RESUMEN
BACKGROUND: A rare case of neuroendocrine cell tumor (NET) having both conventional and mucinous components was reported. Mucinous NET is rarely encountered in the pathological diagnosis of gastrointestinal (GI) tumors. Here we examined the mechanism for transformation of conventional NETs into mucinous NETs. CASE PRESENTATION: Macroscopic examination revealed a tumor with ulceration in the ampulla of Vater that measured 1.7 cm in its largest diameter. Histologically, the tumor comprised two components: a tubular/ribbon-like feature and small nests floating in a mucinous lake. The tumor nests showed sheet, nest and ribbon-like structures of small cells having eosinophilic cytoplasm as well as small-sized nuclei with dense hyperchromatin. Immunohistochemical analysis showed tumor cells positive for pan-endocrine markers (synaptophysin, CD56, INSM1 and chromogranin). Based on the histological findings, the solid and mucinous components were diagnosed as conventional and mucinous NETs, respectively. Grading was NET G2 based on 12.8% and 13.2% Ki-67-positive cells in the solid and mucinous components, respectively. Immunohistochemically, the mucin phenotype of this tumor was gastric and intestinal. Only the mucinous NET component had cytoplasmic CD10 expression. Examination using a customized gene panel detected only a DPC4 mutation, which was limited to the mucinous component. CONCLUSIONS: Coexistence of conventional and mucinous NETs could provide important insight into evaluating the NET subtype histogenesis. Moreover, molecular alterations including cytoplasmic expression of CD10 and the DPC4 mutation can contribute to interpretation of tumor pathogenesis.
Asunto(s)
Ampolla Hepatopancreática , Biomarcadores de Tumor , Tumores Neuroendocrinos , Humanos , Ampolla Hepatopancreática/patología , Ampolla Hepatopancreática/química , Tumores Neuroendocrinos/patología , Tumores Neuroendocrinos/química , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Neoplasias del Conducto Colédoco/patología , Neoplasias del Conducto Colédoco/química , Inmunohistoquímica , Masculino , Femenino , Persona de Mediana EdadRESUMEN
BACKGROUND: HHLA2 is a recently discovered member of the B7-family of immune checkpoint molecules with limited expression in normal tissues but overexpression in several types of cancer. The aim was to determine the expression, prevalence and biological relevance of HHLA2 protein expression in two closely related human cancer types, namely pancreatic cancer and ampullary cancer. METHODS: HHLA2 expression levels were retrospectively determined by immunohistochemistry in tissue micro-arrays of surgically resected tumours of 122 pancreatic cancer patients and 72 patients with ampullary cancer of the pancreato-biliary subtype. RESULTS: HHLA2 was expressed at variable levels by tumour cells in 67% of pancreatic tumours and 93% of ampullary tumours. In the combined cohort high tumoural HHLA2 expression levels were significantly associated with delayed cancer recurrence and improved post-operative cancer-specific survival. The association of HHLA2 expression with cancer-specific survival and recurrence was statistically significant for the pancreatic cancer subgroup while a similar trend was found for the ampullary cancer subgroup. In multivariable analysis together with clinicopathologic characteristics, higher HHLA2 expression was an independent predictor of cancer-specific survival. CONCLUSION: The wide expression of HHLA2 in tumour cells and its association with cancer recurrence and patient survival suggest that HHLA2 represents a relevant immune checkpoint molecule in pancreatic and ampullary cancers.
Asunto(s)
Ampolla Hepatopancreática , Neoplasias del Conducto Colédoco/química , Inmunoglobulinas/análisis , Neoplasias Pancreáticas/química , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias del Conducto Colédoco/mortalidad , Neoplasias del Conducto Colédoco/patología , Neoplasias del Conducto Colédoco/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/cirugía , Pronóstico , Estudios RetrospectivosRESUMEN
Objective: To investigate the expression of immunomarkers CK7, CK20, CK17, CDX2, MUC1 and MUC2 in primary adenocarcinoma of the ampulla of Vater, to explore the role of these markers in the histopathologic subclassification of ampullary carcinoma; and to provide biologic basis for precision treatment of patients with different types of ampullary carcinoma. Methods: Forty-two cases of primary ampullary carcinoma were collected at Peking University People's Hospital, from 2012 to 2018 year. There were 22 males and 20 females. Aged range 42 to 88 years old, with mean aged (62±11) years. Among the patients, 6 was high differentiation, 19 median differentiation, and 17 low differentiation. Immunohistochemical studies on the expression of CK7, CK20, CK17, CDX2, MUC1 and MUC2 were performed in 42 cases of primary ampullary carcinoma. The relationship between different ampullary carcinoma subtypes and clinicopathologic survival data was analyzed using SPSS 16.0 statistical software. Results: Three histopathologic subtypes were observed. Among 42 cases, 8(19.0%)were classified as intestinal subtype, which showed a positive expression rate of 8/8 for both CK20 and CDX2, and 5/8 for MUC2. Both CK7 and CK17 were weakly expressed in one case (1/8). No expression was observed for MUC1 in this subtype. Twenty-two (52.4%,22/42) cases were classified as pancreaticobiliary subtype, which showed a positive expression rate of 100.0%(22/22) for both CK7 and MUC1, and 90.9% (20/22) for CK17. No expression was observed for CK20, CDX2 and MUC2.The remaining 12 (28.6%) cases were classified as mixed subtype, which showed variable expression patterns. The expression frequencies of these 6 immunomarkers in different subtypes of ampullary carcinoma did not correlate with various clinicopathologic factors such as patient gender and age, tumor size, histologic differentiation, pancreatic and bile duct invasion, or the depth of duodenal invasion. However, stage â ¢+â £ diseases were more commonly seen in pancreaticobiliary type (63.6%,14/22) than intestinal type (2/8) and mixed type (3/9; χ(2)=6.508, P=0.039). Follow-up data showed a trend of better survival rate for patients with intestinal subtype than those with mixed and pancreaticobiliary subtypes. Conclusions: Ampullary carcinoma can be subclassified into three different subtypes using a panel of six immunomarkers, especially for the identification of subtypes of poorly differentiated carcinoma. CK7, CK17 and MUC1 are major markers of pancreaticobiliary subtype, whereas CK20, CDX2 and MUC2 are useful markers for intestinal subtype. The mixed subtype variably expresses these markers. The prognosis of patients with intestinal subtype appears better than that of pancreaticobiliary and mixed subtypes. Accurate subtyping of ampullary carcinoma is clinically important to patient management and prognosis assessment.
Asunto(s)
Adenocarcinoma/química , Ampolla Hepatopancreática/química , Biomarcadores de Tumor/análisis , Neoplasias del Conducto Colédoco/química , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Ampolla Hepatopancreática/patología , Factor de Transcripción CDX2/análisis , Neoplasias del Conducto Colédoco/patología , Femenino , Humanos , Inmunohistoquímica , Queratina-17/análisis , Queratina-20/análisis , Queratina-7/análisis , Masculino , Persona de Mediana Edad , Mucina-1/análisis , Mucina 2/análisisRESUMEN
Ampullary adenoma is a common indication for endoscopic papillectomy. Ampullary neuroendocrine tumor (NET) is a rare disease for which complete surgical resection is the treatment of choice. However, because of the morbidity and mortality associated with surgical resection, endoscopic papillectomy is increasingly used in selected cases of low grade, with no metastasis and no invasion of the pancreatic or bile duct. Also, confirmed and complete endoscopic resection of ampullary NET accompanied by adenoma has not been reported to date. We report herein a rare case of an ampullary NET accompanied with adenoma, which was successfully and completely resected via endoscopic papillectomy. Prior to papillectomy, this case was diagnosed as an ampullary adenoma.
Asunto(s)
Adenoma/cirugía , Ampolla Hepatopancreática/cirugía , Neoplasias del Conducto Colédoco/cirugía , Neoplasias Complejas y Mixtas , Tumores Neuroendocrinos/cirugía , Esfinterotomía Endoscópica , Adenoma/química , Adenoma/patología , Ampolla Hepatopancreática/química , Ampolla Hepatopancreática/patología , Biomarcadores de Tumor/análisis , Biopsia , Neoplasias del Conducto Colédoco/química , Neoplasias del Conducto Colédoco/patología , Duodenoscopía , Endosonografía , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Tumores Neuroendocrinos/química , Tumores Neuroendocrinos/patología , Valor Predictivo de las Pruebas , Resultado del TratamientoAsunto(s)
Ampolla Hepatopancreática/patología , Neoplasias del Conducto Colédoco/diagnóstico , Paraganglioma/diagnóstico , Biomarcadores de Tumor/análisis , Neoplasias del Conducto Colédoco/química , Neoplasias del Conducto Colédoco/patología , Humanos , Masculino , Melena/etiología , Persona de Mediana Edad , Polipéptido Pancreático/análisis , Paraganglioma/química , Paraganglioma/patología , Proteínas S100/análisis , Sinaptofisina/análisisRESUMEN
Intraductal papillary neoplasm of the bile duct (IPNB) exists in a pathway of multistep-carcinogenesis toward cholangiocarcinoma. Four subtypes are observed in IPNB, pancreatobiliary type, intestinal type, gastric type, and oncocytic type, similarly to the corresponding disease in the pancreas, intraductal papillary mucinous neoplasm (IPMN). IPNB can present with or without macroscopically visible mucin secretion. IPNB usually progresses to tubular adenocarcinoma. However, there are a limited number of well-described cases of gastric-type IPNB progressing not to tubular adenocarcinoma but to colloid carcinoma. Herein, we present a case of an 82-year-old female patient with gastric-type IPNB in the intrapancreatic common bile duct without macroscopically visible mucin secretion, which progressed to colloid carcinoma. As IPNB, especially without visible mucin secretion, is considered to be a heterogeneous group of diseases, such an unexpected association could occur.
Asunto(s)
Adenocarcinoma Mucinoso/patología , Neoplasias del Conducto Colédoco/patología , Conducto Colédoco/patología , Adenocarcinoma Mucinoso/química , Adenocarcinoma Mucinoso/genética , Adenocarcinoma Mucinoso/cirugía , Anciano de 80 o más Años , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Conducto Colédoco/química , Conducto Colédoco/cirugía , Neoplasias del Conducto Colédoco/química , Neoplasias del Conducto Colédoco/genética , Neoplasias del Conducto Colédoco/cirugía , Progresión de la Enfermedad , Femenino , Humanos , Inmunohistoquímica , Imagen por Resonancia Magnética , Pancreaticoduodenectomía , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
Epidermal growth factor receptor (EGFR) and insulin-like growth factor receptor 1 (IGF-1R) play important roles in cell proliferation, antiapoptosis, angiogenesis, and metastasis and have been used for targeted therapies for patients with advanced colorectal and lung cancers. However, the expression and function of EGFR and IGF-1R in ampullary adenocarcinoma (AA) have not been examined in detail. We examined the expression of EGFR and IGF-1R in 106 AA patients at our institution using tissue microarrays and immunohistochemistry. The results were correlated with the clinicopathological parameters and survival. Overexpression of EGFR and IGF-1R was detected in 18 (17%) and 26 (25%) of AAs, respectively. Patients with EGFR-high tumors had shorter overall survival (mean, 109.8 ± 22.3 months) than those patients whose tumors were EGFR-low in overall study population (mean, 164.2 ± 10.6 months; P = .04). Overexpression of EGFR correlated with poor overall survival in patients with intestinal-type AA (P = .01) but not in those with pancreaticobiliary-type AAs (P = .47). In multivariate analysis, EGFR overexpression was an independent prognostic factor for overall survival (P = .02). In addition, we found that overexpression of IGF-1R correlated with AAs of pancreaticobiliary histology. No additional correlation between the expression of EGFR or IGF-1R and other clinicopathological factors was observed in our patient population. Our study demonstrates that EGFR and IGF-1R appear to be overexpressed in a subset of AAs and that strong membranous expression of EGFR is an independent predictor for overall survival in patients with AA. EGFR and IGF-1R represent potential therapeutic targets for treatment of patient with AAs.
Asunto(s)
Adenocarcinoma/química , Ampolla Hepatopancreática/química , Biomarcadores de Tumor/análisis , Neoplasias del Conducto Colédoco/química , Receptores ErbB/análisis , Receptores de Somatomedina/análisis , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Ampolla Hepatopancreática/patología , Neoplasias del Conducto Colédoco/mortalidad , Neoplasias del Conducto Colédoco/patología , Femenino , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Análisis Multivariante , Valor Predictivo de las Pruebas , Pronóstico , Modelos de Riesgos Proporcionales , Receptor IGF Tipo 1 , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Análisis de Matrices TisularesRESUMEN
The biological relevance of histological subtyping of ampullary carcinoma into intestinal vs pancreaticobiliary types remains to be determined. In an effort to molecularly profile these subtypes of ampullary carcinomas, we conducted a two-phase study. In the discovery phase, we identified 18 pancreatobiliary-type ampullary carcinomas and 14 intestinal-type ampullary carcinomas using stringent pathologic criteria and performed next-generation sequencing targeting 279 cancer-associated genes on these tumors. Although the results showed overlapping of genomic alterations between the two subtypes, trends including more frequent KRAS alterations in pancreatobiliary-type ampullary carcinoma (61 vs 29%) and more frequent mutations in APC in intestinal-type ampullary carcinoma (43 vs 17%) were observed. Of the entire cohort of 32 tumors, the most frequently mutated gene was TP53 (n=17); the most frequently amplified gene was ERBB2 (n=5); and the most frequently deleted gene was CDKN2A (n=6). In the second phase of the study, we aimed at validating our observation on ERBB2 and assessed ERBB2 amplification and protein overexpression in a series of 100 ampullary carcinomas. We found that (1) gene amplification and immunohistochemical overexpression of ERBB2 occurred in 13% of all ampullary carcinomas, therefore providing a potential target for anti-HER2 therapy in these tumors; (2) amplification and immunohistochemical expression correlated in all cases, thus indicating that immunohistochemistry could be used to screen tumors; and (3) none of the 14 ERBB2-amplified tumors harbored any downstream driver mutations in KRAS/NRAS, whereas 56% of the cases negative for ERBB2 amplification did, an observation clinically pertinent as downstream mutations may cause primary resistance to inhibition of EGFR family members.
Asunto(s)
Ampolla Hepatopancreática , Biomarcadores de Tumor/genética , Carcinoma/genética , Neoplasias del Conducto Colédoco/genética , Amplificación de Genes , Perfilación de la Expresión Génica , Receptor ErbB-2/genética , Adulto , Anciano , Anciano de 80 o más Años , Ampolla Hepatopancreática/química , Ampolla Hepatopancreática/patología , Biomarcadores de Tumor/análisis , Carcinoma/química , Carcinoma/patología , Neoplasias del Conducto Colédoco/química , Neoplasias del Conducto Colédoco/patología , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Análisis Mutacional de ADN , Femenino , GTP Fosfohidrolasas/genética , Eliminación de Gen , Perfilación de la Expresión Génica/métodos , Regulación Neoplásica de la Expresión Génica , Predisposición Genética a la Enfermedad , Humanos , Inmunohistoquímica , Hibridación in Situ , Masculino , Proteínas de la Membrana/genética , Persona de Mediana Edad , Mutación , Análisis de Secuencia por Matrices de Oligonucleótidos , Fenotipo , Valor Predictivo de las Pruebas , Proteínas Proto-Oncogénicas p21(ras)/genética , Receptor ErbB-2/análisis , Proteína p53 Supresora de Tumor/genética , Regulación hacia ArribaRESUMEN
Amphicrine carcinoma is a peculiar tumor in which the cells have both exocrine and neuroendocrine differentiation, with mucus and neuroendocrine granules within the cytoplasm. In the 2010 WHO classification of tumors of the digestive tract, they have been included in the intermediate-grade malignant category of mixed adenoneuroendocrine carcinomas (MANECs). These tumors are extremely rare in the gastrointestinal tract. Four cases have been reported in the stomach, three in the pancreas, and one in the liver. To the best of our knowledge, this report describes the first case of amphicrine carcinoma in the ampullary region.
Asunto(s)
Ampolla Hepatopancreática , Biomarcadores de Tumor/análisis , Carcinoma Neuroendocrino/diagnóstico , Neoplasias del Conducto Colédoco/diagnóstico , Anciano , Ampolla Hepatopancreática/patología , Anorexia/etiología , Carcinoma Neuroendocrino/química , Carcinoma Neuroendocrino/complicaciones , Carcinoma Neuroendocrino/patología , Cromograninas/análisis , Neoplasias del Conducto Colédoco/química , Neoplasias del Conducto Colédoco/complicaciones , Neoplasias del Conducto Colédoco/patología , Diagnóstico Diferencial , Humanos , Inmunohistoquímica , Ictericia/etiología , Queratina-7/análisis , Metástasis Linfática , Masculino , Náusea/etiología , Clasificación del Tumor , Receptores de Superficie Celular/análisis , Sinaptofisina/análisis , Tomografía Computarizada por Rayos X , Pérdida de PesoRESUMEN
Mixed adenoneuroendocrine carcinoma (MANEC) is a malignant tumor with adenocarcinoma and neuroendocrine components, with ≥30% of each component required. MANEC of the ampulla is rare. To the best of our knowledge, only 15 cases of MANEC of the ampulla have been reported in the English-language literature. Here, we report two cases of MANEC of the ampulla in two women aged 43 and 60 years, which was confirmed by histology after pancreaticoduodenectomy. These tumors contained neuroendocrine and adenocarcinoma components. The neuroendocrine components were positive for chromogranin A (CgA), synaptophysin (Syn) and CD56 by immunostaining. The adenocarcinoma components were negative for CgA, Syn and CD56. Both cases were T3N0M0 (Stage IIIA). They survived for 15 and 20 mo after surgery, respectively. A brief discussion about the histopathological features, clinical behavior and treatment of MANEC of ampulla, and review of the relevant literature are presented.
Asunto(s)
Adenocarcinoma/patología , Ampolla Hepatopancreática/patología , Neoplasias del Conducto Colédoco/patología , Neoplasias Complejas y Mixtas/patología , Tumores Neuroendocrinos/patología , Adenocarcinoma/química , Adenocarcinoma/cirugía , Adulto , Ampolla Hepatopancreática/química , Ampolla Hepatopancreática/cirugía , Biomarcadores de Tumor/análisis , Biopsia , Colangiopancreatografia Retrógrada Endoscópica , Neoplasias del Conducto Colédoco/química , Neoplasias del Conducto Colédoco/cirugía , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Neoplasias Complejas y Mixtas/química , Neoplasias Complejas y Mixtas/cirugía , Tumores Neuroendocrinos/química , Tumores Neuroendocrinos/cirugía , Pancreaticoduodenectomía , Resultado del TratamientoRESUMEN
OBJECTIVES: Interferons (IFNs) have several anticancer mechanisms. A number of clinical trials have been conducted regarding adjuvant IFN-α therapy in pancreatic cancer. Type I IFNs exert their effect via the type I IFN receptor (IFNAR-1, IFNAR-2c). The aims of the present study were to determine the type I IFN receptor expression in pancreatic and periampullary cancer tissues and to study its relation with clinicopathological factors. METHODS: Receptor expression was determined by immunohistochemistry in paraffin-embedded cancer tissue of 47 pancreatic and 54 periampullary cancer patients. RESULTS: The results demonstrated that 91.5% of the pancreatic tumors and 88.9% of the periampullary tumors showed expression of IFNAR-1, of which 23.4% and 13.0% were strongly positive, respectively. Regarding IFNAR-2c expression, 68.1% of the pancreatic tumors and 68.5% of the periampullary tumors were positive, of which 4.3% of the pancreatic tumors and none of the periampullary tumors had a strong expression. No statistically significant associations were found between type I IFN receptor expression and clinicopathological factors or survival. CONCLUSIONS: Type I IFN receptors are expressed in pancreatic and periampullary cancer tissues although with great intertumoral and intratumoral variability. A small proportion of both tumors showed a strong expression of the IFNAR-1; only a very small percentage of the pancreatic tumors showed strong expression of the IFNAR-2c.
Asunto(s)
Ampolla Hepatopancreática/química , Biomarcadores de Tumor/análisis , Neoplasias del Conducto Colédoco/química , Neoplasias Pancreáticas/química , Receptor de Interferón alfa y beta/análisis , Adulto , Anciano , Anciano de 80 o más Años , Ampolla Hepatopancreática/patología , Ampolla Hepatopancreática/cirugía , Neoplasias del Conducto Colédoco/mortalidad , Neoplasias del Conducto Colédoco/patología , Neoplasias del Conducto Colédoco/terapia , Femenino , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/terapia , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Factores de Tiempo , Resultado del TratamientoRESUMEN
Large cell neuroendocrine carcinoma (LCNEC) in the biliary system is a poorly differentiated, high-grade neuroendocrine tumor. These tumors exhibit aggressive behavior and an increased tendency for early nodal and distant metastases. Herein, we report an unusual case of a pure primary LCNEC of the common bile duct (CBD). A 75-year-old female presented with nausea and jaundice. The patient underwent a CBD excision with lymph node dissection. Upon histological and immunohistochemical examination, the tumor exhibited pure large cell-type neuroendocrine features. Metastases were noted in two of the eight lymph nodes. The patient was administered adjuvant chemotherapy. The patient's cancer recurred 7 mo after surgery, and the patient died from liver failure 5 mo after recurrence. The prognosis of LCNEC of CBD remains poor despite curative resection and adjuvant chemotherapy. The role of additional therapies, such as multimodal treatment including radiation therapy, must be further studied to improve the prognoses of patients.
Asunto(s)
Neoplasias del Conducto Colédoco/patología , Tumores Neuroendocrinos/secundario , Anciano , Biomarcadores de Tumor/análisis , Biopsia , Diferenciación Celular , Quimioterapia Adyuvante , Colangiopancreatografia Retrógrada Endoscópica , Neoplasias del Conducto Colédoco/química , Neoplasias del Conducto Colédoco/cirugía , Resultado Fatal , Femenino , Humanos , Inmunohistoquímica , Escisión del Ganglio Linfático , Metástasis Linfática , Recurrencia Local de Neoplasia , Tumores Neuroendocrinos/química , Tumores Neuroendocrinos/cirugía , República de Corea , Factores de Tiempo , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Carga TumoralRESUMEN
BACKGROUND/AIMS: Clinicopathological investigation of the indications for the use of endoscopic papillectomy as a treatment for carcinoma in situ of the ampulla of Vater (CAV). MATERIALS AND METHODS: Of 97 patients diagnosed with CAV in our department over the last 15 years, the 5 patients who received a carcinoma in situ diagnosis and were included in this retrospective study. RESULTS: The lesions in the patients were classified as either the superficial or luminal type, based on endoscopic findings. Histological findings showed that the major duodenal papilla (Ad) was the main site of CAV in the superficial type and that the common duct into the duodenal lumen (Ac) was the primary site in the luminal type. Immunohistochemical staining showed that the superficial-type lesions were positive for cytokeratin 20, suggesting development of the cancer from the Ad. The luminal-type lesion was positive for cytokeratin 7 and negative for cytokeratin 20, suggesting an origin in the pancreatobiliary duct. Mucin-2 was expressed in the superficial type, and mucin-1 in the luminal type. CONCLUSION: Superficial-type lesions, which are principally located in the Ad, exhibit little tendency to invade surrounding tissues, whereas the luminal-type lesions, which are predominantly located in the Ac, may tend to be more invasive. Although endoscopic papillectomy might be indicated for the superficial-type lesions, caution is needed in the determination of the extent of luminal-type lesions.
Asunto(s)
Ampolla Hepatopancreática/cirugía , Carcinoma in Situ/patología , Carcinoma in Situ/cirugía , Neoplasias del Conducto Colédoco/patología , Neoplasias del Conducto Colédoco/cirugía , Anciano , Carcinoma in Situ/química , Neoplasias del Conducto Colédoco/química , Endoscopía Gastrointestinal , Femenino , Humanos , Queratina-20/análisis , Queratina-7/análisis , Masculino , Persona de Mediana Edad , Mucina-1/análisis , Mucina 2/análisis , Selección de Paciente , Estudios RetrospectivosRESUMEN
Intraductal papillary mucinous neoplasm of the bile duct (IPNB) is recognized as a precancerous lesion; however, both its pathogenesis and progression remain unclear. We present here a case of IPNB arising from the gallbladder accompanied by bile duct tumor thrombus in a 79-year-old female. The resected specimen revealed a tubulopapillary adenoma with no malignant cells. This case suggests that even in the absence of malignant cells, these tumors can behave as malignant tumors requiring aggressive treatment. Even if no malignant cells are present, intraepithelial neoplasms occurring in the ampullopancreatobiliary tract can behave as malignant tumors.
Asunto(s)
Adenoma/patología , Carcinoma in Situ/patología , Neoplasias del Conducto Colédoco/patología , Neoplasias de la Vesícula Biliar/patología , Neoplasias Quísticas, Mucinosas y Serosas/patología , Adenoma/química , Adenoma/diagnóstico por imagen , Adenoma/cirugía , Anciano , Biomarcadores de Tumor/análisis , Biopsia , Carcinoma in Situ/química , Carcinoma in Situ/diagnóstico por imagen , Carcinoma in Situ/cirugía , Colangiopancreatografia Retrógrada Endoscópica , Pancreatocolangiografía por Resonancia Magnética , Colecistectomía , Neoplasias del Conducto Colédoco/química , Neoplasias del Conducto Colédoco/diagnóstico por imagen , Neoplasias del Conducto Colédoco/cirugía , Femenino , Neoplasias de la Vesícula Biliar/química , Neoplasias de la Vesícula Biliar/diagnóstico por imagen , Neoplasias de la Vesícula Biliar/cirugía , Humanos , Inmunohistoquímica , Invasividad Neoplásica , Neoplasias Quísticas, Mucinosas y Serosas/química , Neoplasias Quísticas, Mucinosas y Serosas/diagnóstico por imagen , Neoplasias Quísticas, Mucinosas y Serosas/cirugía , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
Gastrointestinal stromal tumors (GISTs) usually develop in the stomach and small intestine and only rarely occur at the ampulla of Vater, with only 11 cases reported in the literature. We report a case of a GIST of the ampulla of Vater. A 36-year-old, previously healthy man presented with a loss of consciousness lasting a few minutes. A gastroduodenal endoscopy revealed a submucosal tumor with central ulceration at the ampulla of Vater. The enhanced computed tomography scan revealed a smooth-outlined hypervascular solid mass (24 mm × 30 mm) in the second part of the duodenum. Neither lymphadenopathy nor metastasis was observed. Magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography showed normal bile and pancreatic ducts. Biopsies were collected from the ulcerative lesion, and the tumor was diagnosed as a GIST. A submucosal tumor with central ulceration may be a characteristic form of GISTs of the ampulla of Vater, and biopsy studies are useful for the diagnosing such tumors. The patient underwent pancreatoduodenectomy, and the operative specimen revealed a 2.2-cm GIST with 1 mitosis per 50 high-power fields. The gold standard for treatment of GISTs is surgical resection without rupture of a capsule. If technically possible, local resection may be considered. However, when the location of the lesion presents challenges, a pancreatoduodenectomy should be performed for GIST of the ampulla of Vater.
Asunto(s)
Ampolla Hepatopancreática/patología , Neoplasias del Conducto Colédoco/patología , Tumores del Estroma Gastrointestinal/patología , Adulto , Ampolla Hepatopancreática/química , Ampolla Hepatopancreática/diagnóstico por imagen , Ampolla Hepatopancreática/cirugía , Biomarcadores de Tumor/análisis , Proliferación Celular , Colangiopancreatografia Retrógrada Endoscópica , Pancreatocolangiografía por Resonancia Magnética , Neoplasias del Conducto Colédoco/química , Neoplasias del Conducto Colédoco/cirugía , Duodenoscopía , Endosonografía , Tumores del Estroma Gastrointestinal/química , Tumores del Estroma Gastrointestinal/cirugía , Gastroscopía , Humanos , Inmunohistoquímica , Masculino , Índice Mitótico , Pancreaticoduodenectomía , Valor Predictivo de las Pruebas , Tomografía Computarizada por Rayos XRESUMEN
Histologic classification of ampullary carcinomas into intestinal, pancreatobiliary, or other subtypes is easily achievable in some cases but difficult in others. Immunohistochemical (IHC) stains may allow distinction between the subtypes; however, their added value to routine hematoxylin and eosin (H&E) evaluation has not been systematically evaluated. Inconsistent histologic subtyping has hampered current clinical research and therapeutic trials. In this study, a consecutive series of 105 ampullary carcinomas was subtyped first by H&E evaluation and then by the evaluation of an IHC panel composed of CK7, CK20, CDX2, MUC1, and MUC2, and the added value of IHC was analyzed. By H&E, a consensus diagnosis, defined as concordant subtyping among at least 3 of the 4 independent study pathologists, was achieved in 81 of the 105 (77%) cases. There was excellent agreement for poorly differentiated and mucinous subtypes (κ=0.72 and 0.89, respectively) but only good agreement for intestinal and pancreatobiliary subtypes (κ=0.57 and 0.48, respectively) and poor agreement for mixed subtype (κ=0.09). By IHC, CK7 showed no informative value (being positive in ≥70% of the cases in both intestinal and pancreatobiliary subtypes), whereas a subtyping schema incorporating the combination staining patterns of CK20, CDX2, MUC1, and MUC2 did. By this schema, "intestinal subtype" was defined as having (1) positive staining for CK20 or CDX2 or MUC2 and negative staining for MUC1, or (2) positive staining for CK20, CDX2, and MUC2, irrespective of the MUC1 result; and "pancreatobiliary subtype" was defined as having positive staining for MUC1 and negative staining for CDX2 and MUC2, irrespective of CK20 results. Cases not fitting one of these 3 categories were regarded as "ambiguous" immunohistochemically. By combining this schema with H&E evaluation, 97 of the 105 cases (92%) could be classified into either intestinal or pancreatobiliary subtype. In particular, immunophenotyping allowed categorization of 75% of poorly differentiated adenocarcinomas and 69% of cases with mixed histologic features as either intestinal or pancreatobiliary subtype. Most mucinous adenocarcinomas (88%) were clearly intestinal subtype by IHC. Thus, our IHC schema enhanced the subtyping of ampullary carcinoma and, in combination with H&E evaluation, allowed a dichotomous classification in 92% of the cases. Should further independent studies reaffirm our findings, this schema may serve as a valuable tool in both diagnostic and research settings.
Asunto(s)
Adenocarcinoma/química , Ampolla Hepatopancreática/química , Biomarcadores de Tumor/análisis , Neoplasias del Conducto Colédoco/química , Inmunohistoquímica , Adenocarcinoma/clasificación , Adenocarcinoma/patología , Adenocarcinoma Mucinoso/química , Adenocarcinoma Mucinoso/clasificación , Adenocarcinoma Mucinoso/patología , Ampolla Hepatopancreática/patología , Biopsia , Diferenciación Celular , Neoplasias del Conducto Colédoco/clasificación , Neoplasias del Conducto Colédoco/patología , Humanos , Variaciones Dependientes del Observador , Valor Predictivo de las Pruebas , Pronóstico , Reproducibilidad de los Resultados , Estudios RetrospectivosRESUMEN
BACKGROUND: MicroRNA expression patterns in many physiological and oncogenic processes have been established. However, the role of aberrant miRNA expression in periampullary carcinoma (PAC) has not been elucidated. We hypothesize that PAC may have differential expression of miRNAs which may differentiate the tumor histological subtypes. METHODS: Fresh paired tumor and control samples were collected from the PAC patients undergoing Whipple's pancreaticoduodenectomy. Microarray miRNA profiling was performed utilizing tumor (n = 40) and control tissues; adjacent normal pancreas (n = 22), six each distal CBD, duodenum and ampulla. Data obtained was subjected to statistical and bioinformatic analysis. Differentially expressed miRNAs obtained were validated using qPCR in an independent set of samples. RESULTS: Comparison of PAC tissue samples with controls revealed 29 common and differentially expressed miRNAs (20 upregulated and 9 downregulated) with a higher statistical significance (p < 0.001) and fold change (log2 FC > 1.5). A subset of 16 miRNAs (15 overexpressed and 1 underexpressed) differed in expression levels between pancreatobiliary and intestinal subtypes. Among these, miR-375, miR-31 and miR-196a expressions varied significantly between histological subtypes. Differential expression profiles of miRNAs specific to TNM staging was also observed in PAC subtypes. Target gene prediction for the differentially expressed miRNAs in PAC revealed that target genes are enriched for certain pathways. Particularly, Wnt signaling pathway genes appear to be relevant targets for most of the differentially expressed miRNAs. CONCLUSION: Differentially expressed common miRNA signatures identified in PAC subgroups may have a role in pathogenesis of PAC and miR-375, miR-31 and miR-196a expression patterns may differentiate PAC subtypes.
Asunto(s)
Ampolla Hepatopancreática/química , Neoplasias del Conducto Colédoco/genética , MicroARNs/análisis , Neoplasias Pancreáticas/genética , Biomarcadores de Tumor/genética , Carcinoma/genética , Neoplasias del Conducto Colédoco/química , Neoplasias del Conducto Colédoco/patología , Femenino , Humanos , Masculino , MicroARNs/biosíntesis , Persona de Mediana Edad , Neoplasias Pancreáticas/química , Neoplasias Pancreáticas/patología , TranscriptomaAsunto(s)
Neoplasias del Conducto Colédoco/diagnóstico , Leucemia Mieloide Aguda/diagnóstico , Sarcoma Mieloide/diagnóstico , Dolor Abdominal/etiología , Antígenos CD/análisis , Antígenos de Diferenciación Mielomonocítica/análisis , Neoplasias del Conducto Colédoco/química , Neoplasias del Conducto Colédoco/complicaciones , Neoplasias del Conducto Colédoco/patología , Femenino , Humanos , Ictericia Obstructiva/etiología , Queratinas/análisis , Leucemia Mieloide Aguda/complicaciones , Leucemia Mieloide Aguda/patología , Persona de Mediana Edad , Peroxidasa/análisis , Proteínas Proto-Oncogénicas c-kit/análisis , Prurito/etiología , Sarcoma Mieloide/complicaciones , Sarcoma Mieloide/patología , Vimentina/análisisRESUMEN
BACKGROUND: We assessed the expression of cytokeratin (CK) and apomucin (MUC) in ampullary carcinoma (AC) to develop a system for the classification of ACs on the basis of their clinical significance. METHOD: We studied the expressions of CK7, CK20, MUC1, MUC2, MUC5AC, and MUC6 in 43 patients with ACs. Clinical data were obtained retrospectively by examining surgically resected ACs of the patients. RESULTS: We classified the cases into 3 groups: tumors expressing CK20 and lacking MUC1 (intestinal type [I-type], 26%), tumors expressing MUC1 and lacking CK20 (pancreatobiliary type [PB-type], 35%), and those expressing or lacking both CK20 and MUC1 (other type [O-type], 39%). Eight (73%) of 11 I-type carcinomas, 3 (20%) of 15 PB-type carcinomas, and 4 (24%) of 17 O-type carcinomas were classified as pT1. The number of I-type carcinomas in the early tumor stages was significantly higher than the number of PB- and O-type carcinomas (p = 0.014 and p = 0.018, respectively). The 5-year survival rates for pT1, pT2, and pT3 tumors were 76%, 33%, and 22%, respectively (p < 0.001). Rates of MUC5AC and MUC6 coexpression for I-type, PB-type, and O-type tumors were 18%, 13%, and 53%, respectively. There was a significant correlation between MUC5AC and MUC6 coexpression and O-type characteristics (p = 0.031). The five-year survival rates for O-type ACs with and without MUC5AC and MUC6 coexpression were 71% and 17%, respectively (p = 0.048). CONCLUSIONS: The immunohistochemical subtypes based on CK and MUC expression correlated with tumor progression. Gastric MUC5AC and MUC6 coexpression correlated with better prognosis for O-type ACs.
Asunto(s)
Ampolla Hepatopancreática/química , Biomarcadores de Tumor/análisis , Carcinoma/química , Neoplasias del Conducto Colédoco/química , Mucina-1/análisis , Adulto , Anciano , Anciano de 80 o más Años , Ampolla Hepatopancreática/patología , Ampolla Hepatopancreática/cirugía , Carcinoma/clasificación , Carcinoma/mortalidad , Carcinoma/patología , Carcinoma/cirugía , Distribución de Chi-Cuadrado , Neoplasias del Conducto Colédoco/clasificación , Neoplasias del Conducto Colédoco/mortalidad , Neoplasias del Conducto Colédoco/patología , Neoplasias del Conducto Colédoco/cirugía , Progresión de la Enfermedad , Femenino , Humanos , Inmunohistoquímica , Japón , Estimación de Kaplan-Meier , Queratina-20/análisis , Masculino , Persona de Mediana Edad , Mucina 5AC/análisis , Mucina 6/análisis , Estadificación de Neoplasias , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Duodenal gangliocytic paraganglioma is an extremely rare tumor and few cases have been reported to date. CASE PRESENTATION: The authors report a case of gangliocytic paraganglioma verified by post-op pathology after pancreaticoduodenectomy for a tumor in the ampulla of Vater. The 56-year-old male patient concerned visited our emergency room with melena that started one week prior to hospitalization. The patient was diagnosed to have a tumor in the ampulla of Vater with bleeding on its surface. However post-op, he was diagnosed as having gangliocytic paraganglioma by immunohistochemistry. CONCLUSION: This tumor has precise clinical implications, and if continuous follow up is conducted after careful diagnosis and surgical treatment, invasive major operations, such as, radical pancreaticoduodenectomy can be avoided.