Josef Feit

Cutaneous malignant lymphomas: Update 2006

Cutaneous lymphomas represent a unique group of lymphomas and are the second most frequent extranodal lymphomas. As with other neoplasias, the pathogenesis is based mainly on a stepwise accumulation of mutations of suppressor genes and oncogenes caused by genetic, environmental or infectious factors. The diagnostic work‐up includes clinical, histological, imaging and hematological investigations and in many cases immunohistochemical and molecular biological analyses.

Multiple Myeloma Associated IgA Pemphigus: Treatment With Bortezomib- and Lenalidomide-Based Regimen

Generally, monoclonal immunoglobulins do not bind an autologous antigen, except for some cases, when it causes immune damage to body’s own tissues. Vesiculopustulous dermatitis associated with immunoglobulin (Ig) A deposition in the epidermis represents an autoimmune skin manifestation of monoclonal gammopathy. It is commonly referred to as subcorneal pustular dermatosis type of IgA pemphigus.1 In our previous work, we reported on complete and long-term remission of multiple myeloma associated IgA pemphigus after treatment with a bortezomib (Velcade) based regimen.2 In this work, to our knowledge, we are the first to publish a convincing clinical remission and excellent drug tolerance of a subsequent lenalidomide (Revlimid) based regimen used in the same patient for management of the relapsed disease.

Sequestration of MBNL1 in tissues of patients with myotonic dystrophy type 2

The pathogenesis of myotonic dystrophy type 2 includes the sequestration of MBNL proteins by expanded CCUG transcripts, which leads to an abnormal splicing of their target pre-mRNAs. We have found CCUG(exp) RNA transcripts of the ZNF9 gene associated with the formation of ribonuclear foci in human skeletal muscle and some non-muscle tissues present in muscle biopsies and skin excisions from myotonic dystrophy type 2 patients. Using RNA-FISH and immunofluorescence-FISH methods in combination with a high-resolution confocal microscopy, we demonstrate a different frequency of nuclei containing the CCUG(exp) foci, a different expression pattern of MBNL1 protein and a different sequestration of MBNL1 by CCUG(exp) repeats in skeletal muscle, vascular smooth muscle and endothelia, Schwann cells, adipocytes, and ectodermal derivatives. The level of CCUG(exp) transcription in epidermal and hair sheath cells is lower compared with that in other tissues examined. We suppose that non-muscle tissues of myotonic dystrophy type 2 patients might be affected by a similar molecular mechanism as the skeletal muscle, as suggested by our observation of an aberrant insulin receptor splicing in myotonic dystrophy type 2 adipocytes.

Joint analysis of histopathology image features and gene expression in breast cancer.

BackgroundGenomics and proteomics are nowadays the dominant techniques for novel biomarker discovery. However, histopathology images contain a wealth of information related to the tumor histology, morphology and tumor-host interactions that is not accessible through these techniques. Thus, integrating the histopathology images in the biomarker discovery workflow could potentially lead to the identification of new image-based biomarkers and the refinement or even replacement of the existing genomic and proteomic signatures. However, extracting meaningful and robust image features to be mined jointly with genomic (and clinical, etc.) data represents a real challenge due to the complexity of the images.ResultsWe developed a framework for integrating the histopathology images in the biomarker discovery workflow based on the bag-of-features approach – a method that has the advantage of being assumption-free and data-driven. The images were reduced to a set of salient patterns and additional measurements of their spatial distribution, with the resulting features being directly used in a standard biomarker discovery application. We demonstrated this framework in a search for prognostic biomarkers in breast cancer which resulted in the identification of several prognostic image features and a promising multimodal (imaging and genomic) prognostic signature. The source code for the image analysis procedures is freely available.ConclusionsThe framework proposed allows for a joint analysis of images and gene expression data. Its application to a set of breast cancer cases resulted in image-based and combined (image and genomic) prognostic scores for relapse-free survival.

Complete remission of multiple myeloma associated scleredema after bortezomib-based treatment

Scleredema is a rare scleroderma-like fi bromucinosis characterized by progressive thickening of the skin caused by excessive collagen and mucin depositions in the dermis. Various treatment regimens have been proposed, however with inconsistent outcomes. Herein we are the fi rst to report a complete dermatological and hematological remission in a patient with multiple myeloma associated scleredema after bortezomib-based chemotherapy.

Dystrophic epidermolysis bullosa pruriginosa with autoantibodies against collagen VII

ejd.2012.1709 Auteur(s) : Hana JEDLICKOVA1 hana.jedlickova@fnusa.cz, Ralf MULLER2,a, Daniele CASTIGLIA3,a, Milica KOVACEVIC4, Josef FEIT5 1 Dept. of Dermatovenereology, St. Anna University Hospital, Pekarska 53, 65691 Brno, Czech Republic 2 Dept. of Dermatology, Philipps University,35043 Marburg, Germany 3 Laboratory of Molecular and Cell Biology -IRCCS, 00167 Rome, Italy 4 Dept. of Dermatovenereology, 5 Dept. of Pathology, University Hospital Brno, 62500 Brno, Czech Republic a These authors contributed [...]

Hypertext atlas of dermatopathology with expert system for epithelial tumors of the skin

Background:  Image resolution required for reference histological images is high. Obtaining high‐resolution images requires a system, composing large image from individual smaller components. Such systems must thus be capable of automatically taking individual image parts, performing shading compensation and fusion of the image parts into one large image. Distribution of such images over the Internet requires developing a suitable users interface with access to the image details.

Testing of the course of neurogenesis and gliogenesis in the germinative zones of the CNS of embryonal and early postnatal rats by means of the gel reaction for the histochemical demonstration of the thiamine-pyrophosphatase. Histochemical and autoradiographical study

Using the histochemical reaction for the demonstration of TPPase the shape and distribution of the Golgi apparatus (GA) of the ventricular zones of the CNS of rats was studied during embryonal and postnatal development. In the cells of the ventricular zone of the spinal cord, the Hypothalamus, the Thalamus, the N. caudatus and the Cerebral cortex two forms of GA can be distinguished: Form 1 GA has the shape of small rods or grains placed in the ventricular process of the cell at various distances from the nucleus. In the spinal cord and the Hypothalamus the 1st form correlates with the period of neuroblastic production, and the same correlation probably exists in other regions of the CNS also. Form 2 GA is in sequence with form 1; it is characterized by a large beam shape, situated supranuclearly near to the nucleus. The relation of form 2 to gliogenesis is discussed. In the alar region of the spinal cord only form 1 GA occurs. The GA of cells of the subventricular zone has on average a lower enzymatic activity than that of the ventricular zone. By day 18 intra uterinam the subventricular cells have the shape of very small grains (1 micron) or are not visible. From day 18 intra uterinam cells with a large GA begin to appear and steadily grow in number until postnatally they form the majority of the subventricular layer. Autoradiographical investigation and a comparison with published data showed that cells without GA and with discrete GA are stem cells and those with a large GA are glioblasts. Glioblasts are arranged in the subventricular zone with the GA pointing in the direction of migration. According to the ratio of glioblasts and stem cells topographical regions can be divided into early, transitional and permanent phases of glioproduction. The gel method of demonstrating TPPase is highly suitable for study of the differentiation of the CNS and for observing the progress of glioproduction.

Virtual microscope interface to high resolution histological images

The Hypertext atlas of Dermatopathology, the Atlas of Fetal and Neonatal Pathology and Hypertext atlas of Pathology (this one in Czech only) are available at http://www.muni.cz/atlases. These atlases offer many clinical, macroscopic and microscopic images, together with short introductory texts. Most of the images are annotated and arrows pointing to the important parts of the image can be activated.The Virtual Microscope interface is used for the access to the histological images obtained in high resolution using automated microscope and image stitching, possibly in more focusing planes. Parts of the image prepared in advance are downloaded on demand to save the memory of the users computer. The virtual microscope is programmed in JavaScript only, works in Firefox/Mozilla and MSIE browsers without need to install any additional software.

Cutaneous Lymphomas Unusual Cases 2

Mature T-cell and NK-cell Neoplasms.- Familial mycosis fungoides involving a father and daughter.- A case of mycosis fungoides with polyarthritis showing clonal identity in skin and synovial tissue.- Vesicular mycosis fungoides.- Unusual case of mycosis fungoides clinically mimicking a dermatophytosis subsequently evolving in aggressive CD30- cutaneous lymphoma.- Sclero-atrophic mycosis fungoides with a cytotoxic atypical phenotype.- CD56+ early mycosis fungoides.- Sezary syndrome with t(2 5) translocation, as developed after prolonged cyclosporine therapy for actinic reticuloid.- CD8+ Lymphomatoid papulosis with simultaneous Type A, Type B, and Type C lesions.- Lymphomatoid papulosis with a NK-cell phenotype.- Anaplastic large cell lymphoma associated with acquired ichthyosis.- Anaplastic large cell T-cell lymphoma.- Primary cutaneous histiocyte and neutrophil rich CD30+/CD56+ anaplastic large cell lymphoma of the scalp with prominent angio- and neuroinvasion.- Late relapse of primary cutaneous CD30+ anaplastic large cell lymphoma confirmed by T-cell receptor (TCR) PCR analysis.- Peripheral CD4+ T-cell lymphoma with cytotoxic phenotype.- CD8+ disseminated small and medium pleomorphic T-cell lymphoma with blood involvement and secondary hemophagocytic syndrome.- CD8+ cutaneous T-cell lymphoma with an indolent course.- Primary cutaneous pleomorphic small/medium-sized T-cell lymphoma revealed by a plantar callus.- Atypical poorly differentiated cutaneous T-cell lymphoma with an angiocentric growth pattern.- Angiocentric non-Hodgkins lymphoma of the leg.- ?/? cutaneous T-cell lymphoma.- Epidermotropic and subcutaneous ?/? T-cell lymphoma.- Cutaneous T-cell lymphoma presenting as reticular erythematous mucinosis.- Nasal NK-cell lymphoma preceded by a puffy eyelid and swollen cheek due to intramuscular infiltration of Epstein-Barr virus-infected cells.- Epstein-Barr virus-associated lymphoma mimicking hydroa vacciniforme: Final diagnosis of a case reported in 1986.- Epstein-Barr virus-positive blastoid NK-cell lymphoma.- Mature B-cell Neoplasms.- Primary cutaneous marginal zone B-cell lymphoma with secondary anetoderma in a patient with Sjogrens syndrome.- Follicular lymphoma with follicular dendritic cell overgrowth.- Diffuse large B-cell lymphoma with cutaneous and ocular involvement.- EBV-positive cutaneous B-cell lymphoproliferative disease after imatinib mesylate (Glivec).- B-cell chronic lymphocytic leukemia revealed by an erythroderma.- B-cell chronic lymphocytic leukemia (B-CLL) at the site of Borrelia burgdorferi infection.- Scarring leukemia cutis.- Lymphoma-associated insect bite-like reaction arising in a patient with mantle cell lymphoma.- Immature Hematopoietic Malignancies.- Blastic NK-cell lymphoma.- Subcutaneous splenosis of the abdominal wall.- Post-transplant lymphoproliferative disorder.