RESUMEN
BACKGROUND: It is difficult to predict the biologic behavior of pancreatic endocrine tumors in absence of metastases or invasion into adjacent organs. The World Health Organization (WHO) has proposed in 2004 size, angioinvasion, mitotic activity, and MIB1 proliferation index as prognostic criteria. Our aim was to test retrospectively the predictive value of these 2004 WHO criteria and of CK19, CD99, COX2, and p27 immunohistochemistry in a large series of patients with long-term follow-up. DESIGN: The histology of 216 pancreatic endocrine tumor specimens was reviewed and the tumors were reclassified according to the 2004 WHO classification. The prognostic value of the WHO classification and the histopathologic criteria necrosis and nodular fibrosis was tested in 113 patients. A tissue microarray was constructed for immunohistochemical staining. The staining results were scored quantitatively for MIB1 and semiquantitatively for CK19, COX2, p27, and CD99. The prognostic value of these markers was tested in 93 patients. RESULTS: The stratification of the patients into 4 risk groups according to the 2004 WHO classification was reliable with regard to both time span to relapse and tumor-specific death. In a multivariate analysis, the CK19 status was shown to be independent of the WHO criteria. By contrast, the prognostic significance of COX2, p27, and CD99 could not be confirmed. CONCLUSIONS: The 2004 WHO classification with 4 risk groups is very reliable for predicting both disease-free survival and the time span until tumor-specific death. CK19 staining is a potential additional prognostic marker independent from the WHO criteria for pancreatic endocrine tumors.
Asunto(s)
Carcinoma de Células de los Islotes Pancreáticos/diagnóstico , Insulinoma/diagnóstico , Queratina-19/análisis , Neoplasias Pancreáticas/diagnóstico , Organización Mundial de la Salud , Antígeno 12E7 , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antígenos CD/análisis , Carcinoma de Células de los Islotes Pancreáticos/química , Carcinoma de Células de los Islotes Pancreáticos/mortalidad , Carcinoma de Células de los Islotes Pancreáticos/patología , Carcinoma de Células de los Islotes Pancreáticos/cirugía , Moléculas de Adhesión Celular/análisis , Ciclooxigenasa 2/análisis , Supervivencia sin Enfermedad , Femenino , Fibrosis , Estudios de Seguimiento , Humanos , Inmunohistoquímica , Insulinoma/química , Insulinoma/mortalidad , Insulinoma/patología , Insulinoma/cirugía , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Necrosis , Invasividad Neoplásica , Estadificación de Neoplasias , Neoplasias Pancreáticas/química , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/cirugía , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Recurrencia , Reproducibilidad de los Resultados , Estudios Retrospectivos , Factores de Tiempo , Análisis de Matrices Tisulares , Resultado del TratamientoRESUMEN
Although the majority of pancreatic neoplasms are infiltrating ductal adenocarcinomas or other neoplasms with ductal differentiation, neoplasms with acinar, endocrine, mixed, or uncertain differentiation constitute a diverse and distinctive group. The most common and best-characterized nonductal neoplasms are pancreatic endocrine neoplasm, acinar cell carcinoma, pancreatoblastoma, and solid pseudopapillary neoplasm. This review details the clinical and pathologic features of these nonductal neoplasms, highlighting diagnostic criteria including the use of specific immunohistochemical stains to define the cellular differentiation of the neoplasms.
Asunto(s)
Adenocarcinoma Papilar/patología , Adenoma de Células de los Islotes Pancreáticos/patología , Carcinoma de Células Acinares/patología , Carcinoma de Células de los Islotes Pancreáticos/patología , Páncreas/patología , Neoplasias Pancreáticas/patología , Adenocarcinoma Papilar/química , Adenoma de Células de los Islotes Pancreáticos/química , Biomarcadores de Tumor , Carcinoma de Células Acinares/química , Carcinoma de Células de los Islotes Pancreáticos/química , Humanos , Páncreas/química , Neoplasias Pancreáticas/químicaRESUMEN
Hepatoid carcinomas are tumors that display, at least focally, cytologic and/or architectural features of hepatocellular carcinoma. They have been described in several organs, most notably in the stomach and ovary. We report a case of hepatoid carcinoma of the pancreas that developed in a 41-year-old woman in association with a pancreatic endocrine carcinoma. The fine needle aspiration material was characterized by the presence of monotonous, small-to-medium sized tumor cells with round nuclei and finely granular chromatin, intermixed with more atypical tumor cells displaying larger nuclei with coarse clumped chromatin, prominent nucleoli, and moderate amounts of foamy cytoplasm. The excised specimen displayed a poorly differentiated pancreatic endocrine carcinoma associated with well-defined islands of larger tumor cells growing in a perisinusoidal pattern which, based on their immunohistochemical profile and the demonstration of bile, proved to represent a hepatoid component. This case and prior examples in the literature suggest that hepatoid carcinomas of the pancreas appear to be a heterogeneous group of tumors (pure or associated with another histologic component) that are often associated with early liver metastasis and a short survival, although those arising as a component of endocrine tumors seem to fare slightly better. Hepatoid carcinoma of the pancreas should be included in the differential diagnosis of pancreatic tumors composed of large eosinophilic cells.
Asunto(s)
Carcinoma Hepatocelular/patología , Carcinoma de Células de los Islotes Pancreáticos/patología , Neoplasias Pancreáticas/patología , Adulto , Biomarcadores de Tumor/análisis , Carcinoma Hepatocelular/química , Carcinoma Hepatocelular/cirugía , Carcinoma de Células de los Islotes Pancreáticos/química , Carcinoma de Células de los Islotes Pancreáticos/cirugía , Resultado Fatal , Femenino , Humanos , Inmunohistoquímica , Neoplasias Primarias Múltiples , Neoplasias Pancreáticas/química , Neoplasias Pancreáticas/cirugía , Tomografía Computarizada por Rayos X , alfa-Fetoproteínas/análisisRESUMEN
Precise localization and diagnosis of pancreatic endocrine tumors (PETs) is important, because pancreatic PETs have different clinical and biological behavior and treatment modalities than do exocrine pancreatic tumors. In contrast to the much more common exocrine adenocarcinomas, cytologic studies of PET are relatively rare and many cytopathologists lack experience with the cytomorphologic features of these tumors.During the last 10 yr, endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) has matured into an accurate, highly sensitive, and cost-effective modality for the preoperative localization of pancreatic PETs. This has resulted in an increased number of PETs first sampled as cytology specimens. This manuscript focuses on the cytomorphologic features most suggestive of pancreatic PETs, differential diagnosis, and diagnostic pitfalls of PETs. The technical development of EUS-guided FNA and the ancillary studies for pancreatic PETs are also reviewed. The data summarized in this review indicate that EUS-FNA is a valuable method in the recognition of pancreatic PETs and in most cases cytopathologists could reach a correct diagnosis of these tumors, including their hormone producing capability on aspirated cytologic material.
Asunto(s)
Biopsia con Aguja Fina/métodos , Carcinoma de Células de los Islotes Pancreáticos/patología , Endoscopía del Sistema Digestivo/métodos , Insulinoma/patología , Neoplasias Pancreáticas/patología , Ultrasonografía/métodos , Adenocarcinoma Papilar/patología , Biomarcadores de Tumor/análisis , Carcinoma de Células Acinares/patología , Carcinoma de Células de los Islotes Pancreáticos/química , Carcinoma Ductal Pancreático/patología , Diagnóstico Diferencial , Gastrinoma/química , Gastrinoma/patología , Glucagonoma/química , Glucagonoma/patología , Humanos , Inmunohistoquímica , Insulinoma/química , Linfoma/patología , Neoplasias Pancreáticas/químicaRESUMEN
Metastases to the breast are rare, accounting for an estimated 1% to 2% of malignant breast neoplasms. The key histopathologic features supporting a metastasis to the breast have been stated to be the absence of elastosis, presence of a pushing border (circumscribed lesion), multiple satellite foci, lymphatic emboli, and, most importantly, the absence of an in situ carcinoma component. We report a unique case of a pancreatic islet cell tumor metastatic to the breast of an 18-year-old girl. Clinically, the patient was thought to have a mammary primary because on her initial biopsy, the metastasis grew within mammary ducts and colonized a complex sclerosing lesion, simulating an in situ component. However, review of slides from the prior pancreatic neoplasm, review of slides from the subsequent mastectomy, and use of immunohistochemistry allowed recognition of the lesion as a metastasis, which proved to be the first clinical manifestation of a systemic relapse. To our knowledge, this is the second case of islet cell tumor reported to metastasize to the breast, and the first report of a metastasis proven to have grown within existing ducts of the breast by immunohistochemistry.
Asunto(s)
Neoplasias de la Mama/secundario , Carcinoma in Situ/patología , Carcinoma Ductal de Mama/patología , Carcinoma de Células de los Islotes Pancreáticos/secundario , Neoplasias Pancreáticas/patología , Adolescente , Biomarcadores de Tumor/análisis , Neoplasias de la Mama/química , Neoplasias de la Mama/cirugía , Carcinoma in Situ/química , Carcinoma in Situ/cirugía , Carcinoma Ductal de Mama/química , Carcinoma Ductal de Mama/cirugía , Carcinoma de Células de los Islotes Pancreáticos/química , Carcinoma de Células de los Islotes Pancreáticos/cirugía , Diagnóstico Diferencial , Femenino , Humanos , Neoplasias Pancreáticas/química , Neoplasias Pancreáticas/cirugía , Resultado del TratamientoRESUMEN
The cytoplasm of pancreatic endocrine tumors (PET) can show a diverse range of appearances from clear, to oncocytic, to intracellular mucin accumulation, and the presence of intracytoplasmic inclusions. Intracytoplasmic eosinophilic inclusions can vary morphologically and the spectrum ranges from small, dot-like hyaline inclusions, to deeply acidophilic/eosinophilic ones that occupy almost the whole cytoplasm and displace the nucleus eccentrically: the so-called "rhabdoid" phenotype. The aim of this study was to analyze the frequency, morphology, behavior, and relationship to clinicopathological features of large intracytoplasmic inclusions, including the rhabdoid phenotype, in a large number of PET. The morphological features of 84 cases were assessed for the presence of large, globular intracytoplasmic inclusions. Fourteen of 84 cases contained intracytoplasmic inclusions with 5 cases containing cells conforming to the characteristic rhabdoid morphology. The remaining nine cases showed pale intracytoplasmic inclusions. Four of the five cases with rhabdoid cells had spread to lymph nodes and/or peripancreatic fatty tissue. This study confirms that a spectrum of large intracytoplasmic inclusions is encountered in PET, ranging from lightly eosinophilic intracytoplasmic globules to the more typical rhabdoid phenotype (deeply eosinophilic inclusions). This phenotype, in particular the rhabdoid cells, is worthy of attention as a proportion may show lymphovascular invasion with evidence of metastasis at the time of presentation, irrespective of size, mitotic rates, or necrosis.
Asunto(s)
Adenoma de Células de los Islotes Pancreáticos/patología , Carcinoma de Células de los Islotes Pancreáticos/patología , Cuerpos de Inclusión/patología , Neoplasia Endocrina Múltiple Tipo 1/patología , Neoplasias Pancreáticas/patología , Tumor Rabdoide/patología , Adenoma de Células de los Islotes Pancreáticos/química , Adulto , Anciano , Biomarcadores de Tumor/análisis , Carcinoma de Células de los Islotes Pancreáticos/química , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Neoplasia Endocrina Múltiple Tipo 1/química , Neoplasias Pancreáticas/química , Estudios Retrospectivos , Tumor Rabdoide/químicaRESUMEN
AIMS: Pancreatic endocrine tumours (PET) containing ductules are an uncommon histological variant. Considerable conjecture surrounds the origin and histogenesis of the ductules. Opinions range from the ductules being an inherent part of the tumour, to others who feel they are merely entrapped. A study of 21 cases of this variant was undertaken with particular attention paid to the distribution and morphology of the ductules, the presence of entrapped acinar tissue and the surrounding uninvolved pancreatic tissue. METHODS AND RESULTS: Twenty-one cases were detailed occurring in either gender equally and with a wide age range (19-85 years). All cases, except one, were sporadic, the vast majority were located in the tail and were of small size (less than 2.0 cm). All cases were typified by stromal fibrosis, either diffuse (15) or in the form of septae (6). Embedded within the fibrous tissue were ductular structures, some of which were dilated and ectatic. The ductules were centrally located (5), at the periphery of the tumour (9) or diffusely scattered throughout the lesion (7). All cases showed ductulo-insular complexes. Insulin was demonstrated in 15 immunohistochemically. CONCLUSIONS: It is likely that in some cases the ductules are entrapped as the tumour grows into surrounding normal pancreatic tissue and the ductular proliferation is a secondary phenomenon. In a proportion of cases, the ductules are likely to be a part of the tumour arising as part of focal chronic inflammation or as a result of the growth factor effects of insulin, in cases associated with insulin production. There is nothing to suggest that the ductules confer any special biological characteristics to the PET and are merely a histological nuance. However, some cases may have a dominant tubular component, which could present problems at frozen section where the association with fibrosis may invoke a mistaken diagnosis of pancreatic ductal adenocarcinoma or chronic pancreatitis.
Asunto(s)
Carcinoma de Células de los Islotes Pancreáticos/patología , Conductos Pancreáticos/patología , Neoplasias Pancreáticas/patología , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/análisis , Carcinoma de Células de los Islotes Pancreáticos/química , Carcinoma Ductal Pancreático/química , Carcinoma Ductal Pancreático/patología , Diagnóstico Diferencial , Femenino , Fibrosis/patología , Humanos , Inmunohistoquímica , Insulina/análisis , Islotes Pancreáticos/química , Islotes Pancreáticos/patología , Queratinas/análisis , Masculino , Persona de Mediana Edad , Conductos Pancreáticos/química , Neoplasias Pancreáticas/química , Pancreatitis Crónica/patologíaRESUMEN
CONTEXT: Neoplasms of the pancreas usually show ductal, acinar or endocrine differentiation. Tumors with mixed exocrine and endocrine components are unusual. We herein describe a case of a mixed ductal-endocrine tumor. CASE REPORT: A 65-year-old woman was referred to our department with a diagnosis of carcinoma of the tail of the pancreas. The patient had a short history of upper abdominal pain, nausea and melena. Upper gastrointestinal endoscopy revealed gastric fundus varices and CT scan demonstrated an inhomogeneous tumor located in the tail of the pancreas infiltrating the spleen and the splenic vein. The patient underwent distal pancreatectomy and splenectomy, and had an uneventful recovery. Pathological examination revealed a mixed ductal-endocrine tumor. The endocrine component was immunoreactive for glucagon, gastrin and somatostatin, and non-reactive for insulin. CONCLUSIONS: Because of the rarity and unpredictable biologic behavior of these tumors, the need for adjuvant therapy has not yet been well-defined. The patient has had a follow-up CT scan every six months, and one and a half years later remains disease free.
Asunto(s)
Carcinoma de Células de los Islotes Pancreáticos/patología , Carcinoma Ductal Pancreático/patología , Tumor Mixto Maligno/patología , Neoplasias Pancreáticas/patología , Anciano , Carcinoma de Células de los Islotes Pancreáticos/química , Carcinoma de Células de los Islotes Pancreáticos/diagnóstico , Carcinoma Ductal Pancreático/química , Carcinoma Ductal Pancreático/diagnóstico , Cromograninas/análisis , Femenino , Gastrinas/análisis , Glucagón/análisis , Humanos , Inmunohistoquímica , Tumor Mixto Maligno/química , Tumor Mixto Maligno/diagnóstico , Neoplasias Pancreáticas/química , Neoplasias Pancreáticas/diagnóstico , Fosfopiruvato Hidratasa/análisis , Somatostatina/análisisRESUMEN
CONTEXT: Obstructive pancreatitis is a specific form of pancreatitis, which is caused by the obstruction of the main pancreatic duct due to tumors or some other causes. Interleukin-8 is induced in acute pancreatitis, but its expression in obstructive pancreatitis has not been clarified. OBJECTIVE: We attempted to provide some insight into the significance of interleukin -8 in the pathogenesis of pancreatic fibrosis. PATIENTS: Fifteen cases of pancreatic cancer, 7 cases of mucinous cystadenoma, 3 cases of Vater's papilla cancer and 9 normal pancreases were included in this study. MAIN OUTCOME MEASURES: The obstructive pancreatitis portions of the above pathologies were evaluated for interleukin-8 expression by means of immunohistochemistry and in situ hybridization. RESULTS: Interleukin-8 was positive in 72% of cases of obstructive pancreatitis. The positive rate was not significantly related to the etiology of the obstruction (P=0.972). Interleukin-8 was expressed in infiltrating cells, proliferating ductular cells and acinar cells. In contrast, normal pancreases and tumor cells lacked interleukin-8 expression (P<0.001 vs. obstructive pancreatitis). Both immunohistochemistry and in situ hybridization demonstrated that interleukin-8 was expressed mostly in acinar cells in mild pancreatic fibrosis, whereas it was expressed in stromal and ductular cells in moderate and severe pancreatic fibrosis. CONCLUSIONS: These results suggest that interleukin-8 expression is related to the fibrotic process in obstructive pancreatitis.
Asunto(s)
Carcinoma de Células de los Islotes Pancreáticos/química , Carcinoma Ductal Pancreático/química , Cistoadenoma Mucinoso/química , Interleucina-8/biosíntesis , Neoplasias Pancreáticas/química , Pancreatitis/patología , Anciano , Carcinoma de Células de los Islotes Pancreáticos/patología , Carcinoma de Células de los Islotes Pancreáticos/cirugía , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/cirugía , Cistoadenoma Mucinoso/patología , Cistoadenoma Mucinoso/cirugía , Citoplasma/química , Citoplasma/patología , Femenino , Humanos , Inmunohistoquímica/métodos , Interleucina-8/inmunología , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/cirugía , Pancreatitis/cirugía , ARN Mensajero/biosíntesis , ARN Neoplásico/biosíntesis , Células del Estroma/química , Células del Estroma/patologíaRESUMEN
Protein 4.1 family proteins are thought to interact with membrane proteins and membrane skeletons. Immunohistochemical studies by light and electron microscopy were performed on mouse pancreas with a specific antibody against protein 4.1B. Specific protein 4.1B immunolabeling was observed on endocrine cells in the islets of Langerhans. Protein 4.1B localized along the plasma membranes facing adjacent cells. By immunoelectron microscopy, the immunolabeling of the cells was restricted to the cytoplasmic side just beneath their plasma membrane, including the membranes adjacent to neighboring cells, while the plasma membranes facing endothelial cells were not immunolabeled for protein 4.1B. The immunolocalization of E-cadherin was similar, if not identical, to that of protein 4.1B supporting the idea that protein 4.1B may be functionally interconnected with adhesion molecules. In a transgenic mouse model of pancreatic beta-cell carcinogenesis (Rip1Tag2), the loss of protein 4.1B expression coincided with the phenotypic transition from adenoma to carcinoma. Therefore, we propose a role of protein 4.1B as a connecting and/or signaling molecule between membrane architecture, cell adhesion, and tumor cell invasion in mouse pancreatic endocrine cells.
Asunto(s)
Carcinoma de Células de los Islotes Pancreáticos/etiología , Islotes Pancreáticos/química , Proteínas de la Membrana/análisis , Proteínas de la Membrana/fisiología , Neoplasias Pancreáticas/etiología , Adenoma de Células de los Islotes Pancreáticos/química , Adenoma de Células de los Islotes Pancreáticos/patología , Animales , Cadherinas/análisis , Carcinoma de Células de los Islotes Pancreáticos/química , Carcinoma de Células de los Islotes Pancreáticos/patología , Membrana Celular/ultraestructura , Ratones , Proteínas de Microfilamentos , Proteínas de Neoplasias/análisisRESUMEN
Neuroendocrine carcinomas of the pancreas are rare neoplasms whose morphologic features generally mirror those seen in neuroendocrine tumors in other organs. Rarely, however, they may display unusual morphologic appearances that can introduce difficulties for diagnosis. We report four cases of primary neuroendocrine carcinomas of the pancreas (islet cell tumors) that were characterized by prominent "rhabdoid" features of the tumor cells. The lesions occurred in two men and two women 37-79 years of age who presented with symptoms of biliary obstruction and epigastric pain; one patient had recurrent gastric ulcers and an elevated gastrin level. The tumors were located in the head and tail of the pancreas and measured 2.5-4.5 cm in greatest diameter. Histologic examination revealed sheets of monotonous tumor cells with uniform round nuclei showing dispersed chromatin and containing abundant densely eosinophilic cytoplasmic inclusions that displaced the nuclei toward the periphery. In all cases, the rhabdoid elements appeared to merge with areas showing a more conventional neuroendocrine morphology. Immunohistochemical studies in all cases showed strong cytoplasmic positivity of the rhabdoid tumor cells for chromogranin, synaptophysin, and cytokeratin. Recognition of this unusual morphologic appearance is of importance to avoid mistaking these lesions for other types of malignant neoplasm.
Asunto(s)
Carcinoma de Células de los Islotes Pancreáticos/secundario , Neoplasias Pancreáticas/patología , Tumor Rabdoide/secundario , Adenocarcinoma/patología , Adulto , Anciano , Anaplasia/patología , Carcinoma de Células de los Islotes Pancreáticos/química , Carcinoma de Células de los Islotes Pancreáticos/cirugía , Diagnóstico Diferencial , Femenino , Humanos , Técnicas para Inmunoenzimas , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/química , Neoplasias Pancreáticas/secundario , Neoplasias Pancreáticas/cirugía , Tumor Rabdoide/química , Tumor Rabdoide/cirugíaRESUMEN
CONTEXT: Traditional morphologic features of tumor aggression are of limited value in predicting the malignant behavior of endocrine neoplasms. We explored the potential value of nuclear proliferative activity (using Ki-67 immunostaining with semiquantitative scoring) in predicting the clinical behavior of pancreatic islet cell tumors (ICTs), and we correlated this characteristic with hormone expression. OBJECTIVE: To evaluate whether Ki-67 immunostaining using a semiquantitative scoring system has value in predicting the clinical behavior of pancreatic ICTs. DESIGN: We studied 39 pancreatic ICTs from 39 patients. Twenty-two ICTs did not metastasize in a median follow-up period of 91 months. The remaining 17 neoplasms did produce metastases (8 in liver, 7 in regional lymph nodes, and 2 in peritoneum). Immunohistochemistry was performed using antibodies to Ki-67 and pancreatic hormones (insulin, glucagon, gastrin, somatostatin, pancreatic polypeptide, vasoactive intestinal polypeptide, and corticotropin). A semiquantitative Ki-67 grading system was followed. The nuclear proliferative activity, as determined by a positive reaction for Ki-67, was considered low (<5% of cells staining positively), intermediate (5%-25% of cells staining positively), or high (>25% of cells staining positively). RESULTS: The majority of the nonmetastatic ICTs (16 cases, 73%) demonstrated either negative or low staining for Ki-67 (P <.001). Conversely, all metastatic ICTs expressed at least an intermediate-grade reaction. High nuclear proliferative activity was only seen in metastatic neoplasms (3 cases, 17%). There was no relationship between immunoexpression of pancreatic hormones and nuclear proliferative activity by either group of tumors. CONCLUSION: An ICT with low nuclear proliferative activity is unlikely to metastasize, whereas high proliferative activity is associated with a metastatic phenotype. Immunohistochemical assessment of Ki-67 using a semiquantitative scoring system is a simple and reliable detection method of cellular proliferative activity in ICTs of the pancreas.
Asunto(s)
Carcinoma de Células de los Islotes Pancreáticos/patología , Carcinoma de Células de los Islotes Pancreáticos/secundario , Núcleo Celular/patología , Neoplasias Pancreáticas/patología , Adulto , Anciano , Carcinoma de Células de los Islotes Pancreáticos/química , División Celular , Femenino , Estudios de Seguimiento , Humanos , Antígeno Ki-67/inmunología , Antígeno Ki-67/metabolismo , Masculino , Persona de Mediana Edad , Hormonas Pancreáticas/inmunología , Hormonas Pancreáticas/metabolismo , Neoplasias Pancreáticas/química , Fenotipo , Valor Predictivo de las PruebasRESUMEN
The objective of the present study is to compare the cytologic features of islet cell tumor (ICT) of pancreas obtained by endoscopic ultrasound guided fine needle aspiration (EUS-FNA) and computed tomography guided FNA (CT-FNA). We also describe the cytologic features associated with malignant ICT. Eleven cytology samples from 121 CT- FNA and 30 EUS- FNA of the pancreas were obtained from nine patients with ICT. Diff-Quik, Papanicolaou, and immunohistochemical stains to determine neuroendocrine differentiation and the hormonal status were evaluated. Cytologic features and specimen adequacy were compared between the two techniques. Cytologic features noted in both benign and malignant ICT were also compared. Nine patients (5 men, 4 women) ranging in age from 29 to 84 years (mean age, 53.8 years). Diagnoses consisted of benign (4) and malignant (5) ICT. EUS-FNA was superior to CT-FNA in obtaining adequate cells (2/2 v 7/9) for the diagnosis and increased cellularity to perform additional immunohistochemical stains (2/2 v 4/7). Single, plasmacytoid cells with finely granular chromatin distribution characterized ICT on cytology. Mitoses (3/5) and necrosis (1/5) were noted in malignant ICT but not in benign ICT. EUS-FNA is superior to CT- FNA for obtaining cells for the diagnosis of ICT. Detection of mitoses and or necrosis from patients with ICT should initiate a search for metastasis.
Asunto(s)
Adenoma de Células de los Islotes Pancreáticos/patología , Endosonografía/métodos , Neoplasias Pancreáticas/patología , Tomografía Computarizada por Rayos X/métodos , Adenoma de Células de los Islotes Pancreáticos/química , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/análisis , Biopsia con Aguja , Carcinoma de Células de los Islotes Pancreáticos/química , Carcinoma de Células de los Islotes Pancreáticos/secundario , Endoscopía del Sistema Digestivo , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/análisis , Neoplasias Pancreáticas/químicaRESUMEN
We report a rare case of minute (5 mm x 4 mm) mixed ductal-endocrine carcinoma of the pancreas with predominant intraductal growth. A 34-year-old Japanese man was admitted because of elevated serum pancreatic enzymes. Endoscopic retrograde pancreatography revealed an unidentified material of 18 mm within the main pancreatic duct. Stone or parasite with acute pancreatitis was suspected clinically, and the biopsy revealed malignant cells positive for CA19-9, carcinoembryonic antigen (CEA) and synaptophysin. No apparent tumor was identified in the pancreas by various imaging techniques. Resection of pancreatic body and tail was performed. Grossly, the main pancreatic duct in the pancreatic body was occluded by as much as 20 mm. The pancreas had minute carcinoma of 5 mm x 4 mm just around the occluded main pancreatic duct. The tumor cells invaded the main pancreatic duct and spread within it as long as 20 mm. Histologically, the carcinoma had biphasic pattern; one was ductal carcinoma with tubular formations and another was carcinoma with neuroendocrine features. These two elements were admixed, and the ductal element comprised 30% while the endocrine element comprised 70%. The ductal element was immunoreactive for cytokeratins, CEA and CA19-9, while the endocrine element was immunoreactive for chromogranin A and synaptophysin. No immunoreactivity for pancreatic enzymes was noted. Ultrastructural observations showed dense core granules and no zymogen granules. Our case is unique clinically in that the tumor manifested as an intraductal material and no apparent tumor was found by imaging modalities, and pathologically in that the tumor was rare mixed ductal-endocrine carcinoma and the tumor was very small and mainly grew within the main pancreatic duct.
Asunto(s)
Carcinoma de Células de los Islotes Pancreáticos/patología , Carcinoma Ductal Pancreático/patología , Neoplasias Pancreáticas/patología , Adulto , Biomarcadores de Tumor/análisis , Antígeno CA-19-9/análisis , Antígeno Carcinoembrionario/análisis , Carcinoma de Células de los Islotes Pancreáticos/química , Carcinoma de Células de los Islotes Pancreáticos/cirugía , Carcinoma Ductal Pancreático/química , Carcinoma Ductal Pancreático/cirugía , Cromogranina A , Cromograninas/análisis , Humanos , Queratinas/análisis , Masculino , Neoplasias Pancreáticas/química , Neoplasias Pancreáticas/cirugía , Sinaptofisina/análisis , Resultado del TratamientoRESUMEN
The inducibility of pancreatic islet cell tumors by administration of 4-hydroxyaminoquinoline 1-oxide (4HAQO) was investigated in male 6-week-old Sprague-Dawley rats. Rats were given 4HAQO intravenously at a weekly dose of 5 mg/kg 4 times (group 1) or a single dose of 10 mg/kg (group 2). Control rats received the vehicle alone (group 3). Fifty-six weeks after the first 4HAQO administration, all surviving animals were killed and the pancreas was examined histopathologically, immunohistochemically and ultrastructurally. The incidences and multiplicities of islet cell tumors in groups 1, 2, and 3 were 52.3% (p < 0.05 vs group 2, p < 0.01 vs group 3), 19.2% and 0%, and 0.70/animal (p < 0.05 vs group 2, p < 0.01 vs group 3), 0.23 and 0, respectively. Islet cell carcinomas were induced only in group 1, accounting for 6/44 (26%) tumors. Islet cell hyperplasias were found in 61.4% (p < 0.05 vs group 3), 42.3% and 10.0% of groups 1, 2, and 3, with multiplicities of 0.95 (p < 0.05 vs groups 2 and 3), 0.54 and 0.20, respectively. As compared with normal islets from control subjects, islet cell tumors showed an increase in the number of insulin positive cells associated with cytological features indicative of enhanced insulin synthesis and secretion, and a decrease in the number of glucagon positive cells without ultrastructural signs of modified secretory activity. Thus our results indicate that repeated intravenous administration of 4HAQO to rats is useful for the induction of islet cell tumors at high incidence.
Asunto(s)
4-Hidroxiaminoquinolina-1-Óxido/toxicidad , Adenoma de Células de los Islotes Pancreáticos/inducido químicamente , Carcinógenos/toxicidad , Carcinoma de Células de los Islotes Pancreáticos/inducido químicamente , Neoplasias Pancreáticas/inducido químicamente , 4-Hidroxiaminoquinolina-1-Óxido/administración & dosificación , Adenoma de Células de los Islotes Pancreáticos/química , Adenoma de Células de los Islotes Pancreáticos/patología , Animales , Carcinógenos/administración & dosificación , Carcinoma de Células de los Islotes Pancreáticos/química , Carcinoma de Células de los Islotes Pancreáticos/patología , Glucagón/análisis , Hiperplasia , Inmunohistoquímica , Inyecciones Intravenosas , Insulina/análisis , Islotes Pancreáticos/efectos de los fármacos , Islotes Pancreáticos/patología , Masculino , Orgánulos/ultraestructura , Neoplasias Pancreáticas/química , Neoplasias Pancreáticas/patología , Lesiones Precancerosas/inducido químicamente , Lesiones Precancerosas/patología , Ratas , Ratas Sprague-Dawley , Vesículas Secretoras/ultraestructura , Somatostatina/análisisRESUMEN
The dominantly inherited von Hippel-Lindau disease is characterized by clear cell neoplasms in various organs including the kidney and pancreas. Determination of primary versus metastatic lesion in this setting can be a diagnostic dilemma. The authors present five cases of clear cell endocrine pancreatic tumor (EPT) closely mimicking renal cell carcinomas in five patients with a family history or histologic evidence of von Hippel-Lindau disease. In fact, two of these tumors were confused with metastatic renal cell carcinoma by fine-needle aspiration. All five tumors had a component of clear cells arranged in nests, cords, and tubules with central hemorrhage separated by thin-wall vessels resembling renal cell carcinoma. However, these tumors also exhibited cords and festoons and a gyriform pattern suggestive of an endocrine neoplasm, and expressed chromogranin and synaptophysin. Vascular invasion was identified in four tumors, one of which metastasized. The concurrent primary renal cell carcinomas and the multicentric microcystic adenomas found in three patients did not show reactivity for the neuroendocrine markers. Focal clear cell change was noted in only one of 29 endocrine pancreatic tumors arising in patients without von Hippel-Lindau disease. Eleven metastatic renal cell carcinomas in the pancreas did not show immunoreactivity with the endocrine markers. Clear cell EPTs closely mimicking renal cell carcinoma are distinctive neoplasms of von Hippel-Lindau disease. In contrast to clear cell EPT, metastatic renal cell carcinoma does not express neuroendocrine markers and lacks neurosecretory granules by electron microscopy. Von Hippel-Lindau disease should be strongly suspected in patients with renal cell carcinoma, clear cell EPT, and multifocal microcystic serous adenomas.
Asunto(s)
Adenocarcinoma de Células Claras/diagnóstico , Carcinoma de Células de los Islotes Pancreáticos/diagnóstico , Carcinoma de Células Renales/diagnóstico , Neoplasias Renales/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Enfermedad de von Hippel-Lindau/patología , Adenocarcinoma de Células Claras/química , Adenocarcinoma de Células Claras/etiología , Adulto , Biomarcadores de Tumor/análisis , Carcinoma de Células de los Islotes Pancreáticos/química , Carcinoma de Células de los Islotes Pancreáticos/etiología , Carcinoma de Células Renales/secundario , Cistadenoma Seroso/química , Cistadenoma Seroso/diagnóstico , Cistadenoma Seroso/etiología , Citoplasma/ultraestructura , Diagnóstico Diferencial , Femenino , Humanos , Técnicas para Inmunoenzimas , Neoplasias Renales/secundario , Persona de Mediana Edad , Proteínas de Neoplasias/análisis , Neoplasias Primarias Múltiples/química , Neoplasias Primarias Múltiples/patología , Neoplasias Pancreáticas/química , Neoplasias Pancreáticas/etiología , Estudios Retrospectivos , Enfermedad de von Hippel-Lindau/complicaciones , Enfermedad de von Hippel-Lindau/metabolismoRESUMEN
Neoplasms of the pancreas usually show either ductal, acinar, or endocrine differentiation. Mixed exocrine-endocrine pancreatic neoplasms, in which the endocrine component is significant and comprises one-third to one-half of the tumor tissue, are rare. Truly mixed tumors have to be distinguished from exocrine neoplasms with scattered endocrine cells. In ductal adenocarcinomas, the scattered endocrine cells seem to be nonneoplastic. In other malignancies such as acinar cell carcinoma and pancreatoblastoma, scattered endocrine cells most likely represent an integral component of the tumor.
Asunto(s)
Adenocarcinoma/secundario , Carcinoma de Células de los Islotes Pancreáticos/secundario , Islotes Pancreáticos/patología , Neoplasias Complejas y Mixtas/secundario , Neoplasias Pancreáticas/patología , Adenocarcinoma/química , Biomarcadores de Tumor/análisis , Carcinoma de Células de los Islotes Pancreáticos/química , Humanos , Inmunohistoquímica , Proteínas de Neoplasias/análisis , Neoplasias Complejas y Mixtas/química , Neoplasias Pancreáticas/químicaRESUMEN
Ten neuroendocrine tumors (NET) in the liver are presented, in which the diagnosis was made on fine needle aspiration cytology and cell blocks from the aspirate. In seven of the patients with liver metastasis, a biopsy-proven extrahepatic primary NET had been previously diagnosed, while in three patients no extrahepatic neoplasm could be identified, suggesting that the NET may have been a primary in the liver. Based on cytomorphological findings the cases were typed as either round cell type, spindle cell type or polygonal cell type. In all cases, immunopositivity for neuroendocrine markers provided reliable evidence of the cell of origin and distinguished them from well-differentiated hepatocellular carcinoma, adenocarcinomas and other neoplasms, which sometimes may present a diagnostic dilemma.
Asunto(s)
Neoplasias Hepáticas/patología , Neoplasias Primarias Desconocidas/patología , Tumores Neuroendocrinos/patología , Anciano , Biomarcadores de Tumor/análisis , Biopsia con Aguja , Tumor Carcinoide/química , Tumor Carcinoide/patología , Tumor Carcinoide/secundario , Carcinoma de Células de los Islotes Pancreáticos/química , Carcinoma de Células de los Islotes Pancreáticos/patología , Carcinoma de Células de los Islotes Pancreáticos/secundario , Humanos , Técnicas para Inmunoenzimas , Neoplasias Hepáticas/química , Neoplasias Hepáticas/secundario , Persona de Mediana Edad , Neoplasias Primarias Desconocidas/química , Tumores Neuroendocrinos/química , Tumores Neuroendocrinos/secundario , Neoplasias Pancreáticas/química , Neoplasias Pancreáticas/patologíaAsunto(s)
Carcinoma Ductal de Mama/patología , Carcinoma de Células de los Islotes Pancreáticos/patología , Neoplasias Pancreáticas/patología , Somatostatina/análisis , Anciano , Carcinoma Ductal de Mama/química , Carcinoma de Células de los Islotes Pancreáticos/química , Humanos , Inmunohistoquímica , Masculino , Neoplasias Pancreáticas/químicaRESUMEN
UNLABELLED: The objective of this study was to investigate spontaneous islet cell carcinomas with particular reference to possible existing strain differences between Sprague Dawley (SD) and Wistar (W) rats in incidence and immunohistochemical staining pattern. Secondly the occurrence of somatostatin and/or gastrin-positive islet cell tumors should be tested. Islet cell adenocarcinomas (34 from SD, 43 from W-rats) were selected from the RITA-data base and company in-house data base out of an animal pool of 3915 (1681 SD, 2234 W-rats). They were untreated or sham-treated (vehicle) control animals from carcinogenicity studies and whole life-span experiments. Islet cell carcinomas occurred in a higher incidence in male rats (2.98% for SD, 3.23% for W) than in female rats (1.07% for SD, 0.63% for W). All specimens were immunohistologically stained with antibodies against insulin, glucagon, somatostatin and gastrin and, selected specimens with additional antibodies (pancreatic polypeptide, lipase, chymotrypsin, S100-protein, actin and cytokeratin). 94% (SD) and 93% (W), respectively, were insulin-positive and the mean staining intensity (on a scale ranging from 0-4) for insulin was 3.58 (SD) versus 3.37 (W). This high insulin staining incidence and intensity characterized most islet cell carcinomas as malignant insulinomas. 24% (SD) and 37% (W), respectively, were glucagon-positive. Except two tumors in W-rats with a focal strong glucagon expression, the mean staining intensity for glucagon was low (0.38 SD, 0.72 W). 38% (SD) and 44% (W), respectively, were somatostatin-positive, but except for five cases having a focal to multifocal, moderate to marked staining, only a few tumor cells were positive for somatostatin in the other cases and the mean staining intensity for somatostatin was low (0.50 SD, 0.84 W). 6% (SD) and 23% (W), respectively, were gastrin-positive, but only one case of a male Wistar rat exhibited a focal strong staining in parts of the tumor. The other cases showed only a few tumor cells which were positive for gastrin. The mean staining intensity for gastrin was low (0.06 SD, 0.35 W). In all tumors with marked glucagon, somatostatin or gastrin expression, the immunostaining for insulin was still predominating. Thus, insulin was the major hormone produced by most of the tumor cells. Five out of 77 tumors evaluated were immunohistologically negative with all applied antibodies. CONCLUSION: This study presents the first immunohistochemical survey on spontaneous islet cell carcinomas in SD and Wistar rats stained with antibodies against the endocrine pancreas hormones insulin, glucagon, somatostatin and gastrin. No major differences in incidence or immunohistochemical staining pattern between SD and W-rats could be detected. In contrast to SD rats, Wistar rats had multihormonal coexpression in 16.3%. The multihormonal appearance of the neoplasms is well comparable with the findings in other animal species and human insulinomas. Moreover, this is the first study in rats which reports five cases with a marked co-expression of somatostatin and one case with marked focal co-expression of gastrin in malignant islet cell adenocarcinomas.