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Bone marrow - nonneoplastic

Normal

Hematogones


Reviewers: Dragos Luca, M.D. (see Reviewers page)
Revised: 15 October 2012, last major update August 2012
Copyright: (c) 2001-2012, PathologyOutlines.com, Inc.

General
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● Hematogones are lymphoid progenitor cells, usually < 1% of bone marrow cells
● May become hyperplastic (> 5%), markedly hyperplastic (> 25% - uncommon) or very numerous (70% - rare)
● Often found in young children as normal finding, and may be most common lymphoid population in neonates (Biol Neonate 2004;86:247)

Clinical features
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● Also associated with childhood cytopenias, neoplasms, viral infections, ITP (Egypt J Immunol 2005;12:9) and regenerative marrow after chemotherapy or bone marrow transplantation
● Occasionally encountered in adults with lymphoma, myelosuppressive therapy, chronic viral infections and autoimmune diseases (a href="http://www.ncbi.nlm.nih.gov/pubmed/8042590">Am J Clin Pathol 1994;102:202)
● May distort analysis of acute lymphoblastic leukemia in flow cytometry since markers are similar
● Have been separated into three types (Neoplasma 2005;52:502)

Case reports
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● 3 month old boy with CMV and excessive hematogones (Leuk Res 2003;27:193)
● 7 year old girl with Shwachman-Diamond syndrome and CD5+ hematogones (Pediatr Dev Pathol 2001;4:505)
● Sisters with Shwachman-Diamond syndrome who died as neonates (Arch Pathol Lab Med 2000;124:1379)

Micro description
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Hematogones: highly condensed chromatin, inconspicuous nuclei and scant cytoplasm; except for neonates, generally not evident in peripheral blood, but are identifiable in pediatric bone marrow
Lymphoblast: resembles lymphoblasts in ALL; 10-20 microns (small / medium size), round / oval with sparse, deeply basophilic cytoplasm without granules but may have vacuoles; indented nucleus with homogeneous fine, lacy and smudged chromatin; variable nucleoli; not identifiable in normal bone marrow
Prolymphocyte: same size as lymphoblasts (10-20 microns), but more cytoplasm than lymphoblasts or mature lymphocytes, usually homogeneously blue cytoplasm; central round nucleus with single prominent nucleolus; coarser chromatin than lymphoblasts; N/C ratio is 75-85%; not identifiable in normal bone marrow
Lymphocytes: 7-15 microns, round / ovoid but may have notches or indentations; variable light blue cytoplasm (often sparse); dense chromatin, usually no nucleolus; N/C ratio is 35-85%

Micro images
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Various images


Post umbilical cord blood transplant


Hematogones-left vs. ALL-right


Child with three large hematogone cells in upper left that have sparse, lightly basophilic cytoplasm

   
Left: 5 month old with neuroblastoma and increased hematogones evenly distributed; right-hematogones have clumped nuclear chromatin and no distinct nucleoli

Flow cytometry images
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Hematogones

Positive stains
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● Commonly CD10+, CD38 (bright) and CD19+ by flow cytometry
● Heterogeneous expression of CD19, CD20, CD22, CD10, CD34 and TdT
● Also CD38, CD43 (Br J Haematol 2005;128:820)
● More CD20+ cells than CD34 / TdT+ cells (Am J Clin Pathol 2000;114:66); expression of CD20 and CD34 is mutually exclusive
● CD34 and TdT show a biphasic pattern

Negative stains
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● Surface immunoglobulin
● No PAS+ globules

Genetics and molecular
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● Normal karyotype
● Normal DNA content
● Negative clonality studies

Differential diagnosis
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● ALL: homogeneous staining for various markers; maturation arrest, aberrant antigen expression and asynchronous antigen expression (Blood 2001;98:2498, Leuk Lymphoma 2004;45:277)

Additional references
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Carey: Flow Cytometry in Clinical Diagnosis, 2007

End of Bone Marrow - nonneoplastic > Normal > Hematogones


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