antibodies: 94% sensitivity
  • Kenyon stain: 57% sensitivity
  • Fite stain: 66% sensitivity

• In AIDS patients, culture can be positive even in the absence of inflammation or AFB on staining, reflecting overwhelming infection in severely immunocompromised hosts. 3

Clinical Pitfalls and Caveats

Common Diagnostic Errors

• Do not assume tuberculosis without appropriate testing—disseminated MAC can mimic TB clinically. 2

• Subtle granulomas are frequently missed on initial review—almost half of lymphohistiocytic aggregates were overlooked in one series. 3

• Negative AFB staining does not exclude MAC—organisms are rarely visible on routine acid-fast stains despite positive cultures. 3

Limitations of Bone Marrow Assessment

• Bone marrow findings may not correlate with therapeutic response: 6

  • Patients showing decreased blood MAC colony counts after therapy did not demonstrate reduction in bone marrow organism burden
  • Bone marrow may provide a different perspective on infection status than blood cultures

• The invasive nature of bone marrow biopsy must be weighed against the diagnostic yield, particularly when blood cultures are readily available and highly sensitive. 4, 5

Practical Diagnostic Algorithm

For suspected disseminated MAC in HIV patients with CD4 <50 cells/µL: 1, 2, 4

1. Obtain blood cultures first—these detect >90% of cases and are less invasive 2

2. Consider bone marrow examination if:

   • Two blood cultures are negative but clinical suspicion remains high 2
   • Rapid diagnosis is needed (histology provides results in 1-2 days vs. 16-19 days for culture) 5
   • Patient has high fever, prolonged febrile course, or elevated direct bilirubin 4

3. If bone marrow is performed, request:

   • Aspirate for culture (equal sensitivity to blood culture) 4
   • Core biopsy for histopathology with AFB staining 5
   • Consider immunohistochemical staining if available (superior sensitivity) 6

4. If isolated lymphadenopathy without bacteremia, pursue excisional biopsy of accessible nodes rather than bone marrow. 2