RESUMO
The prognosis of aggressive adult T-cell leukemia/lymphoma (ATL) is poor, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative treatment. In order to identify favorable prognostic patients after intensive chemotherapy, and who therefore might not require upfront allo-HSCT, we aimed to improve risk stratification of aggressive ATL patients aged <70 years. The clinical risk factors and genetic mutations were incorporated into risk modeling for overall survival (OS). We generated the m7-ATLPI, a clinicogenetic risk model for OS, that included the ATL prognostic index (PI) (ATL-PI) risk category, and non-silent mutations in seven genes, namely TP53, IRF4, RHOA, PRKCB, CARD11, CCR7, and GATA3. In the training cohort of 99 patients, the m7-ATLPI identified a low-, intermediate-, and highrisk group with 2-year OS of 100%, 43%, and 19%, respectively (hazard ratio [HR] =5.46; P<0.0001). The m7-ATLPI achieved superior risk stratification compared to the current ATL-PI (C-index 0.92 vs. 0.85, respectively). In the validation cohort of 84 patients, the m7-ATLPI defined low-, intermediate-, and high-risk groups with a 2-year OS of 81%, 30%, and 0%, respectively (HR=2.33; P=0.0094), and the model again outperformed the ATL-PI (C-index 0.72 vs. 0.70, respectively). The simplified m7-ATLPI, which is easier to use in clinical practice, achieved superior risk stratification compared to the ATLPI, as did the original m7-ATLPI; the simplified version was calculated by summing the following: high-risk ATL-PI category (+10), low-risk ATL-PI category (-4), and non-silent mutations in TP53 (+4), IRF4 (+3), RHOA (+1), PRKCB (+1), CARD11 (+0.5), CCR7 (-2), and GATA3 (-3).
Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma de Células T do Adulto , Linfoma , Adulto , Humanos , Leucemia-Linfoma de Células T do Adulto/genética , Leucemia-Linfoma de Células T do Adulto/terapia , Prognóstico , Receptores CCR7 , Estudos RetrospectivosRESUMO
Adult T-cell leukemia/lymphoma (ATL) patients have a very poor prognosis. The humanized anti-CCR4 therapeutic monoclonal antibody, mogamulizumab, is a key agent for ATL treatment. Our previous integrated molecular analysis demonstrated that among all the driver genes in ATL, CCR7 gene alterations were significantly associated with clinical response to mogamulizumab. Accordingly, here we investigated the detailed clinical impact of CCR7 alterations in a larger cohort of ATL patients. These CCR7 alterations, most of which lead to C-terminus truncations, were observed in 27 of 223 patients (12%). For patients receiving mogamulizumab but not allogeneic hematopoietic stem cell transplantation (HSCT), CCR7 alterations were significantly associated with worse survival (median survival from the first dose of mogamulizumab of 0.7 years for 12 patients with CCR7 alterations vs. 1.6 years for 72 patients without, p = 0.020). On the other hand, the presence or absence of CCR7 alterations had no significant impact on survival in the entire cohort (median overall survival of 1.4 and 1.8 years, respectively, p = 0.901), or on the survival of patients receiving allogeneic HSCT (median survival from the day of transplantation of 0.9 years for 6 patients with CCR7 alterations and 1.4 years for 48 without, p = 0.543). Multivariate analysis indicated that patients with CCR4 alterations but lacking CCR7 alterations (n = 20) had significantly better survival after receiving mogamulizumab-containing treatments (hazard ratio for survival, 0.437, 95% confidence interval, 0.192-0.994). This study contributes to the establishment of precision medicine for ATL.
Assuntos
Anticorpos Monoclonais Humanizados , Leucemia-Linfoma de Células T do Adulto , Receptores CCR7 , Humanos , Leucemia-Linfoma de Células T do Adulto/tratamento farmacológico , Leucemia-Linfoma de Células T do Adulto/genética , Receptores CCR7/genética , Anticorpos Monoclonais Humanizados/uso terapêuticoRESUMO
CD28, one of the costimulatory molecules, has a pivotal role in T-cell activation, and its expression is strictly regulated in normal T cells. Gain-of-function genetic alterations involving CD28 have been frequently observed in adult T-cell leukemia/lymphoma (ATLL). These abnormalities, such as CD28 fusions and copy number variations, may not only confer continuous, prolonged, and enhanced CD28 signaling to downstream pathways but also induce overexpression of the CD28 protein. In this study, 120 ATLL cases were examined by immunohistochemistry for CD28 and its ligands CD80 and CD86, and their expression on tumor cells was semiquantitatively evaluated. CD28 was overexpressed in 55 (46%) cases, and CD80 or CD86 (CD80/CD86) was infrequently overexpressed in 12 (11%). Compared with non-overexpressers, CD28 overexpressers showed a higher frequency of CD28 genetic alterations and had an increased number of CD80/CD86-positive non-neoplastic cells infiltrating tumor microenvironment. In the entire ATLL patient cohort, CD28 overexpressers showed a significantly poorer overall survival (OS) compared with non-overexpressers (P = .001). The same was true for a subgroup who were treated with multidrug regimens with or without mogamulizumab. CD28 overexpression had no prognostic impact in the group who received allogeneic hematopoietic stem cell transplantation. In the multivariate analysis for OS, CD28 overexpression was selected as an independent risk factor. These results suggest ATLL patients with CD28 overexpression have more aggressive clinical course and are more refractory to treatment with multidrug chemotherapy. CD28 overexpression appears to be a novel unfavorable prognostic marker in ATLL patients, and further prospective studies are warranted to establish its prognostic significance.
Assuntos
Antígeno B7-1/metabolismo , Antígeno B7-2/metabolismo , Antígenos CD28/genética , Antígenos CD28/metabolismo , Leucemia-Linfoma de Células T do Adulto/mortalidade , Regulação para Cima , Adulto , Idoso , Idoso de 80 Anos ou mais , Variações do Número de Cópias de DNA , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Leucemia-Linfoma de Células T do Adulto/genética , Leucemia-Linfoma de Células T do Adulto/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise de Sobrevida , Microambiente TumoralRESUMO
Adult T-cell leukaemia/lymphoma (ATL) patients have a poor prognosis. Here, we investigated the impact of TP53 gene mutations on prognosis of ATL treated in different ways. Among 177 patients, we identified 47 single nucleotide variants or insertion-deletions (SNVs/indels) of the TP53 gene in 37 individuals. TP53 copy number variations (CNVs) were observed in 38 patients. Altogether, 67 of 177 patients harboured TP53 SNVs/indels or TP53 CNVs, and were categorized as having TP53 mutations. In the entire cohort, median survival of patients with and without TP53 mutations was 1·0 and 6·7 years respectively (P < 0·001). After allogeneic haematopoietic stem cell transplantation (HSCT), median survival of patients with (n = 16) and without (n = 29) TP53 mutations was 0·4 years and not reached respectively (P = 0·001). For patients receiving mogamulizumab without allogeneic HSCT, the median survival from the first dose of antibody in patients with TP53 mutations (n = 27) was only 0·9 years, but 5·1 years in those without (n = 42; P < 0·001). Thus, TP53 mutations are associated with unfavourable prognosis of ATL, regardless of treatment strategy. The establishment of alternative modalities to overcome the adverse impact of TP53 mutations in patients with ATL is required.
Assuntos
Genes p53 , Leucemia-Linfoma de Células T do Adulto/genética , Mutação , Adulto , Idoso , Idoso de 80 Anos ou mais , Aloenxertos , Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antígenos CD28/genética , Carboplatina/administração & dosagem , Ciclofosfamida/administração & dosagem , Variações do Número de Cópias de DNA , Doxorrubicina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Mutação INDEL , Estimativa de Kaplan-Meier , Lenalidomida/administração & dosagem , Leucemia-Linfoma de Células T do Adulto/tratamento farmacológico , Leucemia-Linfoma de Células T do Adulto/mortalidade , Leucemia-Linfoma de Células T do Adulto/terapia , Masculino , Pessoa de Meia-Idade , Compostos de Nitrosoureia/administração & dosagem , Polimorfismo de Nucleotídeo Único , Prednisolona/administração & dosagem , Prednisona/administração & dosagem , Prognóstico , Receptores CCR4/genética , Vincristina/administração & dosagem , Vindesina/administração & dosagemRESUMO
Multiple oncogenic events are involved in the development of adult T-cell leukaemia/lymphoma (ATL). Because CD28 plays a pivotal role in T-cell activation, we focused on alterations of the CD28 gene in ATL. We found multiple genetic abnormalities related to CD28 among the 144 patients enrolled in the present study. These involved gene fusions with the cytotoxic T-lymphocyte-associated antigen 4 or the inducible T-cell co-stimulator in 14 patients (10%), CD28-activating mutations in 3 (2%), and CD28 copy number variations in 34 (24%). Patients with such CD28 gene alterations were significantly younger than those without. In patients not receiving allogeneic haematopoietic stem cell transplantation, those with CD28 gene alterations tended to have a worse prognosis than those without. Finally, patients with chronic or smouldering ATL subtypes with CD28 gene alterations had a significantly worse prognosis than those without. These findings indicate that ATL, especially chronic or smouldering subtypes, have a more aggressive clinical course and are more refractory to conventional chemotherapies or mogamulizumab if they harbour CD28 gene alterations, likely because of continuous, prolonged, and enhanced CD28 activatory signalling. Novel treatment strategies to overcome the effects of these CD28 gene alterations are warranted.
Assuntos
Antígenos CD28/genética , Leucemia-Linfoma de Células T do Adulto/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Variações do Número de Cópias de DNA , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Leucemia-Linfoma de Células T do Adulto/diagnóstico , Leucemia-Linfoma de Células T do Adulto/terapia , Masculino , Pessoa de Meia-Idade , Mutação , Fusão Oncogênica , PrognósticoRESUMO
Mogamulizumab targets extracellular N-terminal domain of CCR4, which is expressed in most adult T-cell leukemia/lymphoma (ATL) cases. Recently, we reported that CCR4 C-terminal gain-of-function mutations were frequent in ATL cases, and a subgroup with these mutations who were treated without allogenic hematopoietic stem cell transplantation (HSCT) and with mogamulizumab-containing [HSCT (-) and mogamulizumab (+)] regimens had a superior survival rate. Although these mutations are most likely a biomarker for predicting a strong response to mogamulizumab, their detection is time-consuming and costly. A more convenient screening tool may be necessary in the clinical setting. In this study, the clinicopathological importance of immunohistochemistry for the CCR4 N-terminus (CCR4-N-IHC) and C-terminus (CCR4-C-IHC) was examined in a large ATL cohort (n = 92). We found that CCR4-C-IHC, but not CCR4-N-IHC, was inversely correlated with the CCR4 mutation status. In ATL patients negative for CCR4-C-IHC, a subgroup treated with HSCT (-) and mogamulizumab (+) regimens showed a significantly better prognosis. In addition, CCR4-C-IHC was found to be a useful marker for high-sensitivity screening of the CCR4 mutational status (87%). The present study suggests that CCR4-C-IHC may be useful for identifying ATL patients harboring mutated CCR4 who may benefit from the superior efficacy of mogamulizumab-containing regimens and that CCR4-C-IHC may be a rapid and cost-efficient tool for screening for CCR4 mutation status.
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Biomarcadores Tumorais/genética , Imuno-Histoquímica , Leucemia-Linfoma de Células T do Adulto/tratamento farmacológico , Leucemia-Linfoma de Células T do Adulto/genética , Mutação , Receptores CCR4/genética , Idoso , Tomada de Decisão Clínica , Análise Mutacional de DNA , Feminino , Humanos , Leucemia-Linfoma de Células T do Adulto/imunologia , Masculino , Seleção de Pacientes , Valor Preditivo dos Testes , Domínios Proteicos , Receptores CCR4/antagonistas & inibidores , Resultado do TratamentoRESUMO
We report an AIDS patient with a high HIV RNA copy number in the plasma who was successfully treated for prolonged Mycobacterium avium bacteremia and other complications. An HIV-infected patient with high fever, anemia, high alkaline phosphatase, cystic lung lesions, hepatitis B virus infection and Kaposi's sarcoma was referred to our hospital. PCR of the blood revealed Mycobacterium avium bacteremia and the time to blood culture positivity was 8 days. The HIV-1 RNA copy number in the plasma was more than ten million copies/ml and the CD4-positive T cell count was 21 cells/µL. Although the high fever resolved five days after therapy for Mycobacterium avium was started, the fever recurred just before starting anti-retroviral therapy (ART) including dolutegravir. The patient experienced repeated but self-limiting bouts of severe inflammation. Mycobacteremia was intermittently detected up to 79 days, suggesting that the recurrent episodes of inflammation were due to the intermittent dissemination of mycobacteria, and that persistent treatment is needed. Five months after the beginning of ART, the HIV-1 RNA copy number in the plasma was still 28,000 copies/ml. An HIV drug-resistance test revealed sensitivity to all anti-retroviral drugs. Eleven months after the initiation of ART, the HIV RNA copy number in the plasma decreased to 45 copies/mL and the CD4-positive T cell count recovered to 205 cells/µL. Our case also suggests that dolutegravir can be effective in cases with prolonged high levels of HIV RNA. Our findings emphasize that prompt diagnosis and persistent therapy for mycobacterial infection are important for successful treatment.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Bacteriemia/tratamento farmacológico , Infecção por Mycobacterium avium-intracellulare/tratamento farmacológico , RNA Viral/sangue , Infecções Oportunistas Relacionadas com a AIDS/complicações , Infecções Oportunistas Relacionadas com a AIDS/imunologia , Síndrome da Imunodeficiência Adquirida/complicações , Síndrome da Imunodeficiência Adquirida/imunologia , Adulto , Antibacterianos/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Bacteriemia/complicações , Contagem de Linfócito CD4 , Retinite por Citomegalovirus/complicações , Retinite por Citomegalovirus/tratamento farmacológico , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Inibidores de Integrase de HIV/uso terapêutico , Hepatite B/complicações , Hepatite B/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Humanos , Inflamação/complicações , Masculino , Mycobacterium avium/isolamento & purificação , Infecção por Mycobacterium avium-intracellulare/complicações , Oxazinas , Piperazinas , Piridonas , Sarcoma de Kaposi/complicações , Sarcoma de Kaposi/tratamento farmacológico , Resultado do TratamentoAssuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Leucemia-Linfoma de Células T do Adulto , Mutação , Receptores CCR4/genética , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Leucemia-Linfoma de Células T do Adulto/tratamento farmacológico , Leucemia-Linfoma de Células T do Adulto/genética , Leucemia-Linfoma de Células T do Adulto/mortalidade , Masculino , Pessoa de Meia-Idade , Taxa de SobrevidaRESUMO
Primary cutaneous γδ T-cell lymphoma (PCGD-TCL) is an aggressive lymphoma consisting of clonal proliferation of mature activated γδ T-cells of a cytotoxic phenotype. Because primary cutaneous γδ T-cell lymphoma is a rare disease, there are few clinicopathological studies. In addition, T-cell receptor (TCR) γδ cells are typically immunostained in frozen sections or determined by TCRß negativity. We retrospectively analyzed 17 primary cutaneous T-cell lymphomas of the γδ phenotype (CTCL-γδ) in a clinicopathological and molecular study using paraffin-embedded sections. Among 17 patients, 11 had CTCL-γδ without subcutaneous panniculitis-like T-cell lymphoma (SPTCL) features and six had CTCL-γδ with SPTCL features. Immunophenotypically, some significant differences were found in CD8 and CD56 positivity between our patient series of CTCL-γδ patients with SPTCL features and SPTCL-γδ patients described in the previous literature. A univariate analysis of 17 CTCL-γδ patients showed that being more than 60 years old, presence of visceral organ involvement, and small-to-medium cell size were poor prognostic factors. In addition, the 5-year overall survival rate was 42.4% for the CTCL-γδ patients without SPTCL features and 80.0% for those with SPTCL features. Consequently, there was a strikingly significant difference in overall survival among SPTCL, CTCL-γδ with SPTCL features and CTCL-γδ without SPTCL features (P = 0.0005). Our data suggests that an indolent subgroup may exist in CTCL-γδ. Studies on more cases, including those from other countries, are warranted to delineate the clinicopathological features and the significance in these rare lymphomas.
Assuntos
Linfoma Cutâneo de Células T/mortalidade , Linfoma Cutâneo de Células T/patologia , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Adulto , Idoso , Feminino , Humanos , Imuno-Histoquímica , Imunofenotipagem , Japão , Linfoma Cutâneo de Células T/metabolismo , Masculino , Pessoa de Meia-Idade , Inclusão em Parafina , Prognóstico , Receptores de Antígenos de Linfócitos T/genética , Estudos Retrospectivos , Neoplasias Cutâneas/metabolismoRESUMO
BACKGROUND: Mucins are implicated in survival in various cancers, but there have been no report addressed on survival in appendiceal carcinoma, an uncommon disease with different clinical and pathological features from those of other colon cancers. We aimed to investigate the clinical implications of expression of mucins in appendiceal carcinoma. METHODS: Expression profiles of MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC6, MUC16 and MUC17 in cancer tissue were examined by immunohistochemistry in 108 cases of surgically resected appendiceal carcinoma. RESULTS: The following relationships of mucins with clinicopathologic factors were identified: MUC1 with positive lymphatic invasion (p = 0.036); MUC2 with histological type (mucinous carcinoma, p<0.001), superficial invasion depth (p = 0.007), negative venous invasion (p = 0.003), and curative resection (p = 0.019); MUC3 with non-curative resection (p = 0.017); MUC5AC with histological type (mucinous carcinoma, p = 0.002), negative lymphatic invasion (p = 0.021), and negative venous invasion (p = 0.022); and MUC16 with positive lymph node metastasis (p = 0.035), positive venous invasion (p<0.05), and non-curative resection (p = 0.035). A poor prognosis was related to positive lymph node metastasis (p = 0.04), positive lymphatic invasion (p = 0.02), positive venous invasion (p<0.001), non-curative resection (p<0.001), and positive expression of MUC3 (p = 0.004). In multivariate analysis, positive venous invasion (HR: 6.93, 95% CI: 1.93-24.96, p = 0.003), non-curative resection (HR: 10.19, 95% CI: 3.05-34.07, p<0.001) and positive MUC3 expression (HR: 3.37, 95% CI: 1.13-10.03, p = 0.03) were identified as significant independent prognostic factors in patients with appendiceal carcinoma. CONCLUSIONS: Expression of MUC3 in appendiceal carcinoma is an independent factor for poor prognosis and a useful predictor of outcome in patients with appendiceal carcinoma after surgery.
Assuntos
Neoplasias do Apêndice/diagnóstico , Neoplasias do Apêndice/metabolismo , Perfilação da Expressão Gênica , Mucinas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Apêndice/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Análise de Sobrevida , Adulto JovemRESUMO
BACKGROUND: Castleman's disease is a rare disease characterized by lymph node hyperplasia. Its occurrence in the retroperitoneal space has rarely been reported, making its preoperative diagnosis difficult. Here, we report a case of retroperitoneal Castleman's disease, which radiologically resembled paraspinal schwannoma. CASE PRESENTATION: A 33-year-old Japanese man with epigastric discomfort underwent abdominal ultrasonic examination revealing a solid mass next to the right kidney. Computed tomography demonstrated a well-circumscribed mass with central calcification in the right psoas muscle. Because the mass presented a dumbbell-like shape extending to the intervertebral foramen, neurogenic tumor was suspected. Both iodine-123 metaiodobenzylguanidine and gallium-67 scintigraphies were negative in the mass, whereas thallium-201 mildly accumulated in the tumor, suggesting blood flow to the tumor. Positron emission tomography revealed accumulation of fluorine-18-2-fluoro-2-deoxy-d-glucose in the tumor at a standard uptake value of 4.7, whereas no other abnormal uptake suggestive of metastatic lesion was noted. On the basis of imaging studies, we mostly suspected paraspinal schwannoma, although malignancy was not completely excluded. Angiography showed feeding vessels from the right lumbar arteries, which were embolized with porous gelatin particles in order to reduce intraoperative bleeding. Surgical resection was performed using a retroperitoneal approach, which revealed the tumor in the swollen psoas muscle. Intraoperative pathological examination of a frozen section revealed no evidence of malignancy; thus, marginal excision of the tumor was performed. The tumor adhered tightly to surrounding muscle tissues, resulting in 940 g of intraoperative blood loss. The pathological examination demonstrated infiltration of lymphocytes surrounding small germinal centers with extensive capillary proliferation. Immunostaining revealed that proliferated lymphocytes were CD3-negative and CD79a-positive. CONCLUSIONS: Although a dumbbell-shaped mass in a paraspinal region is indicative of a schwannoma for orthopedic surgeons, the possibility of Castleman's disease should be considered if a central low-signal area in fissured and a radial pattern is detected on computed tomography or magnetic resonance imaging. Appropriate preparation for massive bleeding during the treatment of Castleman's disease, including angiography and embolization, would be helpful for performing surgical procedures safely.
Assuntos
Hiperplasia do Linfonodo Gigante/diagnóstico , Neurilemoma/diagnóstico , Espaço Retroperitoneal/patologia , Neoplasias da Coluna Vertebral/diagnóstico , Adulto , Angiografia , Hiperplasia do Linfonodo Gigante/cirurgia , Diagnóstico Diferencial , Fluordesoxiglucose F18 , Humanos , Masculino , Neurilemoma/cirurgia , Tomografia por Emissão de Pósitrons , Prognóstico , Compostos Radiofarmacêuticos , Espaço Retroperitoneal/cirurgia , Neoplasias da Coluna Vertebral/cirurgia , Tomografia Computadorizada por Raios XRESUMO
Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) consists of a heterogeneous group of lymphomas. Patients generally show an aggressive clinical course and very poor outcome. Although the 2008 World Health Organization classification of PTCL-NOS includes 3 variants, low-grade lymphoma is not included. Of 277 PTCL-NOS cases recorded in our consultation files, we examined the clinicopathologic characteristics of 10 patients with T-cell lymphomas composed of small-sized cells with slight nuclear atypia. Eight patients showed extranodal involvement (5 patients, spleen; 3 patients, thyroid), and 5 patients were at clinical stage I or II. Histologically, all samples presented diffuse infiltrate of small lymphoid cells, with few mitotic figures. Immunohistologically, all samples were positive for CD3, and CD20 was detected in 5 samples. All samples showed a low Ki-67 labeling index (mean, 1.05%), and 7 samples were positive for central memory T-cell markers. Clonal T-cell receptor γ chain and/or α-ß chain gene rearrangements were detected in all 10 patients. Five patients received chemotherapy, whereas for 3 patients, treatment consisted only of observation following surgical resection of the spleen or thyroid. Nine patients were alive at a median follow-up time of 19.5 months, whereas 1 patient died of an unrelated disease. The present study strongly indicates that T-cell lymphoma with small-sized lymphoma cells and a low Ki-67 labeling index is a distinct variant. Recognition of this novel lymphoma subtype, which should not be defined merely as PTCL-NOS, should be seriously considered.
Assuntos
Linfoma de Células T Periférico/patologia , Neoplasias Esplênicas/patologia , Neoplasias da Glândula Tireoide/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Núcleo Celular/patologia , Proliferação de Células , Quimioterapia Adjuvante , Células Clonais , Feminino , Rearranjo Gênico da Cadeia alfa dos Receptores de Antígenos dos Linfócitos T/genética , Rearranjo Gênico da Cadeia beta dos Receptores de Antígenos dos Linfócitos T/genética , Rearranjo Gênico da Cadeia gama dos Receptores de Antígenos dos Linfócitos T/genética , Humanos , Antígeno Ki-67/metabolismo , Linfoma de Células T Periférico/genética , Linfoma de Células T Periférico/metabolismo , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Esplênicas/genética , Neoplasias Esplênicas/metabolismo , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/metabolismoRESUMO
The authors present the case of a 65-year-old woman who initially was diagnosed as having intracranial dural B-cell malignant lymphoma. She survived more than 9 years after surgery and radiation. We re-examined the specimens pathologically. Histological findings confirmed an extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) that showed numerous IgG4-positive plasma cells. MALT lymphomas are already recognized as a distinct clinico-pathological entity. A primary dural MALT lymphoma is very rare and has a favorable clinical outcome, and patients are expected to have an excellent long-term survival with local therapy alone.
Assuntos
Neoplasias Encefálicas/patologia , Dura-Máter/patologia , Linfoma de Zona Marginal Tipo Células B/patologia , Idoso , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/cirurgia , Feminino , Seguimentos , Humanos , Linfoma de Zona Marginal Tipo Células B/diagnóstico , Linfoma de Zona Marginal Tipo Células B/radioterapia , Linfoma de Zona Marginal Tipo Células B/cirurgia , Imageamento por Ressonância Magnética , Resultado do TratamentoRESUMO
Cavernous angiomas or hemangiomas and malignant lymphomas rarely involve the cavernous sinus. We report the case of a 72-year-old man with right circumorbital pain and right oculomotor nerve dysfunction because of a mass in the right cavernous sinus. It was removed via a transsphenoidal approach and histological examination revealed the mass was a cavernous hemangioma containing atypical large B cells in some sinusoidal vessels; no other evidence of lymphoma was detected on (18)F-2-fluoro-2-deoxy-D-glucose positron-emission tomography or bone marrow biopsy. The patient underwent gamma knife radiosurgery (GKS) of the right cavernous sinus, but no systemic chemotherapy was administered. Although good local control was achieved, the patient developed a systemic diffuse large B-cell lymphoma (DLBCL) 1.5 years after the GKS. The atypical lymphocytes of the cavernous hemangioma and biopsied lymph nodes expressed multiple myeloma oncogene-1 protein. This is a rare case of DLBCL occurring within a cavernous sinus that was diagnosed as hemangioma of the cavernous sinus by neuroimaging, surgical findings, and rapid-freezing histological diagnosis. The case indicates a importance of surgical sampling and detailed histopathological analysis.
Assuntos
Neoplasias Encefálicas/patologia , Seio Cavernoso/patologia , Hemangioma Cavernoso do Sistema Nervoso Central/patologia , Linfoma Difuso de Grandes Células B/patologia , Neoplasias Primárias Múltiplas/patologia , Idoso , Neoplasias Encefálicas/cirurgia , Seio Cavernoso/cirurgia , Hemangioma Cavernoso do Sistema Nervoso Central/cirurgia , Humanos , Linfoma Difuso de Grandes Células B/cirurgia , Masculino , Neoplasias Primárias Múltiplas/cirurgia , Resultado do TratamentoRESUMO
A 49-year-old woman presented with severe swelling and pain of the left little finger, which had exacerbated rapidly, in October 2006. The patient had a history of hepatocellular carcinoma and metastatic lung cancer. She had undergone partial hepatectomy for the hepatocellular carcinoma in September 2001 and pulmonary resection for metastatic lung cancer in November 2005. Roentgenogram of the hand on admission showed complete destruction of the distal phalanx of the left little finger. The final pathological result of the tissue obtained by disarticulation was an extrahepatic metastasis of hepatocellular carcinoma. Extrahepatic metastasis from primary hepatocellular carcinoma to the hand is very rare and only four cases have been reported in the literature. All the patients with extrahepatic metastases from the primary hepatocellular carcinoma to the hand had poor prognoses, but the patient presented in this article exhibited an unusual clinical course. The patient is still alive 1 year after the diagnosis of extrahepatic bone metastasis of the distal phalanx.
Assuntos
Neoplasias Ósseas/secundário , Carcinoma Hepatocelular/patologia , Falanges dos Dedos da Mão , Neoplasias Hepáticas/patologia , Neoplasias Ósseas/diagnóstico , Carcinoma Hepatocelular/mortalidade , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Pulmonares/secundário , Pessoa de Meia-Idade , Taxa de SobrevidaRESUMO
Recent reports have discussed the presence of cytotoxic T cells in paraneoplastic cerebellar degeneration (PCD). We report an autopsy case of PCD associated with anti-Hu antibody, in which we revealed infiltration of CD8+ T cells in and around the dentate nucleus but not in the cerebellar cortex, in addition to severe Purkinje cell loss. Some infiltrated mononuclear cells expressed cytotoxic cell marker, Granzyme B. Decrease of neurons and reduced presynapses were demonstrated in the dentate nucleus. This is the first report that suggests the possibility of the dentate nucleus being primarily attacked followed by Purkinje cell loss in PCD.
Assuntos
Linfócitos T CD8-Positivos/patologia , Movimento Celular/imunologia , Núcleos Cerebelares/imunologia , Núcleos Cerebelares/patologia , Degeneração Paraneoplásica Cerebelar/imunologia , Degeneração Paraneoplásica Cerebelar/patologia , Idoso , Córtex Cerebelar/química , Córtex Cerebelar/imunologia , Córtex Cerebelar/patologia , Núcleos Cerebelares/química , Humanos , MasculinoRESUMO
OBJECTIVE: The objective of our study was to clarify which clinicopathologic factors affect the FDG PET visibility of colorectal polyps. MATERIALS AND METHODS: We used statistical methods in a retrospective examination of factors affecting the visibility of 87 colorectal polyps in 50 patients who underwent PET for cancer screening. RESULTS: PET depicted 37% (32/87) of polyps. Univariate analysis revealed significant associations between polyp visibility and polyp size, histologic grade (p < 0.001 each), type (p = 0.004), and patient age (p = 0.049) but not sex or polyp location. The visualization rate increased with increases in polyp size (< or = 5 mm, 12%; 6-10 mm, 47%; > or = 11 mm, 59%) and severity of dysplasia (indefinite or low-grade dysplasia, 13%; high-grade dysplasia, 67%; polyp with early carcinoma, 75%) and was higher for pedunculated polyps (59%) than for nonpedunculated polyps (27%). Multivariate analysis showed that histologic grade was the strongest factor (p < 0.001) among three independent factors (histologic grade, type, and age). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for visualization of high-grade or early carcinoma polyps to be removed were 71%, 87%, 78%, 82%, and 80%. Maximum standardized uptake values did not differ significantly between visualized polyps with indefinite or low-grade dysplasia and visualized polyps with high-grade dysplasia or early carcinoma. CONCLUSION: Histologic grade is the strongest independent factor in FDG PET visibility of colorectal polyps. FDG PET visibility may be helpful for predicting whether a polyp should be removed or observed. FDG PET findings also may suggest the need to alter the treatment of patients with colorectal polyps.
Assuntos
Pólipos do Colo/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Adulto , Idoso , Análise de Variância , Pólipos do Colo/patologia , Detecção Precoce de Câncer , Feminino , Fluordesoxiglucose F18 , Humanos , Interpretação de Imagem Assistida por Computador , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Estatísticas não ParamétricasRESUMO
ITR after BMT in cases of acute lymphoblastic leukemia is relatively rare. Treatment for ITR after BMT generally consists of a combination of local irradiation, orchiectomy, and systemic chemotherapy. However, the effectiveness of these modalities has not been established. Both irradiation and systemic chemotherapy including a second transplantation would result in additional toxicity. In this report we describe a boy with ITR 91 months after BMT who has remained in complete remission more than two yr after a unilateral orchiectomy. We did not treat this patient with systemic chemotherapy, as his ITR developed very late. Our experience suggests that orchiectomy alone is a reasonable option for very late ITR after BMT.
Assuntos
Transplante de Medula Óssea/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Neoplasias Testiculares/diagnóstico , Criança , Humanos , Lactente , Masculino , Recidiva , Indução de Remissão , Neoplasias Testiculares/secundário , Testículo/cirurgia , Resultado do TratamentoRESUMO
Immature-type CD56(+) natural killer (NK)-cell neoplasms are classified as either myeloid/NK-cell precursor acute leukemia or blastic NK-cell lymphoma. We identified two cases of immature-type CD56(+) NK-cell neoplasms that were not categorizable as either of these entities. The first case involved a 74-year-old woman presenting with skin eruptions and pancytopenia due to bone marrow necrosis. Skin biopsy specimen revealed CD4(+), CD7(-), CD34(-), CD43(+), CD56(+), CD68(+), muramidase (lysozyme)(+), and myeloperoxidase (MPO)(-), and immunophenotyping of peripheral blood showed CD4(+), CD7(-), CD13(+), CD33(+), CD34(-), CD43(+), CD56(+), cytoplasmic (cy)CD68(+), CD123(+), and HLA-DR(+). The second case involved a 62-year-old man who had bilateral optic nerve tumor and presented with malignant cells in peripheral blood. Cell surface markers of malignant cells showed CD4(+), CD7(-), CD13(+), CD33(+), CD34(-), CD43(+), CD56(+), cyCD68(+), and HLA-DR(+). The phenotypes of tumor cells in both cases were compatible with blastic NK-cell lymphoma, except for the expression of myeloid antigen. Clinical presentations of these cases showed characteristics of both blastic NK-cell lymphoma and myeloid/NK-cell precursor acute leukemia.
Assuntos
Células Matadoras Naturais/patologia , Leucemia Linfocítica Crônica de Células B/patologia , Leucemia Linfoide/patologia , Leucemia Mieloide Aguda/patologia , Idoso , Antígeno CD56 , Feminino , Humanos , Imunofenotipagem , Masculino , Pessoa de Meia-IdadeRESUMO
We experienced a very rare case of late pulmonary metastasis from ACC. The patient was a 40-year-old woman who had undergone a left adrenectomy 12 years earlier. Instead of a large metastatic lung tumor with hemothorax and the existence of metastases in other organs, combined therapy of repeated resections for metastases and adjuvant therapy allowed for almost a 36-month survival following the first recurrence and a good quality of life. In addition, a blood and pathological study revealed that the tumor in this case was an alpha-fetoprotein-producing ACC, which is, as far as we could ascertain, the first case of its kind.