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1.
Histol Histopathol ; 35(8): 769-778, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32068239

RESUMO

Atypical spindle cell/pleomorphic lipomatous tumor (ASPLT) is a recently described morphologically low-grade and clinically indolent adipocytic tumor, which will be incorporated as a new tumor entity in the upcoming 5th edition of the WHO Classification of Soft tissue and Bone tumors. Histologically, ASPLTs are characterized by ill-defined tumor margins and the presence of variable proportions of mild-to-moderately atypical spindle cells, adipocytes, lipoblasts, pleomorphic multinucleated cells and a myxoid or collagenous extracellular matrix. ASPLTs can show a wide variety of microscopic appearances and there is histologic overlap with diverse mimics. The diagnosis of ASPLT can therefore be challenging. Molecular studies have shown a consistent absence of MDM2 or CDK4 amplification. On the other hand, deletions or losses of 13q14, including RB1, have been identified in a significant subset of cases. This review provides an overview of the currently known clinical and pathological features of ASPLTs, detailing its most relevant differential diagnoses.


Assuntos
Lipoma , Neoplasias de Tecidos Moles , Humanos , Lipoma/diagnóstico , Lipoma/genética , Lipoma/patologia , Neoplasias de Tecidos Moles/diagnóstico , Neoplasias de Tecidos Moles/genética , Neoplasias de Tecidos Moles/patologia
2.
Am J Surg Pathol ; 41(11): 1443-1455, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28877053

RESUMO

The classification of the until recently poorly explored group of atypical adipocytic neoplasms with spindle cell features, for which recently the term atypical spindle cell lipomatous tumor (ASLT) has been proposed, remains challenging. Recent studies have proposed ASLT as a unique entity with (in at least a significant subset of cases) a specific genetic background, namely deletions/losses of 13q14, including RB1 and its flanking genes RCBTB2, DLEU1, and ITM2B. Similar genetic aberrations have been reported in pleomorphic liposarcomas (PLSs). This prompted us to investigate a series of 21 low-grade adipocytic neoplasms with a pleomorphic lipoma-like appearance, but with atypical morphologic features (including atypical spindle cells, pleomorphic [multinucleated] cells, pleomorphic lipoblasts and poor circumscription), for which we propose the term "atypical" pleomorphic lipomatous tumor (APLT). Five cases of PLS were also included in this study. We used multiplex ligation-dependent probe amplification to evaluate genetic changes of 13q14. In addition, array-based comparative genomic hybridization was performed on 4 APLTs and all PLSs. Multiplex ligation-dependent probe amplification showed consistent loss of RB1 and its flanking gene RCBTB2 in all cases of APLT. This genetic alteration was also present in all PLSs, suggesting genetic overlap, in addition to morphologic overlap, with APLTs. However, array-based comparative genomic hybridization demonstrated more complex genetic alterations with more losses and gains in PLSs compared with APLTs. APLTs arose in the subcutis (67%) more frequently than in the deep (subfascial) soft tissues (33%). With a median follow-up of 42 months, recurrences were documented in 2 of 12 APLTs for which a long follow-up was available. Herein, we also demonstrate that APLTs share obvious overlapping morphologic, immunohistochemical, genetic and clinical characteristics with the recently defined ASLT, suggesting that they are related lesions that form a spectrum (atypical spindle cell/pleomorphic lipomatous tumor).


Assuntos
Adipócitos , Biomarcadores Tumorais , Imuno-Histoquímica , Lipoma , Técnicas de Diagnóstico Molecular , Adipócitos/química , Adipócitos/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Biópsia , Cromossomos Humanos Par 13 , Hibridização Genômica Comparativa , Europa (Continente) , Feminino , Humanos , Hibridização in Situ Fluorescente , Lipoma/química , Lipoma/genética , Lipoma/patologia , Lipoma/terapia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Multiplex , Gradação de Tumores , Proteínas de Neoplasias/genética , Recidiva Local de Neoplasia , Valor Preditivo dos Testes , Proteínas de Ligação a Retinoblastoma/genética , Terminologia como Assunto , Fatores de Tempo , Resultado do Tratamento , Ubiquitina-Proteína Ligases/genética
3.
Oncotarget ; 8(29): 47239-47249, 2017 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-28525384

RESUMO

Adipose tissue secretes a plethora of adipokines as evidenced by characterization of subcutaneous and visceral adipose tissue secretomes. However, adipose tissue composition and secretion pattern is depot and disease dependent, influencing the adipose tissue secretome. We investigated the secretome of cancer-associated adipose tissue (CAAT) explants from breast cancer patients and explored its role in breast cancer proliferation. CAAT proteins were identified by LC-MS/MS and human protein antibody arrays and stimulated proliferation of three breast cancer cell lines. Kinomics and transcriptomics of MCF-7 breast cancer cells treated with the secretome of CAAT revealed activation of Akt-, ERK- and JNK-pathways and differential expression of activator protein 1 (AP-1) and cAMP responsive element-binding protein (CREB) target genes. The cyclin-dependent kinase (CDK)4/6-inhibitor palbociclib significantly abrogated CAAT-enhanced breast cancer cell proliferation. Our work characterizes the specific breast CAAT protein secretome and reveals its pro-proliferative potency in breast cancer.


Assuntos
Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Metabolômica , Comunicação Parácrina , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Feminino , Humanos , Metabolômica/métodos , Piperazinas/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Proteômica/métodos , Piridinas/farmacologia , Fator de Transcrição AP-1/metabolismo
4.
Int J Surg Pathol ; 25(4): 374-378, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28193096

RESUMO

A 69-year-old woman with a 10-year medical history of recurrent retroperitoneal dedifferentiated liposarcoma presented with a 3-cm large hemorrhagic and multicystic left-sided retroperitoneal mass. Histopathological examination of the resected specimen showed a heterogeneous, high-grade mesenchymal nonlipogenic tumor with areas of osteoblastic/osteosarcomatous differentiation and aneurysmal bone cyst-like features. Based on the clinical presentation, the morphology, and the supportive immunohistochemical and molecular findings (MDM2 overexpression and amplification of the MDM2 gene, respectively), a diagnosis of a dedifferentiated liposarcoma with heterologous osteosarcomatous differentiation and an aneurysmal bone cyst-like morphology was made. To the best of our knowledge, this is the first description of aneurysmal bone cyst-like morphology in dedifferentiated liposarcoma, further expanding the broad morphological spectrum of dedifferentiated liposarcoma.


Assuntos
Lipossarcoma/patologia , Neoplasias Retroperitoneais/patologia , Idoso , Feminino , Humanos , Recidiva Local de Neoplasia/patologia
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