RESUMEN
Objective: To compare the histologic features of immune-mediated hepatitis (IMH) due to immune checkpoint inhibitors (ICIs) monotherapy and combined ICIs anti-angiogenesis tyrosine kinases (TKIs) targeted therapy. Methods: Twenty-one IMH patients who had liver biopsy during ICIs treatment in Zhongshan Hospital of Fudan University from 2015 to 2019 were included. Among them, ten were treated with ICIs monotherapy, and 11 were treated with combined ICIs and anti-angiogenesis targeted therapy. The histologic features of IMH were assessed by HE staining and PD-L1/2 was evaluated by immunohistochemical staining. Results: Patients treated with monotherapy ICIs presented with different levels of lobular hepatitis and portal inflammation. Besides, there were also cholangitis, endothelialitis, Kupffer cells activation and peliosisi hepatitis. Eight cases (8/10) showed mild and two cases (2/10) showed moderate hepatic injury. As for patients receiving combined ICIs and TKIs therapy, the extent of IMH was more severe, with four cases (4/11) showing moderate-severe liver injury, with confluent or bridging necrosis, portal inflammation, cholangitis, interface hepatitis. Among these, one patient developed acute severe hepatitis with massive hepatocyte necrosis and died of multisystem dysfunction. In those cases with severe liver injury, many CD8 positive lymphocytes aggregated in the portal area and hepatic sinusoid, and PD-L1 was expressed in many endothelial cells. There were both 2 cases of death in ICIs monotherapy and combination therapy group. Among the latter group, 1 patient developed acute severe hepatitis with massive hepatocyte necrosis and died of multisystem dysfunction. Conclusion: Compared with ICIs monotherapy, combined ICIs and anti-angiogenesis targeted TKIs therapy may cause overlapping hepatic injury, leading to severe IMH.
Asunto(s)
Antineoplásicos/uso terapéutico , Células Endoteliales , Hepatitis , Hepatitis/terapia , Humanos , Inmunoterapia , Neovascularización Patológica , Inhibidores de Proteínas QuinasasRESUMEN
BACKGROUND: To retrospectively investigate the clinicopathological features and prognosis of early esophageal squamous cell neoplasm (ESCN) treated with endoscopic resection (ER), especially, to compare the prognosis in patients with sm2 cancer and non-sm2 cancer. METHODS: From 2007 to 2013, 368 patients were included in our analysis. RESULTS: The patients were 252 (68.5 %) men and 116 (31.5 %) women with a median age of 61 (range 16-84 years) years. Hyperplasia, mild dysplasia, moderate dysplasia, severe dysplasia, m1, m2, m3, sm1, and sm2 were diagnosed in 47 (12.8 %), 27 (7.3 %), 34 (9.2 %), 61 (16.6 %), 54 (14.7 %), 38 (10.3 %), 63 (17.1 %), 12 (3.3 %), and 32 (8.7 %) cases. The mean (range) follow-up time was 29 (0-84) months. The cumulative overall 1-, 3-, and 5-year metachronous esophageal lesion rates were 4.1, 12.9, and 32.6 %. The incidence of lymph node or distant metastasis was 1.54 % in m3, 6.25 % in sm2, and 0 in other subgroups. The overall 1-, 3-, and 5-year survival rates were 99.5, 97.3, and 87.5 %. There was significant difference between sm2 and non-sm2 patients in metastatic rate (P = 0.021); however, no difference existed between m3 patients and sm2 patients (P = 0.252). The difference of metachronous esophageal lesion (P = 0.401) and survival (P = 0.634) between sm2 and non-sm2 patients was not obvious. CONCLUSIONS: Our study showed that ER was an effective and relatively safe treatment for superficial ESCN. ER is still appropriate in select sm2 patients. To monitor the second primary cancer in sm2 is necessary during the follow-up.
Asunto(s)
Carcinoma de Células Escamosas/cirugía , Neoplasias Esofágicas/cirugía , Esofagoscopía , Lesiones Precancerosas/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/patología , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago , Femenino , Estudios de Seguimiento , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Lesiones Precancerosas/patología , Pronóstico , Estudios Retrospectivos , Adulto JovenRESUMEN
This study is to examine EGFR and c-Met variation in precancerous lesion, early esophageal squamous cell carcinoma (ESCC), and advanced ESCC and to explore their prognostic significance. EGFR and c-Met were detected by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Of 158 endoscopy resection (ER) specimens, c-Met high expression and FISH positive were 44.9 and 12.6 %, respectively. EGFR high expression and FISH positive were 2.5 and 19.6 %, respectively. Of 84 surgical specimens, c-Met high expression and FISH positive were 50 and 8.3 %, respectively. EGFR high expression and FISH positive were 7.1 and 28.5 %, respectively. A significant correlation was observed between c-Met and EGFR FISH positive both in ER (P < 0.001) and surgical specimens (P = 0.029). Patients with EGFR high expression had poorer disease-free survival (DFS) and overall survival (OS) (P = 0.031 and P = 0.013) in c-Met high-expression group but not in c-Met low-expression group (P = 0.301 and P = 0.439). C-Met FISH positive did not represent a statistically significant adverse prognosis until 24 months later (P = 0.027 and 0.048). EGFR and c-Met might be involved in the tumorigenesis and development of ESCC. EGFR high expression has different prognostic significance in patients with differing c-Met expression status. C-Met FISH positive represent delayed prognostic factor.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/patología , Receptores ErbB/metabolismo , Neoplasias Esofágicas/patología , Proteínas Proto-Oncogénicas c-met/metabolismo , Biomarcadores de Tumor/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Progresión de la Enfermedad , Receptores ErbB/genética , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Femenino , Estudios de Seguimiento , Regulación Neoplásica de la Expresión Génica , Humanos , Técnicas para Inmunoenzimas , Hibridación in Situ , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Pronóstico , Proteínas Proto-Oncogénicas c-met/genética , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
OBJECTIVE: To study the clinicopathological characteristics of hepatic angiomyolipoma (HAML) and to evaluate the correlation between clinicopathological parameters and tumor subtypes. METHODS: Retrospective analysis of clinicopathological features was conducted in 182 cases of HAML. RESULTS: HAML patients were predominantly female (M:F=1:4) and most commonly presented with non-specific symptoms. The median age at diagnosis was 46 years, ranged from 17 to 77 years. Tumor diameter was ranged from 0.3 to 32.0 cm with an average of 5.0 cm. Majority of the tumor was epithelioid type (112/165, 67.9%). Extramedullary hematopoiesis, multinucleated giant cells, intranuclear inclusions, nucleolus, cellular atypia, invasive growth pattern, multiple masses, hyperpigmentation and purpura-like changes mostly occurred in the epithelioid type (P<0.05). Extramedullary hematopoiesis was commonly seen in HAML, the significance of which was still uncertain. CONCLUSIONS: Most of HAML are epithelioid type, characterized by a proliferation of predominantly epithelioid cells, in which extramedullary hematopoiesis is commonly seen. Some morphologic features that may predict malignant such as necrosis, mitotic figures, and tumor emboli are only found in the epithelioid HAML. Mitotic activity, tumor necrosis, tumor thrombus, giant cells, periportal invasion, multiple lesions and tumors size over 10 cm are closely related with tumor recurrence and metastasis.
Asunto(s)
Angiomiolipoma/diagnóstico , Angiomiolipoma/patología , Neoplasias Gastrointestinales/diagnóstico , Neoplasias Gastrointestinales/patología , Adolescente , Adulto , Anciano , Células Epitelioides/citología , Femenino , Células Gigantes/patología , Humanos , Persona de Mediana Edad , Necrosis , Recurrencia Local de Neoplasia , Pronóstico , Estudios Retrospectivos , Adulto JovenRESUMEN
Ciliated muconodular papillary tumor (CMPT) is a rare pulmonary tumor, typically occurring in middle-aged and elderly individuals. The molecular mutation spectrum of CMPT remains insufficiently explored. Commonly known driver gene alterations include KRAS, BRAF, EGFR, and ALK rearrangement. This report details the clinicopathological features of 2 patients presenting with CMPT as pulmonary nodules during clinical examinations. Microscopic analysis revealed tumors with glandular or papillary structures, consisting of mucinous cells, ciliated columnar cells, and basal cells. Notably, both patients exhibited STRN::ALK fusion, a finding not previously associated with CMPT. STRN::ALK fusion serves as a target for therapy in various tumors, including non-small cell lung cancer, thyroid cancer, and colon cancer. Consequently, we conducted a review of relevant literature, summarizing the clinicopathological and molecular characteristics of CMPT to facilitate further research. Our insights enhance the understanding of this uncommon tumor and contribute to the expansion of its molecular alteration spectrum.
RESUMEN
Diffuse gliomas are devastating brain tumors. Here, we perform a proteogenomic profiling of 213 retrospectively collected glioma tumors. Proteogenomic analysis reveals the downstream biological events leading by EGFR-, IDH1-, TP53-mutations. The comparative analysis illustrates the distinctive features of GBMs and LGGs, indicating CDK2 inhibitor might serve as a promising drug target for GBMs. Further proteogenomic integrative analysis combined with functional experiments highlight the cis-effect of EGFR alterations might lead to glioma tumor cell proliferation through ERK5 medicates nucleotide synthesis process. Proteome-based stratification of gliomas defines 3 proteomic subgroups (S-Ne, S-Pf, S-Im), which could serve as a complement to WHO subtypes, and would provide the essential framework for the utilization of specific targeted therapies for particular glioma subtypes. Immune clustering identifies three immune subtypes with distinctive immune cell types. Further analysis reveals higher EGFR alteration frequencies accounts for elevation of immune check point protein: PD-L1 and CD70 in T-cell infiltrated tumors.
Asunto(s)
Glioma , Proteogenómica , Humanos , Proteómica , Estudios Retrospectivos , Glioma/genética , Receptores ErbB/genéticaRESUMEN
Chemotherapy and targeted therapy are the major treatments for gastric cancer (GC), but drug resistance limits its effectiveness. Here, we profile the proteome of 206 tumor tissues from patients with GC undergoing either chemotherapy or anti-HER2-based therapy. Proteome-based classification reveals four subtypes (G-I-G-IV) related to different clinical and molecular features. MSI-sig high GC patients benefit from docetaxel combination treatment, accompanied by anticancer immune response. Further study reveals patients with high T cell receptor signaling respond to anti-HER2-based therapy; while activation of extracellular matrix/PI3K-AKT pathway impair anti-tumor effect of trastuzumab. We observe CTSE functions as a cell intrinsic enhancer of chemosensitivity of docetaxel, whereas TKTL1 functions as an attenuator. Finally, we develop prognostic models with high accuracy to predict therapeutic response, further validated in an independent validation cohort. This study provides a rich resource for investigating the mechanisms and indicators of chemotherapy and targeted therapy in GC.
Asunto(s)
Proteómica , Neoplasias Gástricas , Docetaxel/uso terapéutico , Humanos , Fosfatidilinositol 3-Quinasas , Proteoma , Proteínas Proto-Oncogénicas c-akt , Receptores de Antígenos de Linfocitos T , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/genética , Transcetolasa , Trastuzumab/farmacología , Trastuzumab/uso terapéuticoRESUMEN
OBJECTIVE: To study the clinicopathologic features of focal nodular hyperplasia (FNH) of liver. METHODS: The clinical, radiologic, pathologic findings and follow-up data of 238 cases of FNH were retrospectively analyzed. RESULTS: The patients included 93 females and 145 males. The age of the patients ranged from 11 to 77 years (median = 39.1 years). Amongst the 233 patients who had clinical information available, 188 were asymptomatic, 216 had no history of hepatitis B and/or C infection and 232 had negative serum alpha-fetoprotein level. Amongst the 185 patients who had undergone radiologic examination, 123 (66.5%) were accurately diagnosed as such. Macroscopically, of the 284 lesions from 238 patients, the average diameter was 3.7 cm. Two hundred and fifteen cases (90.3%) were solitary, 172 cases were located in the right lobe and 115(40.5%) had central stellate fibrotic scars or lobulated cut surface. Histologically, 229 lesions belonged to classic type and 9 lesions were of non-classic type. The latter was further classified as the telangiectatic form (6 lesions) and the mixed hyperplastic and adenomatous form (3 lesions). There was no evidence of significant cytologic atypia. Follow-up data were available in 173 patients (72.7%). None of them died of the disease and 2 patients suffered from relapses after 2 and 4 years, respectively. CONCLUSIONS: FNH is a hyperplastic response of normal liver cells to local blood flow anomalies. It has no obvious sex predilection and more than 66% can be diagnosed accurately with radiologic examination. The lesions in the current study show no cytologic atypia.
Asunto(s)
Hiperplasia Nodular Focal/patología , Hígado/patología , Adenoma de Células Hepáticas/patología , Adolescente , Adulto , Anciano , Biopsia , Carcinoma Hepatocelular/patología , Niño , Diagnóstico Diferencial , Femenino , Hiperplasia Nodular Focal/diagnóstico , Hiperplasia Nodular Focal/diagnóstico por imagen , Hiperplasia Nodular Focal/cirugía , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/patología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Ultrasonografía , Adulto JovenRESUMEN
OBJECTIVE: To study the pathologic features and immunophenotype of 3 cases of melanotic epithelioid clear cell tumor of kidney. METHODS: More than 2000 cases of renal tumors were retrospectively reviewed. Three cases of melanotic epithelioid clear cell tumor were identified. Immunohistochemical study was carried out using the paraffin-embedded tissue samples. Electron microscopy was also performed in 1 case. RESULTS: Amongst the 3 cases studied, the male-to-female ratio is 1:2. Histologically, 2 cases showed a clear cell carcinoma-like pattern. Papillary structures covered by clear cells and eosinophilic cells were observed in 1 case. Immunohistochemical study showed that the tumor cells in all cases expressed HMB 45. Two of them were also positive for Melan A. The staining for epithelial markers and S-100 protein was negative. Melanosomes were not identified by ultrastructural examination. CONCLUSIONS: Melanotic epithelioid clear cell tumor is a rarely seen neoplasm of kidney. There are some histologic overlaps with renal cell carcinoma, epithelioid angiomyolipoma and melanoma. Immunohistochemical study is useful in confirming the diagnosis. The tumor represents a morphologic variant of epithelioid angiomyolipoma.
Asunto(s)
Carcinoma de Células Renales/patología , Células Epitelioides/patología , Neoplasias Renales/patología , Antígenos Específicos del Melanoma/metabolismo , Adolescente , Adulto , Angiomiolipoma/metabolismo , Angiomiolipoma/patología , Angiomiolipoma/cirugía , Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/cirugía , Diagnóstico Diferencial , Células Epitelioides/metabolismo , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Renales/metabolismo , Neoplasias Renales/cirugía , Antígeno MART-1/metabolismo , Masculino , Estudios RetrospectivosRESUMEN
OBJECTIVE: To improve the understanding and diagnosis of pulmonary lymphangioleiomyomatosis (LAM). METHODS: Fifteen cases of LAM of our hospital were presented and 73 cases reported in domestic literature from 1993 to 2008 were reviewed. By means of histological and immunohistochemical(IHC)studies, the clinical and pathological features of LAM were analyzed. RESULTS: All the 88 cases were female, with an average age of onset at (37 +/- 9) years. The main clinical manifestations included dyspnea (83/88, 94%), hemoptysis (48/88, 54%), pneumothorax (41/88, 47%), and chylothorax (28/88, 32%). High resolution computerized tomography (HRCT) showed thin-walled air-filled cysts throughout both lungs. Pathological features showed cystic changes in the lung, and abnormal smooth muscle cells (LAM cells) lined the airways, bronchioles, lymphatics and blood vessels leading to airflow obstruction and replacement of the lung parenchyma by cysts. In the autopsy case, extrapulmonary organs (eg, kidney, lymph nodes and soft tissues) were also involved. Abnormal manifestations in abdomen, including renal mass, retroperitoneal mass and retroperitoneal lymphadenopathy, were detected in 23 cases. CONCLUSIONS: LAM is a multisystem disease. Chest HRCT had confirmative value for diagnosis of LAM. In practice, chest HRCT, as well as other routine abdominal and pelvic imaging examinations, should be performed for child-bearing-age women with progressive dyspnea, hemoptysis, or spontaneous pneumothorax.
Asunto(s)
Neoplasias Pulmonares/patología , Linfangioleiomiomatosis/patología , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Linfangioleiomiomatosis/diagnóstico por imagen , Persona de Mediana Edad , Radiografía , Adulto JovenRESUMEN
Amplification of the fibroblast growth factor receptor 1 (FGFR1) is believed to predict response to FGFR inhibitors. The aim of this study was to investigate the frequency and the prognostic impact of FGFR1 amplification in patients with resected esophageal squamous cell carcinoma (ESCC) by using fluorescent in situ hybridization. Microarrayed paraffin embedded blocks were constructed, and the cohort of tissues came from 506 patients with ESCC. FGFR1 high amplification (FGFR1high ) was defined by an FGFR1/centromere 8 ratio of ≥ 2.0, or average number of FGFR1 signals/tumor cell nucleus ≥ 6.0, or percentage of tumor cells containing ≥ 15 FGFR1 signals, or large cluster in ≥ 10% of cancer cells. FGFR1 low amplification was defined by ≥ 5 FGFR1 signals in ≥ 50% of cancer cells. Kaplan-Meier curves with log-rank tests and Cox proportional hazards model were used to analyze patients' survival. Among 506 patients, high amplification, low amplification, and disomy were detected in 8.7%, 3.6% and 87.7%, respectively. In general, the FGFR1high group trended towards worse disease-free survival (DFS) and overall survival (OS) compared to the FGFR1 low amplification/disomy (FGFR1low/disomy ) group (DFS, P=0.108; OS, P=0.112), but this trend was amplified for patients with DFS ≥ 30 months (DFS, P=0.009; OS, P=0.007). Furthermore, when patients were stratified into stage I-II and stage III-IV, the FGFR1high group directly presented with adverse DFS and OS than the FGFR1low/disomy group in stage I-II patients (DFS, P=0.019; OS, P=0.034), especially with DFS ≥ 30 months (DFS, P=0.002; OS, P=0.001). However, for patients in stage III-IV, FGFR1high had no effect on prognosis regardless of DFS time. FGFR1high occurs in a minority of ESCC, and it predicts delayed poor prognosis in stage I and II ESCC patients.
RESUMEN
We undertook a study of tumour infiltrating lymphocytes (TILs) in a large and relatively homogeneous group of patients with completely resected esophageal squamous cell carcinoma (ESCC). Hematoxylin and eosin-stained sections of 235 ESCC tumours were evaluated for density of TILs in intratumoural (iTIL) and stromal compartments (sTIL). Foxp3+, CD4+, and CD8+ T cells in tumoural and stromal areas were evaluated by immunohistochemistry. Of the 235 tumours, high sTIL (>10%), and iTIL (>10%) were observed in 101 (43.0%) and 98 (41.7%), respectively. The median follow-up period was 36.0 months (95% CI 29.929-42.071). Univariate analysis revealed that sTIL (>10%), iTIL (>20%), vessels involvement, lymph node metastasis, and clinical stage were significantly associated with postoperative outcome. In multivariate analysis, high sTIL (HR: 0.664, P = 0.019 for Disease free survival; HR: 0.608, P = 0.005 for Overall survival) was identified as independent better prognostic factor. Further analysis, sTIL was identified as independently prognostic factor in Stage III-IVa disease, which was not found in Stage I-II disease. Our study demonstrated that sTIL was associated with better ESCC patients' survival, especially in Stage III-IVa disease. Assessment of sTIL could be useful to discriminate biological behavior for ESCC patients.
Asunto(s)
Biomarcadores de Tumor , Carcinoma de Células Escamosas/inmunología , Carcinoma de Células Escamosas/mortalidad , Neoplasias Esofágicas/inmunología , Neoplasias Esofágicas/mortalidad , Linfocitos Infiltrantes de Tumor/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/patología , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago , Femenino , Humanos , Estimación de Kaplan-Meier , Linfocitos Infiltrantes de Tumor/metabolismo , Linfocitos Infiltrantes de Tumor/patología , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , Administración de la Seguridad , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Subgrupos de Linfocitos T/patologíaRESUMEN
Accumulating evidence has shown that PD-L1 expression is associated with clinicopathological features in various human malignancies. We searched for correlations between PD-L1 expression and clinicopathological data in esophageal squamous cell carcinoma (ESCC) patients. PD-L1 expression in primary tumors from 278 patients was evaluated using immunohistochemistry (IHC) in ESCC tissue microarray. Survival curves were constructed by using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazard regression models were performed to identify associations with outcome variables. Overall, tumoral PD-L1 expression (≥10%, 20% or 30% as cut-off value) was associated with favorable DFS and OS upon multivariate analysis. When the patients stratified into stage I-II (168, 60.4%) and stage III-IV (110, 39.6%), or with lymph node metastasis (133, 47.8%), the prognostic role was not consistent. In patients with stage I-II disease, tumoral PD-L1 expression (≥5%, 10%, 20% or 30%) was associated with better DFS and OS upon multivariate analysis. In patients without lymph node metastasis, tumoral PD-L1 expression (≥1%, 5%, 10%, 20%, or 30%) was associated with improved DFS and OS in univariate or multivariate analysis. However, PD-L1 expression was not correlated with prognosis in patients with stage III-IV disease or with lymph node metastasis. Our results for the first time showed the prognostic role of tumoral PD-L1 expression was variable in different stages and lymph node status of ESCC. Tumoral PD-L1 expression was independent favorable predictor in ESCC patients with Stage I-II disease or without lymph node metastasis, not in stage III-IV or lymph node metastasis.
Asunto(s)
Antígeno B7-H1/análisis , Biomarcadores de Tumor/análisis , Carcinoma de Células Escamosas/inmunología , Neoplasias Esofágicas/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/secundario , Carcinoma de Células Escamosas/terapia , Distribución de Chi-Cuadrado , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas de Esófago , Femenino , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Metástasis Linfática , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Análisis de Matrices Tisulares , Resultado del TratamientoRESUMEN
OBJECTIVE: To clarify whether the various subtypes of serous cystic neoplasms (SCNs) of the pancreas can be distinguished from each other by marker profiles. METHODS: The immunoprofiles of 13 SCNs were defined by using antibodies against cytoskeletal, neuroendocrine, hormone receptor, and mucin markers. In addition, we examined the expression of calrentinin and alpha-inhibin. RESULTS: SCN included 7 cases of serous microcystic adenomas (SMA), 3 cases of serous oligocystic ill-defined adenomas (SOIA), 1 case of solid serous adenoma (SSA), 1 case of von Hippel-Lindau-associated cystic neoplasm (VHL-CN), and 1 case of serous cystadenocarcinoma (SCC). These neoplasms are histologically similar, but differ in their localization, gross appearance, gender distribution, and biological behavior. The various types of SCNs showed a very similar immunoprofile, characterized by positivity for cytokeratins (100%) and negativity for vimentin and synaptophysin. Other markers that were commonly expressed in the SCNs were alpha-inhibin (85%), MUC1 (69%) and MUC6 (77%). CONCLUSION: The results suggest that, despite their biologic differences, the various types of SCNs have the same (or a very similar) cell type and may therefore have a common direction of differentiation. A centroacinar origin is supported by the finding that a number of SCNs share MUC1 and MUC6 expression with pancreatic centroacinar cells. Alpha-inhibin, and MUC6 may be regarded as new markers for this type of pancreatic tumor.
Asunto(s)
Cistadenoma Seroso/patología , Neoplasias Pancreáticas/patología , Adulto , Biomarcadores de Tumor , Cistadenoma Seroso/diagnóstico por imagen , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/diagnóstico por imagen , Tomografía Computarizada por Rayos XAsunto(s)
Citodiagnóstico/métodos , Linfoma de Células B/patología , Linfoma de Células B Grandes Difuso/patología , Linfoma de Células T/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Ascitis/patología , Biopsia , Biopsia con Aguja Fina , Niño , Diagnóstico Diferencial , Femenino , Humanos , Leucemia-Linfoma de Células T del Adulto/patología , Masculino , Persona de Mediana Edad , Derrame Pleural/patología , Adulto JovenRESUMEN
One paraffin block is routinely used for human epidermal growth factor receptor 2 (Her2/neu) immunohistochemistry (IHC) assessment. Here, we investigated if picking 2 paraffin blocks for Her2/neu evaluation on 1 slide is an economical, efficient, and practical method, which may reduce false negativity of Her2/neu IHC assessment due to intratumoral heterogeneity. A total of 251 gastric cancer (GC) patients were divided into a cohort using 1 tumor tissue paraffin block (single-block group, n = 132) and a cohort using dual tumor tissue paraffin blocks (dual-block group, n = 119) when evaluating Her2/neu expression status by IHC. In dual-block group, we combined the results from 2 different paraffin blocks and used the higher one as the final score. The number of IHC 1+, 2+, and 3+ specimens in the single-block group was 31 (23.5%), 40 (30.3%), and 19 (14.4%), respectively. The combined final IHC score in the dual-block group of 1+, 2+, and 3+ was 26 (21.8%), 34 (28.6%), and 23 (19.3%), respectively. Inconsistent Her2/neu expression between blocks was found in 36 (30.3%) cases in the dual-block group. The pooled data in the single-block group and the dual-block group indicated that, when using dual blocks, the Her2/neu-positive (3+) rate of GC was higher compared to that in the single-block group. Our results implied that using dual paraffin blocks to assess Her2/neu expression of GC may help identify more patients with Her2/neu-positive GC who could benefit from targeted therapy, by reducing false-negative rate of Her2 status assessment. This is an efficient, economical, and practical method for Her2/neu evaluation of GC.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Inmunohistoquímica , Receptor ErbB-2/metabolismo , Neoplasias Gástricas/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Amplificación de Genes/fisiología , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Parafina , Neoplasias Gástricas/metabolismo , Conservación de TejidoRESUMEN
BACKGROUND: Lymphangioleiomyomatosis (LAM) is a rare disease that predominantly affects young females. It is considered as an "orphan" life-threatening disease of unknown etiology, with uncertain clinical prognosis, and no effective treatment. LAM can arise sporadically or in association with tuberous sclerosis complex (TSC), an autosomal inherited syndrome characterized by hamartoma-like tumor growth and pathologic features that are distinct from manifestations of pulmonary LAM. The clinical course of LAM is characterized by progressive dyspnea on exertion, recurrent pneumothorax, and chylous fluid collections. METHODS: Fourteen cases of LAM from Zhongshan Hospital, Fudan University are reviewed, twelve were confirmed by lung biopsy, one by retroperitoneal lymphangioleiomyoma resection, and one by autopsy. RESULTS: All 14 patients were women, aged 18 to 69 years (mean 43.3 years, median 46.5 years). Haemoptysis (57.1%) and chylothorax (35.7%) were more frequent than those described in previous case series. Extrapulmonary findings such as renal angiomyolipoma (AML), enlarged abdominal lymph nodes, liver AML and retroperitoneal lymphangioleiomyoma were seen in 21.4%, 14.3%, 7.14% and 7.14% in 14 cases respectively, which is remarkably lower than in the previously reported. Abnormal smooth muscle cells (LAM cells) were found to line the airways, bronchioles, lymphatics and blood vessels leading to airflow obstruction and replacement of the lung parenchyma by cysts. There were some surprises in the autopsy case as several LAM cell emboli were found in the veins of mediastinum lymph nodes; LAM cells were found to be disseminated in soft tissues adjacent to the ilium. CONCLUSIONS: Women with unexplained recurrent pneumothorax, tuberous sclerosis, or a diagnosis of primary spontaneous pneumothorax or emphysema in the setting of limited or absent tobacco use should undergo high-resolution computed tomography (HRCT) scan screening for LAM. Routine abdominal and pelvic imaging examinations should be performed to detect extrapulmonary involvement. The autopsy studies histologically suggested that LAM could be a multisystemic disease and LAM cells might possess metastatic potential.
Asunto(s)
Linfangioleiomiomatosis/diagnóstico , Linfangioleiomiomatosis/patología , Adolescente , Adulto , Anciano , Anticonceptivos Sintéticos Orales , Femenino , Humanos , Inmunohistoquímica , Linfangioleiomiomatosis/tratamiento farmacológico , Linfangioleiomiomatosis/metabolismo , Linfangioleiomiomatosis/cirugía , Medroxiprogesterona/uso terapéutico , Persona de Mediana Edad , Ovariectomía , Progesterona/uso terapéutico , Progestinas/uso terapéutico , Adulto JovenRESUMEN
<p><b>OBJECTIVE</b>Gastrointestinal stromal tumors (GISTs) have a broad spectrum of biological behaviors ranging from benign, borderline and malignant. This study aimed to screen differentially expressed microRNAs (miRNAs) between malignant and borderline GISTs and to investigate the potential role of miRNAs in the malignant transformation of GISTs.</p><p><b>METHODS</b>Six GIST samples including borderline tumors (n = 3) and malignant tumors (n = 3) were collected based on the clinical and pathological characteristics. Total RNA was extracted, followed by miRNA microarray analysis to screen the differentially expressed miRNAs. The most significantly expressed 4 miRNAs were then chosen for further validation by real-time PCR in 22 additional GIST samples.</p><p><b>RESULTS</b>Direct comparison of malignant group versus borderline group revealed 14 significantly and differentially expressed miRNAs (P < 0.05, with a fold change of < 0.5 or > 2). Five miRNAs were up-regulated and nine were down-regulated in the malignant group. Four miRNAs (miR-221, miR-135b, miR-675(*) and miR-218) were most significantly and differentially expressed between the two groups. The differential expression of 2 miRNAs (miR-221 and miR-675(*)) were subsequently confirmed with good concordance by real-time PCR.</p><p><b>CONCLUSIONS</b>The differential miRNA expression profiles between two groups are revealed by miRNA microarray assay, and confirmed by real-time PCR. Among differentially expressed miRNAs, miR-221 and miR-675(*) might be related to the malignant transformation of GISTs, and have a potential value in predicting biological behavior of GISTs.</p>
Asunto(s)
Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Transformación Celular Neoplásica , Regulación hacia Abajo , Neoplasias Gastrointestinales , Genética , Patología , Tumores del Estroma Gastrointestinal , Genética , Patología , Perfilación de la Expresión Génica , MicroARNs , Genética , Metabolismo , Análisis por Micromatrices , Reacción en Cadena en Tiempo Real de la Polimerasa , Regulación hacia ArribaRESUMEN
AIM: To recognize cystic neoplasia of the pancreas and thus to identify a panel of curable diseases. METHODS: Sixty-four cases of cystic neoplasia of the pancreas, including 28 cases of intraductal papillary mucinous neoplasia (IPMN), 12 cases of serous cystic neoplasia (SCN), 11 cases of mucinous cystic neoplasia (MCN), 11 cases of solid pseudo-papillary neoplasia (SPN), and 2 cases of solid tumor with cystic degeneration were examined immunohistochemically for their expression of MUC1, MUC2, MUC4, MUC5AC, and MUC6, as well as other related antigens. RESULTS: Adenoma type of IPMN and borderline lesions exhibited high expressions of MUC2, and MUC5AC. In contrast, IPMN with invasive carcinoma component showed MUC1 immunoreactivity. SCN was mainly positive for MUC1 and MUC6, while negative for MUC2, MUC4 and MUC5AC. Noninvasive MCN, regardless of its cellular atypia degree, was positive for MUC5AC and negative for MUC1. MUC1 expression was only observed in patients with an invasive component. No mucin expression was found in SPN. CONCLUSION: Mucin profile may, in conjunction with histologic study, provide important information on tumor types and patient treatment of cystic neoplasia of the pancreas.