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1.
Am J Clin Pathol ; 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39259664

RESUMO

OBJECTIVES: CD49f is an adhesion molecule present on malignant lymphoblasts in B-cell acute lymphoblastic leukemia; it is associated with a poor prognosis. CD49f expression has been proposed as a marker for measurable residual disease (MRD) marker, but this marker has yet to be implemented in clinical practice. METHODS: In this study, we used flow cytometry to detect CD49f expression by leukemic blasts in paired bone marrow and cerebrospinal fluid samples at diagnosis and bone marrow at day 15 of treatment. RESULTS: At diagnosis, 93% of bone marrow and 100% of cerebrospinal fluid lymphoblasts expressed CD49f. The intensity of CD49f expression statistically significantly increased during treatment (P < .001). In MRD-negative end-of-treatment samples, only a small population of hematogones expressed CD49f. Interestingly, the intensity of CD49f expression varied among the different groups of recurrent genetic abnormalities. The ETV6::RUNX1 fusion and ETV6::RUNX1 combined with the high hyperdiploid group were associated with increased expression, whereas the Philadelphia-like group showed low CD49f expression. The lower CD49f expression at diagnosis predicted a lower MRD rate at day 15 of treatment. CONCLUSIONS: We concluded that CD49f can be used as an MRD marker and possible prognostic factor in B-cell acute lymphoblastic leukemia.

2.
J Cutan Pathol ; 51(11): 868-875, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39081081

RESUMO

BACKGROUND: Primary cutaneous marginal zone lymphoma (PCMZL) and primary cutaneous CD4+ small/medium T-cell lymphoproliferative disease (CD4+ TLPD) are two distinct entities with excellent prognosis; however, they show profound clinical and histopathological similarities, leading to differential diagnostic uncertainty. AIMS: Our aim was to review and reanalyze cases of primary cutaneous lymphoproliferations diagnosed at Semmelweis University, featuring characteristics of PCMZL and CD4+ TLPD. MATERIALS AND METHODS: Cutaneous lymphoma biopsy specimens between 2018 and 2022 were collected and re-evaluated. Medical history, clinical picture, imaging, and laboratory findings were collected. Immunohistochemical staining for CD20, CD3, BCL6, CD10, PD1, CD3, CD4, CD8, and PCR tests for IGH, IGK, TCRB, and TCRG were repeated in selected cases. RESULTS: Among 55 cases diagnosed as PCMZL (16) or CD4+ TLPD (39), 3 patients had been diagnosed with both LPDs at different time points of their disease course. Four additional patients were identified with single lesions featuring overlapping histopathological characteristics of both LPDs and both monoclonal IGH and TCR rearrangements. All patients are currently in complete remission with local treatment. CONCLUSION: We propose that besides the overlapping histopathological, molecular, and clinical features, the subsequent appearance of PCMZL and CD4+ TLPD in a short timeframe in the same patients may suggest a common pathogenic background.


Assuntos
Linfoma de Zona Marginal Tipo Células B , Neoplasias Cutâneas , Humanos , Linfoma de Zona Marginal Tipo Células B/patologia , Linfoma de Zona Marginal Tipo Células B/metabolismo , Linfoma de Zona Marginal Tipo Células B/diagnóstico , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/metabolismo , Idoso , Adulto , Transtornos Linfoproliferativos/patologia , Transtornos Linfoproliferativos/metabolismo , Transtornos Linfoproliferativos/diagnóstico , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD4-Positivos/imunologia , Diagnóstico Diferencial , Idoso de 80 Anos ou mais , Linfoma Cutâneo de Células T/patologia , Linfoma Cutâneo de Células T/metabolismo , Linfoma Cutâneo de Células T/diagnóstico
4.
Mod Pathol ; 37(5): 100465, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38460675

RESUMO

Primary cutaneous follicle center lymphoma (PCFCL) has an excellent prognosis using local treatment, whereas nodal follicular lymphoma (nFL), occasionally presenting with cutaneous spread, often requires systemic therapy. Distinction of the 2 diseases based on histopathology alone might be challenging. Copy number alterations (CNAs) have scarcely been explored on a genome-wide scale in PCFCL; however, they might serve as potential biomarkers during differential diagnosis and risk stratification. Low-coverage whole-genome sequencing is a robust, high-throughput method for genome-wide copy number profiling. In this study, we analyzed 28 PCFCL samples from 20 patients and compared the copy number profiles with a cohort of diagnostic samples of 64 nFL patients. Although the copy number profile of PCFCL was similar to that of nFL, PCFCL lacked amplifications of 18q, with the frequency peaking at 18q21.33 in nFL cases involving the BCL2 locus (PCFCL: 5.0% vs nFL: 31.3%, P = .018, Fisher exact test). Development of distant cutaneous spread was significantly associated with higher genomic instability including the proportion of genome altered (0.02 vs 0.13, P = .033) and number of CNAs (2 vs 9 P = .017), as well as the enrichment of 2p22.2-p15 amplification involving REL and XPO1 (6.3% vs 60.0%, P = .005), 3q23-q24 amplification (0.0% vs 50.0%, P = .004), 6q16.1-q23.3 deletion (6.3% vs 50.0%, P = .018), and 9p21.3 deletion covering CDKN2A and CDKN2B loci (0.0% vs 40.0%, P = .014, all Fisher exact test) in PCFCL. Analysis of sequential tumor samples in 2 cases harboring an unfavorable clinical course pointed to the acquisition of 2p amplification in the earliest common progenitor underlining its pivotal role in malignant transformation. By performing genome-wide copy number profiling on the largest patient cohort to date, we identified distinctive CNA alterations conceivably facilitating the differential diagnosis of PCFCL and secondary cutaneous involvement of nFL and potentially aiding the risk stratification of patients with PCFCL in the future.


Assuntos
Variações do Número de Cópias de DNA , Linfoma Folicular , Neoplasias Cutâneas , Sequenciamento Completo do Genoma , Humanos , Linfoma Folicular/genética , Linfoma Folicular/patologia , Linfoma Folicular/diagnóstico , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/diagnóstico , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Diagnóstico Diferencial , Prognóstico , Adulto , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética
5.
J Clin Tuberc Other Mycobact Dis ; 31: 100370, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37122612

RESUMO

Tuberculosis remains a global health concern, as the increasing levels of urban poverty, higher number of immunodeficient patients and the development of drug resistance threaten the overall efforts made to induce a downward trend for the disease. Scrofuloderma, also known as tuberculosis cutis colliquativa is a subtype of cutaneous tuberculosis. Here we detail a case of a 70-year-old female patient presented with unilateral, left-sided, multiple palpable, painful, ulcerated and purulent cervical nodules, accompanied by persistent generalized erythematous popular granuloma annulare-like skin lesions on the upper extremities. Based on the result of the PCR assay, culture, imaging and histopathological findings, the diagnosis of scrofuloderma was established. To achieve prompt diagnosis and early treatment, it is crucial to include scrofuloderma in the differential diagnosis of ulcerated lesions in developed countries as well, and also be aware of the additional clinical symptoms, such as granuloma annulare-like lesions, possibly accompanying cutaneous tuberculosis.

6.
Orv Hetil ; 164(5): 172-178, 2023 Feb 05.
Artigo em Húngaro | MEDLINE | ID: mdl-36739549

RESUMO

INTRODUCTION: Lupus erythematous panniculitis (LEP) is a rare type of chronic cutaneous lupus erythematous. Clinical characteristics are tender, subcutaneous nodules, erythematous plaques. Disfigurement of face and body might develop which affects the patient's quality of life. LEP can be the first sign of systemic lupus erythematous (SLE). OBJECTIVE: Our aim was to review the clinicopathological characteristics and the course of LEP through our own patients. METHODS: We retrospectively analyzed the clinical records of 17 LEP patients at Semmelweis University's Department of Dermatology, Venerology and Dermatooncology between 2000 and 2022. RESULTS: The male : female ratio was 1 : 16, average age was 37.8 years. Lesion localisations were proximal lower (8/17) and upper extremities (7/17), face (4/17), breast (3/17), chest (2/17), buttocks (2/17), back (1/17) and distal lower extremity (1/17). Lesion morphologies were nodules (11/17), plaques (7/17), lipoatrophy (4/17), ulceration (3/17), calcification (1/17). Discoid changes covered in 6 cases. In 10 cases, systemic symptoms were observed (arthritis (4/17), haematological (5/17), renal (2/17), anti-phospholipid syndrome (2/17). 7 patients fulfilled the EULAR/ACR criteria for SLE. Histology showed mixed type panniculitis in 8, lobular in 3 cases. Average time until diagnosis was 24.3 months. Among all our SLE patients, skin symptoms regressed following systemic immunosuppressive treatment. LEP patients with only skin manifestation were often resistant for the therapy of cutaneous lupus erythematous. CONCLUSION: The diagnosis of LEP often takes months or years. Wider knowledge of LEP would shorten the time to diagnosis, preventing disfigurement and possible damage of internal organs. Based on our observations, LEP without SLE might be treated with early immunosuppression. Orv Hetil. 2023; 164(5): 172-178.


Assuntos
Lúpus Eritematoso Sistêmico , Paniculite de Lúpus Eritematoso , Paniculite , Humanos , Masculino , Feminino , Adulto , Paniculite de Lúpus Eritematoso/diagnóstico , Paniculite de Lúpus Eritematoso/patologia , Estudos Retrospectivos , Qualidade de Vida , Paniculite/diagnóstico , Paniculite/etiologia , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/patologia
7.
Front Pediatr ; 10: 959307, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36186629

RESUMO

A 5-year-old male child was diagnosed with interdigitating dendritic cell sarcoma (IDCS) during his maintenance therapy for B-cell precursor acute lymphoblastic leukemia (B-ALL). Multiplex lymph node involvements of the neck were found by positron emission tomography CT (PET-CT). Treatments, including surgical and chemotherapy, resulted in complete remission. Four years later, systemic bone infiltration was discovered. Surgical resection of the IV rib and intensive chemotherapy led to a complete morphological remission, and allogeneic bone marrow transplantation was performed. Comprehensive genomic profiling of the formalin fixed the tumor tissue, and the cryopreserved leukemic cells revealed several common alterations and divergent clonal evolution with a novel MAP2K1 mutation of the IDCS, which is responsible for the trans-differentiation of the common lymphoid-committed tumor progenitor.

8.
Pathol Oncol Res ; 28: 1610521, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35979531

RESUMO

The pathomechanism of various autoimmune diseases is known to be associated with the altered function of programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) axis. We aimed to investigate the role of this pathway and inflammatory cell markers in subtypes of cutaneous lupus erythematosus (CLE): discoid lupus erythematosus (DLE), subacute CLE (SCLE) and toxic epidermal necrolysis (TEN)-like lupus, a hyperacute form of acute CLE (ACLE). Ten skin biopsy samples from 9 patients were analyzed with immunohistochemistry regarding the following markers: CD3, CD4, CD8, Granzyme B, CD123, CD163, PD-1, PD-L1. Our group consisted of 4 SCLE (2 idiopathic (I-SCLE) and 2 PD-1 inhibitor-induced (DI-SCLE)), 4 DLE and 1 TEN-like lupus cases. From the latter patient two consecutive biopsies were obtained 1 week apart. Marker expression patterns were compared through descriptive analysis. Higher median keratinocyte (KC) PD-L1 expression was observed in the SCLE group compared to the DLE group (65% and 5%, respectively). Medians of dermal CD4, Granzyme B (GB), PD-1 positive cell numbers and GB+/CD8+ ratio were higher in the DLE group than in the SCLE group. The I-SCLE and DI-SCLE cases showed many similarities, however KC PD-L1 expression and dermal GB positive cell number was higher in the former. The consecutive samples of the TEN-like lupus patient showed an increase by time within the number of infiltrating GB+ cytotoxic T-cells and KC PD-L1 expression (from 22 to 43 and 30%-70%, respectively). Alterations of the PD-1/PD-L1 axis seems to play a role in the pathogenesis of CLE.


Assuntos
Lúpus Eritematoso Cutâneo , Lúpus Eritematoso Discoide , Antígeno B7-H1/metabolismo , Granzimas/metabolismo , Humanos , Lúpus Eritematoso Cutâneo/metabolismo , Lúpus Eritematoso Cutâneo/patologia , Lúpus Eritematoso Discoide/metabolismo , Lúpus Eritematoso Discoide/patologia , Receptor de Morte Celular Programada 1/metabolismo , Pele/patologia
9.
Pathol Oncol Res ; 25(2): 647-652, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30406401

RESUMO

Micro-environment plays important role in the pathogenesis of CLL by providing protective niche for CLL cells. Several molecules play important role in communication between CLL cells and immune cells like CD86.Some of the data suggest that CLL patients with high CD86 level need earlier treatments and cells with higher CD86 expression has higher proliferation rate but the role of CD86 in the survival and proliferation of CLL cells is unclear. We investigated the effect of CD86 expression to CLL cells in 50 peripheral blood and 15 lymph node biopsy samples from CLL patients. Our results showed that the expressions of CD86 increased significantly after 7 day culturing in medium, or in the presence of bone marrow stromal cells (BMSCs). We found positive correlation between CD86 and CD23 expression (p < 0.05), but no correlation with other markers. Furthermore, no correlation were found between the CD86 expression and the proliferation of CLL cells. Analysis of clinical data showed that cases with high CD86 expression had lower level of serum lymphocyte count (p < 0.04) at the time of the diagnosis. CD86 shows multiple appearances in the lymph nodes containing pseudofollicules, but no correlation was found between CD86 positivity, and Ki67 positivity. Our results suggest that the use of CD86 molecule as a proliferation marker for CLL is highly questionable. However, the CD86 molecule may interfere with the immune system of patients with CLL by activating and depleting immune functions. That can be the reason why CD86 positivity may mean worse prognosis.


Assuntos
Antígeno B7-2/metabolismo , Biomarcadores Tumorais/análise , Proliferação de Células/fisiologia , Leucemia Linfocítica Crônica de Células B/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Sobrevivência Celular/fisiologia , Feminino , Humanos , Leucemia Linfocítica Crônica de Células B/metabolismo , Masculino , Pessoa de Meia-Idade
10.
Virchows Arch ; 473(4): 453-462, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29858685

RESUMO

Primary cutaneous follicle center lymphoma (PCFCL) is an indolent variant of follicular lymphoma (FL) with limited information available on the genetic background of the disease. The genetic hallmark of nodal FL, the t(14;18) translocation, affecting the BCL2 gene, is rare in PCFCL. Loss of 1p36, the most common secondary chromosomal abnormality in nodal FL, has been recently reported in 16.7% of PCFCL cases. In order to further characterize PCFCL, 21 cases were analyzed using interphase fluorescence in situ hybridization with BCL2 break apart and 1p36/1q25 dual color probes. Sanger sequencing was used to investigate TNFRSF14 and EZH2 mutations and immunohistochemistry to assess BCL2, EZH2 protein expressions.1p36 deletion occurred in 22% (5/21), BCL2 gene break in 10% (2/20) of the PCFCL cases. Mutations of the candidate tumor suppressor gene of the 1p36 region, TNFRSF14 mutations were detected in 4/17 (23.5%) cases with 2 cases presenting with concurrent 1p36 deletion. EZH2 hotspot mutations at Y641, A682, and A692 were not found. High EZH2 protein expression associated with a BCL2 negative phenotype was observed in 43% (9/21) of the cases. BCL2 gene break or 1p36 deletion did not impact the prognosis; however, they showed association with advanced stages at diagnosis (p = 0.016) and a tendency with shorter event free survival (p = 0.052).In conclusion, 1p36 deletion co-occurs with acquired TNFRSF14 mutations, suggesting a role of this tumor suppressor gene in the development of a subgroup of PCFCL. High EZH2 protein expression associated with BCL2 negative phenotype is common and might represent an ideal therapeutic target.


Assuntos
Biomarcadores Tumorais/genética , Deleção Cromossômica , Cromossomos Humanos Par 1 , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Linfoma Folicular/genética , Mutação , Membro 14 de Receptores do Fator de Necrose Tumoral/genética , Neoplasias Cutâneas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Análise Mutacional de DNA , Intervalo Livre de Doença , Proteína Potenciadora do Homólogo 2 de Zeste/análise , Feminino , Predisposição Genética para Doença , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Linfoma Folicular/química , Linfoma Folicular/patologia , Linfoma Folicular/terapia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Fenótipo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Estudos Retrospectivos , Neoplasias Cutâneas/química , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapia , Fatores de Tempo , Resultado do Tratamento , Regulação para Cima
11.
J Cutan Pathol ; 43(11): 963-973, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27461449

RESUMO

Lymphomatoid papulosis (LyP) belongs to CD30+ lymphoproliferative disorders with indolent clinical course. Classic histological subtypes, A, B and C are characterized by the CD4+ phenotype, while CD8+ variants, most commonly classified as type D, were reported in recent years. We present 14 cases of CD8+ LyP. In all patients, self-resolving or treatment-sensitive papules were observed. Of 14 cases 7 produced results with typical microscopic features of LyP type D mimicking primary cutaneous aggressive epidermotropic CD8+ T-cell lymphoma. The infiltration pattern in 4 of 14 cases were consistent with classic LyP type B, without CD30 expression in two cases, resembling mycosis fungoides (MF). The morphology of 2 of 14 cases shared a certain consistency with classic type A and C, lacking eosinophils and neutrophils. Extensive folliculotropism characteristic to type F was observed in 1 of 14 case. Significant MUM1 and PD1 expression were detected in 2 of 14 and 3 of 14 cases, respectively. We concluded that CD8+ LyP may present with different histopathological features compared with type D, similar to CD4+ LyP variants. Differential diagnoses include CD8+ papular MF, folliculotropic MF and anaplastic large cell lymphoma in addition to primary cutaneous aggressive epidermotropic T-cell lymphoma. We emphasise that rare CD8+ LyP cases may exist with CD30-negativity.


Assuntos
Antígenos CD8/metabolismo , Papulose Linfomatoide/patologia , Neoplasias Cutâneas/patologia , Adulto , Idoso , Pré-Escolar , Diagnóstico Diferencial , Feminino , Humanos , Fatores Reguladores de Interferon/metabolismo , Papulose Linfomatoide/imunologia , Masculino , Pessoa de Meia-Idade , Receptor de Morte Celular Programada 1/metabolismo , Neoplasias Cutâneas/imunologia
12.
Magy Onkol ; 60(2): 99-107, 2016 06 06.
Artigo em Húngaro | MEDLINE | ID: mdl-27275636

RESUMO

Diffuse large B-cell lymphoma (DLBCL) is a high-grade lymphoproliferative disease of mature B cells, representing the most common lymphoid malignancy of adulthood. There are multiple distinct subgroups of DLBCL in the 2008 WHO classification, organ specific forms, DLBCL associated with immunodeficiency and viral infections and rare CD20 negative and intermediate forms. However, most of the cases are still classified under the DLBCL not otherwise specified (NOS) category. This group of disease shows remarkable heterogeneity with respect to clinical presentation, biology and response to treatment, reflecting several molecular subgroups: the origin of B cells at various developmental stages, the oncogenic pathways that drive tumor development and also epigenetic changes and mutations involving the escape of immune surveillance. Contemporary chemo-immunotherapy does not result in durable remissions in as many as 30% of the cases. To achieve longer survival, the definition of new biomarkers are needed for targeted therapy based on better subgrouping of tumors according to the molecular pathways involved in lymphomagenesis. This paper summarizes the most important features influencing the outcome of this broad disease at the level of morphology, phenotype and genotype and gives a guideline for the routine pathological practice at present for the diagnostics of DLBCL treated by chemo-immunotherapy.


Assuntos
Antineoplásicos/uso terapêutico , Imunoterapia/métodos , Linfoma Difuso de Grandes Células B , Linfócitos B , Heterogeneidade Genética , Humanos , Hospedeiro Imunocomprometido , Imunofenotipagem , Linfoma Difuso de Grandes Células B/classificação , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/terapia , Proteínas de Neoplasias/genética , Proteínas Proto-Oncogênicas/genética
13.
Diagn Pathol ; 9: 64, 2014 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-24649966

RESUMO

Castleman disease (CD), described as a heterogeneous lymphoproliferative disorder, can be divided into different subtypes according to clinical appearance (unicentric and multicentric form) and histopathological features (hyaline vascular, plasma cell, mixed type, human herpesvirus 8-associated and multicentric not otherwise specified). Unicentric CD is known to be usually of the hyaline vascular variant, plasma cell and mixed type of this form are quite uncommon. Malignancies are mainly associated with the multicentric form. We report a rare case of unicentric mixed variant CD evolving into intrabronchial, extramedullary plasmacytoma.Intrabronchial mass with consequential obstruction of the left main bronchus, left lung atelectasis and mediastinal lymphadenomegaly was detected by chest CT in our patient suffering from cough and hemoptysis. Pulmonectomy was performed, histopathological and immunhistochemical analysis of lymph nodes revealed mixed type of CD with interfollicular monotypic plasma cell proliferation. The intrabronchial mass consisted of monotypic plasma cells confirming plasmacytoma. Systemic involvement was not confirmed by further tests.Although malignancies more often present in multicentric CD that usually belongs to the plasma cell subtype, this case confirms the neoplastic potential of the rarest, unicentric mixed variant of CD. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2872096831190851.


Assuntos
Hiperplasia do Linfonodo Gigante/complicações , Neoplasias Pulmonares/complicações , Plasmocitoma/complicações , Hiperplasia do Linfonodo Gigante/patologia , Comorbidade , Feminino , Refluxo Gastroesofágico/epidemiologia , Infecções por Helicobacter/epidemiologia , Humanos , Leiomioma/epidemiologia , Neoplasias Pulmonares/patologia , Pessoa de Meia-Idade , Obesidade/epidemiologia , Transtorno de Pânico/epidemiologia , Plasmocitoma/patologia , Neoplasias Uterinas/epidemiologia
14.
Virchows Arch ; 464(2): 229-39, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24306958

RESUMO

Primary bone lymphoma (PBL) comprises 5 % of all extranodal non-Hodgkin's lymphomas (NHLs). Diffuse large B-cell lymphoma (DLBCL) accounts for the majority of cases, which is the most heterogeneous group of lymphomas. Previous studies suggested that besides the tumor cell phenotype, phosphatidylinositol 3-kinase/acutely transforming retrovirus/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway activity and the composition of the immune-microenvironment of DLBCL influence the clinical behavior of the disease. The aim of our study was to determine the relationship between clinical factors, tumor cell phenotype, microenvironment, PI3K/AKT/mTOR pathway activity, and disease outcome in primary bone diffuse large B-cell lymphoma (PB-DLBCL). We constructed tissue-microarrays from 41 cases of PB-DLBCL. To characterize tumor cell phenotype, T-cell subsets, macrophages, and PI3K/AKT/mTOR pathway activity immunohistochemical stainings were evaluated. Kaplan-Meier survival analysis provided evidence that age (≤65), CD3 and CD8+ T cell infiltrations >5 %, low BCL2 expression of the tumor cells (≤30 %), and low proliferation index (Ki67 ≤ 57 %) were associated with favorable outcome of PB-DLBCL patients. Multivariate analysis revealed that CD8+ T cell infiltration >5 % and low BCL2 expression (≤30 %) were independent predictors of survival. Increased macrophage infiltration (>10 %) showed tendency toward an adverse prognostic effect. International prognostic index, tumor cell phenotype (GCB or ABC), MYC protein expression, and activation of PI3K/AKT/mTOR pathway had no significant impact on survival. However, mTOR activity showed a significant correlation with activated B-cell phenotype. We conclude that CD8 and BCL2 expressions are potential prognostic markers for PB-DLBCL patients and the PI3K/AKT/mTOR pathway appears to be an additional therapeutic target in PB-DLBCL with activated-B-cell phenotype.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Linfócitos do Interstício Tumoral/imunologia , Linfoma Difuso de Grandes Células B/imunologia , Linfoma Difuso de Grandes Células B/metabolismo , Adolescente , Adulto , Idoso , Linfócitos T CD8-Positivos/patologia , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Linfócitos do Interstício Tumoral/patologia , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Proteínas Proto-Oncogênicas c-bcl-2/análise , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Análise Serial de Tecidos , Microambiente Tumoral/imunologia , Adulto Jovem
15.
Virchows Arch ; 462(3): 349-54, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23328932

RESUMO

Primary lymphoma of bone is a rare type of extranodal diffuse large B-cell lymphoma with a relatively favourable outcome. Recent scientific interest has focused on elucidating the role of nuclear factor-κB pathway in lymphomagenesis and its potential significance as a therapeutic target. In nodal B-cell non-Hodgkin lymphomas, constitutive activation of nuclear factor-κB appears to be involved in tumour cell survival, notably in the non-germinal centre type of diffuse large B-cell lymphoma. We investigated nuclear factor-κB activation via the classical and alternative pathway in primary lymphoma of bone, through immunohistochemical staining for nuclear factor-κB family members on tumour tissues of 50 patients. Nine cases (18 %) showed nuclear staining for p50, and one case showed nuclear co-expression of p52. None of the cases showed nuclear staining for c-Rel. The nuclear staining of p50 suggests that in a minority of primary lymphomas of bone nuclear factor-κB is constitutively activated via the classical pathway. In contrast to other extranodal types of diffuse large B-cell lymphoma, there was a lack of nuclear co-expression of p65, which might suggest activation of a different pathway. Activation of nuclear factor-κB through the alternative pathway does not appear to be significantly involved, as only one case showed significant nuclear expression for p52. Finally, nuclear expression of p50 was neither preferentially detected in non-germinal centre type or germinal centre type primary lymphoma of bone, nor related to poor prognosis. Therefore, in contrast to nodal diffuse large B-cell lymphoma, the nuclear factor-κB pathway does not appear to be an attractive therapeutic target in primary lymphoma of bone.


Assuntos
Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Linfoma não Hodgkin/metabolismo , Linfoma não Hodgkin/patologia , NF-kappa B/metabolismo , Adolescente , Adulto , Idoso , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Análise Serial de Tecidos , Adulto Jovem
17.
Pathol Oncol Res ; 18(2): 535-8, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21688087

RESUMO

The 15-year-old male patient presented several 2-6 mm large livid reddish-yellowish, shiny, compact papules on the head, trunk and extremities, which had developed within the last 4 months. Histology showed normal epidermis with dense dermal infiltrate of histiocytes accompanied by few eosinophils, Touton or foamy giant cells. The histiocytes were S100 positive, CD1a negative and did not contain Birbeck granules ultrastructurally. Chest X ray, EEG, skull MRI did not show pathology. Opthalmology, neurology, oto-rhino-laryngology did not reveal alterations. Based upon the clinical symptoms and the histopathology, the diagnosis of indeterminate cell histiocytosis was confirmed. Cryotherapy and cauterization did not stop the progression of the disease, however, under thalidomide treatment no new symptoms developed and the lesions healed with pigmentation.


Assuntos
Histiocitose/tratamento farmacológico , Imunossupressores/uso terapêutico , Dermatopatias/tratamento farmacológico , Talidomida/uso terapêutico , Adolescente , Histiocitose/patologia , Humanos , Masculino , Dermatopatias/patologia , Resultado do Tratamento
19.
Leuk Lymphoma ; 52(6): 1080-4, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21417824

RESUMO

In lymph nodes, chronic lymphocytic leukemia (CLL) cells (prolymphocytes and paraimmunoblasts) form proliferation centers (PCs), which are also known as pseudofollicles. To reveal whether PCs play a role in the accumulation of genetic alterations in CLL, we compared deletion at 11q22.3, 13q14.3, and 17p13.1 loci and trisomy 12 by the fluorescence in situ hybridization (FISH) technique in PCs versus surrounding small lymphocytes (SLs) in 12 formalin-fixed paraffin-embedded (FFPE) lymph nodes. The FFPE sections were stained with methylene blue and PCs were marked by laser beam. Subsequent FISH analysis was performed, relocalizing the previously defined regions. Loss of 11q was detected in five cases, loss of 13q in two cases, loss of 17p in two cases, and trisomy 12 in one case. In seven cases PCs contained a significantly higher ratio of cells with genetic alterations compared with the surrounding SLs. Our results show that CLL cells with genetic alterations tend to accumulate in PCs. The clonal expansion of the cell population carrying genetic alterations within PCs may contribute to CLL progression.


Assuntos
Proliferação de Células , Aberrações Cromossômicas , Leucemia Linfocítica Crônica de Células B/genética , Linfonodos/metabolismo , Deleção Cromossômica , Cromossomos Humanos Par 11/genética , Cromossomos Humanos Par 12/genética , Cromossomos Humanos Par 13/genética , Cromossomos Humanos Par 17/genética , Humanos , Hibridização in Situ Fluorescente , Leucemia Linfocítica Crônica de Células B/patologia , Linfonodos/patologia , Linfócitos/metabolismo , Linfócitos/patologia , Trissomia
20.
Int J Hematol ; 93(4): 545-550, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21360009

RESUMO

A 32-year-old male patient was diagnosed with nodular lymphocyte-predominant Hodgkin lymphoma. Staging FDG PET-CT detected a large right axillary lymph node conglomerate and splenic manifestation. Interim PET-CT following two cycles of ABVD chemotherapy revealed good metabolic response with the exception of a single axillary lymph node. A second "interim" PET-CT after two further cycles showed a similar result. A biopsy of the metabolically active non-palpable lymph node was performed using radioguided occult lesion localization (ROLL) with ultrasound guidance. The lymph node was successfully removed by minimally invasive surgery. Histological evaluation of the lymph node revealed a T cell-rich diffuse large B cell lymphoma. Based on this finding, a more aggressive treatment regimen followed by high dose chemotherapy with autologous stem cell rescue was adopted. To our knowledge, this is the first report of a lymphoma case in which the ROLL method was used in the radioguided biopsy of a chemoresistant lymph node detected by interim FDG PET-CT.


Assuntos
Doença de Hodgkin/diagnóstico por imagem , Linfonodos/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Adulto , Fluordesoxiglucose F18 , Doença de Hodgkin/patologia , Humanos , Linfonodos/patologia , Masculino , Estadiamento de Neoplasias , Compostos Radiofarmacêuticos
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