RESUMO
BACKGROUND: Biliary intraepithelial neoplasia (BilIN) is often distinguished by what it is not: the precancerous lesions are not mass-forming, are not the cause of bile duct obstruction, and are small enough (less than 5 mm long) to evade detection by the naked eye. Here, we describe an atypical case of BilIN resembling cholangiocarcinoma (CC) that was large enough to be identified by diagnostic imaging and presented with obstructive jaundice caused by a hematoma in the common bile duct (CBD). CASE PRESENTATION: A 64-year-old man presented to our hospital with upper abdominal pain and anorexia. Initial laboratory examinations revealed increased total bilirubin and a computed tomography (CT) scan revealed a dilated CBD. Gastroenterologists performed an endoscopic sphincterotomy (EST), which revealed that the cause of obstructive jaundice was a hematoma in the CBD. Enhanced CT scan and magnetic resonance cholangiopancreatography (MRCP) performed after the hematoma was drained showed improved dilation of the CBD and an enhanced wall thickness of bile duct measuring 25 × 10 mm at the union of the cystic and common hepatic ducts. A cholangioscope detected an elevated tumor covered by sludge in the CBD, and we performed an extrahepatic bile duct resection and cholecystectomy. The postoperative course was uneventful and the pathological examination of the resected tumor revealed that although the ulcerated lesion had inflammatory granulation tissue, it did not contain the components of invasive carcinoma. Many consecutive intraepithelial micropapillary lesions spread around the ulcerated lesion, and the epithelial cells showed an increased nucleus-to-cytoplasm ratio, nuclear hyperchromasia, and architectural atypia. The pathological diagnosis was BilIN-1 to -2. Immunohistochemical staining showed that S100P was slightly expressed and MUC5AC was positive, while MUC1 was negative and p53 was not overexpressed. CONCLUSION: We experienced an atypical case of BilIN mimicking CC that presented with obstructive jaundice caused by a hematoma in the CBD. Our case suggested that the occurrence of BilIN can be triggered by factors other than inflammation, and can grow to a size large enough to be detected by image analyses.
Assuntos
Dor Abdominal/etiologia , Ducto Colédoco/patologia , Epitélio/patologia , Hematoma/etiologia , Icterícia Obstrutiva/etiologia , Idoso , Neoplasias dos Ductos Biliares/diagnóstico , Colangiocarcinoma/diagnóstico , Colangiopancreatografia por Ressonância Magnética , Colecistectomia , Ducto Colédoco/diagnóstico por imagem , Ducto Colédoco/cirurgia , Diagnóstico Diferencial , Humanos , Icterícia Obstrutiva/cirurgia , Masculino , Prognóstico , Esfinterotomia Endoscópica , Tomografia Computadorizada por Raios X , Resultado do TratamentoAssuntos
Infecções por Helicobacter , Helicobacter pylori , Linfoma de Zona Marginal Tipo Células B , Linfoma Difuso de Grandes Células B , Neoplasias Gástricas , Infecções por Helicobacter/complicações , Humanos , Linfoma de Zona Marginal Tipo Células B/complicações , Linfoma de Zona Marginal Tipo Células B/patologia , Linfoma Difuso de Grandes Células B/patologia , Linfoma não Hodgkin , Neoplasias Gástricas/complicações , Neoplasias Gástricas/patologiaRESUMO
Prominent cyst formation is an unusual feature of liposarcoma. We report here a case of dedifferentiated liposarcoma with huge cystic change without preoperative chemo- or radiation therapy. The lesion arose in the retroperitoneum juxtaposed to the right kidney of a 67-year-old woman. She underwent a surgical removal of the retroperitoneal cyst. The cystic tumor contained 1600 mL of old bloody fluid, and its wall was composed of edematous, inflamed or sclerosing fibrous tissue with fatty tissue containing abundant atypical stromal cells, which were immunohistochemically positive for MDM2 and CDK4, and demonstrated MDM2 gene amplification by fluorescence in situ hybridization. The wall was contiguous to an atypical lipomatous nodule located in the mesentery. The following surgical specimens of the right hemicolectomy and right nephrectomy revealed atypical cells infiltrating into the subserosa of the colon and the perirenal fat tissue or that in the renal sinus. This case indicates that well differentiated or dedifferentiated liposarcoma should be also considered as a differential diagnosis of perirenal cystic mass.
Assuntos
Quinase 4 Dependente de Ciclina/metabolismo , Lipoma/diagnóstico por imagem , Lipossarcoma/diagnóstico por imagem , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Neoplasias Retroperitoneais/diagnóstico por imagem , Idoso , Cistos/diagnóstico por imagem , Cistos/patologia , Diagnóstico Diferencial , Feminino , Humanos , Lipoma/patologia , Lipossarcoma/patologia , Imageamento por Ressonância Magnética , Neoplasias Retroperitoneais/patologiaRESUMO
Translocations involving MYC are highly characteristic for Burkitt lymphoma (BL). BCL2 expression has also been found previously in about 10 to 20% of BL cases, and BCL2 translocation is a major mechanism for the deregulation of BCL2 expression in non-Hodgkin lymphomas. However, we know little about the incidence of MYC/BCL2 double-hit (DH) in BL. We examined BL cases to determine how frequently they contained BCL2 translocations in combination with MYC translocations using fluorescence in situ hybridization. We also determined the effect of BCL2 expression on clinical outcomes of BL. BCL2 translocations were detected in 3.5% (2/57 cases) of the cases, and BCL2 expression was detected in 33%. Two cases with BCL2 translocation also showed BCL2 expression. The incidence of BCL2 expression was significantly higher in patients 16 years of age and older (46%) than in patients under 16 years of age (6%). Among patients 16 years of age and older, we did not detect significant differences in overall survival with respect to BCL2 expression status. In conclusion, BCL2 translocation is a rare cytogenetic abnormality in BL, and BL probably accounts for only a small fraction of MYC/BCL2 DH lymphomas. BCL2 expression in BL is probably not associated with BCL2 translocations.
Assuntos
Linfoma de Burkitt/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-myc/genética , Translocação Genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Linfoma de Burkitt/mortalidade , Linfoma de Burkitt/patologia , Criança , Pré-Escolar , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Hibridização in Situ Fluorescente , Incidência , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Análise de Sobrevida , Adulto JovemRESUMO
Double-hit (DH) lymphomas are B-cell lymphomas characterized by chromosomal rearrangements, specifically of MYC and either BCL2, BCL6 or CCND1. We reviewed 22 cases of DH lymphomas. BCL2/MYCâ DH lymphomas constituted the majority of these DH lymphomas (17 cases; 77%), followed by BCL6/MYC (2 cases; 9%) lymphomas. Assessing morphological features using the 2008 World Health Organization classification system, 15 cases (68%) were determined to be B-cell lymphoma, unclassifiable with features intermediate between diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BCLU) (10 cases; 45%), or as DLBCL (5 cases; 23%), and 2 cases (9%) were classified as morphologically untransformed follicular lymphoma. Burkitt lymphoma was rare (1 case; 5%) among DH lymphomas. Nineteen cases were treated with R-CHOP or a high dose chemotherapy regimen. After a median follow-up of 11 months, 7 patients had died, and the 1-year survival rate was 62.5%. High dose chemotherapy did not improve the outcome. We suggest that screening of genetic variations to detect DH lymphomas is required in diagnosing all lymphomas, even those determined morphologically to be follicular lymphoma.
Assuntos
Predisposição Genética para Doença , Linfoma de Células B/genética , Linfoma de Células B/patologia , Idoso , Idoso de 80 Anos ou mais , Ciclina D1/genética , Proteínas de Ligação a DNA/genética , Feminino , Humanos , Imunofenotipagem/métodos , Hibridização in Situ Fluorescente/métodos , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-6 , Proteínas Proto-Oncogênicas c-myc/genética , Translocação GenéticaRESUMO
CD5-positive follicular lymphoma (FL), although rare, has been described in a number of case reports. However, a statistically valid, clinicopathological comparison between CD5-positive FL and CD5-negative FL has never been performed because of its rarity. We statistically compared clinicopathological characteristics of 22 cases of CD5-positive FL, diagnosed by immunohistochemistry, flow cytometry and morphological findings, with those of 62 cases of FL without CD5 expression (control cases). CD5-positive FL patients showed a higher tendency of peripheral blood involvement (P = 0.076) and a higher frequency of CD25 expression (P = 0.0004) and MUM1 protein expression (P = 0.0008), and a lower frequency of t(14;18)(q32;q21) (P = 0.017). The overall survival (OS) curve of CD5-positive FL was significantly worse than that of control cases (P = 0.0266), although progression-free survival curves did not show a significant difference (P = 0.7899). Moreover, CD5 expression was shown to be an independent poor prognostic factor for OS in both univariate analysis [Hazard Ratio (HR), 3.63; P = 0.0464] and multivariate analysis (HR, 57.16; P = 0.0001). CD5-positive FL showed different clinicopathological characteristics from FL lacking CD5 expression. These results suggest that CD5-positive FL should be considered a different type of FL, and its clinicopathological management should be conducted differently.
Assuntos
Antígenos CD5/metabolismo , Proteínas Cromossômicas não Histona/metabolismo , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Linfoma Folicular/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Cromossomos Humanos Par 14 , Cromossomos Humanos Par 18 , Feminino , Humanos , Linfoma Folicular/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico , Translocação GenéticaRESUMO
OBJECTIVES: Patients with rheumatoid arthritis (RA) may develop lymphoproliferative disorders (RA-LPD). Immunosuppressive states due to methotrexate (MTX) and Epstein-Barr virus (EBV) reactivation have been regarded as causes. Sometimes spontaneous regression occurs after withdrawal of MTX. The objective of this study was to identify factors predictive of relapse and survival in patients with RA-LPD, and spontaneous regression in patients with RA-LPD treated with MTX (MTX-LPD). METHODS: We evaluated the clinicopathological features, clinical characteristics, and treatment outcomes in 102 cases of RA-LPD. In addition, EBV infection and clonality of immunoglobulin heavy chain gene (IGH) were analyzed by in situ hybridization and polymerase chain reaction, respectively. RESULTS: The 102 cases included patients with diffuse large B-cell lymphoma (DLBCL; n = 53), Hodgkin lymphoma (n = 9), polymorphic B-cell LPD (n = 20), reactive lymphadenitis (n = 11), peripheral T-cell lymphoma (PTCL; n = 4), composite lymphoma (n = 2), and follicular lymphoma (n = 3). EBV was detected in 60% (56/93) of patients. Spontaneous regression occurred in 59% (28/47) of patients in whom MTX was withdrawn. Regression was associated with EBV positivity (P = 0.007) and non-DLBCL (P = 0.006), but not with MTX amount and other clinical features. Monoclonal bands of IGH were observed in 31 of 74 cases. In patients with DLBCL, poor disease-free survival (P = 0.05) was associated with clonality of IGH. In all patients, factors predictive of shorter survival were age (>70 yr) and histological type of DLBCL. CONCLUSIONS: Histology, EBV positivity, and monoclonality of IGH are useful for predicting clinical outcomes in patients with RA-LPD.
Assuntos
Artrite Reumatoide/tratamento farmacológico , Herpesvirus Humano 4/isolamento & purificação , Transtornos Linfoproliferativos/induzido quimicamente , Metotrexato/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/uso terapêutico , Artrite Reumatoide/complicações , Artrite Reumatoide/virologia , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Cadeias Pesadas de Imunoglobulinas/genética , Imuno-Histoquímica , Transtornos Linfoproliferativos/complicações , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Resultado do Tratamento , Ativação ViralRESUMO
The 8p11 myeloproliferative syndrome is a rare neoplasm associated with chromosomal translocations involving the fibroblast growth factor receptor 1 (FGFR1) gene located at chromosome 8p11-12. FGFR1 encodes a transmembrane receptor tyrosine kinase. The resultant fusion proteins are constitutively active tyrosine kinases that drive the proliferation of hematopoietic cells, whose uncontrolled growth can present as a myeloproliferative neoplasm. We report here the case of a 50-year-old man harboring the t(8;22)(p12;q11) chromosomal translocation in cells from both bone marrow and lymph nodes. He presented with acute leukemia and lymphoma with trilineage features. A novel mRNA in-frame fusion between exon 4 of the breakpoint cluster region (BCR) gene at chromosome 22q11 and exon 9 of FGFR1 gene on chromosome 8p11-12 was identified by reverse transcription polymerase chain reaction analysis and was confirmed by DNA sequencing. Because the patient was refractory to chemotherapy, cord blood transplantation was performed in progressive disease. It resulted in a successful outcome in which cytogenetic complete remission has been maintained for 2 years till date.
Assuntos
Sangue Fetal/transplante , Transtornos Mieloproliferativos/genética , Proteínas de Fusão Oncogênica/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Proteínas Proto-Oncogênicas c-bcr/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Humanos , Masculino , Pessoa de Meia-Idade , Translocação GenéticaRESUMO
Few studies have statistically investigated reduced CD20 expression in B-cell lymphoma after rituximab therapy and genomic mutation of CD20 associated with reduction. We examined CD20-positive rate in follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) by flow cytometry (FCM) and immunohistochemical staining (IHS), comparing 138 cases after rituximab therapy with 360 initial, not yet treated cases. Sequence analysis of exons 3 to 8 of CD20 was performed on 22 cases with low CD20-positive rate after rituximab treatment. The results showed a statistical correlation between CD20-positive rate in FCM and IHS. By FCM, the CD20-positive rate among post-rituximab cases was significantly lower than among initial cases in DLBCL, non-germinal center origin B-cell type (average values [avg] 57.8 and 87.9, respectively) (P < 0.0001), FL2 (avg, 93.9; 103.2) (P = 0.0083), and FL3A (avg, 90.6; 100.7) (P = 0.033). Stratified analyses of post-rituximab cases showed significantly lower CD20-positive rate in cases that were resistant at the start of the treatment and cases with progressive disease during rituximab therapy before biopsy. Sequence analysis showed silent mutation of exon 4 (632 C/T) in seven cases, although this number was not statistically significant. These results suggest the influence of B-lymphoma subtype and a therapeutic effect before biopsy on CD20 expression at relapse and contribute to a better therapeutic approach for relapse cases after rituximab therapy.
Assuntos
Anticorpos Monoclonais Murinos/uso terapêutico , Antígenos CD20/metabolismo , Antineoplásicos/uso terapêutico , Linfoma Folicular/metabolismo , Linfoma Difuso de Grandes Células B/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD20/genética , Feminino , Citometria de Fluxo , Expressão Gênica , Humanos , Imuno-Histoquímica , Linfoma Folicular/tratamento farmacológico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Rituximab , Análise de Sequência , Adulto JovemRESUMO
Spindle-shaped diffuse large B-cell lymphoma (Sp-DLBCL) has been recognized as a rare morphologic variant of DLBCL. However, the biological processes that contribute to the specific features of Sp-DLBCL remain poorly understood. In this study, a combined immunophenotypic and genetic analysis was performed in 10 Sp-DLBCL. First, we investigated several unique markers for anaplasia (CD30, ALK, CD68, and EBER-ISH), mesenchyma (SMA, desmin, and vimentin), and B-cell differentiation (CD10, BCL6, and MUM1). We also performed conventional cytogenetic and fluorescence in situ hybridization studies to look for common chromosomal break points (BCL2, BCL6, and MYC). We found that most Sp-DLBCLs were germinal center B cell-like and that none had any other specific phenotypes or any karyotypic abnormalities. Instead, T cells, CD68-positive macrophages and SMA-positive myofibroblasts were significantly increased in Sp-DLBCL when compared with conventional GCB origin DLBCL cases (n = 10) (P = 0.012, P < 0.001, and P < 0.0001, respectively). To further characterize Sp-DLBCL, we next compared the expression of fibroblast growth factor 2 (FGF2) and transforming growth factor-ß1 (TGFß1) between the two types of DLBCL. Finally, we confirmed that the number of FGF2- and TGFß1-positive stromal cells was markedly increased in Sp-DLBCL and that the difference between these and conventional GCB origin DLBCLs was significant (P < 0.0001 and P = 0.0017, respectively). Thus, T-cell/myofibrohistio-rich stromal alterations in Sp-DLBCL, especially those mediated by TGFß1 and FGF2, may play a role in the transition of lymphoma cells into those with spindle-shaped features.
Assuntos
Linfoma Difuso de Grandes Células B/patologia , Miofibroblastos/imunologia , Células Estromais/patologia , Linfócitos T/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Aberrações Cromossômicas , Sítios Frágeis do Cromossomo , Feminino , Humanos , Imunofenotipagem , Hibridização in Situ Fluorescente , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/imunologia , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Blastic plasmacytoid dendritic cell neoplasm (BPDC) is a rare hematologic neoplasm, which almost always involves the skin and shows poor prognosis. OBJECTIVE: The aim of our study was to enhance BPDC diagnosis and indications for prognosis. METHODS: This study involved 26 patients with BPDC. To investigate the histogenesis of BPDC, we reviewed the clinical features and stained markers of various hematopoietic lineages, chemokines, and their receptors. RESULTS: Bone-marrow infiltration was detected in 13 of the 19 cases examined and leukemic changes in 18. Complete remission was achieved in 14 cases, but more than half of the patients showed recurrence within a short time, and 14 patients died of the disease after 1 to 25 months (mean 8.5 months). Positivity for CD123 was detected in 18 of 24 cases and for T-cell leukemia 1 in 18 of 22 cases. Of the chemokines and their receptors, 8 of 15 skin biopsy specimens proved to be positive for CXCL12. Leukemic change subsequent to skin lesions occurred in 7 of 8 CXCL12-positive cases (87.5%) and in 3 of 6 CXCL12-negative cases (50%). Seven of the 8 CXCL12-positive patients (87.5%) and two of the 6 CXCL12-negative patients (33.3%) have died, whereas one of 8 CXCL12-positive patients (12.5%) and 4 of 6 CXCL12-negative patients (66.7%) remain alive. LIMITATIONS: The number of patients was limited. CONCLUSIONS: We speculate that the presence of CXCL12-positive cells in the skin may be associated with leukemic change and a poor prognosis.
Assuntos
Quimiocina CXCL12/análise , Células Dendríticas/patologia , Linfoma Cutâneo de Células T/patologia , Neoplasias Cutâneas/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Pré-Escolar , Células Dendríticas/imunologia , Feminino , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/patologia , Humanos , Japão/epidemiologia , Linfoma Cutâneo de Células T/mortalidade , Masculino , Pessoa de Meia-Idade , Transtornos Mieloproliferativos/mortalidade , Transtornos Mieloproliferativos/patologia , Prognóstico , Pele/patologia , Neoplasias Cutâneas/mortalidadeRESUMO
t(14;18) is a common cytogenetic abnormality in B-cell lymphoma, especially in follicular lymphoma (FL), but is rarely seen in Hodgkin's lymphoma (HL). However, due to the small number of cases, the incidence of t(14;18) in HL associated with FL remains unclear. In this study, we applied chromogenic in situ hybridization and fluorescence in situ hybridization for t(14;18) on paraffin-embedded tissue from four HL associated with FL cases and 11 HL cases without a history of FL for comparison. t(14;18) was present in all of the three successfully-tested HL associated with FL cases and one case without a history of FL. The frequency of t(14;18) was significantly high in HL associated with FL (p = 0.013). All Hodgkin's and Reed-Sternberg (HRS) cells having t(14;18) showed immunoreactivity for BCL2 and were negatively stained for nuclear factor-κB (NF-κB), even in Epstein-Barr virus (EBV)-infected cases. However, HRS cells without t(14;18) showed BCL2 and NF-κB immunoreactivity in 33% and 57% of cases, respectively. There was an inverse correlation between t(14;18) and NF-κB. In conclusion, we assume the incidence of t(14;18) in HL associated with FL is higher than previously believed and BCL2 expression derived from t(14;18) may play a role in the pathogenesis of HL associated with FL.
Assuntos
Cromossomos Humanos Par 14 , Cromossomos Humanos Par 18 , Doença de Hodgkin/genética , Linfoma Folicular/genética , Translocação Genética , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/genética , Infecções por Vírus Epstein-Barr/metabolismo , Infecções por Vírus Epstein-Barr/patologia , Herpesvirus Humano 4/isolamento & purificação , Herpesvirus Humano 4/fisiologia , Doença de Hodgkin/metabolismo , Doença de Hodgkin/patologia , Doença de Hodgkin/virologia , Humanos , Hibridização in Situ Fluorescente , Linfoma Folicular/metabolismo , Linfoma Folicular/patologia , Linfoma Folicular/virologia , Masculino , Pessoa de Meia-Idade , NF-kappa B/metabolismo , Neoplasias Primárias Múltiplas , Inclusão em Parafina , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , RNA Viral/análise , Células de Reed-Sternberg/patologiaRESUMO
Primary splenic lymphoma is rare, but malignant lymphoma often produces a lesion in the spleen as part of systemic disease. The frequency of splenic malignant lymphoma in Japan is unknown. We classified 184 specimens of the spleen according to the World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4th edition (2008). Of the 184 specimens, 115 were determined to be lymphoid neoplasm (62.5%). The most common subtype of lymphoid neoplasm was diffuse large B-cell lymphoma (DLBCL) (46 cases), followed by splenic marginal zone lymphoma (SMZL) (28 cases), follicular lymphoma (11 cases), splenic B-cell lymphoma, unclassifiable (SBL-U) (6 cases) and peripheral T-cell lymphoma, not otherwise specified (4 cases). In the SBL-U subtype, 5 of 6 cases were splenic diffuse red pulp small B-cell lymphoma, and one case was the hairy cell leukemia variant. Analysis of clinical features revealed that patients with DLBCL had a higher age, high lactate dehydrogenase and tumor formation in the spleen. On the other hand, it was found that patients with SMZL had splenomegaly but no discrete tumor formation. Most of the patients with SBL-U presented with thrombocytopenia, bone marrow involvement, and advanced stage. Our study revealed the frequency and clinical features of splenic malignant lymphoma in Japan.
Assuntos
Linfoma não Hodgkin/patologia , Neoplasias Esplênicas/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Japão/epidemiologia , Linfoma não Hodgkin/classificação , Linfoma não Hodgkin/epidemiologia , Masculino , Pessoa de Meia-Idade , Esplenectomia , Neoplasias Esplênicas/classificação , Neoplasias Esplênicas/epidemiologia , Esplenomegalia/diagnóstico , Organização Mundial da Saúde , Adulto JovemRESUMO
Human immunodeficiency virus (HIV) infects CD4(+) lymphocytes, leading to a development of malignant lymphomas, such as HIV-associated Hodgkin Lymphoma (HIV-HL). This study aimed to assess the differences in cellular composition of the inflammatory reactive background of HIV-HLs. We examined infiltrating T lymphocytes, specifically regulatory T cells, cytotoxic cells, Epstein-Barr virus (EBV) related antigens and HIV-receptor CCR5. In all HIV-HL cases, Hodgkin and Reed-Sternberg (HRS) cells showed EBER1 expression, LMP-1 staining positivity and EBNA-2 staining negativity, except for one case which showed LMP-1 staining negativity. Our histological findings indicate the percentage of CD8(+) , TIA-1(+) lymphocytes was significantly higher in HIV-HL than in non-HIV-HL cases (P < 0.05). On the other hand, the percentage of CD4(+) , FOXP3(+) lymphocytes was significantly lower in HIV-HL than in non-HIV-HL cases (P < 0.05) but present. The percentage of CCR5(+) lymphocytes was significantly lower in HIV-HL than in non-HIV-HL cases (P < 0.05). Usually, CD4(+) and CCR5(+) lymphocytes are reported to be rarely detected in HIV-associated non-Hodgkin lymphomas, but the presence of CD4(+) and/or FOXP3(+) lymphocytes may be implicated in the pathogenesis of HL. In addition, although additional CD8(+) lymphocytes are probably not EBV-LMP specific cytotoxic T-cells, these lymphocytes may also well be involved in the pathogenesis of HIV-HL.
Assuntos
Fatores de Transcrição Forkhead/metabolismo , Infecções por HIV/imunologia , HIV/imunologia , Doença de Hodgkin/imunologia , Proteínas de Ligação a Poli(A)/metabolismo , Linfócitos T Citotóxicos/metabolismo , Adulto , Infecções por HIV/complicações , Infecções por HIV/metabolismo , Doença de Hodgkin/metabolismo , Doença de Hodgkin/virologia , Humanos , Masculino , Células de Reed-Sternberg/imunologia , Células de Reed-Sternberg/metabolismo , Antígeno-1 Intracelular de Células T , Linfócitos T Citotóxicos/imunologiaRESUMO
Composite lymphomas (CLs) have been reported in 1-4.7% of all lymphomas, however, CLs containing both T- and B-cell lymphomas (CTBLs) are very rare. Here, we examined the clinical and pathological features of 29 CTBLs. These CTBLs included 21 patients with angioimmunoblastic T-cell lymphoma (AITL) and diffuse large B-cell lymphoma (DLBCL), two with adult T-cell leukemia/lymphoma and DLBCL, one with AITL and Follicular lymphoma, one with Lennert lymphoma and DLBCL, one with subcutaneous panniculitis-like T-cell lymphoma and DLBCL, one with peripheral T-cell lymphoma (PTCL) and DLBCL, one with cutaneous T-cell lymphoma and DLBCL, and one with PTCL and chronic lymphocytic leukemia. Eighteen of 27 patients (67%) were shown to be Epstein-Barr virus (EBV)-encoded RNA-positive in their B-cell lymphoma component. T-cell and B-cell clonality were confirmed by flow cytometry, Southern blot analysis, and/or polymerase chain reaction (PCR). Using Southern blot analysis, clonal immunoglobulin heavy chain (IgH) and T-cell receptor (TCR) rearrangements were detected in 11 of 21 and 15 of 24 cases, respectively. Using PCR analysis, clonal IgH and TCR rearrangements were detected in 7 of 8 and 7 of 7 Southern blot-negative cases, respectively. Our results suggested that PCR analysis was useful in diagnosing CTBL.
Assuntos
Linfoma Composto/patologia , Herpesvirus Humano 4/genética , Linfoma de Células B/patologia , Linfoma de Células T/patologia , Idoso , Idoso de 80 Anos ou mais , Southern Blotting , Linfoma Composto/genética , Feminino , Seguimentos , Rearranjo Gênico do Linfócito B , Rearranjo Gênico do Linfócito T , Humanos , Cadeias Pesadas de Imunoglobulinas/genética , Japão , Linfoma de Células B/genética , Linfoma de Células T/genética , Masculino , Pessoa de Meia-Idade , Fenótipo , Reação em Cadeia da Polimerase , Prognóstico , RNA Viral/genética , Receptores de Antígenos de Linfócitos T/genéticaRESUMO
Adult T-cell leukemia/lymphoma (ATLL) is a T-cell malignancy associated with HTLV-1. The HTLV-1 provirus genome has the pX region that encodes tax and HTLV-1 basic leucine zipper factor (HBZ). Previous studies have reported that the tax gene is expressed in few ATLL cases, but the HBZ gene in all ATLL cases. In this study, we used HBZ gene in situ hybridization (HBZ-ISH) for detection of the HBZ gene in formalin-fixed paraffin-embedded tissues. This method showed that all cases (n = 19) were positive for the ATLL cell line (MT-1, MT-2, and MT-4) and ATLL mouse model (HBZ-Tg mice and NOD/SCID/ß2-microglobulin(null) mice with ATLL transplanted), and the HBZ gene was also detected in all human ATLL cases (n = 16). The percentage of positive cells in HBZ-ISH was 5-70%. Immunohistochemical staining for Tax protein showed positivity in seven of 11 cases in NOD/SCID/ß2-microglobulin(null) mice with ATLL transplanted and in six of eight human ATLL cases, but the percentage of positive cells was very low (range, 1-5%). Although HBZ-ISH is unsuitable to detect HTLV-1 clonality, this method is convenient and can be useful for the histological diagnosis of ATLL in HTLV-1 sero-indeterminate patients.
Assuntos
Fatores de Transcrição de Zíper de Leucina Básica/genética , Vírus Linfotrópico T Tipo 1 Humano/isolamento & purificação , Hibridização In Situ/métodos , Leucemia-Linfoma de Células T do Adulto/diagnóstico , Proteínas Virais/genética , Animais , Formaldeído , Produtos do Gene tax/análise , Humanos , Imuno-Histoquímica , Leucemia-Linfoma de Células T do Adulto/virologia , Camundongos , Camundongos SCID , Parafina , Proteínas dos Retroviridae , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Microglobulina beta-2/fisiologiaRESUMO
Mantle cell lymphoma (MCL) is recognized as a well-defined B cell neoplasm characterized by overexpression of cyclin D1 (CCND1), with "classical" and "aggressive" variant subtypes. A small-cell variant of MCL (small-MCL), resembling small lymphocytic lymphoma/chronic lymphocytic lymphoma (CLL/SLL), has been added to the World Health Organization classification. However, to the best of our knowledge, there have been no studies focusing on this neoplasm. In the present study, we analyzed 15 cases of CCND1-positive small-MCL, including immunohistochemical analysis of Ki-67 and CCND1 expression, and compared our findings with those of 151 cases of classical MCL. Morphologically, most small-MCL showed a diffuse growth pattern (76.9%), whereas others featured a very thin mantle zone pattern resembling a reactive follicle (23.1%). Bone marrow involvement and splenomegaly occurred significantly more frequently in small-MCL than in classical MCL (P < 0.05). Ki-67 expression in small-MCL was lower than in classical MCL (mean [± 2 SD] 12.5 ± 17.3% and 25.2 ± 25.5%, respectively; P < 0.001), but there was no significant difference in CCND1 expression (P = 0.2445). The 5-year survival rate in small-MCL was 83.3%. Although there was no significant difference in outcome between small-MCL and classical MCL (P = 0.287), only one small-MCL patient died of the disease. Thus, small-MCL constitutes a specific subset of indolent lymphoma with distinguishing features, possibly making a major contribution to the accuracy of therapeutic decisions. In addition, clinicians should be aware of the possible presence of small-MCL to avoid making a misdiagnosis of follicular hyperplasia or CLL/SLL.
Assuntos
Leucemia Linfocítica Crônica de Células B/diagnóstico , Linfoma de Célula do Manto/diagnóstico , Idoso , Neoplasias da Medula Óssea/secundário , Ciclina D1/análise , Feminino , Humanos , Antígeno Ki-67/análise , Leucemia Linfocítica Crônica de Células B/patologia , Linfoma de Célula do Manto/metabolismo , Linfoma de Célula do Manto/patologia , Masculino , Pessoa de Meia-Idade , EsplenomegaliaRESUMO
This report concerns a unique case of a composite lymphoma composed of T-lymphoblastic leukemia/lymphoma (T-LBL) and diffuse large B-cell lymphoma (DLBCL) in a 72-year-old woman with generalized lymphadenopathy, splenomegaly and ascites. Laboratory findings showed increased lactate dehydrogenase and soluble interleukin-2 receptor. The biopsy specimen showed replacement of the normal architecture of the lymph nodes by a tumor containing a dual cell population composed of large lymphocytes and medium-sized lymphocytes. Sheets of large lymphocytes often were punctuated by clusters of medium-sized lymphocytes. Flow cytometry and immunohistochemical analysis showed a composite lymphoma with both T-LBL and DLBCL. The T-LBL expressed CD1a, CD3, CD4, CD8, and terminal deoxynucleotidyl transferase. The DLBCL expressed CD19 and CD20, CD23, bcl-2, bcl-6, MUM1 and immunoglobulin κ light chain. Polymerase chain reaction detected a monoclonal pattern of T-cell receptor γ and immunoglobulin heavy chain rearrangements in the same specimen. She received eight cycles of R-CHOP (rituximab+cyclophosphamide, doxorubicin, vincristine, prednisone) therapy and achieved complete remission. She has shown no signs of recurrence 20 months after the diagnosis. We describe here a very unusual and, to the best of our knowledge, an as yet never reported case of a primary composite lymphoma of T-LBL and DLBCL.
Assuntos
Anticorpos Monoclonais Murinos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Composto/patologia , Linfoma Difuso de Grandes Células B/patologia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , Idoso , Antígenos CD/metabolismo , Linfoma Composto/sangue , Linfoma Composto/tratamento farmacológico , Ciclofosfamida/uso terapêutico , DNA Nucleotidilexotransferase/metabolismo , DNA de Neoplasias/genética , Doxorrubicina/uso terapêutico , Feminino , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Hibridização In Situ , L-Lactato Desidrogenase/metabolismo , Linfoma Difuso de Grandes Células B/sangue , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/sangue , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico , Prednisona/uso terapêutico , Receptores de Interleucina-2/metabolismo , Rituximab , Resultado do Tratamento , Vincristina/uso terapêuticoRESUMO
Polycythemia vera (PV) is a clonal myeloproliferative neoplasm (MPN) of hematopoietic stem cells. Although the management of MPN patients generally focuses on the prevention of thromboembolic events caused by hypercoagulability, it is true that the patients with hematological malignancy often suffer from pulmonary diseases with atypical radiological patterns. We present here a 56-year-old woman with PV harboring a JAK2(V617F) mutation that had a diffuse reticulonodular pattern on chest radiography and was initially suspected of having military tuberculosis. Pathological assessment of a video-assisted thoracoscopic surgery lung biopsy revealed that the lesions were in fact organizing pneumonia (OP). Interestingly, pulmonary extramedullary hematopoiesis with a diffuse plugging of the alveolar blood capillaries by numerous atypical megakaryocytes was also observed around the granulation components. The histological findings of our case of unusual OP suggest that local activated neoplastic megakaryocytes and platelets played an important role in the development of spreading fibrotic lesions. JAK2 mutation or the preleukemic phase of MPN may accelerate the activation of megakaryocytes and result in the proliferative process of fibrosis.
Assuntos
Megacariócitos/patologia , Pneumonia/diagnóstico , Policitemia Vera/diagnóstico , Tuberculose Miliar/diagnóstico , Diagnóstico Diferencial , Evolução Fatal , Feminino , Hematopoese Extramedular/genética , Humanos , Janus Quinase 2/genética , Janus Quinase 2/metabolismo , Pessoa de Meia-Idade , Mutação , Pneumonia/complicações , Policitemia Vera/complicações , Policitemia Vera/genética , Radiografia TorácicaRESUMO
BACKGROUND: Granulocyte-colony stimulating factor (G-CSF)-producing tumors can cause leukocytosis despite an absence of infection. G-CSF-producing tumors have been reported in various organs such as the lung, esophagus, and stomach but rarely in the breast. We report a case of G-CSF-producing malignant phyllodes tumor of the breast. CASE PRESENTATION: An 84-year-old woman visited our hospital complaining of a lump in her left breast without fever and pain. Laboratory tests revealed elevated white blood cell (WBC) count and G-CSF levels. A malignant tumor of the breast was diagnosed by core needle biopsy. We performed a total mastectomy and sentinel lymph node biopsy. The tumor was identified as a G-CSF-producing malignant phyllodes tumor. Within 7 days after surgery, the patient's WBC count and G-CSF level had decreased to normal levels. She is alive without recurrence 13 months after surgery. CONCLUSIONS: We encountered a rare case of G-CSF-producing malignant phyllodes tumor of the breast. PET-CT revealed diffuse accumulation of FDG in the bone. Phyllodes tumors need to be differentiated from bone metastasis, lymphoma, and leukemia. We must be careful to not mistake this type of tumor for bone marrow metastasis.