Od karcinoida do biološki i prognostički značajne klasifikacije neuroendokrinih tumora probavnog trakta i gušterače

Although well established in the medical terminology, the term carcinoid is no longer adequate to cover the entire morphological and biological spectrum of neoplasms of the disseminated neuroendocrine cell system. Instead of "carcinoid" the WHO classification published in 2000 therefore uses the general terms "neuroendocrine tumor" and "neuroendocrine carcinoma". In this review we describe a classification of gastroenteropancreatic neuroendocrine tumors based on the WHO criteria. We also classify and comment on the most important tumor entities. On the basis of localization and of various morphological and biological criteria we distinguish between benign neuroendocrine tumors, tumors with uncertain malignant potential, and tumors showing low grade and high grade malignancy.Iako je dobro poznat u medicinskoj terminologiji, pojam karcinoid nije više dovoljan da bi pokrio eitav morfološki i biološki spektar neoplazma diseminiranog neuroendokrinog staničnog sustava. Stoga se u klasifikaciji što ju je 2000. godine objavila SZO umjesto "karcinoidi" rabe opći pojmovi "neuroendokrini tumor" i "neuroendokrini karcinom". U ovom preglednom članku opisujemo klasifikaciju gastroenteropankreatičnih neuroendokrinih tumora, koja se temelji na kriterijima SZO. Također dajemo klasifikaciju i primjerene napomene o najvažnijim tumorskim entitetima. Na osnovi lokalizacije i različitih morfoloških i bioloških kriterija razlikujemo benigne neuroendokrine tumore, tumore neodređenog malignog potencijala, te tumore koji pokazuju nizak i visok stupanj malignosti

Human insulinoma: clinical, cellular, and molecular aspects

Insulinoma is the most frequently encountered functioning endocrine pancreatic tumor in humans. In this overview we summarize morphological and clinical features of insulinomas, report about the proinsulin-insulin conversion in normal and neoplastic B-cells, discuss the new classification, the criteria of malignancy, and the clonal composition of endocrine pancreatic tumors, and outline recent findings on the molecular pathology of these tumor

Immunostaining for the tumour suppressor gene p16 product is a useful marker to differentiate melanoma metastasis from lymph-node nevus

Upon the introduction of extensive sampling protocols of sentinel node biopsies, pathologists are increasingly confronted with small melanoma metastases. Using conventional histology, it proves sometimes difficult or impossible to differentiate small melanoma metastases from lymph-node nevi. Loss of the tumour suppressor gene p16 has been shown to be associated with tumour progression of melanoma. We investigated nevus and melanoma cells for the presence of the product of the gene p16, using immunohistochemistry. All nevus cells, independent of their location (nodal or skin) displayed an extensive nuclear and cytoplasmic staining for p16. In contrast, all cells of melanoma metastases, except one skin metastasis, lacked nuclear staining for p16. These findings indicate that p16 is a reliable marker to distinguish lymph-node nevi from melanoma metastasis

Differentiated thyroid carcinoma. Follow-up of 264 patients from one institution for up to 25 years

UNLABELLED The optimum treatment for differentiated thyroid carcinoma (DTC) is still debated. Results obtained using a selective treatment strategy for papillary (PTC) and follicular (FTC) thyroid carcinoma over 25 years in one institution are reported. 149 patients (mean age 46 yrs) had PTC in TNM stages I-IV in 58%, 26%, 15% and 1% respectively. Total thyroidectomy and remnant 131I ablation (43%) were carried out in TNM high-risk patients (stages III and IV) and in low-risk patients (I and II) at risk for a (curable) recurrence (stages pN1 and/or pT4). Hemi- or total thyroidectomy, without radioiodine, was used in 76% of pT1-3 N0 tumours (68%). Central and/or lateral lymphadenectomy was performed in 42% of patients (electively in the last 4 years). The mean follow-up was 7 years. RESULTS 6 patients died of PTC and 8/143 patients treated for cure had a recurrence (6 nodal, 1 contralateral, 1 local). In low-risk patients--including 68% of patients aged > or = 45 yrs--the cause specific 25-year survival rate was 100%, vs. 62% (at 15 years) (p or = 45 yrs) patients with PTC in stages I and II have an excellent prognosis (risk 0). With selective (therapeutic) lymphadenectomy the risk of nodal recurrence may be very low in node negative tumours, without use of radioiodine. Meticulous lymphadenectomy is indicated in pN1 tumours with nodal recurrences despite 131I (5/36 patients). The technique of capsular dissection for extracapsular total uni- or bilateral thyroidectomy provides excellent oncological and surgical results. A decrease in the incidence of FTC parallels a decrease in endemic goitre in Switzerland

Epidermal growth factor receptor is a marker for syncytiotrophoblastic cells in testicular germ cell tumors

The epidermal growth factor receptor (EGFR) has been implicated in the pathogenesis, therapy and prognosis of various tumor types. The aim of this study was to investigate EGFR expression in a large series of testicular germ cell tumors (TGCTs). A total of 88 TGCTs (37 of pure type and 51 of mixed type) comprising a total of 44 seminoma, 49 embryonal carcinoma, 32 yolk sac tumor, 28 teratoma and 7 choriocarcinoma components were immunostained for EGFR. EGFR reactivity was observed in the stromal cells of embryonal carcinoma (29%) and in epithelial compartments of teratoma (71%). In addition, EGFR staining was consistently detected in syncytiotrophoblastic cells of choriocarcinoma, seminoma, embryonal carcinoma and yolk sac tumor components. EGFR staining, similar to β-human chorionic gonadotropin (HCG) immunohistochemistry, was efficiently able to identify syncytiotrophoblastic cells in TGCTs. This study shows that EGFR is expressed in a subset of testicular germ cell tumors and suggests that EGFR may be a useful marker for syncytiotrophoblastic cell

Absence of BRAF gene mutations differentiates spitz nevi from malignant melanoma

BACKGROUND: Distinction of Spitz nevus from malignant melanoma is sometimes difficult on the basis of conventional histology. A high rate of BRAF gene mutations in malignant melanomas (66%) and nevi (82%) has recently been reported. MATERIALS AND METHODS: We screened a series of 20 Spitz nevi for BRAF mutations in exons 11 and 15 by denaturing gradient gel electrophoresis (DGGE). RESULTS: BRAF mutations could not be identified in Spitz nevi. CONCLUSION: Our results show that mutations within the BRAF gene are useful markers for the differential diagnosis between Spitz nevus and malignant melanoma

CGH analysis shows genetic similarities and differences in atypical fibroxanthoma and undifferentiated high grade pleomorphic sarcoma

BACKGROUND: Atypical fibroxanthoma (AFX) and undifferentiated high grade pleomorphic sarcoma (UpS) are histologically very similar, if not identical. However, they differ significantly in clinical outcome. MATERIALS AND METHODS: We used comparative genomic hybridization (CGH) to screen 24 AFX and 12 UpS for genomic alterations. RESULTS: DNA copy number changes were observed in 20/24 AFX and in all UpS. The most frequent alterations occurring with comparable frequency in both tumors were deletions on chromosomes 9p and 13q. We also detected statistically significant differences of genetic alterations between the two tumors concerning deletions on 1q, 3p, 5q, 11p, 11q, gains on 7q, 12q and high level gains on 5p and 11q. CONCLUSION: Despite their very similar histology, AFX and UpS show clear differences in their genetic alterations. This might contribute to the different biological behavior of the two tumors. On the other hand the similarities in genetic alterations on chromosomes 9p and 13q might suggest a common pathogenetic pathway