Myeloid neoplasms
Hematopoiesis starts in the aorta-gonad-mesonephron (AGM), located at the tip of the
aortic arch, then occurs in the yolk sac, fetal liver, spleen and finally bone marrow. Bone
marrow is mainly found in the axial skeleton, especially in the flat bones, pelvis and
vertebrae: here hematopoiesis occurs in the adult, although many cells translocate to
other tissues e.g. lymph nodes after maturation.
Yolk sac hematopoiesis occurs in the first days of life to allow growth, mainly by
producing cells of the myeloid lineage:
- RBCs: erythropoiesis and angiogenesis are essential for delivery of oxygen and
nutrients necessary for growth
- Macrophages:
o programmed cell death regulation: resorption of non-useful structures
e.g. interdigital membranes and embryonic tail
o resident tissue macrophages: closure of BBB around day 15 of life due to
neuroectodermic tissue maturation ensures that no immune cells enter
the CNS except for microglia, which are resident macrophages already
present; resident macrophages in other tissues e.g. Kupffer cells,
Langerhans cells and dendritic cells are tolerogenic, to suppress
excessive immune reaction if bacteria are present (skin and gut).
Adult BM hematopoiesis
Initial adult BM hematopoiesis produces neutrophils and monocytes, which cause
severe system inflammation. The myeloid lineage comes from a common myeloid
progenitor which divides into:
1. Megakaryocyte-erythrocyte progenitor: produces RBCs and platelets:
2. Granulocyte-monocyte progenitor: the most prevalent, producing neutrophils
and macrophages
3. Eosinophil-basophil progenitor: mastocytes, basophils, and eosinophils
,Bone marrow architecture
It is one of the heaviest organs in the human body (1.5-3.7kg) with precise microscopic
architecture:
- Trabecular bone: scaffold.
- Hematopoietic cells: functional unit.
- Arteries and veins: pathway towards and from the BM.
- Autonomic nerves: rough regulators of hematopoiesis (the incidence of
hematopoietic neoplasms is significantly higher in patients with mental illness
compared to the normal population and decreased mood and depression are
linked to higher infection risk due to immune suppression).
- Mesenchymal cells: act as both scaffold and fine tuners of hematopoiesis;
adipocytes are the greatest component of the BM and are needed for cytokines
and adipokines production that stimulate and regulate HSC metabolism.
, Macroscopic architecture:
- Red BM: hematopoietic cells mainly, site
of active hematopoiesis – regulation is by
complexes of transcription factors that
switch DNA transcription to a different set
of transcription factors to produce a
certain lineage.
- Yellow BM: mainly fat cells, no/little
hematopoiesis occurring.
Bone marrow biopsy
BMB is both a diagnostic and staging procedure performed upon suspicion of a
hematopoietic neoplasm e.g. in the presence of either cytopenia or cytosis, after
exclusion of all other possible causes. It is performed with a trephine needle that is
inserted in the pelvis, retrieving at least 1.5cm of tissue to be diagnostic, which is then
fixed in formalin, and decalcified with EDTA, to remove bone without damaging DNA, and
embedded in paraffin. Invasion of the bone marrow in lymphomas means it is a stage 4
cancer; instead in AML, BMB is performed to assess BM proliferation after chemotherapy
or transplant.
Features assessed in BM biopsy include:
- Cellularity: hematopoietic
cells/adipocytes ratio. Normal cellularity
decreases with age; we can calculate it with
the formula: 100 – age and compare it to the
sample obtained:
o Hypocellularity (5-10%) suggests
aplastic anemia (absence of
maturation of hematopoietic cells).
o Hypercellularity instead occurs in case of systemic inflammation or
lymphoma (only hypercellularity visible), metastases (isles of neoplastic
cells).
- Lineages:
o Megakaryocytes: largest cell type, with abundant eosinophilic cytoplasm,
multilobate nucleus, and polymorphic appearance. They can be stained
with CD61 to look for small megakaryocytes (sign of malignancy).
o Erythroid cells: darkest and most rounded cell type, usually produced in
colonies (erythrons) with a single macrophage in the center to eliminate
nuclei and as scavenger for oxidizing agents coming from heme when
inserted inside hemoglobin to avoid cell toxicity. Can be stained with E-
cadherin.
o Granulocytes: remaining cells that are not megakaryocytes or RBCs; they
are characterized by a huge nucleus (very high nuclear/cytoplasmic ratio)
and granulated cytoplasm, visible in all of their maturation stages,
especially in band cells (the stage before neutrophils when they are still
retained in the BM). Myeloid cells maturate from the bone towards the
Hematopoiesis starts in the aorta-gonad-mesonephron (AGM), located at the tip of the
aortic arch, then occurs in the yolk sac, fetal liver, spleen and finally bone marrow. Bone
marrow is mainly found in the axial skeleton, especially in the flat bones, pelvis and
vertebrae: here hematopoiesis occurs in the adult, although many cells translocate to
other tissues e.g. lymph nodes after maturation.
Yolk sac hematopoiesis occurs in the first days of life to allow growth, mainly by
producing cells of the myeloid lineage:
- RBCs: erythropoiesis and angiogenesis are essential for delivery of oxygen and
nutrients necessary for growth
- Macrophages:
o programmed cell death regulation: resorption of non-useful structures
e.g. interdigital membranes and embryonic tail
o resident tissue macrophages: closure of BBB around day 15 of life due to
neuroectodermic tissue maturation ensures that no immune cells enter
the CNS except for microglia, which are resident macrophages already
present; resident macrophages in other tissues e.g. Kupffer cells,
Langerhans cells and dendritic cells are tolerogenic, to suppress
excessive immune reaction if bacteria are present (skin and gut).
Adult BM hematopoiesis
Initial adult BM hematopoiesis produces neutrophils and monocytes, which cause
severe system inflammation. The myeloid lineage comes from a common myeloid
progenitor which divides into:
1. Megakaryocyte-erythrocyte progenitor: produces RBCs and platelets:
2. Granulocyte-monocyte progenitor: the most prevalent, producing neutrophils
and macrophages
3. Eosinophil-basophil progenitor: mastocytes, basophils, and eosinophils
,Bone marrow architecture
It is one of the heaviest organs in the human body (1.5-3.7kg) with precise microscopic
architecture:
- Trabecular bone: scaffold.
- Hematopoietic cells: functional unit.
- Arteries and veins: pathway towards and from the BM.
- Autonomic nerves: rough regulators of hematopoiesis (the incidence of
hematopoietic neoplasms is significantly higher in patients with mental illness
compared to the normal population and decreased mood and depression are
linked to higher infection risk due to immune suppression).
- Mesenchymal cells: act as both scaffold and fine tuners of hematopoiesis;
adipocytes are the greatest component of the BM and are needed for cytokines
and adipokines production that stimulate and regulate HSC metabolism.
, Macroscopic architecture:
- Red BM: hematopoietic cells mainly, site
of active hematopoiesis – regulation is by
complexes of transcription factors that
switch DNA transcription to a different set
of transcription factors to produce a
certain lineage.
- Yellow BM: mainly fat cells, no/little
hematopoiesis occurring.
Bone marrow biopsy
BMB is both a diagnostic and staging procedure performed upon suspicion of a
hematopoietic neoplasm e.g. in the presence of either cytopenia or cytosis, after
exclusion of all other possible causes. It is performed with a trephine needle that is
inserted in the pelvis, retrieving at least 1.5cm of tissue to be diagnostic, which is then
fixed in formalin, and decalcified with EDTA, to remove bone without damaging DNA, and
embedded in paraffin. Invasion of the bone marrow in lymphomas means it is a stage 4
cancer; instead in AML, BMB is performed to assess BM proliferation after chemotherapy
or transplant.
Features assessed in BM biopsy include:
- Cellularity: hematopoietic
cells/adipocytes ratio. Normal cellularity
decreases with age; we can calculate it with
the formula: 100 – age and compare it to the
sample obtained:
o Hypocellularity (5-10%) suggests
aplastic anemia (absence of
maturation of hematopoietic cells).
o Hypercellularity instead occurs in case of systemic inflammation or
lymphoma (only hypercellularity visible), metastases (isles of neoplastic
cells).
- Lineages:
o Megakaryocytes: largest cell type, with abundant eosinophilic cytoplasm,
multilobate nucleus, and polymorphic appearance. They can be stained
with CD61 to look for small megakaryocytes (sign of malignancy).
o Erythroid cells: darkest and most rounded cell type, usually produced in
colonies (erythrons) with a single macrophage in the center to eliminate
nuclei and as scavenger for oxidizing agents coming from heme when
inserted inside hemoglobin to avoid cell toxicity. Can be stained with E-
cadherin.
o Granulocytes: remaining cells that are not megakaryocytes or RBCs; they
are characterized by a huge nucleus (very high nuclear/cytoplasmic ratio)
and granulated cytoplasm, visible in all of their maturation stages,
especially in band cells (the stage before neutrophils when they are still
retained in the BM). Myeloid cells maturate from the bone towards the
