RESUMO
Lymphomatoid papulosis (LyP) has several histopathologic presentations. LyP featuring gamma-delta (γδ) T-cell receptor expression may masquerade as and may be misdiagnosed as aggressive cutaneous T-cell lymphoma, particularly primary cutaneous γδ T-cell lymphoma (PCGDTL) or γδ mycosis fungoides. We performed a clinicopathologic analysis of the largest series of LyP featuring γδ T-cell expression. We identified 26 patients with a diagnosis of LyP with γδ T cells from our institutions, as well as through a comprehensive review of the literature, and characterized these cases. Most cases were treated with topical steroids or not treated at all. The majority of cases showed a CD4 - CD8 + phenotype and featured at least one cytotoxic marker. Histopathologic features included an intraepidermal or dermal infiltrate with large cells and frequent angiotropism. One case was initially misdiagnosed as PCGDTL, requiring further therapy. Our case series, the largest international cohort of γδ T cell predominant LyP cases, confirms marked clinicopathologic heterogeneity that may contribute to misdiagnosis, reasserting the need to identify classic clinical features, CD30 + T-cell components, and markers of cytotoxicity when dealing with this differential diagnosis. A limitation of this study includes somewhat limited follow-up, histologic, and immunophenotypic information for some cases.
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Linfoma Cutâneo de Células T , Papulose Linfomatoide , Micose Fungoide , Neoplasias Cutâneas , Humanos , Papulose Linfomatoide/patologia , Neoplasias Cutâneas/patologia , Micose Fungoide/patologia , Receptores de Antígenos de Linfócitos TRESUMO
Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is the most commonly used regimen for the upfront treatment of diffuse large B-cell lymphoma (DLBCL). However, it is associated with cardiotoxicity, especially in older patients. Substituting doxorubicin with non-PEGylated liposomal doxorubicin (R-COMP) may reduce the risk of cardiac events, but its efficacy has never been demonstrated in prospective trials. We describe the characteristics and outcome of patients with DLBCL aged ≥65 years prospectively enrolled in the Elderly Project by the Fondazione Italiana Linfomi and treated with full doses of R-CHOP or R-COMP per local practice. Starting from 1163 patients, 383 (55%) were treated with R-CHOP and 308 (45%) with R-COMP. Patients treated with R-COMP were older (median age, 76 vs 71 years), less frequently fit at simplified geriatric assessment (61% vs 88%; P < .001), and had a more frequent baseline cardiac disorders (grade >1, 32% vs 8%; P < .001). Three-year progression-free survival (PFS) was similar between R-CHOP and R-COMP (70% and 64%); 3-year overall survival was 77%, and 71% respectively. R-CHOP was associated with better PFS vs R-COMP only in the Elderly Prognostic Index (EPI) low-risk group. The two groups had similar rates of treatment interruptions due to toxicities or of cardiac events (P = 1.00). We suggest R-COMP is a potentially curative treatment for older patients with intermediate- or high-risk EPI, even in the presence of a baseline cardiopathy. R-CHOP is confirmed as the standard therapy for low risk patients.
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Cardiopatias , Linfoma Difuso de Grandes Células B , Idoso , Humanos , Rituximab/efeitos adversos , Vincristina/efeitos adversos , Estudos de Coortes , Estudos Prospectivos , Prednisona/efeitos adversos , Resultado do Tratamento , Linfoma Difuso de Grandes Células B/patologia , Doxorrubicina/efeitos adversos , Cardiopatias/etiologia , Ciclofosfamida/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
Up to 10%-15% of diffuse large B-cell lymphoma (DLBCL) are related to hepatitis C virus (HCV) infection, in particular in elderly patients. The Fondazione Italiana Linfomi has recently published a multicentre prospective observational study, the 'Elderly Project', on the outcome of DLBCL in patients aged ≥65 years, evaluated using a simplified comprehensive geriatric assessment. The aim of this study was to compare biological and clinical features of HCV positive (HCV+) with HCV negative (HCV-) cases. A total of 89 HCV+ patients were identified out of 1095 evaluated for HCV serology (8.1%). The HCV+ patients were older, less fit, and had frequent extranodal involvement. The cell-of-origin determination by Nanostring showed that HCV+ cases less frequently had an activated B-cell profile compared to HCV- patients (18% vs. 43%). In all, 86% of HCV+ patients received rituximab-cyclophosphamide, doxorubicin, vincristine (Oncovin) and prednisone (R-CHOP)-like immunochemotherapy. Grade 3-4 liver toxicity occurred in 3% of cases. Among centrally reviewed cases confirmed as DLBCL, the 3-year overall survival of HCV+ patients was very similar to HCV- (63% vs. 61%, p = 0.926). In all, 20 HCV+ patients were treated with direct-acting antiviral agents (DAAs), with good tolerance and sustained virological response in all cases. The 3-year progression-free survival for this subgroup was excellent (77%), suggesting DAAs' possible role in reducing the risk of relapse by eliminating the viral trigger.
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Hepatite C Crônica , Hepatite C , Linfoma Difuso de Grandes Células B , Idoso , Humanos , Hepacivirus/genética , Antivirais/uso terapêutico , Estudos Prospectivos , Hepatite C Crônica/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Hepatite C/tratamento farmacológico , Hepatite C/epidemiologia , Rituximab/uso terapêutico , Doxorrubicina/uso terapêutico , Vincristina/uso terapêutico , Ciclofosfamida/uso terapêutico , Prednisona/uso terapêuticoRESUMO
Emerging evidence indicates that chemoresistance is closely related to altered metabolism in cancer. Here, we hypothesized that distinct metabolic gene expression profiling (GEP) signatures might be correlated with outcome and with specific fluorodeoxyglucose positron emission tomography (FDG-PET) radiomic profiles in diffuse large B-cell lymphoma (DLBCL). We retrospectively analyzed a discovery cohort of 48 consecutive patients with DLBCL treated at our center with standard first-line chemoimmunotherapy by performing targeted GEP (T-GEP)- and FDG-PET radiomic analyses on the same target lesions at baseline. T-GEP-based metabolic profiling identified a 6-gene signature independently associated with outcomes in univariate and multivariate analyses. This signature included genes regulating mitochondrial oxidative metabolism (SCL25A1, PDK4, PDPR) that were upregulated and was inversely associated with genes involved in hypoxia and glycolysis (MAP2K1, HIF1A, GBE1) that were downregulated. These data were validated in 2 large publicly available cohorts. By integrating FDG-PET radiomics and T-GEP, we identified a radiometabolic signature (RadSig) including 4 radiomic features (histo kurtosis, histo energy, shape sphericity, and neighboring gray level dependence matrix contrast), significantly associated with the metabolic GEP-based signature (r = 0.43, P = .0027) and with progression-free survival (P = .028). These results were confirmed using different target lesions, an alternative segmentation method, and were validated in an independent cohort of 64 patients. RadSig retained independent prognostic value in relation to the International Prognostic Index score and metabolic tumor volume (MTV). Integration of RadSig and MTV further refined prognostic stratification. This study provides the proof of principle for the use of FDG-PET radiomics as a tool for noninvasive assessment of cancer metabolism and prognostic stratification in DLBCL.
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Fluordesoxiglucose F18 , Linfoma Difuso de Grandes Células B , Humanos , Estudos Retrospectivos , Tomografia por Emissão de Pósitrons/métodos , Linfoma Difuso de Grandes Células B/patologia , Perfilação da Expressão GênicaRESUMO
The role and regulation of innate immune cells is poorly understood in B-cell non-Hodgkin lymphoma (NHL). As natural killer (NK) cells, helper innate lymphoid cells (ILCs) are lymphocytes endowed with either anti- or pro-tumour activity and involved in inflammatory processes. In our ex vivo analysis of NK cells and ILCs from NHL patients, we observed that, in comparison to healthy donors (HD), the frequency of the cytotoxic subset of NK cells, the CD16+ NK, decreased in patients' peripheral blood. In general, circulating NK cells showed a pro-tumorigenic phenotype, while ILCs displayed a more activated/cytotoxic phenotype. Conversely, at the tumour site, in patients' lymph nodes, ILCs showed a low expression of granzyme.In vitromixed lymphocyte-tumour cell cultures with HD PBMCs and NHL cell lines demonstrated that ILC cytotoxic potential was lowered by the presence of tumour cells but, in the absence of T regulatory cells (Tregs), their cytolytic potential was recovered. Our data shed novel light on dysfunctional innate immunity in NHL. We suggest a new mechanism of tumour immuno-escape based on the reduction of cell cytotoxicity involving ILCs and likely controlled by Tregs.
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Antineoplásicos , Linfoma não Hodgkin , Neoplasias , Humanos , Evasão Tumoral , Imunidade Inata , Linfócitos , Células Matadoras Naturais , Neoplasias/patologia , Linfoma não Hodgkin/patologiaRESUMO
BACKGROUND: Histiocytic and dendritic cell neoplasms (HDCNs) represent very rare tumors, which have been the subject of debate during the last few years. OBJECTIVES: We aimed to provide a comprehensive review of the subject. MATERIALS AND METHODS: The experience gained by the authors in large international studies and as a national reference center has been summarized to highlight the characteristics of each entity. RESULTS: The clinical, morphologic, phenotypic, and molecular data of the different entities included under the heading of HDCNs are extensively discussed. CONCLUSION: Currently, HDCNs are classified in the group of orphan diseases for which a standardized therapy is lacking. An international registry would facilitate expansion and dissemination of knowledge of these diseases and improve their treatment.
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Células Dendríticas , Neoplasias , Células Dendríticas/patologia , Histiócitos , Neoplasias/patologiaRESUMO
PURPOSE: Peripheral T-cell lymphoma (PTCL) includes heterogeneous clinicopathologic entities with numerous diagnostic and treatment challenges. We previously defined robust transcriptomic signatures that distinguish common PTCL entities and identified two novel biologic and prognostic PTCL-not otherwise specified subtypes (PTCL-TBX21 and PTCL-GATA3). We aimed to consolidate a gene expression-based subclassification using formalin-fixed, paraffin-embedded (FFPE) tissues to improve the accuracy and precision in PTCL diagnosis. MATERIALS AND METHODS: We assembled a well-characterized PTCL training cohort (n = 105) with gene expression profiling data to derive a diagnostic signature using fresh-frozen tissue on the HG-U133plus2.0 platform (Affymetrix, Inc, Santa Clara, CA) subsequently validated using matched FFPE tissues in a digital gene expression profiling platform (nCounter, NanoString Technologies, Inc, Seattle, WA). Statistical filtering approaches were applied to refine the transcriptomic signatures and then validated in another PTCL cohort (n = 140) with rigorous pathology review and ancillary assays. RESULTS: In the training cohort, the refined transcriptomic classifier in FFPE tissues showed high sensitivity (> 80%), specificity (> 95%), and accuracy (> 94%) for PTCL subclassification compared with the fresh-frozen-derived diagnostic model and showed high reproducibility between three independent laboratories. In the validation cohort, the transcriptional classifier matched the pathology diagnosis rendered by three expert hematopathologists in 85% (n = 119) of the cases, showed borderline association with the molecular signatures in 6% (n = 8), and disagreed in 8% (n = 11). The classifier improved the pathology diagnosis in two cases, validated by clinical findings. Of the 11 cases with disagreements, four had a molecular classification that may provide an improvement over pathology diagnosis on the basis of overall transcriptomic and morphological features. The molecular subclassification provided a comprehensive molecular characterization of PTCL subtypes, including viral etiologic factors and translocation partners. CONCLUSION: We developed a novel transcriptomic approach for PTCL subclassification that facilitates translation into clinical practice with higher precision and uniformity than conventional pathology diagnosis.
Assuntos
Linfoma de Células T Periférico , Humanos , Linfoma de Células T Periférico/diagnóstico , Linfoma de Células T Periférico/genética , Transcriptoma , Reprodutibilidade dos Testes , Perfilação da Expressão Gênica , PrognósticoRESUMO
The role of macrophages (Mo) and their prognostic impact in diffuse large B-cell lymphomas (DLBCL) remain controversial. By regulating the lipid metabolism, Liver-X-Receptors (LXRs) control Mo polarization/inflammatory response, and their pharmacological modulation is under clinical investigation to treat human cancers, including lymphomas. Herein, we surveyed the role of LXRs in DLBCL for prognostic purposes. Comparing bulk tumors with purified malignant and normal B-cells, we found an intriguing association of NR1H3, encoding for the LXR-α isoform, with the tumor microenvironment (TME). CIBERSORTx-based purification on large DLBCL datasets revealed a high expression of the receptor transcript in M1-like pro-inflammatory Mo. By determining an expression cut-off of NR1H3, we used digital measurement to validate its prognostic capacity on two large independent on-trial and real-world cohorts. Independently of classical prognosticators, NR1H3high patients displayed longer survival compared with NR1H3low cases and a high-resolution Mo GEP dissection suggested a remarkable transcriptional divergence between subgroups. Overall, our findings indicate NR1H3 as a Mo-related biomarker identifying patients at higher risk and prompt future preclinical studies investigating its mouldability for therapeutic purposes.
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Linfoma Difuso de Grandes Células B , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/genética , Microambiente Tumoral , Receptores X do Fígado/genéticaRESUMO
T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) is a rare and aggressive variant of diffuse large B-cell lymphoma (DLBCL) that usually affects young to middle-aged patients, with disseminated disease at presentation. The tumor microenvironment (TME) plays a key role in THRLBCL due to its peculiar cellular composition (<10% neoplastic B cells interspersed in a cytotoxic T-cell/histiocyte-rich background). A significant percentage of THRLBCL is refractory to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP)-based regimens and to chimeric antigen receptor T-cell therapy; thus, the development of a specific therapeutic approach for these patients represents an unmet clinical need. To better understand the interaction of immune cells in THRLBCL TME and identify more promising therapeutic strategies, we compared the immune gene expression profiles of 12 THRLBCL and 10 DLBCL samples, and further corroborated our findings in an extended in silico set. Gene coexpression network analysis identified the predominant role of the programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) axis in the modulation of the immune response. Furthermore, the PD-1/PD-L1 activation was flanked by the overexpression of 48 genes related to the functional exhaustion of T cells. Globally, THRLBCL TME was highly interferon-inflamed and severely exhausted. The immune gene profiling findings strongly suggest that THRLBCL may be responsive to anti-PD-1 therapy but also allowed us to take a step forward in understanding THRLBCL TME. Of therapeutic relevance, we validated our results by immunohistochemistry, identifying a subset of TCF1+ (T cell-specific transcription factor 1, encoded by the TCF7 gene) progenitor exhausted T cells enriched in patients with THRLBCL. This subset of TCF1+ exhausted T cells correlates with good clinical response to immune checkpoint therapy and may improve prediction of anti-PD-1 response in patients with THRLBCL.
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Antígeno B7-H1 , Linfoma Difuso de Grandes Células B , Apoptose , Antígeno B7-H1/genética , Fator 1-alfa Nuclear de Hepatócito , Histiócitos/metabolismo , Histiócitos/patologia , Humanos , Ligantes , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/genética , Receptor de Morte Celular Programada 1 , Microambiente TumoralRESUMO
BACKGROUND: The mechanisms involved in mycosis fungoides, and Sezary Syndrome progression are largely unknown. Over the last decade the interest in immune system contrast of neoplasm has grown owing to the introduction of immunotherapy. PD-1 and its ligand (PD-L1) are the target of several immunotherapy treatment. In the literature reports on the expression of PD-1 and PD-L1 have provided contrasting results. METHODS: In our analysis we investigated PD-1 expression in neoplastic cells and in tumor infiltrating lymphocytes (TILs) as well as PD-L1 expression in tumor cells and in tumor associated macrophages (TAMs). PD-L1 and PD-1 positive cells were counted in 5 high-power fields (HPF) and scored as the average number of positive neoplastic cells/TILs/TAMs per HPF. RESULTS: From databases of two institutions (Bologna and Florence) thirty-five patients corresponding to 43 biopsies were retrieved. In seven instances sequential biopsies were present. No statistically significant expression was observed comparing early to advanced stages by analysing PD-1 by tumor cells and TILs and of PD-L1 by tumor cells and TAMs. CONCLUSIONS: Our results corroborate that PD-1 and PD-L1 expression is not stage-dependent in mycosis fungoides and Sezary syndrome. However, PD-1 and PD-L1 expression in affected patients provides a rationale to schedule anti PD-1/PD-L1 drugs.
Assuntos
Antígeno B7-H1 , Micose Fungoide , Receptor de Morte Celular Programada 1 , Síndrome de Sézary , Neoplasias Cutâneas , Antígeno B7-H1/genética , Humanos , Linfócitos do Interstício Tumoral , Micose Fungoide/metabolismo , Receptor de Morte Celular Programada 1/genética , Síndrome de Sézary/metabolismo , Neoplasias Cutâneas/metabolismoRESUMO
Standard chemotherapies for diffuse large B-cell lymphoma (DLBCL), based on the induction of exogenous DNA damage and oxidative stress, are often less effective in the presence of increased MYC and BCL-2 levels, especially in the case of double hit (DH) lymphomas harboring rearrangements of the MYC and BCL-2 oncogenes, which enrich for a patient's population characterized by refractoriness to anthracycline-based chemotherapy. Here we hypothesized that adaptive mechanisms to MYC-induced replicative and oxidative stress, consisting in DNA damage response (DDR) activation and BCL-2 overexpression, could represent the biologic basis of the poor prognosis and chemoresistance observed in MYC/BCL-2-positive lymphoma. We first integrated targeted gene expression profiling (T-GEP), fluorescence in situ hybridization (FISH) analysis, and characterization of replicative and oxidative stress biomarkers in two independent DLBCL cohorts. The presence of oxidative DNA damage biomarkers identified a poor prognosis double expresser (DE)-DLBCL subset, characterized by relatively higher BCL-2 gene expression levels and enrichment for DH lymphomas. Based on these findings, we tested therapeutic strategies based on combined DDR and BCL-2 inhibition, confirming efficacy and synergistic interactions in in vitro and in vivo DH-DLBCL models. These data provide the rationale for precision-therapy strategies based on combined DDR and BCL-2 inhibition in DH or DE-DLBCL.
Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Enzimas Reparadoras do DNA/antagonistas & inibidores , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores , Sulfonamidas/farmacologia , Tiofenos/farmacologia , Ureia/análogos & derivados , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/farmacologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Linfoma Difuso de Grandes Células B/metabolismo , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Taxa de Sobrevida , Ureia/farmacologia , Adulto JovemRESUMO
Patients with relapsed/refractory (R/R) peripheral T-cell lymphoma (PTCL) have a poor prognosis, with an expected survival of less than 1 year using standard salvage therapies. Recent advances in our understanding of the biology of PTCL have led to identifying B-Cell Lymphoma 2 (BCL2) protein as a potential therapeutic target. BLC2 inhibitor venetoclax was investigated in a prospective phase II trial in patients with BCL2-positive R/R PTCL after at least one previous standard line of treatment (NCT03552692). Venetoclax given alone at a dosage of 800 mg/day resulted in one complete response (CR) and two stable diseases (SDs) among 17 enrolled patients. The majority of patients (88.2%) interrupted the treatment due to disease progression. No relationship with BCL2 expression was documented. At a median follow-up of 8 months, two patients are currently still on treatment (one CR and one SD). No case of tumor lysis syndrome was registered. Therefore, venetoclax monotherapy shows activity in a minority of patients whose biological characteristics have not yet been identified. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov (NCT03552692, EudraCT number 2017-004630-29).
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The unstructured nature of Real-World (RW) data from onco-hematological patients and the scarce accessibility to integrated systems restrain the use of RW information for research purposes. Natural Language Processing (NLP) might help in transposing unstructured reports into standardized electronic health records. We exploited NLP to develop an automated tool, named ARGO (Automatic Record Generator for Onco-hematology) to recognize information from pathology reports and populate electronic case report forms (eCRFs) pre-implemented by REDCap. ARGO was applied to hemo-lymphopathology reports of diffuse large B-cell, follicular, and mantle cell lymphomas, and assessed for accuracy (A), precision (P), recall (R) and F1-score (F) on internal (n = 239) and external (n = 93) report series. 326 (98.2%) reports were converted into corresponding eCRFs. Overall, ARGO showed high performance in capturing (1) identification report number (all metrics > 90%), (2) biopsy date (all metrics > 90% in both series), (3) specimen type (86.6% and 91.4% of A, 98.5% and 100.0% of P, 92.5% and 95.5% of F, and 87.2% and 91.4% of R for internal and external series, respectively), (4) diagnosis (100% of P with A, R and F of 90% in both series). We developed and validated a generalizable tool that generates structured eCRFs from real-life pathology reports.
Assuntos
Registros Eletrônicos de Saúde , Hematologia , Oncologia , Relatório de Pesquisa , Gerenciamento Clínico , Hematologia/métodos , Hematologia/normas , Humanos , Oncologia/métodos , Oncologia/normas , Processamento de Linguagem Natural , Fluxo de TrabalhoRESUMO
Peripheral T-cell lymphoma, not otherwise specified (PTCL_NOS) corresponds to about one fourth of mature T-cell tumors, which overall represent 10-12% of all lymphoid malignancies. This category comprises all T-cell neoplasms, which do not correspond to any of the distinct entities listed in the WHO (World Health Organization) Classification of Tumours of Haematopoietic and Lymphoid Tissues. In spite of the extreme variability of morphologic features and phenotypic profiles, gene expression profiling (GEP) studies have shown a signature that is distinct from that of all remaining PTCLs. GEP has also allowed the identification of subtypes provided with prognostic relevance. Conversely to GEP, next-generation sequencing (NGS) has so far been applied to a limited number of cases, providing some hints to better understand the pathobiology of PTCL_NOS. Although several pieces of information have emerged from pathological studies, PTCL_NOS still remains a tumor with a dismal prognosis. The usage of CHOEP (cyclophosphamide, doxorubicin, vincristine, prednisone, etoposide) followed by autologous stem cell transplantation may represent the best option, by curing about 50% of the patients whom such an approach can be applied to. Many new drugs have been proposed without achieving the expected results. Thus, the optimal treatment of PTCL_NOS remains unidentified.
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Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and highly aggressive hematologic malignancy originating from plasmacytoid dendritic cells (pDCs). The microRNA expression profile of BPDCN was compared to that of normal pDCs and the impact of miRNA dysregulation on the BPDCN transcriptional program was assessed. MiRNA and gene expression profiling data were integrated to obtain the BPDCN miRNA-regulatory network. The biological process mainly dysregulated by this network was predicted to be neurogenesis, a phenomenon raising growing interest in solid tumors. Neurogenesis was explored in BPDCN by querying different molecular sources (RNA sequencing, Chromatin immunoprecipitation-sequencing, and immunohistochemistry). It was shown that BPDCN cells upregulated neural mitogen genes possibly critical for tumor dissemination, expressed neuronal progenitor markers involved in cell migration, exchanged acetylcholine neurotransmitter, and overexpressed multiple neural receptors that may stimulate tumor proliferation, migration and cross-talk with the nervous system. Most neural genes upregulated in BPDCN are currently investigated as therapeutic targets.
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Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare and newly recognized subtype of T cell Non-Hodgkin Lymphoma (NHLs) associated with breast implants.The mechanism involved in the development of this kind of lymphoma is still uncertain.BIA-ALCL is generally an indolent disease localized to the breast implant and its capsule and effectively treated with capsulectomy alone without chemotherapy.Clinically, BIA-ALCL may typically present a sudden-onset breast-swelling secondary to periimplant effusion. The minority of BIA-ALCL patients present a more aggressive mass-forming subtype, for which systemic therapy is mandatory.Despite the number of cases has recently increased, BIA-ALCL remains a rare disease described mainly in several case reports and small case series.Breast imaging, including mammography, ultrasound and breast MRI are routinely used in the screening of breast cancer; however, guidelines for the imaging and pathological diagnosis of this disease have only recently been proposed and included in the 2019 National Comprehensive Cancer Network (NCCN) consensus guidelines for BIA-ALCL.The main purpose of this pictorial is to illustrate the MRI signs of BIA-ALCL and correlate them with the corresponding pathology features in order to improve the knowledge of the principals MRI features of this type of lymphoma.
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Implantes de Mama/efeitos adversos , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/etiologia , Linfoma Anaplásico de Células Grandes/diagnóstico por imagem , Linfoma Anaplásico de Células Grandes/etiologia , Imageamento por Ressonância Magnética/métodos , Mama/diagnóstico por imagem , Feminino , HumanosRESUMO
Diffuse large B-cell lymphoma (DLBCL) is the commonest form of lymphoid malignancy, with a prevalence of about 40% worldwide. Its classification encompasses a common form, also termed as "not otherwise specified" (NOS), and a series of variants, which are rare and at least in part related to viral agents. Over the last two decades, DLBCL-NOS, which accounts for more than 80% of the neoplasms included in the DLBCL chapter, has been the object of an increasing number of molecular studies which have led to the identification of prognostic/predictive factors that are increasingly entering daily practice. In this review, the main achievements obtained by gene expression profiling (with respect to both neoplastic cells and the microenvironment) and next-generation sequencing will be discussed and compared. Only the amalgamation of molecular attributes will lead to the achievement of the long-term goal of using tailored therapies and possibly chemotherapy-free protocols capable of curing most (if not all) patients with minimal or no toxic effects.