Consideration of exposure to pharmacological agents helps to avoid diagnostic pitfalls in bone marrow histopathology

Summary

Trephine bone marrow biopsy is a frequent routine investigation, particularly important in cases with an unsuccessful aspirate. In addition to a representative trephine biopsy length and quality, the patient's clinical history is of critical importance. Especially drug-induced bone marrow changes are often difficult to interpret without prior knowledge of exposure to respective agents. Since some of these changes mimic malignancies, this can lead to serious misinterpretations. Drugs in general can induce a wide spectrum of bone marrow reactions. Immunosuppressants such as Azathioprine and Methotrexate cause morphological bone marrow changes that can not be distinguished from myelodysplastic syndromes, while cytokines and growth factors induce an overall increase in cellularity and, in particular, a left shift of myelopoiesis with increased myeloblasts and monoblasts, mimicking acute myeloid leukaemia. Moreover, drugs with immuno-allergic- (such as Allopurinol, Carbimazole, Crabamazepine, Clozapine, non-steroidal anti-rheumatics, Phenytoin, Sulfonamides) or direct myelotoxic potential can lead either to T-cell-mediated bone marrow stem cell destruction with the morphological pattern of aplastic anaemia, to direct toxic or immunological burst- or colony-forming units' destruction with isolated erythro- or myelopoietic hypoplasias or to other changes such as eosinophilia, (haemo)phagocytosis, T-cell lymphocytosis (which can be very severe, resembling lymphoma/leukaemia), perivascular plasmacytosis, siderosis or stromal oedema. In summary, clinical information on drug exposure is at least as important as a good quality biopsy for comprehensive histology-based bone marrow diagnostics, hel** to avoid not only misinterpretation but also expensive additional examinations.