Pelger-Huët Anomaly



Pelger-Huët Anomaly


Kathryn Foucar, MD





Key Facts


Terminology



  • Nuclear hyposegmentation of neutrophils and other granulocytic cells producing



    • Bilobed (pince-nez) nuclei


    • Mononuclear (Stodtmeister) nuclei


  • Familial and acquired forms


Etiology/Pathogenesis



  • Autosomal dominant familial PHA



    • Mutations in lamin β-receptor (LBR) gene at 1q41-43


    • Results in defects in scaffolding proteins that control shape of nuclear membrane


    • Nuclear hypolobation results from reduced levels of LBR protein


    • All granulocytic lineages affected


    • Neutrophil function normal


  • Numerous medications linked to acquired, nonneoplastic PHA


  • Chronic infections can cause acquired PHA


  • Clonal myeloid neoplasms linked to acquired PHA


Clinical Issues



  • 1 per 5,000 population for familial PHA


Microscopic Pathology



  • Bilobed or monolobated nuclei of neutrophils, eosinophils, and basophils



    • ≥ 70% of neutrophils are hyposegmented with increased nuclear clumping


    • Neutrophils show normal cytoplasmic granularity


    • Other lineages usually normal in familial PHA


  • Multilineage abnormalities common in acquired, clonal PHA






This blood smear shows a neutrophil with a hyposegmented nucleus in acquired PHA in a patient on numerous medications. Note that the cytoplasm is normal.






This blood smear shows 2 mononuclear (Stodtmeister) PHA-type neutrophils in an asymptomatic young adult with familial PHA. Note lack of segmentation and highly condensed nuclear chromatin.


TERMINOLOGY


Abbreviations



  • Pelger-Huët anomaly (PHA)


Definitions



  • Nuclear hyposegmentation of neutrophils and other granulocytic cells resulting in either bilobed (pincenez) or mononuclear (Stodtmeister) morphology


  • Familial and acquired forms


ETIOLOGY/PATHOGENESIS


Multifactorial Causes



  • Autosomal dominant familial PHA


  • Numerous medications linked to acquired, nonneoplastic PHA



    • Sulfasoxazole


    • Sulfonamides


    • Mycophenolate mofetil


    • Myelosuppressive agents


    • Colchicine


    • Ganciclovir


    • Valproic acid


    • Paclitaxel


    • Other medications


  • Chronic infections can cause acquired PHA



    • HIV


    • Tuberculosis


    • Mycoplasma pneumonia


    • Influenza


    • Malaria


  • Clonal myeloid neoplasms linked to acquired PHA



    • Myelodysplasia (MDS)


    • Acute myeloid leukemia (AML)


    • Myelodysplastic/myeloproliferative neoplasms


    • Neutrophils are component of neoplastic clone


Pathogenesis of Familial PHA



  • Autosomal dominant



    • Mutations in lamin β-receptor (LBR) gene at 1q41-43


    • Results in defects in scaffolding proteins that control shape of nuclear membrane


    • Nuclear hypolobation results from reduced levels of LBR protein


    • All granulocytic lineages affected


    • Neutrophil function normal


  • Neutrophil migratory defect linked to soft tissue infections


Pathogenesis of Acquired Secondary, Nonneoplastic PHA



  • Unknown


Pathogenesis of Acquired, Clonal PHA in Myeloid Neoplasms



  • Possible acquired mutations in LBR


  • Possible apoptotic defect with resulting dense, nonsegmented nuclei


  • Possible acquired clonal 17p deletion linked to prominent PHA


CLINICAL ISSUES


Epidemiology



  • Incidence



    • 1 per 5,000 population for familial PHA


    • Highly variable for acquired PHA dependent upon cause


  • Age



    • Present at birth in familial PHA


    • Wide age range for acquired PHA dependent upon cause


  • Gender



    • No gender predilection except for HIV-associated acquired PHA, which is more common in males



  • Ethnicity



    • No ethnic predilection


Presentation



  • Incidental finding in familial PHA


  • Clinical findings variable in acquired PHA dependent on underlying cause


Laboratory Tests

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Jun 13, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Pelger-Huët Anomaly

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