Blue Rubber Bleb Nevus Syndrome Diagnosed Prenatally as an Epignathus.

The authors present a clinical report of the giant fetal tumor protruding from the oral cavity diagnosed sonographically at 32 weeks of gestation as an epignathus. After delivery, tumor proved to be a presentation of the blue rubber bleb nevus syndrome. To the best of our knowledge, the literature offers no reports on similar cases.

Fetal intra-abdominal tumors: assessment of spectrum, accuracy of prenatal diagnosis, perinatal outcome and therapy at a tertiary referral center.

OBJECTIVE: To describe the varieties and ultrasound characteristics of prenatally diagnosed fetal abdominal tumors and to scrutinize the accuracy of prenatal diagnosis as well as the postnatal outcome and therapy of affected pregnancies. STUDY DESIGN: Retrospective study of 354 fetuses found to have abdominal tumors on prenatal sonogram, identified from 1993 to 2009 at a tertiary referral center for prenatal medicine. The cohort was classified into subgroups according to the sonographic appearance of the fetal tumor and the affected anatomic structure (urinary, gastrointestinal and genital tracts and other locations). Sensitivity, specificity, positive predictive value and false-positive rate of ultrasonography in identifying the system of origin were calculated. Relationships between relevant outcome domains and the different subgroups were assessed using the chi-square test and Fisher's exact test. RESULTS: Our cohort comprised 222 urinary tract lesions, 37 genital tract lesions, 80 gastrointestinal lesions and 15 tumors of other origins. The mean gestational age at diagnosis was 26+0 wks. The prenatally established diagnosis was exactly concordant with postnatal findings in 88.9%. Sensitivity, specificity, positive predictive value and false-positive rate of ultrasonography in identifying the system of origin (urinary, gastrointestinal, genital tracts and other locations) were 98.3%, 97.6%, 92.6% and 2.4%, respectively. The favorable postnatal outcome rate was highest among fetuses with genital tract lesions (95%) and lowest among those with tumors of the urinary tract (62%, p=<0.001). Twenty per cent of tumors regressed spontaneously, mostly gastrointestinal tumors (36%, p=<0.001). In 75/354 cases (21%) the parents opted to terminate the pregnancy: intra-uterine fetal demise and neonatal death were each noted in 4%. Prenatal therapy was performed in 24 of 354 cases (7%) and postnatal surgery in 64 cases (18%). CONCLUSION: The majority of fetal abdominal anomalies were accurately diagnosed and the vast majority of affected fetuses had a favorable outcome, some tumors even resolved with advancing pregnancy. Pre- and post-natal invasive surgical interventions were mandatory in only a small number of cases.

Gastroenteropancreatic neuroendocrine tumor cancer stem cells: do they exist?

Neuroendocrine tumors (NETs) comprise a broad range of neoplasms that share biological and embryological origin. A deeper knowledge in the underlying molecular biology that results in the development and spread of NETs has allowed the use of novel-targeted therapies against angiogenesis and intracellular pathways, key checkpoints that govern growth, and proliferation of these tumors. Unfortunately, the possibility of cure is still far for patients with advanced stages. Cancer stem cells (CSCs) are present in most solid tumors. Nevertheless, there is limited evidence for the presence of CSCs in NETs. In this review, we will discuss the embryonic origin and possible existence of a gastroenteropancreatic neuroendocrine cancer stem cell. Here, we summarize the body of evidence supporting the presence of active embryological pathways like Notch, Wnt-ß-catenin, Hedgehog, or transforming growth factor-ß in NETs. New therapeutic approaches in the field of CSCs seem to have a clear role in the treatment of medulloblastomas and basal cell carcinomas, but their future value in other solid tumor types including NETs remains unclear.

Time-point and dosage of gene inactivation determine the tumor spectrum in conditional Ptch knockouts.

Mutations in Patched (PTCH) have been associated with tumors characteristic both for children [medulloblastoma (MB) and rhabdomyosarcoma (RMS)] and for elderly [basal cell carcinoma (BCC)]. The determinants of the variability in tumor onset and histology are unknown. We investigated the effects of the time-point and dosage of Ptch inactivation on tumor spectrum using conditional Ptch-knockout mice. Ptch heterozygosity induced prenatally resulted in the formation of RMS, which was accompanied by the silencing of the remaining wild-type Ptch allele. In contrast, RMS was observed neither after mono- nor biallelic postnatal deletion of Ptch. Postnatal biallelic deletion of Ptch led to BCC precancerous lesions of the gastrointestinal epithelium and mesenteric tumors. Hamartomatous gastrointestinal cystic tumors were induced by monoallelic, but not biallelic Ptch mutations, independently of the time-point of mutation induction. These data suggest that the expressivity of Ptch deficiency is largely determined by the time-point, the gene dose and mode of Ptch inactivation. Furthermore, they point to key differences in the tumorigenic mechanisms underlying adult and childhood tumors. The latter ones are unique among all tumors since their occurrence decreases rather than increases with age. A better understanding of mechanisms underlying this ontological restriction is of potential therapeutic value.

Neuroectodermal differentiation of the gastrointestinal tumors in the Carney triad. An ultrastructural and immunohistochemical study.

A 16-year-old female with mediastinal paraganglioma and multicentric gastroduodenal "leiomyoblastomas" was thought to have an incomplete form of the Carney triad. The histologic, ultrastructural, and immunohistochemical findings of the gastroduodenal tumors revealed features of neuroectodermal differentiation. The architecture of the smallest duodenal tumors suggested an origin from the myenteric autonomic ganglia.

[The diffuse endocrine system and the carcinoids of the alimentary tract. Part I: Orthological aspects and common morphological features of the carcinoids (author's transl)]. / Das diffuse endokrine System und die Karzinoide des Gastrointestinaltraktes. Teil 1: Orthologische Gesichtspunkte und allgemeine Pathologie der Karzinoide.

Carcinoids arise from the so-called system of diffuse clear cells. Because of common histochemical properties it was proposed in the APUD-concept that these endocrine cells are of neural crest origin. As for the gastrointestinal tract endocrine cells this embryological derivation is disputed. Modern methods have led to the identification of about 18 distinct cell types. - According to the different localization of these cells in the alimentary canal the carcinoids show various histological structures i.e., a solid, trabecular, adenoid, undifferentiated and mixed growth. According to the reactivity to silver salts one can distinguish argentaffin, argyrophil and argyrophobe carcinoids. Biochemically and immunohistochemically some carcinoids are multihormonal, while others show paraendocrine hormone production. Small cell anaplastic carcinomas with endocrine granules are highly malignant variants of the carcinoids. There may be a mixed endo- and exocrine (amphicrine) differentiation in normal cells and in the so-called mucicarcinoids.

Embryogeneic cell type, organ site sequence specificity in human cancers.

An extensive series of cross-hybridization studies were carried out with the DNA-RNA molecular hybridization technique. Molecular 70 S [3H]DNA probes synthesized from human central nervous system, gastrointestinal, pulmonary, and prostatic carcinomas were hybridized to cytoplasmic RNA's isolated from cancers of virtually all organ sites of the human body. Results indicated sequence homology between cancers of the same organ or cell type but not with cancers of different cell types. Thus cell types based on embryological origins determine the organ site specificity of the involved sequences. The designation of 70 S [3H]DNA denotes those [3H]DNA's that were copied off the template 70 S RNA, as distinguished from total [3H]DNA product, which includes all DNA's synthesized. It does not necessarily follow nor is it to be inferred that the 70 S [3H] DNA thus designated contains the full complement of the sequences found in the 70 S RNA template.