Common pitfalls in bone marrow biopsy based diagnostic approach


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Common pitfalls in bone marrow biopsy based diagnostic approach

  1. 1. Common pitfalls in bone marrow biopsy based diagnostic approach Dr. N. Varma Prof. & Head - Hematology PGIMER, Chandigarh
  2. 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. 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. 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. 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. 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. 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. 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.