Molavi Chapter 20 - Bone Marrow Flashcards
Identify those cells
- Erythroid precursors - distinct rim of clear cytoplasm. Centrally located, round nuclei that gradually become smaller and denser as they mature. “Looks kind of like a lymphocyte” until it accumulates heme.
- Myeloid precursors - Everything else. Also accumulate granules.
- Megakaryocytes - Easy to identify.
- Maturing neutrophils - Bands, easy to identify.
Lymphoid cells in the marrow
Generally should not be seen – especially immature lymphoid cells.
Hematogones (non-neoplastic B cell precursors) are the exception and can be more frequent in children.
Identify the cell marked by the arrowhead
This is a blast. Note that we are on Giemsa-Wright cytology, not H and E histology.
The blast nucleus is large and round with very finely textured chromatin and a nonstaining nucleolus that shows up as a “hole” in the chromatin.
The more differentiated precursors (promyelocytes, melocytes) have similar nuclei but acquire cytoplasmic features (granules, a hof).
A normal promyelocyte should have a cearly visible. . .
. . . Golgi apparatus
The absence of this clear Golgi apparatus and increased toxic granulation suggests a dysplastic promyelocyte, such as in APML.
Nucleoli vs Vacuoles
In normal, healthy blasts, nucleoli can look lighter, almost like punched-out holes.
However, true vacuoles within the nucleus are a sign of dysplasia.
Differentiating the two is important.
Erythroblasts
Often described as having “royal blue” cytoplasm and very round nuclei.
Estimating the cellularity of marrow
Roughly 100% - Age (for those ages ~20-70)
Marrow fibrosis
The marrow appears hypercellular at low power, but on high power has clear bands of fibrosis giving it a “streaming” texture.
Hematopoietic cells are divided into nests and chains.
Chronic myeloid leukemia
The marrow is hypercellular and full of small, hypolobated megakaryoytes and mature neutrophils
Remember: Numerous neutrophils may indicate CML, but sheets of multiple lineages of myeloid cells may indicate infection.
Any more than __% of blasts in the bone marrow is abnormal.
More than __% of blasts is necessary for a diagnosis of most leukemias.
Any more than 5% of blasts in the bone marrow is abnormal.
More than 20% of blasts is necessary for a diagnosis of most leukemias.
Dyserythropoiesis features
- Binucleated red cells
- Red cell precursors with irregular nuclear membranes
-
“Megaloblastoid change”
- A softer sign
- “Sliced salami” nuclei within mature (pale gray) cytoplasm
Dysgranulopoiesis features
- Abnormalities in nuclear lobation (“Pelgeroid”, aka bilobated like spectacles)
- Abnormal granluation (absence of granules or occasionally coarse basophilic granules)
- Hypersegmented neutrophils suggest megaloblastic anemia
Plasma cell dyscrasia spectrum
Plasma cells making up >__% of bone marrow cells indicates a possible plasma cell dyscrasia.
Plasma cells making up >10% of bone marrow cells indicates a possible plasma cell dyscrasia.
Prussian blue staining of bone marrow
This staining shows sideroblasts. Some sideroblasts are present at baseline, but the proportion may change with pathology:
- Decreased in iron deficiency anemia
- Increased in sideroblastic anemia (especially ringed sideroblasts, shown here)
- Heritable: One of many AD or X-linked mutations in heme metabolism
- Acquired: Lead toxicity, somatic SF3B1 mutation (MDS, splicing error), B6 deficiency, Cu deficiency, Zn toxicity, some medications.
5 steps to categorizing bone marrow disorders
- What’s the cellularity? (normal/hyper/hypo)
- Is there a dominant cell line?
- Are there too many blasts?
- Are there too many plasma cells?
- Are there any lymphocytes?
Ddx for hypercellular marrow
- Physiologic response to anemia (hemolysis, infection, no dysplasia)
- Ineffective hematopoiesis (megaloblastic, HIV)
- Myelodysplasia (dysplasia in some cell line, <20% blasts)
- Myeloproliferative disorder
- Acute leukemia (>20% blasts with or without dysplasia)
- Other neoplasm (lymphoma, myeloma, metastatic cancer)
- Might present as myelophthisis
Ddx for hypocellular marrow
- Aplastic anemia
- Chemotherapy or toxin-induced
- Infection
- Hypocellular forms of myelodysplatic syndrome or AML (blasts are still increased!)
Diagnostic features of myelodysplastic syndrome
- Dysplasia of at least one cell line
- <20% blasts within the bone marrow
Blasts, MDS, and leukemia
Blast % is important in diagnosis of both diseases.
Generally, leukemias have >20% blasts as a requirement for diagnosis, and MDS must have <20% blasts to be MDS.
However, an MDS may progress to an AML, in which case blasts will go from <20% to >20%. Be aware that this transition is possible.
Nondiagnostic supportive findings of MDS
- Tend to have an erythyroid predominance in the marrow, since the body is appropriately trying to adapt to its anemia
- Decreased M/E ratio
- Ringed sideroblasts, excess blasts, or defining mutations may be involved
“MDS with ringed sideroblasts”
>15% ringed sideroblasts or iron stain
Subcategorizing a diagnosis of MDS
-
“MDS with single lineage dysplasia”
- Erythroid dysplasia with anemia and <5% blasts.
- May or may not have “with ringed sideroblasts”
-
“MDS with multilineage dysplasia”
- Two or more (usually three) lineages
- Dysplasia must be seen in >10% of given cell line to be significant
- <5% blasts
- May or may not have “with ringed sideroblasts”
-
“MDS with excess blasts”
- MDS-EB1 is 5-9% blasts
- MDS-EB2 is 10-19% blasts OR presence of Auer rods OR >5% circulating blasts (high risk of transformation to AML)
MDS/MPN
The overlap category between MDS and MPN
Chronic myelomonocytic leukemia (CMML) is the classic example
It has dysplasia, anemia, thrombocytopenia, monocytosis, <20% blasts and NO Philidelphia chromosome.
2016 WHO classification of acute leukemias
Myeloma
Just sheets and sheets of plasma cells with eccentric nuclei, perinuclera hofs, and clockface chromatin.
Paratrabecular lymphocytic collection within bone marrow
This pattern favors a follicular lymphoma
Nonparatrabecular lymphoid aggregate within the bone marrow
Benign lymphoid aggregates are common in elderly patients, however in a younger patient this raises concern for CLL/SLL.
Interstitial lymphocytic infiltration within the bone marrow
Lymphocytes are intermixed among normal marrow elements without any discrete lymphoid aggregates. May be hard to pick out on simple H&E stain.
Suggests CLL/SLL or Mantle cell lymphoma, especially if in conjunction with nonparatrabecular lymphoid aggregates.
Diffuse lymphocytic infiltration of bone marrow
Sheets of lymphocytes replacing normal marrow elements
Typical of a more aggressive lymphoma, such as Burkitt’s or DLBCL, or an advanced CLL/SLL.
Features of a benign lymphoid aggregate in the bone marrow
- Heterogeneous mixture of lymphocytes, histiocytes, and plasma cells
- Stains with CD3, CD20, CD138
- Well-markated borders
- Germinal centers
- Patient of older age
