Molavi Chapter 20 - Bone Marrow

Question 1

Identify those cells

Answer 1

1. 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.
2. Myeloid precursors - Everything else. Also accumulate granules.
3. Megakaryocytes - Easy to identify.
4. Maturing neutrophils - Bands, easy to identify.

Question 2

Lymphoid cells in the marrow

Answer 2

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.

Question 3

Identify the cell marked by the arrowhead

Answer 3

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).

Question 4

A normal promyelocyte should have a cearly visible. . .

Answer 4

. . . Golgi apparatus

The absence of this clear Golgi apparatus and increased toxic granulation suggests a dysplastic promyelocyte, such as in APML.

Question 5

Nucleoli vs Vacuoles

Answer 5

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.

Question 6

Erythroblasts

Answer 6

Often described as having “royal blue” cytoplasm and very round nuclei.

Question 7

Estimating the cellularity of marrow

Answer 7

Roughly 100% - Age (for those ages ~20-70)

Question 8

Answer 8

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.

Question 9

Answer 9

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.

Question 10

Any more than __% of blasts in the bone marrow is abnormal.

More than __% of blasts is necessary for a diagnosis of most leukemias.

Answer 10

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.

Question 11

Dyserythropoiesis features

Answer 11

• Binucleated red cells
• Red cell precursors with irregular nuclear membranes
• “Megaloblastoid change”
  
  • A softer sign
  • “Sliced salami” nuclei within mature (pale gray) cytoplasm

Question 12

Dysgranulopoiesis features

Answer 12

• Abnormalities in nuclear lobation (“Pelgeroid”, aka bilobated like spectacles)
• Abnormal granluation (absence of granules or occasionally coarse basophilic granules)
• Hypersegmented neutrophils suggest megaloblastic anemia

Question 13

Plasma cell dyscrasia spectrum

Answer 13

Question 14

Plasma cells making up >__% of bone marrow cells indicates a possible plasma cell dyscrasia.

Answer 14

Plasma cells making up >10% of bone marrow cells indicates a possible plasma cell dyscrasia.

Question 15

Prussian blue staining of bone marrow

Answer 15

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.

Question 16

5 steps to categorizing bone marrow disorders

Answer 16

1. What’s the cellularity? (normal/hyper/hypo)
2. Is there a dominant cell line?
3. Are there too many blasts?
4. Are there too many plasma cells?
5. Are there any lymphocytes?

Question 17

Ddx for hypercellular marrow

Answer 17

• 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

Question 18

Ddx for hypocellular marrow

Answer 18

• Aplastic anemia
• Chemotherapy or toxin-induced
• Infection
• Hypocellular forms of myelodysplatic syndrome or AML (blasts are still increased!)

Question 19

Diagnostic features of myelodysplastic syndrome

Answer 19

• Dysplasia of at least one cell line
• <20% blasts within the bone marrow

Question 20

Blasts, MDS, and leukemia

Answer 20

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.

Question 21

Nondiagnostic supportive findings of MDS

Answer 21

• 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

Question 22

“MDS with ringed sideroblasts”

Answer 22

>15% ringed sideroblasts or iron stain

Question 23

Subcategorizing a diagnosis of MDS

Answer 23

• “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)

Question 24

MDS/MPN

Answer 24

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.

Question 25

2016 WHO classification of acute leukemias

Answer 25

Question 26

Answer 26

Myeloma Just sheets and sheets of plasma cells with eccentric nuclei, perinuclera hofs, and clockface chromatin.

Question 27

Answer 27

Paratrabecular lymphocytic collection within bone marrow This pattern favors a **follicular lymphoma**

Question 28

Answer 28

**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.**

Question 29

Answer 29

**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.

Question 30

Answer 30

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.**

Question 31

Features of a benign lymphoid aggregate in the bone marrow

Answer 31

* Heterogeneous mixture of lymphocytes, histiocytes, and plasma cells * Stains with **CD3, CD20, CD138** * Well-markated borders * Germinal centers * Patient of older age