JoVE Visualize What is visualize?
Stop Reading. Start Watching.
Advanced Search
Stop Reading. Start Watching.
Regular Search
Find video protocols related to scientific articles indexed in Pubmed.
Immunohistochemistry as a valuable tool to assess CD30 expression in peripheral T-cell lymphomas: high correlation with mRNA levels.
Blood
PUBLISHED: 09-15-2014
Show Abstract
Hide Abstract
The extended use of brentuximab-vedotin was reported for CD30(+) nonanaplastic peripheral T-cell lymphomas (PTCLs) with promising efficacy. CD30 status assessment is thus a critical factor for therapeutic decision, but the reliability of immunohistochemistry (IHC) in evaluating its expression remains to be defined. This prompted us to investigate the correlation between semiquantitative CD30 protein assessment by IHC and messenger RNA (mRNA) assessment by microarrays in a cohort of 376 noncutaneous PTCLs representative of the main entities. By IHC, CD30 expression was heterogeneous across and within entities and significantly associated with large tumor cell size. In addition to 100% anaplastic large-cell lymphomas, 57% of other PTCL entities were CD30-positive at a 5% threshold. CD30 protein expression was highly correlated to mRNA levels. mRNA levels were bimodal, separating high from low CD30-expressing PTCL cases. We conclude that IHC is a valuable tool in clinical practice to assess CD30 expression in PTCLs.
Related JoVE Video
Breslow Thickness, Clark Index and Ulceration Are Associated with Sentinel Lymph Node Metastasis in Melanoma Patients: A Cohort Analysis of 612 Patients.
Dermatology (Basel)
PUBLISHED: 08-26-2014
Show Abstract
Hide Abstract
Background: Sentinel lymph node biopsy (SLNB) is the most sensitive procedure for assessing nodal status in patients with primary melanoma. Objective: To evaluate the predictive ability of usual primary melanoma prognosis factors of detecting sentinel lymph node (SLN) metastasis in patients with melanoma. Patients and Methods: A cohort of 612 consecutive patients presenting with primary skin melanoma who underwent a SLNB was evaluated. Assessment of the determinants of SLN metastasis was based on general linear model analysis. The model performance was studied using the concordance statistic and the net reclassification index. The calibration was estimated using the Hosmer-Lemeshow test. Results: The discrimination ability did not differ significantly between Breslow thickness (0.57), Clark index (0.61), ulceration (0.57) and histological subtype (0.55). Clark index, ulceration and Breslow thickness were all significant and independent determinants of SLN metastasis. The predictive ability of the final model was 0.657. Conclusion: Breslow thickness, Clark index and ulceration are independent predictors of a SLN metastasis. © 2014 S. Karger AG, Basel.
Related JoVE Video
Clinical analysis and prognostic significance of haemophagocytic lymphohistiocytosis-associated anaplastic large cell lymphoma in children.
Br. J. Haematol.
PUBLISHED: 03-27-2014
Show Abstract
Hide Abstract
Haemophagocytic lymphohistiocytosis (HLH) has been rarely described in children treated for an anaplastic large-cell lymphoma (ALCL). We evaluated the incidence, the clinical and histological characteristics and the prognosis of HLH associated-ALCL. The medical, biological, cytological and histological data of patients treated for ALK-positive ALCL in the paediatric department of a single institution between 1975 and 2008 were analysed and assessed for HLH according to diagnosis criteria of the Histiocyte Society. Data concerning a series of 50 consecutive children with ALCL were reviewed. HLH-associated ALCL was observed in 12% of the patients. Lung involvement was significantly more frequent in HLH-associated ALCL patients than in the group without HLH (P = 0·004), as well as central nervous system (CNS) and bone marrow involvement (P = 0·001 and P = 0·007 respectively). The histological subtype in children with HLH-associated ALCL did not differ from that of the group without HLH. There was no significant difference between the two groups in 5-year EFS and OS (P = 0·91 and P > 0·99 respectively). In conclusion, HLH is not rare in paediatric ALCL. Despite a high incidence of visceral, CNS and bone marrow involvement, HLH does not seem to exert a significant impact on outcome in children treated for ALCL.
Related JoVE Video
Paediatric anaplastic large cell lymphoma with leukaemic presentation in children: a report of nine French cases.
Br. J. Haematol.
PUBLISHED: 02-14-2014
Show Abstract
Hide Abstract
This study aimed to describe the clinical features and outcome of anaplastic large cell lymphoma (ALCL) with leukaemic presentation in children. Among 267 patients included in the French paediatric ALCL database between 1989 and 2012, nine (3%) were described as having cytologically detectable circulating tumour cells. Clinical features combined fever (8/9), nodal and extra-nodal disease (9/9), including hepato-splenic (9/9) and lung involvement (7/9). The level of hyperleucocytosis ranged from 30 to 120 × 10(9) /l, with 12-90% of tumour cells. Diagnosis relied on a lymph node biopsy, with a positive ALK+ antibody immunostain in all nine cases, a T-cell immunophenotype in 7/9 cases and CD3 positivity in 5/9 cases. A small cell component was present in 6/9 cases. Only four patients achieved a complete remission with first-line therapy and 3/4 relapsed. Four patients are alive with a median follow-up of 31 months, two of them after allogeneic haematopoietic stem cell transplantation (HSCT), and five patients died, two of them of disease. In conclusion, ALCL with leukaemic presentation is very unusual and should be considered as high-risk lymphoma requiring new therapeutic strategies. The respective role of new agents and allogeneic HSCT in first complete remission still has to be assessed.
Related JoVE Video
Blastic plasmacytoid dendritic cell neoplasms: clinico-immunohistochemical correlations in a series of 91 patients.
Am. J. Surg. Pathol.
PUBLISHED: 01-21-2014
Show Abstract
Hide Abstract
Blastic plasmacytoid dendritic cell neoplasm is a rare clinicopathologic entity, characterized by strong skin tropism and a poor prognosis. The diagnosis is generally made by skin biopsy with appropriate immunohistochemical studies. To identify potential biological prognostic factors for blastic plasmacytoid dendritic cell neoplasm, we performed an extended clinico-immunohistochemical study on a series of 91 well-documented cases collected since 1995 by the French Study Group on Cutaneous Lymphomas. Skin biopsies were analyzed using a panel of 12 immunohistochemical markers (CD4, CD56, CD123, CD303, TCL1, CD68, CD2, CD7, TdT, Ki-67, S100, and MX-1). The results were correlated with survival. The 5 most characteristic markers of this entity (CD4, CD56, CD123, CD303, and TCL1) were expressed simultaneously in only 46% of patients. However, when 4 markers were expressed the diagnosis could still be reliably made without resorting to any additional stains. Expression of TdT and/or S100 correlated with varying degrees of maturation. Statistical survival analyses showed that CD303 expression and high proliferative index (Ki-67) were significantly associated with longer survival.
Related JoVE Video
Double-positive CD4/CD8 mycosis fungoides: a rarely reported immunohistochemical profile.
J. Cutan. Pathol.
PUBLISHED: 10-10-2013
Show Abstract
Hide Abstract
Mycosis fungoides (MF) represents the most common epidermotropic cutaneous T-cell lymphoma (CTCL), and tumor cells typically express a mature T-helper memory phenotype. A minority of MF patients display an unusual phenotype, which may be either CD4(-)/CD8(+) or double negative. Herein, we report a case of biopsy-proven MF in a 31-year-old woman who presented with infiltrated plaques involving photoprotected areas of the skin. Immunohistochemical study combined with confocal microscopy revealed co-expression of CD4 and CD8 in a subset of atypical T lymphocytes. To our knowledge, this is the second report of a CD4/CD8 dual-positive MF.
Related JoVE Video
STAT3 mutations identified in human hematologic neoplasms induce myeloid malignancies in a mouse bone marrow transplantation model.
Haematologica
PUBLISHED: 07-19-2013
Show Abstract
Hide Abstract
STAT3 protein phosphorylation is a frequent event in various hematologic malignancies and solid tumors. Acquired STAT3 mutations have been recently identified in 40% of patients with T-cell large granular lymphocytic leukemia, a rare T-cell disorder. In this study, we investigated the mutational status of STAT3 in a large series of patients with lymphoid and myeloid diseases. STAT3 mutations were identified in 1.6% (4 of 258) of patients with T-cell neoplasms, in 2.5% (2 of 79) of patients with diffuse large B-cell lymphoma but in no other B-cell lymphoma patients (0 of 104) or patients with myeloid malignancies (0 of 96). Functional in vitro assays indicated that the STAT3Y640F mutation leads to a constitutive phosphorylation of the protein. STA21, a STAT3 small molecule inhibitor, inhibited the proliferation of two distinct STAT3 mutated cell lines. Using a mouse bone marrow transplantation assay, we observed that STAT3Y640F expression leads to the development of myeloproliferative neoplasms with expansion of either myeloid cells or megakaryocytes. Together, these data indicate that the STAT3Y640F mutation leads to constitutive activation of STAT3, induces malignant hematopoiesis in vivo, and may represent a novel therapeutic target in some lymphoid malignancies.
Related JoVE Video
Clonal cytophagic histiocytic panniculitis in children may be cured by cyclosporine A.
Pediatrics
PUBLISHED: 07-15-2013
Show Abstract
Hide Abstract
Cytophagic histiocytic panniculitis (CHP) is a rare panniculitis in childhood, associated either with nonmalignant conditions or with subcutaneous panniculitis-like T-cell lymphoma (SPTCL), and often also associated with macrophage activation syndrome (MAS). Discriminating between these 2 conditions is therapeutically important because nonmalignant CHP often improves under cyclosporine and prednisone, whereas most cases of SPLT may be best treated with more aggressive therapy. We report the cases of a 6-month-old boy and a 16-month-old girl who, after viral infection, developed multiple infiltrating skin nodules on the limbs and face, associated with MAS. Histopathologic findings for skin biopsy specimens revealed CHP associated with heavily cellular lobular panniculitis. Hemophagocytosis and immunohistochemical staining features were consistent with typical characteristics of in situ MAS in adipose tissue: the lymphocytes were mostly TCD8+ cells with an activated phenotype (human leukocyte antigen (HLA) -DR+) and expressed interferon-?; CD68+ macrophages expressed tumor necrosis factor-? and interleukin-6. A monoclonal rearrangement of the T-cell receptor ? gene was present in skin tissue but not in peripheral blood or bone marrow lymphocytes. Cyclosporine A treatment resulted in the complete remission of cutaneous and systemic manifestations in both patients for 66 and 29 months, respectively. This report suggests that the diagnosis of a reactive T-cell lymphoproliferation should be the treatment of choice in young children with severe CHP, even if there is a SPTCL-like aspect with an in situ T-cell clonality. It also suggests that CSA is the optimal treatment of this condition and postulates the possible pathologic process underlying this efficacy.
Related JoVE Video
CD30-positive peripheral T-cell lymphomas share molecular and phenotypic features.
Haematologica
PUBLISHED: 05-28-2013
Show Abstract
Hide Abstract
Peripheral T-cell lymphoma, not otherwise specified is a heterogeneous group of aggressive neoplasms with indistinct borders. By gene expression profiling we previously reported unsupervised clusters of peripheral T-cell lymphomas, not otherwise specified correlating with CD30 expression. In this work we extended the analysis of peripheral T-cell lymphoma molecular profiles to prototypical CD30(+) peripheral T-cell lymphomas (anaplastic large cell lymphomas), and validated mRNA expression profiles at the protein level. Existing transcriptomic datasets from peripheral T-cell lymphomas, not otherwise specified and anaplastic large cell lymphomas were reanalyzed. Twenty-one markers were selected for immunohistochemical validation on 80 peripheral T-cell lymphoma samples (not otherwise specified, CD30(+) and CD30(-); anaplastic large cell lymphomas, ALK(+) and ALK(-)), and differences between subgroups were assessed. Clinical follow-up was recorded. Compared to CD30(-) tumors, CD30(+) peripheral T-cell lymphomas, not otherwise specified were significantly enriched in ALK(-) anaplastic large cell lymphoma-related genes. By immunohistochemistry, CD30(+) peripheral T-cell lymphomas, not otherwise specified differed significantly from CD30(-) samples [down-regulated expression of T-cell receptor-associated proximal tyrosine kinases (Lck, Fyn, Itk) and of proteins involved in T-cell differentiation/activation (CD69, ICOS, CD52, NFATc2); upregulation of JunB and MUM1], while overlapping with anaplastic large cell lymphomas. CD30(-) peripheral T-cell lymphomas, not otherwise specified tended to have an inferior clinical outcome compared to the CD30(+) subgroups. In conclusion, we show molecular and phenotypic features common to CD30(+) peripheral T-cell lymphomas, and significant differences between CD30(-) and CD30(+) peripheral T-cell lymphomas, not otherwise specified, suggesting that CD30 expression might delineate two biologically distinct subgroups.
Related JoVE Video
RhoB Promotes Cancer Initiation by Protecting Keratinocytes from UVB-Induced Apoptosis but Limits Tumor Aggressiveness.
J. Invest. Dermatol.
PUBLISHED: 04-30-2013
Show Abstract
Hide Abstract
The role of UVB-induced apoptosis in the formation of squamous cell carcinoma (SCC) is recognized. We previously identified the small RhoB (Ras homolog gene family, member B) GTPase, an early response gene to cellular stress, as a critical protein controlling apoptosis of human keratinocytes after UVB exposure. Here we generated SKH1 (hairless immunocompetent mouse) mice invalidated for RhoB to evaluate its role in UVB-induced skin carcinogenesis in vivo. We show that rhob-/- mice have a lower risk of developing UVB-induced keratotic tumors and actinic keratosis that is associated with a higher sensitivity of UVB-exposed keratinocytes to apoptosis. We extend this observation to primary cultures of normal human keratinocytes in which RhoB was downregulated with small interfering RNA (siRNA) and further show that the hypersensitivity to apoptosis depends on B-cell lymphoma 2 (Bcl-2) downregulation. In rhob-/- mice, the UVB-induced tumors were preferentially undifferentiated and highly proliferative. Finally, we show in humans an almost constant loss of RhoB expression in undifferentiated SCCs. These undifferentiated and RhoB-deficient tumors have elevated phosphorylated histone H2AX (?H2AX) and 53BP1, two markers of DNA double-strand breaks. Together, our results indicate that UVB-induced RhoB expression participates in in vivo SCC initiation by increasing keratinocyte survival. Conversely, RhoB may limit tumor aggressiveness as loss of RhoB expression in tumor cells is associated with tumor progression.
Related JoVE Video
Prognostic impact of morphologic and phenotypic features of childhood ALK-positive anaplastic large-cell lymphoma: results of the ALCL99 study.
J. Clin. Oncol.
PUBLISHED: 11-14-2011
Show Abstract
Hide Abstract
The prognostic value of pathologic characteristics of childhood ALK-positive anaplastic large-cell lymphomas (ALCL), such as histologic subtypes, immunophenotype, and presence of the t(2;5) translocation or its variants, was assessed.
Related JoVE Video
MiR-29a down-regulation in ALK-positive anaplastic large cell lymphomas contributes to apoptosis blockade through MCL-1 overexpression.
Blood
PUBLISHED: 04-06-2011
Show Abstract
Hide Abstract
Although deregulated expression of specific microRNAs (miRNAs) has been described in solid cancers and leukemias, little evidence of miRNA deregulation has been reported in ALK-positive (ALK(+)) anaplastic large cell lymphomas (ALCL). These tumors overexpress the major antiapoptotic protein myeloid cell leukemia 1 (MCL-1), a situation that could compensate for the lack of BCL-2. We report that ALK(+) ALCL cell lines and biopsy specimens (n = 20) express a low level of miR-29a and that this down-modulation requires an active NPM-ALK kinase. Murine models (transgenic mice and mouse embryonic fibroblast [MEF] cells), which allow conditional NPM-ALK fusion protein expression, showed an increase of miR-29a expression in the absence of NPM-ALK. Concordant results were observed after the abolition of NPM-ALK kinase activity (siALK or PF-2341066) in NPM-ALK(+) ALCL cell lines. In addition, we showed that low expression of miR-29a, probably through methylation repression, plays an important regulatory role in MCL-1 overexpression that could promote tumor cell survival by inhibiting apoptosis. Enforced miR-29a expression was found to modulate apoptosis through inhibition of MCL-1 expression in ALCL cell lines and in a xenografted model, with a concomitant tumor growth reduction. Thus, synthetic miR-29a represents a potential new tool to affect tumorigenesis in these lymphomas.
Related JoVE Video
Limited stage I disease is not necessarily indicative of an excellent prognosis in childhood anaplastic large cell lymphoma.
Blood
PUBLISHED: 03-28-2011
Show Abstract
Hide Abstract
Data on incidence, characteristics, and prognosis in stage I childhood anaplastic large cell lymphoma are scarce. Of 463 patients enrolled in the international ALCL99 trial, 36 (8%) had stage I disease and were treated with a prephase chemotherapy, followed by either 3 chemotherapy courses in case of initial complete resection (6 patients) or otherwise by 6 courses of chemotherapy (30 patients). Disease localization was to the peripheral lymph nodes in 26, soft tissue mass in 8, and solitary bone and bronchial disease in 1 patient each. Of the 6 patients with complete resection, none experienced relapse, whereas of the 30 remaining stage I patients, 9 (30%) relapsed, including in all cases a new site of disease involvement and including 3 of 5 anaplastic lymphoma kinase-negative patients. In summary, the failure rate for incompletely resected stage I disease was similar to that for patients with stage II and stage III/IV disease. Whether anaplastic lymphoma kinase negativity contributed to this moderate outcome has to be proven prospectively. This study was registered at www.clinicaltrials.gov as NCT00006455.
Related JoVE Video
HuR-mediated control of C/EBPbeta mRNA stability and translation in ALK-positive anaplastic large cell lymphomas.
Mol. Cancer Res.
PUBLISHED: 02-22-2011
Show Abstract
Hide Abstract
The CCAAT/enhancer-binding protein ? (C/EBP?) plays a major role in the pathogenesis of anaplastic large cell lymphomas (ALCL) that express the nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) tyrosine kinase (ALK(+)). Although ALK-mediated C/EBP? transcriptional activation has been reported, C/EBP? mRNA possesses U- and AU-rich domains in its 3-untranslated region (3-UTR) that might be privileged targets for posttranscriptional control in ALK(+) ALCLs. The purpose of this study was to explore this possibility. By using human ALCL-derived cells and a murine model of ALK-transformed cells, we show that the AU-binding protein HuR binds to the 3-UTR of C/EBP? mRNA, as previously reported in adipocytes, and that NPM-ALK enhances this interaction. Interaction between HuR and C/EBP? mRNA impacts on C/EBP? gene expression at both the mRNA and protein levels. Indeed, C/EBP? mRNA stability following HuR silencing is reduced and reaches the value observed in ALK-inactivated cells. Remarkably, HuR expression is not modified by NPM-ALK, but its association with actively translating polysomes is dramatically increased in ALK(+) cells. HuR/polysomes association diminishes when NPM-ALK activity is inhibited and is accompanied by a concomitant decrease of C/EBP? mRNA translation. Finally, we show that HuR and NPM-ALK colocalized in cytoplasmic granules and HuR is phosphroylated on tyrosine residues in ALK(+) ALCL cells. Our study thus demonstrates that C/EBP? is indeed regulated at the posttranscriptional level by HuR in ALK(+) cells, leading us to propose that part of NPM-ALK oncogenic properties relies on its ability to modify HuR properties in the cytoplasm and hence to alter expression of key actors of transformation.
Related JoVE Video
A 10 Mb duplication in chromosome band 5q31.3-5q33.1 associated with late-onset lipodystrophy, ichthyosis, epilepsy and glomerulonephritis.
Eur J Med Genet
PUBLISHED: 01-18-2011
Show Abstract
Hide Abstract
We report here a 44 years-old patient with late-onset partial lipodystrophy, mental retardation, epilepsy, ichtyosis and glomerulonephritis, carrying a 10 Mb duplication of the chromosome 5q31.3-5q32.1 region detected by array-CGH.
Related JoVE Video
Vinblastine in children and adolescents with high-risk anaplastic large-cell lymphoma: results of the randomized ALCL99-vinblastine trial.
J. Clin. Oncol.
PUBLISHED: 08-02-2010
Show Abstract
Hide Abstract
The impact of adding vinblastine to a 4-month chemotherapy regimen, based on the Non-Hodgkins Lymphoma Berlin-Frankfurt-Münster 90 protocol, in childhood high-risk anaplastic large-cell lymphoma (ALCL) was assessed.
Related JoVE Video
Purpuric lesions induced by UVA1 spectrum (340-400 nm) phototesting in an adult with persistent and severe hydroa vacciniforme.
Photodermatol Photoimmunol Photomed
PUBLISHED: 04-27-2010
Show Abstract
Hide Abstract
A 28-year-old man had presented a severe photosensitivity since his infancy. In March 2008, the clinical examination showed large crusts on the dorsum of his hands, on the edge of his ears with destruction of the underlying cartilage, and on his nose and cheeks. He also presented erythematosus fibrous scars on the temples. The diagnosis of hydroa vaccinforme was made. Phototesting including repeated UVA1 phototest was strongly positive with purpuric lesions from day 7 to day 10 and hypertrophic scars at day 67. A sequential histological study of the UVA1 triggered lesions was performed and showed bullous cleavage, dense inflammatory infiltrate in the whole dermis with numerous neutrophilic cells, nuclear dusts, superficial focal thrombosis of small blood vessels at day 10. We report an unusual case of hydroa vaccinforme with purpuric lesions leading to fibrous scars and with important infiltration of neutrophils in the dermis of the photoinduced lesions.
Related JoVE Video
mu-Opioid receptor is induced by IL-13 within lymph nodes from patients with Sézary syndrome.
J. Invest. Dermatol.
PUBLISHED: 01-28-2010
Show Abstract
Hide Abstract
Endogenous opioid peptides mainly produced by neurons are also released by immune cells. They bind to mu- (mu-opioid receptor, MOR), delta-, and kappa-opioid receptors. On the basis of studies on mice showing that MOR is the main mediator of the deleterious effects of opioids on immunity, we wondered whether MOR, absent under normal conditions, is expressed in some pathological situations such as lymphomas. mRNA expression for all three opioid receptors was examined in lymph node biopsy samples from patients with non-Hodgkins B-cell and T-cell lymphomas. We found that MOR and one of its ligands (enkephalin) are simultaneously expressed almost exclusively in lymph nodes from patients with Sézary cutaneous T cell lymphoma. As MOR was undetectable in circulating malignant T lymphocytes and in normal immune cells, we hypothesized that tumor-released cytokines might induce MOR expression in non-neoplastic lymph node cells. The correlation between mRNA levels of MOR and interleukin-13 (IL-13) within lymph nodes from Sézary patients led us to investigate the ability of IL-13 to upregulate MOR expression in normal immune cell subsets. We found that IL-13 upregulates MOR in activated Langerhans cells. Thus, our data suggest that, under pathological conditions, IL-13 overexpression might allow immune-derived endogenous opioids to down-modulate immune response.
Related JoVE Video
Elastase 2 is expressed in human and mouse epidermis and impairs skin barrier function in Netherton syndrome through filaggrin and lipid misprocessing.
J. Clin. Invest.
PUBLISHED: 01-06-2010
Show Abstract
Hide Abstract
The human epidermis serves 2 crucial barrier functions: it protects against water loss and prevents penetration of infectious agents and allergens. The physiology of the epidermis is maintained by a balance of protease and antiprotease activities, as illustrated by the rare genetic skin disease Netherton syndrome (NS), in which impaired inhibition of serine proteases causes severe skin erythema and scaling. Here, utilizing mass spectrometry, we have identified elastase 2 (ELA2), which we believe to be a new epidermal protease that is specifically expressed in the most differentiated layer of living human and mouse epidermis. ELA2 localized to keratohyalin granules, where it was found to directly participate in (pro-)filaggrin processing. Consistent with the observation that ELA2 was hyperactive in skin from NS patients, transgenic mice overexpressing ELA2 in the granular layer of the epidermis displayed abnormal (pro-)filaggrin processing and impaired lipid lamellae structure, which are both observed in NS patients. These anomalies led to dehydration, implicating ELA2 in the skin barrier defect seen in NS patients. Thus, our work identifies ELA2 as a major new epidermal protease involved in essential pathways for skin barrier function. These results highlight the importance of the control of epidermal protease activity in skin homeostasis and designate ELA2 as a major protease driving the pathogenesis of NS.
Related JoVE Video
Cutaneous presentation of ALK-positive anaplastic large cell lymphoma following insect bites: evidence for an association in five cases.
Haematologica
PUBLISHED: 11-30-2009
Show Abstract
Hide Abstract
Skin involvement is frequent in ALK-positive anaplastic large cell lymphomas. The role of an insect bite as a triggering event has been postulated but not well documented.
Related JoVE Video
Anaplastic lymphoma kinase-positive diffuse large B-cell lymphoma: a rare clinicopathologic entity with poor prognosis.
J. Clin. Oncol.
PUBLISHED: 07-27-2009
Show Abstract
Hide Abstract
Anaplastic lymphoma kinase (ALK) -positive diffuse large B-cell lymphoma (DLBCL) is a rare variant of DLBCL that has been described only in small case reports. To shed more light on the clinical and pathologic features and outcome of these tumors, we reviewed data from 38 patients.
Related JoVE Video
Cutaneous T cell lymphoma complicating severe atopic dermatitis. Is making a diagnosis the main challenge?
Dermatology (Basel)
PUBLISHED: 06-16-2009
Show Abstract
Hide Abstract
The association between severe long-term atopic dermatitis (AD) and the risk of skin lymphoma is still a matter of debate, since epidemiological studies have shown contradictory results. We report 2 cases of patients with a documented history of severe longstanding atopic disease, who had never been treated with topical or systemic calcineurin inhibitors, and who developed a cytotoxic cutaneous T cell lymphoma (CTCL). For these 2 patients, clinical manifestations preceded the diagnosis of CTCL. The diagnosis was based on histological findings and molecular analysis of the T cell receptor (TCR) clonality. These cases illustrate the difficulty in diagnosing CTCL in patients with severe AD and extensive inflammatory skin lesions. The transition between severe AD and CTCL is progressive; histological findings and molecular evidence of TCR clonality are detected after the clinical changes. These 2 cases lend further support to the hypothesis of an association between severe long-term AD and CTCL.
Related JoVE Video
Milia complicating bullous polymorphic light eruption.
Photodermatol Photoimmunol Photomed
PUBLISHED: 01-21-2009
Show Abstract
Hide Abstract
Polymorphic light eruption (PLE) is the most common photosensitivity disorder. Typically, PLE manifests in the spring or summer months as a recurrent pruritic papular and/or vesicular eruption occurring on photoexposed skin areas following sun exposure. The milia are caused by proliferative tendencies of the epithelium after injury. These may occur in areas of subepidermal bullous eruption. We report an original case of bullous PLE complicated by milia. Such association has not been reported previously.
Related JoVE Video
Related JoVE Video
High endothelial venules (HEVs) in human melanoma lesions: Major gateways for tumor-infiltrating lymphocytes.
Oncoimmunology
Show Abstract
Hide Abstract
The presence of tumor-infiltrating lymphocytes (TILs) is a strong prognostic parameter for local dissemination and overall survival in melanoma. Lymphocyte migration from blood into peripheral tissues is mainly regulated by vascular endothelium. However, the blood vessels and mechanisms governing the recruitment of TILs in melanoma tumors remain poorly understood. Here, we show that high endothelial venules (HEVs), specialized blood vessels for lymphocyte extravasation into lymphoid tissues, are frequently found in melanoma tumors and are associated with high levels of lymphocyte infiltration. The analysis of 225 primary melanomas revealed that lymphocytes specifically infiltrated HEV-rich areas of melanoma tumors and that the density of MECA-79+ HEVs was variable among patients and strongly correlated with CD3+, CD8+ and CD20+ TIL densities. Inflammatory (CCL5, CXCL9, CXCL10 and CXCL11) and lymphoid (CCL21, CCL19 and CXCL13) chemokines as well as TH1 and naïve T-cell genes were overexpressed in melanoma samples with high densities of tumor HEVs. Mature dendritic cells (mDCs) were frequently found around tumor HEVs and densities of HEVs and DC-LAMP+ mDCs within tumor stroma were strongly correlated. DCs which maintain HEVs in lymph nodes, may thus also contribute to the regulation of HEVs in melanomas. Finally, we found significantly higher densities of tumor HEVs in melanomas with tumor regression, low Clark level of invasion and thin Breslow thickness (all p < 0.001). The strong association between tumor HEVs, TILs, mDCs and clinical parameters of melanoma, supports a critical role for HEVs in limiting malignant melanoma development through both naïve and effector T-lymphocyte recruitment and activation.
Related JoVE Video
Long-term outcome of adults with systemic anaplastic large-cell lymphoma treated within the Groupe dEtude des Lymphomes de lAdulte trials.
J. Clin. Oncol.
Show Abstract
Hide Abstract
Systemic anaplastic large-cell lymphoma (ALCL) is a T-cell lymphoma, whose anaplastic lymphoma kinase (ALK) expression varies according to age. Long-term outcomes of chemotherapy-treated adults are not definitively established and should be evaluated.
Related JoVE Video
Anaplastic lymphoma kinase as a therapeutic target.
Expert Opin. Ther. Targets
Show Abstract
Hide Abstract
Anaplastic lymphoma kinase (ALK), a tyrosine kinase receptor, has been initially identified through its involvement in chromosomal translocations associated with anaplastic large cell lymphoma. However, recent evidence that aberrant ALK activity is also involved in an expanding number of tumor types, such as other lymphomas, inflammatory myofibroblastic tumor, neuroblastomas and some carcinomas, including non-small cell lung carcinomas, is boosting research progress in ALK-targeted therapies.
Related JoVE Video
Small nucleolar RNA expression profiling identifies potential prognostic markers in peripheral T-cell lymphoma.
Blood
Show Abstract
Hide Abstract
Peripheral T-cell lymphoma (PTCL) is a rare, heterogeneous type of non-Hodgkin lymphoma (NHL) that, in general, is associated with a poor clinical outcome. Therefore, a current major challenge is the discovery of new prognostic tools for this disease. In the present study, a cohort of 122 patients with PTCL was collected from a multicentric T-cell lymphoma consortium (TENOMIC). We analyzed the expression of 80 small nucleolar RNAs (snoRNAs) using high-throughput quantitative PCR. We demonstrate that snoRNA expression analysis may be useful in both the diagnosis of some subtypes of PTCL and the prognostication of both PTCL-not otherwise specified (PTCL-NOS; n = 26) and angio-immunoblastic T-cell lymphoma (AITL; n = 46) patients treated with chemotherapy. Like miRNAs, snoRNAs are globally down-regulated in tumor cells compared with their normal counterparts. In the present study, the snoRNA signature was robust enough to differentiate anaplastic large cell lymphoma (n = 32) from other PTCLs. For PTCL-NOS and AITL, we obtained 2 distinct prognostic signatures with a reduced set of 3 genes. Of particular interest was the prognostic value of HBII-239 snoRNA, which was significantly over-expressed in cases of AITL and PTCL-NOS that had favorable outcomes. Our results suggest that snoRNA expression profiles may have a diagnostic and prognostic significance for PTCL, offering new tools for patient care and follow-up.
Related JoVE Video
Photoletter to the editor: Blue nevus with satellitosis mimicking melanoma. Contribution of dermoscopy and reflectance confocal microscopy.
J Dermatol Case Rep
Show Abstract
Hide Abstract
Blue nevus is an acquired benign melanocytic nevus that can undergo malignant transformation. We report a 70-year-old man who presented with a recently enlarged long-term blue nodule on his scalp. He reported onset of new satellitosis around the lesion. Although clinically thought to be a malignant melanoma, histopathological, dermoscopic and reflectance confocal-microscopy examinations did not confirm this diagnosis.
Related JoVE Video
PHOX2B immunolabeling: a novel tool for the diagnosis of undifferentiated neuroblastomas among childhood small round blue-cell tumors.
Am. J. Surg. Pathol.
Show Abstract
Hide Abstract
Peripheral neuroblastic tumors are the most commonly occurring extracranial tumors in children. Although a reliable diagnosis is achievable in the majority of cases, diagnosis of a minority of peripheral neuroblastic tumor cases (especially undifferentiated neuroblastoma) poses a challenge compared with that of other pediatric small round blue-cell tumors. A panel of immunohistochemical markers and fusion transcripts is available for the diagnosis of such tumors, but the markers for neuroblastoma lack specificity and sensitivity. As the transcription factor PHOX2B is highly specific for the peripheral autonomic nervous system from which peripheral neuroblastic tumors are derived, we have assessed PHOX2B immunolabeling as a diagnostic tool in pediatric small round blue-cell tumors. We observed PHOX2B expression in all peripheral neuroblastic tumors, paragangliomas, and pheochromocytomas tested but in no other pediatric tumors among the 388 cases studied by expression microarray and the 109 cases studied by immunohistochemical analysis. We then assessed the results of PHOX2B immunohistochemistry in 12 cases of undifferentiated pediatric neoplasms: PHOX2B was expressed in 6/6 undifferentiated neuroblastomas and in no other small round blue-cell tumors. Finally, we showed that PHOX2B immunohistochemical analysis improves the diagnosis of undifferentiated neuroblastoma with high specificity and sensitivity.
Related JoVE Video
ALK-positive anaplastic large cell lymphoma limited to the skin: clinical, histopathological and molecular analysis of 6 pediatric cases. A report from the ALCL99 study.
Haematologica
Show Abstract
Hide Abstract
Anaplastic large cell lymphomas are peripheral T-cell lymphomas that are characterized by a proliferation of large anaplastic blasts expressing CD30. In children, systemic anaplastic large cell lymphomas often present at advanced clinical stage and harbor translocations involving the anaplastic lymphoma kinase (ALK) gene leading to the expression of chimeric anaplastic lymphoma kinase (ALK)-fusion proteins. Primary cutaneous anaplastic large cell lymphoma is regarded as an ALK-negative variant confined to the skin and is part of the spectrum of primary cutaneous CD30-positive T-cell lymphoproliferative disorders. Thirty-three of 487 pediatric patients registered within the Anaplastic Large Cell Lymphoma-99 trial (1999 to 2006) presented with a skin limited CD30-positive lympho-proliferative disorder. In 23 of the 33 patients, material for international histopathological review was available, and the cases were studied for histopathological, immunophenotypical and clinical features as well as for breaks within the ALK gene. Five of 23 cases and one additional case (identified after closure of the trial) expressed ALK-protein. Complete staging excluded any other organ involvement in all children. Expression of ALK proteins was demonstrated by immunohistochemistry in all cases and the presence of breaks of the ALK gene was genetically confirmed in 5 evaluable cases. The histopathological and clinical picture of these skin-restricted ALK-positive lymphomas was indistinguishable from that of cutaneous anaplastic large cell lymphoma. Five children presented with a single skin lesion that was completely resected in 4 and incompletely resected in one. Three of these patients received no further therapy, 2 additional local radiotherapy, and one chemotherapy. All children remain in complete remission with a median follow up of seven years (range 1-8 years). We present 6 pediatric cases of ALK-positive primary cutaneous anaplastic large cell lymphomas. After thorough exclusion of systemic involvement, therapy confined to local measures seems to be sufficient to induce cure.
Related JoVE Video
Recurrent TET2 mutations in peripheral T-cell lymphomas correlate with TFH-like features and adverse clinical parameters.
Blood
Show Abstract
Hide Abstract
Inactivating mutations of the Ten-Eleven Translocation 2 (TET2) gene were first identified in myeloid malignancies and more recently in peripheral T-cell lymphomas (PTCLs). In the present study, we investigated the presence of TET2 coding sequence mutations and their clinical relevance in a large cohort of 190 PTCL patients. TET2 mutations were identified in 40 of 86 (47%) cases of angioimmunoblastic T-cell lymphoma (AITL) and in 22 of 58 (38%) cases of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), but were absent in all other PTCL entities, with the exception of 2 of 10 cases of enteropathy-associated T-cell lymphoma. Among PTCL-NOS, a heterogeneous group of lymphoma-comprising cases likely to derive from Th follicular (T(FH)) cells similarly to AITL, TET2 mutations were more frequent when PTCL-NOS expressed T(FH) markers and/or had features reminiscent of AITL (58% vs 24%, P = .01). In the AITL and PTCL-NOS subgroups, TET2 mutations were associated with advanced-stage disease, thrombocytopenia, high International Prognostic Index scores, and a shorter progression-free survival.
Related JoVE Video
Melanoma chemotherapy leads to the selection of ABCB5-expressing cells.
PLoS ONE
Show Abstract
Hide Abstract
Metastatic melanoma is the most aggressive skin cancer. Recently, phenotypically distinct subpopulations of tumor cells were identified. Among them, ABCB5-expressing cells were proposed to display an enhanced tumorigenicity with stem cell-like properties. In addition, ABCB5(+) cells are thought to participate to chemoresistance through a potential efflux function of ABCB5. Nevertheless, the fate of these cells upon drugs that are used in melanoma chemotherapy remains to be clarified. Here we explored the effect of anti-melanoma treatments on the ABCB5-expressing cells. Using a melanoma xenograft model (WM266-4), we observed in vivo that ABCB5-expressing cells are enriched after a temozolomide treatment that induces a significant tumor regression. These results were further confirmed in a preliminary study conducted on clinical samples from patients that received dacarbazine. In vitro, we showed that ABCB5-expressing cells selectively survive when exposed to dacarbazine, the reference treatment of metastatic melanoma, but also to vemurafenib, a new inhibitor of the mutated kinase V600E BRAF and other various chemotherapeutic drugs. Our results show that anti-melanoma chemotherapy might participate to the chemoresistance acquisition by selecting tumor cell subpopulations expressing ABCB5. This is of particular importance in understanding the relapses observed after anti-melanoma treatments and reinforces the interest of ABCB5 and ABCB5-expressing cells as potential therapeutic targets in melanoma.
Related JoVE Video
ALK+ALCLs induce cutaneous, HMGB-1-dependent IL-8/CXCL8 production by keratinocytes through NF-?B activation.
Blood
Show Abstract
Hide Abstract
Anaplastic large-cell lymphomas (ALCLs) bearing the t(2;5) translocation (ALK(+)ALCLs) are frequently characterized by skin colonization and associated with a poor prognosis. Using conditional transgenic models of anaplastic lymphoma kinase-positive (ALK(+)) lymphomas and human ALK(+)ALCL cell lines, in the present study, we show that high-mobility-group box-1 (HMGB-1), a proinflammatory cytokine, is released by ALK(+) cells, and demonstrate extracellular HMGB-1-stimulated secretion of the IL-8 chemokine by HaCaT keratinocytes through the involvement of MMP-9, PAR-2, and the NF-?B pathway. Furthermore, we demonstrate that, in vitro, IL-8 is able to induce the invasiveness of ALK(+) cells, which express the IL-8 receptors CXCR1 and CXCR2. In vitro and in vivo, HMGB-1 inhibition achieved by glycyrrhizin treatment led to a drastic reduction in ALK(+) cell invasiveness. The pathophysiological relevance of our observations was confirmed by demonstrating that the HMGB-1 and IL-8 receptors are expressed in ALK(+)ALCL biopsies. We have also shown that IL-8 secretion is correlated with leukemic dissemination of ALK(+) cells in a significant number of patients. The results of the present study demonstrate for the first time a relationship among the pro-inflammatory mediators HMGB-1, MMP-9, PAR-2, and IL-8. We propose that these mediators create a premetastatic niche within the skin, thereby participating in ALK(+) lymphoma epidermotropism.
Related JoVE Video
Loco-regional treatments of the metastatic sites for patients with pauci-metastatic cutaneous melanoma (without brain metastasis): French national guidelines.
Bull Cancer
Show Abstract
Hide Abstract
the last years are marked by the emergence of new molecules for the treatment of metastatic cutaneous melanoma with a significant benefit on the survival. Besides, some techniques are in development for the loco-regional treatment of the metastatic sites, bringing new therapeutic perspectives. However, their respective use and place in the therapeutic strategy are debated by healthcare professionals. the French National Cancer Institute leads a national clinical practice guidelines project since 2008. It realized a review of these modalities of treatment and developed recommendations. the clinical practice guidelines development process is based on systematic literature review and critical appraisal by a multidisciplinary expert workgroup. The recommendations are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines are reviewed by independent practitioners in cancer care delivery. this article presents recommendations for loco-regional treatments of the pulmonary, bone, cutaneous, hepatic and digestive metastatic sites for patients with pauci-metastatic cutaneous melanoma.
Related JoVE Video

What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.