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.

Cdx-2 expression in squamous and metaplastic columnar epithelia of the esophagus.

The molecular pathogenesis of Barrett's esophagus is poorly understood. Evidence suggests that at a phenotypic level, the metaplastic process begins with the transformation of squamous epithelium in the distal esophagus to cardiac mucosa, which subsequently becomes intestinalized. The homeobox gene Cdx-2 has been shown to be an important transcriptional regulator of embryonic differentiation and maintenance of adult intestinal type epithelium. We hypothesized that Cdx-2 gene expression levels increase with the phenotypic transformation of normal squamous mucosa to the intestinalized columnar mucosa of Barrett's esophagus. Endoscopic biopsies were obtained at the gastroesophageal junction in patients with symptoms of gastroesophageal reflux disease and classified according to histology: normal squamous mucosa (n = 62), cardiac mucosa (n = 19), oxynto-cardiac mucosa (n = 14), and intestinal metaplasia (n = 15). Duodenal biopsies (n = 26) served as the columnar control. After laser capture microdissection and RNA isolation, gene expression levels of Cdx-2 were measured in each tissue type by quantitative reverse transcription polymerase chain reaction. Consistent with its known function, Cdx-2 gene expression levels were highest in duodenal mucosa and nearly absent in squamous epithelium. There was a stepwise increase in Cdx-2 gene expression from cardiac to Barrett's epithelium (P < 0.001). Expression levels of Cdx-2 in cardiac and oxynto-cardiac mucosa were 40-70 times higher and Barrett's mucosa 400 times higher than that found in squamous epithelium. Relative expression of the homeobox gene Cdx-2, known to induce differentiation of intestinal type epithelium, increases in a stepwise fashion during the phenotypic transformation of distal esophageal squamous mucosa to cardiac columnar mucosa and to the intestinalized columnar mucosa of Barrett's esophagus. Therefore, Cdx-2 may be a potential biomarker to detect the early transition to Barrett's esophagus.

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.

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.

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.

Cytologic features of secretory meningioma.

OBJECTIVE: To describe the cytologic features of secretory meningioma on crush preparations. STUDY DESIGN: In five cases, the diagnosis of secretory meningioma was made and crush preparations were available. In each case, crush preparations were made at the time of intraoperative consultation from an open biopsy specimen or stereotactic biopsy. RESULTS: Hematoxylin and eosin-stained crushes showed the presence of clusters of cohesive cells containing variable numbers of inclusions among less cohesive typical meningothelial cells. In two cases, the inclusions were especially prominent. Inclusions varied in size from 3 to 40 microns, had a well-defined rim and contained finely granular or hyaline material and a central core. CONCLUSION: Secretory meningiomas demonstrate distinct cytologic features on crush preparations. Recognition of these inclusions is important since their prominence in some stereotactic smear preparations may lead to diagnostic problems.

Role of stereotactic biopsy in the diagnosis and management of brain tumors.

Stereotactic biopsy has evolved as a powerful and safe tool to provide tissue diagnoses with minimal disruption of normal functioning brain. It plays a significant role in the management of malignant brain tumors, where the benefit of open surgery might not justify the concomitant risks. Stereotactic procedures are closed procedures, and thus direct feedback is not provided to the surgeon during manipulation of brain tissue. This difference from most other neurosurgical procedures necessitates rigor in the preoperative workup, the planning of the procedure, and the conduct of the procedure. The success of the procedure is measured by the ability of the team to make an accurate histopathological diagnosis of the lesion; in experienced hands, the rate of success should exceed 95%. Complications and mortality can be minimized with appropriate attention to detail.

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.

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.

Paragonimiasis in a cystic breast mass: case report and implications for examination of aspirated cyst fluids.

We report a case of paragonimiasis diagnosed by fine-needle aspiration of a breast mass in a middle-aged Korean female with a history of breast silicone injections. Although parasitoses have been discovered by aspiration of cyst fluid in otherwise sterile sites (i.e., liver and lung), the cystic presentation in the breast of a middle-aged female complicated the diagnosis in this case. Some authors have argued against the routine cytologic examination of nonbloody cyst fluids in premenopausal women, but this protocol may lead to a false negative diagnosis in the rare instance of a parasitic cyst. While microscopic examination of breast cyst fluid is probably not warranted in every patient, it may be useful in patients at risk for unusual cystic lesions, especially if clinical and mammographic signs of fibrocystic change are absent.

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.

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.

Cytomorphology of subependymal giant cell astrocytoma. A case report.

Cytologic smears made from minute fragments of tissue removed during neurosurgical procedures are a useful alternative to frozen sections for rapid diagnosis. We describe the cytomorphologic features of a rare brain neoplasm, subependymal giant cell astrocytoma (SEGA). On cytologic grounds this neoplasm is difficult to separate from gemistocytic astrocytoma. The clinical presentations of the two neoplasms, however, are quite distinct, with SEGA an intraventricular neoplasm mostly seen in young adults with tuberous sclerosis, whereas gemistocytic astrocytoma occurs in the cerebral hemisphere of older adults.

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.

Abdominal angiostrongyliasis mimicking acute appendicitis and Meckel's diverticulum: report of a case in the United States and review.

Two cases of children with abdominal angiostrongyliasis acquired within the United States are reported. The index patient presented with complaints consistent with appendicitis, but at surgery findings were thought to represent an atypical presentation of a Meckel's diverticulum. His sole sibling (sister) had eosinophilia, no other intestinal parasites on fecal examination, and a positive serologic test, all suggesting infection with Angiostrongylus costaricensis. Because infections with this parasite are not known to result from human-to-human transmission, his sister's infection represents a second case.

Diagnosis of pulmonary blastoma by fine-needle aspiration biopsy: cytologic and immunocytochemical findings.

A preoperative diagnosis of pulmonary blastoma was established by fine-needle aspiration (FNA) cytology in a patient who presented with a pulmonary mass discovered incidentally on chest x-ray. At the time of computed tomography-guided FNA, an on-site preliminary diagnosis of poorly differentiated carcinoma was made after examination of a rapid hematoxylineosin (H&E)-stained smear. Malignant epithelial and stromal elements could be demonstrated on smears subsequently stained with the H&E, Papanicolaou, and Diff-Quik methods. The cell block preparation showed a distinctly biphasic malignant tumor with classic morphologic features of pulmonary blastoma. We present the clinical, cytologic, immunocytochemical, and histologic findings of this case and re-emphasize the valuable contribution of adequate cell block preparations to accurate diagnosis of fine-needle aspiration material.

Lhermitte-Duclos disease: CT and MR findings.

The typical CT findings of Lhermitte-Duclos disease (dysplastic gangliocytoma of the cerebellum) are a hypodense nonenhancing unilateral posterior fossa mass, with or without adjacent occipital thinning, hydrocephalus, and calcification. Magnetic resonance (MR) has been found to be very helpful, and superior to CT, in delineating the margins of the lesion for determining the extent of surgical resection. Since recurrence is known, MR is important in the follow-up of these patients. To our knowledge this is the first reported case that included MR examination with administration of gadolinium. There was no enhancement of the lesion, consistent with previous reports of no contrast enhancement on CT.