case report

The Two Types of Detached Nuclear Fragments Behind the Howell-Jolly Eponyme

Margarida Dantas Brito1*, Kristin Singsdal2, Harald Holte1

1Department of Lymphoma, The Norwegian Radium Hospital, Oslo University Hospital, Norway

2Haematology laboratory, The Norwegian Radium Hospital, Oslo University Hospital, Norway

*Corresponding author: Margarida Dantas Brito, Department of Lymphoma, The Norwegian Radium Hospital, Oslo University Hospital, Norway. Email: ana.margarida.dantas@gmail.com

Received Date: 18 April, 2018; Accepted Date:  27 April, 2018; Published Date: 08 May, 2018

Citation: Brito MD, Singsdal K, Holte H (2018) The Two Types of Detached Nuclear Fragments Behind the Howell-Jolly Eponyme. Hem Disease Therapies: JHDT-114. DOI: 10.29011/2577-1418. 000014


1.       Case

We share the photographs of a blood film where the neutrophils exhibit morphological changes, including the rare Howell-Jolly like bodies. The patient was a 74-year-old man with a history of lymphoplasmacytic lymphoma treated with several chemotherapy regimens over the last 10 years. At the time he had disease progression and histological transformation to large B-cell lymphoma. He was under cytostatic treatment with R-CHOP protocol and G-CSF. He was admitted with neutropenic fever and the blood film showed neutrophils with dysplastic features. There were nuclear segmentation abnormalities (Figures1-2), polarized granules and cytoplasmic vacuoles (Figure 2).

All these changes are often seen after cytotoxic chemotherapy, G-CSF and severe infection. Additionally, the cells showed what is known to be detached nuclear fragments (Figures 1-3). This is quite rare and might confuse an unaware microscopist. These fragments are named Howell-Jolly like bodies due to their morphological similarity to the erythrocytic Howell-Jolly bodies. In this article we review the two types of detached nuclear fragments named after the Howell-Jolly eponyme.

The Howell-Jolly bodies are found in red cells and were first described in the early years of the 20th century [1].  They are nuclear remnants and can arise as a result of chromosomes separated from the mitotic spindle during abnormal mitosis or as a result of karyorrhexis at terminal stages of maturation [2]. This morphological finding is rather common in red cells and often related with increased red cell production (hemolytic anemia) or abnormal nuclear maturation (as megaloblastic anemia, where sometimes there are multiple Howell-Jolly bodies in a single red cell). It is seen in asplenic patients or patients with decreased splenic function. It can be a clue to functional hyposplenism as seen in poorly controlled celiac disease, ulcerative colitis and Crohn’s disease, where the severity of the hyposplenism fluctuates with the activity of the disease [3-4]. It is a morphological finding that can be diagnostically important and should alert the physician [5].

Howell-Jolly like bodies in neutrophils have been reported in a small number of case reports [6-10]. It is proven that they are nuclear fragments, but the mechanism that causes the occurrence of these structures remains unknown [11-12] They do not represent a specific disease entity, but are invariably associated with impaired immunity. They can appear as feature of dysplastic granulopoiesis secondary to immunosuppressive therapy as chemotherapy [6] azathioprine [5] tacrolimus monotherapy [8] or in combination with mycophenolate mofetil [10]. Howell-Jolly like bodies are also reported in patients with acquired immunodeficiency syndrome [7-13], after G-CSF [14] and in cases of ganciclovir induced neutropenia [15]. Howell-Jolly like bodies have been described in the whole granulocytic lineage [16].

They are not a typical feature of myelodysplastic syndrome. In certain geographical regions this morphological finding can raise alarm for infectious diseases that can course with cytoplasmic inclusions in neutrophils as Anaplasmosis or Ehrlichiosis [17]. We believe the Howell-Jolly like bodies were secondary to chemotherapy or G-CSF in our patient´s case. A blood film some weeks after was morphologically unremarkable.


Figure 1: Neutrophils with abnormal nuclear segmentation, polarized granules and Howell-Jolly like bodies. Peripheral blood film, Wright-Giemsa stain, original magnification 400x.



Figure 2: Howell-Jolly like bodies. Peripheral blood film, Wright-Giemsa stain, original magnification 400x.



Figure 3: Howell-Jolly like bodies. Peripheral blood film, Wright-Giemsa stain, original magnification 400x.




1.                   Sears DA, Udden M (2012) Howell Jolly bodies: A brief historical review. The Am J Med Sci 343: 407-409.

Jensen WN, Moreno GD, Bessis MC (1965) An electron microscopic description of basophilic stippling in red cells. Blood 25: 933-943.

2.       Jensen WN, Moreno GD, Bessis MC (1965) An electron microscopic description of basophilic stippling in red

cells. Blood 25: 933-943.

3.                   Mathur SC, Hutchison RE, Mohi G (2017) Henry's Clinical Diagnosis and Management by Laboratory Methods, 23 ed. In: St. Louis, Missouri, Elsevier.

4.                   O’Grady JG, Stevens FM, Harding B, O’Gorman TA, McNicholl B, et al. (1984) Hyposplenism and gluten-sensitive enteropathy: Natural history, incidence, and relationship to diet and small bowel morphology. Gastroenterology 87: 1326-1331.

5.                   Bain BJ (2005) Diagnosis from the blood smear. Engl J Med 353: 498-507.

6.                   Bain BJ (1989) Blood Cells: A Practical Guide, 1st ed. In: Philadelphia, PA: J. B. Lippincott.

7.                   Slagel DD, Lager DJ, Dick FR (1994) Howell-Jolly body-like inclusions in the neutrophils of patients with acquired immunodeficiency syndrome. Am J Clin Pathol 101: 429-431.

8.                   Kahwash E, Gewirtz AS (2003) Howell-Jolly body-like inclusions in neutrophils. Arch Pathol Lab Med 127: 1389-1390.

9.                   Rowe RG, Esrick E (2015) Howell-Jolly-like bodies in neutrophils. Blood 125: 2729.

10.                Akhtari M, Waller EK (2009) Howell-Jolly body-like inclusions in neutrophils. Blood 114: 2860.

11.                Omman R, Kwong C, Shephered D, Molnar JA, Milind M. Velankar, et al. (2017) Revisiting Howell-Jolly Body-like cytoplasmic inclusions in neutrophils: A report of two cases and confirmation of nuclear origin. J Hematol 6: 101-104.

12.                Ong MC, Veillon DM, Nordberg ML, Cote lingam JD (2010) Karyopyknotic cytoplasmic inclusions in neutrophils. The Journal of the Louisiana State Medical Society: Official Organ of the Louisiana State Medical Society 162: 228-230.

13.                Bain BJ (1997) The haematological features of HIV infection. Br J Haematol 99: 1-8.

14.                Bain BJ, Nam D (2010) Neutrophil dysplasia induced by granulocyte colony-stimulating factor. Am J Hematol 85: 354.

15.                Ghosh K, Muirhead D, Christie B, Hiwase D (1999) Ultrastructural changes in peripheral blood neutrophils in a patient receiving ganciclovir for CMV pneumonitis following allogenic bone marrow transplantation. Bone Marrow Transplantation 24: 429-431.

16.                Revol B, Thiebaut-Bertrand A, Carré M, Bulabois CE, Pascal Mossuz et al. (2015) Quantification of HowellJolly bodylike inclusions in ganciclovir toxicity using CellaVision DM96 analyser, British Journal of Haematology 174.

17.                Bakken JS, Aguero-Rosenfeld ME, Tilden RL, Wormser GP, Horowitz HW, et al. (2001) Serial Measurements of Hematologic Counts during the Active Phase of Human Granulocytic Ehrlichiosis, Clinical Infectious Diseases 32: 862-870.

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