pseudo-Pelger-Huet

Pseudo-Pelger-Huët (pseudo-PH) anomaly describes neutrophils with abnormal nuclear hyposegmentation (typically bilobed with coarse, clumped chromatin) that resemble those seen in the true Pelger-Huët anomaly, a benign autosomal dominant condition caused by mutations in the LBR (lamin B receptor) gene. Unlike the inherited form, pseudo-PH is an acquired finding and is a red flag for underlying pathology.

Causes include: - Myelodysplastic syndromes (MDS) - most important association; pseudo-PH cells are considered a dysplastic feature of the granulocytic lineage. - Acute myeloid leukemia (especially post-chemotherapy/therapy-related AML). - Myeloproliferative neoplasms. - Drug effects (e.g., chemotherapy agents like mycophenolate mofetil, sulfonamides, colchicine). - Severe infections or sepsis (transient). - HIV infection.

Pathophysiology: The exact mechanism in acquired cases is not fully understood but is thought to relate to disordered granulocyte maturation and nuclear segmentation, often reflecting clonal hematopoiesis or marrow stress in MDS, or direct cytotoxic/antimetabolite effects on dividing myeloid precursors.

Clinical significance: On peripheral blood smear, finding pseudo-PH cells (especially along with other dysplastic features like hypogranular cytoplasm, Döhle bodies, or abnormal platelet morphology) should prompt consideration of MDS and warrant further workup including CBC with differential, bone marrow biopsy, and cytogenetic analysis. Distinguishing pseudo-PH from true Pelger-Huët is done via clinical history (acquired vs. congenital), family history, and the presence of other cytopenias/dysplastic features. True Pelger-Huët is benign and does not require treatment, whereas pseudo-PH signals investigation into potentially serious underlying disease.

Key distinguishing feature: in true Pelger-Huët, ALL neutrophils typically show the bilobed/hyposegmented pattern uniformly; in pseudo-PH, there is more heterogeneity in the degree of hyposegmentation and often coexisting dysplastic features in other cell lines.