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/genéticaAssuntos
Transformação Celular Neoplásica/genética , Células Dendríticas/metabolismo , Células Dendríticas/patologia , Genes do Retinoblastoma , Transtornos Histiocíticos Malignos/genética , Transtornos Histiocíticos Malignos/metabolismo , Leucemia Mielomonocítica Crônica/genética , Leucemia Mielomonocítica Crônica/patologia , Alelos , Biópsia , Medula Óssea/metabolismo , Evolução Clonal , Progressão da Doença , Inativação Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Sequenciamento do ExomaRESUMO
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/metabolismoRESUMO
Histiocytic disorders represent clonal disorders of cells believed to be derived from the monocyte, macrophage, and/or dendritic cell lineage presenting with a range of manifestations. Although their nature as clonal versus inflammatory nonclonal conditions have long been debated, recent studies identified numerous somatic mutations that activate mitogen-activated protein kinase signaling in clinically and histologically diverse forms of histiocytosis. Clinical trials and case series have revealed that targeting aberrant kinase signaling using BRAF and/or MEK inhibitors may be effective. These findings suggest that a personalized approach in which patient-specific alterations are identified and targeted may be a critically important therapeutic approach.
Assuntos
Antineoplásicos/farmacologia , Descoberta de Drogas , Transtornos Histiocíticos Malignos/genética , Inibidores de Proteínas Quinases/farmacologia , Proteínas Quinases/genética , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ensaios Clínicos como Assunto , Transtornos Histiocíticos Malignos/diagnóstico , Transtornos Histiocíticos Malignos/tratamento farmacológico , Transtornos Histiocíticos Malignos/metabolismo , Humanos , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Mutação , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/metabolismo , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Quinases/metabolismo , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas B-raf/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteínas ras/genética , Proteínas ras/metabolismoRESUMO
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 UnidoRESUMO
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 TratamentoRESUMO
Cathepsin K is consistently and diffusely expressed in alveolar soft part sarcoma (ASPS) and a subset of translocation renal cell carcinomas (RCCs). However, cathepsin K expression in human neoplasms has not been systematically analyzed. We constructed tissue microarrays (TMA) from a wide variety of human neoplasms, and performed cathepsin K immunohistochemistry (IHC). Only 2.7% of 1,140 carcinomas from various sites exhibited cathepsin K labeling, thus suggesting that among carcinomas, cathepsin K labeling is highly specific for translocation RCC. In contrast to carcinomas, cathepsin K labeling was relatively common (54.6%) in the 414 mesenchymal lesions studied, including granular cell tumor, melanoma, and histiocytic lesions, but not paraganglioma, all of which are in the morphologic differential diagnosis of ASPS. Cathepsin K IHC can be helpful in distinguishing ASPS and translocation RCC from some but not all of the lesions in their differential diagnosis.
Assuntos
Adenocarcinoma/metabolismo , Adenoma/metabolismo , Catepsina K/metabolismo , Imuno-Histoquímica/métodos , Neoplasias/metabolismo , Adenocarcinoma/patologia , Adenoma/patologia , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/metabolismo , Diagnóstico Diferencial , Feminino , Tumor de Células Granulares/metabolismo , Tumor de Células Granulares/patologia , Transtornos Histiocíticos Malignos/metabolismo , Transtornos Histiocíticos Malignos/patologia , Humanos , Neoplasias Renais/diagnóstico , Neoplasias Renais/metabolismo , Masculino , Melanoma/metabolismo , Melanoma/patologia , Neoplasias/patologia , Paraganglioma/metabolismo , Paraganglioma/patologia , Sarcoma Alveolar de Partes Moles/diagnóstico , Sarcoma Alveolar de Partes Moles/metabolismo , Análise Serial de TecidosRESUMO
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/cirurgiaRESUMO
CD137 (also known as 4-1BB and TNFRSF9) is a member of the tumor necrosis factor receptor superfamily. Originally identified as a costimulatory molecule expressed by activated T cells and NK cells, CD137 is also expressed by follicular dendritic cells, monocytes, mast cells, granulocytes, and endothelial cells. Anti-CD137 immunotherapy has recently shown promise as a treatment for solid tumors and lymphoid malignancies in preclinical models. We defined the expression of CD137 protein in both normal and neoplastic hematolymphoid tissue. CD137 protein is expressed by follicular dendritic cells in the germinal center and scattered paracortical T cells, but not by normal germinal-center B cells, bone marrow progenitor cells, or maturing thymocytes. CD137 protein is expressed by a select group of hematolymphoid tumors, including classical Hodgkin lymphoma, T-cell and NK/T-cell lymphomas, and follicular dendritic cells neoplasms. CD137 is a novel diagnostic marker of these tumors and suggests a possible target for tumor-directed antibody therapy.
Assuntos
Transtornos Histiocíticos Malignos/diagnóstico , Transtornos Histiocíticos Malignos/metabolismo , Doença de Hodgkin/metabolismo , Doença de Hodgkin/terapia , Linfoma de Células T/diagnóstico , Linfoma de Células T/metabolismo , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/metabolismo , Biomarcadores Tumorais/metabolismo , Células Dendríticas Foliculares/metabolismo , Células Dendríticas Foliculares/patologia , Citometria de Fluxo , Transtornos Histiocíticos Malignos/patologia , Transtornos Histiocíticos Malignos/terapia , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/patologia , Humanos , Imuno-Histoquímica , Subpopulações de Linfócitos/metabolismo , Tecido Linfoide/metabolismo , Tecido Linfoide/patologia , Linfoma de Células B/metabolismo , Linfoma de Células B/patologia , Linfoma de Células T/patologia , Linfoma de Células T/terapiaRESUMO
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a clinically aggressive tumor derived from the precursor of plasmacytoid dendritic cells. We describe two cases of BPDCN. In case 1, the patient presented with multiple erythema on the trunk and arms. Histopathology of a skin biopsy specimen and immunohistochemistry demonstrated that the tumor cells were small to medium-sized with a blastoid morphology and positive for CD4, CD56, CD123 and T-cell leukemia-1 (TCL-1). In case 2, the patient presented with a solitary skin nodule and rapidly developed involvement of the bone marrow and peripheral blood. Although immunohistochemistry of the infiltrating tumor cells demonstrated positivity for CD4, CD56, CD123 and TCL-1, the cells were large with a distinct nucleolus, and different from those of typical BPDCN. The atypical morphological features of BPDCN may be diagnostically problematic, and should therefore be recognized correctly.
Assuntos
Células Dendríticas/patologia , Transtornos Histiocíticos Malignos/patologia , Plasmócitos/patologia , Neoplasias Cutâneas/patologia , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/imunologia , Antígenos CD/metabolismo , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Transtornos Histiocíticos Malignos/imunologia , Transtornos Histiocíticos Malignos/metabolismo , Humanos , Masculino , Plasmócitos/imunologia , Plasmócitos/metabolismo , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/metabolismoRESUMO
Dendritic cell tumors are extremely rare neoplasms arising from antigen-presenting cells of the immune system. We report a case of a 69-year-old man with an unremarkable medical history who presented with a 2-months history of a gradually enlarging painless, firm, mobile, 2 × 2-cm swelling at the caudal pole of the left parotid gland without systemic symptoms. Histologically, the tumor consisted of a spindle cell proliferation in an intraparotideal lymph node. Based on the histopathologic, immunohistochemical and electron microscopic findings, a dendritic cell tumor, not otherwise specified (NOS) in an intraparotideal lymph node was diagnosed.The patient underwent complete tumor resection, and is currently free of disease, 2 years after surgery. These extremely rare tumors must be distinguished from other more common tumors in the salivary glands. Awareness that dendritic cell tumors may occur in this localization, careful histologic evaluation and ancillary immunohistochemical and electron microscopical analyses should allow for recognition of this entity.
Assuntos
Transtornos Histiocíticos Malignos/patologia , Linfonodos/patologia , Neoplasias Parotídeas/patologia , Idoso , Células Dendríticas/patologia , Diagnóstico Diferencial , Transtornos Histiocíticos Malignos/metabolismo , Humanos , Imuno-Histoquímica , Imunofenotipagem , Linfonodos/metabolismo , Masculino , Microscopia Eletrônica de Transmissão , Neoplasias Parotídeas/metabolismoRESUMO
The T cell immunoglobulin mucin (TIM) proteins are a family of cell surface phosphatidyserine receptors that are important for the recognition and phagocytosis of apoptotic cells. Because TIM-4 is expressed by macrophages and dendritic cells in human tissue, we examined its expression in a range of histiocytic and dendritic cell neoplasms and found moderate to strong immunohistochemical staining in cases of juvenile xanthogranuloma and histiocytic sarcoma, and lower level staining in interdigitating dendritic cell sarcoma, Langerhans cell histiocytosis, acute monocytic leukemia (leukemia cutis), and blastic plasmacytoid dendritic cell neoplasm (hematodermic tumor). TIM-3 was first described on activated T(H)1 cells but was recently shown to also be a phosphatidylserine receptor and mediate phagocytosis. We found TIM-3 was expressed by peritoneal macrophages, monocytes and splenic dendritic cells. We found that it, like TIM-4, is expressed in a range of histiocytic and dendritic cell neoplasms, typically with strong immunohistochemical staining. Cases of diffuse large B cell lymphoma, anaplastic large cell lymphoma, metastatic malignant melanoma, and metastatic poorly differentiated carcinoma generally exhibited negative to minimal heterogenous staining for TIM-4 and TIM-3. We conclude that histiocytic and dendritic cell neoplasms consistently express TIM-3 and TIM-4 and that these molecules are new markers of neoplasms derived from histiocytic and dendritic cells.
Assuntos
Biomarcadores Tumorais/metabolismo , Células Dendríticas/metabolismo , Histiócitos/metabolismo , Transtornos Histiocíticos Malignos/metabolismo , Proteínas de Membrana/metabolismo , Receptores de Superfície Celular/metabolismo , Células Dendríticas/patologia , Receptor Celular 2 do Vírus da Hepatite A , Histiócitos/patologia , Transtornos Histiocíticos Malignos/patologia , Sarcoma Histiocítico/metabolismo , Sarcoma Histiocítico/patologia , Humanos , Imuno-Histoquímica , Especificidade de ÓrgãosRESUMO
Histiocytic/dendritic cell sarcomas arising from follicular lymphoma are very rare and poorly understood lesions. We describe a case, which is unique in that it presented with a hipbone lesion simultaneously with axillary lymphadenopathy. Biopsy of the axillary lymph node showed a low-grade follicular lymphoma. The hipbone lesion was comprised two cell populations, one representing diffuse large B cell lymphoma and the other a histiocytic/dendritic sarcoma. The cells of all three lesions contained an IGH/BCL2 rearrangement, suggesting that both diffuse large B cell lymphoma and histiocytic/dendritic sarcoma differentiation developed from the same low grade precursor (follicular lymphoma). This case illustrates that sarcomatous transdifferentiation of follicular lymphoma can be an unpredictable local phenomenon and that it can occur extra nodally in the bone marrow. It may also occur concurrently with the progression of follicular lymphoma to a diffuse large B cell lymphoma.
Assuntos
Neoplasias Ósseas/secundário , Transtornos Histiocíticos Malignos/patologia , Linfoma Folicular/patologia , Antígenos CD/metabolismo , Neoplasias Ósseas/metabolismo , Transtornos Histiocíticos Malignos/metabolismo , Humanos , Imuno-Histoquímica , Linfoma Folicular/metabolismo , Masculino , Pessoa de Meia-IdadeRESUMO
Histiocytic sarcoma is an uncommon neoplasm of mature histiocytes with a poor clinical outcome. We report a case of a true histiocytic sarcoma with prominent and evenly distributed multinucleated giant cells that mimics a giant cell tumor of soft tissue. The tumor was located between the appendix, right ovary, and the terminal ileum with severe adhesion. The liver and spleen were not enlarged. Grossly, the tumor appeared grayish white, solid, and soft. Microscopically, polygonal mononuclear tumor cells aggregated to form somewhat epithelioid nests, which occasionally showed coagulative necrosis. Prominent and evenly scattered giant cells were present in all sections. In addition, tumor cell infiltration was noted in regional lymph nodes. The tumor cells were positive for lysozyme, CD68, CD163, and negative for T- and B-cell lineage markers, follicular dendritic cell, megakaryocytic, epithelial, muscular, and melanocytic markers, CD1a and CD30. This case posed great difficulty in clinical and pathological diagnoses. Gross pictures, microscopic findings, and extensive immunostains are important for the differential diagnosis.
Assuntos
Tumores de Células Gigantes/diagnóstico , Células Gigantes/patologia , Histiócitos/patologia , Transtornos Histiocíticos Malignos/diagnóstico , Sarcoma/diagnóstico , Adulto , Antígenos CD/análise , Linhagem da Célula , Diagnóstico Diferencial , Feminino , Tumores de Células Gigantes/química , Tumores de Células Gigantes/patologia , Células Gigantes/química , Histiócitos/química , Transtornos Histiocíticos Malignos/metabolismo , Transtornos Histiocíticos Malignos/patologia , Transtornos Histiocíticos Malignos/terapia , Humanos , Muramidase/análise , Invasividade Neoplásica , Sarcoma/química , Sarcoma/patologia , Sarcoma/terapia , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
Histiocytic sarcoma is a rare, malignant neoplasm of the lymphohematopoietic system that usually occurs in the skin, lymph node, and intestinal tract. Here we describe a unique case of primary central nervous system histiocytic sarcoma that initially showed an indolent clinical course following local resection and radiotherapy. However, relapse of disease within the mediastinum was noted 3 1/2 years later. Biopsies of the initial brain lesion and subsequent mediastinal recurrence each revealed an identical, diffuse proliferation of histiocytes with expression of CD45, CD68, and CD163 but not pan-cytokeratin, epithelial membrane antigen, CD3, CD15, CD20, CD30, CD43, CD79a, CD138, myeloperoxidase, ALK-1, PAX-5, CAM 5.2, S100, CD1a, or glial fibrillary acidic protein. In the literature, central nervous system histiocytic sarcoma portends a poor prognosis with median survival of 4.5 months. To our knowledge, this case represents the first case of "low-grade" primary central nervous system histiocytic sarcoma with relatively indolent clinical course. A thorough discussion of the differential diagnosis of histiocytic sarcoma and a review of primary central nervous system histiocytic sarcoma are also presented.
Assuntos
Neoplasias Encefálicas/patologia , Transtornos Histiocíticos Malignos/patologia , Neoplasias do Mediastino/secundário , Sarcoma/secundário , Biomarcadores Tumorais/análise , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/terapia , Diagnóstico Diferencial , Feminino , Transtornos Histiocíticos Malignos/metabolismo , Transtornos Histiocíticos Malignos/terapia , Humanos , Imuno-Histoquímica , Neoplasias do Mediastino/metabolismo , Pessoa de Meia-Idade , Sarcoma/metabolismo , Sarcoma/terapiaAssuntos
Transtornos Histiocíticos Malignos/patologia , Sarcoma/patologia , Neoplasias Cutâneas/patologia , Idoso , Antineoplásicos/uso terapêutico , Antígeno B7-2/análise , Diagnóstico Diferencial , Seguimentos , Transtornos Histiocíticos Malignos/tratamento farmacológico , Transtornos Histiocíticos Malignos/metabolismo , Humanos , Masculino , Sarcoma/química , Sarcoma/tratamento farmacológico , Neoplasias Cutâneas/química , Neoplasias Cutâneas/tratamento farmacológicoRESUMO
To determine whether cyclooxygenase-2 (COX-2) is expressed in canine hemangiosarcoma (HSA), histiocytic sarcoma (HS), and grade-II mast cell tumor (MCT), we performed immunohistochemistry using COX-2 antibodies in the aforementioned tumors. Twenty cases of each tumor type were selected initially from the Laboratory of Pathology archives of cases submitted through the Matthew J. Ryan Veterinary Hospital of the University of Pennsylvania. Immunohistochemistry was performed, using a polyclonal antiprostaglandin endoperoxide synthase immunoglobulin G COX-2 antibody. Sections from the kidneys of young dogs, in which the macula densa stains positive for COX-2, served as positive controls. Slides were reviewed by a single pathologist (M. H. Goldschmidt) and graded for COX-2 expression according to previously established scales. Descriptive data is given for each tumor type. COX-2 expression was identified in 0 of 19 HSA, 1 of 20 HS, and 1 of 17 grade-II MCT. Although COX-2 has been shown to be overexpressed in selected human sarcomas and hematopoeitic tumors, these results indicate that canine HSA, HS, and MCT do not express COX-2 in any appreciable fashion.
Assuntos
Doenças do Cão/metabolismo , Hemangiossarcoma/veterinária , Transtornos Histiocíticos Malignos/metabolismo , Sarcoma de Mastócitos/metabolismo , Prostaglandina-Endoperóxido Sintases/metabolismo , Animais , Ciclo-Oxigenase 2 , Cães , Hemangiossarcoma/metabolismo , Imuno-Histoquímica/veterináriaRESUMO
Histiocytic sarcoma (HS) is a rare but controversial hematopoietic neoplasm. In the past, malignancies have been misclassified as histiocytic tumors due to overlapping histologic features and inadequate phenotypic data. CD163, a recently characterized hemoglobin scavenger receptor, appears to be a 'specific' marker of histiocytic lineage and a promising diagnostic tool for evaluating histiocytic neoplasms. Five cases of HS were studied to further elucidate the clinicopathologic features of these rare tumors and to demonstrate the diagnostic utility of CD163. Criteria for diagnosis included histologic and immunohistochemical evidence of histiocytic differentiation, CD45 positivity, and exclusion of lymphoid, epithelial, melanocytic and dendritic cell phenotype. Sites of disease included the colon (two cases), palate, inguinal lymph node, and testis. The clinical course was aggressive in 4/5 patients (survival=2-15 months). One patient with localized disease of the palate, survived 17 years after diagnosis. All patients with poor survival had tumors > or =3.5 cm. Histologically, all cases showed diffuse architecture with large, discohesive polygonal cells. Spindling of cells was focally noted. Hemophagocytosis was identified in 3/5 cases. A prominent inflammatory background was present in 4/5 tumors. All cases were immunoreactive for CD45, CD163, CD68, and lysozyme. S-100 was focally positive in 4/5 cases. Antibodies for melanocytic, epithelial, lymphoid, and dendritic cell markers were negative. Molecular studies showed monoclonal IgH gene rearrangements in three cases. Our findings suggest that HS is an uncommon neoplasm frequently extranodal in presentation and aggressive in behavior, with rare exceptions. Stage of disease and possibly tumor size are significant prognostic indicators. Molecular studies remain controversial in the diagnosis. The morphologic and phenotypic features are relatively uniform; however, the diagnosis requires exclusion of more common neoplasms by extensive immunophenotypic studies. CD163 appears to be a specific histiocytic marker and is important in establishing the diagnosis of HS.