Bone marrow neoplastic
Bone marrow - neoplastic myeloid
AML not otherwise specified
AML M6
Author: Huifei Liu, M.D., Ph.D.
Deputy Editor-in-Chief: Genevieve M. Crane, M.D., Ph.D.
Last author update: 11 May 2020
Last staff update: 24 March 2022
Copyright: 2001-2024, PathologyOutlines.com, Inc.
PubMed Search: Acute erythroid leukemia [title] AML-M6
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Clinical features | Diagnosis | Prognostic factors | Case reports | Treatment | Microscopic (histologic) description | Microscopic (histologic) images | Cytology images | Peripheral smear description | Peripheral smear images | Positive stains | Negative stains | Molecular / cytogenetics description | Sample pathology report | Differential diagnosis | Additional references | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Liu H. AML M6. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/leukemiaM6.html. Accessed December 23rd, 2024.
Definition / general
- Acute erythroid leukemia (AML-M6)
- A neoplastic proliferation of immature cells (undifferentiated or proerythroblastic in appearance) committed exclusively to the erythroid lineage (> 80% of the bone marrow cells are erythroid, with ≥ 30% proerythroblasts), with no evidence of a significant myeloblastic component (Swerdlow: WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4th Edition, 2017)
- Note: per WHO 2016, the category of acute erythroleukemia M6a no longer exists; cases previously classified as M6a are either myelodysplastic syndrome (MDS) or AML depending on the myeloblast percentage in bone marrow or peripheral blood
Essential features
- A rare aggressive acute myeloid leukemia (Am J Hematol 2017;92:292)
- Erythroid precursors > 80% and proerythroblasts ≥ 30% of the bone marrow cells
- Myeloblasts are not increased
- Therapy related cases should be diagnosed as therapy related myeloid neoplasms
Terminology
- Acute myeloid leukemia, M6 type
- Acute erythroid leukemia
- Erythroleukemia
- Pure erythroid leukemia M6b
- Di Guglielmo disease
- Acute erythraemic myelosis
- Acute erythraemia
ICD coding
- ICD-10: C94.00 - acute erythroid leukemia, not having achieved remission
Epidemiology
- Extremely rare, < 1% of all AML (Am J Hematol 2017;92:292)
- Any age, can be congenital (Int J Hematol 2017;106:711)
- Both de novo and secondary (Mod Pathol 2018;31:705, Mod Pathol 2011;24:375)
Sites
- Bone marrow or peripheral blood (Am J Hematol 2017;92:292)
- Mass lesion (erythroblastic sarcoma) in tissue such as central nervous system, orbit, liver, ovary, etc. (Haematologica 2020 Jan 16 [Epub ahead of print])
Clinical features
- Anemia (Am J Hematol 2017;92:292)
- Circulating erythroblasts
- Mass (Haematologica 2020 Jan 16 [Epub ahead of print])
Diagnosis
- Erythroblasts > 80% in bone marrow or peripheral blood with proerythroblasts ≥ 30%
- Myeloblasts are not increased (< 5%)
- For extramedullary mass lesion, sheets of erythroid precursor cells with proerythroblasts ≥ 30%
Prognostic factors
- Usually poor with median survival of 1.4 to 3 months (Mod Pathol 2018;31:705, Mod Pathol 2011;24:375)
Case reports
- 3 month old girl with low grade fever and cough, pure erythroid leukemia and bilateral ovarian erythroid sarcoma (Hum Pathol 2011;42:749)
- 15 month old boy with a history of failure to thrive, vomiting and high fever, prolonged diarrhea and pure erythroid leukemia (Leukemia 2011;25:1510)
- 2 year old girl presenting with headache, vomiting and a de nova erythroid sarcoma in third ventricle (Haematologica 2020 Jan 16 [Epub ahead of print])
- 44 year old woman with progressive fatigue, pancytopenia and pure erythroid leukemia (Clin Case Rep 2019;7:1829)
- 48 year old man with shortness of breath, weight loss and pure erythroid leukemia (Hematol Rep 2015;7:5674)
Treatment
- AML treatment protocol (Am J Hematol 2017;92:292)
- Radiation therapy can be considered for localized mass lesion in orbit or CNS (Haematologica 2020 Jan 16 [Epub ahead of print])
- Bone marrow transplant
Microscopic (histologic) description
- Bone marrow biopsy: sheets or clusters of immature cells, tumor cells may show intrasinusoidal growth pattern (Am J Hematol 2017;92:292)
- Bone marrow aspirate: erythroid precursors > 80% and proerythroblasts ≥ 30% of bone marrow cells
- Proerythroblasts have round nuclei, fine chromatin and one or more prominent nucleoli, deeply basophilic cytoplasm with vacuoles, often agranular
- Ring sideroblasts are common
- Myeloblasts are not increased
- Dysmegakaryopoiesis is common and dysgranulopoiesis is infrequent
- Mass in tissue: poorly differentiated tumor cells (Haematologica 2020 Jan 16 [Epub ahead of print])
Microscopic (histologic) images
Contributed by Huifei Liu, M.D., Ph.D.
Erythroblastic sarcoma
E-cadherin
CD43
AFIP images
Bone marrow smear (Wright-Giemsa)
Cytology images
Contributed by Huifei Liu, M.D., Ph.D.
CSF erythroblasts
Peripheral smear description
- Anemia, thrombocytopenia or pancytopenia (Am J Hematol 2017;92:292)
- Circulating erythroblasts
Peripheral smear images
Contributed by Huifei Liu, M.D., Ph.D.
Circulating erythroblasts
Positive stains
- Erythroid specific markers: E-cadherin (positive in majority cases), hemoglobin A and glycophorin A (usually positive but can be negative in poorly differentiated erythroblasts) (Am J Hematol 2017;92:292)
- Not lineage-specific markers: CD36, CD43, CD71, CD117, GATA1, Ferritin H
- These markers are unusually positive; however, they can be positive in other type of hematopoietic neoplasms
- CD36 is commonly positive on monocytic leukemia and acute megakaryocytic leukemia
- CD43 is positive in most AML, T-ALL as well as some B-ALL; it is a very useful marker for extramedullary poorly differentiated tumor to confirm hematopoietic lineage
- CD71 can be positive in other leukemic blasts although its expression levels in PEL should be very bright
- CD117 is positive in most AML and some T-ALL
- GATA1 is a transcription factor for erythroid development and it is positive in both PEL and acute megakaryocytic leukemia (Am J Clin Pathol 2017;147:420)
- Ferritin H is expressed in erythroid precursors as well as macrophages
- Special stains: PAS (usually in block-like pattern), alpha naphthyl acetate esterase, acid phosphatase
Negative stains
- Myeloid markers (CD13, CD33, myeloperoxidase) (Am J Hematol 2017;92:292)
- Megakaryocytic makers (CD41 and CD61), usually negative but may be partially expressed in some cases
- CD34, CD45, HLA-DR
- Note: these markers are generally negative but can be weakly or partially positive in some cases
Molecular / cytogenetics description
- Often complex karyotype, frequently -5/del(5q) and -7/del(7q) (Am J Hematol 2017;92:292)
- t(1;16)(p31;q24) has only been described in a total of 5 cases of pure erythroid leukemia, with fusion of NFIA/CBFA2T3 confirmed in 2 cases of pure erythroid leukemia, likely a pure erythroid leukemia specific rearrangement (Haematologica 2020;105:e194, Leukemia 2013;27:980)
- t(11;20)(p11;q11)/ZMYND8-RELA was reported in 1 case of pure erythroid leukemia (Am J Hematol 2017;92:292)
- p53 mutation was detected in a significant portion of adult cases (Nat Genet 2019;51:694)
Sample pathology report
- Bone marrow, right, biopsy, clot section, aspirate smears, touch imprint and peripheral blood smear:
- Pure erythroid leukemia, blasts 95% of total nucleated cells (see comment)
- Comment:
- Peripheral blood:
- Red blood cells: Normocytic normochromic anemia with slight anisopoikilocytosis.
- White blood cells: Leukopenia with few large proerythroblasts. The blasts have scant basophilic cytoplasm, round nuclei, open chromatin and few have prominent nucleoli. Cytoplasmic vacuoles are noted in some blasts.
- Platelets: Decreased with rare giant forms.
- Bone marrow biopsy:
- Decalcification procedures performed to allow for histological assessment of submitted tissue.
- Gross measurement: 0.5 cm
- Quality: Adequate
- Cellularity: 100%
- Megakaryocytes: Rare
- Infiltrate: The marrow is nearly completely replaced by sheets of immature cells with high nuclear to cytoplasmic ratio, open chromatin and some with prominent nucleoli.
- Bone marrow clot:
- Quality: Inadequate, blood only, no particles with many immature cells
- Bone marrow smears:
- Quality / cellularity: Adequate
- Granulocytes: Markedly decreased
- Erythrocytes: Markedly increased erythroid precursors with increased proerythroblasts.
- Megakaryocytes: Not seen
- Lymphocytes: Decreased, few small and mature cells.
- bone marrow differential count: 500 total cells counted
- Blasts percentage (0-5): 95
- Promyelocytes percentage (2-8): 0
- Myelocytes percentage (5-20): 0
- Metamyelocytes percentage (13-32): 0
- Granulocytes percentage (7-30): 2
- Monocytes percentage (0-5): 0
- Lymphocytes percentage (3-17): 3
- Plasma cells percentage (0-2): 0
- Eosinophils percentage (0-4): 0
- Basophils percentage (0-1): 0
- Pronormoblasts percentage (1-8): 80
- Normoblasts percentage (7-32): 15
- M:E ratio (2-4): N/A
- Bone marrow touch imprint:
- Quality: Adequate, similar to smear with increased erythroid blasts.
- Flow cytometric analysis:
- Aberrant erythroid blasts, 95.2% of total nucleated cells (F19-160).
- Pending tests:
- Cytogenetic karyotype and FISH.
- Peripheral blood:
Differential diagnosis
- Other type of acute leukemia, especially acute megakaryocytic leukemia
- Other poorly differentiated malignancy or small blue round cell tumor
- Reactive erythroid hyperplasia
- Pure erythroid leukemia should not be diagnosed as AML with myelodysplasia related change (AML with MRC) even if there is prior history of myeloid neoplasm, significant dysplasia of 2 lineages and a defining cytogenetic abnormality
- AML with MRC requires minimal 20% myeloblasts while pure erythroid leukemia should not have a significant component of myeloblasts
Additional references
Board review style question #1
Which of the following markers is most useful in diagnosing pure erythroid leukemia?
- CD117
- CD34
- Myeloperoxidase
- E-cadherin
- CD71
Board review style answer #1
Board review style question #2
A 7 year old boy presented with leukocytosis (55K), anemia (Hb 7.5 g/dl) and thrombocytopenia (52k). Peripheral blood smear (see photo) shows many mononucleated cells of variable sizes with high nuclear:cytoplasmic ratio, round nuclei, open chromatin and deep blue cytoplasm. Some large cells have conspicuous nucleolus. By flow cytometric immunophenotyping, these cells are positive for CD36, CD117 (heterogeneous) and negative for CD34, CD45, HLA-DR and all other lymphoid, myeloid and monocytic markers. Which of the following sentences is correct regarding this disease?
- These cells are positive for CD61
- These cells show reactivity with alpha-naphthyl acetate esterase, acid phosphatase and PAS
- These cells most likely have a normal karyotype (46, XY)
- A percentage of ≥ 20% of these cells in blood or bone marrow is required for diagnosis as pure erythroid leukemia
- The prognosis for this patient is good
Board review style answer #2
B. These cells show reactivity with alpha-naphthyl acetate esterase, acid phosphatase and PAS.
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Reference: Acute erythroid leukemia (AML-M6)
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Reference: Acute erythroid leukemia (AML-M6)
