Myelokathexis and Monocytosis in a Patient with Gastric Cancer

Maran, R.; Mittelman, Moshe; Cohen, Amos; Djaldetti, M

doi:10.1159/000204770

Cited by 11 publications

(9 citation statements)

References 7 publications

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“…Although infection susceptibility is on the contrary almost always present, severe infections are rare. Finally, myelokathexis is not pathognomomic of WS, as it is observed in other situations such as in neutropenia linked to the glucose 6 phosphatase, catalytic subunit 3 ( G6PC3) [57], CXCR2 loss-of-function mutations [58] or in gastric cancer [59]. In addition, for three patients from this study, BM smears were initially described as showing only an absence of myeloid blockage, while we identified the typical multi-lobular nuclei of myelokathexis only at the time of the central review.…”

Section: Discussionmentioning

confidence: 99%

Description and outcome of a cohort of 8 patients with WHIM syndrome from the French Severe Chronic Neutropenia Registry

Beaussant-Cohen

Fenneteau

Plouvier

et al. 2012

Orphanet J Rare Dis

107

130

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BackgroundWHIM syndrome (WS), a rare congenital neutropenia due to mutations of the CXCR4 chemokine receptor, is associated with Human Papillomavirus (HPV)-induced Warts, Hypogammaglobulinemia, bacterial Infections and Myelokathexis. The long term follow up of eight patients highlights the clinical heterogeneity of this disease as well as the main therapeutic approaches and remaining challenges in the light of the recent development of new CXCR4 inhibitors.ObjectiveThis study aims to describe the natural history of WS based on a French cohort of 8 patients.MethodsWe have reviewed the clinical, biological and immunological features of patients with WS enrolled into the French Severe Chronic Neutropenia Registry.ResultsWe identified four pedigrees with WS comprised of eight patients and one foetus. Estimated incidence for WS was of 0.23 per million births. Median age at the last visit was 29 years. Three pedigrees encompassing seven patients and the fetus displayed autosomal dominant heterozygous mutations of the CXCR4 gene, while one patient presented a wild-type CXCR4 gene. Two subjects exhibited congenital conotruncal heart malformations. In addition to neutropenia and myelokathexis, all patients presented deep monocytopenia and lymphopenia. Seven patients presented repeated bacterial Ears Nose Throat as well as severe bacterial infections that were curable with antibiotics. Four patients with late onset prophylaxis developed chronic obstructive pulmonary disease (COPD). Two patients reported atypical mycobacteria infections which in one case may have been responsible for one patient’s death due to liver failure at the age of 40.6 years. HPV-related disease manifested in five subjects and progressed as invasive vulvar carcinoma with a fatal course in one patient at the age of 39.5 years. In addition, two patients developed T cell lymphoma skin cancer and basal cell carcinoma at the age of 38 and 65 years.ConclusionsContinuous prophylactic anti-infective measures, when started in early childhood, seem to effectively prevent further bacterial infections and the consequent development of COPD. Long-term follow up is needed to evaluate the effect of early anti-HPV targeted prophylaxis on the development of skin and genital warts.

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Section: Discussionmentioning

confidence: 99%

Description and outcome of a cohort of 8 patients with WHIM syndrome from the French Severe Chronic Neutropenia Registry

Beaussant-Cohen

Fenneteau

Plouvier

et al. 2012

Orphanet J Rare Dis

107

130

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“…Myelokathexis, however, is also characterised by accumulations of hypersegmented neutrophils with dense pyknotic nuclei (13) (14) and the presence of binucleate myelocytes (15), but these features were not seen in the affected pups.…”

Section: Discussionmentioning

confidence: 99%

“…The female pup's rectal temperature was greater than 39.0 °c on 3 out of the 10 days that it was recorded. She was able to walk with an awkward gait on days [12][13][14][15][16][17][18] but for the remainder of the 23 days that she was hospitalised she was unable to stand. No diarrhoea was observed.…”

Section: History and Clinical Findingsmentioning

confidence: 99%

Neutropenia with a probable hereditary basis in Border Collies

Allan

Thompson

Jones

et al. 1996

New Zealand Veterinary Journal

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This paper documents a disease of Border Collies characterised by chronic neutropenia which probably resulted in recurrent bacterial infections manifesting as osteomyelitis and sometimes gastroenteritis. The neutropenia occurred despite hyperplasia of the myeloid cells in the bone marrow and a shift to the right in myeloid cell maturation. The underlying defect is currently unknown but may result from the inability of neutrophils to escape from the bone marrow into the peripheral circulation. Necrosis and new bone formation commonly involved the metaphyseal regions of long bones. Other findings included a fasting hypercholesterolaemia and the occasional presence of nucleated red blood cells in circulation, despite a non-regenerative anaemia. An autosomal recessive mode of inheritance is suspected. This condition has some features of a rare human disease called myelokathexis which is also believed to have in autosomal recessive mode of inheritance.

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“…This condition accounts for an increased myeloid:erithroid ratio in BM caused by hypercellularity of mature neutrophils, especially clustered next to the vessels that show aberrant morphology with nuclear hypersegmentation, cytoplasmic vacuolization, and separated nuclear lobes connected by bridges of chromatin (3, 4). In literature, few other conditions, like hematological or solid neoplasia, are characterized by hypersegmentation of chromatin and early apoptosis of neutrophils (5, 6). Further, myelokathexis has been reported to be associated with retardation of skeletal growth and other malformations (7).…”

Section: Discussion and Concluding Remarksmentioning

confidence: 99%

Dysplasia of Granulocytes in a Patient with HPV Disease, Recurrent Infections, and B Lymphopenia: A Novel Variant of WHIM Syndrome?

et al. 2017

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WHIM syndrome is a condition in which affected persons have chronic peripheral neutropenia, lymphopenia, abnormal susceptibility to human papilloma virus infection, and myelokathexis. Myelokathexis refers to the retention of mature neutrophils in the bone marrow (BM), which accounts for degenerative changes and hypersegmentation. Most patients present heterozygous autosomal dominant mutations of the gene encoding CXCR4. Consequently, aberrant CXCL12/CXCR4 signaling impairs the receptor downregulation causing hyperactivation (gain-of-function) that affects BM homing for myelopoiesis and lymphopoiesis and the release of neutrophils in the bloodstream. We report the case of a 26-year-old female with severe foot and hand cutaneous warts since childhood, recalcitrant genital condylomatas, bacterial infections, and intraepithelial cervical neoplasia. Laboratory tests revealed severe B lymphopenia and HPV high and low risk types. HIV testing was negative. Not only CXCR4 but also GATA2, NEMO, and CD40L gene mutations were excluded. BM smears revealed, in the presence of a normal cellularity, hyperplasia of myeloid cells (MPO positive) and karyorrhexis, especially in neutrophils and eosinophils. Of note, neutrophils with altered lobation of nuclei connected by long thin chromatin filaments were observed. Our patient presented a clinical and histological picture reminiscent of WHIM in the presence of normal peripheral neutrophil counts and wild-type CXCR4 gene. Although the BM did not reveal a classical pattern of myelokathexis, the observation of consistent signs of neutrophil dysplasia has fuelled the hypothesis of a novel WHIM variant or a novel immunodeficiency. We speculate that abnormalities that affect CXCR4/CXCL12 pair, including GRK levels or activity, might be responsible for this WHIM-like disorder.

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Myelokathexis and Monocytosis in a Patient with Gastric Cancer

Cited by 11 publications

References 7 publications

Description and outcome of a cohort of 8 patients with WHIM syndrome from the French Severe Chronic Neutropenia Registry

Description and outcome of a cohort of 8 patients with WHIM syndrome from the French Severe Chronic Neutropenia Registry

Neutropenia with a probable hereditary basis in Border Collies

Dysplasia of Granulocytes in a Patient with HPV Disease, Recurrent Infections, and B Lymphopenia: A Novel Variant of WHIM Syndrome?

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