RESUMO
BACKGROUND: In familial adenomatous polyposis (FAP) patients, fundic gland polyps (FGPs) have been considered a risk factor for gastric neoplasms. We speculated that FGPs in FAP patients spread directionally from the greater to the lesser curvature of the gastric body and investigated the relationship between the distribution of FGPs and gastric neoplasm development. METHODS: We extracted 195 FAP patients from two institutions and reviewed their medical records. Gastric polyposis was classified based on the FGP distribution (P0, no FGPs; P1, localized in the fundus or greater curvature of the gastric body; P2, spreading to the anterior or posterior wall; P3, involving the proximal half of the lesser curvature; and P4, spreading from P3 to the anal side of the lesser curvature). RESULTS: The 195 eligible patients were divided into the neoplasm group (n = 54, 28%) and the non-neoplasm group (n = 141, 72%). Overall, 24% of the patients were Helicobacter pylori (H. pylori)-positive. In the FGP distribution, the rate of patients with gastric neoplasm tended to increase significantly with each step towards an increasingly wide distribution from P0 to P4 in H. pylori-negative patients, but not in H. pylori-positive ones. In addition, in H. pylori-negative patients, the likelihood of neoplasm increased consistently from P0 to P4, with the highest odds ratio (95% confidence interval) at P4 of 14.1 (2.5-154.4). Furthermore, multivariate analysis showed P4 and Spigelman stage ≥III were significantly associated with gastric neoplasm development. CONCLUSION: FGP distribution was correlated with gastric neoplasm development in FAP patients.
RESUMO
A 67-year-old man underwent renal transplantation in his twenties. He developed refractory pleural effusion, with many large lymphocytes with severe atypia and mitosis in the effusion, indicating malignant lymphoma. He finally died of respiratory failure. An autopsy revealed atypical lymphocytes positive for CD3, CD4, and CD30 and negative for CD8, CD20, PAX5, human herpesvirus (HHV) 8, and Epstein-Barr virus-encoded small RNAs by immunohistochemistry and in situ hybridization. Atypical lymphocytes also had T-cell receptor gene rearrangements Jß2, Jγ2, and Jδ1 and chromosomal aberrations der(8)t(1;8)(q21;p21), add(13)(q12), add(14)(q32), and add(16)(q12-13). A few atypical lymphocytes were present at other sites. We finally diagnosed this case as monomorphic T-cell post-transplant lymphoproliferative disorder with features of HHV8-negative primary effusion lymphoma. A literature review only identified six cases (four HHV8-negative, two HHV8-positive) of effusion lymphoma of T-cell type, including the present case. Interestingly, about half of HHV8-negative and HHV8-positive cases had a history of renal transplantation in their twenties. All cases showed tumor CD30 expression, whereas CD4 and CD8 expressions were inconsistent. These findings indicated that this lymphoma may be associated with post-transplant lymphoproliferative disorder by renal transplantation at a young age, although further cases need to be analyzed.
Assuntos
Autopsia , Herpesvirus Humano 8 , Transplante de Rim , Linfoma de Efusão Primária , Humanos , Masculino , Idoso , Linfoma de Efusão Primária/patologia , Linfoma de Efusão Primária/virologia , Transplante de Rim/efeitos adversos , Herpesvirus Humano 8/isolamento & purificação , Herpesvirus Humano 8/genética , Linfócitos T/imunologia , Transtornos Linfoproliferativos/patologia , Transtornos Linfoproliferativos/virologia , Transtornos Linfoproliferativos/etiologia , Evolução FatalRESUMO
Familial adenomatous polyposis (FAP) patients develop various life-threatening extracolonic comorbidities that appear individually or within a family. This diversity can be explained by the localization of the adenomatous polyposis coli (APC) variant, but few reports provide definitive findings about genotype-phenotype correlations. Therefore, we investigated FAP patients and the association between the severe phenotypes and APC variants. Of 247 FAP patients, 126 patients from 85 families identified to have APC germline variant sites were extracted. These sites were divided into six groups (Regions A to F), and the frequency of severe comorbidities was compared among the patient phenotypes. Of the 126 patients, the proportions of patients with desmoid tumor stage ≥III, number of FGPs ≥1000, multiple gastric neoplasms, gastric neoplasm with high-grade dysplasia, and Spigelman stage ≥III were 3%, 16%, 21%, 12%, and 41%, respectively, while the corresponding rates were 30%, 50%, 70%, 50%, and 80% in patients with Region E (codons 1398-1580) variants. These latter rates were significantly higher than those for patients with variants in other regions. Moreover, the proportion of patients with all three indicators (desmoid tumor stage ≥III, number of FGPs ≥1000, and Spigelman stage ≥III) was 20% for those with variants in Region E and 0% for those with variants in other regions. Variants in Region E indicate aggressive phenotypes, and more intensive management is required.
Assuntos
Polipose Adenomatosa do Colo , Fibromatose Agressiva , Neoplasias Gástricas , Humanos , Genes APC , Fibromatose Agressiva/genética , Genótipo , Polipose Adenomatosa do Colo/genética , Polipose Adenomatosa do Colo/patologia , Fenótipo , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Estudos de Associação Genética , MutaçãoRESUMO
BACKGROUND: Underwater endoscopic mucosal resection (UEMR) has been developed as an effective endoscopic intervention for colon, rectum, and duodenum neoplasms. However, there are no comprehensive reports regarding the stomach, and its safety and efficacy are unknown. We aimed to examine the feasibility of UEMR for gastric neoplasms in patients with familial adenomatous polyposis (FAP). METHODS: We retrospectively extracted data of patients with FAP who underwent endoscopic resection (ER) for gastric neoplasms at Osaka International Cancer Institute from February 2009 to December 2018. Elevated gastric neoplasms of ≤ 20 mm in diameter were extracted, and conventional endoscopic mucosal resection (CEMR) and UEMR were compared. Furthermore, outcomes after ER until March 2020 were examined. RESULTS: 91 endoscopically resected gastric neoplasms were extracted from 31 patients with 26 pedigrees, and 12 neoplasms underwent CEMR and 25 neoplasms underwent UEMR was compared. The procedure time was shorter for UEMR than for CEMR. There was no significant difference between en bloc resection and R0 resection rates by EMR methods. CEMR and UEMR showed postoperative hemorrhage rates of 8% and 0%, respectively. Residual/local recurrent neoplasms were identified in four lesions (4%), but additional endoscopic intervention (three UEMR and one cauterization) resulted in a local cure. CONCLUSION: UEMR was feasible in gastric neoplasms of FAP patients, especially in elevated lesions and those of ≤ 20 mm in diameter.
Assuntos
Polipose Adenomatosa do Colo , Ressecção Endoscópica de Mucosa , Neoplasias Gástricas , Humanos , Colonoscopia/métodos , Ressecção Endoscópica de Mucosa/métodos , Neoplasias Gástricas/cirurgia , Estudos Retrospectivos , Estudos de Viabilidade , Polipose Adenomatosa do Colo/cirurgiaRESUMO
Adrenal incidentaloma is a clinically unapparent adrenal mass more than one cm in diameter detected during imaging performed not for adrenal disease. A 34-year-old man was evaluated for AI with a diameter of 3.5 cm in the left adrenal. He was obese with body mass index of 33,9. Blood pressure was 110-120/90 mmHg. The general laboratory tests were unremarkable. An adrenal hormone screening set revealed that ACTH was 6.9 pg/mL, cortisol 14.9 µg/dL, renin activity 0.9 ng/mL/h, aldosterone 79.4 pg/mL, dehydroepiandrosterone-sulfate (DHEA-S) measured on two occasions 5,217 ng/mL and 6,477 ng/mL (gender- and age-adjusted reference values, 1,060-4,640 ng/mL). The levels of metanephrine and normetanephrine were normal. The tumor was thought to produce solely DHEA-S. The excised left adrenal tissue contained a tumor with a diameter of 26 mm and neighboring adrenal tissue. The tumor consisted mostly of acidophil cells without necrosis, capsular or vascular invasion, and mitosis. Immunohistochemical study revealed followings: the cells of the tumors were stained positive for 3ß-hydroxysteroid dehydrogenase, and 17α-hydroxylase, and 11ß-hydroxylase, weakly positive for DHEA sulphotransferase, and negative for aldosterone synthetase. The atrophy of neighboring tissue was presumably caused by excess cortisol production. Four months after surgery, the cortisol level was 11.2 µg/dL and DHEA-S level 1,462 ng/mL. The tumor is considered to be a cortisol-producing adenoma with modestly excessive DHEA-S production rather than isolated DHEA-S-producing adenoma. Immunohistochemical study of steroidogenic enzymes is a valuable addition to blood hormone measurement to clarify steroid production profile.
Assuntos
Adenoma , Neoplasias das Glândulas Suprarrenais , Masculino , Humanos , Adulto , Sulfato de Desidroepiandrosterona , Hidrocortisona , Aldosterona , Neoplasias das Glândulas Suprarrenais/diagnóstico , Adenoma/patologia , Oxigenases de Função Mista , Sulfatos , DesidroepiandrosteronaRESUMO
AIMS: Follicular lymphoma (FL), comprising a minor subset of primary thyroid lymphomas, is divided into two groups based on Bcl-2 expression and IGH-BCL2 translocation. The clinicopathological features exhibited by Bcl-2-negative IGH-BCL2 translocation-negative FL of the thyroid (Bcl-2- /IGH-BCL2- tFL) are different from those of conventional FL; however, its lymphomagenesis remains unclear. Here, we collected samples from seven patients with Bcl-2- /IGH-BCL2- tFL to investigate their epigenetic and genetic aberrations. METHODS AND RESULTS: The immunohistochemical profiles of epigenetic modifiers and the methylation status of histones were examined, including EZH2, MLL2/KMT2D, CBP/CREBBP, EP300, H3K27me3 and H3K4me3, in Bcl-2- /IGH-BCL2- tFL and Bcl-2-positive IGH-BCL2 translocation-positive FL of the thyroid (Bcl-2+ /IGH-BCL2+ tFL). Most Bcl-2- /IGH-BCL2- tFLs retained the positivity of epigenetic modifiers and lower expression of H3K27me3, although Bcl-2+ /IGH-BCL2+ tFLs exhibited aberrant immunohistochemical patterns of EZH2 and CBP/CREBBP and overexpression of H3K27me3. Samples from seven cases were further analysed using targeted sequencing, focusing on the exons of 409 key tumour suppressor genes and oncogenes. Bcl-2- /IGH-BCL2- tFLs do not have pathogenic mutations of epigenetic modifiers, such as EZH2, MLL2/KMT2D, MLL3/KMT2C, EP300 and ARID1A, which have been reported in FLs in the literature, whereas Bcl-2+ /IGH-BCL2+ tFLs are probably pathogenic/pathogenic missense mutations or frameshift mutations of these genes. Additionally, novel mutations in TET2 and EP400 were detected in Bcl-2- /IGH-BCL2- tFLs. CONCLUSIONS: Different genetic and epigenetic abnormalities might be involved in the oncogenesis of Bcl-2- /IGH-BCL2- tFLs from Bcl-2+ /IGH-BCL2+ tFLs and other FLs.
Assuntos
Regulação Neoplásica da Expressão Gênica/genética , Linfoma Folicular/genética , Linfoma Folicular/patologia , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , Idoso , Idoso de 80 Anos ou mais , Epigênese Genética , Feminino , Genes de Cadeia Pesada de Imunoglobulina , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-bcl-2/genética , Translocação GenéticaRESUMO
BACKGROUND AND AIMS: Gastric neoplasms in patients with familial adenomatous polyposis (FAP) occur at a high rate and can cause death. The endoscopic findings of gastric neoplasms in these patients are characteristic but not well recognized. To identify the relevant characteristics to enable early detection, we retrospectively investigated endoscopic findings of gastric neoplasms in patients with FAP and then compared the clinical, histopathologic, and genetic features among subgroups. METHODS: Of 234 patients with 171 pedigrees at 2 institutes, 56 cases (24%, 133 gastric neoplasms) with 44 pedigrees were examined. Immunostaining was performed for histopathologic evaluation by 1 blinded pathologist. According to the endoscopic findings, gastric neoplasms were divided into 4 types based on location (L: antrum and pylorus, UM: the rest of the stomach) and color (W: white, T: translucent, R: reddish) and their clinicopathologic features examined. RESULTS: Of the cases, 93% could be classified into a single type. Among histologic phenotypes, high-grade dysplasia was present in 26% (type L), 41% (type UM-W), 0% (type UM-T), and 22% (type UM-R). The immunologic phenotype comprised the gastric type in 69% (93% in Type UM) and the intestinal phenotype, including the mixed type, in 31% (61% in type L). Moreover, 96% of patients had concurrent duodenal neoplasms. Adenomatous polyposis coli gene status was identified in 93% of patients; the pathogenic variant was detected in 98% but did not influence any endoscopic features. CONCLUSIONS: Gastric neoplasms in patients with FAP were stratified into 4 types according to their endoscopic findings. The endoscopic phenotype was related to the histopathologic phenotype but not to germline variants.
Assuntos
Polipose Adenomatosa do Colo , Neoplasias Duodenais , Neoplasias Gástricas , Polipose Adenomatosa do Colo/complicações , Polipose Adenomatosa do Colo/genética , Endoscopia , Humanos , Estudos RetrospectivosRESUMO
ABSTRACT: Adenoid cystic carcinoma (ACC) is an infiltrating carcinoma composed of 2 cell types, myoepithelial and ductoglandular epithelial cells. Although approximately 70% of ACC exhibit translocations of the MYB proto-oncogene or MYB proto-oncogene like 1 (MYBL1), expression of MYB is known to be limited in myoepithelial cells. We investigated the histopathologic and genetic characteristics of ACC in 6 primary cutaneous cases. Histopathologically, 3 cases (50%) exhibited well-demarcated nodules composed of large nests, easily misdiagnosed as polymorphous sweat gland carcinoma. Two cases (33%) harbored large cystic structures resembling spiradenoma, hidradenoma, and digital papillary adenocarcinoma. A papillary pattern was focally observed in 2 cases (33%). A melting phenomenon within the myxoid stroma was seen in one case (17%). Fluorescence in situ hybridization (FISH) revealed MYB break-apart in 3 cases (50%). A combined FISH and immunohistochemical method revealed MYB break-apart signals in both p63-positive myoepithelial and p63-negative ductoglandular epithelial cells, suggesting that both cell types constitute elements of the tumor in ACC. Moreover, we established a well-circumscribed variant of ACC and proposed 3 new patterns of cystic, papillary, and melting in addition to the 3 patterns of cribriform, tubular, and solid growth.
Assuntos
Biomarcadores Tumorais/genética , Carcinoma Adenoide Cístico/genética , Carcinoma Adenoide Cístico/metabolismo , Proteínas Proto-Oncogênicas c-myb/genética , Neoplasias das Glândulas Sudoríparas/genética , Neoplasias das Glândulas Sudoríparas/patologia , Translocação Genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Carcinoma Adenoide Cístico/química , Feminino , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Japão , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Proto-Oncogene Mas , Neoplasias das Glândulas Sudoríparas/química , Fatores de Transcrição/análise , Proteínas Supressoras de Tumor/análiseRESUMO
Lymphoepithelial carcinoma (LEC) shows characteristic histology of nesting growth of tumor cells with unclear differentiation against the lymphoid stroma background. Although rare in salivary glands, it has previously been recognized as a type of undifferentiated carcinoma but is currently clearly defined as an independent disease separate from undifferentiated carcinoma. We report a case of LEC that developed in the parotid gland and was immunohistochemically positive for p16, which suggested the causative involvement of human papillomavirus (HPV). The patient was a 38-year-old Japanese male aware of mass formation in the left parotid area for 8 years. Parotidectomy was performed and there have been no signs of recurrence or metastasis for 18 month post-operation. The tumor was histologically typical except for Epstein-Barr virus (EBV)-encoded small RNA (EBER)-negative in situ hybridization (ISH), but p16-positivity by immunohistochemistry, and also frequent contact with extended and expanded pre-existing ductal structures. Although usually strongly associated with EBV infection, the tumor could be regarded to have eventually reached completion as a LEC lesion associated with HPV infection possibly through the pathway shared with squamous cell carcinoma. EBER-ISH remains the most promising index for confirming diagnosis of LEC, but EBV-negative result alone should not prevent diagnosis of LEC.
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Carcinoma de Células Escamosas , Infecções por Vírus Epstein-Barr , Adulto , Herpesvirus Humano 4/genética , Humanos , Hibridização In Situ , Masculino , Glândula Parótida/diagnóstico por imagem , Glândula Parótida/cirurgiaRESUMO
Sclerosing mucoepidermoid carcinoma (SMC) is described as a "sclerosing variant" of mucoepidermoid carcinoma, and it is characterized by dense fibrosis and sclerosis of the stroma. SMC with eosinophilia (SMCE) is another and more rare subtype characterized by eosinophilia in addition to the sclerotic stroma common to SMC. However, unlike SMC, SMCE is not listed in the current 4th edition of WHO classification. Here, we describe three cases: one SMC in the parotid gland, one SMCE in the submandibular gland and one SMCE in the minor salivary gland of the oral cavity. The patients included a 71-year-old Japanese male, a 74-year-old Japanese female, and an 81-year-old Japanese female. They each complained of mass formation and underwent surgical resection. Histologically, the tumors mainly consisted of squamous cells with scarce keratinization that formed irregular large and small nests along with cystic structures containing mucous cells against the background of sclerotic stroma. One oral SMCE showed fine nesting and trabecular invasion. The two SMCEs included dense aggregates of eosinophils as well as more prominent lymphoid infiltration. Fluorescence in situ hybridization for MAML2 confirmed split signals in SMC, but not in SMCE.
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Carcinoma Mucoepidermoide/diagnóstico , Eosinofilia/complicações , Neoplasias das Glândulas Salivares/diagnóstico , Esclerose , Idoso , Idoso de 80 Anos ou mais , Carcinoma Mucoepidermoide/complicações , Carcinoma Mucoepidermoide/patologia , Carcinoma Mucoepidermoide/cirurgia , Feminino , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Masculino , Neoplasias das Glândulas Salivares/complicações , Neoplasias das Glândulas Salivares/patologia , Neoplasias das Glândulas Salivares/cirurgia , TransativadoresRESUMO
Secretory carcinoma of the salivary glands is a relatively new disease concept, and is characterized by "morphological resemblance to mammary secretory carcinoma and ETV6-NTRK3 gene fusion." Herein we describe a confusing case and briefly discuss practical diagnostic problems. The patient was a 71-year-old Japanese man who had a tumor consistent with secretory carcinoma at the microscopic and immunohistochemical levels. Immunohistochemically, EMA and S100 protein were noted to be positive along with various cytokeratins as well as mammaglobin and pSTAT5. Moreover, vimentin was focally positive. Smooth muscle actin, p63, p40, and androgen receptor were negative. However, a search using fluorescence in situ hybridization did not reveal a definite split signal for the ETV6 gene. It is presumed that confirming the diagnosis of secretory carcinoma without genetic retrieval will be accepted as a diagnostic method, and we hope that worldwide general recognition may earlier reach "gradual acceptance."
Assuntos
Biomarcadores Tumorais/análise , Carcinoma Secretor Análogo ao Mamário/diagnóstico , Neoplasias Parotídeas/diagnóstico , Proteínas Proto-Oncogênicas c-ets/análise , Proteínas Repressoras/análise , Idoso , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Queratinas/análise , Queratinas/genética , Masculino , Carcinoma Secretor Análogo ao Mamário/metabolismo , Carcinoma Secretor Análogo ao Mamário/patologia , Neoplasias Parotídeas/metabolismo , Neoplasias Parotídeas/patologia , Proteínas S100/análise , Proteínas S100/genética , Fator de Transcrição STAT5/análise , Fator de Transcrição STAT5/genética , Variante 6 da Proteína do Fator de Translocação ETSRESUMO
Secretory carcinoma (SC) of the salivary gland is a relatively newly described disease, separate from acinic cell carcinoma (ACC), which frequently displays ETV6-NTRK3 gene fusion. However, the differences between SC and ACC remain unclear. Here, histological reevaluation of 12 formerly diagnosed ACC cases was performed, which yielded a new diagnosis of SC in four cases due to a lack of obvious acinar-like cells. Immunohistochemically, phosphorylated signal transducer and activator of transcription 5 (p-STAT5) was expressed in SC but not in ACC, whereas discovered on GIST-1 (DOG1) was expressed in ACC but not in SC. Molecular analysis was possible in three SC cases, of which two showed the ETV6-NTRK3 fusion transcript on reverse-transcription polymerase chain reaction, as well as breaks in the ETV6 gene on fluorescence in situ hybridization. However, the remaining SC cases did not show this fusion transcript. Recently, several reports have suggested that SC might not be adequately diagnosed if the focus is placed solely on the ETV6-NTRK3 fusion gene due to genetic diversity. In this regard, immunohistochemistry of p-STAT5 and DOG1 is expected to be a useful alternative diagnostic tool to discriminate SC from ACC.
Assuntos
Biomarcadores Tumorais/análise , Carcinoma de Células Acinares/diagnóstico , Imuno-Histoquímica , Proteínas de Fusão Oncogênica/genética , Neoplasias Parotídeas/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anoctamina-1/análise , Anoctamina-1/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Acinares/genética , Carcinoma de Células Acinares/patologia , Erros de Diagnóstico , Feminino , Heterogeneidade Genética , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/análise , Proteínas de Neoplasias/metabolismo , Glândula Parótida/patologia , Neoplasias Parotídeas/genética , Neoplasias Parotídeas/patologia , Fator de Transcrição STAT5/análise , Fator de Transcrição STAT5/metabolismo , Adulto JovemRESUMO
Localized thyroid diffuse large B-cell lymphoma stage with stage IE according to the Ann Arbor clinical staging system was diagnosed in a 75-year-old woman. The patient was treated with three courses of chemotherapy followed by radiotherapy. Positron emission tomography/computed tomography (PET-CT) using 2-deoxy-2-[F-18] fluoro-D-glucose (FDG) PET-CT was performed two months after chemotherapy showed increased FDG uptakes in systemic lymph nodes and gluteal muscles. Standardized uptake value in the region of interest ranged from 7.1-26.1. Since it seemed too sudden to be a recurrence, a repeat biopsy was performed from inguinal lymph nodes. Histology revealed that there were no malignant lymphoma cells but noncaseous epithelioid granuloma with multinucleated giant cells. Taken together with the findings of bilateral hilar mediastinal lymphadenopathy and elevated serum angiotensin converting enzyme (ACE) levels (32.4 U/l), sarcoidosis secondary to lymphoma was diagnosed in this patient. Subsequently, both FDG uptake and serum ACE gradually improved without any therapy. The present case strongly suggests the importance of a re-biopsy when the clinical course of recurrence is unusual.
Assuntos
Linfoma Difuso de Grandes Células B , Sarcoidose , Idoso , Quimiorradioterapia , Feminino , Fluordesoxiglucose F18 , Humanos , Linfoma Difuso de Grandes Células B/terapia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons , Glândula TireoideRESUMO
BACKGROUND: Lugol chromoendoscopy has been conventionally used for the detection and delineation of esophageal squamous cell carcinoma (SCC). However, the boundaries of some lesions are unclear even with Lugol chromoendoscopy, and there is a risk of residual lesions or over-excision. This study aimed to evaluate the utility of narrow-band imaging (NBI) for the delineation of esophageal SCC in endoscopic resection. METHODS: Among 367 esophageal SCCs endoscopically resected between January and December 2019 at our institute, this retrospective study included consecutive lesions, which were first marked with NBI, followed by Lugol chromoendoscopy. The proportion of residual cancer, which was defined as histologically proven cancer confirmed adjacent to the scar within 1 year after endoscopic resection, was evaluated. To evaluate whether the marks added by Lugol chromoendoscopy after NBI marking were more reliable, we evaluated the presence of cancer in the iodine-unstained area outside the NBI-determined marks, i.e., the cancerous area missed by NBI. The presence of cancer in the iodine-stained areas inside the NBI-determined marks, i.e., the cancerous area missed by Lugol, was also evaluated. These were compared to assess the risk of residual cancer in endoscopic resection with NBI and Lugol chromoendoscopy. RESULTS: Among 304 lesions, 2 (0.7%) residual cancers were detected. The cancerous area missed by NBI and the cancerous area missed by Lugol were identified in 18 (6%) and 43 (14%) lesions, respectively (P = 0.001). CONCLUSIONS: NBI might be acceptable for delineating the extent of esophageal SCCs that are difficult to delineate with Lugol chromoendoscopy.
Assuntos
Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Carcinoma de Células Escamosas/patologia , Corantes , Neoplasias Esofágicas/patologia , Esofagoscopia/métodos , Humanos , Estudos RetrospectivosRESUMO
BACKGROUND AND AIM: The true incidence of incomplete muscularis mucosa resection with cold snare polypectomy (CSP) is unknown. We examined the incidence of incomplete muscularis mucosa resection both with and without cold snare defect protrusion (CSDP). METHODS: We prospectively enrolled patients undergoing polypectomy for 4 to 9mm nonpedunculated polyps. We evaluated the presence of CSDP immediately following CSP and biopsied the CSDP or the center of the mucosal defect without CSDP. The presence of the muscularis mucosa and any residual polyp in the biopsies was evaluated histologically. The primary outcome was the incidence of incomplete mucosal layer resection defined as the presence of muscularis mucosa or residual polyp in the biopsies. RESULTS: From August 2017 to October 2018, 188 patients were screened, and 357 polyps were included. CSDP was detected in 122/355 (34%) evaluated mucosal defects. Excluding five lesions requiring hemostasis immediately following CSP, 352 mucosal defects were biopsied. After excluding 102 biopsies containing normal mucosa, we evaluated 250 biopsies. The overall incidence of incomplete mucosal layer resection was 63% (159/250), 76% (68/90) with CSDP and 57% (91/159) without CSDP (P < 0.01). Both univariate and multivariate analyses showed that size (≥ 6 mm), resection time (≥ 5 s), and serrated lesions were risk factors for CSDP. CONCLUSIONS: Cold snare defect protrusion (CSDP), which was present with 36%, was a good indicator for incomplete mucosal layer resection. Even in nonCSDP polypectomies, 57% of the mucosal layer was not removed completely. Thus, CSP should be used for intra-epithelial lesions only, and careful pretreatment evaluation is recommended.
Assuntos
Procedimentos Cirúrgicos do Sistema Digestório/métodos , Mucosa Gástrica/cirurgia , Pólipos Intestinais/cirurgia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
Aim: We aimed to improve the success rate of NGS (next-generation sequencing) analysis through improved strategies of lung cancer sampling. Materials & methods: The improvement strategies are as follows. Surgically resected specimens were preferentially submitted in cooperation with pathologists and surgeons. In bronchoscopic samples, the size of the sample collection device and the number of samples collected was increased. Results: The strategies increased the success rate of NGS analysis of DNA from 69.3 to 91.1%, and that of RNA from 64.6 to 90.0%. Discussion: The introduction of strategies aimed at improving the success of NGS analysis resulted in an improvement in the success rate and brought us closer to the delivery of effective precision medicine in cancer therapy.
Assuntos
Sequenciamento de Nucleotídeos em Larga Escala/métodos , Neoplasias Pulmonares/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , DNA/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medicina de Precisão , Estudos ProspectivosRESUMO
Objectives: To assess the clinicopathologic features of Multicentric Castleman disease (MCD) patients in Japan.Methods: We assessed baseline data for 342 Japanese MCD patients with a biopsy-proven diagnosis, enrolled in a prospective, observational study for tocilizumab treatment.Results: Of 342 patients, 86.0% had plasma-cell type. None had a family history of MCD. Median disease duration of MCD was 3.7 years. Mean body weight and body mass index tended to be lower than those in the general Japanese population. The most common clinical presentations besides lymphadenopathy included fatigue (61.7%), pulmonary involvement (42.7%), and splenomegaly (41.8%). Secondary amyloidosis was reported in 34 patients (9.9%). Laboratory abnormalities included decreased hemoglobin and albumin, and increased acute-phase proteins, serum immunoglobulins, and interleukin-6 (IL-6). IL-6 levels among the MCD patients tested in this study were correlated with levels of albumin, hemoglobin, triglyceride, total cholesterol, C-reactive protein, fibrinogen and immunoglobulin G (Spearman's correlation coefficient, |r| = 0.28-0.59).Conclusion: The clinical features and laboratory abnormalities are similar to those previously reported in other countries, besides higher rates of pulmonary involvement, secondary amyloidosis, and ECG abnormalities. Our results imply that IL-6 is involved in MCD pathogenesis. These findings would be informative for diagnosis and appropriate treatment for MCD.
Assuntos
Amiloidose/epidemiologia , Hiperplasia do Linfonodo Gigante/patologia , Linfadenopatia/epidemiologia , Adulto , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Biomarcadores/sangue , Proteína C-Reativa/análise , Hiperplasia do Linfonodo Gigante/sangue , Hiperplasia do Linfonodo Gigante/complicações , Hiperplasia do Linfonodo Gigante/tratamento farmacológico , Feminino , Hemoglobinas/análise , Humanos , Imunoglobulina G/análise , Interleucina-6/sangue , Japão , Masculino , Pessoa de Meia-IdadeRESUMO
Carcinosarcoma is a clonal tumor developed through sarcomatoid changes in a carcinoma via the epithelial-mesenchymal transition (EMT). Here, we present an extremely rare case of pulmonary carcinosarcoma characterized by components suggesting pluripotency, namely neuroendocrine, myogenic, and chondrogenic differentiation, based on immunohistochemical analysis. A 42-year-old Japanese man was admitted to our hospital. Analysis of tumor tissue after right upper lobe lobectomy revealed a transition between carcinomatous and sarcomatous components. Immunohistochemical analysis suggested immortality owing to complete loss of p53 and diffuse expression of p16 in both the carcinomatous and sarcomatous components. There were also scattered cell groups expressing aldehyde dehydrogenase 1 family member A1, SOX2, CD133, and c-kit, suggesting the possible presence of cancer stem cells. Our findings in this case suggested that the EMT may play a key role in mediating the immortality of tumor cells in carcinosarcoma and facilitating the pluripotency of cancer stem cells.
Assuntos
Carcinossarcoma/patologia , Transição Epitelial-Mesenquimal , Neoplasias Pulmonares/patologia , Proteína Supressora de Tumor p53/metabolismo , Adulto , Biomarcadores Tumorais/metabolismo , Carcinossarcoma/metabolismo , Diferenciação Celular , Humanos , Neoplasias Pulmonares/metabolismo , Masculino , Células-Tronco Neoplásicas/patologia , Células-Tronco Pluripotentes/patologiaRESUMO
Pembrolizumab, a humanized monoclonal immunoglobulin (Ig) G4 antibody that is directed against the human cell surface receptor PD-1, is a PD-1 pathway inhibitor that has been approved to treat various malignant diseases, including advanced non-small cell lung cancer (NSCLC). PD-1 is the major inhibitory receptor regulating T-cell exhaustion, and T-cells with high PD-1 expression lose their ability to eliminate cancer. PD-1 pathway blockade by pembrolizumab reinvigorates exhausted T-cells and restores their antitumor immune responses. However, reinvigorated T-cells also evoke immune-related adverse effects (irAEs), which stem from the restored activity. Currently, the pathogenic mechanisms of irAEs have not been sufficiently determined. We experienced a patient with NSCLC with high PD-L1 expression and cervical lymph node metastases, who demonstrated a good clinical response to first line pembrolizumab but suffered from a severe cutaneous adverse event. Both of his skin lesions and cervical metastases showed extensive CD8(+) PD-1(+) T-cell infiltration in immunofluorescence analysis. This finding suggests a possible contribution of reinvigorated CD8(+) PD-1(+) T-cells in anti-PD-1 therapy-induced skin rash. Intriguingly, CD8(+) T-cells in the skin rash showed higher Ki-67 expression, a proliferation marker, than those in the cervical lymph node lesion. This is the first report of an association between proliferative CD8(+) PD-1(+) T-cells and irAEs.
Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Linfócitos T CD8-Positivos/imunologia , Linfócitos do Interstício Tumoral/imunologia , Receptor de Morte Celular Programada 1/metabolismo , Dermatopatias/induzido quimicamente , Dermatopatias/patologia , Proliferação de Células/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVES: To determine the tentative diagnostic criteria and disease severity classification for Castleman disease (CD) and describe the clinical and pathologic features among human herpesvirus 8 (HHV-8) negative idiopathic multicentric CD (iMCD) in the Japanese population. METHODS: We established the working groups for the research of CD in Japan and had meetings to discuss and define the tentative diagnostic criteria and disease severity classification for CD. We subsequently analyzed 142 patients classified into iMCD by using the nationwide Japanese patient registry. RESULTS: We proposed the preliminary diagnostic criteria and disease severity classification for CD based on our discussion. In addition, we made a proposal for the disease activity score. We identified clinical and pathological features of patients with iMCD diagnosed by these diagnostic criteria. In the disease severity classification, 37, 33 and 30% patients were categorized into mild, moderate and severe diseases, respectively. CONCLUSION: This is the first proposal for diagnosis and classification of CD by the Japanese group. Further studies are required to validate whether they can distinguish CD from other inflammatory diseases and to determine their sensitivity and specificity.