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Aberrant activation of the Wnt/ß-catenin signaling pathway plays a crucial role in the development and progression of colorectal cancer. Previously, we identified a set of candidate genes that were regulated by this signaling pathway, and the present study focused on motile sperm domain containing 1 (MOSPD1). Immunohistochemical staining revealed that the expression of MOSPD1 was elevated in tumor cells from colorectal cancer tissues compared with in non-tumor cells. Using ChIP-seq data and the JASPAR database, the regulatory region(s) in the MOSPD1 gene as a target of the Wnt/ß-catenin signaling pathway were searched, and a region containing three putative TCF-binding motifs in the 3'-flanking region was identified. Additional analyses using reporter assay and ChIP-quantitative PCR suggested that this region harbors enhancer activity through an interaction with transcription factor 7 like 2 (TCF7L2) and ß-catenin. In addition, chromatin conformation capture assay revealed that the 3'-flanking region interacts with the MOSPD1 promoter. These data suggested that MOSPD1 was regulated by the ß-catenin/TCF7L2 complex through the enhancer element located in the 3'-flanking region. These findings may be helpful for future studies regarding the precise regulatory mechanisms of MOSPD1.
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BACKGROUND: Currently, there is an unwavering consensus that the standard surgery for congenital biliary dilation (CBD) is extrahepatic bile duct resection and choledochojejunostomy. However, decades prior, choledochocyst-gastrointestinal anastomosis without extrahepatic bile duct resection (internal drainage surgery, IDS) was preferred for CBD because of its simplicity. Currently, there is almost no chance of a surgeon encountering a patient who has undergone old-fashioned IDS, which has been completely obsolete due to the risk of carcinogenesis from the remaining bile duct. Moreover, the pathological condition long after IDS is unclear. Herein, we report a case of life-threatening bile duct bleeding as well as carcinoma of the bile duct 62 years after IDS in a patient with CBD. CASE PRESENTATION: An 82-year-old Japanese woman with hemorrhagic shock due to gastrointestinal bleeding was transferred to our hospital. She had a medical history of unspecified surgery for CBD at the age of 20. Based on imaging findings and an understanding of the historical transition of the surgical procedure for CBD, the cause of gastrointestinal bleeding was determined to be rupture of the pseudoaneurysm of the dilated bile duct that remained after IDS. Hemostasis was successfully performed by transcatheter arterial embolization (TAE) in an emergency setting. Then, elective surgery for extrahepatic bile duct resection and choledochojejunostomy was performed to prevent rebleeding. Pathological examination revealed severely and chronically inflamed mucosa of the bile duct. Additionally, cholangiocarcinoma (Tis, N0, M0, pStage 0) was incidentally revealed. CONCLUSION: It has been indicated that not only carcinogenesis, but also a risk of life-threatening bleeding exists due to long-lasting chronic inflammation to the remnant bile duct after IDS for CBD. Additionally, both knowledge of which CBD operation was performed, and an accurate clinical history are important for the diagnosis of hemobilia.
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Biliary tract cancer (BTC) is one of the most devastating types of malignant neoplasms worldwide. However, the mechanisms underlying the development and progression of BTC remain unresolved. BTC includes extrahepatic bile duct carcinoma (EBDC), gallbladder carcinoma (GBC) and ampulla of Vater carcinoma (AVC), named according to the location of the tumor. Although genetic alterations of intrahepatic cholangiocarcinoma have been investigated, those of EBDC, GBC and AVC have not yet been fully understood. The present study analyzed somatic mutations of 50 cancer-associated genes in 27 Japanese BTC cells, including: 11 EBDC, 14 GBC and 2 AVC. Next-generation sequencing using an Ion AmpliSeq Cancer Panel identified a total of 44 somatic mutations across 14 cancer-associated genes. Among the 44 mutations, 42 were judged as pathological mutations. Frequent mutations were identified in tumor protein 53 (TP53) (14/27), SMAD family member 4 (SMAD4) (6/27), phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit α (PIK3CA) (6/27), and Kirsten rat sarcoma (KRAS) (6/27); no significant differences were identified between EBDC and GBC tissues. Notably, the frequency of the PIK3CA mutation was higher when compared with previous reports. This result may suggest that the activation of the PIK3CA-protein kinase B signaling pathway, in addition to the abrogation of p53, SMAD4 and RAS mitogen-activated protein kinase may have a crucial role in the carcinogenesis of Japanese BTC. These findings may be useful for the development of personalized therapies for BTC.
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Three patients under hemodialysis (HD) with relapsed/refractory multiple myeloma (MM) were administered panobinostat/bortezomib/dexamethasone (FVD). Case 1: The patient was a 66-year-old male with BJP-κ. FVD was effective, but HD could not be discontinued. He developed Grade 3 adverse events (AEs), including nausea, dehydration, and fatigue, following the common terminology criteria for adverse events v4.0. FVD was discontinued after the third course, while HD was continued. Case 2: The patient was a 65-year-old female with IgG-λ + BJP-λ. Amyloidosis was complicated. The first course of FVD was effective, but HD could not be discontinued. She developed G2 AEs, including nausea and fatigue. The cardiac amyloidosis worsened, and she died of heart and renal failure. Case 3: The patient was a 79-year-old male with BJP-κ. FVD was effective, and the HD could be discontinued on day 12 of treatment. No AEs were noted. However, he declined continuation of the FVD and died of MM relapse and renal failure. We analyzed the pharmacokinetics of panobinostat. There were no correlations between dose level and blood level of panobinostat or between blood level, efficacy, and incidence of AEs. We additionally measured the rate of elimination of the drug by HD.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Mieloma Múltiplo/terapia , Diálise Renal , Insuficiência Renal/terapia , Idoso , Bortezomib/administração & dosagem , Bortezomib/farmacocinética , Dexametasona/administração & dosagem , Dexametasona/farmacocinética , Feminino , Humanos , Ácidos Hidroxâmicos/administração & dosagem , Ácidos Hidroxâmicos/farmacocinética , Indóis/administração & dosagem , Indóis/farmacocinética , Masculino , Mieloma Múltiplo/sangue , Panobinostat , Recidiva , Insuficiência Renal/sangueRESUMO
PURPOSE: To clarify the development of HCC, temporal change of steatosis and Gd-EOB-DTPA enhancement of non-alcoholic steatohepatitis (NASH) model mice by magnetic resonance imaging (MRI). MATERIALS AND METHODS: All animal experiments were approved by the institution's Animal Research Committee. MRI was performed on six NASH and six simple steatosis (SS) model mice every 2weeks from the ages of 8weeks to 16weeks. The sequential changes in the number and size of the focal liver lesions detected on Gd-EOB-DTPA-enhanced MRI were evaluated. Additionally, the hepatic fat fraction (HFF), contrast-to-noise ratio (CNR) and relative enhancement (RE) were calculated at each time point. The temporal changes and correlations in these parameters were evaluated. RESULTS: All alive NASH model mice demonstrated focal liver lesions from week 10, at the latest. Number of the lesions increased with time, and all the lesion enlarged with time. All the lesions larger than 1mm were confirmed as hepatocellular carcinoma (HCC) pathologically. While the HFF remained constant in NASH model mice, HFF in SS model mice dramatically increased with time. CNR of the NASH model mice remained constant through the study period, while CNR in SS model mice decreased with time. Although no correlation was seen in NASH model mice, the HFF showed a negative correlation against CNR and RE in SS model mice. CONCLUSION: Development of HCC was observed using Gd-EOB-DTPA-enhanced MRI only in NASH model mice. Degree of steatosis and hepatic enhancement by Gd-EOB-DTPA was both constant in NASH model mice, while steatosis increased and hepatic enhancement decreased with time in SS model mice.
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Carcinoma Hepatocelular/diagnóstico por imagem , Gadolínio DTPA/química , Neoplasias Hepáticas/diagnóstico por imagem , Imageamento por Ressonância Magnética , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Animais , Animais Recém-Nascidos , Meios de Contraste , Modelos Animais de Doenças , Feminino , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , EstreptozocinaRESUMO
BACKGROUND: Plexiform angiomyxoid myofibroblastic tumor (PAMT) is a very rare mesenchymal tumor of the stomach. Here we report a case of pathologically confirmed PAMT with an unique cyst formation. CASE PRESENTATION: A 55-year-old male with a 10-year history of a gastric subepithelial tumor underwent computed tomography (CT) and magnetic resonance imaging (MRI). Two cysts were observed in the tumor, and the cyst wall showed moderately high intensity on T2-weighted images compared with the gastric wall. On dynamic study, the cyst wall showed a gradual enhancement pattern, and prominent enhancement was observed in the delayed phase. Laparoscopic partial gastric resection was performed, and a pathological diagnosis of PAMT was rendered. CONCLUSION: We present a rare case of gastric PAMT, which was uniquely presented as cysts. One of the cysts in the tumor had an epithelial wall lining, which had never been reported before in gastric mesenchymal tumor, in addition to partial glandular structure. We reviewed our case, focusing on radiologic-pathologic correlation, and suggested hypothesis of cyst formation. According to our findings, PAMT with cyst formation would be included of differential diagnosis of gastric subepithelial tumors.
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Tumores do Estroma Gastrointestinal/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Miofibroblastos/patologia , Mixoma/diagnóstico por imagem , Neoplasias Gástricas/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Carga TumoralRESUMO
BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare disease with an estimated incidence of 1-2 cases per million individuals per year. PMP is characterized by the accumulation of abundant mucinous or gelatinous fluid derived from disseminated tumorous cells. Most of the tumorous cells are originated from rupture of appendiceal neoplasms, but some are from the metastasis of cancer of the colon, ovary, fallopian tube, urachus, colorectum, gallbladder, stomach, pancreas, lung and breast. Although frequent mutations in KRAS and/or GNAS genes have been reported, precise molecular mechanism underlying PMP remains to be elucidated. It is of note that mucinous tumour is one of the frequent histological features of colorectal cancer (CRC) in Lynch syndrome (LS), an autosomal dominantly inherited disease caused by a germline mutation of the DNA mismatch repair (MMR) genes including human mutL homolog 1 (MLH1), human mutS homolog 2 (MSH2), human mutS homolog 6 (MSH6), and postmeiotic segregation increased 2 (PMS2). Therefore, typical LS-associated tumours show mismatch repair instability. Although LS patients are most strongly predisposed to CRC, PMPs from mucinous CRC have not been reported in LS patients. CASE PRESENTATION: In this report, we report a case of PMP originating from an ovarian teratoma in a LS patient. The patient had surgical treatment of PMP arising from an ovarian teratoma at the age of 38 years, and later developed a transverse colon cancer at the age of 40. The patient's family history fulfilled the Amsterdam criteria, and genetic analysis of the peripheral leukocytes identified a germ line mutation in the MLH1 gene (MLH1 c.1546dupC p.Q516PfsX3). Interestingly, immunohistochemical staining showed that the expression of MLH1 was lost in the colon cancer as well as the ovarian teratoma. Consistent with the loss of MLH1 expression, both tumours showed high microsatellite instability (MSI-H). CONCLUSION: This case suggested that LS patients may develop various types of tumours including ovarian PMP, and that mismatch repair deficiency may play a role in the development of PMP derived from, at least, a part of ovarian teratomas.
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Neoplasias Colorretais Hereditárias sem Polipose/complicações , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Neoplasias Ovarianas/complicações , Neoplasias Ovarianas/genética , Pseudomixoma Peritoneal/complicações , Pseudomixoma Peritoneal/genética , Teratoma/complicações , Teratoma/genética , Abdome/diagnóstico por imagem , Adulto , Neoplasias do Colo/diagnóstico , Neoplasias do Colo/secundário , Neoplasias Colorretais Hereditárias sem Polipose/genética , DNA/química , DNA/isolamento & purificação , DNA/metabolismo , Reparo de Erro de Pareamento de DNA , Feminino , Mutação em Linhagem Germinativa , Humanos , Imageamento por Ressonância Magnética , Instabilidade de Microssatélites , Proteína 1 Homóloga a MutL/genética , Neoplasias Ovarianas/diagnóstico , Linhagem , Pseudomixoma Peritoneal/cirurgia , Recidiva , Teratoma/diagnóstico , Tomografia Computadorizada por Raios XRESUMO
TAFRO syndrome is a systemic inflammatory disorder characterized by thrombocytopenia, anasarca including pleural effusion and ascites, fever, renal insufficiency, and organomegaly including hepatosplenomegaly and lymphadenopathy. Its onset may be acute or sub-acute, but its etiology is undetermined. Although several clinical and pathological characteristics of TAFRO syndrome resemble those of multicentric Castleman disease (MCD), other specific features can differentiate between them. Some TAFRO syndrome patients have been successfully treated with glucocorticoids and/or immunosuppressants, including cyclosporin A, tocilizumab and rituximab, whereas others are refractory to treatment, and eventually succumb to the disease. Early and reliable diagnoses and early treatments with appropriate agents are essential to enhancing patient survival. The present article reports the 2015 updated diagnostic criteria, disease severity classification and treatment strategy for TAFRO syndrome, as formulated by Japanese research teams. These criteria and classification have been applied and retrospectively validated on clinicopathologic data of 28 patients with this and similar conditions (e.g. MCD with serositis and thrombocytopenia).
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Hiperplasia do Linfonodo Gigante/diagnóstico , Hiperplasia do Linfonodo Gigante/classificação , Diagnóstico Diferencial , Edema , Glucocorticoides/uso terapêutico , Guias como Assunto , Humanos , Imunossupressores/uso terapêutico , Estudos Retrospectivos , Índice de Gravidade de Doença , Síndrome , TrombocitopeniaRESUMO
Pseudomyxoma peritonei (PMP) is a rare disease exhibiting a distinct clinical feature caused by cancerous cells that produce mucinous fluid in the abdominal cavity. PMPs originate most frequently from the appendix and less frequently from the ovary. This disease can range from benign to malignant, and histologically, PMP is classified into two types: disseminated peritoneal adenomucinosis (DPAM) representing the milder phenotype, and peritoneal mucinous adenocarcinomas (PMCA) representing the aggressive phenotype. Although histological classification is clinically useful, the pathogenesis of PMP remains largely unknown. To elucidate the molecular mechanisms underlying PMP, we analyzed 18 PMP tumors comprising 10 DPAMs and 8 PMCAs. DNA was extracted from tumor and matched non-tumorous tissues, and was sequenced using Ion AmpliSeq Cancer Panel containing 50 cancer-related genes. Analysis of the data identified a total of 35 somatic mutations in 10 genes, and all mutations were judged as pathological mutations. Mutations were frequently identified in KRAS (14/18) and GNAS (8/18). Interestingly, TP53 mutations were found in three of the eight PMCAs, but not in the DPAMs. PIK3CA and AKT1 mutations were also identified in two PMCAs, but not in the DPAMs. These results suggested that KRAS and/or GNAS mutations are common genetic features of PMP, and that mutations in TP53 and/or genes related to the PI3K-AKT pathway may render malignant properties to PMP. These findings may be useful for the understanding of tumor characteristics, and facilitate the development of therapeutic strategies.
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Perfilação da Expressão Gênica , Neoplasias Peritoneais/genética , Neoplasias Peritoneais/patologia , Pseudomixoma Peritoneal/genética , Pseudomixoma Peritoneal/patologia , Transcriptoma , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Terapia Combinada , Análise Mutacional de DNA , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Mutação , Gradação de Tumores , Neoplasias Peritoneais/terapia , Pseudomixoma Peritoneal/terapia , Proteína Supressora de Tumor p53/metabolismoRESUMO
A 41-year-old man presented with the chief complaint of right hip pain that had persisted for 6 months. F18-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) imaging showed FDG accumulation in the right pubic bone. A bone biopsy specimen from the site revealed findings suggestive of a plasma cell tumor. Bone marrow examination and serum and urine immunofixation tests showed no abnormalities. Based on these findings, the patient was diagnosed as having non-secretory multiple myeloma. FDG accumulation in the right pubic bone diminished following four cycles of weekly bortezomib and concomitant dexamethasone therapy. Tandem autologous peripheral blood stem cell transplantation was performed, followed by monthly bortezomib/dexamethasone maintenance therapy. A further FDG-PET/CT scan 9 months after the start of therapy indicated that FDG accumulation in the right pubic bone had worsened. Consequently, the therapy was switched to twice-weekly bortezomib/dexamethasone as remission re-induction therapy. New FDG uptake in the right hip bone was noted after six cycles of the therapy, and plain X-ray examination revealed osteolytic changes. The patient was then administered eight cycles of combined lenalidomide-dexamethasone therapy, which resulted in a marked decrease of the FDG accumulation in the right pubic bone and disappearance of uptake in the right hip bone. There was radiographic evidence of bone formation at these sites. This is only the second reported case in which treatment with the immunomodulatory drug lenalidomide and concomitant dexamethasone has been found to induce bone formation.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fatores Imunológicos/administração & dosagem , Mieloma Múltiplo/tratamento farmacológico , Osteogênese/efeitos dos fármacos , Adulto , Bortezomib/uso terapêutico , Dexametasona/administração & dosagem , Humanos , Lenalidomida , Masculino , Recidiva Local de Neoplasia/tratamento farmacológico , Transplante de Células-Tronco de Sangue Periférico , Terapia de Salvação/efeitos adversos , Terapia de Salvação/métodos , Talidomida/administração & dosagem , Talidomida/análogos & derivadosRESUMO
A 68-year-old man presented to us with pancytopenia, erythroderma, and multiple lymphadenopathies. Lymph node biopsy led to the diagnosis of peripheral T-Cell lymphoma-not otherwise specified (PTCL-NOS). Immunostaining of the lymph node biopsy specimens for cytokines revealed that the tumor cells were positive for plated-derived growth factor (PDGF), basic fibroblast growth factor (b-FGF), vascular endothelial growth factor (VEGF), tumor necrosis factor α (TNF-α), interferon-γ (IFN-γ), interleukin-1ß (IL-1ß), interleukin-2 (IL-2), and transforming growth factor-ß (TGF-ß). Bone marrow biopsy revealed infiltration by the PTCL-NOS and myelofibrosis (MF). Bone marrow blood was negative for JAK-2V617F. Bone marrow immunostaining for cytokines showed that the tumor cells were positive for PDGF, b-FGF, VEGF, TNF-α, IFN-γ, IL-1ß, IL-2, and TGF-ß. The patient was initiated on treatment, and after the first course of CHOP therapy, the bone marrow infiltration by the PTCL-NOS and MF improved. Repeat immunostaining of bone marrow biopsy specimens for cytokines showed that the tumor cells had become negative for PDGF, VEGF, TNF-α and TGF-ß. However, after the second course of CHOP therapy, the bone marrow infiltration by the PTCL-NOS and MF worsened. Immunostaining of bone marrow specimens for cytokines again revealed positive staining results of the tumor cells for PDGF, TNF-α, and TGF-ß. At the completion of the first course of treatment, the infiltration by the PTCL-NOS improved, but not the pancytopenia.
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Medula Óssea , Linfonodos , Linfoma de Células T Periférico , Mielofibrose Primária , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/sangue , Biópsia , Medula Óssea/efeitos dos fármacos , Medula Óssea/imunologia , Medula Óssea/patologia , Exame de Medula Óssea , Ciclofosfamida/uso terapêutico , Citocinas/sangue , Doxorrubicina/uso terapêutico , Humanos , Imuno-Histoquímica , Linfonodos/efeitos dos fármacos , Linfonodos/imunologia , Linfonodos/patologia , Linfoma de Células T Periférico/sangue , Linfoma de Células T Periférico/tratamento farmacológico , Linfoma de Células T Periférico/imunologia , Linfoma de Células T Periférico/patologia , Masculino , Prednisolona/uso terapêutico , Mielofibrose Primária/sangue , Mielofibrose Primária/tratamento farmacológico , Mielofibrose Primária/imunologia , Mielofibrose Primária/patologia , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Vincristina/uso terapêuticoRESUMO
Pressure ulcers result from tissue hypoxia caused by external forces. Thrombosis due to external forces is considered important, and hypoxia inducible factor-1 (HIF-1) is a master regulator of pressure ulcer development. To date, however, their causal relationship has not been determined. This study therefore investigated the mutual relationship between thrombosis and HIF-1 activation in compressed mouse skin, based on a hypothesis that HIF-1 regulation by plasminogen activator inhibitor-1 (PAI-1) enhances thrombosis. Compression of mouse skin significantly increased the numbers of thrombi and HIF-1α-positive cells compared with control skin. A thrombosis inhibitor significantly reduced the numbers of HIF-1α-positive cells and an HIF-1 inhibitor significantly inhibited thrombosis in compressed skin tissue, suggesting a mutual relationship between thrombosis and HIF-1 activation. Compression of mouse skin also enhanced the level of Pai-1 messenger RNA expression, but this increase was significantly reduced by treatment with an HIF-1 inhibitor, whereas a thrombosis inhibitor had no effect. These results suggested the involvement of PAI-1 in HIF-1-enhanced thrombosis and that an additional factor participates in regulating Pai-1 expression in compressed skin. These findings may suggest new strategies in pressure ulcer management.
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Regulação da Expressão Gênica , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , RNA Mensageiro/genética , Serpina E2/genética , Pele/metabolismo , Trombose/genética , Ferimentos e Lesões/genética , Animais , Modelos Animais de Doenças , Subunidade alfa do Fator 1 Induzível por Hipóxia/biossíntese , Imuno-Histoquímica , Masculino , Camundongos , Pressão , Reação em Cadeia da Polimerase em Tempo Real , Serpina E2/biossíntese , Pele/lesões , Pele/patologia , Estresse Mecânico , Trombose/etiologia , Trombose/metabolismo , Cicatrização , Ferimentos e Lesões/complicações , Ferimentos e Lesões/metabolismoRESUMO
A 61-year-old woman was diagnosed as having rheumatoid arthritis (RA) and began treatment with salazosulfapyridine (SASP) and methotrexate (MTX) in 2008; the administration of concomitant tacrolimus (TAC) was initiated in 2010. She subsequently developed concurrent multiple myeloma (MM), immunoglobulin G (IgG)-κ type, in 2012. A portion of the tumor cells tested positive for Epstein-Barr virus-encoded small RNA (EBER). MTX treatment was discontinued in 2014, and the exacerbation of MM ensued. The patient received two cycles of bortezomib plus dexamethasone (BD) therapy and attained a complete response (CR). She then underwent an autologous peripheral blood stem cell transplantation. The Epstein-Barr (EB) virus infection arising from the increased RA disease activity and immunosuppressant medication might have influenced the development of MM in this case. Most reported patients with EB virus-positive plasmacytoma are in a state of immunosuppression, and this condition may fall within the category of other iatrogenic immunodeficiency-associated lymphoproliferative disorders. No other reports of plasmacytoma occurring in a background of RA or after TAC or MTX therapy have been made, and the present case is the first such report.
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Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Herpesvirus Humano 4/isolamento & purificação , Imunossupressores/efeitos adversos , Metotrexato/efeitos adversos , Mieloma Múltiplo/patologia , Antirreumáticos/uso terapêutico , Feminino , Humanos , Imunossupressores/uso terapêutico , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Mieloma Múltiplo/etiologia , Mieloma Múltiplo/virologiaRESUMO
A 36-year-old woman with a left lung tumor was referred to our hospital since a pathological diagnosis had not been obtained at a previous medical institution. We carried out CT-guided percutaneous lung biopsy with an 18-gauge needle and obtained four samples. Immunological staining revealed the specimens to be CD30- and PAX5-positive, with large dysplastic lymphocytes negative for Bob-1 and Oct-2 with a background of small lymphocytes and eosinophils. Primary pulmonary Hodgkin lymphoma (PPHL) was diagnosed. Although PPHL is very rare, it should be included in the differential diagnosis of lung tumors and immunological staining with CD15 and CD30 is recommended. Furthermore, carefully planned CT-guided lung biopsy is useful for diagnosing PPHL.
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Doença de Hodgkin/diagnóstico , Doença de Hodgkin/patologia , Neoplasias Pulmonares/patologia , Tomografia Computadorizada por Raios X , Adulto , Biópsia por Agulha , Feminino , Humanos , Neoplasias Pulmonares/diagnósticoRESUMO
A 50-year-old woman who presented with a mass in the thyroid gland was diagnosed as having diffuse large B-cell lymphoma (DLBCL) by biopsy in August 2011. The tumor had a complex chromosomal karyotype, including 8q24 (C-MYC) and 18q21(BCL-2), and fluorescence in situ hybridization confirmed split signals of C-MYC and BCL-2. BCL-2/IgH and C-MYC/IgH fusion signals were also observed. Three courses of rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone (R-CHOP) therapy were given, followed by thyroid gland irradiation. She was achieved complete remission (CR). In January 2012, a mass appeared in the right breast, which was diagnosed as relapse by biopsy. CR was achieved again after the 4th course of R-CHOP therapy, and one course of rituximab, etoposide, methylprednisolone, cytarabine, cisplatin (R-ESHAP) therapy was given. Thereafter, CR has been maintained after high-dose chemotherapy and autologous peripheral blood stem cell transplantation. There have been only 3 reported cases of primary thyroid C-MYC and BCL-2 double-hit lymphoma, including the present case; 2 of the cases were cases of DLBCL. R-CHOP therapy, irradiation and autologous peripheral blood stem cell transplantation are expected to be effective for such patients.
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A 70-year-old man presented to us with the chief complaints of a generalized rash and a mass in the right clavicular region that he first noticed in the year 2012. Biopsy of the mass led to the diagnosis of cutaneous nodular mass-type adult T-cell leukemia/lymphoma (ATLL) in March 2013. Phototherapy was started, and the symptoms improved temporarily. However, in late June 2013, the serum lactate dehydrogenase (LDH) level increased to 358 IU/L, which was 1.6 times higher than the upper limit of the reference range; based on the findings, transformation of the disease to the acute type was diagnosed. The patient was treated with 6 courses of CHOP therapy (cyclophosphamide, doxorubicin, vincristine, and prednisolone), which resulted in complete remission (CR). However, the rash recurred in late October 2013, and treatment with mogamulizumab was initiated. A total of 8 courses of mogamulizumab were administered, which resulted in CR. The rash and cutaneous nodular masses recurred again in January 2014, and a total of 8 courses of mogamulizumab were administered again starting in February 2014. However, the patient's symptoms began to worsen gradually. Phototherapy was also initiated, but had to be discontinued due to the development of photosensitivity. Treatment with the combination of mogamulizumab and etoposide (25 mg/day for 21 days) was started in May 2014. The nodular mass rapidly decreased in size. The rash or cutaneous nodular mass had not recurred as of August 2014. Thus, combined therapy with mogamulizumab plus etoposide is considered to be effective for resolution of the cutaneous nodular masses in patients with ATLL.
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Anticorpos Monoclonais Humanizados/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Etoposídeo/administração & dosagem , Leucemia-Linfoma de Células T do Adulto/tratamento farmacológico , Pele/efeitos dos fármacos , Idoso , Biomarcadores Tumorais/análise , Biópsia , Humanos , Imuno-Histoquímica , Leucemia-Linfoma de Células T do Adulto/metabolismo , Leucemia-Linfoma de Células T do Adulto/patologia , Masculino , Tomografia por Emissão de Pósitrons , Valor Preditivo dos Testes , Recidiva , Indução de Remissão , Pele/química , Pele/patologia , Fatores de Tempo , Resultado do Tratamento , Imagem Corporal Total/métodosRESUMO
A 61-year-old woman was diagnosed in June 2011 as having immunoglobulin G (IgG) ĸ-type multiple myeloma (MM), stage II, according to the International Staging System (ISS). Chromosome analysis showed a complex karyotype, including t(11;14) and del 13q. Analysis of the cell surface markers revealed that the cells were positive for mature plasma cell-1 (MPC-1), and negative for cluster of differentiation (CD) 45 and CD49e, suggestive of an intermediate level of maturity of the cells. The disease was refractory to bortezomib-dexamethasone (BD) therapy and progressed to plasma cell leukemia despite the treatment. Treatment was therefore switched to lenalidomide-dexamethasone (RD) therapy, however, the condition again proved to be refractory to this therapy. A partial response (PR) was achieved with vincristine-doxorubicin-dexamethasone (VAD) therapy. The residual plasma cells became CD45-positive, suggesting a change of the cells from an intermediate level of maturity to mature cells. In December, autologous peripheral blood stem cell transplantation (Auto-PBSCT) was performed after high-dose melphalan therapy (melphalan 200 mg/m(2)) as pretreatment. PR was observed and a second Auto-PBSCT was performed in July 2012. Stringent complete remission (sCR) has been maintained for 2 years since, without any further treatment. This is the first reported case of secondary plasma cell leukemia (sPCL) resistant to new drugs that was successfully treated by high-dose melphalan in combination with VAD therapy and Auto-PBSCT.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Substituição de Medicamentos , Leucemia Plasmocitária/terapia , Mieloma Múltiplo/terapia , Transplante de Células-Tronco de Sangue Periférico , Plasmócitos/efeitos dos fármacos , Biomarcadores Tumorais/análise , Exame de Medula Óssea , Ácidos Borônicos/administração & dosagem , Bortezomib , Dexametasona/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Humanos , Imuno-Histoquímica , Lenalidomida , Leucemia Plasmocitária/diagnóstico , Leucemia Plasmocitária/imunologia , Antígenos Comuns de Leucócito/análise , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/imunologia , Plasmócitos/imunologia , Plasmócitos/patologia , Pirazinas/administração & dosagem , Indução de Remissão , Talidomida/administração & dosagem , Talidomida/análogos & derivados , Fatores de Tempo , Tomografia Computadorizada por Raios X , Transplante Autólogo , Resultado do Tratamento , Vincristina/administração & dosagemRESUMO
Angioimmunoblastic T cell lymphoma (AITL) is a distinct subtype of peripheral T cell lymphoma characterized by generalized lymphadenopathy and frequent autoimmune-like manifestations. Although frequent mutations in TET2, IDH2 and DNMT3A, which are common to various hematologic malignancies, have been identified in AITL, the molecular pathogenesis specific to this lymphoma subtype is unknown. Here we report somatic RHOA mutations encoding a p.Gly17Val alteration in 68% of AITL samples. Remarkably, all cases with the mutation encoding p.Gly17Val also had TET2 mutations. The RHOA mutation encoding p.Gly17Val was specifically identified in tumor cells, whereas TET2 mutations were found in both tumor cells and non-tumor hematopoietic cells. RHOA encodes a small GTPase that regulates diverse biological processes. We demonstrated that the Gly17Val RHOA mutant did not bind GTP and also inhibited wild-type RHOA function. Our findings suggest that impaired RHOA function in cooperation with preceding loss of TET2 function contributes to AITL-specific pathogenesis.
Assuntos
Proteínas de Ligação a DNA/genética , Linfadenopatia Imunoblástica/genética , Linfoma de Células T Periférico/genética , Proteínas Proto-Oncogênicas/genética , Proteína rhoA de Ligação ao GTP/genética , Animais , Sequência de Bases , Bromodesoxiuridina , DNA (Citosina-5-)-Metiltransferases/genética , DNA Metiltransferase 3A , Dioxigenases , Exoma/genética , Humanos , Isocitrato Desidrogenase/genética , Células Jurkat , Linfoma de Células T Periférico/patologia , Camundongos , Dados de Sequência Molecular , Mutação de Sentido Incorreto/genética , Células NIH 3T3 , Análise de Sequência de DNARESUMO
A 60-year-old man complained of nausea, vomiting, decreased appetite, and a feeling of abdominal fullness in August 2013. Based on biopsy findings from an upper gastrointestinal endoscopy examination, a diagnosis of non-Hodgkin's lymphoma (NHL), diffuse large B-cell lymphoma (DLBCL), non-GC type, was made. F18-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) revealed abnormal accumulations solely in the gastric wall (SUVmax = 14.5), the left adrenal gland (SUVmax = 14.3), and the right adrenal gland (SUVmax = 8.5). The clinical stage (Ann Arbor) was IVA, the serum LDH level was within the reference range, and the International Prognostic Index (IPI) was low-intermediate. The serum soluble IL-2 receptor level was within the reference range, and there was no evidence of HIV, EB virus, or autoimmune disease. After the completion of 4 cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) and 2 parallel cycles of prophylactic intrathecal (I.T.), an upper gastrointestinal endoscopy and a FDG-PET/CT examination showed complete remission (CR). The patient received 8 cycles of ritsuximab therapy, 6 cycles of CHOP, and 3 cycles of I.T. The patient has maintained a CR for about 14 months. A literature search revealed that malignant lymphoma with involvement confined to the adrenal gland and gastrointestinal tract is exceedingly rare, and only 3 cases of malignant lymphoma have been reported, with involvement of the stomach in 2 cases and the duodenum in 1 case. All of the cases were diagnosed as DLBCL. The case described herein represents the third case with involvement of the stomach.