Table 2.
Peripheral blood smear and bone marrow findings in IEI associated with neutropenia
| Hematopathologic finding | IEI to consider in differential | Additional comments |
|---|---|---|
| Absent or decreased neutrophil granules |
GFI1-related neutropenia JAGN1-related neutropenia Specific granule deficiency |
In specific granule deficiency, neutrophils with bilobed nuclei are commonly observed. |
| Atypical megakaryocytes | GATA2 haploinsufficiency | Megakaryocytes may be small or mononuclear or may have separated nuclear lobes. Often associated with marrow fibrosis.21 |
| Giant cytoplasmic granules | Chediak-Higashi syndrome | Giant azurophilic granules within the lysosomes are considered pathognomonic for the disorder and are easily visible in neutrophils, eosinophils, and other granulocytes.51 Additional findings in the marrow include extensive vacuolization, acidophilic inclusion (esp in promyelocytes), specific granules easily recognized as early as the myelocyte stage.9 |
| Myelofibrosis | DADA215 GATA2 haploinsufficiency21 VPS45-related neutropenia52 |
DADA2 is also associated with lymphoid aggregates in the marrow. |
| Myelokathexis | WHIM syndrome23 G6PC3-related neutropenia53 |
Neutrophils are also often hypersegmented with thin, long isthmi, pyknotic nuclei, and cytoplasmic vacuoles in WHIM syndrome. |
| Neutrophil nuclei herniation | WDR1 deficiency54 | In addition to herniation of the nuclear lobes, neutrophils also have agranular regions within the cytosol. |
| PHA | NBAS deficiency | Pseudo-PHA is associated with various medications (eg, immunosuppressive agents, antimicrobials, growth factors). The pseudo-PHA is generally reversible with medication cessation.54 PHA also seen in association with MDS. |
| Promyelocyte arrest | Severe, permanent arrest:55 ELANE-related neutropenia (severe congenital phenotype) HAX-1-related neutropenia CSF3R-related neutropenia G6PC3-related neutropenia WAS-related neutropenia JAGN1-related neutropenia56 Mild, intermittent arrest: GFI1-related neutropenia Neutropenia associated with poikiloderma |
Copper deficiency can also result in maturation arrest; reversible with copper administration. Promyelocytic AML can mimic the promyelocytic arrest associated with IEI but is easily differentiated by additional flow and/or cytogenetic studies. |
AML, acute myeloid leukemia; MDS, myelodysplastic syndrome; PHA, Pelger-Huet anomaly.