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1.
Blood ; 124(9): 1473-80, 2014 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-24894770

RESUMO

Anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma (ALCL) is a CD30-positive T-cell non-Hodgkin lymphoma that morphologically resembles ALK-positive ALCL but lacks chromosomal rearrangements of the ALK gene. The genetic and clinical heterogeneity of ALK-negative ALCL has not been delineated. We performed immunohistochemistry and fluorescence in situ hybridization on 73 ALK-negative ALCLs and 32 ALK-positive ALCLs and evaluated the associations among pathology, genetics, and clinical outcome. Chromosomal rearrangements of DUSP22 and TP63 were identified in 30% and 8% of ALK-negative ALCLs, respectively. These rearrangements were mutually exclusive and were absent in ALK-positive ALCLs. Five-year overall survival rates were 85% for ALK-positive ALCLs, 90% for DUSP22-rearranged ALCLs, 17% for TP63-rearranged ALCLs, and 42% for cases lacking all 3 genetic markers (P < .0001). Hazard ratios for death in these 4 groups after adjusting for International Prognostic Index and age were 1.0 (reference group), 0.58, 8.63, and 4.16, respectively (P = 7.10 × 10(-5)). These results were similar when restricted to patients receiving anthracycline-based chemotherapy, as well as to patients not receiving stem cell transplantation. Thus, ALK-negative ALCL is a genetically heterogeneous disease with widely disparate outcomes following standard therapy. DUSP22 and TP63 rearrangements may serve as predictive biomarkers to help guide patient management.


Assuntos
Linfoma Anaplásico de Células Grandes/genética , Linfoma Anaplásico de Células Grandes/metabolismo , Receptores Proteína Tirosina Quinases/genética , Receptores Proteína Tirosina Quinases/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Quinase do Linfoma Anaplásico , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Criança , Fosfatases de Especificidade Dupla/genética , Feminino , Rearranjo Gênico , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Fatores Reguladores de Interferon/genética , Estimativa de Kaplan-Meier , Linfoma Anaplásico de Células Grandes/patologia , Masculino , Pessoa de Meia-Idade , Fosfatases da Proteína Quinase Ativada por Mitógeno/genética , Prognóstico , Fatores de Transcrição/genética , Proteínas Supressoras de Tumor/genética , Adulto Jovem
2.
J Investig Med High Impact Case Rep ; 11: 23247096231168105, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37073478

RESUMO

Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults and is characterized by monoclonal proliferation of B-cell lymphocytes which are morphologically mature, but immunologically dysfunctional. The primary sites of disease involvement include peripheral blood, lymph nodes, spleen, and bone marrow. CLL can also present locally and aggressively at extranodal sites. We describe the case of a 74-year-old gentleman with multiple medical comorbidities who was Foley catheter-dependent at baseline for bladder outlet obstruction. He was detected to have Rai stage I CLL following an inguinal lymph node biopsy and was on regular outpatient surveillance. Later, he underwent a prostate biopsy for evaluation of hematuria, results of which were consistent with CLL involvement in the prostate and urinary bladder. The patient was started on single-agent ibrutinib, and demonstrated an excellent clinical response to bladder outlet obstruction. His long-term Foley catheter was discontinued within 5 days of ibrutinib therapy. Unfortunately, 1 year later, he had disease progression, and therapy was changed to a single-agent rituximab, to which he is responding well. Our case is unique as it brings up the first reported case of prostate and bladder wall CLL.


Assuntos
Leucemia Linfocítica Crônica de Células B , Obstrução do Colo da Bexiga Urinária , Masculino , Adulto , Humanos , Idoso , Leucemia Linfocítica Crônica de Células B/complicações , Leucemia Linfocítica Crônica de Células B/patologia , Bexiga Urinária/patologia , Próstata , Rituximab/uso terapêutico
3.
Am J Surg Pathol ; 40(1): 36-43, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26379151

RESUMO

Systemic anaplastic large cell lymphomas (ALCLs) are classified into ALK-positive and ALK-negative types. We recently reported that ALK-negative ALCLs are genetically heterogenous. The largest subset, representing 30% of cases, had rearrangements of the DUSP22 locus. These cases had favorable outcomes similar to ALK-positive ALCL, and superior to other ALK-negative ALCLs. Here, we examined the morphologic features of these cases in more detail. First, we conducted blinded review of hematoxylin and eosin slides of 108 ALCLs from our previous study, scoring cases for the presence of 3 histologic patterns and 5 cell types. Cases then were unblinded and re-reviewed to understand these features further. DUSP22-rearranged ALCLs were more likely than other ALK-negative ALCLs to have so-called doughnut cells (23% vs. 5%; P=0.039), less likely to have pleomorphic cells (23% vs. 49%; P=0.042), and nearly always (95%) had areas with sheet-like growth (common pattern). To examine the reproducibility of these findings, we conducted blinded review of hematoxylin and eosin slides of 46 additional ALK-negative ALCLs using a 0 to 3 scoring system to predict likelihood of DUSP22 rearrangement, the results of which correlated strongly with subsequent findings by fluorescence in situ hybridization (P<0.0001). Although all ALCLs share certain morphologic features, ALCLs with DUSP22 rearrangements show significant differences from other ALK-negative ALCLs, typically showing sheets of hallmark cells with doughnut cells and few large pleomorphic cells. These morphologic findings and our previous outcome data suggest that ALK-positive ALCLs and DUSP22-rearranged ALCLs represent prototypical ALCLs, whereas ALCLs lacking rearrangements of both DUSP22 and ALK require further study.


Assuntos
Biomarcadores Tumorais/genética , Fosfatases de Especificidade Dupla/genética , Rearranjo Gênico , Linfoma Anaplásico de Células Grandes/genética , Linfoma Anaplásico de Células Grandes/patologia , Fosfatases da Proteína Quinase Ativada por Mitógeno/genética , Receptores Proteína Tirosina Quinases/genética , Adolescente , Adulto , Idoso , Quinase do Linfoma Anaplásico , Biópsia , Criança , Feminino , Predisposição Genética para Doença , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Linfoma Anaplásico de Células Grandes/enzimologia , Masculino , Pessoa de Meia-Idade , Fenótipo , Valor Preditivo dos Testes , Adulto Jovem
4.
Acta Cytol ; 48(2): 207-10, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15085753

RESUMO

BACKGROUND: Large cell lymphoma involving the vitreous humor is uncommon, and its diagnosis in the absence of central nervous system disease can be difficult. The major diagnostic difficulties with vitreous washings in the absence of ancillary studies are in the distinction of inflammatory lymphoid infiltrate from intraocular lymphoma or diagnosing lymphoma when only very few neoplastic cells are present. CASE: A 75-year-old, white male sought medical attention for bilateral blurred vision and decreased visual acuity of recent onset. A clinical diagnosis of bilateral uveitis to rule out primary intraocular lymphoma or an infectious process was made, and a right vitrectomy was performed. An unequivocal diagnosis of lymphoma could not be made due to the paucity of neoplastic cells on that specimen. Two months later smears from the Cytospin (Thermo Shandon, Pittsburgh, Pennsylvania, U.S.A.) prepared on the specimen from a left vitrectomy showed a greater number of large, pleomorphic cells. In addition, immunocytochemical staining confirmed the B-cell lineage of the neoplastic cells. Immunoglobulin gene rearrangement analysis performed by the polymerase chain reaction method on the frozen cell pellet from the left vitrectomy demonstrated the presence of a monoclonal B-cell population, confirming the diagnosis of large B-cell lymphoma. CONCLUSION: Vitreous cytology in conjunction with ancillary studies is a sensitive procedure in the diagnosis of intraocular lymphoma.


Assuntos
Neoplasias Oculares/patologia , Linfoma de Células B/patologia , Segunda Neoplasia Primária/patologia , Corpo Vítreo/patologia , Idoso , Anticorpos Monoclonais/genética , Antígenos CD20/metabolismo , Linfócitos B/imunologia , Linfócitos B/metabolismo , Linfócitos B/patologia , Biomarcadores Tumorais/metabolismo , Linhagem da Célula/genética , Núcleo Celular/patologia , Células Clonais/imunologia , Células Clonais/metabolismo , Células Clonais/patologia , Diagnóstico Diferencial , Neoplasias Oculares/imunologia , Neoplasias Oculares/fisiopatologia , Evolução Fatal , Humanos , Imunoglobulina G/genética , Imuno-Histoquímica , Linfoma de Células B/imunologia , Linfoma de Células B/fisiopatologia , Masculino , Segunda Neoplasia Primária/imunologia , Segunda Neoplasia Primária/fisiopatologia , Transtornos da Visão/etiologia , Transtornos da Visão/patologia , Transtornos da Visão/fisiopatologia , Corpo Vítreo/fisiopatologia
5.
J Urol ; 173(1): 70-2, 2005 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-15592031

RESUMO

PURPOSE: High grade prostatic intraepithelial neoplasia (HGPIN) and atypical small acinar proliferation (ASAP) in the sextant biopsy had been associated with a high risk of prostate cancer. We determined whether the extended biopsy schemes used in the contemporary era have altered the prognostic value of these lesions at repeat biopsies. MATERIALS AND METHODS: From 1998 to 2003, 105 of 1,188 men had at least 1 repeat extended biopsy due to the presence of HGPIN (33 men) or ASAP (72 men) in a previous extended biopsy. Median biopsy interval for HGPIN and ASAP was 15 and 10 weeks (p <0.05), respectively. Differences in cancer detection rates were analyzed using the Pearson chi-square test. RESULTS: In the HGPIN group only 1 of 22 (4.5%) men had cancer on 1st repeat biopsy and 0 of 11 men had cancer on 2nd repeat biopsy. In men with ASAP 19 of 53 (36%, p <0.005) had cancer on 1st repeat biopsy, and 3 of 19 (16%) had cancer on 2nd repeat biopsy. Cancer was confined to a single core in 16 of 22 (73%) men. Median Gleason score was 6. Patient age, digital rectal examination status, prostate specific antigen, free prostate specific antigen, number of cores and biopsy interval were not independent predictors of cancer in men with ASAP. CONCLUSIONS: HGPIN found in the contemporary extended biopsy does not warrant repeat biopsy. ASAP continues to be associated with a high risk of cancer and requires at least 1 repeat biopsy using the extended biopsy scheme.


Assuntos
Neoplasia Prostática Intraepitelial/patologia , Neoplasias da Próstata/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Antígeno Prostático Específico/sangue
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