Pseudo-Pelger-Huet anomaly

Pseudo-Pelger-Huet anomaly describes neutrophils with abnormal nuclear hyposegmentation (typically bilobed, dumbbell, or peanut-shaped nuclei with coarse, clumped chromatin) that are morphologically identical to the congenital Pelger-Huet anomaly but occur as an acquired phenomenon. Unlike the hereditary form, which results from autosomal dominant mutations in the LBR (lamin B receptor) gene and is a benign finding with normal neutrophil function, pseudo-Pelger-Huet cells indicate underlying hematologic or systemic disease.

Causes include myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) transformation—where it reflects dysplastic granulopoiesis—as well as exposure to cytotoxic chemotherapy or drugs (e.g., sulfonamides, ganciclovir), severe infections (e.g., HIV, mycoplasma, tuberculosis), and other marrow stress states. It is also an important feature of MDS classification, where dysplastic neutrophils with hypolobation are counted among the dysplastic features used for diagnosis.

Clinically, differentiating true (congenital) from pseudo (acquired) Pelger-Huet anomaly requires clinical context: family history and lifelong stable blood counts favor congenital Pelger-Huet, while new-onset cytopenias, abnormal blood counts, or history of chemotherapy favor the acquired pseudo form. Peripheral blood smear review showing coarse chromatin clumping (vs. the fine, evenly dispersed chromatin of true Pelger-Huet) can be a distinguishing microscopic feature. Bone marrow biopsy may be needed to evaluate for MDS if pseudo-Pelger-Huet cells are identified, especially in the setting of unexplained cytopenias.

This anomaly is high-yield because it serves as a peripheral smear clue pointing toward MDS, a key differential in cases of unexplained cytopenia, especially in older patients, and underscores the importance of correlating morphology with clinical history.