Leukemia - Acute
Acute lymphoblastic leukemia (ALL)

Author: Daniela Mihova, M.D. (see Authors page)

Revised: 10 April 2018, last major update March 2013

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

PubMed Search: Acute lymphoblastic leukemia ALL [title] pathology

Cite this page: Mihova, D. Acute lymphoblastic leukemia (ALL) - general. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/leukemiaALL.html. Accessed August 20th, 2018.
Definition / general
  • 6050 cases / year in US in 2012 (National Cancer Institute), peaks at age 4; usually age 15 years or less
  • 80% of childhood leukemia is ALL
  • Higher incidence in whites, males and advanced (not developing) countries
  • 85% are B cell, 15% are T cell, but both often express aberrant myeloid or lymphoid associated antigens
  • Note that only 10 - 20% of lymphoblastic lymphoma is B cell lineage
  • Risk factors: in utero radiation, Down syndrome, ataxia telangiectasia, but most cases have no known cause
  • Symptoms: abrupt stormy onset, symptoms related to bone marrow depression (fatigue, fever, bleeding), bone pain and tenderness (due to marrow expansion), joint pain, generalized lymphadenopathy, hepatosplenomegaly, testicular involvement, CNS manifestations
  • Atypical presentation: hypercalcemia, bone lesions and no circulating blasts
  • Laboratory: anemia common, platelet count < 100K in 75% and < 10K in 15%; leukopenia (25%), WBC > 100K (10%)
  • Diagnosis: immunostains required for diagnosis
  • Relapse: blasts usually unchanged; may progress from L1 to L2, TdT positive to negative (25%), gain or lose an antigen (CD10, HLA-DR), evolve clonally (75%) or evolve to AML; CNS relapse common
Prognostic factors
  • Cytogenetics / FISH is single most important prognostic factor for adults (Blood 2008;111:2563)
  • Favorable prognosis: age 1 - 10 years, female, white; preB phenotype, hyperdiploidy > 50, t(12,21), normal WBC count at presentation, non-traumatic tap with no blasts, rapid response to chemotherapy, CD10+
  • Intermediate prognosis: hyperdiploidy 47 - 50, diploid, 6q- and rearrangements of 8q24
  • Unfavorable prognosis: under age 2 (usually have 11q23 translocations) or over age 10; t(9;22) (but not if age 59+ years, Am J Clin Pathol 2002;117:716); male, > 50x108/L, hypodiploidy, near tetraploidy, 17p-, MLL rearrangements and t(v;11q23); CD10- preB ALL; non-traumatic tap with > 5% blasts or traumatic tap with 7%+ blasts, also increased microvessel staining using CD105 in children (Leuk Res 2007;31:1741), MDR1 expression in children (Oncol Rep 2004;12:1201) or adults (Blood 2002;100:974)
Case reports
Microscopic (histologic) description
  • Blasts have scant agranular cytoplasm, no Auer rods, coarse to fine chromatin, often indistinct nucleoli and no dysplastic myeloid cells
  • Peripheral smear: leukoerythroblastosis common with granulocyte precursors and nucleated RBCs, lymphoblasts, occasionally reactive lymphocytes and rarely marked eosinophilia
  • Bone marrow: hypercellular, high percentage of lymphoblasts
  • Children: 80% are L1, 10 - 20% L2 and < 5% L3
  • Adults: 35% are L1, 60% L2 and < 5% L3
Microscopic (histologic) images

Images hosted on PathOut server:

L1 type (blood smears):
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Blasts have minimal cytoplasm, variable
nuclear size and chromatin density, irregular
nuclear contour, some small nucleoli

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Blasts have moderate cytoplasm, round
nuclei of variable size, coarse chromatin and
some resemble mature lymphocytes

L1 type (bone marrow smears):
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Blasts contain large cytoplasmic azurophilic
granules (uncommon), but were B
cells by IHC and cytochemistry

L1 type (bone marrow biopsy):
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Markedly hypercellular marrow
with lymphoblasts replacing
normal marrow elements

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Lymphoblasts occupy marrow,
have minimal cytoplasm and
indistinct cell borders, convoluted
nuclei, angulated borders

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Lymphoblasts are small with
more condensed chromatin

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Marrow contains lymphoblasts,
one megakaryocyte, normoblasts in
upper half and occasional eosinophils
and eosinophil precursors

L1 type (stains):
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Lymphoblasts have block and
coarse granular PAS staining

L2 type (blood smears):
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Three large lymphoblasts have
moderate cytoplasm, large nuclei
with coarsely reticular chromatin
and 1 - 3 prominent nucleoli

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Lymphoblasts have variable size,
moderate cytoplasm, markedly
irregular nuclei with coarse
chromatin and distinct nucleoli

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Most lymphoblasts have variable
size, reticular chromatin with
prominent nucleoli and some
have L1 features

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Blasts have cytoplasmic
azurophilic granules (uncommon)

L2 type (bone marrow smears):
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Large lymphoblasts with cytoplasm that has numerous,
sharply defined clear vacuoles similar to L3, non-L3 features
are reticular chromatin, prominent nucleoli, TdT+ and CD10+

L2 type (bone marrow biopsy):
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Relatively large lymphoblasts with
variable nuclear shape, dispersed
chromatin and prominent nucleoli

L3 type (bone marrow smears):
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No prominent vacuoles, dispersed chromatin and
more obvious nucleoli than usually observed in L3,
diagnosed as ALL-L3 and non-Burkitt type

L3 type (stains):
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Strong cytoplasmic staining by methyl green pyronine (left),
vacuoles are Oil Red O positive (right)

Images hosted on other servers:

Peripheral smear images:
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Blasts with scant cytoplasm
and prominent nucleoli

Enzyme cytochemistry
  • Negative for myeloperoxidase, chloroacetate esterase, nonspecific esterase (usually) and only rarely positive for Sudan Black B (Mod Pathol 1992;5:68)
  • Positive for PAS (75%, coarse clumping corresponds to glycogen), acid phosphatase (T-ALL has focal paranuclear staining)
  • Only L3 stains for glycogen with Sudan Black B and PAS
Positive stains
Negative stains
Molecular / cytogenetics description
  • 90% have cytogenetic abnormalities, usually hyperdiploidy (> 50 chromosomes), also pseudodiploidy (46 chromosomes but structural anomalies), t(12,21); t(9,22) [Philadelphia chromosome] and t(4,11)
Electron microscopy images

Images hosted on PathOut server:

L1 type:
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Cytoplasm has small mitochondria, small Golgi region, scattered polyribosomes and
occasional strands of round endoplasmic reticulum, nucleus is indented with a small
nucleolus, chromatin is condensed and concentrated at nuclear periphery

L2 type:
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Large lymphoblast with moderate cytoplasm, dispersed chromatin
with peripheral condensation and large prominent nucleolus

L3 type:
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Abundant cytoplasm with numerous polyribosomes and large lipid vacuoles (arrow)
nuclei have peripherally condensed chromatin and 1+ prominent nucleoli

Differential diagnosis