Histological, immunohistochemical, ultrastructural and biochemical study of human gastric composite tumor: expression of the serotonin-2B receptor by the neuroendocrine component.

We report a case of a human gastric composite tumor occurring seven years after a partial gastrectomy for a low grade B cell MALT lymphoma. Histological examination of the tumor revealed two intimately intermingled components: 1. A moderately to poorly differentiated tubulo-acinar adenocarcinoma with signet-ring cells; and 2. Isolated or clustered small neuroendocrine cells without atypia expressing chromogranin A, somatostatin and/or glucagon, serotonin (5-HT) and, the 5-HT2B receptors. In addition to immunohistochemical detection, the presence of 5-HT2B receptors was shown pharmacologically through [125I]-DOI binding. Since 5-HT2B receptors have been demonstrated to have autocrine functions and, mitogenic and transforming properties, these results suggest a role of 5-HT in neuroendocrine malignant transformation. On the other hand, the expression of somatostatin and the detection by reverse transcriptase polymerase chain reaction (RT-PCR) of somatostatin receptor subtypes 2, 3, and 5, which have been shown to be involved in tumor regression, might account for the long evolution of this case (> 5 yr). This case illustrates the importance of local humoral modulation in tumor growth. Moreover, ultrastructural results favor a unique origin of the tumor cells from one amphicrine cell type.

[Duodenal somatostatinoma. Anatomic/clinical study of 12 operated cases]. / Le somatostatinome duodénal. Etude anatomoclinique de 12 cas opérés.

STUDY AIM: Duodenal somatostatinomas (DS) are very rare neuro-endocrine tumours. The aim of this retrospective and multicentric study was to report the clinical and pathological characteristics of these neoplasms in a series of 12 patients and to compare them with the literature. PATIENTS AND METHODS: From 1987 to 1998, 12 patients were operated for a DS. There were seven women and five men ranging in age from 23 to 72 years (mean age: 56.6 years). Four patients had an associated von Recklinghausen's disease, one of them with multiple endocrine neoplasia (MEN type IIa) and medullary carcinoma of the thyroíd. The surgical procedures were pancreaticoduodenectomy (n = 8), small bowel resection (n = 2), inferior gastrectomy (n = 1) and gastrojejunostomy with hepatic metastases biopsies (n = 1). The tumour was mainly located on the 2nd duodenum (n = 10), with a mean size of 2.7 cm (ranging from 0.4 to 6 cm) and with a pancreatic invasion in three patients. A metastatic disease was present at the time of diagnosis in eight patients. There were, according to Capella's classification, two patients in the groups I and II, and ten patients in group III (83%), respectively. RESULTS: There was one postoperative death after a pancreaticoduodenectomy. Three patients secondarily died from tumoral progression. Eight patients were alive, with a mean follow-up of 84 months (ranging from 5 to 290 months), at the end-point of the study. CONCLUSION: Duodenal somatostatinomas are rare neuroendocrine, generally non-functioning, well-differentiated tumours with a low grade of malignancy. The association with the von Recklinghausen's disease is frequent. The clinical somatostatinoma syndrome with diabetes, diarrhea and biliary lithiasis is rare. The treatment is surgical even with a metastatic disease. The 5-year survival rate is better than those of the pancreatic somatostatinomas or the duodenal gastrinomas.

Nuclear medicine applications for neuroendocrine tumors.

Sensitive, specific radiopharmaceuticals are available for scintigraphic diagnosis and internal radiotherapy of neuroendocrine tumors. (123)I-MIBG (metaiodobenzylguanidine) scintigraphy is the examination of choice for visualizing tumor sites of pheochromocytoma. In the event of malignant pheochromocytoma or carcinoid tumor, this examination allows assessment of the presence or absence of tumor uptake and can guide radiotherapy with (131)I-MIBG. The peptides secreted by neuroendocrine tumors can be radiolabeled for targeting of their specific receptors. Scintigraphy using a (111)In-labeled somatostatin analog (octreotide) is the examination of choice for diagnosis of the spread of gastroenteropancreatic and carcinoid tumors, as it is more sensitive than morphologic imaging techniques. It can also guide radiotherapy performed with the same pharmaceutical vector. These same two agents (MIBG and octreotide) can be used therapeutically by replacing (123)I with (131)I and (111)In by (90)Y. A transient palliative effect is obtained for a variable number of tumors (most often large ones) that take up the radiopharmaceutic agent well. There is general consensus that, for relatively radioresistant solid tumors, this type of radiotherapy is efficient only in the event of small tumor targets (a few millimeters in diameter) whose uptake is maximal, allowing more homogeneous distribution than that achieved with large tumors. Thus for optimal control of the disease it is recommended first to use scintigraphic imaging to confirm that the tumor takes up the radiopharmaceutical agent in question ((123)I-MIBG or (111)In-octreotide) and then reduce the tumor burden surgically before injecting high therapeutic activity (possibly with reinjection of peripheral stem cells). This treatment can be repeated three times every 3 months before evaluating the response. In these conditions, internal radiotherapy can be beneficial or even determinant for controlling disease progression.

Prognostic and immunohistochemical validation of the capella classification of pancreatic neuroendocrine tumours: an analysis of 82 sporadic cases.

AIMS: To study the clinical outcome of 82 cases of pancreatic neuroendocrine tumours classified according to the recent histological and prognostic classification of Capella. METHODS AND RESULTS: Eighty-two surgical cases of pancreatic neuroendocrine tumours were examined histologically with immunohistochemical staining of paraffin sections using streptavidin-biotin complex and application of antibodies against chromogranin A and 10 hormonal peptides. Classification in four groups correlated with long follow-up and outcome of these cases. Histological examination showed 30 group I, four group II, 41 group III and seven group IV tumours. Twenty-one (70%) of group I tumours were insulinomas, whereas 25% of group III tumours were glucagonomas and 25% were unclassified. Most group IV tumours were unclassified, showing no immunohistochemical staining with any of the 10 hormonal peptides tested. Outcome was clearly correlated with tumour group. Among the 14 patients who died of the disease, four had group IV and 10 group III tumours. Thus, unclassified asymptomatic tumours without immunohistochemical staining had a poorer prognosis than asymptomatic tumours with staining. CONCLUSION: This study validates the Capella classification as easy to apply and useful in predicting clinical outcome.

Localization of cervical node metastasis of papillary thyroid carcinoma.

Precise localization of cervical node metastasis of papillary thyroid carcinoma is rarely described. The aim of this retrospective study was to map their cervical involvement. Between 1974 and 1996 a series of 119 patients had total thyroidectomy with bilateral cervical lymph node dissection. Patients who had secondary node dissection for a cervical recurrence were excluded. Eight node sites were distinguished (ipsilateral and contralateral): paratracheal, mid-jugular, supraclavicular, subdigastric. All pathologic specimens were reviewed by a single pathologist. Twenty-five patients had lymph node involvement clinically before surgery. Seventy-two (60.5%) had cervical metastasis (N+: node positive patients), with bilateral involvement in 28 cases. In cases of bilateral thyroid tumor localization, ipsilateral dissection designated the side with the largest nodule. The main ipsilateral involved sites were paratracheal (60 patients), mid-jugular (44 patients), and supraclavicular (26 patients). Contralateral paratracheal nodes were involved in 25 patients and mid-jugular nodes in 12. Among the N+ patients, node involvement was absent in 11 cases at paratracheal, 28 jugular, and 46 subclavicular sites. Cervical node metastases concerned 60.5% of the patients, with bilateral involvement in 40.8% of the N+ patients. Ipsilateral paratracheal and jugular sites were most frequently involved. The lateral compartment was sometimes involved independent of the central compartment.

Predictive factors for node involvement in papillary thyroid carcinoma. Univariate and multivariate analyses.

For patients with papillary thyroid carcinoma, lymph node involvement is a common complication, resulting in node dissection and its resulting morbidity. To determine means of limiting lymph node dissections, we attempted to define intra-operative criteria predictive of node metastasis and so identify the patients likely to benefit from this procedure. This retrospective study concerned 158 patients (118 female) treated between 1974 and 1996 for papillary thyroid carcinoma by total thyroidectomy associated with bilateral (central and lateral) (n = 119) or unilateral (n = 39) dissection. The following criteria were used to study the predictive value of node involvement: age, sex, tumour size, tumour site, uni- or multifocality, existence or not of a tumour capsule, existence or not of perithyroid involvement and presence or not of vascular invasion. 99 patients (63%) had node involvement. Four factors showed predictive value for node involvement in univariate analysis: vascular invasion (P = 0.02), male sex (P = 0.008), absence of a tumour capsule (P < 0.0001) and perithyroid involvement (P < 0.0001). Two factors were predictive in multivariate analysis: absence of a tumour capsule and perithyroid involvement. Our results enabled us to calculate the risk of node involvement for each patient as a function of the existence of a peritumoral capsule and/or perithyroid involvement and to determine the indication for dissection. When neither of these factors was present, the risk of node involvement was 38.3% and dissection was not considered essential. If both risk factors were found, the risk was 87.1% and dissection was considered necessary.

[Extension of an acinar cell pancreatic carcinoma with cystic changes invading the Wirsung canal]. / Carcinome à cellules acineuses pancréatique d'allure kystique, envahissant le canal de Wirsung.

We report a case of acinar cell carcinoma of the pancreas with misleading cystic changes. A 32-year-old woman presented with symptoms suggesting acute pancreatitis on chronic pancreatitis. The abdominal computed tomography and the endoscopic retrograde pancreatography demonstrated hypertrophy of the pancreatic head associated with global dilatation of main pancreatic duct and secondary canals and a 5 cm communicating cyst. A intraductal papillary-mucinous tumor was suggested. Microscopic findings showed a poorly differentiated adenocarcinoma. Six months later, a liver metastasis was detected. The microscopic appearance was different, suggesting acinar cell carcinoma, confirmed by immunohistochemistry. Only two other cases of acinar cell carcinoma with cystic component have been reported in the literature.

Medullary thyroid carcinoma: search for histological predictors of survival (109 proband cases analysis).

A group of 13 pathologists belonging to the French Calcitonin Tumor Study Group (GETC: Groupe d'Etude des Tumeurs à Calcitonine) examined the histological slides and medical records of 109 proband cases of medullary thyroid carcinoma (MTC) diagnosed on clinical features. The cases belonged to the various forms of the disease (80 sporadic and 29 familial MTC). The aim of the study was to detect histological predictors for survival by comparing morphological data from patients killed by the disease versus the others. Twenty-seven histological parameters were considered, including cellular heterogeneity, shape of the cells, and cytoplasmic characteristics. Other parameters such as sex, age, and phenotype of the disease were also studied. First, predictive parameters of interest on survival function were selected by univariate analysis (Mantel-Cox test). Then, the extracted parameters were tested in a multifactorial analysis using the Cox's forward stepping proportional hazard model. Five parameters were significantly associated with a lower survival function: presence of necrosis in the tumor (P = .001), squamous pattern (P = .002), age over 45 years (P = .004), presence of oxyphil cells in the tumor and absence of cells with intermediate cytoplasm (P = .025), less than 50% of calcitonin immunoreactive cells in the tumor (P = .04).

[Cystic and papillary tumor of the pancreas: diagnostic and developmental uncertainties. Apropos of a case]. / Tumeur papillaire et kystique du pancréas: incertitudes diagnostiques et évolutives. A propos d'un cas.

We reported a case of papillary and cystic tumor (Frantz's Tumor) associated with familial adenomatous polyposis in a young man, 29 years old. This case emphasized the interest of fine needle biopsy and the difficulties for determination of the final pathology. Close long term follow up is essential as local recurrencies and metastasis in the long term had been recorded, undergoing resection with curative intent. Papillary and cystic tumors should be resected.

[Thymic and bronchial neuroendocrine tumors in multiple endocrine neoplasia type 1. GENEM1]. / Tumeurs neuro-endocrines thymiques et bronchiques au cours des néoplasies endocrines multiples de type 1. GENEM1.

OBJECTIVES: Multiple endocrine neoplasia type 1 (MEN 1) mainly affects parathyroid glands, pancreatic islets and pituitary gland. The aim of this study in 95 MEN 1 patients was to examine less frequent localizations thymic and bronchic neuroendocrine tumors (NET). PATIENTS AND METHODS: Two cases of bronchic NET were observed, both in women, and 4 cases of thymic NET, all in men, giving a prevalence of 7.3%. These NET were often asymptomatic. A metastatic diffusion was observed in 3 cases. Elevated plasma levels of glycoprotein hormone alpha subunit (SU) and FSH were observed in 3 and 1 cases respectively. Immunohistochemistry indicated the tumor cells to be frequently positively stained for HCG alpha and FSH. DISCUSSION: We conclude that all patients with MEN 1 should undergo screening for thoracic NET, especially in high risk familial subgroups and in case of elevated plasma alpha SU or FSH.

Immunohistochemical study of 100 pancreatic tumors in 28 patients with multiple endocrine neoplasia, type I.

One hundred pancreatic tumors ranging in size from 0.3 to 7 cm were studied in 28 patients (17 male and 11 female patients; mean age 35 years) with multiple endocrine neoplasia, type I. An immunohistochemical study was performed on deparaffinized sections using the following antibodies: neuron-specific enolase, chromogranin A or synaptophysin, insulin, glucagon, somatostatin, pancreatic polypeptide (PP), vasoactive intestinal peptide (VIP), gastrin, adrenocorticotropic hormone, alpha-subunit of human chorionic gonadotropin, gonadotropin-releasing factor, serotonin, and calcitonin. Among the 100 tumors (all multiple), seven were unclassified, 10 were plurihormonal, and 83 produced a predominant hormonal secretion (with 50-90% of the same cell type), including 37 "A-cell tumors" (glucagon), 27 "B-cell tumors" (insulin), 11 PP-cell tumors, one G-cell tumor (gastrin) and one vasoactive intestinal peptide (VIP)-cell tumor. These multiple tumors had a different predominant hormonal secretion in the same patient in 23 of the 28 cases. There was a preferential association of A-cell tumor and B-cell tumor. Hyperplasia of the islets of Langerhans was not detected in adjacent pancreas. Nesidioblastosis was observed in 30% of cases.

[Pathologic study with immunohistochemistry of 61 pancreatic endocrine tumors in 16 patients suffering from multiple endocrine neoplasia type I (MEN I). Review of the literature]. / Etude anatomopathologique avec immunohistochimie de 61 tumeurs endocrines pancréatiques chez 16 patients atteints de néoplasies endocriniennes multiples de type I (NEM I). Revue de la littérature.

The Multiple Endocrine Neoplasia (MEN I) or Wermer's syndrome is an uncommon disease which is most often inherited and affects mainly parathyroid glands, pancreatic islets and pituitary gland. The aim of this study concerning 61 pancreatic tumors in 16 patients suffering from MEN I was to define the macroscopic, histological and immunohistochemical characteristics of these tumors. The pancreatic endocrine tumors as part of the MEN I syndrome concern multiple tumors of small size, localized most often to the pancreas's tail. In 79% of cases, these tumors have a different predominating peptidic hormonal secretion in a same patient though most of them have plurihormonal secretions. The pancreatic polyendocrinopathy detection imposes a family investigation to look for a type I polyendocrinopathy.

[Immunohistochemical study of 17 cases of rectal neuroendocrine tumors]. / Etude immunohistochimique de 17 cas de tumeurs neuro-endocrines rectales.

Seventeen rectal neuroendocrine tumors ("Rectal Carcinoids") were studied by immunohistochemistry using antibodies directed against neuroendocrine markers: chromogranin A, neuron-specific enolase, synaptophysin, neuroendocrine peptides (ACTH, glicentin, glucagon, pancreatic polypeptide, somatostatin, vasoactive intestinal peptide) and antibody against serotonin. All patients with tumors measuring 1 cm or less had no specific symptoms and survived between fifteen months and eight years. Only one patient with a 6 cm poorly differentiated neuroendocrine carcinoma died less than one year after diagnosis. Only five out of seventeen tumors secreted serotonin. Most tumors were derived from L cell secreting glucagon, glicentin or pancreatic polypeptide.

[Neuroendocrine carcinoma of the larynx with secretion of calcitonin: primary tumor or metastasis of the medullary thyroid carcinoma?]. / Carcinome neuroendocrine laryngé avec sécrétion de calcitonine: cancer primitif ou métastase d'un cancer médullaire de la thyroïde?

Neuroendocrine carcinomas of the larynx are rare and their links with thyroid neoplastic lesions are not specified in most reported cases. We report such a case secondary to medullary thyroid carcinoma. In a 63-year-old man, a supra glottic laryngeal carcinoma confirmed by biopsy was initially treated by chemotherapy. A second biopsy of the laryngeal lesion after incomplete remission displayed a neuroendocrine carcinoma with calcitonin in neoplastic cells. Laryngectomy, cervical bilateral neck dissection and thyroid isthmic adenoma dissection were performed. Numerous neoplastic cells from these tissues contained calcitonin revealed by immunohistochemical method. Calcitoninemia was highly increased and multiple bone metastases were discovered. Secondary total thyroidectomy was not possible and the patient died 6 months after. In this case the neuroendocrine laryngeal carcinoma was probably secondary to a latent medullary thyroid carcinoma. Medullary thyroid carcinoma is most often unknown in similar previously reported cases of neuroendocrine laryngeal carcinoma. Thus a neuroendocrine tumour of the larynx should require search for extra thyroid and over all thyroid neuroendocrine carcinoma, even limited to a small and latent lesion.

[Multiple endocrine neoplasia type I. Review and presentation of the study group of multiple endocrine neoplasia type I (GENEM I)]. / Les néoplasies endocriniennes multiples de type I. Mise au point et présentation du groupe d'étude des néoplasies endocriniennes multiples de type I (GENEM I).

Multiple endocrine neoplasia type I, also known as Wermer's syndrome, is characterized by the presence of functioning or nonfunctioning tumors or hyperplasia of the parathyroid glands, pancreatic islet cells and pituitary gland. MEN I syndrome may be either familial or sporadic. MEN I locus has recently been mapped to chromosome 11, and further characterization of the abnormal gene appears imminent. The GENEM I, a multidisciplinary study group is in the process of formation. Pathologists have to specify the morphological criteria of hyperplasia vs tumor. Further characterization of the gene and its product requires the application of molecular biology methods to the pathologic tissues of these patients.

[Reproducibility of histological criteria of dysplasia in Barrett mucosa]. / Reproductibilité des critères histologiques de dysplasie sur muqueuse de Barrett.

Barrett's mucosa is a precancerous condition. The goal of endoscopic surveillance for patients with Barrett's esophagus is to grade dysplasia. The diagnosis of dysplasia is difficult. The aim of this study was to determine the observer variation in diagnosis of dysplasia. Thirty-seven biopsies selected from Barrett's mucosa reported as having dysplasia between 1987 and 1988 were reviewed by 4 pathologists. The biopsies were classified according to the method of Riddell, as no dysplasia, indefinite for dysplasia, low-grade dysplasia and high-grade dysplasia. Each pathologist reviewed the biopsies alone and then together. There was a total agreement between the 4 pathologists in 20 out of 37 biopsies (54%). The pair-wise agreement varied between 65 and 84%. It was 84% when the pathologists belonged to the same institution. Of 222 double reviews made by 6 pairs of pathologists (37 biopsies x 6 pairs of pathologists), there were 58 disagreements: 19 low grade/high grade dysplasia, 2 high grade/indefinite for dysplasia, 1 high grade/no dysplasia, 18 low grade/indefinite for dysplasia, 2 low grade/no dysplasia, 16 indefinite for dysplasia/no dysplasia. At the second review when the pathologists evaluated the biopsies together, the agreement was 92%; there were 3 biopsies on which there was total disagreement: twice between high grade and low grade dysplasia, once between low grade dysplasia, indefinite for dysplasia and no dysplasia. This retrospective study has shown that disagreement between pathologists was rarely found on the biopsies diagnosed as having high grade dysplasia, more often on those diagnosed as having low grade dysplasia or indefinite for dysplasia.(ABSTRACT TRUNCATED AT 250 WORDS)

[Diffuse sclerosing papillary carcinoma of the thyroid. Report of a case]. / Carcinome papillaire sclérosant diffus de la thyroide. Présentation d'un cas.

The authors report the case of a 12-year-old girl presenting with a diffuse sclerosing papillary carcinoma of the thyroid. The diagnosis was made on a total thyroidectomy specimen three months after thyroid enlargement was detected. This child had previously been treated medically for thyroiditis because of an enlarged thyroid gland with serum antithyroid autoantibodies. A few cases have been described in the literature. Six morphologic findings define this variant of papillary carcinoma: a diffuse growth pattern involving one or both lobes of the thyroid, prominent fibrosis, heavy lymphocytic infiltration with germinal centers, large numbers of psammoma bodies, squamous metaplasia and papillae within cleft-like tissue spaces. Some authors stated that this variant has a poorer prognosis than the usual papillary carcinoma of the thyroid. However, in some series a few patients survive without local recurrence or distant metastasis at a mean follow-up period of more than 10 years. Immunohistochemical studies have shown high accumulation of S-100 protein positive dendritic cells. Such an infiltration has been correlated with a better prognosis.

[Leiomyoma of the rectum]. / Les léïomyomes du rectum.

Most of the 150 leiomyomas of the rectum reported since 1872 were no larger than 5 cm. The authors report 3 new observations of leiomyomas of the rectum measuring more than 5 cm. The diagnosis of leiomyoma is difficult. The physical examination and rectoscopy suggest a submucal tumour of the rectum and endoendoscopy helps, describe the relations with the urogenital tract and the sphincters. Due to the lack of distinctive pathology features of malignancy, a leiomyosarcoma cannot be totally eliminated. The prognosis is uncertain due to the rate of relapse and the short follow-up (less than one year) in the previously reported cases. A slow spontaneous clinical course is however possible. The treatment goal is complete surgical removal. While local exeresis is indicated in tumours less than 5 cm in size, echo-guided endorectal protectomy with or without amputation of the sphincter should be discussed for larger tumours.