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Pseudo-Pelger-Huet anomaly occurring with the use of mycophenolate mofetil and ganciclovir following renal transplantation.

Pseudo-Pelger-Huet anomaly occurring with the use of mycophenolate mofetil and ganciclovir following renal transplantation.
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Author: Dr Rupali Parikh M.D; Dr Paresh Marathe M.D; Dr Maya Parihar Malhotra M.D; Dr Richa Bhartiya M.D
Category: Laboratory Hematology > Basic cell morphology > Morphologic variants of white blood cells > Hyposegmented neutrophil  
Published Date: 05/31/2022

Pseudo-Pelger-Huet Anomaly can be present in congenital or acquired forms. The acquired form referred as Pseudo Pelger Huët anomaly (PPHA) which is a marker of granulocytic dysplasia seen in myelodysplastic syndrome (MDS). It can also be seen in acute Myeloid Leukemia, infections like Tuberculosis, Mycoplasma and with use of certain drugs such as immunosuppressants.1, 2

Pelger Huët cells are morphologically abnormal neutrophils characterized by abnormal condensation of chromatin, hypolobation and round, oval, or symmetrically bilobed nucleus (dumb bell shaped) with normal cell size and cytoplasmic granules.

A 57year-old female patient presented with history of renal transplantation. An automated complete blood count (CBC) demonstrated Hemoglobin 70g/L (reference range 130-160g/L), white blood cell count 2.2 x 109/L (reference range 4-10 x 10 9/L) Platelet count 146 x 10 9/L (reference range 150-450 x 109/L), Absolute neutrophil count 1.4 x 10 9/L (reference range 2-7 x 109/L). A concurrent peripheral blood smear showed few unilobed neutrophils with clumped chromatin and pink cytoplasm suggestive of Pelger Huët anomaly. (Figure-A to F) On further investigation we found that the patient was receiving mycophenolate mofetil in combination with Ganciclovir.

The drugs commonly implicated in development of this morphological anomaly are in patients of transplant medications like Tacrolimus,  mycophenolate mofetil, ganciclovir, cotrimoxazole, Itraconazole, fludrabine, lorezepam, rituximab & citralopam.2

In medication induced pseudo Pelger Huët anomaly neutrophils are unilobed, hyposegmented and show excessive nuclear clumping.2 unlike MDS, which is classically characterized by bilobed neutrophils. This morphologic difference can be exploited in the diagnostic dilemma of MDS, AML-MRC, and drug-induced PPHA

These changes are reversible in neutrophils as neutrophils resume their normal morphology on drug dose reduction or discontinuation

Therefore it is of extreme importance to differentiate Pseudo Pelger Het anomaly in MDS/ Acute Myeloid Leukemia, or possible myeloproliferative disorder form other acquired causes to prevent unnecessary investigation. 3, 4

peripheral blood smear examination by pathologist and awareness of drug induced Pseudo Pelger Huët anomaly by clinician can prevent unnecessary work up leading to improved patient care.

References

1. Cunningham JM, Patnaik MM, Hammerschmidt DE, Vercellotti GM. Historical perspective and clinical implications of the Pelger-Hüet cell.Am J Hematol.2009;84(2):116–9.

2. Wang E, Boswell E, Siddiqi I, et al. Pseudo-pelger-Huët anomaly induced by medications: a clinic pathologic study in comparison with myelodysplastic syndrome-related pseudopelger-Huët anomaly. Am J Clin P.

3. Asmis LM, Hadaya K, Majno P, et al. Acquired and reversible Pelger-Huët anomaly of polymorphonuclear neutrophils in three transplant patients receiving mycophenolate mofetil therapy. Am J Hematol.2003;73(4):244–8.

4. Arnand M Kumar R Raina V. Pelger Huët anomaly: a case report. Indian J Pathol Microbiol.2007; 50(3):661–2. 10. Best S, Salvati F, Kallo J, et al. Lamin B-receptor mutations in Pelger-Huet anomaly. Br J Haematol.2003;123(3):542–544.