Corticosteroid‐induced morphological changes in cells of the myeloid lineage
Authors: Sunyoung Lee, Pouya Khankhanian, John O. Mascarenhas
Journal: American Journal of Hematology (2015)

A 60-year-old woman with no known past medical history presented with generalized body swelling. She was found to have nephrotic range proteinuria and an elevated creatinine of 1.9 mg/dL with no known baseline creatinine. White blood cell count was 6,000/µL with an unremarkable manual differential: hemoglobin, 11.5 g/dL and platelet, 249,000/µL. Human immunodeficiency virus was negative, and vitamin B12 and folic acid level were within normal limits. A renal biopsy demonstrated IgA nephropathy with additional features of focal crescent formation. The patient received intravenous pulse corticosteroids, followed by prednisone 60 mg daily. Her symptoms improved, and she was discharged on a monotherapy of prednisone 60 mg daily for a 6 month course. Peripheral blood smears were examined before initiation of steroid therapy, one month after, and after the discontinuation of steroid therapy. The 1-month blood smear showed morphological changes in the nuclei and granules of myeloid cells, which were not present on the initial blood smears and smears after steroid therapy was discontinued. Bone marrow biopsy was not considered due to low suspicion of underlying hematological diseases. In response to chronic steroid exposure, neutrophils displayed a variety of nuclear morphologies with a high degree of heterogeneity (Image 1). We observed ring-shaped nuclei (Image 1A) such as those reported in myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) with MDS-related features. Nuclear projections including clubs and hooks (Image 1B,C), previously reported in patients with androgen-secreting tumors 1, were also seen. These clubs and hooks are distinct from “drumstick” projections which represent Barr bodies 1. We observed hypo-segmentation of nuclei (pseudo-Pelger-Huët anomaly, Image 1C) 2, which have been documented in MDS, AML with MDS-related features, or severe infections. Hyper-segmented nuclei were also seen (Image 1D), as has been previously reported in vitamin B12 deficiency. We also observed a highly clumped single-lobed nucleus (Image 1E), a form of granulocytic dysplasia seen in MDS or AML with MDS-related features. Multiple nuclear lobes connected with long intersegmental filaments (“Pseudo-myelokathexis”, Image 1F) were seen, as has been shown in the WHIM syndrome (warts, hypogammaglobulinemia, infections, and myelokathexis) 3. Neutrophils in a patient with IgA nephropathy on prednisone 60 mg daily for more than one month. (A) Shows a closed loop or ring-shaped nucleus. (B) Demonstrates a nuclear club in the upper lobe of the nucleus. The neutrophil in (C) is a pseudo-Pelger-Huët cell with nuclear hooks in the upper lobe of the nucleus. (D) An example of hyper-segmented neutrophils. A neutrophil in (E) is mono-lobed with a highly clumped chromosome. Nuclear lobes in (F) are interconnected via thin filaments, resembling myelokathexis in the WHIM syndrome. Wright's stain, ×1,000. Nuclei of eosinophils also displayed a wide range of morphological changes and heterogeneity in response to steroid exposure (Image 2). Nuclear projections (Image 2A,C,F) were seen, such as those reported in patients with AML 4. While nuclear projections have been previously demonstrated in steroid-exposed neutrophils, to our knowledge they have never been reported in eosinophils. We observed hypolobated eosinophils (Image 2B), termed pseudo-Pelger-Huët anomaly of eosinophils seen in MDS or AML with MDS-related features 5. A number of hypersegmented eosinophils (Image 2C) were also seen on peripheral smears, a morphology reported in vitamin B12 deficiency, MDS, or AML with MDS-related features. Many eosinophils showed “satellite” nuclear lobes, highly clumped and lightly stained but smaller than other lobes of eosinophils (Image 2D). A large number of eosinophils had cytoplasmic clearing with reduced cytoplasmic areas occupied by eosinophilic granules (Image 2A,E,F), a feature reported in patients with hypereosinophilic syndrome 6, 7. Another striking feature was eosinophils with both eosinophilic and basophilic granules (Image 2A,C,D,F), previously reported as pro-eosinophilic granules in chronic myeloid leukemia or AML with inv(16)(p13.1q22) 8, 9. Eosinophils in a patient on prednisone 60 mg daily for more than one month. (A) Shows dysmorphic nucleus with clubs and hooks. The cytoplasm reveals cytoplasmic clearing and basophilic granules. The eosinophil in (B) demonstrates pseudo-Pelger-Huët anomaly with an indented single-lobed nucleus. (C) Shows a hyper-segmented nucleus. This cell displays basophilic cytoplasmic granules. (D) An example of a large number of eosinophils demonstrating a “satellite” nuclear lobe that is highly clumped, lightly stained, and smaller than other lobes. This cell also shows a small number of basophilic cytoplasmic granules. (E) An eosinophil with a highly clumped chromosome and a large degree of cytoplasmic clearing. (F) A bi-lobed eosinophil with cytoplasmic clearing, basophilic granules, and a nuclear hook in the lower lobe. Wright's stain, ×1,000. Steroid-exposed basophils were partially degranulated with cytoplasmic vacuoles abundant near the plasma membrane. Normally, basophillic granules are uniformly distributed in size, but the steroid-exposed basophils demonstrated granules of variable size (Image 3A). These features of steroid-exposed basophils are similar to morphological abnormalities reported in AML 10. In response to steroid exposure, monocytes showed pseudo-Pelger-Huët anomaly with irregular nuclear membrane contour (Image 3B) as previously reported in a leukemoid reaction or severe infection 5. Another striking feature of steroid-exposed monocytes was nuclear projections (Image 3C), which to our knowledge has not been reported previously. A basophil and monocytes in a patient on prednisone 60 mg daily for more than one month. A basophil in (A) reveals the cytoplasmic granules displaying a large degree of heterogeneity in size with empty granules near the plasma membrane, suggesting partial degranulation. A monocyte in (B) shows a highly dysmorphic nucleus, previously reported as monocytic pseudo-Pelger-Huët anomaly. (C) Displays a highly clumped nucleus with a nuclear club in a monocyte. Wright's stain, ×1,000.