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1.
Pathobiology ; : 1-18, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31802761

RESUMO

Most cases of mastocytosis are indolent, usually cutaneous mastocytosis or indolent systemic mastocytosis (SM). Aggressive mast cell (MC) diseases are very rare and often fatal. They can develop de novo or due to progression of indolent forms and can present in different ways; either as MC sarcoma or as advanced SM which includes aggressive SM, MC leukemia, and SM with an associated hematological neoplasm. This review will describe these different aggressive forms of mastocytosis, illustrated by cases submitted to the workshop of the 18th Meeting of the European Association for Haematopathology, Basel 2016, organized by the European Bone Marrow Working Group. In addition, the diagnostic criteria for identifying myelomastocytic leukemia, an aggressive myeloid neoplasm with partial MC differentiation that falls short of the criteria for SM, and disease progression in patients with established mastocytosis are discussed.

2.
Ann Hematol ; 97(11): 2117-2128, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30084011

RESUMO

The bone marrow is a preferential site for both reactive and neoplastic histiocytic proliferations. The differential diagnosis ranges from reactive histiocyte hyperplasia in systemic infections, vaccinations, storage diseases, post myeloablative therapy, due to increased cell turnover, and in hemophagocytic lymphohistiocytosis, through extranodal Rosai-Dorfman disease to neoplasms derived from histiocytes, including histiocytic sarcomas (HS), Langerhans cell histiocytoses (LCH), Erdheim-Chester disease (ECD), and disseminated juvenile xanthogranuloma (JXG). One of the most important recent developments in understanding the biology of histiocytic neoplasms and in contributing to diagnosis was the detection of recurrent mutations of genes of the Ras/Raf/MEK/ERK signaling pathway, in particular the BRAFV600E mutation, in LCH and ECD. Here, we summarize clinical and pathological findings of 17 histiocytic neoplasms that were presented during the bone marrow symposium and workshop of the 18th European Association for Haematopathology (EAHP) meeting held in Basel, Switzerland, in 2016. A substantial proportion of these histiocytic neoplasms was combined with clonally related lymphoid (n = 2) or myeloid diseases (n = 5, all ECD). Based on the latter observation, we suggest excluding co-existent myeloid neoplasms at initial staging of elderly ECD patients. The recurrent nature of Ras/Raf/MEK/ERK signaling pathway mutations in histiocytic neoplasms was confirmed in 6 of the 17 workshop cases, illustrating their diagnostic significance and suggesting apotential target for tailored treatments.


Assuntos
Neoplasias da Medula Óssea , Hematologia , Histiocitose , Sociedades Médicas , Substituição de Aminoácidos , Neoplasias da Medula Óssea/genética , Neoplasias da Medula Óssea/metabolismo , Neoplasias da Medula Óssea/patologia , Neoplasias da Medula Óssea/terapia , Congressos como Assunto , Europa (Continente) , Histiocitose/genética , Histiocitose/metabolismo , Histiocitose/patologia , Histiocitose/terapia , Humanos , Sistema de Sinalização das MAP Quinases/genética , Mutação de Sentido Incorreto , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo
3.
Blood ; 130(3): 323-327, 2017 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-28533310

RESUMO

Pediatric-type follicular lymphoma (PTFL) is a B-cell lymphoma with distinctive clinicopathological features. Recently, recurrent genetic alterations of potential importance for its pathogenesis that disrupt pathways associated with the germinal center reaction (TNFRSF14, IRF8), immune escape (TNFRSF14), and anti-apoptosis (MAP2K1) have been described. In an attempt to shed more light onto the pathogenesis of PTFL, an integrative analysis of these mutations was undertaken in a large cohort of 43 cases previously characterized by targeted next-generation sequencing and copy number array. Mutations in MAP2K1 were found in 49% (20/41) of the cases, second in frequency to TNFRSF14 alterations (22/41; 54%), and all together were present in 81% of the cases. Immunohistochemical analysis of the MAP2K1 downstream target extracellular signal-regulated kinase demonstrated its phosphorylation in the evaluable cases and revealed a good correlation with the allelic frequency of the MAP2K1 mutation. The IRF8 p.K66R mutation was present in 15% (6/39) of the cases and was concomitant with TNFRSF14 mutations in 4 cases. This hot spot seems to be highly characteristic for PTFL. In conclusion, TNFRSF14 and MAP2K1 mutations are the most frequent genetic alterations found in PTFL and occur independently in most cases, suggesting that both mutations might play an important role in PTFL lymphomagenesis.


Assuntos
Regulação Neoplásica da Expressão Gênica , Fatores Reguladores de Interferon/genética , Linfoma Folicular/genética , MAP Quinase Quinase 1/genética , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/genética , Membro 14 de Receptores do Fator de Necrose Tumoral/genética , Alelos , Carcinogênese/genética , Carcinogênese/metabolismo , Carcinogênese/patologia , Criança , Variações do Número de Cópias de DNA , Feminino , Perfilação da Expressão Gênica , Frequência do Gene , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Fatores Reguladores de Interferon/metabolismo , Linfoma Folicular/diagnóstico , Linfoma Folicular/metabolismo , Linfoma Folicular/patologia , MAP Quinase Quinase 1/metabolismo , Masculino , Análise em Microsséries , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Mutação , Fosforilação , Membro 14 de Receptores do Fator de Necrose Tumoral/metabolismo
4.
Ann Hematol ; 96(5): 765-777, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28191591

RESUMO

Two distinct forms of neoplasms derived from plasmacytoid dendritic cells (PDC) exist: mature PDC proliferations associated with myeloid neoplasms and blastic PDC neoplasms (BPDCN). Ten cases of PDC proliferations and neoplasms in the bone marrow have been submitted to the bone marrow workshop held at the 18th EAHP meeting. Based on observations from the submitted cases, scattered PDC (≤1% of cells) and PDC aggregates (≤10 PDC/HPF) reflect the normal bone marrow composition, while in myelodysplastic syndromes (MDS), there is a propensity for larger/more PDC aggregates (1-5% and 35 PDC/HPF). A shared PTPN11 mutation between a mature PDC proliferation and an accompanying MDS provides evidence of clonal relationship in such instances and shows that PDC are a part of the malignant clone. CD123 and CD303 should be considered backbone markers to histopathologically establish the diagnosis of BPDCN, since they are detectable in almost all cases and properly well on biopsies subjected to different fixations. Expression of some T-cell markers (e.g., CD2 and CD7 but not CD3), B-cell markers (e.g., CD79a but not CD19 and CD20), and myeloid markers (e.g., CD33 and CD117 but not myeloperoxidase) can be observed in BPDCN. Genetical data of the summarized cases corroborate the important role of chromosomal losses in BPDCN. Together with five previously reported instances, one additional workshop case with MYC rearrangement proposes that translocations of MYC may be recurrent. The frequent nature of deleterious mutations of IKZF3 and deletions of IKZF1 suggests a role for the Ikaros family proteins in BPDCN.


Assuntos
Medula Óssea/patologia , Células Dendríticas/patologia , Transtornos Histiocíticos Malignos/diagnóstico , Biópsia , Medula Óssea/metabolismo , Proliferação de Células , Variação Genética , Genômica/métodos , Transtornos Histiocíticos Malignos/etiologia , Transtornos Histiocíticos Malignos/mortalidade , Transtornos Histiocíticos Malignos/terapia , Humanos , Gradação de Tumores , Fenótipo , Recidiva
5.
Blood ; 128(8): 1101-11, 2016 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-27257180

RESUMO

Pediatric-type follicular lymphoma (PTFL) is a variant of follicular lymphoma (FL) with distinctive clinicopathological features. Patients are predominantly young males presenting with localized lymphadenopathy; the tumor shows high-grade cytology and lacks both BCL2 expression and t(14;18) translocation. The genetic alterations involved in the pathogenesis of PTFL are unknown. Therefore, 42 PTFL (40 males and 2 females; mean age, 16 years; range, 5-31) were genetically characterized. For comparison, 11 cases of conventional t(14:18)(-) FL in adults were investigated. Morphologically, PTFL cases had follicular growth pattern without diffuse areas and characteristic immunophenotype. All cases showed monoclonal immunoglobulin (IG) rearrangement. PTFL displays low genomic complexity when compared with t(14;18)(-) FL (mean, 0.77 vs 9 copy number alterations per case; P <001). Both groups presented 1p36 alterations including TNFRSF14, but copy-number neutral loss of heterozygosity (CNN-LOH) of this locus was more frequently observed in PTFL (40% vs 9%; P =075). TNFRSF14 was the most frequently affected gene in PTFL (21 mutations and 2 deletions), identified in 54% of cases, followed by KMT2D mutations in 16%. Other histone-modifying genes were rarely affected. In contrast, t(14;18)(-) FL displayed a mutational profile similar to t(14;18)(+) FL. In 8 PTFL cases (19%), no genetic alterations were identified beyond IG monoclonal rearrangement. The genetic landscape of PTFL suggests that TNFRSF14 mutations accompanied by CNN-LOH of the 1p36 locus in over 70% of mutated cases, as additional selection mechanism, might play a key role in the pathogenesis of this disease. The genetic profiles of PTFL and t(14;18)(-) FL in adults indicate that these are two different disorders.


Assuntos
Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Linfoma Folicular/genética , Mutação/genética , Membro 14 de Receptores do Fator de Necrose Tumoral/genética , Adolescente , Adulto , Criança , Pré-Escolar , Cromossomos Humanos Par 14/genética , Cromossomos Humanos Par 18/genética , Células Clonais , Análise Citogenética , Variações do Número de Cópias de DNA/genética , Análise Mutacional de DNA , Éxons/genética , Feminino , Humanos , Hibridização in Situ Fluorescente , Perda de Heterozigosidade/genética , Linfoma Folicular/patologia , Masculino , Pseudolinfoma , Translocação Genética , Adulto Jovem
6.
Histopathology ; 69(3): 349-73, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27208429

RESUMO

Small B cell lymphoid neoplasms are the most common lymphoproliferative disorders involving peripheral blood (PB) and bone marrow (BM). The Bone Marrow Workshop (BMW) organized by the European Bone Marrow Working Group (EBMWG) of the European Association for Haematopathology (EAHP) during the XVIIth EAHP Meeting in Istanbul, October 2014, was dedicated to discussion of cases illustrating how the recent advances in immunophenotyping, molecular techniques and cytogenetics provide better understanding and classification of these entities. Submitted cases were grouped into following categories: (i) cases illustrating diagnostic difficulties in chronic lymphocytic leukaemia (CLL); (ii) cases of BM manifestations of small B cell lymphoid neoplasms other than CLL; (iii) transformation of small B cell lymphoid neoplasms in the BM; and (iv) multiclonality and composite lymphomas in the BM. This report summarizes presented cases and conclusions of the BMW and provides practical recommendations for classification of the BM manifestations of small B cell lymphoid neoplasms based on the current state of knowledge.


Assuntos
Linfócitos B/patologia , Linfoma de Células B/diagnóstico , Medula Óssea/patologia , Humanos
7.
Scott Med J ; 61(3): 171-173, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25634914

RESUMO

A management algorithm for large renal cyst in autosomal dominant polycystic kidney disease (ADPKD) is lacking despite the potential to cause widespread medical and surgical complications. We report the case of a 37-year-old gentleman with ADPKD and large (>5 cm diameter) cysts who suffered sudden death due to autopsy-proven inferior vena cava and pulmonary arterial thrombosis. In this article, we discuss the possible pathophysiological factors at play in this catostrophic complication of ADPKD. We also review available literature to establish the prevalence of such a complication and also establish current thoughts and opinions as to the optimal management strategy for giant cysts in the context of ADPKD.


Assuntos
Rim Policístico Autossômico Dominante/complicações , Veia Cava Inferior/patologia , Trombose Venosa/fisiopatologia , Adulto , Autopsia , Morte Súbita , Evolução Fatal , Humanos , Masculino , Rim Policístico Autossômico Dominante/fisiopatologia , Trombose Venosa/etiologia
8.
Pediatr Dev Pathol ; 19(4): 334-7, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26529397

RESUMO

We present a case of pure erythroleukemia, diagnosed at autopsy, in a dysmorphic premature infant who died of multiorgan failure within 24 hours of birth. Dysmorphic features included facial and limb abnormalities with long philtrum, microagnathia, downturned mouth, short neck as well as abnormal and missing nails, missing distal phalanx from the second toe, and overlapping toes. Internal findings included gross hepatomegaly and patchy hemorrhages in the liver, splenomegaly, and cardiomegaly; and subdural, intracerebral, and intraventricular hemorrhages. Histology revealed infiltration of bone marrow, kidney, heart, liver, adrenal, lung, spleen, pancreas, thyroid, testis, thymus, and placenta by pure erythroleukemia. Only 6 cases of congenital erythroleukemia have been previously reported with autopsy findings similar to those of this case. The dysmorphic features, although not fitting any specific syndrome, make this case unique. Congenital erythroleukemia and possible syndromes suggested by the dysmorphic features are discussed.


Assuntos
Anormalidades Múltiplas , Doenças do Recém-Nascido , Leucemia Eritroblástica Aguda/congênito , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Masculino
11.
Haematologica ; 97(3): 360-5, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22058215

RESUMO

BACKGROUND: The World Health Organization classification of myeloproliferative neoplasms discriminates between essential thrombocythemia and the prefibrotic phase of primary myelofibrosis. This discrimination is clinically relevant because essential thrombocythemia is associated with a favorable prognosis whereas patients with primary myelofibrosis have a higher risk of progression to myelofibrosis or blast crisis. DESIGN AND METHODS: To assess the reproducibility of the classification, six hematopathologists from five European countries re-classified 102 non-fibrotic bone marrow trephines, obtained because of sustained thrombocytosis. RESULTS: Consensus on histological classification defined as at least four identical diagnoses occurred for 63% of the samples. Inter-observer agreement showed low to moderate kappa values (0.28 to 0.57, average 0.41). The percentage of unclassifiable myeloproliferative neoplasms rose from 2% to 23% when minor criteria for primary myelofibrosis were taken into account. In contrast, the frequency of primary myelofibrosis dropped from 23% to 7%, indicating that the majority of patients with a histological diagnosis of primary myelofibrosis did not fulfill the complete criteria for this disease. Thus, over 50% of cases in this series either could not be reproducibly classified or fell into the category of unclassifiable myeloproliferative neoplasms. CONCLUSIONS: World Health Organization criteria for discrimination of essential thrombocythemia from prefibrotic primary myelofibrosis are poorly to only moderately reproducible and lead to a higher proportion of non-classifiable myeloproliferative neoplasms than histology alone.


Assuntos
Mielofibrose Primária/diagnóstico , Trombocitemia Essencial/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Mieloproliferativos/classificação , Transtornos Mieloproliferativos/diagnóstico , Prognóstico , Reprodutibilidade dos Testes , Organização Mundial da Saúde , Adulto Jovem
13.
Histopathology ; 56(4): 530-41, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20459560

RESUMO

AIMS: Because of the clinical difficulty in identifying the early stages of human immunodeficiency virus (HIV) infection, the histopathologist often has to consider the diagnosis of HIV in tissue samples from patients with no previous suspicion of HIV infection. The aim was to investigate the practicality and utility of routine HIV-1 p24 immunohistochemistry on tissue samples received at a London histopathology laboratory. METHODS AND RESULTS: Over a 3-year period, HIV-1 p24 was evaluated immunohistochemically on 123 cases. Of these, 37 (30%) showed positive expression of p24 in lesional follicular dendritic cells (FDCs). Of these 37 cases, 11 were not clinically suspected to be HIV+ and had no prior serological evidence of HIV infection. These cases represented lymph node biopsies, tonsillar and nasopharyngeal biopsies and a parotid excision. In addition to expression on FDCs, in 22 cases (60%), p24 also highlighted mononuclear cells and macrophages. p24 was also useful in confirming the presence of HIV in lymphoid tissue in non-lymphoid organs such as the lung, anus, salivary gland and brain. Immunonegativity occurred in occasional known HIV+ cases, probably related to treatment or tissue processing. CONCLUSIONS: This study confirms the usefulness of this technique in detecting unsuspected HIV infection in lymphoid and non-lymphoid organs on histopathological material and should be part of routine evaluation of lymph nodes and lymphoid tissue in other organs if morphological or clinical features suggest HIV infection.


Assuntos
Citodiagnóstico/métodos , Proteína do Núcleo p24 do HIV/análise , HIV-1/metabolismo , Adolescente , Adulto , Biópsia , Criança , Pré-Escolar , Diagnóstico Precoce , Feminino , Proteína do Núcleo p24 do HIV/imunologia , HIV-1/genética , Humanos , Imuno-Histoquímica , Linfonodos/química , Linfonodos/metabolismo , Linfonodos/patologia , Tecido Linfoide/metabolismo , Tecido Linfoide/patologia , Tecido Linfoide/virologia , Masculino , Pessoa de Meia-Idade , Inclusão em Parafina , Estudos Retrospectivos
16.
J Hematop ; 2(2): 97-102, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19669192
17.
J Hematop ; 2(1): 42-4, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19669222
18.
J Hematop ; 2(3): 151-6, 2009 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-20309423

RESUMO

The second quarter of 2009 saw steady advances in bone marrow biopsy (BMB) pathology. The following publications are a personal selection of the highlights. Quality issues in diagnostic immunohistochemistry for BMB have largely been ignored in external quality assurance programmes, and this issue is highlighted. In other areas, publications reflecting advances in flow cytometry and aspirate morphology are discussed where translation to the BMB is possible. Classifications undergo constant change, and several publications address the redefinition of the cut off points between malignancy, benign, and normal. Lastly, current scientific research is presented where it is relevant to the understanding of BMB pathobiology.

19.
Adv Anat Pathol ; 14(6): 431-43, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18049132

RESUMO

The gastrointestinal (GI) tract is a common internal organ to be involved by human immunodeficiency virus (HIV)-related malignancies. It is the second most common site for Kaposi sarcoma after skin, and the commonest visceral site, for Kaposi sarcoma in AIDS patients. GI lymphomas have been documented in approximately 25% of AIDS patients with systemic lymphomas. Moreover, GI involvement of AIDS-lymphoma has been associated with poor prognosis and short survival. Several other malignancies that occur in the GI tract are also closely related to HIV-infected or immunosuppressed individuals; these include posttransplant lymphoproliferative disorder, Epstein-Barr virus-associated smooth muscle tumors, anal precancerous lesions, and squamous cell carcinoma. As a result of active antiretroviral therapy, patients infected with HIV are living longer and are consequently at increased risk for development of cancer. Therefore, it is possible that the number of AIDS-associated malignancies will rise and the pattern of tumors may change in the future. In this paper, the clinicopathologic features of GI malignancies associated with AIDS patients are reviewed and the differential diagnosis with other mimic lesions is discussed.


Assuntos
Síndrome de Imunodeficiência Adquirida/patologia , Neoplasias Gastrointestinais/patologia , Hospedeiro Imunocomprometido , Imunossupressão , Linfoma Relacionado a AIDS/patologia , Sarcoma de Kaposi/patologia , Síndrome de Imunodeficiência Adquirida/complicações , Síndrome de Imunodeficiência Adquirida/imunologia , Neoplasias Gastrointestinais/etiologia , Neoplasias Gastrointestinais/imunologia , Humanos , Linfoma Relacionado a AIDS/etiologia , Linfoma Relacionado a AIDS/imunologia , Sarcoma de Kaposi/etiologia , Sarcoma de Kaposi/imunologia
20.
Ren Fail ; 29(6): 763-5, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17763176

RESUMO

Renal dysfunction is uncommon in patients with leukemic infiltration of the kidney due to Chronic Lymphocytic Leukanemia (CLL). Granulomatous interstitial nephritis (GIN) is also rare, but a characteristic hallmark of certain diseases such as sarcoidosis and tuberculosis. GIN has been associated with medications, infections, inflammation, Wegener's granulomatosis, and jejuno-ileal bypass. GIN combined with leukemic infiltration by CLL is very uncommon. We present a 72-year-old male with Binet stage A CLL who developed progressive renal failure over a period of four years requiring maintenance dialysis. During the course of his illness, he underwent renal biopsies at different time intervals, revealing varying degrees of involvement by GIN together with leukemic infiltration.


Assuntos
Rim/patologia , Leucemia Linfocítica Crônica de Células B/patologia , Infiltração Leucêmica , Nefrite Intersticial/etiologia , Insuficiência Renal/etiologia , Idoso , Humanos , Leucemia Linfocítica Crônica de Células B/complicações , Masculino , Nefrite Intersticial/patologia
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