Diffuse neuroendocrine differentiation in a morphologically composite mammary infiltrating ductal carcinoma: a case report and review of the literature

Neuroendocrine differentiation has been reported in both in situ and infiltrating breast cancers. The prognostic significance of neuroendocrine differentiation in mammary carcinoma is unclear. We report a case of infiltrating ductal carcinoma in which there was a morphologically conventional-appearing infiltrating ductal component admixed with nests of cells that resembled a carcinoid tumor and initially mimicked the appearance of intraductal carcinoma. Immunohistochemical stains for synaptophysin and chromogranin demonstrated diffuse, strong positivity uniformly throughout the tumor, even in the more conventional-appearing areas. Electron microscopic examination of tissue retrieved from paraffin blocks was attempted unsuccessfully. We concluded that this was an infiltrating ductal carcinoma with morphologic and immunohistochemical evidence of neuroendocrine differentiation. The case is discussed with a review of the literature and a discussion of nomenclature for tumors of the breast showing variable degrees of neuroendocrine differentiation.     

Anti-Mullerian Hormone: A New Marker of Ovarian Function

Objectives

The aim of this study was to determine day 3 Serum AMH, FSH, LH, Estradiol (E₂), Inhibin B levels, ovarian volume, and antral follicular count to assess ovarian function.

Methods

This study was conducted on 130 infertile women between age 18 and 43 years. Day 3 Serum AMH level was estimated by sandwich enzyme immunoassay; Serum FSH, S. LH, S. E₂, by solid-phase two-site chemiluminescent immunometric assay; Inhibin B by ELISA; and Ovarian volume and AFC, by transvaginal ultrasonography.

Results

With advancing age, Serum AMH level (p < 0.0001), AFC (p < 0.05), ovarian volume (>0.05), and Inhibin B (>0.05) were decreased, and Serum FSH (p < 0.05), LH (p > 0.05), and E₂ (p < 0.05) were increased. Serum AMH level was 4–6.8 ng/ml with optimal fertility in 26.15 % cases and 2.2–4.0 ng/ml with satisfactory fertility in 53.85 % cases. Serum AMH levels were more strongly correlated with AFC (p < 0.0001) and ovarian volume (p < 0.0001).

Conclusion

Serum AMH levels were more robustly correlated with AFC than FSH, LH, E₂, and Inhibin B on day 3 of the cycle. This suggested that serum AMH might be taken as single test to reflect ovarian reserve.     

Stem cell marker nestin and c-Jun NH2-terminal kinases in tumor and peritumor areas of glioblastoma multiforme: possible prognostic implications.

PURPOSE: It has been hypothesized that brain tumors are derived from stem cell or transiently dividing precursor transformation. Furthermore, c-Jun NH(2)-terminal kinases (JNKs) have been involved in gliomagenesis. This study analyzes stem cell marker nestin and JNK expression in glioblastoma multiforme (GBM) and peritumor tissue and assesses their possible prognostic implications. EXPERIMENTAL DESIGN: Nestin and both total JNK (tJNK) and phosphorylated JNK (pJNK) expression was investigated by immunohistochemistry in 20 GBMs. Samples were derived from tumors (first area), from tissues at a distance <1 cm (second area), and between 1 and 3.5 cm (third area) from the macroscopic tumor border. The relationships between patients' age, Karnofsky performance status, gender, protein expression, and survival were analyzed. RESULTS: Nestin cytoplasmic immunoreactivity was observed in the majority of cells in tumor but infrequently in peritumor areas. tJNK, observed in the nucleus and cytoplasm, was widely expressed in the three areas; pJNK, mostly located in the nuclei, was found in a variable percentage of cells in the tumor and peritumor tissue. Nestin and JNK expression in peritumor areas was independent of the presence of neoplastic cells. Univariate analysis indicated that survival was longer (19 versus 12 months; P = 0.01) for patients whose pJNK/nestin and (pJNK/tJNK)/nestin ratios in the second area were > or =2.619 and > or =0.026, respectively. The same variables showed an independent prognostic value in multivariate analysis. CONCLUSIONS: Nestin and JNK expression indicates that peritumor tissue, independently of the presence of neoplastic cells, may present signs of transformation. Moreover, pJNK/nestin and (pJNK/tJNK)/nestin ratios in that tissue seem to have some prognostic implications in GBM patients.     

Psychotic depression and mortality

OBJECTIVE: Major depressive disorder is associated with elevated mortality rates that increase with the severity of depression. The authors hypothesized that patients with psychotic depression would have higher mortality rates than patients with nonpsychotic depression. METHOD: Survival analytic techniques were used to compare the vital status of 61 patients with psychotic major depression with that of 59 patients with nonpsychotic major depression up to 15 years after hospital admission. Medical status was assessed with the Cumulative Illness Rating Scale. Dexamethasone suppression test (DST) data were available for 101 patients. RESULTS: The mortality rate for subjects with psychotic depression was significantly greater than that for those with nonpsychotic depression, with 41% versus 20%, respectively, dying within 15 years after hospital admission. A proportional hazards model with age and medical status entered as covariates confirmed a significantly higher mortality rate in patients with psychotic depression (hazards ratio=2.31). A positive DST result was associated with psychotic depression but was not related to vital status. CONCLUSIONS: Patients with psychotic depression have a two-fold greater risk of death than do patients with severe, nonpsychotic major depression.     

GABAergic immunoreactivity is predominant in neurons derived from expanded human neural precursor cells in vitro

Neural precursor cells have been previously isolated from the developing human nervous system and their properties studied both in vitro and in transplantation paradigms in vivo. However, their ability to differentiate into neurons of different neurochemical phenotypes remains poorly defined. In this study, the default in vitro neuronal differentiation of hENPs derived from five different regions of the human embryonic brain (cerebral cortex, striatum, cerebellum, ventral mesencephalon, and spinal cord) was studied after varying periods of time in culture. The results were directly compared to those from similarly prepared murine ENPs. hENPs prepared from all five regions showed a significant reduction in the number of neurons generated at each passage, such that by passage 4 only between 5 and 10% of cells spontaneously adopted a neuronal phenotype after differentiation in vitro. A similar observation was obtained with murine ENPs. hENPs prepared from more caudal parts of the developing neuroaxis generated fewer neurons compared to the more rostral regions. The only neuronal phenotype identified in these cultures was GABA, with 15-60% of the neurons immunopositive for this neurotransmitter. Thus there appears to be important differences between hENPs dependent on region of origin and time in vitro under standard culture conditions, forming decreasing numbers of neurons with increasing time in culture and more caudal sites of harvest, and with the major identifiable neurotransmitter being GABA. Such characterisation is important in the process of learning how to manipulate the neuronal phenotype of these cells.     

Ground scratching and preferred leg use in domestic chicks: changes in motor control in the first two weeks post-hatching

Lateralisation of a variety of visual functions: food discrimination, fear response, copulation, and performance of topographical and other tasks, such as olfactory and auditory functions, have been described in the domestic chick, Gallus gallus domesticus. A bias to left hemisphere control on day 8 and to the right on day 11 has also been demonstrated in the domestic chick. In this study we show that motor control as to foot preference in initiating a scratching bout and a tape-removing task is lateralised in both adults and chicks. There was a preference for the right leg to initiate a bout of ground scratching in both male and female adult birds. Second, foot preference is also affected by the changes in shifts of bias on day 8 and day 11. The right leg preference in initiating a ground scratching bout observed on day 5 is reversed to a left leg preference on day 8. This then reverts to the right leg preference after day 11. Hence it is postulated that the hemisphere that is not activated due to the bias of age controls the first leg to be used in initiating routine movements such as ground scratching. For the tape-removing task the right leg was used to remove a tape adhered to the beak of the chick for the trained group on day 8; but there was no preference in the naive group. Similarly, on day 11 a left foot bias was observed for the trained group and right foot bias for the naive group. To remove a tape the activated hemisphere on days of bias is used; whereas in a novel situation the foot use is reversed. Thus, footedness is affected by age, type of task, and changing hemispheric dominance.     

The kinetics of deregulation of expression by de novo methylation of the h19 imprinting control region in cancer cells

Epigenetic lesions are common in neoplasia and range from hypermethylation of subsets of CpG islands to loss of imprinting. By exploiting an episomal model system and the strong de novo methylation capacity of a human cancer cell line, we show that an H19 minigene rapidly becomes methylated and silenced, mimicking the inactivation of the maternal H19 allele in a range of cancers. Although the H19 imprinting control region (ICR) initially displayed methylation protection, it eventually succumbed to the pressure mounted by the de novo methylation machinery of the JEG-3 cells. Importantly, we were able to visualize the kinetics of the loss of the H19 ICR chromatin insulator function in association with chromatin compaction. Our results document that a strong de novo methylation machinery leads to loss of methylation privilege states of H19 ICR to functionally manifest loss of insulator function in a matter of only a few days in human cancer cells.     

Gastric phytobezoar associated with impaired gastric motility in a patient with spinal cord injury

Impaired gastrointestinal motility as a result of interruption of sympathetic outflow is a common occurrence in the spinal cord injury (SCI) population. In addition, frequent use of medications with anticholinergic properties in this population results in further impairment of peristalsis resulting in gastrointestinal stasis. Since SCI patients often lack sensation below the level of injury, they may present with vague symptoms, which complicates the diagnosis of intestinal obstruction. We report the first case of gastric phytobezoar in a patient with T4 ASIA A paraplegia who presented with vague upper abdominal discomfort, anorexia, weight loss, and vomiting. Because mortality rates can be as high as 30% if phytobezoars remain untreated, gastrointestinal phytobezoars should be considered in the differential diagnosis of abdominal discomfort in SCI patients. Etiologic factors for phytobezoars are discussed for the general population and in particular, for patients with SCI.