Week 2 Lecture 3 - Characteristics of Bone Marrow Flashcards
Assessing Aspiration and Trephine Biopsy Allows for…
Assessment fine cytological detail (AB)
Organisation of the marrow (TB)
The presence of focal abnormalities (TB)
Often collected at the same time
Sites for Bone Marrow Collection
Posterior, superior iliac spine
Iliac crest
Sternum
Preparation of Aspirate
Anticoagulant, EDTA (+/-)
Wedge method to spread generally ideal
At least 1 squash preparation for systemic mastocytosis, myeloma (i.e. where cells of interest may be trapped within marrow particles)
Dry thoroughly before fixation, staining
- Romanowsky stain
- iron stain (e.g. Perl’s
Prussian blue)
- cytochemical stains
How might the Preparation of Aspirates Affect Cellular Characteristics?
Wedge method more prone to haemodilution
Haemodilution => decreased cellularity
=> less reliable interpretation
Haemodilution may also occur during collection, esp. with large volumes
Recommended initial small volume collected for films, then additional volume for ancillary tests
Preparation of Trephine Biopsy
Touch imprint = rolled specimen along slide
Fixative (tissue)
Decalcification (+/-)
Embed (plastic, paraffin), section
Stains H & E, reticulin, Giemsa
Pitfalls in Bone Marrow Assessment
Pancytopenia
- actually artefactual due to collection near IV infusion
Neutropenia
- factitious due to myeloperoxidase deficiency => HA not recognisingneutrophils
EDTA Induced Morphological Atypia
Use of excessive EDTA may result in morphological abnormality of bone marrow cells
- damage to nuclear & cytoplasmic membranes
- nuclear contour irregularities
- non-lobulated nucleus (neutrophils)
- small cells
- cytoplasmic contraction
- nuclear contraction
Characteristics of Normal Bone Marrow
Mixed adipose & haematopoietic tissue
Haematopoietic component varies with stage of life
- normal adult: 30-80%
- normal elderly: 20-50%
- normal adolescent: 50-90%
- normal newborn: 75-100%
Haematopoietic tissue composed of
- erythroid, myeloid, megakaryocytic lines
Myeloid:Erythroid ratio: 1.5 - 4.0 : 1.0
Orderly maturation sequence within each line
Range of ‘other’ cell types normally encountered
Cells found in Bone Marrow Not Normally Found in FBP
Adipocytes
Endothelial cells
Osteoblasts
Osteoclasts
Stromal cells
Mast cells
Plasma cells
Mott cells
Macrophages
Siderophage/ ‘nurse cell’
Disorders of Bone Marrow
Many haematological disorders arise from the bone marrow
Many disorders promote a response from the bone marrow
Acquired
- inflammation
- neoplasia
- therapy
Inherited
- Diamond-Blackfan anaemia
- Fanconi anaemia
- congenital neutropenia
Acquired Disorders of the Bone Marrow
Disorders of the bone marrow due to therapy/treatment
- cytotoxic chemotherapy
- radiotherapy
- therapy related myeloid neoplasms
- haematopoietic growth factors
- haematopoietic stem cell transplantation
Cytotoxic Chemotherapy
Affect haematopoietic cells (as well as neoplastic cells)
Typically results in 3 stages
- week 1; cell death
- week 1-2; hypocellularity
- week 2; regeneration
The first post-therapy marrow is typically taken at two weeks
- => initial death of cells is often not observed
Cytotoxic Chemotherapy - Hypocellularity
At 10-14 days: the marrow is depleted of cells
Sections show absence of haematopoietic cells with relative increase in lymphocytes/plasma cells
Marrow sinusoid contain; fibrin, haemorrhage, foamy macrophages
Adipocytes are shrunken & surrounded by amorphous extracellular eosinophilic material
Persistence of blasts at this stage is a poor prognosis
Cytotoxic Chemotherapy - Regeneration
Begins with the appearance of small erythroid colonies in the interstitial space
Followed by scattered myeloid precursor cells
Finally appearance of megakaryocytes
Haematopoietic dysplasia may be evident during this period
Hyperplasia may result
NB => it may be difficult to distinguish these changes from previous neoplastic changes
Peripheral blood typically reflects the marrow composition
Radiotherapy
Effects assessed via histology and imaging studies of the bone marrow
Temporal effects on the bone marrow:
2 weeks after initiation of therapy
- edema & necrosis
- also osteopenia, osteosclerosis, focal fibrosis & inflammation
2-3 months after initiation of therapy
- adipose tissue replaces haematopoietic tissue
- => hypoplasia (‘aplasia’)
- persistent cytopenia
Granulocyte and Granulocyte Macrophage Colony Stimulating Factors
G-CSF, GM-CSF used to correct neutropenia (& => prevent infections)
After therapy;
PB:
- rapid increase [WBC]
- >90 x10^9/L
Predominantly neutrophils (mature & immature)
