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Biomedical subjects

Valérie Hervieu

Publications and source records attributed to Valérie Hervieu.

14 recordsLinked to original sources

HIP/PAP, a member of the reg family, is expressed in glucagon-producing enteropancreatic endocrine cells and tumors.

Hepatocarcinoma-intestine-pancreas/pancreatitis-associated protein (HIP/PAP) protein, a member of the reg family, is constitutively expressed by some specialized epithelial cell subsets in the digestive tract and the pancreas. We performed a detailed analysis of the expression of HIP/PAP protein in normal digestive endocrine cells according to their localization, lineage, and differentiation stage, and in digestive endocrine tumors according to their site of origin and hormonal profile. In both adult and fetal normal tissues, HIP/PAP expression was detected only in endocrine cells of the small intestine, ascending colon, and pancreas. Two different expression patterns were identified: (a) a strong cytoplasmic labeling observed in the endocrine cells of the digestive mucosa and the outer rim of Langerhans islets specialized in the synthesis of glucagon and glucagon-like peptides; (b) a weak cytoplasmic immunoreactivity observed in the other pancreatic endocrine cell populations. HIP/PAP expression was detected in 36 of the 184 cases of digestive endocrine tumors examined; 32 of these cases (89%) were pancreatic. The 2 patterns observed in the normal state were retained: (a) a strong labeling was observed in 5% to 100% of tumor cells in 26 tumors, all expressing glucagon or glucagon-like peptides; (b) a weak labeling was present in 10 tumors, presenting various hormonal profiles. In conclusion, a strong expression of HIP/PAP is characteristic of glucagon-producing normal and neoplastic enteropancreatic endocrine cells. Our results lend further support to the concept that members of the reg family play regulatory roles in various endocrine cell populations and that their expression in endocrine cells is lineage-specific.

Adolescent↗

[Mixed endocrine tumors].

Mixed endocrine tumors are tumors composed of at least two distinct tumor populations, one of which is endocrine. Because of their rarity and unusual presentation, endocrine mixed tumors raise many problems of diagnosis, management and therapy. Three main types of endocrine mixed tumors are recognized: The existence of these various types has been confirmed by recent molecular studies, even if the same studies have also shown that the histogenesis of a mixed endocrine tumor cannot be predicted from its histological features. Composite tumors are the less rare mixed tumors. The recent WHO classification recommends to restrict the term of composite endocrine tumor to the epithelial tumors containing at least 30% of obviously tumoral endocrine cells; some authors recommend to use higher thresholds, of at least 50%, in order to avoid overdiagnosis. The endocrine component is usually well differentiated, easily identified by its suggestive histological features; the endocrine nature of tumor cells is confirmed by the immunodetection of specific endocrine and neuro-endocrine markers (such as chromogranin A and synaptophysin). In some cases, the endocrine component is poorly differentiated: the demonstration of neuro-endocrine markers is necessary to confirm the diagnosis. Mixed tumors can occur in every anatomical site; they are more frequent in organs containing endocrine cells in the normal state (especially the digestive tract and the pancreas), but they can also be observed in organs devoid of endocrine cells (such as the mammary gland). The management of mixed endocrine tumors must take into account the more aggressive component. Mixed tumors containing a well differentiated endocrine component and an adenocarcinomatous component are to be treated like adenocarcinomas. Mixed tumors containing a poorly differentiated endocrine component must be considered as poorly differentiated endocrine carcinomas.

Colonic Neoplasms↗

Clear cell myomelanocytic tumor (PEComa) of the duodenum in a child with a history of neuroblastoma.

We report herein a case of digestive clear cell myomelanocytic tumor (PEComa) that is unique in its location and presentation. The lesion, located in the duodenal wall, was diagnosed in a child with a history of cervical neuroblastoma that was in remission after surgical resection and chemotherapy. The diagnosis was obtained by examination of a biopsy specimen taken during laparoscopy. The decision was made to perform surgical resection. Examination of the surgical specimen confirmed the diagnosis of PEComa. No metastasis was found. After 2 years of follow-up, the patient is alive, without evidence of metastasis or recurrence. This case highlights the distinctive characteristics of the cells in PEComa, recognizable even on limited biopsy material. It also suggests a possible association between PEComa and neuroblastoma, 2 unusual tumors that belong to the spectrum of lesions known to occur in patients with tuberous sclerosis and that may share a possible common pathogenetic mechanism.

Adenocarcinoma↗

Endothelial cell differentiation in hepatocellular adenomas: implications for histopathological diagnosis.

BACKGROUND/AIMS: Little information is available about the patterns of endothelial cell differentiation observed in hepatocellular adenomas. We therefore aimed to analyze the endothelial cell immunophenotype in a large series of these tumors and evaluate its possible diagnostic relevance. METHODS: The expression of continuous and sinusoidal endothelial cell markers and of extracellular matrix proteins was analyzed by immunoperoxidase in 56 adenomas, as compared with 30 cases of focal nodular hyperplasia (FNH), 2 cases of telangiectatic FNH and 40 cases of hepatocellular carcinoma (HCC). RESULTS: Twenty-eight adenomas (50%) presented a sinusoidal pattern of endothelial cell differentiation, characterized by the expression of specific sinusoidal endothelial cell markers and the presence of a subendothelial matrix resembling the normal perisinusoidal matrix. Eleven tumors (19.5%) presented a continuous pattern of endothelial cell differentiation. Seventeen tumors (30.5%) showed a mixed pattern. Twenty-eight FNH presented a sinusoidal pattern of endothelial cell differentiation; all HCC presented a continuous pattern of endothelial cell differentiation. CONCLUSIONS: In hepatocellular adenomas, intra-tumoral vessels usually present a sinusoidal pattern of endothelial cell differentiation. However, the vascular phenotypic heterogeneity observed in our study questions the potential relevance of endothelial cell immunophenotyping for the differential diagnosis between hepatocellular adenomas and well differentiated HCC.

Adenoma, Liver Cell↗

[Adenocarcinomas of the stomach and distal esophagus. Incidence and phenotypic characteristics of EBV-associated cases in the Lyons area, France].

AIMS: Our study aimed to evaluate the incidence of EBV-associated adenocarcinomas of the stomach and distal esophagus in Lyons area and to assess their phenotypic characteristics. METHODS: 85 cases of gastric adenocarcinomas and 40 cases of esophageal adenocarcinomas were screened for EBV by in situ hybridization (EBER-1 and -2) and immunohistochemistry (LMP1 and EBNA-1); all cases positive for EBER by in situ hybridization were studied by PCR for demonstration of EBV DNA. The clinical, histological and immunophenotypic features of EBV-associated adenocarcinomas were assessed. RESULTS: 5 cases of EBV-associated adenocarcinomas, all gastric, were identified in our series (5.8%); one was diagnosed in a migrant from Algeria, a region of high endemia of EBV infection. 3 cases were located in the proximal stomach, 1 in the distal; 1 was diffuse. 4 cases were of the intestinal histological type. Proliferation index and microvessel density were high in all 5 cases. The expression of tumor markers was markedly heterogeneous from one case to another. CONCLUSIONS: Our study shows that EBV infection is restricted to gastric adenocarcinomas. Its incidence is evaluated to 5.8% in our series: this shows that Lyons area must be considered as a low risk area. In the absence of specific histological or phenotypic features, the screening of EBV+gastric adenocarcinomas is possible only with special techniques.

Adenocarcinoma↗

Low microvessel density is an unfavorable histoprognostic factor in pancreatic endocrine tumors.

BACKGROUND AND AIMS: In many malignant tumors, intratumoral microvascular density (MVD) has been suggested to be a prognostic parameter. We aimed to provide a quantitative evaluation of intratumoral microvascular density in a large series of resected endocrine tumors of the pancreas and to evaluate the potential prognostic significance of this parameter. METHODS: Eighty-two tumors from 77 patients have been studied. MVD was evaluated by 2 observers after CD34 immunostaining and correlated with the following parameters: WHO classification, hormonal profile, tumor size, vascular endothelial growth factor expression, occurrence of metastasis, duration of survival. RESULTS: MVD ranged from 5 to 92 vessels/field. MVD was significantly higher in well-differentiated benign endocrine tumors than in tumors of uncertain behavior and in carcinomas. No close correlation was found between MVD and the hormonal profile. MVD was significantly higher in tumors characterized by the following histoprognostic parameters: size <2 cm, proliferation index <2%, no evidence of metastasis. No close correlation was observed between MVD and VEGF expression. Finally, a MVD <30 vessels/field was associated with the occurrence of metastasis in tumors <2 cm and/or with a proliferation index <2% and with a significantly shorter survival after surgery. CONCLUSIONS: The quantitative analysis of microvessel density in pancreatic endocrine tumors may identify patients who, despite favorable conventional histoprognostic factors, are at risk of unfavorable evolution.

Arterioles↗

[Amphicrine carcinoma of the pancreas. Report of two cases].

Amphicrine carcinomas are rare tumors defined by the presence of tumor cells showing evidence of both exocrine and endocrine differentiation. We here report two cases of amphicrine carcinomas of the pancreas, an exceedingly rare localization for this type of tumors. Diagnosis was made in respectively, a 32-year-old woman and a 66-year-old man; tumors measured 7 and 3 cm in diameter; metastatic dissemination was present in both cases. The first patient, treated by surgery and chemotherapy, is alive, without disease progression, after 26 months; the second patient deceased early after the diagnosis. In both cases, the first diagnosis considered at cytological and histological examination was endocrine carcinoma. The amphicrine nature of the lesion was ascertained by the combined demonstration of mucus staining and chromogranin A expression in the same cells. In one case, the amphicrine nature of tumor cells was confirmed by the ultrastructural examination. The identification of the amphicrine nature of an apparently endocrine tumor is of relevance, because of the poor prognosis of amphicrine carcinomas as compared to endocrine carcinomas and the requirement for aggressive therapy.

Adult↗

[Endocrine carcinoma of the pancreas revealed by a pseudocyst].

Pancreatic pseudocysts are the most frequent cystic lesions of the pancreas. They always are associated with acute or chronic pancreatitis. We here report the case of a pseudocyst of the pancreas associated with obstructive chronic pancreatitis and diagnosed in a 47-year-old man without previous history of acute pancreatitis and without risk factor. The examination of the surgical specimen resulted in the incidental discovery of an obstructive nodule of endocrine carcinoma, measuring 9 mm in diameter and located immediately at the contact of the pseudocyst. The tumor was ill limited and associated with metastatic spread in 2 peripancreatic lymph nodes. Immunohistochemical studies showed that 60% of tumor cells expressed serotonin. This case report underlines that the diagnosis of pseudocyst must be done much cautiously in patients without a clinical history of pancreatitis and without risk factor. In most cases, the lesion corresponds to a misdiagnosed cystic tumor. Even if the lesion actually corresponds to a pseudocyst, as in the present case, an unusual cause, and particularly, an obstructive tumor, must be searched for.

Endocrine Gland Neoplasms↗