Magnification chromoendoscopy for the detection of intestinal metaplasia and dysplasia in Barrett's oesophagus.

BACKGROUND: The presence of intestinal metaplasia (IM) in the columnar lined distal oesophagus defines Barrett's oesophagus with the risk of future malignant transformation. The distribution of both IM and dysplasia (low grade (LGD) and high grade (HGD)) within the columnar lined oesophagus is patchy and mosaic requiring random biopsies. Techniques that could help target areas of high yield within Barrett's mucosa would be helpful. AIM: To study the utility of high magnification chromoendoscopy (MCE) in the detection of IM, LGD, and HGD in patients with Barrett's oesophagus. METHODS: Consecutive patients detected with columnar mucosa in the distal oesophagus were studied using an Olympus magnification endoscope (GIF-Q16OZ, 115x). The distal oesophagus was sprayed with indigo carmine solution and the oesophageal columnar mucosa patterns were noted under high magnification and targeted for biopsy. All biopsies were read by pathologists blinded to the endoscopic findings. RESULTS: Eighty patients with suspected Barrett's oesophagus (that is, columnar lined distal oesophagus) were studied: mean age 62.7 years (range 35-81). Mean length of columnar mucosa was 3.7 cm (range 0.5-17). Three types of mucosal patterns were noted within the columnar mucosa after spraying indigo carmine and using MCE: ridged/villous pattern, circular pattern, and irregular/distorted pattern. The yield of IM on target biopsies according to the patterns was: ridged/villous 57/62 (97%) and circular 2/12 (17%). Six patients had an irregular/distorted pattern and all had HGD on biopsy (6/6 (100%)). Eighteen patients had LGD on target biopsies; all had the ridged/villous pattern. All patients with long segment Barrett's were identified using MCE whereas 23/28 patients (82%) with short segment Barrett's had the ridged/villous pattern. CONCLUSIONS: MCE helps visually identify areas with IM and HGD having specific patterns but not patients with LGD (appear similar to IM). MCE may be a useful clinical tool for the increased detection of patients with IM as well as for surveillance of patients for the detection of HGD. If these preliminary results are validated, MCE would help identify high yield areas, potentially eliminating the need for random biopsies.

Methylene blue chromoendoscopy for detection of short-segment Barrett's esophagus.

BACKGROUND: The yield of intestinal metaplasia (IM) with randomly obtained biopsy specimens in patients with short lengths of columnar-appearing mucosa in the distal esophagus is low (30%-50%). Vital staining would be beneficial if it identified more patients with short-segment Barrett's esophagus (SSBE). Our aim was to compare the confirmation of IM in patients with suspected SSBE (columnar-appearing mucosa <3 cm in length) by using methylene blue (MB)-directed versus random biopsies. METHODS: Consecutive patients undergoing EGD in whom columnar-appearing mucosa less than 3 cm in length was visualized underwent MB staining. Stained areas within suspected SSBE segments were targeted for biopsies. All biopsy specimens were stained with H & E with alcian blue at pH 2.5 and evaluated by a single pathologist. A historical control group (different from patients undergoing MB staining) consisted of patients with less than 3 cm of columnar-appearing mucosa in whom biopsy specimens were obtained randomly without MB staining. RESULTS: The MB group included 75 patients (mean age 63.8 +/- 10.9 years) with a mean length of columnar-appearing mucosa of 1.2 cm (range 0.5-2.5 cm). The control group included 83 patients (mean age 60.5 +/- 12.9 years) with a mean length of columnar-appearing mucosa of 1.16 cm (range 0.5-2.5 cm). IM (i.e., confirmed SSBE) was detected in 61% of the MB group versus 42% of the control group (p = 0.0237). Patients in the MB group required significantly fewer biopsies (4.3 +/- 1.5 vs. 5.1 +/- 12.3, p = 0.0162). Confirmation of IM by length was as follows: less than 1 cm (irregular Z line), MB 17.4% versus control 25% (p = 0.73); 1 to less than 2 cm, MB 77% versus control 45% (p = 0.03); 2 to less than 3 cm, MB 90% versus control 58% (p = 0.02). CONCLUSIONS: MB chromoendoscopy significantly increases the detection of IM and requires fewer biopsies in patients with suspected SSBE with greater than 1 cm of columnar-appearing mucosa. It does not appear to be beneficial in patients with irregular Z lines (<1 cm).

Scabies associated with radiation therapy for cutaneous T-cell lymphoma.

Scabies, infection with Sarcoptes scabiei, is known to be predisposed to by poor body hygiene, environmental exposure, and systemic immunodeficiency. We report the case of an 83-year-old man with Sezary's syndrome who developed scabies limited to the skin of the upper chest, the same location where he had previously received electron beam radiation treatments for cutaneous T-cell lymphoma. Histologic and immunohistochemical studies demonstrated that sections of the previously irradiated right and left chest skin, compared to non-irradiated chest, abdominal, and leg skin, had infestation by scabies, diminished involvement by T-cell lymphoma, and notably reduced numbers of Langerhans cells. These findings suggest that the development of scabies may be predisposed to by local cutaneous radiation therapy, and that it may be mediated by local cutaneous immunodeficiency secondary to reduced numbers of Langerhans cells.

Helicobacter pylori eradication dramatically improves inflammation in the gastric cardia.

OBJECTIVES: Inflammation of the gastric cardia, i.e., "carditis," has been associated with Helicobacter pylori (H. pylori) infection; however, some investigators believe carditis to be a histological marker for gastroesophageal reflux disease. The aim of this study was to investigate the role of H. pylori eradication on the grade of carditis scored according to the updated Sydney classification. METHODS: Consecutive patients presenting for upper endoscopy underwent systematic gastric biopsies (eight antral, 12 corpus, and four cardia). Patients with H. pylori infection and carditis were identified and followed prospectively before and after H. pylori treatment. At pretreatment and, on average, 2 yr after eradication of H. pylori, the degree of inflammation in the gastric cardia and H. pylori status were blindly assessed by a single pathologist. RESULTS: A total of 31 patients with H. pylori infection and carditis were identified. The mean age was 70 yr (range: 37-81 yr); all were male. Four were African-American and 27 were Caucasian. All patients were treated with standard anti-H. pylori therapy, including a proton pump inhibitor in combination with two antibiotics for 2 wk. Eradication of H. pylori was successful in 23 patients (group I), whereas eight patients had persistent infection (group II). Patients were followed after eradication therapy for a mean of 23.2 months (range: 6-48 months). After eradication therapy, there was a significant decrease (p < 0.0001) in the carditis scores (activity and inflammation scores) in group I, whereas the scores remained unchanged in group II patients. In both groups, there were no significant changes in the degree of intestinal metaplasia or atrophy. There were four patients with intestinal metaplasia, and one with atrophy. CONCLUSIONS: There is a dramatic improvement in the degree of inflammation and activity scores in the gastric cardia of patients with successful H. pylori eradication compared to those with persistent infection. By fulfilling one of Koch's postulates (i.e., improvement in the disease after cure of the possible etiological organism), these data support H. pylori as being the etiological agent for carditis in this group of patients.

Long-term follow-up of Barrett's high-grade dysplasia.

OBJECTIVE: The management of Barrett's high-grade dysplasia (HGD) remains controversial. The aims of this study were to evaluate prospectively the outcome of unifocal HGD (uHGD) in patients with Barrett's esophagus, and to determine demographic and endoscopic features predictive of progression to multifocal HGD (mHGD) and/or adenocarcinoma. METHODS: Consecutive Barrett's patients in whom uHGD was found at initial endoscopy or during surveillance underwent intensification of medical treatment and repeat endoscopy. The study endpoint was progression to mHGD or adenocarcinoma or HGD in conjunction with a dysplasia-associated lesion or mass (DALM). HGD diagnosis was confirmed by a second, blinded pathologist. RESULTS: A total of 15 Barrett's patients with uHGD met inclusion criteria and have been prospectively followed for a mean +/- SD of 36.8 +/- 23.2 months. All were white and male, with a mean age +/- SD of 61.4 +/- 14.9 yr. Barrett's length varied from 1 to 13 cm (mean, +/- SD, 6.8 +/- 4 cm). Overall, eight (53.3%) uHGD progressed: four of 15 (26.7%) to frank cancer between 17 and 35 months of follow-up, two of 15 (13.3%) to mHGD with DALM in conjunction with one or more foci of possible intramucosal cancer after 12-91 months of follow-up, one of 15 (6.7%) to mHGD with a focus of possible intramucosal cancer after 14 months, and one of 15 (6.7%) to mHGD after 29 months. Seven of 15 (46.7%) uHGD have regressed, five to no dysplasia and two to LGD, over the course of follow-up ranging from 24 to 73 months (mean +/- SD, 43.3 +/- 19.9). All three patients with short-segment Barrett's esophagus with uHGD regressed. Fisher's exact test revealed that Barrett's length > or =3 cm and presence of hiatal hernia approached significance (p < 0.08) in predicting uHGD progression to mHGD/DALM/cancer. However, use of the log-rank test to account for differences in length of follow-up show no significance for hiatal hernia or Barrett's length. CONCLUSIONS: Barrett's uHGD has a high risk for progressing to mHGD or cancer. Justification of an observational approach to uHGD should be discouraged. Markers of uHGD progression, as well as regression, are needed.

Prospective evaluation of the prevalence of gastric Helicobacter pylori infection in patients with GERD, Barrett's esophagus, Barrett's dysplasia, and Barrett's adenocarcinoma.

OBJECTIVE: This study was undertaken to prospectively determine the prevalence of gastric H. pylori infection in Barrett's esophagus and Barrett's complicated by dysplasia or adenocarcinoma. METHODS: The prevalence of H. pylori was determined in Barrett's esophagus patients compared to a control population of patients with gastroesophageal reflux disease (GERD) only. All patients had a minimum of 10 gastric surveillance biopsies obtained. H. pylori colonization was determined upon the basis of hematoxylin and eosin and use of a modified Giemsa and or Steiner's silver stain of all gastric biopsy specimens. RESULTS: Two hundred and eighty-nine Barrett's patients and 217 GERD control patients were included in the study. H. pylori was found in 95/289 (32.9%) of the Barrett's patients, compared with 96/217 (44.2%) of the GERD controls (NS). Forty-seven of the Barrett's patients had low-grade dysplasia/indefinite dysplasia, 14 high-grade dysplasia, and 20 Barrett's adenocarcinoma. When Barrett's was subgrouped according to absence of dysplasia, and presence of low-grade dysplasia, high-grade dysplasia, or adenocarcinoma, H. pylori prevalence was found to be significantly less for patients with Barrett's high-grade dysplasia (14.3%) and adenocarcinoma (15.0%) versus patients with GERD alone (44.2%), Barrett's alone (35.1%), or Barrett's with low-grade dysplasia (36.2%) (p = 0.016). This difference could not be explained by differences between Barrett's esophagus patients infected with H. pylori and those who were not with respect to gender, smoking history, alcohol consumption, use of proton pump inhibitor, or length of Barrett's mucosa. CONCLUSIONS: Barrett's high-grade dysplasia and adenocarcinoma are significantly more prevalent in patients who are not infected with H. pylori. H. pylori appears to have a protective effect against the development of Barrett's adenocarcinoma.

Relative risk of dysplasia for patients with intestinal metaplasia in the distal oesophagus and in the gastric cardia.

BACKGROUND: Biopsy specimens obtained from the gastro-oesophageal junction can reveal intestinal metaplasia in patients presenting for routine upper endoscopy. The site of biopsy may play a critical role in determining the dysplasia risk of a patient. AIMS: To evaluate prospectively the dysplasia risk in patients with intestinal metaplasia of the distal oesophagus or within the gastric cardia. METHODS: Patients with short segment Barrett's oesophagus (SSBO) and cardia intestinal metaplasia (CIM) were followed prospectively. RESULTS: 177 patients with SSBO were identified (mean age 62 years, range 38-82; 91% whites). Twenty prevalence cases of dysplasia in SSBO were detected: 17 low grade dysplasia (LGD), three high grade dysplasia (HGD). Seventy six patients with CIM were identified (mean age 67 years, range 37-81; 81% whites). A single prevalence case of LGD in CIM was detected. During follow up of 78 SSBO and 34 CIM patients, dysplasia developed in nine (seven LGD, two HGD) with SSBO and in one (LGD) with CIM. There were significant differences between the two groups with respect to age, ethnicity, dysplasia prevalence, and incidence. Time to dysplasia progression was significantly longer in CIM compared with SSBO patients. Of the five patients with SSBO and HGD, one developed adenocarcinoma of the oesophagus on follow up. No HGD or cancers have been detected over this time period in CIM patients. CONCLUSIONS: The dysplasia risk is significantly greater in SSBO than in CIM patients, indicating two potentially different clinical processes. Future studies should separate SSBO from CIM in order to enhance the understanding of the pathophysiology and malignant potential of each entity.

Lymphoma of the breast. A clinicopathologic study of primary and secondary cases.

BACKGROUND: Primary lymphomas of the breast are rare, accounting for 1.7% to 2.2% of extranodal lymphomas and 0.38% to 0.7% of all non-Hodgkin lymphomas. Although secondary breast lymphomas are also rare, they represent the largest group of metastatic tumors of the breast. OBJECTIVES: To investigate the clinicopathologic and immunophenotypic characteristics of breast lymphomas, the relative frequency of primary and secondary mammary lymphomas, and in selected cases, the role of gene rearrangement analysis in diagnosis and staging of these lymphomas. RESULTS: We conducted a retrospective review of 22 cases of breast lymphoma diagnosed at William Beaumont Hospital, Royal Oak, Mich, during a 30-year period (1963-1994). Eleven of the 22 cases fulfilled the criteria for primary breast lymphoma; these cases represented 0.6% of all non-Hodgkin lymphomas seen in our hospital. Of the 11 cases, 5 were diffuse large B-cell lymphomas, 2 were follicle center lymphomas, 2 were marginal zone B-cell lymphomas (mucosa-associated lymphoid tissue type), 1 was a lymphoplasmacytoid lymphoma, and 1 was a peripheral B-cell neoplasm, unclassified. Using a panel of immunohistochemical stains (CD45RO, CD45RA, CD43, CD3, CD20, CD30, CD68, and HLA-DR), 8 cases demonstrated unequivocal B-cell phenotype and 3 cases had equivocal or weak staining patterns for B-cell markers. We identified no cases of T-cell lymphoma. Of 7 cases that had bone marrow biopsies for staging, 3 were positive morphologically for bone marrow involvement. Molecular analysis of B- and T-cell gene rearrangement was used to exclude bone marrow involvement in one case with bone marrow lymphoid aggregates and to confirm negativity in a case that was morphologically negative. Of the 11 secondary breast lymphomas, 5 were diffuse large B-cell lymphomas; 1 was diffuse large B-cell, primary mediastinal subtype; and 5 were follicle center lymphomas. CONCLUSIONS: Breast lymphomas represented 1.2% of all non-Hodgkin lymphomas in this study; the frequency of primary and secondary cases was equal. In both groups, right breast lesions were predominant, and the most frequent morphologic type was diffuse large B-cell lymphoma. Gene rearrangement analysis is helpful in selected cases to rule out bone marrow involvement, especially in older patients, in whom lymphoid aggregates are common.

Prospective evaluation of intestinal metaplasia and dysplasia within the cardia of patients with Barrett's esophagus.

The prevalence of cardia versus noncardia gastric intestinal metaplasia in patients with Barrett's esophagus was assessed prospectively. Four-quadrant biopsies were obtained from the cardia from 119 consecutive patients with Barrett's esophagus and 64 control patients. Gastric surveillance biopsies were obtained in 108 of the Barrett's patients and 58 control patients. There was a significantly greater prevalence of cardia intestinal metaplasia in short-segment Barrett's (10.2%), but not traditional Barrett's (3.3%), compared to control patients (0%) (P = 0.009). Dysplastic changes were significantly more frequent in the metaplastic epithelium within the esophagus than in the cardia (P < 0.0001). A significantly greater prevalence of noncardia intestinal metaplasia compared to cardia intestinal metaplasia was found in each of the three groups of patients; however, the prevalence of noncardia intestinal metaplasia between short-segment, traditional, and control patients was not significantly different. Cardia intestinal metaplasia was an infrequent finding in patients with Barrett's esophagus and appears to develop independently from that in the remainder of the stomach.

Myeloperoxidase mRNA analysis in acute lymphoblastic leukemia.

Expression of the myeloperoxidase (MPO) gene at the mRNA level is a better lineage marker than enzymatic activity in early myeloid precursors and their leukemic counterparts. Its diagnostic use depends on the specificity of expression for myeloblasts and its absence in blasts of lymphoid lineage. The present study investigates MPO mRNA expression in adult acute lymphoblastic leukemia (ALL), using reverse transcription-polymerase chain reaction. Of a total of 13 cases, six were found to have blasts positive for MPO mRNA; in all of these cases, the blasts were cytochemically negative for MPO. This unexpected finding of MPO mRNA positivity in six of 13 cases was further investigated at the molecular level. Bcr gene rearrangement analysis was positive in all six cases for the bcr breakpoint diagnostic of chronic myelogenous leukemia (CML). Only three of these six cases were cytogenetically positive for a Philadelphia (Ph) chromosome. Based on molecular analysis, these cases are considered as CML presenting in blast crisis of lymphoid lineage, as opposed to de novo ALL. The remaining seven cases were Ph negative at the cytogenetic and molecular levels; the leukemic blasts were MPO mRNA negative, confirming the lack of MPO gene expression in de novo ALL.

Ploidy analysis of products of conception by image and flow cytometry with cytogenetic correlation.

Ploidy analysis of hydropic placentas is used in conjunction with morphology and clinical data to classify hydatidiform moles and hydropic abortuses. In most studies, ploidy has been assessed by flow cytometry (FCM). To validate image cytometry (ICM) as a method to determine ploidy in this setting, the authors used both FCM and ICM to study 19 hydropic placentas in which cytogenetic analysis was available. Nuclear suspensions from paraffin-embedded tissue were used for both ICM and FCM. Image cytometry of tissue sections was performed in some cases. Image cytometry and FCM were concordant in all 19 cases, but discordant with cytogenetics in 2 of 19 cases. Two hydropic abortuses (HA) with a diploid karyotype were triploid and tetraploid, respectively, by both ICM and FCM, which suggested that the cultured tissue was not representative. DNA indices were most accurate when an internal diploid control was used as the reference. In ICM, higher resolution was achieved by analyzing cell suspensions rather than tissue sections. This study shows that ICM is a valid method of determining ploidy of hydropic placentas and partial hydatidiform moles in archival tissue.

Listeriosis of the placenta: clinicopathologic study of seven cases.

OBJECTIVE: The purpose of our study was to evaluate the usefulness of placental examination in the diagnosis of prenatal listeriosis. STUDY DESIGN: Over a 7-year period, 4597 placentas with clinical indications for examination were retrospectively studied for morphologic evidence of listeriosis. The microbiology laboratory file records of positive Listeria monocytogenes cultures were used to confirm the diagnosis. The clinical records were studied for manifestations of the infection both in the neonates and in the mothers. RESULTS: Seven placentas were identified as having listeriosis. The presence of macroabscesses, as opposed to microabscesses, was the most characteristic finding in this study, and the silver impregnation method was more reliable in identification of the bacilli in the tissue sections than the tissue Gram stains. CONCLUSIONS: Listeriosis could be diagnosed by placental examination alone, and this examination frequently strengthened the clinical diagnosis. When the infection was not suspected clinically, the examination helped us reach the correct diagnosis.