Morphological Variations of Neutrophils Nuclear Appendages: Sex-Based Differences and Contextual Insights from Sudan

Abstract

Background: Neutrophil nuclear morphology, with its typical multilobation and other nuclear appendages, is a complex and intriguing area of study.  The sex-chromatin drumstick, a well-acknowledged physical characteristic in females, is indicative of the dormant X chromosome. However, its identification is often complicated by non-specific nuclear projections, including sessile nodules, tags, clubs, and hooks, which can manifest in both sexes. The accurate distinction between authentic sex-chromatin appendages and non-specific variations underscores the importance of morphological precision and diagnostic expertise.

Objective: To examine and elucidate the morphological spectrum of neutrophil nuclear appendages, highlight sex-based disparities, and address diagnostic factors pertinent to the Sudanese setting.

Materials and Methods: A narrative mini-review style was used to synthesize insights from traditional hematology literature and contemporary studies (2018–2024) on neutrophil nuclear morphology, sex-chromatin characteristics, and morphological aberrations, including drumstick and sessile nodule alterations.  Local environmental, dietary, and viral aspects relevant to Sudan were integrated to offer contextual interpretation.  A functional text-based diagnostic flowchart was created for laboratory use. 

Results: True drumstick appendages are present in roughly 1–5% of neutrophils in females and are characterized morphologically by a tiny, compact spherical head linked by a slender filament.  Non-specific appendages, such as sessile nodules, tags, and hooks, are devoid of this distinguishing filament and are present in both sexes.  The Pelger-Huët anomaly (PHA) and acquired pseudo-Pelger-Huët anomaly (PPHA) have distinctive bilobed ("pince-nez") nuclei that are not associated with sex chromatin.  In Sudan, folate insufficiency, tuberculosis, HIV infection, and drug exposure may induce morphological heterogeneity and complicate interpretation.

Conclusion: Accurate identification of authentic drumstick morphology necessitates stringent criteria to prevent misdiagnosis. Drumsticks indicate sex chromatin; however, other nuclear appendages are non-specific and should not be utilized for sex determination. Nutritional and pathogenic variables may alter neutrophil morphology in the Sudanese population; therefore, local reference data are necessary. The included diagnostic flowchart facilitates uniform classification and reporting in resource-constrained laboratory settings.

Keywords:

Neutrophil morphology, Drumstick appendage, Sex chromatin, Pelger-Huët anomaly, Sudan, Peripheral smear, Hypersegmentation

References

Bashir Abdrhman Bashir. Peripheral Blood Picture; The Science Beyond the Technique. IJCMCR. 2023; 25(1): 005.

Manley HR, Keightley MC, Lieschke GJ. The Neutrophil Nucleus: An Important Influence on Neutrophil Migration and Function. Front Immunol. 2018 Dec 4;9:2867. doi: 10.3389/fimmu.2018.02867. PMID: 30564248; PMCID: PMC6288403.

Sharmila Tupakula, Subhadra devi Velichety, Thyagaraju K. SEXUAL DIMORPHISM IN MORPHOLOGY AND MORPHOMETRY OF NEUTROPHIL DRUMSTICKS. Int J Anat Res 2014;2(4):720-726. DOI: 10.16965/ijar.2014.510

Miknienė Z, Ivanauskaitė R. Sex Chromatin in Peripheral Blood Neutrophils and Sex Determination. Case Reports in Clinical Medicine. 2018;7(1):55–62.

Zilio S, Serafini P. Neutrophils and Granulocytic MDSC: The Janus God of Cancer Immunotherapy. Vaccines (Basel). 2016 Sep 9;4(3):31. doi: 10.3390/vaccines4030031. PMID: 27618112; PMCID: PMC5041025.

Pattamshetty P, Mantri H, Mohan V. Rare Disorder of Sexual Differentiation with a Mosaic 46, XX/47, XXY in a Klinefelter Syndrome Individual. J Reprod Infertil. 2020 Jul-Sep;21(3):222-224. PMID: 32685420; PMCID: PMC7362088.

Salafranca J, Ko JK, Mukherjee AK, Fritzsche M, van Grinsven E, Udalova IA. Neutrophil nucleus: shaping the past and the future. J Leukoc Biol. 2023 Nov 24;114(6):585-594. doi: 10.1093/jleuko/qiad084. PMID: 37480361; PMCID: PMC10673716.

Padmapriya, B; Venkata Satya Kartheek, B; Bodhireddy, Sridhar Reddy; Atla, Bhagyalakshmi. Pelger-Huet anomaly: A Rare case report. Journal of Dr. NTR University of Health Sciences 9(4):p 255-258, Oct–Dec 2020. | DOI: 10.4103/JDRNTRUHS.JDRNTRUHS_23_20

Ayan MS, Abdelrahman AA, Khanal N, Elsallabi OS, Birch NC. Case of acquired or pseudo-Pelger-Huët anomaly. Oxf Med Case Reports. 2015 Apr 1;2015(4):248-50. doi: 10.1093/omcr/omv025. PMID: 26634137; PMCID: PMC4664885.

Kwiecień I, Rutkowska E, Gawroński K, Kulik K, Dudzik A, Zakrzewska A, Raniszewska A, Sawicki W, Rzepecki P. Usefulness of New Neutrophil-Related Hematologic Parameters in Patients with Myelodysplastic Syndrome. Cancers (Basel). 2023 Apr 26;15(9):2488. doi: 10.3390/cancers15092488. PMID: 37173954; PMCID: PMC10177198.

Hellebrekers P, Vrisekoop N, Koenderman L. Neutrophil phenotypes in health and disease. Eur J Clin Invest. 2018 Nov;48 Suppl 2(Suppl Suppl 2): e12943. doi: 10.1111/eci.12943. Epub 2018 May 25. PMID: 29682724; PMCID: PMC6282827.

Atallah-Yunes SA, Ready A, Newburger PE. Benign ethnic neutropenia. Blood Rev. 2019 Sep; 37:100586. doi: 10.1016/j.blre.2019.06.003. Epub 2019 Jun 21. PMID: 31255364; PMCID: PMC6702066.

Homeida A. The complexities of conflict-induced severe malnutrition in Sudan. BMJ Glob Health. 2023 Dec 18;8(12):e014152. doi: 10.1136/bmjgh-2023-014152. PMID: 38114238; PMCID: PMC10749032.

Htwe TT, Anis S, Nurul A, Syuhada AM, Zafira N, Ismail S. Detection of Nuclear Appendage in Peripheral Blood Neutrophil Leukocytes for Sex Determination. Asian J Med Health Sci. 2019;2 (2): 23 – 29.

Lokwani R, Wark PAB, Baines KJ, Barker D, Simpson JL. Hypersegmented airway neutrophils and its association with reduced lung function in adults with obstructive airway disease: an exploratory study. BMJ Open. 2019 Jan 28;9(1): e024330. doi: 10.1136/bmjopen-2018-024330. PMID: 30696679; PMCID: PMC6352776.

Sharifi MJ, Gheibi N, Panahi F, Sharifzadeh S, Nasiri N. MDS-Type Morphologic Abnormalities of Peripheral Blood Granulocytes in Symptomatic COVID-19 Patients. Int J Hematol Oncol Stem Cell Res. 2024 Jul 1;18(3):249-253. doi: 10.18502/ijhoscr. v18i3.16105. PMID: 39257703; PMCID: PMC11381661.

Shahzad M, Ali F, Shirazi SH, Rasheed A, Ahmad A, Shah B, Kwak D. Blood cell image segmentation and classification: a systematic review. PeerJ Comput Sci. 2024 Feb 2;10: e1813. doi: 10.7717/peerj-cs.1813. PMID: 38435563; PMCID: PMC10909159.

Ayan MS, Abdelrahman AA, Khanal N, Elsallabi OS, Birch NC. Case of acquired or pseudo-Pelger-Huët anomaly. Oxf Med Case Reports. 2015 Apr 1;2015(4):248-50. doi: 10.1093/omcr/omv025. PMID: 26634137; PMCID: PMC4664885.

Wang E, Boswell E, Siddiqi I, Lu CM, Sebastian S, Rehder C, Huang Q. Pseudo-Pelger-Huët anomaly induced by medications: a clinicopathologic study in comparison with myelodysplastic syndrome-related pseudo-Pelger-Huët anomaly. Am J Clin Pathol. 2011 Feb;135(2):291-303. doi: 10.1309/AJCPVFY95MAOBKRS. PMID: 21228370.

Chen MH, Raffield LM, Mousas A, Sakaue S, Huffman JE, Moscati A, Trivedi B, Jiang T, et al. Trans-ethnic and Ancestry-Specific Blood-Cell Genetics in 746,667 Individuals from 5 Global Populations. Cell. 2020 Sep 3;182(5):1198-1213.e14. doi: 10.1016/j.cell.2020.06.045. PMID: 32888493; PMCID: PMC7480402.

Moro RN, Johnson JL, Martinson N, Muzanyi G, Leung CC, Chang KC, Waja Z, Goldberg SV. Differences in Neutrophil Counts Between African and non-African Countries in two International Clinical Trials. J Infect Dis. 2025 May 31:jiaf291. doi: 10.1093/infdis/jiaf291. Epub ahead of print. PMID: 40447276.