Perren, A.

Neuroendocrine gastro-entero-pancreatic tumors: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up (Article)

2012-10-01T00:00:00Z

ENETS consensus guidelines for the management of Brain, cardiac and ovarian metastases from neuroendocrine tumors (Article)

2010-06-01T00:00:00Z

An immunohistochemical procedure to detect patients with paraganglioma and phaeochromocytoma with germline SDHB, SDHC, or SDHD gene mutations: a retrospective and prospective analysis (Article)

2009-08-01T00:00:00Z

Background: Phaeochromocytomas and paragangliomas are neuro-endocrine tumours that occur sporadically and in several hereditary tumour syndromes, including the phaeochromocytoma-paraganglioma syndrome. This syndrome is caused by germline mutations in succinate dehydrogenase B (SDHB), C (SDHC), or D (SDHD) genes. Clinically, the phaeochromocytoma-paraganglioma syndrome is often unrecognised, although 10-30% of apparently sporadic phaeochromocytomas and paragangliomas harbour germline SDH-gene mutations. Despite these figures, the screening of phaeochromocytomas and paragangliomas for mutations in the SDH genes to detect phaeochromocytoma-paraganglioma syndrome is rarely done because of time and financial constraints. We investigated whether SDHB immunohistochemistry could effectively discriminate between SDH-related and non-SDH-related phaeochromocytomas and paragangliomas in large retrospective and prospective tumour series. Methods: Immunohistochemistry for SDHB was done on 220 tumours. Two retrospective series of 175 phaeochromocytomas and paragangliomas with known germline mutation status for phaeochromocytoma-susceptibility or paraganglioma-susceptibility genes were investigated. Additionally, a prospective series of 45 phaeochromocytomas and paragangliomas was investigated for SDHB immunostaining followed by SDHB, SDHC, and SDHD mutation testing. Findings: SDHB protein expression was absent in all 102 phaeochromocytomas and paragangliomas with an SDHB, SDHC, or SDHD mutation, but was present in all 65 paraganglionic tumours related to multiple endocrine neoplasia type 2, von Hippel-Lindau disease, and neurofibromatosis type 1. 47 (89%) of the 53 phaeochromocytomas and paragangliomas with no syndromic germline mutation showed SDHB expression. The sensitivity and specificity of the SDHB immunohistochemistry to detect the presence of an SDH mutation in the prospective series were 100% (95% CI 87-100) and 84% (60-97), respectively. Interpretation: Phaeochromocytoma-paraganglioma syndrome can be diagnosed reliably by an immunohistochemical procedure. SDHB, SDHC, and SDHD germline mutation testing is indicated only in patients with SDHB-negative tumours. SDHB immunohistochemistry on phaeochromocytomas and paragangliomas could improve the diagnosis of phaeochromocytoma-paraganglioma syndrome. Funding: The Netherlands Organisation for Scientific Research, Dutch Cancer Society, Vanderes Foundation, Association pour la Recherche contre le Cancer, Institut National de la Santé et de la Recherche Médicale, and a PHRC grant COMETE 3 for the COMETE network.

ENETS consensus guidelines for the standards of care in neuroendocrine tumors: Biotherapy (Article)

2009-08-01T00:00:00Z

ENETS consensus guidelines for the standards of care in neuroendocrine tumors: Somatostatin receptor imaging with IIIIn-pentetreotide (Article)

2009-08-01T00:00:00Z

ENETS consensus guidelines for the standards of care in neuroendocrine tumors: Follow-up and documentation (Article)

2009-08-01T00:00:00Z

ENETS consensus guidelines for the standards of care in neuroendocrine tumors: Chemotherapy in patients with neuroendocrine tumors (Article)

2009-08-01T00:00:00Z

ENETS consensus guidelines for the standards of care in neuroendocrine tumors: Radiological examinations (Article)

2009-08-01T00:00:00Z

ENETS consensus guidelines for the standards of care in neuroendocrine tumors: Biochemical markers (Article)

2009-08-01T00:00:00Z

ENETS consensus guidelines for the standards of care in neuroendocrine tumors: Towards a standardized approach to the diagnosis of gastroenteropancreatic neuroendocrine tumors and their prognostic stratification (Article)

2009-08-01T00:00:00Z

ENETS consensus guidelines for the standards of care in neuroendocrine tumors: Pre- and perioperative therapy in patients with neuroendocrine tumors (Article)

2009-08-01T00:00:00Z

ENETS consensus guidelines for the standards of care in neuroendocrine tumors: Echocardiography (Article)

2009-08-01T00:00:00Z

ENETS consensus guidelines for the standards of care in neuroendocrine tumors: Peptide receptor radionuclide therapy with radiolabeled somatostatin analogs (Article)

2009-08-01T00:00:00Z

The purpose of this guideline is to assist physicians caring for patients with neuroendocrine tumors in considering eligibility criteria for peptide receptor radionuclide therapy (PRRT), and in defining the minimum requirements for PRRT. This guideline also makes recommendations on what minimal patient, tumor, and treatment outcome characteristics should be reported for PRRT in order to make comparisons between studies possible. It is not this guideline's aim to give specific recommendations on the use of specific radiolabeled somatostatin analogs for PRRT because different analogs are being used, and their availability depends on national law and local permissions.

Familial endocrine tumours: phaeochromocytomas and extra-adrenal paragangliomas (Article)

2009-02-01T00:00:00Z

About 30% of phaeochromocytomas (PCCs), sympathetic paragangliomas (sPGLs) and parasympathetic paragangliomas (pPGLs) are due to a familial syndrome. In half of these patients the presentation is syndromic or accompanied by a positive family history. However, over 10% of patients with clinically sporadic disease are still affected by an inheritable disease. Patients with multiple and/or bilateral tumours or disease onset at a young age are at an increased likelihood of such a syndrome and require genetic counselling and DNA testing. A genotype-phenotype correlation is emerging: multiple endocrine neoplasia type 2 (MEN-2) and von Hippel - Lindau disease-associated adrenal PCCs are often bilateral. Extra-adrenal (malignant) sPGLs are more typical in SDHB families. Multiple pPGLs (sometimes together with PCCs) occur in the setting of SDHD mutations, and SDHC families suffer from familial singular pPGLs. Some familial tumours also show typical histological features which should be looked for and reported by the pathologist. We review endocrine tumour syndromes with PCCs and/or PGLs, and summarize their genetic background and clinical and morphological features, and give recommendations for genetic testing.

Poorly-differentiated endocrine carcinomas of midgut and hindgut origin (Article)

2007-12-01T00:00:00Z

Consensus guidelines for the management of patients with digestive neuroendocrine tumors - Well-differentiated jejunal-ileal tumor/carcinoma (Article)

2007-12-01T00:00:00Z

Consensus guidelines for the management of patients with liver metastases from digestive (neuro)endocrine tumors: Foregut, midgut, hindgut, and unknown primary (Article)

2007-12-01T00:00:00Z

Consensus guidelines for the management of patients with digestive neuroendocrine tumours: Well-differentiated colon and rectum tumour/carcinoma (Article)

2007-12-01T00:00:00Z

Consensus guidelines for the management of patients with digestive neuroendocrine tumours: Well-differentiated tumour/carcinoma of the appendix and goblet cell carcinoma (Article)

2007-12-01T00:00:00Z

DNA copy number status is a powerful predictor of poor survival in endocrine pancreatic tumor patients (Article)

2007-09-01T00:00:00Z

The clinical behavior of endocrine pancreatic tumors (EPTs) is difficult to predict in the absence of metastases or invasion to adjacent organs. Several markers have been indicated as potential predictors of metastatic disease, such as tumor size ≥ 2 cm, Ki67 proliferative index ≥ 2%, cytokeratin (CK) 19 status, and recently in insulinomas, chromosomal instability (CIN). The goal of this study was to evaluate the value of these markers, and in particular of the CIN, to predict tumor recurrence or progression and tumor-specific death, using a series of 47 insulinomas and 24 non-insulinoma EPTs. From these EPT cases, a genomic profile has been generated and follow-up data have been obtained. The proliferative index has been determined in 68 tumors and a CK19 expression pattern in 50 tumors. Results are statistically analyzed using Kaplan-Meier plots and the log-rank statistic. General CIN, as well as specific chromosomal alterations such as 3p and 6q loss and 12q gain, turned out to be the most powerful indicators for poor tumor-free survival (P ≤ 0.0004) and tumor-specific death (P ≤ 0.0113) in insulinomas. The CIN, chromosome 7q gain, and a proliferative index ≥ 2% were reliable in predicting a poor tumor-free survival in non-insulinoma EPTs (P < 0.0181, whereas CK19 expression was the most optimal predictor of tumor-specific death in these tumors. In conclusion, DNA copy number status is the most sensitive and efficient marker of adverse clinical outcome in insulinomas and of potential interest in non-insulinoma EPTs. As a consequence, this marker should be considered as a prognosticator to improve clinical diagnosis, most practically as a simple multi-target test.

Candidate gene mutation analysis in bilateral adrenal pheochromocytoma and sympathetic paraganglioma (Article)

2007-06-01T00:00:00Z

Pheochromocytomas (PCCs) are rare tumors that arise from chromaffin tissue in the adrenal medulla, but can also occur in the abdomen outside the adrenals and are then called sympathetic paragangliomas (sPGLs). According to the literature, between 15 and 25% of apparently sporadic adrenal PCC and sPGL are caused by germline mutations in RET, von Hippel-Lindau disease (VHL), succinate dehydrogenase subunit B (SDHB), or subunit D SDHD. However, few studies have addressed the mutation frequency of these candidate genes in selected subgroups of PCC and sPGL, such as bilateral adrenal PCC or extra-adrenal sPGL, and none have looked at somatic mutations by analyzing tumor tissue. Therefore, we have investigated the occurrence of germline and somatic mutations in RET, VHL, SDHB, and SDHD in comparatively large series of bilateral adrenal PCC (n=33 patients) and sPGL (n=26 patients), with the aim of determining the mutation frequency of each of these genes and to establish a genetic testing algorithm. Twenty-one RET, two VHL germline, and one SDHD mutations were found in the patients with bilateral adrenal PCC. In sPGL, one novel SDHB germline and one novel SDHB somatic mutation were observed. In addition, two SDHD germline mutations were found. We conclude that germline RET mutations are predominantly found in bilateral PCC, and that somatic and germline SDHB and SDHD mutations usually occur in sPGL, which has practical consequences for genetic testing algorithms. We suggest that sequential mutation analysis should be directed first at RET, followed by VHL and SDHD for patients with bilateral adrenal PCC at diagnosis, and at SDHB and SDHD for patients with sPGL.

Well-differentiated pancreatic tumor/carcinoma: Insulinoma (Article)

2007-02-01T00:00:00Z

Well-differentiated gastric tumors/carcinomas (Article)

2007-02-01T00:00:00Z

Poorly differentiated carcinomas of the foregut (gastric, duodenal and pancreatic) (Article)

2007-02-01T00:00:00Z

Well-differentiated duodenal tumor/carcinoma (excluding gastrinomas) (Article)

2007-02-01T00:00:00Z

Gastrinoma (duodenal and pancreatic) (Article)

2007-02-01T00:00:00Z

Well-differentiated pancreatic nonfunctioning tumors/carcinoma (Article)

2007-02-01T00:00:00Z

Rare functioning pancreatic endocrine tumors (Article)

2007-02-01T00:00:00Z