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1.
J Cutan Pathol ; 50(7): 606-610, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37069795

RESUMO

Aleukemic leukemia cutis (ALC) is a rare condition that is characterized by leukemic cells in the skin before presenting in the peripheral blood or bone marrow. We report a case of a 43-year-old woman who underwent assessment for bilateral facial nodules arising 1 month after COVID-19 infection. A punch biopsy specimen showed a malignant neoplasm primarily composed of immature blasts dissecting through the collagen in the dermis, concerning for myeloid sarcoma versus leukemia cutis. Bone marrow and blood specimens were negative for hematologic malignancy. The patient was appropriately treated with chemotherapy and is recovering well. This report highlights an interesting case of ALC following COVID-19 infection presenting as an isolated facial rash. Whether there is a true relationship between the patient's COVID-19 infection and her abrupt presentation of leukemia remains unclear, but we present this case regardless, in an effort to highlight a potentially unique association requiring further study.


Assuntos
COVID-19 , Exantema , Leucemia , Neoplasias Cutâneas , Feminino , Humanos , Adulto , COVID-19/patologia , Leucemia/patologia , Neoplasias Cutâneas/patologia , Pele/patologia , Exantema/patologia
2.
J Cutan Pathol ; 50(4): 349-357, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36285428

RESUMO

BACKGROUND: BRCA1-associated protein 1 (BAP-1) is a deubiquitylase that functions as a tumor suppressor, regulating multiple cellular processes including cell cycle control, differentiation, cell death, and DNA repair. BAP-1-inactivated melanocytic tumors (BIMTs) have recently been described and are characterized by epithelioid cytomorphology, are often clonal in appearance, and typically do not recur or show malignant transformation on follow-up. AIM: To describe the histopathologic and molecular characterization of five cases of BAP-1-inactivated cutaneous malignant melanomas. METHODS: The archives at two separate institutions were retrospectively searched for tumors classified as melanoma with loss of BAP-1 via immunohistochemistry. Five cases were identified. These cases were classified as malignant melanoma based on cytomorphology, immunohistochemistry, and ancillary molecular testing. The clinical demographics were recorded, along with the histomorphologic features of each case. Genomic analysis for all cases was performed via OncoScan. RESULTS: The five reviewed cases consisted of two females and three males ranging from 67 to 74 years in age. Molecular characterization of each case was performed using OncoScan. Microarray assay showed that there was a complete deletion of 3p in all cases, BRAF V600E mutation in two cases, NRAS missense variant in one case, and loss of 9p in three cases. All cases showed malignant copy number alterations. CONCLUSIONS: Herein we describe five cases of BAP-1-inactivated melanomas confirmed by histomorphology and immunohistochemistry, all of which show malignant copy number profiles including loss of 3p. In addition, we provide a case of a likely BIMT showing progression to BAP-1-inactivated melanoma on a 16-year follow-up.


Assuntos
Melanoma , Neoplasias Cutâneas , Feminino , Humanos , Masculino , Melanoma/genética , Melanoma/patologia , Mutação , Recidiva Local de Neoplasia , Proteínas Proto-Oncogênicas B-raf/genética , Estudos Retrospectivos , Neoplasias Cutâneas/patologia , Idoso , Melanoma Maligno Cutâneo
3.
J Cutan Pathol ; 48(11): 1367-1378, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34089205

RESUMO

BACKGROUND: Cutaneous involvement by classic Hodgkin lymphoma (CHL) is an extraordinarily rare phenomenon in the current era. To date, no single large case series of cutaneous involvement by Hodgkin lymphoma has ever been reported in the literature. METHODS: A comprehensive search for cases designated "skin" and "Hodgkin" was performed at different institutions between 1990 and 2020. Twenty-five cases were identified, and each case was independently reviewed by at least three board-certified dermatopathologists and/or hematopathologists. RESULTS: All cases represented examples of systemic CHL with secondary skin dissemination. A single lesion, usually a tumor, nodule or infiltrative plaque was observed in 56% of cases and multiple lesions were present in 28% of cases. Most patients (86%-12/14) had a diagnosis of stage IV disease at first diagnosis. The interval between the clinical (first) diagnosis of HL and the development of skin lesions ranged between 6 and 108 months (average 33.75 months). Comprehensive histopathologic evaluation of these cases (at the initial diagnosis) revealed a diagnosis of classic HL not otherwise specified (NOS) in 60% of cases (15/25), nodular sclerosis type in 24% (6/25), mixed cellularity in 12% (3/25), and lymphocyte depleted in 4% (1/25). CONCLUSIONS: We provide documentation of a large series of CHL with secondary skin involvement in association with CHL with additional clinical, morphologic, and immunophenotypic features.


Assuntos
Doença de Hodgkin/patologia , Neoplasias Cutâneas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
4.
Adv Anat Pathol ; 25(3): 197-215, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29189208

RESUMO

Extraneuraxial hemangioblastoma occurs in nervous paraneuraxial structures, somatic tissues, and visceral organs, as part of von Hippel-Lindau disease (VHLD) or in sporadic cases. The VHL gene plausibly plays a key role in the initiation and tumorigenesis of both central nervous system and extraneuraxial hemangioblastoma, therefore, the underlying molecular and genetic mechanisms of the tumor growth are initially reviewed. The clinical criteria for the diagnosis of VHLD are summarized, with emphasis on the distinction of sporadic hemangioblastoma from the form fruste of VHLD (eg, hemangioblastoma-only VHLD). The world literature on the topic of extraneuraxial hemangioblastomas has been comprehensively reviewed with ∼200 cases reported to date: up to 140 paraneuraxial, mostly of proximal spinal nerve roots, and 65 peripheral, 15 of soft tissue, 6 peripheral nerve, 5 bone, and 39 of internal viscera, including 26 renal and 13 nonrenal. A handful of possible yet uncertain cases from older literature are not included in this review. The clinicopathologic features of extraneuraxial hemangioblastoma are selectively presented by anatomic site of origin, and the differential diagnosis is emphasized in these subsets. Reference is made also to 10 of the authors' personal cases of extraneuraxial hemangioblastomas, which include 4 paraneuraxial and 6 peripheral (2 soft tissue hemangioblastoma and 4 renal).


Assuntos
Hemangioblastoma/diagnóstico , Hemangioblastoma/patologia , Humanos , Doença de von Hippel-Lindau/complicações
6.
Ann Hematol ; 95(6): 881-91, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27044389

RESUMO

Burkitt lymphoma (BL) is an aggressive B cell lymphoma characterized by the reciprocal translocation of the c-Myc gene with immunoglobulin genes. Recently, MYC has been shown to maintain the neoplastic state via the miR-17-92 microRNA cluster that suppresses chromatin regulatory genes and the apoptosis regulator Bim. However, the expression and prognostic impact of miR-17-92 members in pediatric BL (pBL) are unknown. Therefore, we investigated miR-17, miR-19a, miR-19b, miR-20, and miR-92a expression and prognostic impact in a series of 41 pBL samples. In addition, Bim protein expression was evaluated and compared to miR-17, miR-19a, miR-19b, miR-20, and miR-92a levels and patient outcomes. The expression of miR-17-92 members was evaluated by qPCR and Bim protein by immunohistochemistry. Log-rank test was employed to assess prognostic impact. We found that upregulated expression of miR-17 and miR-20a correlates with lack of pro-apoptotic Bim expression. Patients bearing tumors with upregulated miR-17 displayed decreased overall survival (OS), and multivariate analysis revealed that miR-17 was a significant predictor of shortened OS. Using hairpin inhibitors, we showed that inhibition of miR-17 resulted in enhanced Bim expression in a BL cell line overexpressing the miR-17-92 cluster. Our results describe for the first time miR-17, miR-19a, miR-19b, miR-20a, and miR-92a expression profiles in pBL. The prognostic impact of miR-17 should be validated in a larger series, and may provide new therapeutic avenues in the era of anti-miRNA therapy research. Additional functional studies are further required to understand the specific role of miR-17-92 cluster members in BL.


Assuntos
Linfoma de Burkitt/diagnóstico , Linfoma de Burkitt/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Adolescente , Linfoma de Burkitt/metabolismo , Criança , Pré-Escolar , Análise por Conglomerados , Feminino , Seguimentos , Humanos , Masculino , MicroRNAs/biossíntese , Prognóstico , RNA Longo não Codificante
7.
Ann Diagn Pathol ; 21: 1-6, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27040923

RESUMO

We have studied 22 cases of mammary lipophyllodes tumors (LPT), analyzing their clinicopathologic features along with available follow-up. All cases were tested for cytokeratins, S100 protein, and MDM2, and in selected cases for estrogen receptor, smooth muscle actin, bcl2, desmin, and myogenin. Patients were women aged 21 to 69 years (average, 45 years), and LPT size ranged from 1.6 to 30 cm (average, 9.7 cm). Microscopically, LPT segregated as follows: atypical lipoma-like tumor/well-differentiated liposarcoma (ALT/WDL), 8 cases; myxoid, 6; and pleomorphic/poorly differentiated/round cell, 8, including a case of dedifferentiated liposarcoma. Immunohistochemistry studies showed focal positive staining for S100 and CD34 in most ALT/WDL, and desmin and myogenin in 2 cases with evidence of rhabdomyoblastic differentiation. MDM2 positivity was focally seen in 1 case. Follow-up was available in 8 cases. Multiple recurrent tumors were seen in 2 patients, and metastatic disease to the lung was seen in 2 patients. In 4 patients with a follow-up between 2 and 15 years there was no evidence of recurrent or metastatic disease. Patients with ALT/WDL (2/2) were alive with no evidence of disease; 2 of 4 patients with myxoid liposarcoma component experienced tumor recurrence, whereas pleomorphic liposarcoma LPT pursued a less favorable course although only 1 patient died of the condition. Absence of MDM2 reactivity in most cases seems not as meaningful as in fatty tumors of somatic soft parts.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/diagnóstico , Lipoma/diagnóstico , Lipossarcoma/diagnóstico , Tumor Filoide/diagnóstico , Adulto , Idoso , Mama/metabolismo , Mama/patologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/cirurgia , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Lipoma/metabolismo , Lipoma/cirurgia , Lipossarcoma/metabolismo , Lipossarcoma/cirurgia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Tumor Filoide/metabolismo , Tumor Filoide/cirurgia , Proteínas Proto-Oncogênicas c-mdm2/genética , Adulto Jovem
8.
Histopathology ; 66(6): 856-63, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25330326

RESUMO

AIMS: Unusual cytoplasmic alterations have recently been reported in poorly differentiated cutaneous angiosarcoma, making an accurate diagnosis challenging. As these tumours remain poorly documented, we aimed to study their clinicopathological characteristics more comprehensively. METHODS AND RESULTS: Six cutaneous angiosarcomas with unusual cytoplasmic alterations were identified from referral files. All tumours arose as nodules or plaques (range: 05-195 mm) on sun-damaged skin of the head and neck of elderly males (median age: 76.5 years). Histologically, the tumours were composed of enlarged epithelioid cells showing prominent signet ring (n = 3), foam (n = 2) or granular cell (n = 1) change. Vasoformative elements were only focally noted. By immunohistochemistry, all tumours expressed CD31 and avian v-ets erythroblastosis virus E26 oncogene homologue (ERG). Foam cell change was associated with additional expression of CD68 and CD163. Follow-up (median: 8 months) showed death from disease (n = 1), death from a gastrointestinal bleed (n = 1), and a cutaneous metastasis (n = 1). Only two patients are alive with no evidence of disease. CONCLUSIONS: Our findings outline the morphological spectrum of cytoplasmic change in cutaneous angiosarcoma. Awareness and a high degree of suspicion in the context of tumours affecting sun-damaged skin of the elderly are necessary to direct appropriate immunohistochemical work-up with inclusion of the endothelial cell markers CD31 and ERG.


Assuntos
Hemangioendotelioma Epitelioide/patologia , Neoplasias Cutâneas/patologia , Idoso , Biomarcadores Tumorais/análise , Humanos , Imuno-Histoquímica , Masculino
9.
Blood ; 119(23): 5478-91, 2012 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-22517897

RESUMO

LMO2 regulates gene expression by facilitating the formation of multipartite DNA-binding complexes. In B cells, LMO2 is specifically up-regulated in the germinal center (GC) and is expressed in GC-derived non-Hodgkin lymphomas. LMO2 is one of the most powerful prognostic indicators in diffuse large B-cell (DLBCL) patients. However, its function in GC B cells and DLBCL is currently unknown. In this study, we characterized the LMO2 transcriptome and transcriptional complex in DLBCL cells. LMO2 regulates genes implicated in kinetochore function, chromosome assembly, and mitosis. Overexpression of LMO2 in DLBCL cell lines results in centrosome amplification. In DLBCL, the LMO2 complex contains some of the traditional partners, such as LDB1, E2A, HEB, Lyl1, ETO2, and SP1, but not TAL1 or GATA proteins. Furthermore, we identified novel LMO2 interacting partners: ELK1, nuclear factor of activated T-cells (NFATc1), and lymphoid enhancer-binding factor1 (LEF1) proteins. Reporter assays revealed that LMO2 increases transcriptional activity of NFATc1 and decreases transcriptional activity of LEF1 proteins. Overall, our studies identified a novel LMO2 transcriptome and interactome in DLBCL and provides a platform for future elucidation of LMO2 function in GC B cells and DLBCL pathogenesis.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Linfócitos B/metabolismo , Proteínas com Domínio LIM/genética , Linfoma Difuso de Grandes Células B/genética , Proteínas Proto-Oncogênicas/genética , Transcriptoma , Linfócitos B/patologia , Sequência de Bases , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células , Centrossomo/ultraestrutura , Regulação Neoplásica da Expressão Gênica , Humanos , Linfoma Difuso de Grandes Células B/patologia , Dados de Sequência Molecular , Regiões Promotoras Genéticas , RNA Longo não Codificante , Transferases , Proteínas Supressoras de Tumor/genética
10.
BMC Womens Health ; 14: 102, 2014 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-25174527

RESUMO

BACKGROUND: To compare the distribution of the intrinsic molecular subtypes of breast cancer based on immunohistochemical profile in the five major geographic regions of Brazil, a country of continental dimension, with a wide racial variation of people. METHODS: The study was retrospective observational. We classified 5,687 invasive breast cancers by molecular subtype based on immunohistochemical expression of estrogen-receptor (ER), progesterone-receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67 proliferation index. Cases were classified as luminal A (ER and/or PR positive and HER2 negative, Ki-67 < 14%), luminal B (ER and/or PR positive, HER2 negative, and Ki-67 > 14%), triple-positive (ER and/or PR positive and HER2 positive), HER2-enriched (ER and PR negative, and HER2- positive), and triple-negative (TN) (ER negative, PR negative, and HER2- negative). Comparisons of the ages of patients and molecular subtypes between different geographic regions were performed. RESULTS: South and Southeast regions with a higher percentage of European ancestry and higher socioeconomic status presented with the highest proportion of luminal tumors. The North region presented with more aggressive subtypes (HER2-enriched and triple-negative), while the Central-West region predominated triple-positive carcinomas. The Northeast--a region with a high African influence--presented intermediate frequency of the different molecular subtypes. The differences persisted in subgroups of patients under and over 50 years. CONCLUSIONS: The geographic regions differ according to the distribution of molecular subtypes of breast cancer. However, other differences, beside those related to African ancestry, such as socioeconomic, climatic, nutritional, and geographic, have to be considered to explain our results. The knowledge of the differences in breast cancer characteristics among the geographic regions may help to organize healthcare programs in large countries like Brazil with diverse economic and race composition among different geographic regions.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/epidemiologia , Carcinoma/epidemiologia , Neoplasias de Mama Triplo Negativas/epidemiologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , População Negra/estatística & dados numéricos , Brasil/epidemiologia , Neoplasias da Mama/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Antígeno Ki-67/metabolismo , Pessoa de Meia-Idade , Epidemiologia Molecular , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Estudos Retrospectivos , Neoplasias de Mama Triplo Negativas/metabolismo , População Branca/estatística & dados numéricos , Adulto Jovem
11.
Am J Surg Pathol ; 48(9): 1082-1092, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38946053

RESUMO

A type of cholangiocarcinoma (CCA) characterized by peculiar histologic patterns and underlying adenofibromatous lesions has been reported in the literature mostly as individual case reports. This study aims to further clarify the defining characteristics of this spectrum of lesions. Clinicopathologic analysis of 8 biliary tumors with tubulocystic architecture arising in the background of adenofibroma-type lesions was performed. Three of these were also investigated with next-generation sequencing with a 174 genes panel. The patients were 5 males and 3 females, with a mean age of 64.6. All tumors were intrahepatic except for one perihilar that protruded into soft tissues. The mean size was 4.4 cm. At histology, all cases showed a peculiar and cytologically bland tubulocystic pattern that closely resembled tubulocystic-type kidney cancers, including back-to-back microcystic units that formed relatively demarcated nodules, and occurring in the background of adenofibromatous lesions. One case showed perineural invasion by otherwise deceptively benign-appearing microcystic structures, one had areas transitioning to intraductal tubulopapillary neoplasm, and 3 cases harbored more conventional small-duct CCA foci. In those 3 cases, both the tubulocystic and conventional CCA components were investigated by next-generation sequencing separately, and they shared the molecular alterations, including recurrent mutations in chromatin remodeling genes, such as ARID1A , BAP1 , and PBRM1 , and the actionable FGFR2-MCU fusion gene. In the limited follow-up, all but one were alive and free of disease after surgical resection. In conclusion, we described a distinct entity of CCA with specific histo-molecular features, for which we propose the designation of tubulocystic carcinoma of bile ducts.


Assuntos
Adenofibroma , Neoplasias dos Ductos Biliares , Biomarcadores Tumorais , Colangiocarcinoma , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/cirurgia , Feminino , Pessoa de Meia-Idade , Colangiocarcinoma/genética , Colangiocarcinoma/patologia , Colangiocarcinoma/cirurgia , Idoso , Adenofibroma/patologia , Adenofibroma/genética , Adenofibroma/cirurgia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/análise , Mutação , Ductos Biliares Intra-Hepáticos/patologia , Ductos Biliares Intra-Hepáticos/cirurgia , Fenótipo
12.
Mod Pathol ; 26(9): 1183-96, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23599146

RESUMO

Follicular lymphoma is clinically heterogenous, and therefore necessitates the identification of prognostic markers to stratify risk groups and optimize clinical management. It is relatively rare in patients younger than 40 years, and the clinicopathologic characteristics and biological behavior in this age group are poorly understood. In the current study, samples from a cohort of 200 patients between 19 and 40 years were evaluated retrospectively with respect to clinical, histologic, and genetic features. These were then correlated with clinical outcome. The median age at presentation was 35 years with a slight female prepoderance (56%). Most of the cases are presented with nodal disease (90%). Concomitant follicular lymphoma and diffuse large B-cell lymphoma were observed in 7 (4%) patients. Immunohistologic studies showed the expression of CD10 (91%), BCL6 (97%), BCL2 (95%), MUM1/IRF4 (12%), MDM2 (17%), and CD23 (25%). BCL2 rearrangement was present in 74%, and BCL6 in 20%. The estimated overall survival of patients was 13 years (mean). The presence of anemia, elevated lactose dehydrogenase, bone marrow involvement, and high-risk follicular lymphoma international prognostic index correlated with adverse overall survival. Our findings revealed that follicular lymphoma in young adults demonstrate similarities with that of older adults, including the frequency of presentation at various anatomic sites, grade, and adverse prognostic factors.


Assuntos
Biomarcadores Tumorais/análise , Linfoma Folicular/diagnóstico , Linfoma Difuso de Grandes Células B/diagnóstico , Adulto , Fatores Etários , Biomarcadores Tumorais/genética , Análise por Conglomerados , Feminino , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Estimativa de Kaplan-Meier , Modelos Logísticos , Linfonodos/química , Linfonodos/patologia , Linfoma Folicular/química , Linfoma Folicular/genética , Linfoma Folicular/mortalidade , Linfoma Folicular/patologia , Linfoma Folicular/terapia , Linfoma Difuso de Grandes Células B/química , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/patologia , Masculino , Gradação de Tumores , Estadiamento de Neoplasias , Razão de Chances , Valor Preditivo dos Testes , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
13.
Mod Pathol ; 26(10): 1329-37, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23599149

RESUMO

ALK-positive large B-cell lymphoma is an aggressive lymphoid neoplasm characterized by a monomorphic proliferation of immunoblast-like cells expressing a plasmablastic phenotype and carrying ALK rearrangements. MYC rearrangements are frequent in plasmablastic lymphomas, advanced plasma cell myelomas and a subgroup of diffuse large B-cell lymphomas, but their presence in ALK-positive large B-cell lymphomas is unknown. MYC expression is downregulated by BLIMP1, a master modulator of plasma cell differentiation. BLIMP1 and MYC are upregulated by STAT3, a signal transducer activated by ALK. To determine the role of BLIMP1, MYC and STAT3 in the pathogenesis of ALK-positive large B-cell lymphomas, we investigated MYC rearrangement and the expression of MYC, phosphorylated STAT3, BLIMP1, PAX5 and XBP1 in 12 ALK-positive large B-cell lymphomas. All cases expressed ALK with a granular cytoplasmic pattern. Nine cases had a split signal consistent with an ALK rearrangement. Three additional cases showed a deletion of the 5' or 3' end of the ALK probe consistent with cryptic translocation. PAX5 was virtually negative in all cases tested, whereas BLIMP1 was expressed in all tumors and XBP1 in 11 of 12. Phosphorylated STAT3 was observed in all cases with a strong and diffuse nuclear pattern. MYC rearrangements were not identified in any tumor, but MYC gains and amplification were detected in six cases and one case, respectively. MYC protein was expressed in all tumors independently of MYC gene alterations. These results indicate that ALK-positive large B-cell lymphomas express a complete plasmablastic differentiation program but, contrary to plasmablastic lymphomas, do not have MYC rearrangements. STAT3 is constantly activated and may be an alternative mechanism to promote MYC expression in these tumors. The relevance of the ALK/STAT3 pathway in the pathogenesis of ALK-positive large B-cell lymphomas may offer an attractive target for new therapies.


Assuntos
Linfócitos B/metabolismo , Linfoma Difuso de Grandes Células B/genética , Proteínas Proto-Oncogênicas c-myc/genética , Receptores Proteína Tirosina Quinases/genética , Fator de Transcrição STAT3/genética , Adulto , Quinase do Linfoma Anaplásico , Linfócitos B/patologia , Diferenciação Celular/genética , Feminino , Humanos , Linfoma Difuso de Grandes Células B/metabolismo , Linfoma Difuso de Grandes Células B/patologia , Masculino , Fosforilação , Fator 1 de Ligação ao Domínio I Regulador Positivo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/genética
14.
Am J Dermatopathol ; 35(6): 671-5, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23538897

RESUMO

We report 2 cases of cutaneous epithelioid angiosarcoma featuring predominantly signet ring cells. The patients-a woman, 68 years of age, and a man, 85 years of age, respectively-were referred for slowly growing indurated plaques on their parietal and retroauricular skin. Microscopic examination showed diffuse dermal proliferations comprising polygonal cells and relatively abundant cytoplasm. Because the tumor cells often were distended by variably sized vacuoles pushing the nuclei to the periphery, the nuclear profile tended toward a crescent-like morphology. Abortive luminal formations were recognized. The tumor cells were positive for CD31, CD34, and D2-40/podoplanin, with no expression of epithelial or melanocytic markers. In 1 case, upon ultrastructural examination of paraffin-embedded tissue-cut from wax tissue and reprocessed-the optically empty spaces were surrounded by a membrane with ultrastructural features identical to those of the outer cell membrane, suggesting that these spaces corresponded to the formation of primitive intracytoplasmic lumina within the tumor cells. A few Weibel-Palade bodies also were noted. Our report offers further evidence that epithelioid angiosarcoma of the skin has a broad microscopic spectrum and that tumors displaying a preponderant population of signet ring cells pose further diagnostic challenges. A brief overview of cutaneous malignant tumors in the differential diagnosis of signet ring cell angiosarcoma is provided.


Assuntos
Carcinoma de Células em Anel de Sinete/diagnóstico , Células Epitelioides/patologia , Hemangiossarcoma/diagnóstico , Neoplasias Cutâneas/diagnóstico , Pele/patologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Biópsia , Carcinoma de Células em Anel de Sinete/química , Carcinoma de Células em Anel de Sinete/patologia , Proliferação de Células , Diagnóstico Diferencial , Células Epitelioides/química , Células Epitelioides/ultraestrutura , Feminino , Hemangiossarcoma/química , Hemangiossarcoma/patologia , Humanos , Imuno-Histoquímica , Masculino , Microscopia Eletrônica de Transmissão , Valor Preditivo dos Testes , Pele/química , Pele/ultraestrutura , Neoplasias Cutâneas/química , Neoplasias Cutâneas/patologia
15.
Ann Diagn Pathol ; 17(3): 250-5, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23246412

RESUMO

Aggressive B-cell lymphomas incorporate a wide spectrum of lymphomas that pose challenges in diagnosis as well as treatment. We evaluated the clinicopathological features of 44 patients with aggressive B-cell lymphomas which were classified into 3 groups based on the World Health Organization 2008 classification as follows: including 30 cases of diffuse large B-cell lymphoma (DLBCL), 8 cases of Burkitt lymphoma (BL) and 6 cases of B-cell lymphoma, unclassifiable, with features intermediate between Burkitt lymphoma and diffuse large B-cell lymphoma (BCLU). Male predominance was observed in BL and BCLU groups and the mean age varied from 29 years in BL, 61 years in DLBCL and 70 years in BCLU. Patients with BCLU presented at more advanced stages and had a higher international prognostic index. By immunohistochemistry, they shared characteristics of both BL (including more frequent expression of SOX11) and DLBCL. FISH analyses showed three cases with more than one rearrangement: one MYC/BCL2 and two BCL2/BCL6, in addition to which one case with BCL2/IGH translocation and another with MYC rearrangement were also detected. The mean follow-up survival time of BCLU was 6.6 months, which was significantly shorter in comparison to DLBCL (31 months) and BL (30 months), respectively. The importance of recognizing this BCLU group relies on its different clinical course, poor prognosis and shorter survival than DLBCL and BL. An accurate diagnosis is critical for risk stratification and to improve therapeutic approaches and outcomes.


Assuntos
Linfoma de Burkitt/diagnóstico , Linfoma Difuso de Grandes Células B/diagnóstico , Adulto , Idoso , Argentina/epidemiologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Linfoma de Burkitt/genética , Linfoma de Burkitt/metabolismo , Linfoma de Burkitt/mortalidade , Feminino , Rearranjo Gênico , Humanos , Hibridização in Situ Fluorescente , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/metabolismo , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Fatores de Transcrição SOXC/metabolismo , Taxa de Sobrevida , Análise Serial de Tecidos , Translocação Genética
16.
Mod Pathol ; 25(5): 661-74, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22222636

RESUMO

B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma, is a diagnostic provisional category in the World Health Organization (WHO) 2008 classification of lymphomas. This category was designed as a measure to accommodate borderline cases that cannot be reliably classified into a single distinct disease entity after all available morphological, immunophenotypical and molecular studies have been performed. Typically, these cases share features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma, or include characteristics of both lymphomas. The rarity of such cases poses a tremendous challenge to both pathologists and oncologists because its differential diagnosis has direct implications for management strategies. In this study, we present 10 cases of B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma and have organized the criteria described by the WHO into four patterns along with detailed clinical, morphological and immunophenotypic characterization and outcome data. Our findings show a male preponderance, median age of 37 years and a mediastinal presentation in 80% of cases. All cases expressed at least two markers associated with B-cell lineage and good response to combination chemotherapy currently employed for non-Hodgkin lymphomas.


Assuntos
Doença de Hodgkin/patologia , Linfoma Difuso de Grandes Células B/patologia , Neoplasias do Mediastino/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/metabolismo , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Rearranjo Gênico do Linfócito B , Doença de Hodgkin/genética , Doença de Hodgkin/metabolismo , Doença de Hodgkin/terapia , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/metabolismo , Linfoma Difuso de Grandes Células B/terapia , Masculino , Neoplasias do Mediastino/metabolismo , Neoplasias do Mediastino/terapia , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Radioterapia Adjuvante , Rituximab , Vincristina/uso terapêutico , Adulto Jovem
17.
Mod Pathol ; 25(11): 1439-45, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22743653

RESUMO

Diffuse large B-cell lymphoma can be subclassified into at least two molecular subgroups by gene expression profiling: germinal center B-cell like and activated B-cell like diffuse large B-cell lymphoma. Several immunohistological algorithms have been proposed as surrogates to gene expression profiling at the level of protein expression, but their reliability has been an issue of controversy. Furthermore, the proportion of misclassified cases of germinal center B-cell subgroup by immunohistochemistry, in all reported algorithms, is higher compared with germinal center B-cell cases defined by gene expression profiling. We analyzed 424 cases of nodal diffuse large B-cell lymphoma with the panel of markers included in the three previously described algorithms: Hans, Choi, and Tally. To test whether the sensitivity of detecting germinal center B-cell cases could be improved, the germinal center B-cell marker HGAL/GCET2 was also added to all three algorithms. Our results show that the inclusion of HGAL/GCET2 significantly increased the detection of germinal center B-cell cases in all three algorithms (P<0.001). The proportions of germinal center B-cell cases in the original algorithms were 27%, 34%, and 19% for Hans, Choi, and Tally, respectively. In the modified algorithms, with the inclusion of HGAL/GCET2, the frequencies of germinal center B-cell cases were increased to 38%, 48%, and 35%, respectively. Therefore, HGAL/GCET2 protein expression may function as a marker for germinal center B-cell type diffuse large B-cell lymphoma. Consideration should be given to the inclusion of HGAL/GCET2 analysis in algorithms to better predict the cell of origin. These findings bear further validation, from comparison to gene expression profiles and from clinical/therapeutic data.


Assuntos
Algoritmos , Biomarcadores Tumorais/análise , Imuno-Histoquímica , Linfoma Difuso de Grandes Células B/química , Proteínas de Neoplasias/análise , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Distribuição de Qui-Quadrado , Criança , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Modelos Lineares , Linfoma Difuso de Grandes Células B/patologia , Masculino , Proteínas dos Microfilamentos , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Análise Serial de Tecidos , Adulto Jovem
18.
Int J Gynecol Pathol ; 31(1): 8-14, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22123718

RESUMO

Lymphatic vessels serve as major routes for regional dissemination, and therefore, lymph node status is a key indicator of prognosis. To predict lymph node metastasis, tumor lymphatic density and lymphangiogenesis-related molecules have been studied in various tumor types. To our knowledge, no previous studies have evaluated the role of intratumoral lymphatic vessel density (LVD) in the behavior of vulvar carcinomas. The aim of this study was to analyze intratumoral LVD in relation to patient survival and well-characterized prognostic factors for cancer. Thirty-five patients with vulvar squamous cell carcinoma underwent vulvectomy and dissection of regional lymph nodes. Clinical records were reviewed, in addition to histological grade, peritumoral lymphatic invasion, and depth of infiltration for each case. Tissue microarray paraffin blocks were created, and lymphatic vessels were detected using immunohistochemical staining of podoplanin (D2-40 antibody). Intratumoral LVD was quantified by counting the number of stained vessels. Higher values for intratumoral LVD were associated with low-grade and low-stage tumors, and with tumors without lymphatic invasion and reduced stromal infiltration. In a univariate analysis, high intratumoral LVD was associated with a higher rate of overall survival and a lower rate of lymph node metastasis. Our results suggest that increased intratumoral LVD is associated with favorable prognosis in vulvar squamous carcinomas.


Assuntos
Carcinoma de Células Escamosas/patologia , Linfonodos/patologia , Vasos Linfáticos/patologia , Neoplasias Vulvares/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/cirurgia , Intervalos de Confiança , Feminino , Humanos , Estimativa de Kaplan-Meier , Linfangiogênese , Metástase Linfática , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Inclusão em Parafina , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias Vulvares/mortalidade , Neoplasias Vulvares/cirurgia
19.
Am J Dermatopathol ; 34(6): 619-25, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22421295

RESUMO

Clear cell sarcoma is a unique soft tissue tumor with distinct microscopic features that include a nested or fascicular pattern of spindle cells accompanied by larger wreath-like giant cells scattered throughout. It harbors a unique EWSR1-ATF1 gene fusion secondary to a t(12;22)(q13;q12) translocation. Recently, it was reported that clear cell sarcoma can occur in the skin and mimic a broad spectrum of entities, including spindle cell melanoma. Here, we describe 3 new cases of clear cell sarcoma of the skin, all of which were confirmed molecularly. The patients, a 12-year-old boy, a 29-year-old woman, and a 60-year-old man, had cutaneous lesions on the thigh, dorsum of foot, and sole, respectively. All 3 lesions were originally considered suspicious of spindle cell melanoma. Microscopically, the lesions featured nodular proliferation centered in the dermis that consisted of discrete fascicles of spindle cell enmeshed by thin fibrous strands. Wreath-like cells were present in all cases. Tumor cells were positive for S100 protein (3 of 3 cases), melan A (2 of 3 cases), HMB 45 (1 of 3 cases) although a junctional melanocytic proliferation was seen in 1 case. Sentinel lymph node biopsy was negative in 2 patients. Follow-up was uneventful in 2 patients, whereas the other patient developed a lymph node metastasis 5 months after primary tumor excision. This study confirms that malignant dermal tumors that mimic but do not exactly replicate spindle cell melanoma should raise suspicion for cutaneous clear cell sarcoma and prompt the investigation for the confirmatory gene fusion t(12;22).


Assuntos
Melanoma/diagnóstico , Sarcoma de Células Claras/diagnóstico , Sarcoma/diagnóstico , Neoplasias Cutâneas/diagnóstico , Adulto , Criança , Diagnóstico Diferencial , Feminino , Humanos , Antígeno MART-1/metabolismo , Masculino , Melanoma/metabolismo , Melanoma/patologia , Antígenos Específicos de Melanoma/metabolismo , Pessoa de Meia-Idade , Proteínas S100/metabolismo , Sarcoma/metabolismo , Sarcoma/patologia , Sarcoma de Células Claras/metabolismo , Sarcoma de Células Claras/patologia , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Antígeno gp100 de Melanoma
20.
Head Neck Pathol ; 16(3): 746-754, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35303277

RESUMO

The archetypal solitary fibrous tumor (SFT) features fibroblastic cells with varying cellularity without any particular architectural arrangement in a collagenous matrix, with staghorn vessels, CD34 and STAT6 expression, and NAB2::STAT6. To date, this fusion is thought to be specific for SFT. With more routine use of fusion gene panels, the histologic diversity of NAB2::STAT6-positive tumors is increasingly appreciated. Here we present four head and neck tumors harboring NAB2::STAT6 but exhibiting remarkably unusual morphologic features for SFT. All cases were pulled from the authors' consultation files. Immunohistochemistry was performed, along with targeted RNA sequencing in all cases, plus DNA next-generation sequencing on two. The cases arose in the nasal cavity (n = 2), retromolar trigone (n = 1) and parapharynx (n = 1), in patients ranging from 39 to 54 (mean, 44). Both nasal cases were biphasic, with a variably cellular collagenized stroma that resembled SFT but also interspersed malignant epithelial and neuroepithelial nests. One of the nasal cases also exhibited overt rhabdomyoblastic differentiation within both components. The two non-nasal cases were comprised of plump, epithelioid cells that were diffusely positive for pan-cytokeratin. One of these cases had prominent cystic change lined by overtly squamous epithelium. STAT6 immunostaining was positive in all cases, although the epithelial/neuroepithelial nests in the sinonasal cases were negative. All cases were confirmed to harbor NAB2::STAT6 by RNA sequencing. The two sinonasal cases were also found to harbor oncogenic mutations. The presented cases highlight a much broader histologic diversity than previously known for neoplasms with NAB2::STAT6. The biphasic nasal cases closely resemble teratocarcinosarcoma, while the epithelioid, cytokeratin-positive cases could be conceptualized as "adamantinoma-like," to borrow terminology already in use for Ewing sarcomas with complex epithelial differentiation. To identify similar cases, pathologists should have a low threshold for using STAT6 immunohistochemistry on any difficult-to-characterize head and neck tumor.


Assuntos
Adamantinoma , Ameloblastoma , Neoplasias de Cabeça e Pescoço , Tumores Fibrosos Solitários , Biomarcadores Tumorais , Humanos , Queratinas , Proteínas Repressoras , Fator de Transcrição STAT6
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