Rheumatoid arthritis Part 1, case based approach with application of the late...
Common pitfalls in bone marrow biopsy based diagnostic approach
1. Common pitfalls in bone marrow
biopsy based diagnostic approach
Dr. N. Varma
Prof. & Head - Hematology
PGIMER, Chandigarh
2. Bone marrow (BM) examination
• Gold standard investigation for diagnosing and
monitoring many hematological diseases
• Useful for investigating various non-hematological
conditions
• Combination of bone marrow aspirate and trephine
biopsy: fine cytological detail, the organization of
BM, and the presence of focal abnormalities
3. Good-to-have Information
• Accurate clinical information; context and questions being
asked; details of previous investigations
• For neoplastic diseases: ? primary diagnostic investigation/
staging procedure/ re-examination to assess response to
treatment (including transplantation)
• The type and timing of previous BM transplantation are
also important factors; kinetics of engraftment differ
between conditioning regimes and graft types
• Knowledge of the recent therapeutic use of growth factors
such as G-CSF; these may transiently have major modifying
effects on hemopoiesis that can mask or mimic genuine
pathology
4. Pitfalls in obtaining and interpreting
bone marrow aspirates
• BM aspiration done when not needed
• BM aspiration not done when needed
• BM aspiration done on the wrong site
• The clinical context not adequately assessed and the correct range
of tests is therefore not done on the aspirate
• False negative result as a consequence of a sampling error
• The aspirate is not interpreted together with the trephine
biopsy sections
• The aspirate is misinterpreted
– Problems relating to technical quality
– Correct stains not performed
– Features present not noted
– Misinterpretation of an adequate aspirate
5. Limiting factors for interpretation of BMB
• Inadequate clinical, hematological (blood and aspirate findings),
genetic and radiological information
• Inadequate specimen
– Too small
– Too crushed/distorted
– Both
– Poorly decalcified/processed
• Inadequate sections (thickness, number of levels)
• Inadequate stains (poor technical quality, range too limited)
• Insufficient experience to avoid common pitfalls (eg, differential
diagnosis of granulomas or fibrosis)
• Insufficient confidence to avoid concluding ‘consistent with’
• ‘Invisible’ pathology
• Forgetting to look at the bone trabeculae and stroma
6. A systematic approach to diagnosis is
required for:
• Assessing patterns of lymphoid infiltration associated
with various lymphomas, especially small B-cell
lymphomas
• D/D of granulomatous pathologies
• Assessing key histological features of myelodysplastic
and myeloproliferative haemopoiesis
• D/D of bone marrow fibrosis
• D/D of hypoplasia/aplasia
7. Few representative examples will be shown
• Assessment of focal lesions
• Differentiation between reactive lymphoid infiltrate and NHL
• Differentiation between reactive and malignant plasma cells
• Identification of malignancies with associated fibrosis
• Effect of growth factors
• Differentiation between hematogones and blasts
• Differentiation between megaloblastic anemia and acute leukemia
• Differentiation between aplastic bone marrow and hypoplastic
myelodysplastic syndrome or hypoplastic acute leukemia
• Identification of lymphomas having a tendency for intravascular
infiltration in the BM
• Subtle amyloid deposition
• Differentiation of macrophage infiltrates and other pathologies that
resemble granulomatous infiltration
• Procedure related artefacts
8. Take home message
• Integration of clinical, laboratory and imaging information
• Not to assess histology in isolation
• Components of an integrated approach to interpretation are:
– A trephine core of adequate size with minimal disruption by trauma caused
during collection.
– Access to detailed clinical information and results of additional tests (specially,
peripheral blood cell counts, blood and BM aspirate cytomorphology, flow
cytometry, cytogenetic analysis and radiological imaging).
– Systematic assessment of all BM components, including trabecular bone and
interstitial stroma.
– Awareness of pathologies that may be ‘invisible’ in trephine specimens
without immunostaining.
– Use of preselected antibody panels for immunostaining and familiarity with
the expected results, including controls.
– Experience in interpreting additional molecular studies, such as clonality PCR
and fluorescence in-situ hybridisation, in the particular context of decalcified
tissue.
– Familiarity with the major patterns of bone marrow involvement by reactive
and neoplastic conditions and their differential diagnosis.
– A collaborative approach to working with diverse clinical and laboratory
colleagues.