Observer variation in the diagnosis of superficial oesophageal adenocarcinoma.

BACKGROUND AND AIMS: When to perform oesophagectomy for neoplastic progression in Barrett's oesophagus is controversial. Some resect for high grade dysplasia whereas others defer treatment until intramucosal adenocarcinoma is diagnosed. Interobserver agreement for a diagnosis of high grade dysplasia or intramucosal adenocarcinoma remains unknown and may have therapeutic implications. METHODS: Histological slides from 75 oesophagectomy specimens with high grade dysplasia or T(1) adenocarcinoma were blindly reviewed by two gastrointestinal pathologists and one general surgical pathologist, and classified as high grade dysplasia, intramucosal adenocarcinoma, or submucosal adenocarcinoma. A subsequent re-review of all 75 cases by the same observers following establishment of uniform histological criteria was undertaken. Interobserver agreement was determined by kappa statistics. Coefficients <0.21, 0.21-0.40, 0.41-0.60, 0.61-0.80, and >0.80 were considered poor, fair, moderate, good, and very good agreement, respectively. RESULTS: Interobserver agreement among all pathologists and between gastrointestinal pathologists when comparing high grade dysplasia with intramucosal adenocarcinoma was only fair (k=0.42; 0.56, respectively) and did not substantially improve on subsequent re-evaluation following establishment of uniform histological criteria (K=0.50; 0.61, respectively). CONCLUSIONS: When evaluating resection specimens and after implementation of uniform histological criteria, even experienced gastrointestinal pathologists frequently disagree on a diagnosis of high grade dysplasia versus intramucosal adenocarcinoma. Treatment strategies based on the histological distinction of high grade dysplasia from intramucosal adenocarcinoma using limited biopsy specimens should be re-evaluated.

Angiogenic polypoid proliferation adjacent to ileal carcinoid tumors: a nonspecific finding related to mucosal prolapse.

Case reports have highlighted angiogenic polypoid proliferation in the mucosa adjacent to ileal carcinoid tumors, describing them as granulation tissue polyposis and florid angiogenesis. Some authors have proposed that the ileal carcinoid tumors themselves produce growth factors that cause the change. The purpose of this study was to determine the frequency of angiogenic polypoid proliferation in a large cohort of resected ileal carcinoid tumors compared with control groups. Search of the Cleveland Clinic and Summa Health System pathology files (1985 to 1999) yielded 65 resected ileal carcinoid tumors. Mucosal abnormalities adjacent to the ileal carcinoid tumors were graded 0 to 4+. Twenty ileal resection margins from colonic carcinoma cases served as normal controls. Ileal mucosa adjacent to 22 noncarcinoid neoplasms were also examined. The mucosa adjacent to 54/65 ileal carcinoid tumors (83%) showed mucosal abnormalities (vs. 3/20 normal controls), including mucosal edema, capillary ectasia, muscularis mucosae hypertrophy, fibrosis/smooth muscle proliferation within the lamina propria, club-shaped villi, and intramucosal capillary proliferation. Forty ileal carcinoid tumor cases (61%) showed some degree of angiogenic polypoid proliferation characterized by club-shaped villi and prominent intramucosal capillaries, with 17 (26%) graded as 3+ or 4+. Angiogenic polypoid proliferation was associated with hypertrophy of the muscularis mucosae, lamina proprial fibrosis/smooth muscle proliferation, and capillary ectasia similar to that described with gastrointestinal mucosal trauma/prolapse. This trauma/prolapse change was identified in 45 cases (69%) and was graded 3+ or 4+ in 23 (35%). Seventeen (77%) of the noncarcinoid neoplasms showed trauma/prolapse changes, with 7 (32%) graded as 3+ or 4+. Angiogenic polypoid proliferation also correlated with trauma/prolapse change in the noncarcinoid neoplasm controls. Neither APP (P =.24) nor the prolapse changes (P =.33) were found to be statistically different between the two tumor groups. Angiogenic polypoid proliferation of the adjacent ileal mucosa is common in patients with ileal carcinoid tumors and with noncarcinoid neoplasms. Angiogenic polypoid proliferation almost invariably coexists with fibromuscular change and capillary ectasia within the lamina propria, suggesting that mucosal trauma/prolapse plays a role in the histogenesis. The association of angiogenic polypoid proliferation with a variety of different neoplasms makes it unlikely that the tumors themselves secrete growth factors.

Endoscopic and histologic evaluation together with symptom assessment are required to diagnose pouchitis.

BACKGROUND & AIMS: Pouchitis often is diagnosed based on symptoms alone. In this study, we evaluate whether symptoms correlate with endoscopic and histologic findings in patients with ulcerative colitis and an ileal pouch-anal anastomosis. METHODS: Symptoms, endoscopy, and histology were assessed in 46 patients using Pouchitis Disease Activity Index (PDAI). Patients were classified as either having pouchitis (PDAI score > or =7; N = 22) or as not having pouchitis (PDAI score <7; N = 24). RESULTS: Patients with pouchitis had significantly higher mean total PDAI scores, symptom scores, endoscopy scores, and histology scores. There was a similar magnitude of contribution of each component score to the total PDAI for the pouchitis group. Of note, 25% of patients with symptoms suggestive of pouchitis did not meet the PDAI diagnostic criteria for pouchitis. In both groups, the correlation coefficients between symptom, endoscopy, and histology scores were near zero (range, -0.26 to 0.20; P > 0.05). CONCLUSIONS: The symptom, endoscopy, and histology scores each contribute to the PDAI and appear to be independent of each other. Symptoms alone do not reliably diagnose pouchitis.

Methylene blue staining of dysplastic and nondysplastic Barrett's esophagus: an in vivo and ex vivo study.

BACKGROUND AND STUDY AIMS: Methylene blue selectively stains specialized columnar epithelium in Barrett's esophagus with high accuracy. We prospectively evaluated the methylene blue staining properties of dysplastic and nondysplastic Barrett's esophagus and the association of these properties with the risk for dysplasia and cancer. PATIENTS AND METHODS: In a ex vivo study, we mapped, photographed, and sampled esophagectomy specimens with high grade dysplasia and/or early adenocarcinoma before and after methylene blue staining. In a concurrent in vivo study, we performed methylene blue staining and characterized methylene blue stain characteristics. Pathologists estimated the proportion of specialized columnar epithelium in each specimen and graded dysplasia. RESULTS: We examined 551 biopsies from 47 patients with biopsy-proven Barrett's esophagus and 48 sections from five surgical specimens with Barrett's esophagus and dysplasia and early adenocarcinoma. The accuracy of ex vivo and in vivo methylene blue staining for specialized columnar epithelium was 87% and 90%, respectively. It was influenced by the length of Barrett's esophagus, biopsy location, and the presence of esophagitis and/or dysplasia. Light to absent staining (p = 0.01) and moderate to marked heterogeneity (p = 0.01) were significantly associated with high grade dysplasia or cancer in the univariate analysis and in a multivariate model that adjusted for the length of Barrett's esophagus and the presence of a lesion. These staining characteristics were present in all patients with severe dysplasia and/or adenocarcinoma. CONCLUSIONS: Highly dysplastic or malignant Barrett's esophagus stains differently with methylene blue. Increased heterogeneity and decreased methylene blue stain intensity are significant independent predictors of high grade dysplasia and/or cancer. These features may help to direct biopsies in patients without a lesion.

Association of susceptibility locus for inflammatory bowel disease on chromosome 16 with both ulcerative colitis and Crohn's disease.

A susceptibility locus for inflammatory bowel disease (IBD) on chromosome 16 (IBD1) has been linked to Crohn's disease in genome-wide linkage studies. We performed a case-control study with two markers for this locus using leukocyte DNA from 127 Crohn's patients, 83 ulcerative colitis patients, and 74 control patients. Allele, genotype, and haplotype frequencies of the polymerase chain reaction products were determined using autoradiography. Haplotype frequencies differed for ulcerative colitis and Crohn's disease, particularly for haplotype CC (22% ulcerative colitis vs 10% Crohn's disease, P = 0.002 Chi2 = 10.0) and haplotype CD (18% Crohn's disease vs 9% ulcerative colitis, P = 0.025 Chi2 = 5.02). These data demonstrate the association of the IBD1 locus with both ulcerative colitis and Crohn's disease in a group of unrelated IBD patients. The use of such microsatellite markers when combined with others, might help distinguish ulcerative colitis from Crohn's disease in patients with ambiguous clinical and histological features.

The importance of diagnostic accuracy in colonic inflammatory bowel disease.

OBJECTIVE: Crohn's disease (CD) and ulcerative colitis (UC) may both affect the colon. However, in approximately 10-20% of these cases, it is impossible to distinguish between these two entities either clinically or histologically, and a diagnosis of indeterminate colitis (IC) is made. Correct diagnosis is important because surgical treatment and long-term prognosis differ for UC and CD. The purpose of this study was to determine the extent of interobserver agreement among board-certified pathologists and a specialist gastrointestinal (GI) pathologist regarding the histological diagnosis of colonic inflammatory bowel disease (IBD). METHODS: A total of 24 university medical center pathologists from eight institutions evaluated 84 colectomy specimens and 35 sets of biopsy specimens from 119 consecutive patients with colonic IBD. A specialist GI pathologist subsequently reviewed all cases without knowledge of clinical data and prior diagnosis. RESULTS: The GI pathologist's diagnoses differed from the initial diagnoses in 45% of surgical specimens and 54% of biopsy specimens. Of 70 cases initially diagnosed as UC, 30 (43%) were changed to CD or IC, whereas 4 of 23 cases (17%) initially diagnosed as CD were changed to UC or IC. The kappa coefficient for the overall agreement of initial diagnoses with the specialist GI pathologist's diagnoses was -0.01 (p = 0.98). CONCLUSIONS: There is significant interobserver variation in the histological diagnosis of colonic IBD. This may have a profound effect on clinical patient care and, especially, on the choice of operation. More accurate diagnostic criteria are needed to facilitate patient care and to optimize treatment outcome.

Immunohistochemistry in the differential diagnosis of acinar and endocrine pancreatic neoplasms.

Histologic differential diagnosis of acinar cell carcinoma (ACC), mixed acinar-endocrine cell carcinoma (MAEC), and pancreatic endocrine tumors (PET) can be difficult but is important because of differences in their clinical behavior. This study investigates the utility of immunohistochemistry (IHC) in this differential diagnosis using immunohistochemical stains that are available in most laboratories. IHC was performed on paraffin-embedded tissue in ACC (n = 6), MAEC (n = 2), and PET (n = 13), using synaptophysin (SYN), chromogranin (CHR), chymotrypsin (CHY), and alpha-1-antitrypsin (AAT). Electron microscopy (EM) was performed in all cases to confirm the diagnosis. Long-term follow-up and death of disease (DOD) was known in all patients. The ACCs stained as follows: CHY (4/6), AAT (3/6), SYN (4/6); CHR was negative in all cases. Both cases of MAEC stained with CHY, AAT, and SYN (2/2); CHR was negative. PET stained as follows: SYN (13/13), CHR (8/13), CHY (4/13), AAT (5/13). In the ACC/ MAEC group, six of eight patients were DOD at mean follow-up of 11 months. Among the PET, two of 16 patients were DOD at mean follow-up of 37 months. Considerable immunophenotypic overlap exists between ACC, MAEC, and PET. Consequently, one can neither confirm nor rule out a diagnosis of ACC or MAEC using generally available immunohistochemical stains alone. These findings support a role for EM in the evaluation of exocrine and endocrine pancreatic neoplasms.

Short- and long-term follow-up of treatment for lymphocytic and collagenous colitis.

Collagenous colitis and lymphocytic colitis cause chronic watery diarrhea. Multiple therapies have been found to improve symptoms but there have been few long-term follow-up studies. Our goal was to obtain long-term clinical follow-up on a cohort of patients with independently confirmed typical histopathologic changes. Pathology slides from 32 cases of collagenous or lymphocytic colitis patients from 1988-1992 were independently reviewed. Twenty-five cases were confirmed by both groups of pathologist as collagenous or lymphocytic colitis. For these 25 patients, charts were reviewed and telephone follow-up interviews were performed in 1992 and 1995. Seven of 32 (22%) of the original cases were not confirmed on independent pathologic interpretation. A 15.8% discordance rate was found between the different groups of pathologists. Patient demographics were similar to previously published reports except one-half of our patients had diarrhea of only 6 months or less. Eighty-one percent of patients receiving 5-ASA agents reported improvement as well as 100% of those receiving prednisone. At 23 month follow-up 86% of patients reported improvement in diarrhea and only 32% required routine medications. At 47 month follow-up all patients reported improved diarrhea and only 29% required routine medications. Collagenous and lymphocytic colitis can sometimes be identified in patients with relatively brief duration diarrhea. Clinical parameters and response to therapy are similar for collagenous or lymphocytic colitis. Most patients with lymphocytic and collagenous colitis improve with therapy such as 5-ASA preparations or steroids. Over a follow-up period of several years, most patients have improvement in diarrhea and generally do not require maintenance medications. Independent pathologic confirmation of the diagnosis should be obtained in patients not responding to therapy.

The diagnosis of low-grade dysplasia in Barrett's esophagus and its implications for disease progression.

OBJECTIVE: The reported risk of progression from low-grade dysplasia (LGD) to high-grade dysplasia (HGD) or carcinoma (CA) in Barrett's esophagus varies. However, the validity of a diagnosis of LGD may be questioned because of interobserver variability. METHODS: A search of the Cleveland Clinic Foundation surgical pathology files between 1986 and 1997 yielded biopsy specimens from 43 patients with Barrett's esophagus diagnosed and coded as LGD. Patients with concurrent or prior diagnoses of HGD or carcinoma were excluded. The LGD cases were randomized and blindly reviewed by three gastrointestinal (GI) pathologists along with cases originally diagnosed as Barrett's esophagus without dysplasia (ND; n = 28), indefinite for dysplasia (IND; n = 14), or HGD (n = 15). Each pathologist classified every biopsy specimen as ND, IND, LGD, or HGD, and interobserver agreements were determined by kappa statistics (K). Follow-up data were available on 25 patients originally diagnosed with LGD. Progression was defined as a subsequent diagnosis of HGD or CA on esophageal biopsy or resection specimens. RESULTS: Agreement between two GI pathologists for a diagnosis of LGD was fair (K = 0.28) and poor (K = 0.21 and -0.04). Individual GI pathologists agreed with the original diagnosis of LGD in 70%, 56%, and 16% of cases. The 25 patients with follow-up included 21 men and four women (mean age, 67 yr) with a mean follow-up of 26 months (range: 2-84 months). Seven patients (28%) with follow-up developed HGD (five patients) or CA (two patients), 2-43 months (median: 11 months) after a diagnosis of LGD. The individual GI pathologists' diagnosis did not correlate with progression. However, when at least two GI pathologists agreed on LGD, there was a significant association with progression (seven of 17 patients, 41%, p = 0.04). When all three GI pathologists agreed on a diagnosis of LGD, four of five patients progressed (p = 0.012). In contrast, of the eight patients with follow-up and no agreement among GI pathologists for a diagnosis of LGD, none progressed. CONCLUSIONS: A high degree of interobserver variability is seen in the histological diagnosis of Barrett's esophagus-related LGD. Although the number of observations is low, a consensus diagnosis of LGD among GI pathologists suggests an increased risk of progression from LGD to HGD or carcinoma.

Incidence and natural history of dysplasia of the anal transitional zone after ileal pouch-anal anastomosis: results of a five-year to ten-year follow-up.

PURPOSE: Preservation of the anal transitional zone during ileal pouch-anal anastomosis is still controversial because of the risk of dysplasia and the theoretical risk of associated cancer. Without long-term follow-up data, the natural history and optimal treatment of anal transitional zone dysplasia are unknown. The aim of this study was to determine the long-term risk of dysplasia in the anal transitional zone and to evaluate the outcome of a conservative management policy for anal transitional zone dysplasia. METHODS: Two hundred ten patients undergoing anal transitional zone-sparing ileal pouch-anal anastomosis for ulcerative or indeterminate colitis between 1987 and 1992 and who were studied with serial anal transitional zone biopsies for at least five years postoperatively were included. Median follow up was 77 (range, 60-124) months. RESULTS: Anal transitional zone dysplasia developed in seven patients 4 to 51 (median, 11) months postoperatively. There was no association with gender, age, preoperative disease duration or extent of colitis, but the risk of anal transitional zone dysplasia was significantly increased in patients with prior cancer or dysplasia in the colon or rectum. Dysplasia was high grade in one and low grade in six. Two patients each with low-grade dysplasia detected on three separate occasions underwent mucosectomy 29 and 38 months after detection of low-grade dysplasia, but no cancer was found. The five other patients with dysplasia on one or two occasions were treated expectantly and were apparently dysplasia-free for a median of 72 (range, 48-100) months. CONCLUSIONS: Anal transitional zone dysplasia after ileal pouch-anal anastomosis is infrequent, is most common in the first two to three years postoperatively and may apparently disappear on repeated biopsy. Anal transitional zone preservation did not lead to the development of cancer in the anal transitional zone after five to ten years of follow-up. Long-term surveillance is recommended to monitor dysplasia. If repeat biopsy confirms persistent dysplasia, anal transitional zone excision with neoileal pouch-anal anastomosis is recommended.

Colonic epithelial lymphocytosis without a thickened subepithelial collagen table: a clinicopathologic study of 40 cases supporting a heterogeneous entity.

Lymphocytic colitis (LC) is classically described as a triad of chronic nonbloody, watery diarrhea, normal or nearly normal endoscopy findings, and colonic epithelial lymphocytosis without a thickened subepithelial collagen table (SECT). It is unknown how often patients with colonic epithelial lymphocytosis without a thickened SECT actually present with this classic triad. Cases diagnosed histologically as lymphocytic or microscopic colitis were reviewed. Criteria for inclusion were the presence of at least 15 surface lymphocytes per 100 epithelial cells and the absence of a thickened SECT (<12 microm). Clinical features and course were recorded by chart review and telephone follow-up. Forty patients met the inclusion criteria, including 25 women and 15 men with a mean age of 63.2 years (range, 25-83 years). Twenty-eight patients had the classic triad and were designated as having classic LC. The other 12 patients fulfilled the histologic criteria but not the clinical or endoscopic criteria for classic LC and were classified as having atypical LC (constipation, five patients; macroscopic colitis at endoscopy, five patients; hematochezia, one patient; and incidental finding, one patient). Clinically, patients with classic LC were predominantly women and had a higher incidence of autoimmune disease (p = 0.03) than did those with atypical LC. Histologically, surface eosinophilia was significantly greater in patients with classic LC (p = 0.04). Twenty patients were using nonsteroidal antiinflammatory drugs at the time of their colonic biopsy. Surface epithelial lymphocyte counts were higher in these patients, particularly in the distal sigmoid colon (p = 0.02). Fourteen patients had associated autoimmune disease, including three patients with sprue diagnosed by small bowel biopsy, all of whom responded to gluten withdrawal. Diarrhea present in 25 patients, without documented evidence of celiac sprue, was self-limited in five, resolved with treatment in three, required intermittent treatment in eight, daily treatment in five, and was refractory to treatment in four. All eight patients who experienced spontaneous or treatment-related symptom resolution had classic LC. No histologic feature correlated with clinical course. In conclusion, our study shows that colonic epithelial lymphocytosis without a thickened SECT is a histologic finding seen in a heterogeneous group of patients. Within this heterogeneous group is a distinct subset of patients who have the classic clinicopathologic triad of LC. This subset of patients has striking similarities to patients with collagenous colitis, lending further support to a close relationship between these two entities. Atypical LC comprises a heterogeneous group and includes patients with idiopathic constipation, coexisting LC and inflammatory bowel disease, and possibly infectious colitides. Because of the clinical heterogeneity among our study population, the descriptive term colonic epithelial lymphocytosis may be a more prudent diagnosis than lymphocytic colitis in the absence of adequate clinical information.

Intestinal adenocarcinoma in Crohn's disease: a report of 30 cases with a focus on coexisting dysplasia.

There are relatively few reports that detail the types of intestinal adenocarcinoma complicating Crohn's disease and examine associated epithelial dysplasia. We determined the prevalence, grade, and type of dysplasia found adjacent to and distant from Crohn's-related adenocarcinomas. Thirty cases of resected Crohn's-related adenocarcinoma were reviewed, and histologic type, degree of differentiation, TNM stage, and the presence or absence, grade, and location of dysplasia were recorded. Most of the patients were male (70%). The median ages at diagnosis of Crohn's disease and adenocarcinoma were 34 and 49 years, respectively. The extent of Crohn's disease included ileocolitis in 21 patients, only colonic disease in six, and only small bowel disease in three. In most cases (67%), carcinoma was found incidentally at surgery. All carcinomas arose in areas involved by Crohn's disease. Eight (27%) adenocarcinomas arose in the small bowel, and 22 (73%) arose in the colon, including two in out-of-circuit rectums. Most carcinomas (63%) were poorly differentiated. Dysplasia was found adjacent to the carcinoma in 26 (87%) cases. Of the colorectal carcinomas, 19 (86%) had adjacent dysplasia, and nine (41%) had distant dysplasia. In conclusion, most cases of Crohn's-related intestinal adenocarcinoma have dysplasia in adjacent mucosa, and 41% of those arising in the colorectum have distant dysplasia, supporting a dysplasia-carcinoma sequence in Crohn's disease.

Acquired increase in leucocyte binding by intestinal microvascular endothelium in inflammatory bowel disease.

BACKGROUND: Endothelial cells that line microvascular blood vessels have an important role in inflammation through their ability to bind and recruit circulating leucocytes. Endothelial cells from the intestines of patients with chronically inflamed Crohn's disease and ulcerative colitis--the two forms of inflammatory bowel disease--display an increased leucocyte-binding capacity in vitro. We investigated whether this enhanced leucocyte binding is a primary or an acquired defect. METHODS: We cultured human intestinal microvascular endothelial cells (HIMEC) from the uninvolved intestine and chronically inflamed bowel of three patients with inflammatory bowel disease (two Crohn's disease, one ulcerative colitis). We assessed HIMEC binding to polymorphonuclear leucocytes and U937 cells by means of an adhesion assay. FINDINGS: After activation with interleukin-1beta or lipopolysaccharide, HIMEC from the chronically inflamed tissue in all three patients with inflammatory bowel disease bound twice as many polymorphonuclear leucocytes and U937 cells as endothelial cells from uninvolved tissue. INTERPRETATION: Enhanced leucocyte binding by HIMEC from chronically inflamed tissue in patients with inflammatory bowel disease is an acquired defect since it is not found in the uninvolved intestinal segments from the same individuals. Because interaction between endothelial cells and leucocytes is a key regulatory step in the inflammatory process, this enhanced binding may contribute to the pathophysiology of chronic intestinal inflammation.

Solitary pulmonary papillomas in adults: a clinicopathologic and in situ hybridization study of 14 cases combined with 27 cases in the literature.

Solitary endobronchial papillomas in adults are rare neoplasms. Only sporadic cases have been documented. The histologic classification of these tumors remains problematic, and little is known about their clinical behavior. The clinical and pathologic features of 13 endobronchial papillomas and a single endobronchiolar papilloma were reviewed. In situ hybridization for human papillomavirus (HPV) types 6/11, 16/18, and 31/33/51 was performed on seven cases. Twenty-seven additional well-documented cases were identified in a literature review. Human papillomavirus studies were performed in four of the previously reported cases. The 41 neoplasms combined from the Armed Forces Institute of Pathology and literature review were divided into three groups according to their histologic features. Thirty-one of 41 (76%) patients were men. The ages of the patients ranged from 26 to 74 years (median, 57 years). Three morphologically distinct histologic types were recognized; 27 squamous cell papillomas, 7 glandular papillomas, and 7 mixed squamous and glandular papillomas. Squamous papillomas: 23 of 27 (85%) patients were men, and the median age was 54 years. Six of eleven (55%) of these patients smoked. Twenty-six lesions were exophytic and a single lesion had an inverted pattern. Seven of 24 (29%) lesions featured cytologic atypia and 5 of 24 (14%) had viral cytopathic effect. Five of seven (71%) cases examined for HPV DNA were positive. Three of 18 (17%) recurred. Glandular papillomas: Four of seven (57%) patients were women. The mean age was 67 years. One of five (20%) patients smoked. Five lesions were central, and two were peripheral. Four lesions had columnar epithelium, and three had ciliated epithelium. One of six (17%) lesions recurred. Mixed papillomas: five of seven (71%) patients were men. The median age was 64 years. Three of five (60%) patients smoked. Three of seven (43%) lesions featured cytologic atypia. Four of five lesions were examined for HPV DNA and all were negative. No lesions recurred. This study demonstrates that solitary endobronchial papillomas can be separated into three distinct morphologic categories. Squamous cell and mixed papillomas are predominantly lesions of male smokers in their 6th decade. Although cytologic atypia is observed in many cases, the rarity of these tumors and difficulty in separating papillomas from endobronchial papillary squamous carcinomas make generalizations regarding the risk of progression to carcinoma tenuous at best. Human papillomavirus appears to play a pathogenetic role in some squamous cell papillomas, but not in mixed papillomas, yet its presence in the squamous lesions does not correlate with recurrence or malignancy. The first report of an inverted squamous cell papilloma indicates clinical features similar to the more common exophytic squamous cell papillomas. Glandular papillomas, the rarest of all endobronchial papillomas, are found in an older age group than squamous and mixed papillomas, and most-patients are nonsmokers. Based on these findings, all endobronchial papillomas should be completely excised.

Sarcoidosis presenting as granulomatous colitis.

Sarcoidosis presenting solely as a granulomatous colitis is rare and appears identical to Crohn's disease. A 56-yr-old woman developed a Crohn's-like illness, which remitted after 5-ASA therapy. Two months later, she developed fever, adenopathy, muscle weakness, and peripheral neuropathy. A diagnosis of sarcoidosis was made after an extensive search for an infectious or rheumatological cause. This case illustrates the utility of serum angiotensin converting enzyme level in differentiating sarcoidosis from Crohn's disease.

Surveillance of patients with Barrett's esophagus for dysplasia and cancer with balloon cytology.

BACKGROUND & AIMS: A less costly cancer surveillance method for Barrett's esophagus is desirable. The aim of this study was to compare nonendoscopic balloon cytology with biopsy and brush cytology for detecting dysplasia and carcinoma in patients with Barrett's esophagus. METHODS: Patients in a surveillance program underwent balloon cytology before endoscopy with biopsy and brush cytology. Results of cytology were compared with those of histology. RESULTS: Adequate columnar epithelium was obtained in 52 of 63 (83%) patients with balloon cytology and 59 of 61 (97%) with brush cytology. Balloon cytology obtained abnormal cells in 6 of 8 patients with adenocarcinoma, 2 of 2 patients with high-grade dysplasia, and 2 of 8 patients with low-grade dysplasia. Sensitivity of balloon cytology for high-grade dysplasia or carcinoma was 80% but only 25% for low-grade dysplasia. No patients without dysplasia or carcinoma had abnormal cells. Brush cytology was abnormal in all 11 patients with high-grade dysplasia or carcinoma but only 2 of 9 patients with low-grade dysplasia (sensitivity, 22%). Two of 39 patients without dysplasia had abnormal cells (specificity, 95%). Balloon cytology cost was sixfold less than endoscopy with biopsy. CONCLUSIONS: Balloon cytology detected 80% of patients with high-grade dysplasia or carcinoma when sampling was adequate. Brush cytology data suggest that a more abrasive balloon may improve balloon cytology sensitivity. The potential cost savings of balloon cytology compared with endoscopic cancer surveillance in Barrett's esophagus support further studies of this technique.

Colonic epithelial lymphocytosis associated with an epidemic of chronic diarrhea.

The term Brainerd diarrhea has been applied to outbreaks of chronic watery diarrhea of unknown etiology characterized by acute onset and prolonged duration. Our aim was to describe the histologic changes in gastrointestinal biopsy specimens from patients with Brainerd diarrhea. We examined 52 colonic and 12 small bowel biopsy specimens from 22 patients who were involved in an outbreak of Brainerd diarrhea that was linked to the water supply of a cruise ship visiting the Galapagos Islands. Small bowel biopsy specimens from seven patients were histologically normal. One patient had a duodenal biopsy specimen that resembled celiac sprue. Colonic biopsy specimens from 20 patients revealed surface epithelial lymphocytosis without distortion of mucosal architecture, surface degenerative changes, or thickened subepithelial collagen plates. The degree of surface epithelial lymphocytosis was greater than that seen in control groups of persons with normal colons, acute colitis, and ulcerative colitis (p < 0.001), similar to that seen with collagenous colitis, and less than that seen with lymphocytic colitis (p < 0.001). Three patients showed focal active colitis similar to that described in acute infectious-type colitis in addition to the epithelial lymphocytosis. Two patients had colonic biopsy specimens that were histologically normal. In summary, histologic abnormalities in the small bowel are generally absent in Brainerd diarrhea. Colonic biopsy specimens in Brainerd diarrhea frequently show epithelial lymphocytosis similar to that seen in collagenous and lymphocytic colitis. Although currently Brainerd diarrhea can be diagnosed only with epidemiologic data indicating an epidemic and a point source, the lack of surface degenerative changes and the relatively lower lymphocyte counts seen in our cases of Brainerd diarrhea may serve to distinguish it from lymphocytic colitis, and the lack of a thickened subepithelial collagen plate distinguishes it from collagenous colitis.

Detection of dysplasia at colonoscopy using laser-induced fluorescence: a blinded study.

BACKGROUND: Laser-induced fluorescence spectroscopy has the potential to detect colonic dysplasia in vivo. However, previous studies have limited their analyses to multivariate regression techniques and unblinded retrospective evaluation. The purpose of this study was to develop a probability-based algorithm to detect colonic dysplasia using laser-induced fluorescence spectroscopy and to evaluate it in a blinded manner. METHODS: Fluorescence spectra were collected from normal mucosa and colonic polyps during colonoscopy using 370 nm excitation. Tissue was classified as normal, hyperplastic, or adenomatous by histologic examination. Preliminary data was used to devise an algorithm to differentiate tissue type based on probability distributions of the fluorescence intensity at 460 nm and the ratio of the intensity at 680 nm to that at 600 nm. The algorithm was then tested in a blinded fashion. RESULTS: The algorithm correctly determined the tissue type in 88% of cases, equal to the agreement of independent pathologists. Sensitivity, specificity, and positive predictive value for the detection of dysplasia was 90%, 95%, and 90%, respectively. CONCLUSIONS: Dysplasia was detected in vivo using fluorescence spectroscopy and a probability-based algorithm. This method may form the basis for a new surveillance technique for patients with increased risk for dysplastic transformation.

Methylene blue selectively stains intestinal metaplasia in Barrett's esophagus.

BACKGROUND: Specialized columnar epithelium in Barrett's esophagus resembles gastric intestinal metaplasia, which selectively stains with methylene blue. METHODS: We prospectively evaluated the safety, accuracy, reproducibility, cost, and diagnostic yield of methylene blue-directed biopsy in detecting specialized columnar epithelium and dysplasia in Barrett's esophagus. We performed upper endoscopy with methylene blue-directed biopsy and obtained 236 large cup biopsy specimens (145 stained, 91 unstained) from 14 patients with Barrett's esophagus of any length (Group 1) and 12 control patients. Biopsy specimens were independently examined by two pathologists unaware of the endoscopic results. RESULTS: Methylene blue stained specialized columnar epithelium in 18 of the 26 patients, including those with intramucosal carcinoma (1), high-grade dysplasia (1), and indefinite/low-grade dysplasia (6). Methylene blue staining pattern, which was focal in 72% and diffuse in 28% of patients, was reproduced in 8 patients who had repeat staining within 4 weeks. The overall accuracy of methylene blue staining for detecting specialized columnar epithelium was 95%. The diagnostic yield of methylene blue staining for specialized columnar epithelium in "control" patients was 42%. The risk for dysplasia in stained biopsy specimens was greater than in unstained ones (odds ratio 17.7, p = .0004). CONCLUSIONS: Methylene blue mucosal staining is a safe, inexpensive, reproducible, and highly accurate method of diagnosing specialized columnar epithelium in Barrett's esophagus.