RESUMO
Syphilis is an infectious disease caused by the spirochete bacterium Treponema pallidum. Neurosyphilis results from the infection of the nervous system with Treponema pallidum, which can occur at any stage of syphilis. Neurosyphilis is often overlooked because of its rarity. Early-stage neurosyphilis with brain mass formation is rare. We present a case of early-stage neurosyphilis with prominent Epstein-Barr virus (EBV)-positive monoclonal lymphoplasmacytic proliferation in an immunocompetent patient. A 36-year-old man presented with a chief complaint of a progressively worsening headache, a newly developed skin rash, and a fever. Magnetic resonance imaging showed a mass lesion, which measured 18 mm in diameter, in the left frontal lobe of the cerebrum. The patient underwent an emergency operation to remove the abscess. A pathological investigation revealed complex findings. There was an abscess in the cerebrum. Lymphoplasmacytic meningitis was also noted. In addition, a vaguely nodular lesion, which was composed of plasmacytoid and lymphoid cells, was observed around the abscess. Immunohistochemically, an anti-Treponema pallidum antibody revealed numerous Treponemas around the abscess. In situ hybridization revealed that the plasmacytoid and lymphoid cells were Epstein-Barr encoding region (EBER)-positive; κ-positive cells were significantly more prevalent than λ-positive cells, suggesting light-chain restriction. Postoperatively, parenteral antibiotics were administered for four weeks. The patient has been free of recurrence for two years since the surgery. No association between neurosyphilis and EBV-positive lymphoplasmacytic proliferation has ever been reported. Mass formation in early-stage neurosyphilis is an exceptionally rare event. The present case indicates that in syphilis patients, lymphoproliferative disorders that lead to mass formation may be caused by concomitant EBV reactivation. Furthermore, when treating patients with mass lesions of the central nervous system, it is important to check their medical history and perform laboratory screening for infectious diseases to avoid overlooking syphilis infections.
Assuntos
Infecções por Vírus Epstein-Barr , Neurossífilis , Sífilis , Masculino , Humanos , Adulto , Sífilis/complicações , Herpesvirus Humano 4 , Infecções por Vírus Epstein-Barr/complicações , Abscesso/complicações , Neurossífilis/complicações , Neurossífilis/diagnóstico , Treponema pallidum , Proliferação de CélulasRESUMO
BACKGROUND: Pulmonary inflammatory leiomyosarcoma (PILMS) is a rare type of myogenic tumor with prominent lymphohistiocytic infiltration. Despite their histological similarities, PILMS is immunohistochemically and genetically distinct from soft tissue inflammatory leiomyosarcoma, and its clinicopathological picture including DNA methylome data remains still unknown. CASE PRESENTATION: Here we present a case of PILMS in an 18-year-old male who underwent lobectomy. As reported previously, the current case demonstrated spindle myoid cell proliferation with smooth muscle differentiation within a prominent lymphohistiocytic infiltration and a diploid genome with a MUC3A gene alteration. DNA methylation analysis predicted this case to be an "inflammatory myofibroblastic tumor" (IMT) according to the Deutsches Krebsforschungszentrum (DKFZ) classifier. The data was analyzed by t-distributed stochastic neighbor embedding, which plotted the case tumor in the vicinity of IMT, however, there were no IMT histological features. These discordant results could be due to background non-neoplastic inflammatory cells. CONCLUSIONS: As the DNA methylation classification of PILMS might be a potential diagnostic pitfall, an integrative histological and genetic approach is required for its accurate diagnosis.
Assuntos
Leiomiossarcoma , Neoplasias Pulmonares , Sarcoma , Masculino , Humanos , Adolescente , Leiomiossarcoma/diagnóstico , Leiomiossarcoma/genética , Leiomiossarcoma/cirurgia , Metilação de DNA , Sarcoma/diagnóstico , Sarcoma/genética , Sarcoma/cirurgia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirurgia , Diferenciação CelularAssuntos
Astrocitoma , Neoplasias Encefálicas , Glioblastoma , Glioma , Humanos , Glioblastoma/diagnóstico , Glioblastoma/genética , Epigenoma , Glioma/genética , Astrocitoma/genética , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Isocitrato Desidrogenase/genética , Mutação , PrognósticoRESUMO
A 74-year-old woman was found to have a hepatic mass based on CT findings. She was diagnosed as having cecum cancer, and it was difficult to distinguish whether the hepatic mass was liver metastasis or biliary cystadenocarcinoma. We proceeded with the surgery for cecum cancer, and laparoscopic ileocecal resection with D3 lymph node dissection was performed. The histopathological diagnosis was mucinous adenocarcinoma, and the pathological stage was T3N2H1P0M1a, Stage IV. After the surgery, her CEA level was elevated, and we diagnosed the hepatic mass as a liver metastasis. A CapeOX plus bevacizumab regimen was administered but was discontinued for 2 courses due to the development of adverse effects and her decision. Gd-EOB-DTPA-enhanced MRI revealed a multilocular and lobulated mass, which was a low-intensity area in T1WI and high-intensity area in T2WI, and the mass had no significant contrast effects. These images were unspecific for liver metastasis of colorectal cancer, and we performed segmental 6 hepatectomy for diagnosis and curative surgery. A histopathological diagnosis of liver metastasis of cecum cancer was made. Here, we report a case of liver metastasis of colorectal cancer that was undifferentiated from biliary cystadenocarcinoma.
Assuntos
Neoplasias do Apêndice/patologia , Neoplasias dos Ductos Biliares/diagnóstico , Cistadenocarcinoma/diagnóstico , Neoplasias Hepáticas/secundário , Idoso , Neoplasias do Apêndice/tratamento farmacológico , Neoplasias do Apêndice/cirurgia , Neoplasias dos Ductos Biliares/patologia , Colectomia , Diagnóstico Diferencial , Feminino , Hepatectomia , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgiaRESUMO
Succinate dehydrogenase-deficient renal cell carcinoma (SDH-deficient RCC) is a newly introduced histological type of RCC, which is caused by loss of subunit genes of SDH. It is known to frequently demonstrate familial occurrence and be frequently associated with gastrointestinal stromal tumors and paraganglioma. To date, only 53 cases have been reported. Here, we present an additional case of SDH-deficient RCC occurring in a 40-year-old female. The tumor was histologically biphasic, consisting of tubular and solid architectures. The tumor cells possessed oval nuclei with small nucleoli, and an eosinophilic granular cytoplasm with occasional vacuoles. These cells completely lost the immunohistochemical expression of B subunit of SDH (SDHB). Consequently, the tumor was diagnosed as SDHB-deficient RCC. We identified a novel germ line mutation of the SDHB gene, and also confirmed a hemizygous deletion of the wild-type allele in the tumor cells. To define the pathological characteristics of SDH-deficient RCC, precise diagnosis and accumulation of more cases are required.
Assuntos
Carcinoma de Células Renais/genética , Neoplasias Renais/genética , Succinato Desidrogenase/deficiência , Adulto , Carcinoma de Células Renais/patologia , Feminino , Mutação em Linhagem Germinativa , Humanos , Neoplasias Renais/patologia , Succinato Desidrogenase/genéticaRESUMO
UNLABELLED: Epstein-Barr virus (EBV) is one of the major oncogenic viruses and is found in nearly 10% of gastric carcinomas. EBV is known to encode its own microRNAs (miRNAs); however, their roles have not been fully investigated. The present report is the largest series to comprehensively profile the expression of 44 known EBV miRNAs in tissue samples from patients with EBV-associated gastric carcinoma. Several miRNAs were highly expressed in EBV-associated gastric carcinoma, and in silico analysis revealed that the target genes of these EBV miRNAs had functions associated with cancer-related pathways, especially the regulation of apoptosis. Apoptosis was reduced in EBV-associated gastric carcinoma tissue samples, and gastric carcinoma cell lines infected with EBV exhibited downregulation of the proapoptotic protein Bid (the BH3-interacting domain death agonist), a member of the Bcl-2 family. The luciferase activity of the reporter vector containing the 3' untranslated region of BID was inhibited by an ebv-miR-BART4-5p mimic in gastric cancer cell lines. Transfection of an ebv-miR-BART4-5p mimic reduced Bid expression in EBV-negative cell lines, leading to reduced apoptosis under serum deprivation. The inhibition of ebv-miR-BART4-5p expression was associated with partial recovery of Bid levels in EBV-positive cell lines. The results demonstrated the antiapoptotic role of EBV miRNA via regulation of Bid expression in EBV-associated gastric carcinoma. These findings provide novel insights in the roles of EBV miRNAs in gastric carcinogenesis, which would be a potential therapeutic target. IMPORTANCE: This report is the largest series to comprehensively profile the expression of 44 known EBV miRNAs in clinical samples from EBV-associated gastric carcinoma patients. Of the EBV miRNAs, ebv-miR-BART4-5p plays an important role in gastric carcinogenesis via regulation of apoptosis.
Assuntos
Infecções por Vírus Epstein-Barr/genética , Infecções por Vírus Epstein-Barr/virologia , Herpesvirus Humano 4/genética , MicroRNAs/genética , RNA Viral/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/virologia , Idoso , Idoso de 80 Anos ou mais , Animais , Apoptose/genética , Proteína Agonista de Morte Celular de Domínio Interatuante com BH3/genética , Sequência de Bases , Carcinogênese/genética , Linhagem Celular Tumoral , Regulação para Baixo , Infecções por Vírus Epstein-Barr/etiologia , Feminino , Perfilação da Expressão Gênica , Herpesvirus Humano 4/patogenicidade , Humanos , Masculino , Camundongos , Camundongos SCID , Pessoa de Meia-Idade , Neoplasias Gástricas/etiologiaRESUMO
Adiponectin is a cytokine secreted by adipocytes, whose plasma levels are decreased in obesity. Adiponectin has insulin-sensitizing, antiatherogenic, and antidiabetogenic effects. It has been shown that adiponectin may also exert antineoplastic activity through suppression of tumor proliferation and neoangiogenesis and through induction of apoptosis. Recently, low adiponectin serum concentration has been found in obesity-related malignancies, including endometrial cancer. In addition, the expression of adiponectin receptors (AdipoR1 and AdipoR2) has been documented in several human cancer tissues, but the expression has previously not been assessed in human endometrial cancer tissues. In this study, we analyzed the immunohistochemical expression of AdipoR1 and AdipoR2 in a series of surgically resected human endometrioid adenocarcinoma tissues from a total of 141 cases. Decreased AdipoR1 or AdipoR2 expression was significantly associated with histological higher grade (P=0.0026 and 0.0004, respectively). Decreased expression of AdipoR1 was associated with myometrial invasion and lymph node metastasis of endometrioid adenocarcinoma (P=0.0039 and P=0.0069, respectively). AdipoR1 and AdipoR2 immunoexpression was significantly associated with the expression of the progesterone receptor, although it was not significantly correlated with the expression of the estrogen receptor, Ki-67 or p53. Our present study raises the possibility that decreased expression of adiponectin receptors is implicated in the development, invasion, and metastasis of human endometrioid adenocarcinoma. Our findings, moreover, indicate that adiponectin receptors could be considered as therapeutic targets for endometrioid adenocarcinoma. In adiponectin receptor-positive endometrioid adenocarcinoma, we think adiponectin-based anticancer therapy is useful; however, in histological high-grade endometrioid adenocarcinoma, in which the expression levels of adiponectin receptors are relatively low, adiponectin therapy supported by adiponectin receptor induction is needed.
Assuntos
Carcinoma Endometrioide/metabolismo , Neoplasias do Endométrio/metabolismo , Receptores de Adiponectina/biossíntese , Carcinoma Endometrioide/genética , Carcinoma Endometrioide/patologia , Distribuição de Qui-Quadrado , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Receptores de Adiponectina/genética , Estudos RetrospectivosRESUMO
BACKGROUND: Primary malignant melanoma of the lung (PML) is extremely rare. No precursor lesions of PML have been identified, and little is known about the genetic mutations associated with the disease. Typically, 15-20% of malignant melanomas possess NRAS gene mutations, but no cases of NRAS-mutated PML have been reported in the English literature. We present a case of PML involving an NRAS mutation. CASE PRESENTATION: Clinical summary A 74-year-old Japanese female presented with worsening dyspnea and was admitted to hospital. Computed tomography (CT) revealed a right lung (S10) mass and pleural dissemination. Cytology of the pleural effusion in the right lung was performed, and malignant melanoma or clear cell sarcoma was suspected. A dermatological examination and gallium scintigraphy were conducted to determine the primary tumor site, but no suspicious lesions, expect for the right lung mass, were found. After admission, CT showed complicating bilateral pneumonia, and an antibiotic drug was administered, but the pleural effusion got worse. About 2 weeks later, the patient died of respiratory failure and cardiac arrest. An autopsy was performed to determine the histological diagnosis. Autopsy findings A 26x15x20-mm black and pale yellow mass was found in the right lower lobe. Many disseminated nodules were found in the right lobe. The tumor had invaded the right diaphragm. Subcarinal lymph node metastasis was also detected. Immunohistochemically, the tumor cells exhibited positivity for S-100 and HMB45 staining. The patient was diagnosed with malignant melanoma. Sanger sequencing of the tumor detected an NRAS mutation. CONCLUSIONS: We found an NRAS D54N mutation in PML, which has not been reported previously anywhere in the world. Previous reports indicated that most cases of PML can be classified into the triple-wild-type, but BRAF mutation status was only analyzed in a few cases. We should analyze the mutation patterns of PML to determine whether any subtypes other than the triple-wild-type exist. PML might be a form of de novo cancer.
Assuntos
GTP Fosfo-Hidrolases/genética , Neoplasias Pulmonares/genética , Melanoma/genética , Proteínas de Membrana/genética , Mutação/genética , Proteínas Proto-Oncogênicas B-raf/genética , Idoso , Feminino , Humanos , Melanoma/diagnóstico , Melanoma/patologiaRESUMO
Chronic tonsillitis has been attracted attention as a source of abnormal immune responses and a possible trigger of autoimmune diseases such as IgA nephritis, IgA vasculitis, palmoplantar pustulosis, psoriasis, rheumatoid arthritis, Behçet's disease, and myositis. Here we present the first report of anti-signal recognition particle antibody-associated necrotizing myopathy (anti-SRP myopathy) with IgA nephropathy and chronic tonsillitis in which the therapeutic response to intravenous immunoglobulin (IVIG) treatment was dramatically improved after tonsillectomy and accompanied by a rapid increase in ΔIgG, defined as the change in serum IgG levels 2 weeks after the start of IVIG treatment relative to pre-treatment levels. Moreover, serum anti-SRP antibody titers became undetectable after tonsillectomy even though the resected tonsils did not produce anti-SRP antibodies. Tonsillectomy should be considered when chronic tonsillitis is observed in patients with autoimmune diseases showing poor response to treatment, including anti-SRP myopathy.
Assuntos
Glomerulonefrite por IGA/cirurgia , Doenças Musculares/cirurgia , Partícula de Reconhecimento de Sinal/imunologia , Tonsilectomia , Tonsilite/cirurgia , Doença Crônica , Feminino , Glomerulonefrite por IGA/tratamento farmacológico , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Pessoa de Meia-Idade , Doenças Musculares/tratamento farmacológico , Tonsilite/tratamento farmacológicoRESUMO
Background: Neuroendocrine tumors (NETs) are rare, but their worldwide incidence is gradually increasing. NETs are generally heterogeneous; however, in rare cases, they have been shown to change their phenotype (i.e., nonfunctional to functional or one functional phenotype to the addition of another functional phenotype). Here, we present two cases of liver metastatic NETs with phenotype transformation at the advanced stage that led to life-threatening events. Case presentation: A 73-year-old woman had a small intestinal nonfunctional NET with liver metastasis. After uncontrollable liver metastasis at the advanced stage, she developed duodenal perforation with hypergastremia. The patient was treated with octreotide and proton pump inhibitors and underwent endoscopic closure for duodenal perforation, but her general condition gradually deteriorated, and she died 2 weeks after duodenal perforation. Another patient, a 50-year-old man, had a functional NET (gastrinoma) with liver metastasis and duodenal ulcer. After uncontrollable liver metastasis at the advanced stage, he developed hypoglycemia. Although octoreotide and diazoxide were administrated for hyperalimentation, his hypoglycemia was uncontrollable, and he died after 4 months owing to general deterioration. Conclusion: The present cases show that advanced NETs with treatment-uncontrollable liver metastasis can transform their phenotype, specifically from a nonfunctional NET into a functional NET, and from one functional NET into the addition of another functional NET. These experiences suggest that the presence of treatment-resistant liver metastasis might be a hallmark of the potential to gain novel functions.
Assuntos
Neoplasias Ovarianas , Proteína FUS de Ligação a RNA , Tumores do Estroma Gonadal e dos Cordões Sexuais , Neoplasias Testiculares , Feminino , Humanos , Biomarcadores Tumorais/genética , Proteínas de Fusão Oncogênica/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Proteína FUS de Ligação a RNA/genética , Tumores do Estroma Gonadal e dos Cordões Sexuais/genética , Tumores do Estroma Gonadal e dos Cordões Sexuais/patologia , Neoplasias Testiculares/genética , Neoplasias Testiculares/patologia , IdosoRESUMO
AIMS: Hidradenoma papilliferum (HP) is a benign vulvar neoplasm that arises from anogenital mammary-like glands, and its morphology is similar to mammary intraductal papilloma. The aim of this study was to investigate oncogenic mutations involved in the tumourigenesis of HP. We focused specifically on PIK3CA and AKT1 mutations, which are both reported to be detected in 33% of mammary intraductal papillomas. METHODS: In total, seven HP cases were analysed. Clinicopathological analyses and immunohistochemistry for oestrogen receptor, p63, smooth muscle actin (SMA), p53 and ß-catenin were performed. Furthermore, PIK3CA, AKT1, BRAF and KRAS hot spot mutations were examined by Sanger sequencing. RESULTS: Morphologically, all HPs had a papillary and tubular architecture with a biphasic pattern of epithelial and myoepithelial cells. Immunohistochemistry revealed that oestrogen receptor expression was restricted to epithelial cells, whereas p63 and SMA were exclusively expressed in myoepithelial cells. The patterns of p53 and ß-catenin immunostaining suggested wild-type genotypes. Direct sequencing revealed the presence of somatic PIK3CA mutations (Ex9. c.1633G>A, p.E545K and Ex20. c.3140A>G, p.H1047R) in two of the HPs and an AKT1 (c.49G>A, p.E17K) mutation in one. BRAF and KRAS mutations were not found in any of the HP cases. CONCLUSIONS: PIK3CA and AKT1 are frequently mutated in HP tumours (29% and 14%, respectively). PIK3CA/AKT1 pathway alterations in HP further support the hypothesis that HP is the vulvar (anogenital mammary-like gland) analogue of breast intraductal papilloma.
Assuntos
Acrospiroma/genética , Biomarcadores Tumorais/genética , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Neoplasias Cutâneas/genética , Neoplasias das Glândulas Sudoríparas/genética , Neoplasias Vulvares/genética , Acrospiroma/diagnóstico , Acrospiroma/patologia , Adulto , Biomarcadores Tumorais/metabolismo , Transformação Celular Neoplásica , Classe I de Fosfatidilinositol 3-Quinases , Feminino , Genótipo , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Mutação , Fenótipo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Análise de Sequência de DNA , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologia , Neoplasias das Glândulas Sudoríparas/diagnóstico , Neoplasias das Glândulas Sudoríparas/patologia , Neoplasias Vulvares/diagnóstico , Neoplasias Vulvares/patologiaRESUMO
A 45-year-old woman with dyspnea and appetite and weight loss was admitted to our hospital. Computed tomography (CT) revealed a right hypovascular renal tumor with tumor thrombus in the inferior vena cava and metastases in the liver, stomach, and left kidney. The renal tumor was diagnosed as a mucinous tubular and spindle cell carcinoma (MTSCC) by pathological examination of a percutaneous needle biopsy specimen. She was treated with temsirolimus (25 mg per week). Five weeks after initiation of this treatment, her liver metastases had clearly decreased in size and her appetite had been restored. However, progressive disease was diagnosed by CT scan revealing expansion of tumor thrombus after 7 weeks, prompting a switch in treatment to axitinib. Approximately 6 months after the diagnosis, she died of cancer. MTSCC is considered to have relative good prognosis, however, many cases with poor prognoses have been reported recently. Our experience with this patient suggests that temsirolimus may be effective treatment for metastatic MTSCC.
Assuntos
Endoscopia , Neoplasias de Cabeça e Pescoço/cirurgia , Linfangioma Cístico/cirurgia , Adulto , Feminino , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Linfangioma Cístico/diagnóstico por imagem , Linfangioma Cístico/patologia , Imageamento por Ressonância Magnética , Tomografia Computadorizada por Raios XRESUMO
SOX9 is a member of the SOX [Sry-related high-mobility group (HMG) box] family and is required for the development and differentiation of multiple cell lineages. To clarify the significance of SOX9 in gastric carcinoma (GC), immunohistochemical expression of SOX9 and the CpG island methylation status of SOX9 were evaluated and compared with clinicopathological factors including overall survival. SOX9 expression was immunohistochemically evaluated in 382 GC tumors and the methylation status was examined in 121 GC tumors. SOX9 expression and its methylation status in six GC cell lines, their Epstein-Barr virus (EBV)-infected cell lines, and two EBV-associated GC cell lines was also examined. The SOX9 expression increased from non-neoplastic mucosa to early cancer. High expression of SOX9 was seen in 212 cases (56%). SOX9 expression was inversely related to advanced tumor stage, vessel infiltration, nodal metastasis, and EBV infection. Fifty-eight (48%) of 121 GC tumors had a methylated promoter in GC and the methylated status was related to low expression. The expression and methylation status were not related to prognosis. Three of six cell lines had increased methylation through EBV infection and decreased SOX9 expression. Upregulation of SOX9 is related to GC development. Downregulation by promoter methylation is related to GC progression and EBV infection. SOX9 is closely related to GC carcinogenesis and EBV-associated GC carcinogenesis.