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Case 4 - Discussion

Hematopathology Case


Flow cytometric study:

An aberrant population is detected by flow cytometry, expressing dim CD45, CD13, CD33, CD117, CD71, CD38 and dim CD11b, and negative CD34, HLA-DR, CD14 and CD15.

Total events 		H gate Dim 		A gate Bright CD45
analyzed = 48568	CD45+ events = 38061    Positive events =1158
			(88% of total)		(3% of total)
  CD45+/CD14-		 97%			  100%
  Total CD14+		  3%
  Total CD13+		 99%
  CD34+/CD13+		 <2%
  Total CD15+		  4%
  CD34+/CD15+		 <2%
  Total CD33+		 99%
  CD34+/CD33+		 <2%
  Total CD34+		 <2%
  Total CD11b+		 87%
  Total CD41+		  4%
  Total CD71+		 96%
  CD34+/CD71+		 <2%
  Total CD117+		 98%
  CD34+/CD117+		 <2%
  Total HLA DR+		 <2%
  CD34+/HLA DR+		 <2%
  Total CD38+		100%			  73%

Cytogenetic result:



Acute Myeloid Leukemia with t(15;17)

(Acute Promyelocytic Leukemia, Hypogranular Type)


Key Features

  • t(15;17)(q22;q12), PML-RARA

  • Nuclei: kidney-shaped, bilobed or butterfly shape

  • Cytoplasmic granules, Auer rods, faggot cells

  • Frequent association with DIC

  • Positive: CD13, CD15, CD33, MPO

  • Negative: HLA-DR, CD34

  • Often negative for CD11b and CD11c



  • An acute leukemia with predominant abnormal promyelocytes, 5-8% of AML

  • Age: all age, but most in mid-life

  • Clinical features: a clinical emergency due to frequent association with DIC


  • Variable nuclear size and shape, often kidney-shaped or bilobed / butterfly shape

  • In most cases, myeloblasts are a minor component and rarely > 20%

  • Hypergranular APL (2/3)

    • Often leukopenia, abnormal promyelocytes with bilobed nuclei

    • Dense cytoplasmic granules; packed or coalescent large, or dust-like; bright pink, red or purple

    • Auer rods:  in 90% cases, can be multiple, numerous and intertwined

    • Faggot cell: cell with bundles of Auer rods

  • Hypogranular/Microgranular APL

    • Peripheral leukocyte count is elevated or markedly elevated due to a rapid doubling time

    • Cytoplasm has a paucity or absence of fine granules, and nuclei are predominantly bilobed

    • Scant Auer rods may be identified

    • More often positive for CD34, CD2 and CD64

    • Strongly associated with FLT3 ITD

    • Can resemble AML with monocytic differentiation, but the "butterfly" nuclei should prompt workup for APL


  • Markedly increased orthogonal (side) scatter

  • Positive: CD33, CD13, MPO

  • Frequent coexpression of CD2 and CD9

  • Negative: HLA-DR, CD34, CD15

  • NSE weakly positive in 25% cases


  • Auer rods: hexagonal arrangement of tubular structures with a specific periodicity of about 250nm.


  • t(15;17)(q22;q12):  98% cases, PML-RARA

  • t(11;17)(q23;q12): ZBTB16-RARA, ATRA resistant, non-bilobed, no Auer rods or Pelgeroid cells

  • t(11;17)(q13;q12): NUMA1-RARA, ATRA responsive

  • t(5;17)(q32;q12): NPM-RARA fusion gene. Responsive to ATRA

  • t(17;17)(q11.2;q12): STAT5B-RARA, ATRA resistant


  • Both hypergranular and hypogranular APLs have the same characteristic ultrastructural, cytogenetic, molecular and clinical features and both response to treatment with ATRA. They defer mainly in the peripheral blood count, the size and number of the visible granules and the prominence of the abnormal nuclear shape.

  • Particularly sensitive to treatment with all trans-retinoic acid that acts as a differentiating agent

  • Favorable prognosis when treated with all trans-retinoic acid and an anthracycline