Hematopathology Notes

Question 1

PNH-type cells (CD55 and CD59 negative) may also be found in. . .

Answer 1

. . . aplastic anemia. Around 40-60% of cells!

Since these are often on the ddx for one another, this can be confusing.

Question 2

The many contexts of JAK2

Answer 2

• Seen dysregulated in:
  
  • ~99% of polycythemia vera
  • ~50% of essential thrombasthemia
  • Some cases of myelofibrosis
  • Some cases of myelodysplastic syndrome (~3%)

Question 3

Skin biopsy for inherited BM failure gene sequencing

Answer 3

Some patients develop MDS or AML as a result of a BM failure mutation, sometimes at a young age.

Since the bone marrow is paucicellular, you need to try looking somewhere else!

So, look in the skin to see if there is a germline predisposition.

Question 4

UBA1 p.MET41 missense

Answer 4

VEXAS syndrome, Acquiried somatic mutation

Ubiquitin-activating enzyme 1, encoding the major E1-activating enzyme required for initiation of all cellular ubiquitin signaling. A heritable mutation in this gene causes x-linked spinal muscular atrophy.

Manifests as severe relapsing inflammatory polychondritis, thrombocytopenia, and macrocytic anemia. Sometimes associated with Sweet’s syndrome (~33%). Observed only in males (other X may be protective). High mortality.

Bone marrow biopseis showed cytoplasmic vacuoles in early myeloid and erythroid precursors.

Vacuoles, E1, x-linked, autoinflammatory, somatic

Treatment is allogeneic bone marrow transplant.

Question 5

Other morphologic features of APML

Answer 5

• Perinuclear vacuoles in promyelocytes
• Many granules in promyelocytes
• “Sliding plates” nuclear deformity

Question 6

CD34+HLA-DR+

Answer 6

Blast cells

Question 7

Treatment of APML

Answer 7

• All-trans retinoic acid
• Arsenic oxide
• Monitor for DIC
• Note: Because the complication of DIC is so dangerous and this treatment is SO effective, if APML is even on the differential you should contact the clinical team so they can initiate empiric treatment – DON’T wait for confirmation of t(15:17).

Question 8

Mixed-field agglutination

Answer 8

Two different, distinct cell populations with different agglutination properties

Can be seen in patients with recent transfusions.

Question 9

Classic immunophenotype of APML

Answer 9

• CD34 negative
• MHCII negative
• Also: CD45+ blast gate extends as a blur into the granulocyte gate