Acute basophilic leukemia

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]

Table of Contents

Cite this page: Khattar, P. Acute basophilic leukemia. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/leukemiabasophil.html. Accessed September 22nd, 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

9870 / 3

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:

Most blasts lack
differentiation but
1 blast has coarse
azurophilic granules

Bone marrow biopsy:

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

Stains:

Maturing basophils
have metachromatic
granules with
toluidine blue stain

Images hosted on other servers:

Basophilic leukemia

Positive stains

CD13 or CD33, CD123, CD203c, CD11b, CD34
Some cases may be positive for CD22 or TdT
Most characteristic cytochemical reaction is metachromatic staining with toluidine blue, acid phosphatase (diffuse pattern), periodic acid Schiff (PAS) positivity in large blocks

Negative stains

Myeloperoxidase (MPO), Sudan Black B (SBB) or naphthol ASD chloroacetate esterase (CAE) 
CD117, tryptase, CD25, monocytic and lymphoid associated markers

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:

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

Includes other myeloid leukemias associated with basophilia, such as:
- Acute promyelocytic leukemia with basophilic differentiation (Leukemia 1994;8:1441)
- AML M0 (acute myeloid leukemia with minimal differentiation)
- AML with BCR-ABL1:
  - New entity; defined as de novo AML in which patients show no evidence (before or after therapy) of chronic myeloid leukemia
  - Tends to be aggressive disease with poor response to traditional AML therapy or TKI inhibitors alone (Clin Case Rep 2017;5:757)
- AML with t(6;9)(p23;q34.1) DEK-NUP214:
  - Seen in older children; rare in infants
  - Often associated with basophilia, multilineage dysplasia and poor prognosis (Br J Haematol 2014;166:254)
- AML with t(8;21) RUNX1-RUNX1T1 and basophilia:
  - Seen in younger patients
  - Blasts are large with abundant basophilic cytoplasm containing numerous azurophilic granules and perinuclear hofs
  - Often with large granules (pseudo-Chédiak-Higashi granules)
  - Usually associated with high rate of complete remission and longterm disease survival (Rinsho Ketsueki 2017;58:991)
- Blast phase of myeloproliferative neoplasm (Am J Clin Pathol 2015;144:188)
- Lymphoblastic leukemia with prominent coarse granules (rare)
- Mast cell leukemia: immunophenotypic detection of abnormal mast cells expressing CD117, mast cell tryptase and CD25 will distinguish mast cell leukemia from acute basophilic leukemia (Diagn Pathol 2018;13:14)

Additional references

Swerdlow: WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th Edition, 2017, Br J Haematol 2003;120:774

Board review question #1

What is the most specific marker for basophils in peripheral blood ?

CD25
CD117
CD123
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.