Bone marrow neoplastic

Bone marrow - neoplastic myeloid

Recurrent genetic abnormalities

APL with PML-RARA



Last author update: 1 February 2013
Last staff update: 12 January 2023 (update in progress)

Copyright: 2001-2023, PathologyOutlines.com, Inc.

PubMed Search: Acute promyelocytic leukemia (APL) with t(15;17)(q22;q12)

See Also: PML::RARA


Syed Zaidi, M.D.
Page views in 2022: 10,176
Page views in 2023 to date: 824
Cite this page: Zaidi S. APL with PML-RARA. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/leukemiaAPL.html. Accessed January 29th, 2023.
Definition / general
  • Either hypergranular (this section) or microgranular / hypogranular
  • 5 - 8% of AML cases
  • Formerly called AML M3
  • Median age 35 - 40 years but can occur at any age
  • Decreased WBC count (hypergranular variant) at presentation with abnormal promyelocytes
  • Usually disseminated intravascular coagulation (DIC) and hemorrhage before or during induction chemotherapy, which may cause early death
  • Rarely organomegaly, extramedullary disease, skin involvement (detect with FISH, Mod Pathol 2005;18:1569)
  • Criteria for diagnosis: most cells (> 50%) are abnormal promyelocytes with heavy cytoplasmic granulation that may obscure the nuclear cytoplasmic margin, often reniform or bilobed nucleus; cells with multiple Auer bodies usually present; also bundles of Auer rods ("faggot cells" - resembles bundle of sticks)
  • Note: if t(15;17) present, diagnose as AML even if initial blast count is < 20%
Prognostic factors
  • In children, age < 10 years is favorable (Cancer 2006;106:2495)
  • Survival: excellent if DIC and hemorrhage are adequately controlled; excellent in adults with complete remission
APL microgranular variant
  • Formerly called AML-M3v
  • Note: "variant" APL without further description may mean microgranular variant or an APL variant other than t(15;17)
  • Peripheral blood white blood count usually elevated, in contrast to hypergranular form
  • Diagnosis: cytogenetics recommended because other AML cases may appear similar (Am J Clin Pathol 2002;117:651)
APL with t(V;17)(V;q12)
  • Note: "variant" APL without further description may mean microgranular (morphologic) variant or cytogenetic variant other than t(15;17)
  • Uncommon, involves retinoic acid receptor alpha on #17 but not PML gene on #1
  • t(11;17) is most common; also called ZBTB16-RARα variant
  • Symptoms: disseminated intravascular coagulation / DIC common (Atlas of Genetics and Cytogenetics: t(11;17)(q23;q21) ZBTB16/RARA [Accessed 2 April 2018])
  • May NOT respond to all-trans retinoic acid therapy; may be more aggressive than classic APL (Blood 1995;85:1083)
  • Recommended to combine cytogenetics, FISH and molecular biology to document presence / absence of PML-RARα fusion gene in complex cases (Cancer Genet Cytogenet 2005;159:69)
Case reports
Treatment
  • Combination chemotherapy required for sustained remissions (Hematology Am Soc Hematol Educ Program 2006:147)
  • All trans retinoic acid (ATRA) causes neoplastic promyelocytes to rapidly differentiate into bizarre maturing neutrophils, but patients eventually relapse
  • Arsenic trioxide (ATO) for ATRA-refractory patients; induces differentiation at low doses, marrow necrosis at high doses (Mod Pathol 2000;13:954)
Microscopic (histologic) description
  • Most cells are hypergranular promyelocytes (abundant cytoplasm, round / oval and frequently eccentric nuclei with occasional clefts or indentations, moderately condensed chromatin and indistinct nucleoli) with heavy red / purple cytoplasmic granulation that may obscure nuclear borders
  • 90% have multiple Auer rods in some cells, which may resemble bundles of sticks
  • Reniform (kidney shaped) nucleus; may have basophilic cytoplasm, < 20% myeloblasts
  • Post-treatment: may be difficult to differentiate residual disease (promyelocytes not in any particular location) from regenerating marrow (promyelocytes are perivascular and endosteal)
  • Microgranular variant: predominatly bilobed leukemic cells have fewer and smaller cytoplasmic granules, usually multiple Auer rods but less than classic (hypergranular) promyelocytic leukemia; nuclei is folded, convoluted and markedly irregul
  • APL with t(V;17)(V;q12): Features are intermediate between hypergranular acute promyelocytic leukemia (M3) and acute leukemia with maturation (M2), most cells have many granules and regular nuclei; usually no Auer rods but increased pseudo Pelger-Huet cells
Microscopic (histologic) images

AFIP images
Bone marrow biopsy Bone marrow biopsy

Bone marrow biopsy


Contributed by @sanamloghavi on Twitter
APL with PML-RARA APL with PML-RARA

APL with PML-RARA

Cytology images

AFIP Images
Bone marrow smear (Wright-Giemsa)

Bone marrow smear (Wright-Giemsa)

Treatment related

Treatment related

Microgranular variant Microgranular variant

Microgranular variant


Contributed by @sanamloghavi on Twitter
APL with PML-RARA APL with PML-RARA

APL with PML-RARA



Images hosted on other servers:

Abundant azurophilic granules (Wright-Giemsa)

Positive stains
Negative stains
Molecular / cytogenetics description

Table 3: cytogenetic abnormalities in APL (eMedicine: Acute Myeloid Leukemia (AML) Workup [Accessed 2 April, 2018]):

Translocation    Genes Involved    All-Trans-Retinoic Acid Response
t(15;17)(q21;q11) PML/RARα      Yes
t(11;17)(q23;q11) PLZF/RARα      No
t(11;17)(q13;q11) NuMA/RARα    Yes
t(5;17)(q31;q11)   NPM/RARα     Yes
t(17;17)     stat5b/RARα    Unknown

Molecular / cytogenetics images

AFIP images
Missing Image

t(15;17): arrowheads
at breakpoints
on abnormal
chromosomes



Images hosted on other servers:
Missing Image

t(11;17)(q23;q21) variant

Electron microscopy description
  • Auer rods have tubular substructure, markedly dilated endoplasmic reticulum and stellate complexes of rough ER
  • Nucleus has dispersed chromatin and prominent nucleolus
Electron microscopy images

AFIP images
Missing Image

Cytoplasm and nucleus

Missing Image

Cross section of Auer rod

Missing Image

Microgranular variant

Missing Image

Small granules and stellate array

Differential diagnosis
Back to top
Image 01 Image 02