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1.
Surg Pathol Clin ; 12(3): 805-829, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31352989

RESUMO

Histiocytic and dendritic cell neoplasms are very rare, belonging to a group that share morphologic, immunophenotypic, and ultrastructural characteristics of mature histiocytic/dendritic neoplasms. Histiocytic and dendritic cell neoplasms may arise de novo or in association with B-cell, T-cell, or myeloid neoplasms. Recent molecular findings, particularly the discoveries of the mutations in the RAS-RAF-MEK-ERK pathway, have greatly advanced the diagnosis and treatment options. Histiocytic and dendritic cell neoplasms may closely resemble each other, non-hematopoietic neoplasms, and even reactive processes. Therefore, it is essential to understand the clinicopathologic characteristics, differential diagnoses, and pitfalls of each entity.


Assuntos
Células Dendríticas/patologia , Transtornos Histiocíticos Malignos/patologia , Diagnóstico Diferencial , Humanos , Prognóstico
2.
Nature ; 567(7749): 521-524, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30867592

RESUMO

Histiocytic neoplasms are a heterogeneous group of clonal haematopoietic disorders that are marked by diverse mutations in the mitogen-activated protein kinase (MAPK) pathway1,2. For the 50% of patients with histiocytosis who have BRAFV600 mutations3-5, RAF inhibition is highly efficacious and has markedly altered the natural history of the disease6,7. However, no standard therapy exists for the remaining 50% of patients who lack BRAFV600 mutations. Although ERK dependence has been hypothesized to be a consistent feature across histiocytic neoplasms, this remains clinically unproven and many of the kinase mutations that are found in patients who lack BRAFV600 mutations have not previously been biologically characterized. Here we show ERK dependency in histiocytoses through a proof-of-concept clinical trial of cobimetinib, an oral inhibitor of MEK1 and MEK2, in patients with histiocytoses. Patients were enrolled regardless of their tumour genotype. In parallel, MAPK alterations that were identified in treated patients were characterized for their ability to activate ERK. In the 18 patients that we treated, the overall response rate was 89% (90% confidence interval of 73-100). Responses were durable, with no acquired resistance to date. At one year, 100% of responses were ongoing and 94% of patients remained progression-free. Cobimetinib treatment was efficacious regardless of genotype, and responses were observed in patients with ARAF, BRAF, RAF1, NRAS, KRAS, MEK1 (also known as MAP2K1) and MEK2 (also known as MAP2K2) mutations. Consistent with the observed responses, the characterization of the mutations that we identified in these patients confirmed that the MAPK-pathway mutations were activating. Collectively, these data demonstrate that histiocytic neoplasms are characterized by a notable dependence on MAPK signalling-and that they are consequently responsive to MEK inhibition. These results extend the benefits of molecularly targeted therapy to the entire spectrum of patients with histiocytosis.


Assuntos
Azetidinas/uso terapêutico , Transtornos Histiocíticos Malignos/tratamento farmacológico , Transtornos Histiocíticos Malignos/enzimologia , Histiocitose/tratamento farmacológico , Histiocitose/enzimologia , Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores , Piperidinas/uso terapêutico , Azetidinas/farmacologia , Transtornos Histiocíticos Malignos/genética , Transtornos Histiocíticos Malignos/patologia , Histiocitose/genética , Histiocitose/patologia , Humanos , MAP Quinase Quinase 1/antagonistas & inibidores , MAP Quinase Quinase 2/antagonistas & inibidores , MAP Quinase Quinase 2/genética , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Mutação , Piperidinas/farmacologia , Intervalo Livre de Progressão , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas c-raf/genética
4.
Semin Cell Dev Biol ; 86: 62-76, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-29526544

RESUMO

The systemic histiocytoses encompass a clinically heterogeneous group of disorders leading to tissue damage secondary to the accumulation and infiltration of pathological cells thought to be derived from the dendritic or monocytic lineages with accompanying inflammation. For decades, whether or not the histiocytoses were inflammatory or neoplastic disorders was unclear, and their cellular origins have long been obscure and heavily debated. However, the rise of the molecular era led to the discovery of recurrent BRAFV600E mutations in approximately 50% of patients with Langerhans cell and non-Langerhans cell histiocytoses, which provided the first convincing evidence that these are indeed histiocytic neoplasms. This also supplied a molecular biomarker for potentially mapping the cell(s)-of-origin of these neoplasms. The purpose of this review will be to highlight the barrage of recent molecular advancements in the histiocytic neoplasms and discuss the impact these insights have had on our understanding of the molecular pathophysiology and cellular origins of these rare, enigmatic diseases.


Assuntos
Células Dendríticas/metabolismo , Células Dendríticas/patologia , Transtornos Histiocíticos Malignos/genética , Transtornos Histiocíticos Malignos/patologia , Macrófagos/metabolismo , Macrófagos/patologia , Transtornos Histiocíticos Malignos/metabolismo , Humanos , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Mutação , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/genética
6.
Pediatr Dev Pathol ; 21(2): 208-251, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29607757

RESUMO

This article focuses on cutaneous hematopoietic neoplasms that are more likely to be encountered in the pediatric age-group and includes both lymphoproliferative and histiocytic disorders. The cutaneous hematologic disorders in children have a different epidemiologic profile to what is seen during adulthood. Although mycosis fungoides is the most frequent form of cutaneous lymphoma in adults, it is very rare in children. Because lymphoblastic leukemias and lymphomas are more frequent in the pediatric setting, cutaneous leukemic infiltrates are relatively common in this age-group. Similarly, histiocytic disorders are more common in children, particularly Langerhans cell histiocytosis and juvenile xanthogranuloma. Notably, the histiocytic disorders have undergone significant modifications on their nomenclature in the basis of the molecular characteristics that are present in them. A summary of the most frequent cutaneous hematopoietic disorders in children will be discussed further in this review.


Assuntos
Neoplasias Hematológicas/patologia , Transtornos Histiocíticos Malignos/patologia , Transtornos Linfoproliferativos/patologia , Neoplasias Cutâneas/patologia , Criança , Diagnóstico Diferencial , Neoplasias Hematológicas/diagnóstico , Transtornos Histiocíticos Malignos/diagnóstico , Humanos , Transtornos Linfoproliferativos/diagnóstico , Neoplasias Cutâneas/diagnóstico
7.
Mod Pathol ; 31(4): 553-561, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29327713

RESUMO

EZH2 is an important enzymatic subunit of the epigenetic regulator polycomb repressive complex 2 (PRC2), which controls gene silencing through post-translational modification, and is overexpressed in various carcinomas and hematopoietic neoplasms. We found that the majority of cases of histiocytic and dendritic cell neoplasms, including histiocytic sarcoma, follicular dendritic cell sarcoma, Langerhans cell histiocytosis, and interdigitating dendritic cell sarcoma, show strong EZH2 expression by immunohistochemical staining, in contrast to benign histiocytic lesions and normal cellular counterparts, which did not show EZH2 expression, suggesting that this molecule may function as an oncogenic protein in these neoplasms. We correlated EZH2 expression with that of p-ERK1/2, MYC, and p-STAT3, potential regulators of EZH2, and found that 60-80% of these cases showed strong p-ERK1/2 expression, and only a minority of cases showed positivity for MYC or p-STAT3 in neoplastic cells. In cases of follicular dendritic cell sarcoma, Langerhans cell histiocytosis, histiocytic sarcoma, and interdigitating dendritic cell sarcoma with strong EZH2 expression, 90%, 89%, 70%, and 100% of cases showed co-expression of p-ERK1/2 with EZH2, respectively, while only a small percentage of these cases showed MYC or p-STAT3 co-expression with EZH2 (≤30%). These findings suggest that the p-ERK1/2 signaling cascade, but not the p-STAT3 and MYC signaling cascades, may regulate EZH2 expression in histiocytic and dendritic cell neoplasms, and that EZH2 and the p-ERK1/2 signaling cascade could serve as therapeutic targets for the treatment of these neoplasms. Interestingly, only a minority of cases of blastic plasmacytoid dendritic cell neoplasm exhibited high EZH2 expression, and only a minority of these cases showed p-ERK1/2 co-expression, suggesting that alternative mechanisms may contribute to tumorigenesis in this aggressive neoplasm.


Assuntos
Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Transtornos Histiocíticos Malignos/metabolismo , Histiocitose de Células de Langerhans/metabolismo , Sistema de Sinalização das MAP Quinases/fisiologia , Transdução de Sinais/fisiologia , Biomarcadores Tumorais/análise , Transtornos Histiocíticos Malignos/patologia , Histiocitose de Células de Langerhans/patologia , Humanos , Proteínas Proto-Oncogênicas c-myc/metabolismo , Fator de Transcrição STAT3/metabolismo
9.
Vnitr Lek ; 63(4): 284-288, 2017.
Artigo em Tcheco | MEDLINE | ID: mdl-28520453

RESUMO

Indeterminate cell histiocytosis is a rare disease belonging to the group of malignant histiocytic diseases. The disease predominantly affects the skin. The disease appeared in the described patient at the age of 80 years. Morphs began to develop on the skin and rapidly spread over the whole body including the face. Only the hands and feet were left uncovered. The patients skin samples were taken from 2 sites for histological examination. The resulting conclusion was indeterminate cell histiocytosis. The treatment we chose was analogous to the procedures for Langerhans cell histiocytosis. We chose PUVA phototherapy as the first-line treatment. This treatment is frequently efficient for skin forms of Langerhans cell histiocytosis. In the described case, however, PUVA phototherapy did not influence the disease activity at all. As the second-line treatment, we used low-energy electron beam irradiation in the total dose of 36.2 Gy. This treatment had a positive impact, morphs began to diminish and slowly disappear from the skin. But they have not disappeared completely, therefore we assessed the treatment effect of the radiotherapy itself as partial remission of the disease. Within the third-line treatment, we used 2-chlorodeoxyadenosine in a dose of 5 mg/m2/per day, administered via subcutaneous injection over 5 consecutive days in monthly intervals. There were three cycles of this treatment administered overall. The treatment with 2-chlorodeoxyadenosine was tolerated without any adverse effects. The patient aged 82 years was only administered 3 cycles of 2-chlorodeoxyadenosine. When after the 3rd cycle the skin was free from any pathological morphs and only some pigmentation spots remained, we finished the treatment. The skin expressions of indeterminate cell histiocytosis completely disappeared after electron beam irradiation and the following administration of 3 cycles of 2-chlorodeoxyadenosine. The remission was short, however, after 6 months the disease recurred and the treatment is planned to resume. We assume the disease regresses following administration of 2-chlorodeoxyadenosine, but more than 3 treatment cycles will probably be needed to reach a longer-term response.Key words: electron beam irradiation - indeterminate cell histiocytosis - 2-chlorodeoxyadenosine.


Assuntos
Antineoplásicos/uso terapêutico , Cladribina/uso terapêutico , Transtornos Histiocíticos Malignos/terapia , Terapia PUVA/métodos , Radioterapia/métodos , Neoplasias Cutâneas/terapia , Idoso de 80 Anos ou mais , Transtornos Histiocíticos Malignos/patologia , Humanos , Injeções Subcutâneas , Masculino , Neoplasias Cutâneas/patologia
10.
Histopathology ; 70(6): 1000-1008, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28074480

RESUMO

AIMS: The aims of this study were to define whether diffuse cutaneous reticulohistiocytosis could be underpinned by somatic genetic alterations and represent a precursor of more aggressive forms of disease. METHODS AND RESULTS: A 59-year-old man with diffuse cutaneous reticulohistiocytosis experienced bone marrow localization of the disease, with associated systemic mastocytosis and acute myeloid leukaemia. Cytogenetic analyses of the bone marrow aspirate revealed the presence of a derivative chromosome giving rise to a partial trisomy of chromosome 1q and a partial monosomy of chromosome 9q. Therefore, we characterized the cutaneous lesions before and after chemotherapy by using an integrative approach combining histopathology, electron microscopy, and fluorescence in-situ hybridization. Histologically, the skin lesions belonged to the spectrum of diffuse cutaneous reticulohistiocytoses, as confirmed by immunohistochemistry and ultrastructural analyses. Fluorescence in-situ hybridization in the skin nodules confirmed the presence of the genetic alterations previously detected in the bone marrow. CONCLUSIONS: Here, we provide circumstantial evidence to suggest that at least a subset of cutaneous reticulohistiocytoses harbour clonal molecular alterations. Furthermore, we confirm that these lesions have the potential to arise in the setting of concurrent haematological disorders. In this hypothesis-generating study, two possible tumorigenesis models are proposed.


Assuntos
Neoplasias da Medula Óssea/complicações , Transtornos Histiocíticos Malignos/complicações , Leucemia Mieloide Aguda/complicações , Mastocitose Sistêmica/complicações , Neoplasias Cutâneas/complicações , Medula Óssea/patologia , Neoplasias da Medula Óssea/genética , Neoplasias da Medula Óssea/patologia , Células Clonais/patologia , Transtornos Histiocíticos Malignos/genética , Transtornos Histiocíticos Malignos/patologia , Humanos , Hibridização in Situ Fluorescente , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Masculino , Mastocitose Sistêmica/genética , Mastocitose Sistêmica/patologia , Pessoa de Meia-Idade , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia
11.
Vet Comp Oncol ; 15(1): 65-77, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25665137

RESUMO

Information about histiocytic disease in cats is limited. The aim of this study was to document clinical findings and outcome in feline histiocytic disorders, and characterize the expression of PDGFRß and KIT in order to identify potential treatment targets. Morphologically diagnosed feline histiocytic tumours were reviewed and characterized by immunohistochemistry (IHC). Five cases of feline progressive histiocytosis (FPH), eight histiocytic sarcomas (HS) and two haemophagocytic histiocytic sarcomas (HaeHS) were confirmed. PDGFRß was variably positive in most histiocytic cases, while KIT was negative in all. Clinical presentation, treatment and outcome were also evaluated. Partial responses were recorded in measurable disease with tyrosine kinase inhibitors and lomustine, and radiotherapy achieved long-term control in some cases. Survival times were shortest in HaeHS and disseminated disease. PDGFRß, but not KIT, may represent a therapeutic target in feline histiocytic disorders but more studies are needed to investigate other potential treatment targets.


Assuntos
Doenças do Gato/metabolismo , Transtornos Histiocíticos Malignos/veterinária , Proteínas Proto-Oncogênicas c-kit/biossíntese , Receptor beta de Fator de Crescimento Derivado de Plaquetas/biossíntese , Animais , Biomarcadores Tumorais , Doenças do Gato/diagnóstico , Doenças do Gato/patologia , Gatos , Bases de Dados como Assunto , Feminino , Transtornos Histiocíticos Malignos/metabolismo , Transtornos Histiocíticos Malignos/patologia , Transtornos Histiocíticos Malignos/terapia , Imuno-Histoquímica/veterinária , Masculino , Estadiamento de Neoplasias , Resultado do Tratamento , Reino Unido
12.
Oncotarget ; 7(48): 78355-78362, 2016 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-27823979

RESUMO

The 2008 World Health Organization (WHO) diagnostic criteria of histiocytic and dendritic cell neoplasms from hematopoietic and lymphoid tissues no longer required the absence of clonal B-cell/T-cell receptor gene rearrangements. It is true that the clonal B-cell/T-cell receptor gene rearrangements have been identified in rare cases of histiocytic and dendritic cell neoplasms, such as those with or following lymphoma/leukemia or in some sporadic histiocytic/dendritic cell sarcomas, but the clonal features of such group of tumor are still not clear. Here we investigated the clonal status of 33 samples including Langerhans cell histiocytosis (LCH), Langerhans cell sarcoma (LCS), follicular dendritic cell sarcoma (FDCS), interdigitating dendritic cell sarcoma (IDCS) and histiocytic sarcoma (HS). Among them, twenty-eight cases were sporadic without current or past lymphoma/leukemia. Three cases were found with a past history of T-cell lymphoma, one case was followed by extraosseous plasmacytoma, and one case was found with diffuse large B-cell lymphoma (DLBCL). Our results showed that there was a high frequency of clonal IG and T-cell receptor gene rearrangements in these cases. Notably, 4 cases of LCH and 2 cases of FDCS showed both B and T cell receptor gene rearrangements concurrently. One case of FDCS synchronous with DLBCL showed identical clonal IGH in both tumor populations and clonal TCRß in FDCS alone. No matter if the presence of clonal receptor gene rearrangements was associated with the tumor origin or tumorigenesis, it might serve as a novel tumor marker for developing target therapy.


Assuntos
Biomarcadores Tumorais/genética , Rearranjo Gênico da Cadeia beta dos Receptores de Antígenos dos Linfócitos T , Rearranjo Gênico da Cadeia gama dos Receptores de Antígenos dos Linfócitos T , Genes de Cadeia Pesada de Imunoglobulina , Genes Codificadores da Cadeia beta de Receptores de Linfócitos T , Genes Codificadores da Cadeia gama de Receptores de Linfócitos T , Transtornos Histiocíticos Malignos/genética , Histiocitose de Células de Langerhans/genética , Cadeias kappa de Imunoglobulina/genética , Adolescente , Adulto , Idoso , Criança , Sarcoma de Células Dendríticas Foliculares/genética , Sarcoma de Células Dendríticas Foliculares/imunologia , Sarcoma de Células Dendríticas Foliculares/patologia , Sarcoma de Células Dendríticas Interdigitantes/genética , Sarcoma de Células Dendríticas Interdigitantes/imunologia , Sarcoma de Células Dendríticas Interdigitantes/patologia , Feminino , Predisposição Genética para Doença , Transtornos Histiocíticos Malignos/imunologia , Transtornos Histiocíticos Malignos/patologia , Sarcoma Histiocítico/genética , Sarcoma Histiocítico/imunologia , Sarcoma Histiocítico/patologia , Histiocitose de Células de Langerhans/imunologia , Histiocitose de Células de Langerhans/patologia , Humanos , Sarcoma de Células de Langerhans/genética , Sarcoma de Células de Langerhans/imunologia , Sarcoma de Células de Langerhans/patologia , Masculino , Pessoa de Meia-Idade , Fenótipo , Adulto Jovem
13.
Blood ; 127(22): 2672-81, 2016 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-26966089

RESUMO

The histiocytoses are rare disorders characterized by the accumulation of macrophage, dendritic cell, or monocyte-derived cells in various tissues and organs of children and adults. More than 100 different subtypes have been described, with a wide range of clinical manifestations, presentations, and histologies. Since the first classification in 1987, a number of new findings regarding the cellular origins, molecular pathology, and clinical features of histiocytic disorders have been identified. We propose herein a revision of the classification of histiocytoses based on histology, phenotype, molecular alterations, and clinical and imaging characteristics. This revised classification system consists of 5 groups of diseases: (1) Langerhans-related, (2) cutaneous and mucocutaneous, and (3) malignant histiocytoses as well as (4) Rosai-Dorfman disease and (5) hemophagocytic lymphohistiocytosis and macrophage activation syndrome. Herein, we provide guidelines and recommendations for diagnoses of these disorders.


Assuntos
Células Dendríticas , Transtornos Histiocíticos Malignos , Histiocitose de Células de Langerhans , Histiocitose de Células não Langerhans , Macrófagos , Adulto , Células Dendríticas/classificação , Células Dendríticas/patologia , Feminino , Transtornos Histiocíticos Malignos/classificação , Transtornos Histiocíticos Malignos/patologia , Histiocitose de Células de Langerhans/classificação , Histiocitose de Células de Langerhans/patologia , Histiocitose de Células não Langerhans/classificação , Histiocitose de Células não Langerhans/patologia , Humanos , Macrófagos/classificação , Macrófagos/patologia , Masculino
14.
Pathologe ; 36(5): 443-50, 2015 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-26292932

RESUMO

Histiocytic diseases are generally rare with a variable clinical course and variable morphology which often have a peak frequency of occurrence in childhood and adolescence. Histiocytoses are subdivided into Langerhans cell histiocytosis and the so-called non-Langerhans cell histiocytosis, such as juvenile xanthogranuloma, Erdheim-Chester disease and Rosai-Dorfman disease. The most common forms of histiocytosis in childhood are Langerhans cell histiocytosis and juvenile xanthogranuloma. In contrast, forms of histiocytosis which occur more frequently in adulthood, such as Erdheim-Chester disease and Rosai-Dorfman disease are rare in childhood. Some forms of histiocytosis harbor BRAFv600E mutations. In Langerhans cell histiocytosis they have been found in 50-55 % of the cases examined and in Erdheim-Chester disease in up to 100 % of cases. In the remaining forms of histiocytosis (especially juvenile xanthogranuloma and Rosai-Dorfman disease) BRAF mutations could not be detected. A prognostic relevance could not be shown so far; however, in individual cases a mutation analysis of BRAF could provide help in the differential diagnostic considerations or the option of a therapy approach with BRAF inhibitors.


Assuntos
Histiócitos/patologia , Transtornos Histiocíticos Malignos/patologia , Histiocitose/patologia , Adolescente , Criança , Histiocitose/classificação , Humanos , Monócitos/patologia , Fagócitos/patologia
16.
Am J Surg Pathol ; 39(4): 573-80, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25768257

RESUMO

Fibroblastic reticular cell (FRC) neoplasms, which are one of the histiocyte tumor types, are very rare. Here we report a cytokeratin (CK)-positive FRC neoplasm having features of follicular dendritic cells in a 54-year-old woman with right axillary lymph node swelling. The resected lymph node showed multiple nodular aggregations simulating and replacing normal follicles. The tumor cells had a uniform, large and oval to polygonal shape, abundant cytoplasm, and various sizes of nuclei with central eosinophilic nucleoli and coarse nuclear chromatin. They were positive for CK AE1/AE3+CAM5.2, CK7, tenascin C, l-caldesomone, and CD21, weakly positive for S100, and negative for CD1a. Ultrastructurally, the tumor cells had long interdigitating microvillus-like cell processes and oval to elongated vesicular nuclei. In addition, the intercellular spaces contained accumulations of collagen, and some tumor cells had desmosomal-like junctions. These findings suggest that the present case is a CK-positive FRC tumor with follicular dendritic cell features.


Assuntos
Biomarcadores Tumorais/análise , Células Dendríticas Foliculares , Transtornos Histiocíticos Malignos , Queratinas/análise , Linfonodos , Células Estromais , Biomarcadores Tumorais/genética , Biópsia , Células Dendríticas Foliculares/química , Células Dendríticas Foliculares/ultraestrutura , Feminino , Transtornos Histiocíticos Malignos/genética , Transtornos Histiocíticos Malignos/metabolismo , Transtornos Histiocíticos Malignos/patologia , Transtornos Histiocíticos Malignos/cirurgia , Humanos , Imuno-Histoquímica , Cariotipagem , Excisão de Linfonodo , Linfonodos/química , Linfonodos/cirurgia , Linfonodos/ultraestrutura , Microscopia Eletrônica , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Células Estromais/química , Células Estromais/ultraestrutura , Tomografia Computadorizada por Raios X , Resultado do Tratamento
17.
Vet Clin Pathol ; 43(3): 428-36, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24820657

RESUMO

BACKGROUND: Feline Progressive Histiocytosis (FPH) is a cutaneous dendritic cell neoplasm characterized by slow progression and spread to internal organs in the terminal stage. FPH is often misdiagnosed as an inflammatory reaction and has not been fully characterized from a cytologic diagnostic perspective. OBJECTIVES: The purpose of the study was to characterize the cytologic and immunocytochemical aspects useful for FPH diagnosis. METHODS: Fine-needle aspiration cytologic samples of 5 cases of FPH confirmed by skin biopsy and necropsy were evaluated. Immunocytochemistry with antibodies recognizing CD1a, CD1c, CD3, CD11b, CD18, CD21, and MHCII was performed on air-dried, acetone-fixed smears. E-cadherin expression was assessed on paraffin-embedded skin biopsies. Transmission electron microscopy (TEM) was performed in one case. RESULTS: Main cytologic findings on variably cellular samples were characterized by single to cohesive large, round to polygonal cells with intermediate to low N/C ratio, abundant clear homogeneous cytoplasm, and round to oval nuclei with rare bi- to multinucleated atypical cells, associated with low numbers of small lymphocytes and/or neutrophils. Neoplastic cells expressed CD1a, CD1c, CD11b, CD18, and MHCII. Anti-CD3 antibodies identified reactive T cells admixed with the neoplastic cells. E-cadherin expression was observed in all but one case. TEM failed to identify Birbeck granules in one case. CONCLUSIONS: FPH is a distinctive neoplastic lesion composed of nonphagocytizing histiocytes variably admixed with neutrophils and small mature lymphocytes. Immunocytochemical analysis with CD1 is mandatory to confirm a dendritic cell origin. Immunocytochemistry and cytomorphology allowed the specific and rapid diagnosis of FPH on cytologic samples.


Assuntos
Anticorpos Monoclonais/imunologia , Antígenos CD1/imunologia , Doenças do Gato/diagnóstico , Transtornos Histiocíticos Malignos/veterinária , Neoplasias Cutâneas/veterinária , Animais , Biópsia por Agulha Fina/veterinária , Doenças do Gato/patologia , Gatos , Feminino , Transtornos Histiocíticos Malignos/diagnóstico , Transtornos Histiocíticos Malignos/patologia , Imuno-Histoquímica/veterinária , Imunofenotipagem/veterinária , Masculino , Microscopia Eletrônica de Transmissão/veterinária , Sensibilidade e Especificidade , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologia , Fatores de Tempo
19.
Crit Rev Oncol Hematol ; 88(2): 253-71, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23755890

RESUMO

Dendritic cell tumors are extremely rare and current knowledge on these tumors is limited. The characteristics of three dendritic cell sarcoma subtypes and their optimal treatment approaches are not fully clarified. We aimed to make a systematic review of the literature and enrich the current data with five new cases. Pooled analysis of 462 reported cases revealed that the tumor had no age, gender or racial predilection. Our analysis suggests that the young age, advanced stage, intraabdominal involvement and unfavorable histological features (i.e. large tumor size, absence of lymphoplasmacytic infiltration, coagulative necrosis, high mitotic count) may predict poor prognosis. Subtypes of this tumor have different clinical behaviors with interdigitating dendritic cell sarcoma being the most aggressive form. In general, surgery is the most effective treatment modality and adjuvant radiotherapy has no significant effect on overall survival of patients. The role of chemotherapy for the management of advanced disease is controversial.


Assuntos
Células Dendríticas/patologia , Transtornos Histiocíticos Malignos/patologia , Sarcoma/patologia , Adulto , Feminino , Transtornos Histiocíticos Malignos/diagnóstico , Transtornos Histiocíticos Malignos/mortalidade , Transtornos Histiocíticos Malignos/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Sarcoma/diagnóstico , Sarcoma/mortalidade , Sarcoma/terapia , Resultado do Tratamento , Carga Tumoral
20.
Am J Dermatopathol ; 35(4): e60-2, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23291584

RESUMO

Xanthogranuloma (XG) is a benign cutaneous histiocytic tumor occurring mainly in young children. Onset in adulthood is rarely observed. We encountered an unusual case of an XG-like cutaneous tumor on the scalp of a 50-year-old man. The tumor recurred with multiple satellite nodules soon after surgical excision. This unusual clinical behavior has not previously been described for XG and caused a diagnostic challenge; it was unclear whether the tumor was an atypical XG or a malignant dermal tumor mimicking an XG. Our analyses favored an XG-like dermal histiocytic tumor. A longer follow-up and reports of similar cases will reveal its true nature.


Assuntos
Granuloma/patologia , Transtornos Histiocíticos Malignos/patologia , Recidiva Local de Neoplasia , Couro Cabeludo/patologia , Neoplasias Cutâneas/patologia , Xantomatose/patologia , Biomarcadores Tumorais/análise , Biópsia , Granuloma/metabolismo , Granuloma/cirurgia , Transtornos Histiocíticos Malignos/metabolismo , Transtornos Histiocíticos Malignos/cirurgia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Reoperação , Couro Cabeludo/química , Couro Cabeludo/cirurgia , Neoplasias Cutâneas/química , Neoplasias Cutâneas/cirurgia , Resultado do Tratamento , Xantomatose/metabolismo , Xantomatose/cirurgia
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