Cancer 3 revealed only one additional lymphoma with the t(2;12)(p12;p13), which was also diagnosed as typical MCL. 4 Unfortunately, gene expression profiling was not available in the cases presented here. Nevertheless, the typical morphologic and immunophenotypic features of our cases indicate that rare cyclin D1-negative MCLs exist, in which deregulation of cyclin D2 due to a t(2;12)(p12;p13) substitutes for t(11;14)-driven cyclin D1 expression. Phenotype of neoplastic cells in angioimmunoblastic T-cell lymphoma is consistent with activated follicular B helper T cellsWe read the letter by Grogg et al, 1 recently published in Blood, with great interest. The authors demonstrated that CD10 ϩ T cells in angioimmunoblastic T-cell lymphoma 2 (AITL) coexpress CXCL13 and proposed that AITL is a neoplasm of germinal center (GC) T-helper cells.We have hypothesized that neoplastic T cells may be related to follicular B helper T (T FH ) cells, 3-6 since CD10 ϩ atypical T cells were found to be in intimate contact with the expanded meshwork of proliferating follicular dendritic cells (FDCs), a characteristic of AITL. Therefore, we have performed consecutive double immunolabeling to analyze expression of some known T FH cell functional antigens (CXCR5, CD154/CD40L, CD134/OX40, and CD57) in the CD10 ϩ T cells in 20 paraffin-embedded AITL cases. Since Kim et al 7 and Chtanova et al 8 established that CXCL13 is highly up-regulated in T FH cells, expression of this antigen was also investigated; the same has also been done by Grogg et al. 1 In 18 of 20 cases, the expression of CD10 on 5% to 30% of T cells strongly correlated with CXCL13 production. The remaining 2 cases exhibited CXCL13 ϩ atypical T cells without apparent CD10 expression. The neoplastic T cells, as defined by CD10 as well as CXCL13 expression, revealed a CXCR5 ϩ CD134 ϩ CD154 ϩ CD57 Ϫ/ϩ immunophenotype (Figure 1), which is most consistent with GC outer-zone T FH cells. 6 All cases displayed concomitant Figure 1. Histologic, immunophenotypic, and cytogenetic findings in 2 cyclin D1-negative/cyclin D2-positive MCLs with IGK-CCND2 fusion. (A,D) Hematoxylin and eosin (H&E)-stained lymph node biopsies of cases 1 (A) and 2 (D) showing the typical morphology of MCL. (B) Chromosome R-banding analysis of case 1 revealing the karyotype 48,XX,t(2;12)(p12;p13),ϩ3,ϩ21. (C insert, E) Interphase FISH analysis using double-color, double-fusion probes spanning the IGK (green) and CCND2 (red) loci.
Gangliosides are abundantly occurring sialylated glycosphingolipids serving diverse functions in the nervous system. Membrane-localized gangliosides are important components of lipid microdomains (rafts) which determine the distribution of and the interaction among specific membrane proteins. Different classes of gangliosides are expressed in nociceptive primary sensory neurons involved in the transmission of nerve impulses evoked by noxious mechanical, thermal, and chemical stimuli. Gangliosides, in particular GM1, have been shown to participate in the regulation of the function of ion channels, such as transient receptor potential vanilloid type 1 (TRPV1), a molecular integrator of noxious stimuli of distinct nature. Gangliosides may influence nociceptive functions through their association with lipid rafts participating in the organization of functional assemblies of specific nociceptive ion channels with neurotrophins, membrane receptors, and intracellular signaling pathways. Genetic and experimentally induced alterations in the expression and/or metabolism of distinct ganglioside species are involved in pathologies associated with nerve injuries, neuropathic, and inflammatory pain in both men and animals. Genetic and/or pharmacological manipulation of neuronal ganglioside expression, metabolism, and action may offer a novel approach to understanding and management of pain.
In many cases, particularly in retrospective studies, only formalin-fixed and paraffin-embedded (FFPE) tissue samples are available for molecular studies. DNA recovered from FFPE tissues generally consists of fragmented small target sequences with chemical alterations. Clonality analysis is not easy on FFPE samples, in fact, it requires even more experience than that of performed on fresh samples or is more complicated than most genomic PCR amplifications for somatic genes. In our study, we have performed a multi-parameter PCR evaluation investigating immunoglobulin heavy chain gene (IgH) and T-cell receptor gamma gene (TCRgamma) rearrangements on non-purified crude lysates of FFPE samples, in order to establish the significance of different variables on performance of PCR amplification. The results showed that a slight decrease in the concentration of primers in combination with a slight increase in MgCl2 and Taq polymerase concentrations, as well as the use diluted crude template and a standard amount of dNTPs can be the modifications of choice while adjusting IgH and TCRgamma clonality tests on poor quality DNA FFPE samples. Using our improved protocol, 74% (17/23) of the tested B-cell lymphomas and 68% (31/46) of the tested T-cell lymphomas demonstrated monoclonal PCR product, proving the applicability of our optimized method. Our experience may be of help during the optimization process in technically difficult cases as well as to determine which parameters and how should be changed to minimize false-negative and false-positive results.
The distribution of spinal primary afferent terminals labeled transganglionically with the choleratoxin B subunit (CTB) or its conjugates changes profoundly after perineural treatment with capsaicin. Injection of CTB conjugated with horseradish peroxidase (HRP) into an intact nerve labels somatotopically related areas in the ipsilateral dorsal horn with the exceptions of the marginal zone and the substantia gelatinosa, whereas injection of this tracer into a capsaicin-pretreated nerve also results in massive labeling of these most superficial layers of the dorsal horn. The present study was initiated to clarify the role of C-fiber primary afferent neurons in this phenomenon. In L5 dorsal root ganglia, analysis of the size frequency distribution of neurons labeled after injection of CTB-HRP into the ipsilateral sciatic nerve treated previously with capsaicin or resiniferatoxin revealed a significant increase in the proportion of small neurons. In the spinal dorsal horn, capsaicin or resiniferatoxin pretreatment resulted in intense CTB-HRP labeling of the marginal zone and the substantia gelatinosa. Electron microscopic histochemistry disclosed a dramatic, ∼10-fold increase in the proportion of CTB-HRP-labeled unmyelinated dorsal root axons following perineural capsaicin or resiniferatoxin. The present results indicate that CTB-HRP labeling of C-fiber dorsal root ganglion neurons and their central terminals after perineural treatment with vanilloid compounds may be explained by their phenotypic switch rather than a sprouting response of thick myelinated spinal afferents which, in an intact nerve, can be labeled selectively with CTB-HRP. The findings also suggest a role for GM1 ganglioside in the modulation of nociceptor function and pain.
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