Barrett's esophagus in Latinos undergoing endoscopy for gastroesophageal reflux disease symptoms.

Previous studies comparing the prevalence of Barrett's esophagus in Latinos and non-Latino whites are inconsistent. The aim of the study is to compare the prevalence of Barrett's esophagus in Latinos and non-Latino whites and to determine risk factors associated with Barrett's esophagus. Between March 2005 and January 2009, consecutive Latino and non-Latino white patients who underwent endoscopy for primary indication for symptoms of gastroesophageal reflux disease were identified by examining the internal endoscopy database at Los Angeles County + USC Medical Center. Barrett's esophagus was defined by columnar-lined distal esophagus on endoscopy confirmed by intestinal metaplasia on histology. Clinical features and endoscopic findings were retrospectively reviewed. The mean age of the 663 patients was 50 ± 12 years, 30% were male, and 92% were Latino. Compared with non-Latino whites, Latinos had more females (72% vs. 46%; P = 0.0001) and more Helicobacter pylori infection (53% vs. 24%; P = 0.003) but less tobacco use (7% vs. 17%; P = 0.01). Overall, 10% (68/663) of all patients had Barrett's esophagus whereas the prevalence was 10% (62/611) among the Latinos and 12% (6/52) among the non-Latino whites (OR 0.9, 95% CI 0.4-2.1; P = 0.75). One patient in the Latino group had high-grade dysplasia. On multivariate analysis, male gender (AOR 2.3, 95% CI 1.4-4.1; P = 0.002), diabetes (AOR 2.2, 95% CI 1.1-4.5; P = 0.03), and age ≥55 years (AOR 2.2, 95% CI 1.3-3.8; P = 0.006) were independently associated with Barrett's esophagus; Latino ethnicity remained nonsignificant (AOR 1.1, 95% CI 0.4-2.7; P = 0.88). In Latinos undergoing endoscopy for gastroesophageal reflux disease symptoms, the prevalence of Barrett's esophagus was 10%, comparable with non-Latino white controls as well as the prevalence previously reported among Caucasians. In addition to established risk factors, diabetes was associated with Barrett's esophagus.

The gene expression profile of cardia intestinal metaplasia is similar to that of Barrett's esophagus, not gastric intestinal metaplasia.

The etiology and significance of cardia intestinal metaplasia (CIM) is disputed. CIM may represent a form of Barrett's esophagus due to reflux or could reflect generalized gastric intestinal metaplasia due to Helicobacter pylori. The aim of this study was to utilize gene expression data to compare CIM to Barrett's and gastric intestinal metaplasia. Endoscopic biopsies were classified by endoscopic and histologic criteria as CIM (n= 33), Barrett's (n= 25), or gastric intestinal metaplasia of the antrum or body (n= 18). The squamocolumnar and gastroesophageal junctions were aligned in CIM patients and patients with diffuse gastric intestinal metaplasia were excluded. H. pylori was tested for in the biopsies of all patients. After laser-capture microdissection, quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to measure the mRNA expression of a panel of nine genes that has been shown to differentiate Barrett's from other foregut mucosa. Cluster analysis with linear discriminant analysis of the expression data was used to classify each sample into groups based solely on similarity of gene expression. Cluster analysis was performed for three groups (CIM vs. Barrett's vs. gastric intestinal metaplasia) and two groups (CIM + Barrett's vs. gastric intestinal metaplasia). There was no difference in H. pylori infection among groups (P= 0.66). Clustering into three groups resulted in frequent misclassification between CIM and Barrett's while misclassification of gastric intestinal metaplasia was uncommon. The CIM and Barrett's groups were then combined for two group clustering and linear discriminant analysis correctly predicted 95% of CIM and Barrett's samples and 83% of gastric intestinal metaplasia samples based on gene expression alone. In conclusion, the gene expression profiles of CIM and Barrett's esophagus were similar in 95% of biopsies and differed significantly from that of gastric intestinal metaplasia. The indistinguishable gene expression profile of CIM and BE suggests that they may share a common etiology in the majority of patients with a similar biology, and calls into question the perception that CIM is an innocuous process.

Presence of p53 mutations in primary nasopharyngeal carcinoma (NPC) in non-Asians of Los Angeles, California, a low-risk population for NPC.

Mutatins of the p53 tumor suppressor gene are rare in nasopharyngeal carcinoma (NPC) patients who reside in high-risk areas, such as Southeastern China. Among this high-risk group, a pre-existing infection with the EBV and consumption of Cantonese salted fish are closely associated with NPC. We investigated the prevalence of p53 mutations in 28 primary NPC specimens from white (including Hispanic) and African-American patients in Los Angeles, who are at low risk for NPC. Using PCR-based single-strand conformational polymorphism and direct sequencing, we found four mutations (14%) in exons 5-8 of the p53 gene in four patients. All were C-to-T transition mutations: two were present in exon 5-one at codon 142 [CCT (Pro)-->CTT (Leu)] and another at codon 144 [CAG (Gln)-->TAG (stop codon)]. The other two mutations were identified in exon 8: one at codon 273 [CGT (Arg)-->CAT (His)], a CpG site, and one at codon 271, a silent mutation [GAG (Glu)-->GAA (Glu)]. This is the first report investigating the presence of p53 missense mutations in NPC among a low-risk population. Our data indicate that p53 is also an infrequent event among NPC patients at low risk for the disease.

Familial visceral myopathy. Evidence of diffuse involvement of intestinal smooth muscle.

We report the histologic and ultrastructural findings on two sisters with familial visceral myopathy who presented with acquired megacolon that necessitated subtotal colectomy. Both patients were mentally retarded and had repeated episodes of constipation and fecal impaction. Each presented near the age of 30 with massive dilatation of the colon and without clinical evidence of small intestinal involvement. Histologic abnormalities primarily involved smooth muscle and included marked nuclear enlargement and irregularity, interstitial fibrosis, and cytoplasmic vacuolation. These changes were most severe in the muscularis propria, but similar abnormalities were found in the muscularis mucosae and blood vessels. In the most advanced stages, collagen had completely replaced the muscularis propria, with extreme thinning of the intestinal wall. Abnormalities were noted in all segments of the colon and the appendix, but there was little correlation between severity of involvement and the segment examined. This study not only confirms the variable nature of morphologic changes in familial visceral myopathy, but also provides evidence of more extensive involvement of intestinal smooth muscle than has been previously reported.

Granulomatous inflammation in pineal germinoma. A cause of diagnostic failure at stereotaxic brain biopsy.

We report four patients with pineal germinoma in whom the initial procedure for obtaining a tissue diagnosis was a stereotaxic biopsy. In all four cases, the biopsy showed granulomatous inflammation with epithelioid cells and lymphocytes. In one case, the granulomatous inflammation was accompanied by classical germinoma. Another case exhibited malignant cells considered nondiagnostic for a specific neoplasm. Two cases had no evidence of a malignant tumor; they were composed entirely of granulomatous inflammation. In two of the three cases where the diagnosis was not established by the first biopsy, a second stereotaxic biopsy showed pineal germinoma. Tissue obtained at resection in the third patient revealed large areas of granulomatous inflammation accompanying the germinoma. Immunoperoxidase stains for ferritin and placental alkaline phosphatase did not increase diagnostic yield. We conclude that a finding of granulomatous inflammation in a stereotaxic biopsy specimen of a pineal mass should suggest a diagnosis of germinoma, followed by sampling from several different target points within the lesion.

Sporadic visceral myopathy with inclusion bodies. A light-microscopic and ultrastructural study.

We report the clinical and pathologic findings of two patients with sporadic visceral myopathy. Both presented with chronic intestinal pseudo-obstruction that necessitated colectomy. Microscopically, typical changes of primary visceral myopathy were present, including variable fibrous replacement of the muscularis externa and vacuolar degeneration of myocytes. In addition, the muscle cells contained cytoplasmic inclusions that have only been recently reported in visceral myopathy. These inclusions were numerous and easily visible in routine hematoxylin-eosin-stained sections but greatly enhanced by periodic acid-Schiff staining. They were reactive immunohistochemically at their periphery and were seen to be myofibrils at various stages of degeneration on electron microscopy. Inclusions were present in both muscularis externae and muscularis mucosae and were identified in mucosal biopsy specimens, providing a means of diagnosing this type of myopathic change on endoscopic biopsies.

Histology of the gastroesophageal junction: an autopsy study.

Current diagnostic criteria for reflux disease and Barrett's esophagus are based on the belief that the gastroesophageal junction normally contains 2 cm of cardiac mucosa composed of mucous glands devoid of parietal cells. This autopsy study disproves this belief. Even when the entire circumference of the gastroesophageal junction is examined, pure cardiac mucosa was completely absent in 56% of patients. All patients had oxyntocardiac mucosa, in which glands contained a mixture of mucous and parietal cells. Cardiac and oxyntocardiac mucosae were present only in part of the circumference of the junction in 50% of patients. The measured maximum length of cardiac plus oxyntocardiac mucosa was less than 0.5 cm in 76% of patients. There was a tendency for the presence and extent of cardiac mucosa to increase with age. Cardiac mucosa at the junction is therefore frequently absent, has considerable individual variation, is very small in extent when present, is commonly absent from some part of the circumference of the junction, and increases in prevalence and length with age. These characteristics of cardiac mucosa make it highly unlikely that it is a normal structure. We develop the hypothesis that cardiac mucosa represents an early histologic manifestation of gastroesophageal reflux.

Distribution and significance of epithelial types in columnar-lined esophagus.

An abnormal columnar-lined esophagus (CLE) is characterized by the presence of cardiac mucosa (CM) oxynto-cardiac mucosa (OCM), and intestinal metaplastic epithelium (IM) between gastric oxyntic mucosa and esophageal squamous epithelium. Thirty-two patients with CLE measuring 2-16 cm long had 5-37 biopsies per patient that showed CM, OCM, or IM for a total of 424 biopsies. Detailed mapping of the distribution of epithelial types within the CLE showed a distinct zonation of epithelial types; CM was present throughout the CLE, whereas OCM and IM tended to occur in the distal and proximal part of the CLE, respectively. All 32 patients (64 of 68 biopsies) showed IM at the most proximal level, compared with 22 of 32 patients (40 of 102 biopsies) in the most distal level biopsies. The density of goblet cells was highest in the most proximal level. The differences in prevalence and density of goblet cells between most proximal and most distal level biopsies were highly significant. These data suggest that for a given number of biopsies within the CLE, the likelihood of finding IM is greatest when the biopsies are concentrated in the most proximal area of the CLE. We suggest that glandular transformation of squamous epithelium results in CM. which evolves into OCM and IM by development of specialized parietal cells and goblet cells, respectively. The severity and nature of reflux cause these epithelial transformations in a constant and predictable manner. Recognition of these changes permits the development of morphologic definitions of reflux disease and the characterization of the sequence of epithelial changes that represent the reflux-adenocarcinoma sequence.

Intermediate filament expression in astrocytic neoplasms.

Immunohistochemical analysis of 30 paraffin-embedded astrocytic neoplasms was performed to correlate the expression of intermediate filament proteins with histologic subtype. Each tumor was studied with monoclonal antibodies to keratin, vimentin, desmin, 200-kd neurofilament protein, and glial fibrillary acidic protein (GFAP). Immunoreactivity with the anti-keratin monoclonal antibodies AE1 and AE3 was demonstrated in 24 cases (80%) including 4 of 6 (66%) well-differentiated astrocytomas (WDAs), 10 of 12 (83%) anaplastic astrocytomas (ANAs), and 10 of 12 (83%) glioblastomas multiforme (GBMs). These cases were further studied with the monoclonal antikeratin antibodies 34 beta E12 and 34 beta H11. Of the 24 AE1/AE3-positive cases, 14 (58%) reacted with 34 beta E12. None of the cases was reactive with 34 beta H11. Vimentin expression was demonstrated in 24 cases (80%), including 2 of 6 (33%) WDAs, 11 of 12 (92%) ANAs, and 11 of 12 (92%) GBMs. Coexpression of keratin and vimentin was observed in 20 cases (67%), including 2 of 6 WDAs, 9 of 12 (75%) ANAs, and 9 of 12 (75%) GBMs. Immunoreactivity with GFAP antibody was present in all 30 (100%) cases, but none of the tumors was reactive with antibodies to desmin or 200-kd neurofilament protein. These findings demonstrate that expression of both keratin and vimentin intermediate filaments is common in astrocytic neoplasms regardless of histologic grade.

Definition of histopathologic changes in gastroesophageal reflux disease.

A series of 71 patients with multiple measured biopsies of the gastroesophageal junctional region permitting assessment of the presence and length of different glandular epithelial types is presented. All but nine of 53 patients in whom a 24-hour pH study was performed had abnormal reflux, suggesting that endoscopic recognition of an abnormal columnar mucosa at the gastroesophageal junction sufficient to precipitate multiple-level biopsies indicates a high probability of abnormal reflux. All patients had cardiac mucosa (CM) or oxyntocardiac mucosa (OCM). CM was present in 68 of 71 patients. The prevalence of intestinal metaplasia increased with increasing CM+OCM length, and was present in all 22 patients with a CM+OCM length >2 cm and in 20 of 49 patients with a CM+OCM length <2 cm. Patients with a CM+OCM length >2 cm had a markedly higher acid exposure than patients with a CM+OCM length <2 cm. The findings suggest that the presence of CM and OCM in the junctional region are predictive of abnormal acid exposure, and that increasing OCM+CM length correlates strongly with the amount of acid exposure. The histologic finding of CM and OCM represents a sensitive histologic criterion for gastroesophageal reflux rather than normal epithelia. These diagnostic criteria represent the first useful histologic definitions for assessing the presence and severity of reflux.

Primary mucosal malignant melanoma: an immunohistochemical study of 12 cases with comparison to cutaneous and metastatic melanomas.

Immunohistochemical analysis of 40 formalin-fixed, paraffin-embedded malignant melanomas (12 primary mucosal, 16 primary cutaneous, and 12 metastatic cutaneous) was performed to study the possible differences in immunostaining profiles according to location. The majority of melanomas were reactive with a polyclonal antibody to S100 protein (P-S100; 85%), a monoclonal melanoma-specific antibody (HMB-45; 88%), and a monoclonal antibody to vimentin (90%), and there were no differences in staining profiles for these antibodies by anatomic location. In contrast, while 13 of 16 cutaneous melanomas (81%) and ten of 12 metastatic melanomas (83%) were reactive with a monoclonal antibody to S100 protein (MoAb-079), only five of 12 mucosal tumors (42%) showed positive staining for MoAb-079. Similarly, 14 cutaneous melanomas (88%) and 11 metastatic melanomas (92%) showed positive staining for neuron specific enolase (NSE), while only four mucosal melanomas (33%) were NSE-positive. Of the 40 melanomas, all but two were reactive with either P-S100, MoAb-079, or HMB-45. These findings suggest that MoAb-079 and NSE may be less sensitive markers than P-S100 and HMB-45 for routinely processed mucosal melanomas as compared with cutaneous and metastatic tumors.

Flow cytometric DNA and nuclear antigen content in astrocytic neoplasms.

Simultaneous flow cytometric DNA content and proliferation-associated nuclear antigen (p105) quantitation was performed on 23 astrocytic tumors and the results correlated with histologic subtype. Three of nine anaplastic astrocytomas and one of ten glioblastomas had an identifiable aneuploid peak, while all four well differentiated astrocytomas were diploid. Cell cycle analysis of malignant gliomas revealed a higher mean percentage of S and G2M cells compared to well differentiated astrocytomas but there was considerable overlap between histologic subtypes. Nuclear antigen analysis of diploid tumors showed a higher mean p105 fluorescence of S + G2M cells than G0G1 cells from the same case but there were no apparent differences in p105 expression by histologic subtype. Aneuploid tumors showed enhanced expression of p105 relative to diploid cells. The findings suggest that the aggressive course of high grade glial tumors may be related to an abnormal DNA stemline or an increase in proliferative activity.

Filarial infection of the breast.

The breast is a common site of filarial infection in females in Sri Lanka. We report our experience with 13 cases of filarial breast nodules, 12 containing adult worms and the other only microfilariae. In five of these cases the species was identified as Wuchereria bancrofti.

Enterobius vermicularis in ectopic sites.

We document six cases in which tissues were invaded by Enterobius vermicularis. These cases illustrate several mechanisms whereby the worms form granulomata in ectopic sites. In three cases, the worms passed through pre-existing breaches in the intestinal mucosa. In one case, a gravid worm migrated via the female genital tract to ther peritoneal cavity. In two other cases, male worms were found on the outer surface of the intestine, suggesting active penetration of the intestinal wall.

Microfilarial granuloma of the breast in a patient with tropical pulmonary eosinophilia.

Microfilariae found in a breast nodule of a patient with tropical pulmonary eosinophilia were identified as Wuchereria bancrofti, confirming that the tropical pulmonary eosinophilia syndrome may be associated with infections caused by this species of filarial worm.

Papillary adenocarcinoma of the rete testis: a case report and review of the literature.

Adenocarcinoma of the rete testis is a rare neoplasm with 40 reported cases in the world literature to our knowledge. Although the natural history of this tumor is not well known, it appears highly malignant even in localized forms. Adenocarcinoma of the rete testis is highly resistant to adjuvant radiotherapy and any known chemotherapeutic regimen. We recommend radical orchiectomy followed by a retroperitoneal lymphadenectomy as the treatment for clinically localized Stage A tumors and minimal or microscopic Stage B disease. We report a case of adenocarcinoma of the rete testis and review the world literature.

Cerebrovascular histopathology after intracarotid infusion of Gelfoam in the rat.

To evaluate the histopathology of Gelfoam on the cerebral vasculature, 42 Sprague-Dawley rats weighing 250 to 300 g received internal carotid artery infusions of 0.3 ml of Gelfoam solution (5 mg/ml) or normal saline (0.9%). The animals were killed at 1 hour, 5 hours, 3 days, 1 week, 2 weeks, and 4 weeks after the infusion. The brains were removed, sectioned, and stained with hematoxylin and eosin. Examination of brain sections revealed Gelfoam emboli lodged primarily in the small leptomeningeal arteries. At 5 hours after infusion, inflammatory cells were noted in the arterial walls with vessel occlusion. Further canalization of vessels was noted at 1 week. At 4 weeks, Gelfoam was not seen in the specimens. This study suggests that Gelfoam acts as an embolic agent in vessels over short periods of time with no residual inflammatory activity postinfusion.

Stereotactic biopsy in the diagnosis of brain masses: comparison of results of biopsy and resected surgical specimen.

We report the pathological accuracy of image-directed stereotactic brain biopsy in 30 patients who had mass lesions of the brain and subsequently underwent resection of the mass. The histological diagnosis at stereotactic biopsy was appropriate for direction of clinical management in 28 of 30 patients. Correlation between the stereotactic and resection diagnoses was exact in 19 of 30 cases. These included 11 of 12 nonastrocytic neoplasms and 8 of 13 astrocytic neoplasms. Correlation was imperfect in 9 of 30 cases, but not to the extent of having significant clinical impact. These included 2 cases of anaplastic astrocytoma that were upgraded to glioblastoma multiforme, 2 cases of astrocytoma that had a significant oligodendroglial component, and 5 non-neoplastic lesions that were reported on biopsy as showing nonspecific reactive changes. In 2 of 30 patients, the stereotactic biopsy was not accurate. This included one patient who had glioblastoma multiforme whose stereotactic biopsy showed only necrotic tissue. Serious diagnostic error that resulted in clinical mismanagement occurred in one patient who had a pineal germinoma that had large areas of granulomatous inflammation at which the stereotactic biopsy was directed. This study provides evidence that, with careful target placement, stereotactic biopsy can provide biopsy material that represents the entire lesion with an accuracy that is sufficient for clinical management.

Multiparameter flow cytometric analysis of neoplasms of the central nervous system: correlation of nuclear antigen p105 and DNA content with clinical behavior.

Analysis of the DNA content of various solid tumors and hematological malignancies may provide useful prognostic information. To date, however, there has been a striking lack of correlation between DNA content in neoplasms of the central nervous system and clinical behavior. Simultaneous quantitation of DNA content and proliferation-associated nuclear antigen (p105) by flow cytometry was performed on paraffin-embedded tissues representing three major groups of central nervous system neoplasms--1) 21 astrocytic tumors, 2) 13 pituitary tumors, and 3) 19 meningiomas--and the results were correlated with clinical behavior. All 4 well-differentiated gliomas were diploid, while 3 of 9 anaplastic astrocytomas and 1 of 8 glioblastomas had a demonstrable aneuploid peak. Three of 13 pituitary tumors had an identifiable aneuploid peak, while only 2 of 19 meningiomas had an aneuploid DNA content. Cell-cycle analysis of the malignant gliomas revealed a significantly higher proliferative index (PI, %S + G2M) compared with the well-differentiated astrocytomas (P less than 0.05). Within the subgroup of diploid anaplastic astrocytomas, however, extended patient survival appeared to be associated with a higher PI. For diploid pituitary adenomas, the PI was consistently lower in the 3 tumors that recurred than it was in the remaining 8 adenomas. Nuclear antigen quantitation of diploid tumors showed a wide range of p105 expression in G0G1 cells, suggesting that, within each tumor, the cells are heterogeneous with respect to proliferative activity. Aneuploid nuclei of glial tumors showed enhanced expression of p105 relative to diploid cells of the same specimen. In pituitary tumors, the median G2M/G0G1 fluorescence ratio for p105 was significantly higher (P less than 0.05) for the 3 diploid recurrent tumors than for those that did not recur. These data support the assumption that the aggressive clinical course of malignant glial neoplasms may be related to an abnormal DNA stemline and/or an alteration in cell proliferative activity. Cell cycle analysis and measurement of p105 by this technique may provide information useful from both a prognostic standpoint and in directing adjuvant therapy.

Meningeal melanocytoma: diagnostic criteria for a rare lesion.

A case of meningeal melanocytoma, the 14th in the literature, is presented. Neurodiagnostic imaging, with both computed tomographic scan and magnetic resonance imaging, is included. Pathological examination of the tumor consisted of light microscopy, electron microscopy, and immunohistochemistry. The literature is reviewed and pathological criteria are presented to distinguish meningeal melanocytoma from meningiomas containing melanin pigment and from malignant melanoma.