Case Of Anaplastic Large Cell Lymphoma Research Articles

RIP1 expression is necessary for CD30-mediated cell death induction in anaplastic large-cell lymphoma cells

CD30, a member of the tumor necrosis factor receptor (TNFR) superfamily, is consistently expressed by tumor cells of anaplastic large-cell lymphoma (ALCL). CD30 stimulation induces massive caspase-dependent cell death of ALCL cells in case of canonical NFκB inhibition or proteasome inhibition. However, CD30, a TNFR lacking a death domain (DD), is unable to recruit a death inducing complex containing TRADD (TNFR1-associated DD-protein) or FADD (FAS-associated DD-domain protein) together with the receptor-interacting protein 1 (RIP1) and caspase-8. Thus, the mechanism explaining CD30-induced cell death of lymphocytes remains obscure. Here, we demonstrate that blockage of RIP1 by siRNA or pharmacological inhibition of RIP1 by Necrostatin-1 almost completely prevented CD30-induced cell death. In addition, we revealed CD30-induced accumulation of RIP1 at the cytoplasma membrane of NFκB-inhibited ALCL cells by confocal laser scanning microscopy. Finally, primary ALCL cases can be subdivided into two groups based on the presence or absence of RIP1 as revealed by immunohistology. Taken together, our study identified RIP1 as a crucial mediator of CD30-induced cell death that bears features of apoptosis as well as necroptosis. RIP1 expression in ALCL tumor cells might eligible for the therapeutic application of CD30 antibodies in combination with NFκB/proteasome inhibitors that should result in CD30-induced cell death.

Identification of C/EBPβ Target Genes in ALK+ Anaplastic Large Cell Lymphoma (ALCL) by Gene Expression Profiling and Chromatin Immunoprecipitation

C/EBPβ (CCAAT enhancer binding protein) is a transcription factor that plays a crucial role in survival and transformation of ALK+ anaplastic large cell lymphoma (ALCL). The aim of this study was to identify the downstream targets of C/EBPβ responsible for ALK-mediated oncogenesis. C/EBPβ was knocked down in ALK+ ALCL cell lines with a C/EBPβ-shRNA, followed by gene expression profiling (GEP). GEP analysis revealed a reproducible signature of genes that were significantly regulated by C/EBPβ. Classification into biological categories revealed overrepresentation of genes involved in the immune response, apoptosis and cell proliferation. Transcriptional regulation by C/EBPβ was found in 6 of 11 (BCL2A1, G0S2, TRIB1, S100A9, DDX21 and DDIT4) genes investigated by chromatin immunoprecipitation. We demonstrated that BCL2A1, G0S2 and DDX21 play a crucial role in survival and proliferation of ALK+ ALCL cells. DDX21, a gene involved in rRNA biogenesis, was found differentially overexpressed in primary ALK+ ALCL cases. All three candidate genes were validated in primary ALCL cases by either immunohistochemistry or RT-qPCR. In conclusion, we identified and validated several key C/EBPβ-regulated genes with major impact on survival and cell growth in ALK+ ALCL, supporting the central role of C/EBPβ in ALK-mediated oncogenesis.

Clinical presentation of anaplastic large-cell lymphoma in the central nervous system

The majority of primary central nervous system (CNS) lymphomas are diffuse large B-cell lymphomas (DLBCLs) and anaplastic large-cell lymphoma (ALCL) is a type of T-cell tumor that is rare in the CNS. The aim of this study was to elucidate the clinical presentation and standard therapy of ALCLs by investigating reported cases. Additionally, a case of anaplastic lymphoma kinase (ALK)-positive ALCL in a 20-year-old man who exhibited no recurrence for >5 years following high-dose methotrexate (HD-MTX) treatment was described. Twenty-six immunocompetent patients with ALCL of the CNS that were previously reported and 1 case of ALCL of the CNS treated at our hospital were investigated. Overall survival (OS) was analyzed in relation to survival factors such as age, ALK status and the treatment regimen. The male:female ratio of the patients was 19:8. Of the 27 patients, 13 (48.1%) were ALK-positive, 9 (33.3%) were ALK-negative and the ALK status was not determined in the remaining 5 patients (18.5%). ALK-positive ALCL occurred at a younger age (median age, 17 years) and exhibited a favorable course (5-year OS, 75.0%), whereas ALK-negative ALCL presented at an older age (median age, 65 years) and resulted in fatal outcomes (5-year OS, <12.5%). Similar to the findings for systemic ALCL, ALK positivity, age <40 years and chemotherapy are associated with long-term survival for ALCL of the CNS. Chemoradiotherapy including methotrexate is recommended for ALCL and the possibility of treatment with chemotherapy alone for ALK-positive ALCL is currently under consideration.

Intravascular ALK-negative Anaplastic Large Cell Lymphoma With Localized Cutaneous Involvement and an Indolent Clinical Course

Intravascular large T-cell or NK-cell lymphomas rarely present with cutaneous involvement. Intravascular cytotoxic T or NK lymphomas presenting in the skin (cIT/NKL) are often EBV, and reported cases follow a highly aggressive clinical course. Intravascular anaplastic large cell lymphoma (ALCL) by contrast is extraordinarily rare and, when it presents in the skin, raises the question of aggressive clinical behavior in the manner of cIT/NKL versus indolent clinical behavior in the manner of primary cutaneous ALCL. Here we describe a case of localized cutaneous intravascular anaplastic lymphoma kinase-negative ALCL (cIALCL) with a very indolent clinical course. The patient experienced a single cutaneous relapse and remains alive without disease 4 years after diagnosis. Review of the literature reveals multiple clinicopathologic differences between cIALCL and cIT/NKL: distribution (cIALCL, single skin region, P=0.021, Fisher exact test); histology (cIALCL, cohesive with necrosis, P=0.005); immunophenotype (cIALCL, strongly CD30, P=0.021; cIT/NKL, CD56 and/or EBV, P=0.003); and indolent clinical behavior with a trend toward better overall survival (P=0.067, Kaplan-Meier survival analysis). Our index case of cIALCL and 1 other tested case were immunohistochemically confirmed to be intralymphatic (contained within D2-40+vessels) as compared with the blood vessel localization of cIT/NKL. Recognition of cIALCLs as a distinct clinicopathologic entity, and in particular their distinction from aggressive, usually EBV cIT/NKLs, may be possible on the basis of a combination of clinicopathologic criteria, allowing for localized therapy in a subset of patients.

Frequent expression of follicular dendritic cell markers in Hodgkin lymphoma and anaplastic large cell lymphoma

AimsAlthough the tumour cells of Hodgkin lymphoma (HL) are derived from mature B-cells, the lineage infidelity of Hodgkin/Reed–Sternberg cells (HRSs) often causes diagnostic problems. Recently introduced HRS markers are also...

Anaplastic large cell lymphoma associated with breast prostheses

Background In 2011 the Therapeutic Goods Administration (TGA) released a summary report 1 in response to concerns from the US Food and Drug Administration (FDA) review of anaplastic large cell lymphoma (ALCL) associated with breast prostheses. 2 The TGA has received notification of six cases 3 of ALCL associated with breast implants in the Australian population. However the rarity of breast ALCL in the setting of breast implants as well as the background population makes the association controversial. In excess of 30 cases of ALCL associated with breast implants have been published worldwide. 4 Both silicone and saline filled implants have been associated with this disease. 5 Case report We present the histopathological findings in a case of ALCL seen in our institution, including cytological, pathological and immunohistochemical findings. This 33-year-old woman presented with recurrent peri-prosthetic seroma. This case is compared and added to the current literature which is reviewed. Discussion While there is majority agreement of an increase association with breast implant and ALCL the causation in still debated. While it may be premature to include this in the consent process for breast implantation, the available evidence does not support the removal of non-complicated breast implants. Fluid accumulating around an implant more than 6 months after surgery should be sent for cytological evaluation. 6

Gingival Anaplastic Large-Cell Lymphoma Mimicking Hyperplastic Benignancy as the First Clinical Manifestation of AIDS: A Case Report and Review of the Literature

This paper presents an unusual case of gingival ALCL, which mimicked a benign hyperplastic lesion that occurred in a 57-year-old white man representing the first clinical manifestation of acquired immunodeficiency syndrome (AIDS). The patient was referred to the Dental Clinic of PUCPR complaining of a lobulated nodule on the gingiva of his upper central incisors. The presence of advanced chronic periodontitis and dental plaque raised suspicion for a benignancy. An excisional biopsy was performed, and large pleomorphic cells with an abundant cytoplasm, sometimes containing prominent nucleoli and “Hallmark” cells, were observed through hematoxylin and eosin staining. The tumor cells showed strong CD30 expression, EMA, Ki-67, and LCA, and negative stain for p80NPM/ALK, CKAE1/AE3, CD20, CD3, CD56, and CD15. The final diagnosis was ALCL (ALK-negative). Further laboratory tests revealed positivity for human immunodeficiency virus (HIV). The patient was submitted to chemotherapy, but four months after diagnosis, the patient died due to pneumonia and respiratory failure. Oral anaplastic large-cell lymphoma (ALCL) is a rare disorder. Only 5 cases involving the gingiva have been reported, and to our knowledge, this is the first case reported of the ALCL, which mimicked a hyperplastic benignancy as the first clinical manifestation of AIDS.

Primary Central Nervous System ALK Positive Anaplastic Large Cell Lymphoma with Predominantly Leptomeningeal Involvement in an Adult

A 31-year-old Korean male presented with altered consciousness and severe headache. Brain MRI delineated focal leptomeningeal enhancement without any intracerebral lesions. Diagnosis was made based on a brain biopsy showing anaplastic large cell lymphoma (ALCL), immunohistochemical stains revealing positivity for anaplastic lymphoma kinase (ALK) and an absence of involvement in any other organs; specifically, the primary central nervous system ALK+ALCL. Complete remission was achieved following 5 cycles of systemic chemotherapy with a high dose of Methotrexate and a simultaneous 7 cycles of intrathecal triple chemotherapy. Diagnosis of primary leptomeningeal ALK+ALCL is challenging given its rarity and non-specific symptoms along with non-pathognomonic radiologic findings. We present the first case of primary leptomeningeal ALK-positive ALCL where the clinical course, pathologic characteristics and treatment modality are described as well as a review of literature.

Successful treatment of small cell variant anaplastic large cell lymphoma with allogeneic peripheral blood stem cell transplantation, and review of the literature

The small cell variant of anaplastic large cell lymphoma (ALCL) presents in a nearly identical manner to the more common ALK(+) primary ALCL, with the exception that it is more frequently associated with leukemic involvement, and the prognosis has been reported to be poor. We report a 40-year-old Japanese male who was diagnosed with small cell variant ALCL with peripheral blood involvement stage IVB, age-adjusted international prognostic index 3. Conventional cytogenetics of the bone marrow aspirate specimen showed abnormal metaphases with the following karyotype: 47, XY, +X, t(2;5)(p23;q35). The patient was treated with acute lymphoblastic leukemia-oriented intensive chemotherapy. He underwent allogeneic peripheral blood stem cell transplantation from his HLA-DR1 locus mismatch sister. Prior to transplant, the patient had residual lymphadenopathy considered to be in partial remission. As of August 2012, the patient has achieved 18months of continuous complete remission (CCR), with a Karnofsky score of 100%. We have identified a total of seven cases of small cell variant ALCL treated with allogeneic hematopoietic stem cell transplantation (HSCT) in the literature. Of these, no relapse was reported, and four patients were CCR more than 1year. Allogeneic HSCT appears to represent a promising treatment option for small cell variant ALCL.

Cutaneous CD30‐positive lymphoproliferative disorders with CD8 expression: a clinicopathologic study of 21 cases

Lymphomatoid papulosis (LyP) and cutaneous anaplastic large cell lymphoma (ALCL) belong to the spectrum of cutaneous CD30+ lymphoproliferative disorders, an indolent form of T-cell lymphoproliferative disease. We reviewed 21 cases of CD30+ lymphoproliferative lesions expressing cytotoxic profile (CD8+). Seven cases of cutaneous ALCL, 2 cases of systemic ALCL involving the skin, and 12 cases of LyP. The cases of LyP were predominated by small lymphocytes exhibiting a prominent epidermotropic pattern consistent with either type B or type D LyP. Four cases showed co-expression of CD56. The ALCL cases included myxoid features, pseudoepitheliomatous change, and an intravascular component. In all cases that were primary in the skin an indolent clinical course was seen while one patient with systemic myxoid ALCL is in remission following systemic multiagent chemotherapy. The paucity of other neutrophils and eosinophils and concomitant granulomatous inflammation were distinctive features in cases of type B and type D LyP. CD30 and CD45 Ro positivity and a clinical course typical of LyP were useful differentiating features from an aggressive cytotoxic CD8+ T cell lymphoma. In all cases that were primary in the skin an indolent clinical course was observed. CD30 and CD45 Ro positivity and a clinical course typical of LyP were useful in preventing a misdiagnosis of an aggressive cytotoxic CD8+ T cell lymphoma.

Primary hepatic anaplastic large cell ki-1 lymphoma and celiac disease: a casual association?

Although liver is one of the extranodal organs commonly involved in both Hodgkin and non-Hodgkin lymphoma, Primary Hepatic Lymphoma (PHL) is rare. In non-immunocompromised patients, primary hepatic malignant non-hodgkin’s lymphoma is a rare disease, with less than 100 cases reported (1). Anaplastic large-cell lymphomas (ALCL) were first described by Stein et al. in 1985 (2) as large-cell neoplasms with a pleomorphic appearance, subtotal effacement of the lymph node structure and expression of the lymphoid activation antigen CD-30 (ki-1). ALCL frequently involves both lymph nodes and extranodal sites (3). The most common extra-nodal sites affected by ALCL include skin, bone, soft tissue, lung, and liver. However, is extremely rare for ALCL to present as a liver primary lymphoma, and only eight cases have been reported. ALCL accounts for approximately 3% of adult non-Hodgkin lymphomas. The neoplastic cells consistently express CD30 molecule in all variants. Most cases of ALCL are associated with the characteristic chromosomal translocation t[2;5], which results in up regulation of anaplastic lymphoma kinase (ALK) protein. We report a case of a primary hepatic anaplastic large T-cell ki-1 non-Hodgkin lymphoma in a 55-year-old patient with celiac disease.

HIV‐associated primary cutaneous anaplastic large cell lymphoma: a clinicopathological subset with more aggressive behavior? Case report and review of the literature

Human immunodeficiency virus (HIV)-infected patients carry an increased risk of lymphomagenesis. Although the majority of HIV-related lymphomas have a B-cell phenotype, the incidence of peripheral T-cell lymphomas (PTCL), including primary cutaneous subtypes, may be up to 15-fold higher than in the general population, with anaplastic large cell lymphomas (ALCL) accounting for 18-28% of HIV-associated PTCL. In contrast to systemic ALCL, the relation between HIV infection and primary cutaneous ALCL has been relatively neglected in the literature. We report the case of a primary cutaneous ALCL occurring in a 76-year-old patient with advanced HIV infection, and showing unusually aggressive course. Neither ALK1 immunohistochemical positivity nor evidence of EBV infection were detected; staging procedures at initial presentation ruled out systemic involvement. We provide a summary of the literature regarding primary cutaneous ALCL in HIV-infected patients. We draw attention to clinicopathological features, prognostic implications and therapeutic quandaries of HIV-related primary cutaneous ALCL. Further, we propose that a significant fraction of HIV-associated cases might represent a more aggressive subset of primary cutaneous ALCL.

EL6 - Lung Cancer: Driver Oncogene and Molecular-Targeted Therapies

ABSTRACT Identification of oncogenic genomic alterations is expected to facilitate the development of new molecularly targeted therapies for cancer. The first identified ‘driver oncogene’ directly associated with molecular targeted therapies for non-small-cell lung cancer (NSCLC) is mutated epidermal growth factor receptor (EGFR) which is found in up to 30% of Asian NSCLC patients. Preclinical studies demonstrated that EGFR mutation-positive tumors are dependent on, or ‘addicted’ to, EGFR signaling for their growth and survival and exposure of those tumors to EGFR tyrosine kinase inhibitors (TKIs), thus results in EGFR-signaling pathways being turned off and the cancer cells undergoing apoptosis. These findings did quickly translate into clinical trials. Asian landmark phase III trials have now led to the new paradigm of using EGFR-TKIs such as gefitinib or elrotinib for first-line treatment of EGFR-mutation-positive advanced NSCLC. Such findings indicate that the use of molecularly targeted therapy in genetically defined subsets of NSCLC patients may prove to be an effective strategy. Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase whose gene was initially identified as part of the NPM-ALK fusion gene that contributes to the pathogenesis of a subset of anaplastic large cell lymphoma cases. In 2007, a fusion of ALK with the echinoderm microtubule-associated protein-like 4 gene (EML4) was identified by a Japanese group led by Hiroyuki Mano. EML4-ALK undergoes constitutive oligomerization mediated by the coiled-coil domain of the EML4 portion of the fusion protein, and it manifests marked oncogenic activity both in vitro and in vivo. Crizotinib was the first ALK inhibitor to be tested in the clinical setting. On the basis of its dramatic clinical activity, crizotinib was approved by the FDA for treatment of ALK rearrangement-positive NSCLC in August 2011. The promise of molecular targeted drugs against these driver gene alterations brings us closer to personalized lung cancer therapy.

Clinicopathologic study of 20 cases of anaplastic large-cell lymphoma

间变性大细胞淋巴瘤(ALCL)是非霍奇金淋巴瘤的一种少见类型,可分为原发系统型和原发皮肤型.因ALCL的临床表现、形态学和免疫表型上具有多样性,日常工作中易被误诊.为了解ALCL患者的临床病理特点、免疫表型和生物学行为,对20例系统性ALCL标本进行临床病理分析,以期提高对此类少见淋巴瘤的认识.一、材料与方法1.材料:回顾性分析新疆医科大学第一附属医院病理科2006年1月至2011年12月确诊非霍奇金淋巴瘤共850例,参照2008年WHO造血与淋巴组织肿瘤分类的诊断标准[1],收集同期确诊为系统性ALCL 20例,复习其临床病理资料.其中本院16例,会诊4例。

Linfomas primarios del sistema nervioso central

IntroductionPrimary central nervous system lymphoma is a rare subtype of extranodal non-Hodgkin lymphoma that accounts for 4% of central nervous system tumours. Patients and methodsRetrospective review of 24 patients diagnosed with primary central nervous system lymphoma between 1990 and 2010. All patients were diagnosed using magnetic resonance imaging and the diagnosis was confirmed surgically. ResultsOf the 24 patients analysed, all except 4 were immunocompetent. Median age at diagnosis was 59.3 years (range 13-79) and the sex ratio (male to female) was 1:1.1. Cognitive decline (in 33.4%) and headache (in 25%) were the most common complaints. Diagnosis was performed In 13 cases (54%) following craniotomy and in the other 11 cases (46%) after stereotactic biopsy. Breakdown by pathology was as follows: 22 cases of B-cell lymphoma (91.6%), 1 case of anaplastic large-cell lymphoma, and 1 case of T-cell lymphoma. Mean survival time was 12.8 months with an overall 1-year survival rate of 37.5%. ConclusionsPrimary central nervous system lymphoma often presents in the sixth decade with cognitive decline, headache, and focal neurological deficits. A single intracranial lesion was present in 75% of the patients (18 cases), and the remaining 25% (6 cases) had between 2 and 4 lesions. Preoperative clinical status was the most important factor determining prognosis.

Detection of chromosomal translocations involving ALK gene in anaplastic large cell lymphoma by fluorescence in-situ hybridization and its clinical significance

To investigate clinicopathologic features and clinical value of the chromosomal translocation involving anaplastic lymphoma kinase (ALK) in anaplastic large cell lymphoma (ALCL) by fluorescence in situ hybridization (FISH). A total of 55 cases, including 45 cases of ALCL and 10 reactive lymphoid hyperplasia, were collected during 1999 to 2006 in the Department of Pathology, Fudan University Shanghai Cancer Center, and Xinhua Hospital Affiliated to Shanghai Jiaotong University. All cases were studied by FISH using dual color break apart probes of ALK for detection of chromosomal translocation, compared with the previous results of immunohistochemistry (IHC) and reverse-transcriptase polymerase chain reaction (RT-PCR) for the detection of ALK aberrations. The result of FISH showed that the clear red and green fluorescence signals were detected in 38 cases of ALCL, in which conspicuous split signals were observed in tumor cells in 24 cases (63.2%), suggesting the rearrangement of the ALK locus, with multiple copies of ALK gene in one case. In addition, the rearrangement of the ALK locus was not identified in 14 of 38 cases (36.8%); and the FISH results were unable to be evaluated in 7 cases, because no fluorescent signals involving ALK gene were found or signals were too weak to be analyzed. The concordance for the detection ALK aberrations in ALCL between FISH and RT-PCR, FISH and IHC were both statistically significant (P < 0.01). Chromosomal translocation involving ALK gene was not found in all 10 cases of reactive lymphoid hyperplasia. ALCL is an entity of lymphoma characterized by special clinical presentation, morphology, and ALK aberrations. FISH is helpful for detection of the chromosomal translocations involving ALK in ALCL, however, the detection efficiency by FISH may be affected by storage time of the paraffin-embedded tissue; and therefore combined detection with IHC and RT-PCR could complement each other and help for differential diagnosis of ALK(+)ALCL from ALK(-)ALCL.

Risk of lymphoma in women with breast implants

Large studies suggest that the overall rate of lymphoma in women with breast implants is no greater than in the general population; clinical reports suggest an association between breast implants and the rare non-Hodgkin lymphoma, anaplastic large cell lymphoma (ALCL). Observed cases of lymphoma reported in Allergan-sponsored breast implant clinical studies were compared with expected cases on the basis of the incidence of lymphoma among women in the National Cancer Institute's Surveillance Epidemiology and End Results program, using standardized incidence ratios (SIRs) and 95% confidence intervals (CIs). In clinical studies, there were 28 observed cases of lymphoma among 89 382 patients and 204 682 person-years of follow-up compared with 43 expected cases [SIR: 28/43=0.65 (95% CI: 0.43-0.94), P=0.02]. SIRs were calculated stratifying by baseline cancer history: women without prior cancer [SIR: 17/24=0.70 (95% CI: 0.41-1.13), P=0.17] and women with prior cancer [SIR: 11/14=0.79 (95% CI: 0.39-1.41), P=0.52]. SIRs were calculated by implant shell type: textured shell implants [SIR: 16/23=0.70 (95% CI: 0.40-1.13), P=0.16] and smooth shell implants [SIR: 12/19=0.63 (95% CI: 0.33-1.10), P=0.12]. Surveillance Epidemiology and End Results reported 12 cases of primary breast ALCL in women between 1996 and 2007 without a history of cancer, for an average annual incidence of 4.28 (95% CI: 3.51-5.05)/100 million women in the US - these women may or may not have breast implants. In clinical studies, three ALCL cases were reported in women with breast implants and a history of breast cancer, yielding a crude incidence rate of 1.46 (95% CI: 0.30-4.3)/100 000 person-years. Large clinical studies, based on over 200 000 person-years of follow-up, suggest no evidence of an increased risk of lymphoma among women who have received breast implants.

The PIP mammary prosthesis: A product recall study

Concerns about the durability of silicone breast implants manufactured by Poly Implant Prothèse (PIP) have been expressed for several years prior to their formal withdrawal from the market in March 2010. Although precise details of what elements were at fault remain unclear, concerns have been raised about both the elastomer and the filler gel. Media speculation has focussed on device safety, longevity and, recently, a possible association with lymphoma, specifically anaplastic large cell lymphoma (ALCL). There is however, no actual data concerning these implants with which to guide and inform when concerned patients seek advice. PIP mammary prostheses were used by the senior author for both primary and revision breast augmentation (BA) during the period January 2000-August 2005. A database of patients was constructed and attempts made to contact each patient offering a free consultation and referral for ultrasound scan (USS). Chief outcome measures included secondary surgery, the implant rupture rate and time to rupture. 453 consecutive patients with PIP devices were identified. Of this number 30 had already undergone implant exchange for a variety of reasons. 180 (39.7%) could not be contacted and 19 had undergone explantation elsewhere, including the NHS. Of those who could be contacted, 47 declined consultation as they had no concerns. 97 had neither clinical signs nor radiographic evidence of implant rupture and elected to remain under regular review. At the time of writing, 38 have undergone implant exchange after ultrasonographic indication of rupture and the overall patient rupture rate for the PIP implant is 15.9-33.8%. This cohort correlates reduced implant longevity with each successive year from 2000 and no cases of ALCL have been diagnosed. Long-term studies such as this are difficult to undertake for a number of reasons as they place a significant additional burden of resources on a practice. They are, however, essential from an industry perspective both for the provision of information and supporting audit and professional standing. Being only a single-handed practice, this initial study is the tip of an iceberg that may affect 40,000 women in the UK with PIP implants, but it does provide some hard data with which to guide our patients. It is also believed to be the first independent product recall study in aesthetic breast surgery.

Galectin-1-mediated cell death is increased by CD30-induced signaling in anaplastic large cell lymphoma cells but not in Hodgkin lymphoma cells

Endogenous β-galactose-binding lectins have many biological functions, but their biological significance in Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL) remains unclear. By immunohistochemistry, we analyzed the expression of galectin-1 and galectin-3 in HL and ALCL cases as well as in cell lines, and investigated the pharmacological effects of galectin-1 treatment with and without CD30 pre-stimulation of HL and ALCL cell lines. The galectin-3-negative human embryonic kidney cell line (HEK-293) was transfected with galectin-3 cDNA. Galectin-3 is differentially expressed in HL and ALCL. CD30 stimulation of the ALCL cell line Karpas 299 activates NF-κB without induction of apoptosis. Galectin-1 treatment of Karpas 299 induces cell death, which is significantly increased by CD30 pre-stimulation. The CD30-mediated increase of galectin-1-induced cell death is to some extent caspase independent and does not influence the expression of tumor necrosis factor-associated factor 1 (TRAF1), TRAF2, and cellular inhibitor of apoptosis 2 protein (cIAP2), as revealed in Karpas 299 cells. In other cell lines except Karpas 299, CD30 pre-stimulation did not significantly enhance galectin-1-induced cell death. Galectin-3 transfection of HEK-293 cells resulted in cell surface expression of galectin-3, associated with marked cell aggregation. CD30-targeted therapy in combination with galectin-1 treatment may induce effective killing of ALCL cells but not of HL cells.

Prothèse mammaire et lymphome T anaplasique à grandes cellules : que savons-nous ?

There is a new concern about a possible association between anaplastic large cell lymphoma (ALCL) and breast implants. The purpose of this review was to identify and analyze all reported cases of ALCL occurring in patients with breast implants. Therefore, we reviewed all articles published concerning this subject between 1991and 2011. We found 41cases of ALCL. The mean age of the patients was 51years old with an average of 108months between the implantation and the diagnosis. Over 60% of the reported cases were aesthetic augmentations. However, none of the published study managed to highlight a correlation between the prosthesis and this lymphoma. Therefore, we believe that for the moment, we can reassure our patients, but we must be aware of this association if a late seroma or a tumefaction occur on prosthesis. The surgical management seems to be essential for the diagnosis and the treatment, especially by the negative ALK and CD 30expression of this lymphoma.