Secondary neurulation of human embryos: morphological changes and the expression of neuronal antigens.

PURPOSE: The morphological changes and expression patterns of neuronal antigens of human embryos, obtained from the therapeutic termination of pregnancy or from surgical procedures, were analyzed in order to characterize the secondary neurulation. METHODS: A total of 21 human embryos from Carnegie stages 12 to 23 and two fetuses in early stages were studied. The markers used for immunohistochemical study were neural cell adhesion molecule (N-CAM), neuronal nuclear antigen (NeuN), neurofilament-associated protein (3A10), synaptophysin, and glial fibrillary acidic protein (GFAP). RESULTS: The formation of the caudal neural tube to the tip of the caudal portion of the embryo was finished at stage 17. The postcloacal gut had completely disappeared at stage 18, and multiple cavities of the caudal neural tube were clearly visible. The caudal portion of the neural tube showed findings suggestive of involution at stage 19. The expression patterns of neuronal antigens were as follows: N-CAM and NeuN showed immunoreactivity at the germinal layer of the spinal cord at stages 17 and 18. Neurofilament-associated protein (3A10) showed persistent immunoreactivity at the caudal cell mass and notochord during the observation period, along with the spinal cord, and the positive reactions were mainly located at the dorsal white matter at stage 17. Synaptophysin showed a weak positive reaction at the caudal cell mass and notochord at stages 13 and 14, evident by staining observed at the spinal cord at stages 15 and 16. There was no definite positive reaction for GFAP. CONCLUSIONS: These characteristic patterns might be helpful for the understanding of human congenital anomalies involving secondary neurulation processes.

Identification and morphologic assessment of mesocoelic recess by in vivo human brain imaging with 7.0-T magnetic resonance imaging.

OBJECTIVE: The mesocoelic recess (MCR) is found in the brain of human embryos and fetuses. The mesocoelic recess seems to be functionally related to the subcommissural organ that is one of neurosecretory organs involved in osmoregulation on the basis of data from other species. Subsequently, recent speculation as to the importance of the subcommissural organ in the development of congenital hydrocephalus has been raised. Yet unlike other mammals, MCR is known to be a vestigial structure in the adult human brain. Here, we performed the in vivo imaging identification of this space to investigate functional and clinical correlations. METHODS: We studied adult human brains using a 7.0-T magnetic resonance imaging (MRI). Twenty healthy individuals aged 22 to 30 years were selected, and they were all volunteers. The parasagittal images through the intercommissural line were examined. We determined the type of shape of the MCR; a triangular C shape was classified as type 1, and a trapezoidal concave shape was classified as type 2. RESULTS: In 14 brains, the recesses were radiologically demonstrated just rostral to the tectal plate of the midbrain and covered the ventral aspect of the posterior commissure and pointed the opening into the aqueduct. The average size of the circumference of the MCR measured from the end point of the C-shaped cup was 6.82 mm. CONCLUSIONS: This study on the anatomy of the MCR of adult brains in vivo is the first of its kind, thanks to the availability of 7.0-T MRI because it has been barely discernible even in autopsy specimens as well as in radiology owing to the resolution limit of the currently available imaging system. The current study raises awareness of the MCR, an important but little-known anatomic structure in adult human brain. This visualization of MCR in human in vivo with ultrahigh-field MRI will certainly provide us important clues including the functional information of MCR, a mystery of modern neurological science.

Gnathostoma hispidum infection in a Korean man returning from China.

Human Gnathostoma hispidum infection is extremely rare in the world literature and has never been reported in the Republic of Korea. A 74-year-old Korean man who returned from China complained of an erythematous papule on his back and admitted to our hospital. Surgical extraction of the lesion and histopathological examination revealed sections of a nematode larva in the deep dermis. The sectioned larva had 1 nucleus in each intestinal cell and was identified as G. hispidum. The patient recalled having eaten freshwater fish when he lived in China. We designated our patient as an imported G. hispidum case from China.

Absence of the septum pellucidum associated with a midline fornical nodule and ventriculomegaly: a report of two cases.

We report two autopsy cases that revealed the partial absence of the septum pellucidum with ventriculomegaly. In each case, the brain showed mild dilatation of both frontal horns of the lateral ventricles, normal third and fourth ventricles and no aqueductal stenosis. The posterior portion of the septum pellucidum was absent and the fornices were fused in a single midline nodule, abnormally displaced to a caudal position and lodged in the foramina of Monro. The brain base showed no apparent abnormalities; the optic nerves were well developed. We conclude that the caudally displaced fornix in the absence of the septum pellucidum may have intermittently obstructed the foramina of Monro and induced mild ventriculomegaly.

Nodular lymphoid hyperplasia and histologic changes mimicking celiac disease, collagenous sprue, and lymphocytic colitis in a patient with selective IgA deficiency.

Selective IgA deficiency is the most common primary immunoglobulin deficiency. The clinical manifestations of selective IgA deficiency, including gastrointestinal (GI) complications, are rare and typically milder than those seen with common variable immunodeficiency or X-linked agammaglobulinemia. We present a rare case of selective IgA deficiency that shows a number of interesting histological features in the GI tract, including diffuse nodular lymphoid hyperplasia involving the entire small and large intestine, celiac disease-like and collagenous sprue-like changes in the small intestine, as well as lymphocytic colitis pattern. However, this patient had no particular GI symptoms suggestive of celiac sprue or microscopic colitis. These findings suggest that the GI tract in patients with selective IgA deficiency can show peculiar histologic changes that mimic celiac disease, collagenous sprue, or lymphocytic colitis, which may be a pattern of injury related to infection or immunoglobulin immunodeficiency-associated autoimmune phenomena.

Helicobacter heilmannii-associated gastritis: clinicopathologic findings and comparison with Helicobacter pylori-associated gastritis.

The aims of this study were to evaluate the clinicopathologic features of Helicobacter heilmannii-associated gastritis and to compare H. heilmannii-associated gastritis with H. pylori-associated gastritis. We reviewed 5,985 consecutive gastric biopsy specimens. All cases of chronic gastritis with Helicobacter infection were evaluated with the Updated Sydney System, and the grades of all gastritis variables were compared between H. heilmannii-associated gastritis and H. pylori-associated gastritis groups. There were 10 cases of H. heilmannii-associated gastritis (0.17%) and 3,285 cases of H. pylori-associated gastritis (54.9%). The organisms were superficially located within the mucous layer without adhesion to epithelial cells. Interestingly, in one case many intracytoplasmic H. heilmannii organisms were observed in parietal cells with cell damage. A case of low-grade mucosa-associated lymphoid tissue (MALT) lymphoma concomitant with H. heilmannii infection was detected. Compared to H. pylori-associated gastritis, H. heilmannii-associated gastritis showed less severe neutrophilic activity (p<0.0001), mononuclear cell infiltration (p=0.0029), and endoscopic findings of chronic gastritis devoid of erosion or ulcer (p=0.0309). In conclusion, we present the detailed clinicopathologic findings of H. heilmanniiassociated gastritis compared to H. pylori-associated gastritis. H. heilmannii-associated gastritis is uncommon and milder than H. pylori-associated gastritis, however it may be noteworthy with respect to the development of MALT lymphoma.

A case of histologically diagnosed tick infestation on the scalp of a Korean child.

A scalp mass surgically excised from a 4-year-old Korean boy was identified as a tick through histological observations. In sections of the mass, characteristic features of a tick, including its gross contour, cuticular structures, well developed musculature and salivary glands, and the capitulum, were discovered. In particular, the capitulum is anteriorly protruded, which strongly suggests that the specimen be a hard tick of family Ixodidae. However, the present histological features were not enough to determine the genus and species of the tick, because information on sectional morphologies of different tick species is unavailable. This is a rare case of tick infestation on the scalp diagnosed in histological sections.

Cytokinetics of secondary neurulation in chick embryos: Hamburger and Hamilton stages 16-45.

OBJECTIVES: In an attempt to understand the events in the secondary neurulation in embryonic stage, we investigated cytokinetic changes in the tail bud of normal developing chick embryos. MATERIALS AND METHODS: We investigated chick embryos of Hamburger and Hamilton stages 16-45 by staining for proliferating cell nuclear antigen (PCNA) and applying the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) method. RESULTS AND CONCLUSIONS: The cytokinetics of secondary neurulation have several distinctive properties: a general chronological delay compared to primary neurulation; absence of ventrodorsal differences; larger rostrocaudal differences; and degeneration of the distal end of the spinal cord in the later stages of development. These differences in morphogenetic and cytokinetic behavior between primary and secondary neurulation may help to improve our understanding of anomalies originating during secondary neurulation.

Coexistence of colloid cyst and neuroglial heterotopia.

INTRODUCTION: Colloid cyst is a rare intracranial tumor in childhood. This is the first report on the coexistence of a colloid cyst and the neuroglial heterotopia. DISCUSSION: A 3-year-old boy presented with a 10-day history of headache. Radiological findings revealed a cyst in the third ventricle and a solid mass protruding into the lateral ventricle causing obstructive hydrocephalus. The cyst was attached to the solid mass. Endoscopic aspiration and removal of the cyst followed by biopsy of the protruding mass was performed. Headache and vomiting then disappeared and the patient returned to normal life. CONCLUSION: The pathologic diagnosis was a colloid cyst associated with neuroglial heterotopia. We experienced a case of coexistent colloid cyst and neuroglial heterotopia, which have different embryonal origins.

Surgical outcome and prognostic factors of pediatric epilepsy caused by cortical dysplasia.

OBJECTS: We analyzed 30 patients with cortical dysplasia (CD) and epilepsy to evaluate the clinical characteristics and surgical outcome of both epilepsy control and neurocognition. MATERIALS AND METHODS: The mean ages at seizure onset and at the time of the operation were 3.6 years (range, 1 month-12.6 years) and 10.3 years (range, 1.5-18.3 years), respectively. The mean follow-up period was 3.2 years (range, 1-5.3 years). (18)FDG-positron emission tomography was the most sensitive and magnetic resonance imaging was the most specific in localizing the lesion. Developmental/intellectual delay was predominant in the early-onset group (n=18, seizure onset <3 years), with intelligence tending to be normal in the late-onset group (n=12, seizure onset >or=3 years). Mild CD predominated in the late-onset epilepsy group and moderate or severe CD in the early-onset group (p=0.005). The surgical success rate of epilepsy control was 87%. A better outcome was obtained if the lesion was confined to the temporal lobe. School performance was favorable in 43%. The age at seizure onset and preoperative developmental/intellectual delay were the important prognostic factors in school performance as well as the epilepsy control. A total of 77% of patients had relatively good social adaptation. Successful epilepsy control and good school performance were affirmative conditions precedent to social adaptation. CONCLUSIONS: Due to the favorable control of epilepsy and its effect on school performance and social adaptation, surgical treatment is strongly recommended for cortical dysplasia and intractable epilepsy.

Expressions of HSP70 and HSP27 in hepatocellular carcinoma.

The heat shock proteins (HSPs) are ubiquitous molecules induced in cells exposed to various stress conditions, including carcinogenesis. The HSP70 and HSP27 among HSPs are of special relevance in human cancer inhibiting apoptosis. The aim of this study is to investigate the expressions of HSP70 and HSP27 in hepatocellular carcinoma (HCC) in association to tumor cell proliferation and apoptosis. We examined the expressions of HSP70 and HSP27 by immunohistochemical staining in 71 cases of HCC, and then related their expressions to clinicopathologic parameters and expressions of p53, Ki-67 and Apotag. HSP70 and HSP27 were frequently stained in the cytoplasm and nuclei of tumor cells, but not in the non-neoplastic hepatocytes. Immunoreactivities of HSP70 and HSP27 were observed in 56.3% and 61.9% of HCCs, respectively. HSP70 immunoreactivity correlated with high Ki-67 labeling indices (LIs) (p=0.0159), large tumor size (p=0.0129), presence of portal vein invasion (p=0.0231), and high tumor stage (p=0.0392). HSP27 immunoreactivity significantly related with the subgroup of HBV-associated HCCs (p=0.0003), but not with the others. Both HSP70 and HSP27 immunoreactivities showed no relation to Apotag LIs or p53 immunoreactivity. In conclusion, expressions of HSP70 and HSP27 may play an important role in hepatocarcinogenesis, and especially HSP70 showed a close relationship to the pathological parameters associated with tumor progression and high Ki-67 LIs. Our results could be additional evidence that HSP70 expressions can contribute to not only hepatocarcinogenesis but also tumor progression by promoting tumor cell proliferation.

Immunohistochemical studies of pediatric intestinal pseudo-obstruction: bcl2, a valuable biomarker to detect immature enteric ganglion cells.

To identify the diagnostic pitfalls as well as the value of immunohistochemical studies in making a pathologic evaluation of a pediatric intestinal pseudo-obstruction (IPO), this study reassessed the pathology of 87 surgically resected intestines from 80 patients under the impression of IPO and 10 normal controls using immunohistochemical studies. The main diagnostic pitfall was the interpretation of the enteric nervous plexuses in the transitional zone and the detection of the indistinct or immature neurons indistinguishable from enteric glial cells or satellite cells. Immunohistochemical study was a very helpful diagnostic adjunct to delineating the immature neurons (bcl2), the size of the enteric ganglia and neuromuscular innervation (S-100 protein, synaptophysin, and CD56), and the interstitial cell of Cajal (c-Kit) and myopathy (SMA). With help of immunohistochemistry, our series of IPO could classify as neuropathy (92.5%), myopathy (2.5%), and the idiopathic forms (3.8%) more clearly. In terms of the types of neuropathy, Hirschsprung's disease (HD), pure hypoganglionosis, and intestinal neuronal dysplasia (IND-B) were diagnosed in 71.3%, 6.3%, and 48.8% of patients, respectively. IND-B was associated with other neuropathies, HD in 77.0% and hypoganglionosis in 7.7%, rather than being present in a pure form. Immature ganglion cells were found in 48.8%. Because a reduced number of interstitial cells of Cajal was commonly associated with HD in 84.2%, hypoganglionosis in 40%, and IND-B in 76.9% of cases, it might be a preceding or aggravating factor related to an IPO. In terms of detecting immature ganglion cells, we found bcl2 most helpful.

Hepatocellular carcinoma occurring in alagille syndrome.

Hepatocellular carcinoma only rarely occurs in Alagille syndrome. Here, we report on three cases of hepatocellular carcinoma associated with Alagille syndrome. All three patients were boys and presented with jaundice. In addition, they had the characteristic facial appearance of Alagille syndrome with cardiac, vertebral, and eye anomalies, and all had passed acholic stools from the neonatal period. Liver biopsies were diagnosed as bile duct paucity, compatible with Alagille syndrome in two cases, but the third case showed marked bile duct proliferation at the initial liver biopsy when 7 months old, which made diagnosis difficult. Eventually, all three cases progressed to biliary cirrhosis and hepatocellular carcinoma, which occurred at 17 months, 4 years, and 7 years, respectively. Because of the unusual liver histology and early onset of hepatocellular carcinoma, careful clinicopathologic correlations and close monitoring are required for the diagnosis of Alagille syndrome and for the early detection of hepatocellular carcinoma.

Cortical laminar disorganization is correlated with severity of the cortical dysplasia and surgical outcome--experience with 150 cases.

The aim of this study is to evaluate that the cortical laminar disorganization (CLD) and its correlation with the severity of the cortical dysplasia (CD) and surgical outcome. The cohort consists of 150 patients (101 males and 49 females) who underwent surgical resection of the epileptic area due to medically intractable epilepsy. Histologically, the CLD was divided into three grades according to the degree of disarrangement of the clear-cut six-layered cortex and the pathological features on MAP2 and NeuN immunostaining; normal to mild, moderate and severe CLD in 58 (38.7%), 47 (31.3%) and 45 (30.0%) cases, respectively. The histopathological grading of CLD had significant correlation with severity of CD (p<0.001), number of single heterotopic neurons in white matter (p=0.009), presence of neurons in molecular layer (p<0.001), persistent subpial granular cells (p=0.017), cytomegalic neurons (p<0.001) and balloon cells (p<0.001), and gray-white matter blurring (p<0.001), and had inverse correlation with surgical outcome (<0.001). Since statistically correlated with the known parameters of CD and surgical outcome, the grading of CLD could be used as another histological parameter for CD.

Parietal lobe epilepsy: surgical treatment and outcome.

OBJECTIVE: Parietal lobe epilepsy (PLE) is neither common nor easily diagnosed because of its variable clinical features. To elucidate its characteristics and surgical outcome, the authors reviewed their surgical experiences. METHODS: Between September 1994 and August 2001, 38 patients with PLE received surgical treatment at the Seoul National University Hospital. All patients underwent resection, mainly involving the parietal lobe. RESULTS: Preoperatively, over 60% of the cases were not considered to be PLE, even though PLE was the most common diagnosis (15/38, 39.8%). An invasive study was performed in 37 of the 38 patients. Awake operations under regional anesthesia were performed in 20 patients (52.6%). Seizure disappeared in 15 (Engel's classification I, 39.5%), and rare seizure remained in 5 (Engel II, 13.2%). Thirteen patients showed a worthwhile improvement (Engel III, 34.2%), whereas 5 exhibited no worthwhile improvement (Engel IV, 13.2%). Pathologies were diverse, the most common being cortical dysplasia (94.3%). CONCLUSION: Since PLE is difficult to diagnose preoperatively, an invasive study covering the parietal lobe is mandatory, if PLE is suspected. Cortical dysplasia was the most common etiology, thus awake operation under regional anesthesia and intraoperative brain mapping is helpful during extensive resection in order to spare the eloquent cortex.

Cytoplasmic crystalline inclusions in a anaplastic oligoastrocytoma.

A 41-year-old male presented with an ill-demarcated mass involving the left fronto-temporal lobe and the basal ganglia. Light microscopically the tumor was diagnosed as an anaplastic oligoastrocytoma. Electron microscopy revealed several cytoplasmic crystalline inclusions in tumor cells of oligodendroglial lineage. No crystalline inclusions were membrane bound. The morphologic features with unique ultrastructural findings are presented.

Multiple small intestinal stromal tumors associated with neurofibromatosis-1.

Gastrointestinal stromal tumors (GISTs) are rarely noted in association with neurofibromatosis-1 (NF-1, von Recklinghausen disease) as an individual gastrointestinal manifestation. We report here a case of multiple GISTs with an abundant skeinoid fiber in the jejunum of a 43-year-old woman diagnosed as NF-1. Histologically, the tumors were composed of uniform spindle-shaped cells with a fascicular pattern, almost indistinguishable from the histology characteristic of usual GISTs. However, multiple synchronous tumor occurrence, abundant skeinoid fiber, and presence of microscopic miniatures of stromal tumors are additional characteristic features of this case.

Overexpression of cyclooxygenase-2 in childhood ependymomas: role of COX-2 inhibitor in growth and multi-drug resistance in vitro.

The management of ependymomas remains one of the most frustrating issues in pediatric neuro-oncology. Gross total resection is not always possible, and intensive chemotherapy and craniospinal radiotherapy have made no clear advances. Moreover, the chemoresistance of ependymomas may be explained by the expression of membrane transport molecule P-glycoprotein (P-gp). In this study the expression of cyclooxygenase 2 (COX-2) and the role of the specific COX-2 inhibitor NS-398 in growth and multi-drug resistance of ependymomas were investigated. COX-2 protein expression was assessed in 19 ependymomas immunohistochemically, and the effect of NS-398 on growth and multi-drug resistance was investigated using two primary cultured ependymoma cell lines. COX-2 protein expression was observed in 15 (79%) of the 19 ependymomas. NS-398 was found to reduce the proliferation of monolayer cell cultures in a dose- and time-dependent manner and to induce apoptosis and lower bcl-2 protein levels. After NS-398 treatment, Western blotting showed reduced P-gp expression and a rhodamine 123 efflux assay demonstrated a significant decrease in P-gp activity. Our findings demonstrate that COX-2 is overexpressed in ependymomas and that NS-398 is able to induce apoptosis and suppress P-gp expression and activity.

Sclerosing meningioma: clinicopathological study of four cases.

Sclerosing meningioma is a distinct histologic subtype of meningioma, however, it is often confused with other tumors, especially malignant tumors. To widen our knowledge of sclerosing meningioma and to help neurosurgeons and neuropathologists diagnose this clinically and pathologically unfamiliar disease entity, we reviewed four such cases, which were originally misdiagnosed. Sclerosing meningiomas were assessed for cellularity, cellular pleomorphism, mitotic activity, brain invasion, and necrosis. Immunohistochemical staining was performed on paraffin-embedded sections using the avidin-biotin-peroxidase complex method. The histologic appearance of the underlying cerebral parenchyma invasion by tumor cells led to a diagnosis of malignant meningioma or to the completely erroneous diagnosis of ganglioglioma. The most conspicuous histologic finding of these four sclerosing meningiomas was extensive collagen deposition, so called 'sclerosis' and an intermingled small population of spindle or round cells with clear cytoplasmic halos, giving a 'fried egg' appearance. However, a typical meningothelial whorl pattern was identified in all cases. Tumor cells exhibited positive immunoreactivity for epithelial membrane antigen and vimentin, but were negative for glial fibrillary acidic protein, p53, S-100, and neuronal markers. Proliferative indices, using Ki-67, ranged from 0% to 4%, and brain invasion was present in three of four tumors. All four patients are doing well with no evidence of tumor recurrence (follow-up duration of 25 months to 12 years). Brain invasion needs to be re-evaluated as a criterion of malignancy in meningioma. Special attention should be paid to the diagnosis of this subtype of meningioma to prevent unnecessary postoperative radiotherapy and to ensure correct therapeutic decision.

Ultrastructural studies of gastrointestinal stromal tumors.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors in the gastrointestinal tract (GIT). Although interstitial cells of Cajal has been suggested as origin of this tumor, the cytological and ultrastructural features of GISTs are heterogeneous and unclear. A total 10 cases of normal gastrointestinal tissue (control), 13 GISTs of the stomach (8), small intestine (3), mesocolon (1) and liver (1), and 2 gastrointestinal autonomic nervous tumor (GANT) of small intestine were ultrastructurally studied. Normal interstitial cells of Cajal (ICC) were abundantly present around the myenteric plexuses or individually scattered through the wall of GIT. ICC was characterized by slender cytoplasmic processes, well-developed endoplasmic reticulum (ER), mitochondria, Golgi apparatus, caveolae and intermediate filaments. The GISTs and GANTs had overlapping ultrastructures. The most common and important ultrastructural features of GISTs were rich villous cytoplasmic processes, dispersed intermediate filaments and abundant SER, and those of GANTs were neurosecretory granules and skenoid fibers. Compared with ICC, the GISTs and GANTs had remarkably reduced caveolae and gap junctions. Our study suggested that ultrastructural analysis gives much information to investigate lineage differentiation of neoplastic cells and make a differential diagnosis of these tumors from other mesenchymal tumors and between GISTs and GANTs.