Neutrophilic Panniculitis in a Patient with Myelodysplastic Syndrome / 대한피부과학회지

Myelodysplastic syndrome (MDS) is a heterogeneous group of stem cell disorders characterized by morphological abnormalities of the erythroid, granulocytic, and megakaryocytic cells. Cutaneous lesions associated with MDS are classified as either specific or non-specific. Specific leukemic infiltrates are often referred to as leukemia cutis, and non-specific inflammatory lesions, historically called leukemids, include cutaneous infections, vasculitis, and neutrophilic dermatoses. We report the case of a 53-year-old man who had been diagnosed with MDS 8 months ago when he developed multiple erythematous tender nodules on the trunk and upper extremities for 8 days. Histopathologic findings from an erythematous nodule on his chest showed lymphohistiocytic and neutrophilic infiltration in the septa and periphery of the fat lobules consistent with neutrophilic panniculitis. Most neutrophils observed in our case had the pseudo-Pelger-Huet anomaly. Herein we present a rare case of neutrophilic panniculitis associated with MDS showing specific groups and the pseudo-Pelger-Huet anomaly.

Lymphohematopoietic licence: Sterol C-14 reductase activity of lamin B receptor (Lbr) is essential for neutrophil differentiation.

Bertie Wooster, PG Wodehouse’s fictional character, proudly fancied himself a writer for having once contributed an article (‘What the Well-Dressed Man Is Wearing’) to Milady’s Boudoir, his Aunt Dahlia’s weekly magazine for women. My conceit of expertise in vertebrate lamin B receptor (Lbr) research is slightly less dubious. I co-authored two papers (Papavinasasundaram and Kasbekar 1994 and Prakash et al. 1999) that established that the C-terminal two-thirds of Lbr has sterol Δ14,15 reductase activity. An interloping article (Silve et al. 1998) reached pretty much the same conclusion (and to my chagrin, garnered the lion’s share of the citations). So the recent demonstration by Peter Gaines and coworkers that the Lbr sterol reductase regulates differentiation of neutrophils (Subramanian et al. 2012) filled me with proprietary pride, especially since neutrophils are the most abundant white blood cells in circulation and present the critical first line of defence against infectious microbes. Lbr is an integral protein of the vertebrate nuclear envelope inner membrane. Its N-terminal ~200 residues are hydrophilic, bind to B-type lamins, DNA and HP1-type chromatin proteins, and provide a substrate for p34cdc2, a key mitotic protein kinase. The ~420 residue hydrophobic, membrane-spanning, C-terminal domain (CTD) with sterol reductase activity anchors the nucleoplasmic domain to the inner nuclear membrane. Mutations in human LBR cause Pelger-Huët anomaly (PHA), a benign dominant disorder characterized by hyposegmentation of the neutrophil nucleus (Hoffmann et al. 2002). A spontaneously aborted fetus with Greenberg/HEM dysplasia was homozygous for LBR mutations, and peripheral blood neutrophils from the fetus’ mother displayed PHA (Waterham et al. 2003). Greenberg/HEM dysplasia and PHA reflect the pleiotropism of LBR mutations. In mouse, the Lbr gene is defined by the ichthyosis (ic) mutations (Shultz et al. 2003). Neutrophils from ic/ic mice display bilobed or ovoid nuclei typical of PHA. Additionally, ic/ic homozyogotes exhibit sparse hair, decreased body size and occasionally hydrocephalus and syndactyly. It was of interest to understand the functional significance of the Lbr protein’s sterol reductase activity, especially since KO mice for another locus, Tm7sf2, that encodes SR-1, a 418 residue protein with 58% identity with the Lbr CTD and possessing sterol C−14 reductase activity, do not display an observable phenotype (Bennati et al. 2006, 2008). First, a quick flashback to another 1994 paper: Tsai et al. (1994) had shown that transduction of normal mouse bone marrow cells with a retroviral vector harbouring a dominant-negative retinoic acid receptor (RARα403) could reproducibly immortalize lymphohematopoietic progenitors as stem-cell-factor-dependent clonal lines, designated as EML cells for their ability to subsequently undergo erythroid, myeloid and lymphoid differentiation in vitro. A 3-day treatment of EML cells with stem cell factor, IL-3, and high concentrations of all-trans retinoic acid, and then washing and switching them into GM-CSF, induced their differentiation into promyelocytes, designated as EPRO cells (EML-derived promyelocytes), that can be maintained in GM-CSF. Treatment of EPRO cells with high concentrations of retinoic acid in the presence of GM-CSF induced them to terminally differentiate into mature neutrophils with characteristic nuclear lobulation and respiratory burst response phenotypes. Several years later, Gaines et al. (2008) generated EML- and EPRO-like cells frombonemarrow of a C57BL/6J-Lbric-J/Lbric-J (ic/ic) mouse and a normal (+/ic) littermate, and found that neutrophils derived from EPRO-ic/ic cells exhibited nuclear hypolobulation identical to that seen in ichthyosis mice and displayed a deficient respiratory burst, whereas those from.

Anomalía de Pelger Hüet: a propósito de un caso / Pelger-Hüet anomaly: apropos of a case

La anomalía de Pelger Hüet fue descrita inicialmente en 1928 por el médico holandés Pelger y su origen genético fue descubierto más tarde por el pediatra Hüet. Se transmite con un carácter autosómico dominante y consiste en una mutación del gen que codifica el receptor de la lámina B. A partir de esta mutación se producen alteraciones en el núcleo de los leucocitos, fundamentalmente en los neutrófilos, con afectación de la segmentación nuclear y trastornos en la cromatina. Presentamos a un paciente que fue ingresado en el hospital por una mordedura de animal y se describió en la lámina periférica la presencia de neutrófilos hipolobulados. El carácter familiar se confirmó por el hallazgo de esta alteración en la madre del paciente.

The Pelger-Hüet anomaly was described firstly in 1928 by the Holland physician Pelger and its genetic origin was discovered later by the pediatrician Hüet. It is transmitted with a dominant autosomal character and it is a mutation of the gene codifying the plate B receptor. Beginning from this mutation, the alteration of white cells core took place, mainly in neutrophils, with affectations of the nuclear segmentation and chromatin disturbances. We present a patient entering our hospital as a cause of an animal bite, and there were discovered hypolobulated neutrophils in the periferal plate. The familiar character was confirmed with the finding of this alteration in the patient's mother.

Estudo da anomalia de Pelger-Huët em núcleo familiar: [carta ao editor] / Pelger-Huët anomaly study in a family: [letter to the editor]

The Pelger-Huët anomaly is a dominant autosomal disease, characterized by the incomplete segmentation of the granulocytes nucleus without lost of the cellular function. The heterozygotes form of this anomaly is assintomatic and it did not possess physic meant, while the homozygote form is rare and can be lethal, being therefore, important differentiates of other infectious alterations. The pseudo-anomaly can occasionally be observed in cases of granulocitic leukemia, mieloproliferatives Diseases, some infections and after exposition the determined drugs. We evaluate eleven members of a familiar nucleus and, after the blood cells analysis, six of then had presented neutrophils and eosinophils with nuclei characteristic of the heterozygotes form of the Pelger-Huët anomaly. The recognition of this leukocyte anomaly, mainly in patients without infection and presenting great number of not segmented neutrophils, can prevent wrong interpretations of the blood cells count and unnecessary clinical and therapeutically behaviors.

A case of congenital Pelger-Huet anomaly

No abstract available.