Pancreatic endocrine tumors or apudomas.

INTRODUCTION AND OBJECTIVE: pancreatic endocrine tumors (PET) are difficult to diagnose. Their accurate localization using imaging techniques is intended to provide a definite cure. The goal of this retrospective study was to review a PET series from a private institution. PATIENTS AND METHODS: the medical records of 19 patients with PETs were reviewed, including 4 cases of MEN-1, for a period of 17 years (1994-2010). A database was set up with ten parameters: age, sex, symptoms, imaging techniques, size and location in the pancreas, metastasis, surgery, complications, adjuvant therapies, definite diagnosis, and survival or death. RESULTS: a total of 19 cases were analyzed. Mean age at presentation was 51 years (range: 26-67 y) (14 males, 5 females), and tumor size was 5 to 80 mm (X: 20 mm). Metastatic disease was present in 37% (7/19). Most underwent the following imaging techniques: ultrasounds, computed tomography (CT) an magnetic resonance imaging (MRI). Fine needle aspiration punction (FNA) was performed for the primary tumor in 4 cases. Non-functioning: 7 cases (37%), insulinoma: 2 cases [1 with possible multiple endocrine neoplasia (MEN)], Zollinger-Ellison syndrome (ZES) from gastrinoma: 5 (3 with MEN-1), glucagonoma: 2 cases, 2 somatostatinomas; carcinoid: 1 case with carcinoide-like syndrome. Most patients were operated upon: 14/19 (73%). Four (4/14:28%) has postoperative complications following pancreatectomy: pancreatitis, pseudocyst, and abdominal collections. Some patients received chemotherapy (4), somatostatin (3) and interferon (2) before or after surgery. Median follow-up was 48 months. Actuarial survival during the study was 73.6% (14/19). CONCLUSIONS: age was similar to that described in the literature. Males were predominant. Most cases were non-functioning (37%). Most patients underwent surgery (73%) with little morbidity (28%) and an actuarial survival of 73.6% at the time of the study.

Diagnostic and prognostic implications of the World Health Organization classification of neuroendocrine tumors.

BACKGROUND: Neuroendocrine differentiation of tumors is often difficult to establish. In the same manner, the evaluation of the prognostic role of neuroendocrine differentiation may constitute a relevant clinical problem. Although different classifications are used for neuroendocrine tumors (NET) of different origin, the last World Health Organization (WHO) classification of NET, originally proposed for gastroenteropancreatic tumors, has proved to be a practical tool to allow pathologists to uniform the diagnoses and re-classify these tumors into 3 main categories. AIM: The present study was carried out in order to evaluate diagnostic and prognostic implications of NET reclassification according to the last WHO classification of NET. MATERIALS AND METHODS: Thirty-one tumors with an initial diagnosis referable to a NET achieved before 1999 were independently evaluated by 3 pathologists on the basis of the 2000 WHO classification of NET. Immunohistochemistry for panneuroendocrine markers and Ki-67 was also performed in all cases. RESULTS: Twelve, 14, and 4 tumors were respectively reclassified as well-differentiated NET, well-differentiated neuroendocrine carcinoma and poorly differentiated neuroendocrine carcinoma; 1 tumor was reclassified as mixed endocrine-exocrine tumor. Two or more neuroendocrine markers were expressed in all NET regardless of histotype, differentiation degree, and site of primary tumor. After revision, 10 of the 31 tumors under study (32%) changed histo-prognostic category when compared to the initial diagnosis. Ki-67 score was the best predictor of survival at the multivariate analysis. CONCLUSION: The WHO classification is suitable to accurately reclassify tumors with an initial diagnosis referable to a NET and to separate these tumors in 3 well-distinct histo-prognostic categories with relevant clinical implications. Ki-67 score seems to be a better predictor of survival than the degree of differentiation.

[Apudoma of Vater's ampulla: case report and review of the literature]. / Apudoma dell'ampolla di Vater: caso clinico e revisione della letteratura.

The Authors report a case of Vater's ampulla apudoma and after having examined the characteristics of these neoplasms they discuss clinical presentation, diagnostic and treatment problems of islet cell adenomas. They review the literature and make some remarks.

[Imaging of neuroendocrine tumors]. / Imaging dei tumori neuroendocrini.

Neuroendocrine tumors (NET) of the pancreas are distinguished in functional (85%) and non functional (15%) in relation to the production and release of the hormone produced. Functional tumors show early, because the neoplasm release the hormone produced when they are still small. Non functional tumors show late when the tumor grows. The localization and the evaluation of the extensive of these tumors has come fundamentally important both in correct presurgical detection and also in the diagnosis of metastases which excluded surgery. Also, as the survival of 20% of the patients with metastases is only five years, the use of non-invasive imaging techniques is very important for the evaluation of results of the various therapies (chemotherapy, interferon, somatostatin). Recent studies have shown that in patients with Zollinger-Ellison syndrome, SRS is the most sensitive non invasive method in localizing primitive tumors and metastases. The accuracy of this technique has not yet been provided in the study of tumors like insulinomas which do not have a high percentage of somatostatine receptors on their cell membranes. The sensitivity obtained in recent studies on a large number of patient and the low cost, lower than all the other imaging technique in use today, surely make SRS the first choice in the study of NET. Where SRS is negative and surgery is possible, Spiral CT or better still MRI is the best tool to check the results of chemotherapy in patients with hepatic metastases (already detected by SRS), because it is easier to compare the changes in size and morphology of metastases.

[Oncocytoma of the pancreas. A case report]. / Vurkhu edin sluchai s onkotsitom na pankreasa.

For the first time in the bulgarian literature a case with pancreatic oncocytoma is described, initially diagnosed as carcinoma. The patient survived for 13 years being nowadays in perfect condition.

Pancreatic endocrine tumors: recent advances.

Pancreatic endocrine tumors (PET's) can be divided on a clinical and pathologic basis into ten classes [insulinomas, gastrinomas (Zollinger-Ellison syndrome), VIPomas (Verner-Morrison syndrome, WDHA, pancreatic cholera), glucagonomas, somatostatinomas, ACTH-releasing tumors (ACTHomas), growth hormone-releasing factor secreting tumors (GRFomas), nonfunctioning or pancreatic polypeptide secreting tumors (non-functioning PET), PET's causing carcinoid syndrome and PET's causing hypercalcemia)]. Recent reports suggest calcitonin-secreting PET's also rarely occur but whether they cause a distinct clinical syndrome is unclear. PET's resemble carcinoid tumors histologically; in their ability to synthesize and frequently secrete multiple peptides such as neuroendocrine cell markers (chromogranins); their biologic behavior and their tumor growth patterns. Both groups of tumors are highly vascular, have high densities of somatostatin receptors and similar tumor localization studies including somatostatin receptor scintigraphy are used for both. PET's, similar to carcinoids causing the carcinoid syndrome, require two separate treatment options be considered: treatment directed against the hormone-excess state and treatment directed against the tumor per se because of their malignant nature. In the last few years there have been advances in tumor diagnosis, localization methods, treatment approaches particularly related to the use of synthetic somatostatin analogues, and the definition of the role of surgical procedures in these diseases. Important other advances include insights into the long-term natural history of PET's particularly from studies of gastrinomas, which allow prognostic factors to be identified and the timing of treatment options to better planned, as well as insights into the molecular basis of these disorders. The latter includes both a description of the molecular basis of the genetic inherited syndromes associated with PET's or carcinoid tumors, as well as an increased understanding of the molecular basis for sporadic PET's or carcinoid tumors. Each of these areas will be briefly highlighted in this presentation.

Gastrinomas and the change in their presentation and management in Northern Ireland, UK, from 1970 to 1996.

Thirty-five new cases of gastrinomas were diagnosed in N. Ireland between 1970 and 1996. Over this period, patient care has improved, with advances in imaging techniques and therapeutic regimens. Patients are now no longer presenting in the classical way with severe ulcer diathesis. Diarrhoea is often a major feature, occurring in 46% of patients. Thirty-one percent of patients presented with mixed amine precursor, uptake and decarboxylation (APUD) tumours. Survival has improved, most likely as a result of better detection of tumours, as well as treatment that is aimed at resection and removal of the gastrinoma. The advent of proton pump inhibitors has ensured symptom control in those for whom total tumour removal is impossible. Owing to improved survival, metastatic complications are often associated with patient mortality.

[Apudomas: nosographic and physiopathological aspects]. / Apudomi. Aspetti nosografici e fisiopatologici.

The authors intend to contribute to the knowledge of this complex and in part not fully defined subject of apudomas, in particular with regard to classification criteria and physiopathological aspects. After having examined the characteristics of these neoplasias (probably common embryonal origin, similar radioimmunological, immunohistochemical and ultrastructural characteristics, the capacity to convert amine precursors into amines), the authors focus on the most significant aspect of these carcinoids which, in the light of current knowledge, possess varying but undisputed degrees of biological aggressiveness. They also highlight the importance of the gastroenteric tract as an organ with an endocrine function and lastly affirm the value of the classification which, using the pancreas as the reference organ, distinguishes endocrine neoplasias in this tract into entopic and ectotopic examples.

Apudoma vesical / Bladder apudoma

Se presenta un caso de paraganglioma vesical, un tumor poco frecuente del sistema APUD

Cartinoid tumor of the middle ear and mastoid.

Primary cartinoid tumors in the middle ear and mastoid are rare. They are also very difficult to distinguish from adenomas and adenocarcinomas, using conventional histological stains. We present clinical, histological, immunohistochemical and ultrastructural findings of a cartinoid tumor in the middle ear and mastoid in a 40-year-old male. A soft tumor was revealed in the posterior mesotympanum and mastoid cavity, and a radical tympanomastoidectomy was performed. The tumor cells were stained by chromogranin A, and neurosecretory granules were confirmed with electron microscopy. We also review 20 previously reported cases in regard to their presentation, symptoms, signs, tumor extension, treatments, and histopathology.

[Endocrine tumors of the pancreas. Status of the question]. / Tumeurs endocrines du pancréas. Le point sur la question.

Progress in radioimmunology and immunohistochemistry and the use of intraoperative ultrasonography has considerably improved the diagnosis of endocrine tumors. These advances have changed the prognosis of these tumors since the outcome directly depends on early diagnosis. Surgery is the treatment of choice, in many cases even in the presence of hepatic metastasis. Medical treatment should be used when surgery is contraindicated and includes cytostatic agents (e.g. streptozotocin, 5-FU) or interferons and drugs preventing hormone release such as long-acting somatostatin analogs (SMS 201-995). Finally, symptomatic treatment alone should be confined to cases of unresectable tumors with diffuse metastasis.

Carcinoma de células de Merkel / Merkel cell carcinoma

El carcinoma de células de Merkel es un tumor maligno de la piel poco frecuente, descrito en los últimos años como una nueva entidad. Probablemente se origina en las células de Merkel, únicas células de la piel con gránulos neuroendócrinos citoplasmáticos. Afecta predominantemente a mujeres añosas y su localización más frecuente es en zonas expuestas. Puede manifestarse clínicamente como un tumor solitario eritematoso; múltiples tumores en un área (remedando satelitosis de melanoma) o múltiples tumores generalizados (merkeliomatosis cutánea). Existen tres patrones histopatológicos, que en orden de frecuencia son sólido o nodular, difuso (tipo linfomatoso) y trabecular. La microscopía electrónica revela dos estructuras citoplasmáticas típicas: gránulos revestidos de membrana y espirales perinucleares de filamentos intermedios (cuerpos fibrosos). Pueden reconocerse tres grupos de marcadores inmunohistoquímicos:filamentos intermedios (citoqueratinas y neurofilamentos); neuropéptidos pan-neuroendócrinos (enolosa, cromogranina y sinaptofisina) y marcadores de diferenciación epitelial (citoqueratina, EMA y desmoplaquina). Pero la coexpresión de citoqueratinas y neurofilamentos es considerada como la de mayor valor diagnóstico. El diagnóstico se basa en la clínica, la histopatología e inmunohistoquímica, siendo la microscopía electrónica una técnica opcional. El tratamiento de elección es la cirugía con amplios márgenes a la que puede agregarse vaciamiento ganglionar. El tumor es radiosensible y responde a la quimioterapia

CT, MR imaging and angiography in pancreatic apudomas.

Findings at CT, MR imaging and angiography in 29 patients with pancreatic apudomas are presented. CT and angiography were performed in all the patients, MR imaging in 10. Twenty-five patients underwent laparotomy. The ability of the different imaging methods to localize the primary tumor and detect hepatic metastases was compared. CT and MR imaging depicted the primary tumor in 79% and 88% of the cases respectively, angiography in 72%. Enhancement patterns at CT and signal intensity variations at MR imaging were unspecific parameters regarding different types of tumors. CT and MR imaging were considerably more accurate than angiography in evaluating local tumor resectability. Angiography revealed more numerous small hepatic metastases (< 0.5 cm) than CT or MR imaging, but missed metastases in the left lobe in 5 patients. MR imaging seems promising in localizing and characterizing pancreatic apudomas, but further evaluation is needed before any conclusion can be drawn. At present dynamic incremental CT seems mandatory in the evaluation of pancreatic apudomas. Angiography is of value for preoperative and preembolization vascular mapping, and in localizing small pancreatic apudomas not shown at CT or MR imaging. Faster dynamic thin slice CT scanning and fast-sequence MR imaging may increase the sensitivity of detecting small primary pancreatic apudomas.

Diagnostic advances in APUDomas and other endocrine tumors: imaging and localization.

The different diagnostic imaging modalities available for determining the location of the various APUDomas are discussed with reference to their advantages and disadvantages. The ability to image these lesions, and to be confident in their role in the underlying pathophysiology, and clinical neuroendocrine syndrome causing symptomatology and illness, has proved to be the key to successful treatment. In many instances it is not the diagnosis that is in question, but it is the extent of disease, the location of the lesion, or whether the anatomical abnormality under study is responsible for the complicating symptoms being considered, that are the crucial questions. The ability to locate APUDomas by a variety of direct and indirect imaging or regionalizing modalities, represent a magnificent advance in the management of these tumors. It should, however, be kept in mind that no one modality or diagnostic method can uniformly be relied upon. It is evident that a multimodal, interactive medical team approach is essential to the successful overall management of patients afflicted with these fascinating tumors.