Pelger-Huet Anomaly Workup

Updated: Aug 04, 2020
  • Author: Vikramjit S Kanwar, MBBS, MBA, MRCP(UK); Chief Editor: Hassan M Yaish, MD  more...
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Laboratory Studies

The diagnosis of Pelger-Huët anomaly (PHA) is based on the morphologic characteristics of the neutrophils observed on peripheral blood film examination. When a complete blood count (CBC) is requested, digital analyzers will report a shift to the left without identifying the specific anomaly of the neutrophils.

Neonatologists frequently utilize the ratio of mature to immature neutrophils reported by autoanalyzers for evaluating the risk of sepsis in the neonate. In the rare newborn with PHA, this can lead to a report of large numbers of immature neutrophils and an incorrect diagnosis of sepsis. Unless a peripheral blood smear is examined, the anomaly will not be identified and the report will be deceiving to the neonatologist. [19]

Examination of a peripheral blood smear in an individual heterozygous for PHA is remarkable for neutrophils with a predominance of bilobed, spectacle-shaped nuclei, an appearance often described as pince-nez. Neutrophils with bilobed nuclei make up 60-90% of the neutrophils seen; those with a single, nonlobulated nucleus account for 10-40%, with normal-appearing neutrophils with three-lobed nuclei sometimes accounting for as little as 10%. Most neutrophils have excessively coarse clumping of the nuclear chromatin. 

Although extremely rare, the homozygous state results in neutrophils that contain a single, round, eccentric nucleus with clumped chromatin and little or no nuclear segmentation, and basophils, eosinophils, and megakaryocytes also show dense nuclear chromatin and rounded nuclear lobes. The bone marrow of homozygous patients reveals normal morphologic features in the myeloid precursors to the myelocyte stage.

When Pelger-Huët cells are identified, initially attempt to determine if the patient has a benign inherited anomaly or an acquired morphologic feature (ie, pseudo–Pelger-Huët anomaly). In pseudo–Pelger-Huët anomaly, cells may appear morphologically similar to PHA, but absence of these findings in other family members, a low percentage of affected cells (usually 5-20%), and involvement of other cell lines (eg, anemia or thrombocytopenia) suggest an acquired anomaly. Pseudo-PHA may be predictive of the clinical onset of myelodysplastic disorders, myeloid leukemias, or myelofibrosis, and bone-marrow aspiration and biopsy may be warranted. A molecular technique that extracts and analyzes the nuclear skeleton can also be used to differentiate PHA from pseudo-PHA with a sensitivity and specificity of over 80% but is not in routine use. [20]

A study by Sasada et al found that on hematopoietic cell images from peripheral blood smears belonging to patients with myelodysplastic syndrome, observers often missed signs of pseudo–Pelger-Huët anomaly (pseudo-PHA) unless nuclei had the characteristic pince-nez appearance. Cytoplasmic hypogranularity was also often not recognized on the images. The investigators suggested that in order to increase the likelihood that myelodysplastic syndrome will be accurately diagnosed, morphologic cell classification must be further standardized and automatic cell classification–supporting devices need to be developed. [21]