Leukemia - acute
AML not otherwise categorized
Acute basophilic leukemia

Author: Pallavi Khattar, M.D. (see Authors page)
Editor: Mariko Yabe, M.D., Ph.D.

Revised: 11 June 2018, last major update April 2018

Copyright: (c) 2001-2018, PathologyOutlines.com, Inc.

PubMed Search: Acute basophilic leukemia[TIAB]

Cite this page: Khattar, P. Acute basophilic leukemia. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/leukemiabasophil.html. Accessed July 19th, 2018.
Definition / general
  • Defined as acute myeloid leukemia (AML) with primary differentiation to basophils
  • Does not fulfill the criteria for any previously described groups (i.e. AML with myelodysplasia related changes, therapy related AML or AML with recurrent genetic abnormalities)
  • Clinical presentation is often rapid and associated with poor prognosis
  • Survival of 2 - 16 months
Essential features
  • Criteria for diagnosis: circulating peripheral blood and bone marrow blasts that are positive with metachromatic staining (toluidine blue), acid phosphatase (diffuse pattern), some cases with periodic acid Schiff (PAS) positivity in large blocks while negative for myeloperoxidase (MPO), Sudan Black B (SBB) or naphthol ASD chloroacetate esterase (CAE) by enzyme cytochemistry
  • Immunophenotyping and electron microscopy features are essential to identify basophilic lineage; the latter, although not often used for leukemia diagnosis, is especially crucial to differentiate basophilic cells from closely related mast cells (J Clin Oncol 2011;29:e623)
Terminology
  • "Basophilic leukemia" is no longer used
ICD-O coding
Epidemiology
  • Rare, < 1% of acute myeloid leukemia cases
  • Frst described ("basophilic leukemia") in 1906 by Joachim (Dtsch Arch Klin Med 1906;87:437)
Sites
  • Peripheral blood, bone marrow, cutaneous involvement, organomegaly
Etiology
  • Unknown
Clinical features
  • Wide age range: 1 day to 82 years (Leuk Lymphoma 1999;32:269)
  • Typically presents with bone marrow failure, variable circulating blasts
  • Skin conditions due to high histamine levels are pruritus, edema, urticarial rashes, focal hyperpigmentation
  • GI symptoms: nausea, vomiting, diarrhea, dyspepsia, abdominal swelling or ulcers
  • Organomegaly and lytic lesions
Diagnosis
Proposed diagnostic criteria for basophilic leukemias:
  • It is important to distinguish acute basophilic leukemia (ABL) from chronic basophilic leukemia (CBL):
    • ABL: myeloblasts and metachromatic blasts ≥ 20% and basophils ≥ 40% of nucleated bone marrow (BM) or peripheral blood (PB) cells (and hyperbasophilia [HB] criteria are fulfilled - persistent basophilia with basophil count of > 1,000 per μl of blood)
      • Primary ABL: no preceding or underlying bone marrow neoplasm
      • Secondary ABL: known preceding / underlying bone marrow neoplasm
    • CBL: myeloblasts and metachromatic blasts < 20% and basophils ≥ 40% of nucleated BM or PB cells (and HB criteria are fulfilled)
      • Primary CBL: no preceding or underlying BM neoplasm
      • Secondary CBL: known preceding / underlying BM neoplasm

  • Basophils must belong to the malignant clone as evidenced by:
    • (Immature) morphology of basophils
    • Type of underlying neoplasm (myeloid) if present
    • Presence of a clonal (cytogenetic or molecular) marker (Leukemia 2017;31:788)
Laboratory
  • Peripheral blood examination, bone marrow biopsy, radiology (Xrays for lytic lesions), increased histamine levels, genetic profiling
Case reports
  • 63 year old woman with FLT3 ITD+ acute basophilic leukemia with rare complex karyotype presenting with acute respiratory failure (Rev Romana Med Lab 2018;26:87)
  • 82 year old woman with acute basophilic leukemia associated with loss of gene ETV6 and protean complications (J Clin Oncol 2011;29:e623)
  • Acute basophilic leukemia with add(3)(q12) accompanied by histamine excess symptoms (Ann Hematol 2017;96:1197)
Treatment
  • Stem cell transplant
  • When stem cell transplant is not possible, patients should receive polychemotherapy, targeted drugs or palliative therapy (Leukemia 2017;31:788)
Microscopic (histologic) description
  • Hypercellular bone marrow with medium sized blasts with high nuclear to cytoplasmic ratio, an oval, round or bilobed nucleus, dispersed chromatin with 1 - 3 prominent nucleoli
  • Moderate amounts of basophilic cytoplasm that contains a variable number of coarse basophilic granules, some with vacuolation
  • Mature basophils are usually sparse
  • Dysplastic features in the erythroid precursors may be present
Microscopic (histologic) images

Images hosted on PathOut server:

Bone marrow smears:
Missing Image

Most blasts lack
differentiation but
1 blast has coarse
azurophilic granules


Bone marrow biopsy:
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Blasts and immature basophils with
variable nuclear size and nucleoli;
also plasma cells, endothelial
cells and hemosiderophages


Stains:
Missing Image

Maturing basophils
have metachromatic
granules with
toluidine blue stain



Images hosted on other servers:
Missing Image

Basophilic leukemia

Positive stains
Negative stains
Flow cytometry description
  • Cell surface antigens specifically expressed on basophils include IL3 R alpha chain (CD123), Fcε receptor type I (IgE-R), Bsp-1 and ectoenzyme ENPP3 (CD203c)
  • CD203c is largely specific for basophils in the peripheral blood
  • In bone marrow (BM) samples, normal and neoplastic mast cells also react with antibodies against CD203c
  • Therefore, additional markers, including CD117 / KIT (usually not expressed on basophils) and CD123 (usually not expressed on mast cells) should be applied when BM cells are examined (Leukemia 2017;31:788)
Electron microscopy description
  • Granules contain an electron dense particulate substance and are internally bisected, e.g. have a theta character (θ) or contain crystalline material arranged in a pattern of scrolls or lamellae
  • Coexistence of basophil and mast cell granules may be identified in the same immature cells
Electron microscopy images

Images hosted on PathOut server:
Missing Image

Granules contain
amorphous speckled
substance, 1 granule
has a myelin figure



Images hosted on other servers:

Ultrastructural features of ABL blasts

Molecular / cytogenetics description
  • No consistent chromosomal abnormality identified
  • Recurrent t(X;6)(p11.2;q23.3) resulting in MYB-GATA1 appears to occur in male infants (Blood 2011;117:5719)
  • t(3;6)(q21;p21)
  • Acute myeloid leukemia with t(6;9)(p23;q34.1) and BCR-ABL1 cases are excluded
Differential diagnosis
Board review question #1
What is the most specific marker for basophils in peripheral blood ?

  1. CD25
  2. CD117
  3. CD123
  4. CD203c
Board review answer #1
D. CD203c is the largely specific marker for basophils in peripheral blood. Other markers such as CD13 or CD33, CD123, CD11b, CD34 are also positive, while CD25, CD117 and tryptase are negative. This immunophenotype helps to differentiate acute basophilic leukemia from mast cell leukemia.