Presence or absence of intestinal metaplasia but not its burden is associated with prevalent high-grade dysplasia and cancer in Barrett's esophagus.

Universal agreement on the inclusion of intestinal metaplasia to diagnose Barrett's esophagus (BE) is lacking. Our aim was to determine the association of intestinal metaplasia and its density with the prevalence of dysplasia/cancer in columnar lined esophagus (CLE). Patients with CLE but no intestinal metaplasia (CLE-no IM) were identified by querying the clinical pathology database using SNOMED codes for distal esophageal biopsies. CLE-IM patients were identified from a prospectively maintained database of BE patients. Subsequently, relative risks for prevalent dysplasia and cancer were calculated. Since patients with CLE-no IM are not usually enrolled in surveillance, only prevalent dysplasia/cancer on index endoscopy was analyzed. Goblet cell density and percent intestinal metaplasia were estimated. All biopsy slides were reviewed for dysplasia by two experienced gastrointestinal pathologists. Two hundred sixty-two CLE-IM and 260 CLE-no IM patients were included (age 64±12 vs. 60±11 years, P=0.001; whites 92% vs. 82%, P=0.001; males 99.7% vs. 99.3%, P=NS; CLE length 3.4±3.2 vears 1.4±0.4 cm, P=0.001 and hiatus hernia 64% vs. 56%, P=0.013). The odds of finding low-grade dysplasia and of high-grade dysplasia (HGD)/cancer were 12.5-fold (2.9-53.8, P=0.007) and 4.2-fold (95% CI 1.4-13, P=0.01) higher, respectively, in the CLE-IM group. Reanalysis after controlling for important variables of age, race, and length did not significantly alter the overall results. In CLE-IM group, when patients with high (>50/LPF) versus low goblet cell density (<50/LPF) and <10% versus >10% intestinal metaplasia were compared, the odds of HGD/cancer, OR 1.5 (0.5-4.9, P=0.5) and 1.97 (0.54-7.22), respectively, were not significantly higher. Demonstration of intestinal metaplasia continues to be an essential element in the definition of BE, but its quantification may not be useful for risk stratification of HGD/cancer in BE.

Evaluation of the updated confocal laser endomicroscopy criteria for Barrett's esophagus among gastrointestinal pathologists.

Previously developed novel probe-based confocal laser endomicroscopy (pCLE) criteria have been found to have high accuracy and substantial interobserver agreement (IOA) for diagnosing dysplasia in Barrett's esophagus (BE) when used by endoscopists. These updated criteria are: (i) epithelial surface: saw toothed, (ii) cells: enlarged, (iii) cells: pleomorphic, (iv) glands: not equidistant, (v) glands: unequal in size and shape, and (vi) goblet cells: not easily identified. The accuracy and IOA among pathologists in the diagnosis of dysplasia using the novel pCLE criteria is not known. The primary objective of the study was to evaluate the accuracy, overall IOA and learning curve among three gastrointestinal (GI) pathologists in diagnosing dysplasia in BE using the updated pCLE criteria. The secondary aim was to compare the accuracy and IOA between GI pathologists and gastroenterology endoscopists. Ninety pCLE videos and respective histology were retrieved from a previously conducted multicenter, prospective, randomized, controlled trial evaluating the utility of pCLE in BE patients. Videos were obtained from 101 BE patients previously enrolled for surveillance or endoscopic treatment of high-grade dysplasia or early esophageal adenocarcinoma. Three GI pathologists reviewed 90 pCLE video clips for dysplasia versus no dysplasia, confidence in their diagnosis, and image quality. The overall accuracy for the diagnosis of dysplasia (low-grade dysplasia/high-grade dysplasia/esophageal adenocarcinoma) was 77.8% (95% confidence interval [CI]: 72.4-82.3). The accuracy was higher when pathologists had 'high confidence' in their assessment of the videos (93.8% vs. 69.3%, P < 0.001). There was no significant difference in accuracy between the first set of 30 and second set of 60 videos (84% vs. 74%, P = 0.065). IOA among GI pathologists was substantial, k = 0.65 (95% CI: 0.53-0.73). The sensitivity for detecting dysplasia was 85% (95% CI: 78.1-90.7) and the specificity was 70% (95% CI: 61.91-77.92). These results were comparable with the evaluation of the same set of videos by endoscopists. GI pathologists have high accuracy and substantial IOA for diagnosing BE dysplasia with pCLE. Pathologists appear to have similar accuracy and IOA as endoscopists. These results provide further support of endoscopists accurately interpreting the in vivo optical histology provided by pCLE.

Cerebral, myocardial and cutaneous ischemic necrosis associated with calcific emboli from aortic and mitral valve calcification in a patient with end-stage renal disease.

We report the case of a 57-year-old diabetic male with chronic renal failure who developed secondary hyperparathyroidism and calcification of mitral and aortic valves and interatrial septum. Multiple ischemic lesions developed in the skin of hands, feet and penis, and in the brain, and these were presumed to be due to septic emboli from cardiac valvular infective endocarditis. Multiple blood cultures were negative, however, and despite antibiotic therapy the patient expired. Autopsy (limited to trunk) demonstrated multiple calcific emboli in the heart and spleen, apparently derived from the prominent calcific deformities in the aortic and mitral valves. These were associated with acute and organizing myocardial infarcts and acute splenic infarcts, suggesting that the multiple ischemic lesions in the brain were also due to calcific emboli. A possible contributory component of infective endocarditis, however, was indicated by postmortem cultures of aortic and mitral valves positive for Enterococcus faecium. Calcific embolism is a rarely recognized but potentially lethal complication of end-stage renal disease, and the clinical diagnosis and the preventive therapeutic options for the control of the product of calcium and phosphate and/or parathyroidectomy should be considered.

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.

Adenocarcinoid of ileum and appendix, incidentally discovered during exploratory laparotomy for gastric MALT lymphoma, with subsequent diffuse prostatic metastases: report of a case with light, immunohistochemical, and electron microscopic studies.

The diagnosis of adenocarcinoid (mucinous/goblet cell carcinoid) is usually unexpected by both clinicians and pathologists. We report here the case of a 74-year-old man with gastric lymphoma (B-cell MALToma) diagnosed by endoscopy, who was found on exploratory laparotomy also to have extensive intraabdominal involvement by adenocarcinoid, arising from the ileum and/or appendix. The patient died two years after diagnosis with bladder outlet and small bowel obstruction due to diffuse metastases. In addition to mucin positivity, immunohistochemical stains demonstrated the tumor to be positive for chromogranin, synaptophysin, serotonin, gastrin, and glucagon. Of histogenetic interest, some individual neoplastic cells appeared to be positive for both mucin and chromogranin, and this was confirmed by the electron microscopic finding of microvilli, intracytoplasmic mucin droplets, and neurosecretory granules involving the same neoplastic cells. This also appears to be the first reported case of adenocarcinoid associated with lymphoma and demonstration of histochemical/immunohistochemical and ultrastructural evidence of cellular components with dual mucinous adenocarcinoma and neuroendocrine features, and the second reported case to have prostatic metastases.

Prospective, multivariate evaluation of CLOtest performance.

OBJECTIVES: To determine prospectively the effect of aspirin, nonsteroidal anti-inflammatory drugs, H2-receptor antagonists, proton pump inhibitors, alcohol intake, race, age, history of Helicobacter pylori eradication attempts, and gastric biopsy location on CLOtest performance. METHODS: Biopsy specimens were obtained from the antrum, greater curve, and proximal stomach. One biopsy specimen from each site (except for the proximal stomach) was used for the CLOtest and two or more specimens were used for histopathology. Giemsa staining was used for the definitive determination of H. pylori status. RESULTS: One hundred seventeen patients were included in the study, and 50 of these were infected with H. pylori. The sensitivity and specificity of an antral CLOtest, based on the results of Giemsa-stained sections from the antrum alone, were 72.7 and 98.6%, respectively, whereas they were 66.0 and 100% when based on the results of Giemsa-stained sections from all three gastric biopsy sites. The sensitivity and specificity of a body CLOtest, based on the results of Giemsa-stained sections from the body alone, were 80.5% and 93.4%, whereas they were 76.0% and 100% when based on the results of Giemsa-stained sections from all three gastric biopsy sites. Combining CLOtest results from the antrum and body increased CLOtest sensitivity to 82.0%. Univariate analysis revealed only one factor significantly associated with CLOtest concordance: absence of alcohol consumption (p < 0.02). Stepwise logistic regression demonstrated that absence of alcohol use again was independently associated with the concordance between overall CLOtest and all Giemsa-stained biopsy specimen results (p < 0.03) as well as between body CLOtest and body Giemsa-stained biopsy specimen results (p < 0.03). Additional independent and significant associations were noted between antral CLOtest-antral Giemsa-stained biopsy specimen results and no history of H. pylori eradication attempts (p = 0.04) and between body CLOtest-body Giemsa-stained biopsy specimen results and race (African-American) (p < 0.03). CONCLUSIONS: Obtaining a gastric biopsy specimen from the antrum as well as from the body increased CLOtest detection of H. pylori. CLOtest performance was shown to be affected by several demographic and clinical factors.

Retrospective DNA ploidy analysis by image and flow cytometry in head and neck cancer.

A retrospective analysis of DNA content (DNA ploidy) was conducted in formalin-fixed specimens from patients with advanced, unresectable head and neck cancer who were treated on a single defined protocol with accelerated fractionation radiation therapy and concomitant cisplatin (Platinol) chemotherapy. Specimens from 31 tumor sites were analyzed by image cytometry using the Feulgen staining method. Fifteen specimens were analyzed by flow cytometry after deparaffinization, nuclear disaggregation, and staining with propidium iodide. By image analysis, 10 (32%) of 31 specimens contained only diploid tumor cells, while 21 (68%) specimens exhibited at least one aneuploid tumor component. Seven of the eight tumors with a single G0/G1 peak by image analysis had a single peak by flow analysis. Five of the seven tumors with multiple peaks by image analysis had multiple peaks by flow analysis. Histology was also reevaluated, and tumor grade was determined, reflecting tumor cell differentiation based on keratinization, mitotic activity and the degree of nuclear polymorphism. For this well-defined patient population managed according to a uniform therapeutic approach, DNA ploidy status and histology provided a suggestion of prognostic separation; however, statistical significance was not obtained, most likely due to the small number of patients.

Short segment Barrett's esophagus: clinical and histological features, associated endoscopic findings, and association with gastric intestinal metaplasia.

OBJECTIVES: To prospectively determine the clinical features, associated esophageal endoscopic lesions, associated gastric intestinal metaplasia, and prevalence of dysplasia and adenocarcinoma of short segment Barrett's. METHODS: All patients undergoing upper endoscopy over a 5-month period were scrutinized for endoscopic features suggestive of short segment Barrett's, and, if present, multiple biopsies were obtained from the suspicious areas. Prevalence of gastric intestinal metaplasia was determined by obtaining biopsies from the antrum, body, and cardia. RESULTS: Two hundred thirty seven patients were examined. Short segment Barrett's was suspected in only 42 patients, and traditional Barrett's was noted in 45 patients. Short segment Barrett's was confirmed by biopsy in 48%. Clinical presentation of short segment Barrett's was that of typical or complicated gastroesophageal reflux disease in 53%. A hiatal hernia was the most common associated esophageal endoscopic finding; however, none of the endoscopic findings differed significantly from findings of patients who did not have short segment Barrett's. Diagnosis of short segment Barrett's required histological analysis. A significant difference was noted in the prevalence of intestinal metaplasia between the esophagus and stomach in patients with Barrett's. No dysplasia or adenocarcinoma was detected in patients with short segment Barrett's. CONCLUSIONS: Short segment Barrett's is a frequent finding in patients undergoing upper endoscopy. All patients with short tongues or patches of red mucosa lying less than 2 cm above the esophagogastric junction should be biopsied to exclude short segment Barrett's. Large scale endoscopic and histological surveillance studies along with long-term follow-up are required to clarify short segment Barrett's prevalence and cancer risk.

Nonfamilial tumoral calcinosis associated with chronic renal failure and secondary hyperparathyroidism: report of two cases with clinicopathological, immunohistochemical, and electron microscopic findings.

The clinical and pathological findings, including those of immunohistochemical and ultrastructural studies, of two cases of tumoral calcinosis-like lesion (TCL) are described. Both cases were associated with chronic renal failure and hyperparathyroidism. One case presented as a rapidly growing 20-cm multiloculated, cystic, calcific gluteal mass on the sacrum, which was not clinically suspected to be related to hyperparathyroidism. The other case presented as a 2.5-cm calcific mass on the right foot that recurred after surgical excision as a 7-cm mass, which was clinically presumed to be related to secondary hyperparathyroidism. Light microscopic and immunohistochemical studies on both cases and ultrastructural studies on one case indicated that the calcifying process involved histiocytes and osteoclast-like giant cells of histiocytic origin lining the cystic cavities. Hydroxyapatite crystal formation and calcification appeared to develop predominantly from intracytoplasmic membrane bound vesicles and also from mitochondria. These findings are similar to those recently reported for familial tumoral calcinosis, which support its having a mechanism of calcification comparable with that of a TCL.

Endoscopic and histologic resolution of gastric pseudolymphoma (reactive lymphoid hyperplasia) following treatment with bismuth and oral antibiotics.

Gastric pseudolymphoma is a rare disorder of unknown etiology that can undergo transformation into malignant lymphoma. This report describes the first case of a gastric pseudolymphoma associated with Helicobacter pylori infection that underwent complete clinical, endoscopic, and histologic resolution following treatment with bismuth subsalicylate, amoxicillin, and metronidazole. The eradication of Helicobacter pylori may have eliminated ongoing antigenic stimulation that has previously been postulated to be responsible for the development and subsequent progression of gastric pseudolymphoma.

Case reports: heterotopic brain tissue of middle ear associated with cholesteatoma.

Heterotopic brain tissue reportedly occurs occasionally in various sites, including rare occurrences in the middle ear. Association with cholesteatoma in middle ear cases, however, has not been reported yet. In this article, the authors describe three cases of heterotopic brain tissue in the middle ear associated with cholesteatoma: a 3-year-old boy with recurrent meningitis resulting in right acute otitis media and bony dehiscence of the right attic; a 36-year-old man with chronic right ear infections, right radical mastoidectomy 2 years previously, and brain herniation through the tegmen tympani; and a 65-year-old man with chronic otitis for many years, right ear surgery 25 years previously, and extensive involvement of right middle ear ossicles and mastoid antrum by cholesteatoma. The heterotopic brain tissue in each of these cases was diagnosed by histologic examination, and its glial component was confirmed by immunohistochemical staining for glial fibrillary acidic protein. After a microscopic review of 40 additional surgical pathology cases of cholesteatoma, no evidence of heterotopic brain tissue was found. With these findings, it is suggested that the unusual occurrence of heterotopic brain tissue in the middle ear associated with cholesteatoma may result from local destruction of bone secondary to the cholesteatoma, otitis media, meningitis, or previous surgery.

Pulmonary mucinous cystic tumor. Case report with review of the literature.

Mucinous cystic tumors of the lung are exceedingly rare. We describe the case of a 59-year-old white man with a left upper lobe mass documented on chest radiographs 11 years before thoracotomy. Grossly, the lobectomy specimen contained a 4.5 x 4.5 x 4.0 cm cystic gelatinous mass with complete occlusion of the anterior segmental bronchus by mucinous material. Although microscopically this pulmonary mucinous cystic tumor contained a focus of marked glandular atypia consistent with adenocarcinoma, the patient has remained free of recurrence or metastasis during 5 years of close postoperative follow-up. Pulmonary mucinous cystic tumors appear to have a remarkably favorable prognosis and should be distinguished from other common lung neoplasms.

Histologic features predictive of basal cell carcinoma recurrence: results of a multivariate analysis.

Previous univariate analysis of 30 recurrent and 74 non-recurrent basal cell carcinomas identified 6 histologic parameters predictive of recurrence: distance to the closest resection margin, growth pattern, shape of cell groups, contour of invading edge, degree of peripheral palisading, and nuclear pleomorphism. Re-analysis of the data by multivariate analysis to select the few most important independent prognostic variables identified two parameters in each of two final models: resection margin distance and growth pattern (Model 1), and resection margin distance and shape of cell groups (Model 2). Based on these variables, a logistic regression equation could be derived for each model to calculate the predicted probability of recurrence or non-recurrence.

Case report: gastric angiolipoma with chronic hemorrhage and severe anemia.

Lipomas are benign tumors that are common in other sites but rare in the stomach. They are usually submucosal and, when symptomatic, are most often accompanied by gastrointestinal hemorrhage. Angiolipoma is a not uncommon benign lipomatous neoplasm with a characteristic vascular component that almost exclusively occurs in the subcutaneous tissue. A case of gastrointestinal angiolipoma, which appears to be only the second one reported, is discussed. The patient, a 69-year-old man, presented with signs and symptoms of chronic hemorrhage and severe anemia (hemoglobin 6, hematocrit 19.9). The patient's condition was found to have resulted from ulceration of the gastric mucosa overlying a submucosal angiolipoma, and the anemia resolved after local surgical resection of the tumor. Electron microscopic studies supported the light microscopic diagnosis of angiolipoma. The absence of fibrin thrombi in this and other nonsubcutaneous angiolipomas and the possible significance of the vascularity of these tumors is discussed. The literature regarding gastric lipoma and angiolipoma is reviewed.

Lipohyperplasia of the ileocecal valve.

Submucosal lipohyperplasia of the ileocecal valve (ICV) is reportedly a rarely diagnosed lesion of uncertain significance. Eight cases of ICV lipohyperplasia diagnosed in surgical specimens (seven resections, one biopsy) are reviewed: three cases were associated with right lower abdominal quadrant pain and ICV mass on barium enema or operative examination, two were associated with ICV mucosal acute inflammation and necrosis, and three were incidental in resections for cecal, appendiceal, and sigmoid neoplasia. To evaluate the frequency of ICV lipohyperplasia and any associated processes, a series of 51 autopsies was studied. Regarding lipohyperplasia in these valves, 10 (19.6%) were determined to have none, 14 (27.5%) were mild, 20 (39.2%) were moderate, and 7 (13.7%) were marked cases. Degree of lipohyperplasia correlated statistically with degree of cardiac right ventricular fatty infiltration (p = 0.0001), pancreatic fatty infiltration (p = 0.0314), and greater body weight of patient (p = 0.0009). No definite correlation was demonstrated with left ventricular, adrenal, or lymph node fatty infiltration, or with hepatic fatty change, body height, age of patient, or blood glucose. Various gastrointestinal symptoms and lesions accompanied lipohyperplasia, but no definite causal relationship was identified, except for one case of marked lipohyperplasia associated with marked mucosal necrosis and acute inflammation of ICV. In conclusion, ICV lipohyperplasia is a common finding that occasionally may be associated with clinical symptoms and other valve pathology. It correlates to some extent with right ventricular and pancreatic fatty infiltration and with greater body weight.

Polypoid adenosquamous carcinosarcoma of the epiglottis with blastomatous features.

A case is reported of polypoid adenosquamous carcinosarcoma with blastomatous features arising in the epiglottis. A 69-year-old man with hoarseness and sore throat was found to have a six cm pedunculated mass located on the epiglottis. Upon examination by light microscopy, it was found that the tumor was composed of not only well to poorly differentiated in situ and invasive squamous cell carcinoma but also adenocarcinoma with blastomatous features and a malignant primitive stroma, with features of undifferentiated sarcoma and focal chondrosarcomatous differentiation. To the best of our knowledge, this appears to be the second case of laryngeal adenosquamous carcinosarcoma with blastomatous features reported in the English literature and the third case in the world literature.

Metastatic basal cell carcinoma: report of a case presenting with respiratory failure.

Metastasis from basal cell carcinoma (BCC) of skin is rare. A case of a 58-year-old male presenting with increasing shortness of breath and right pleural effusion is described. Open right pleural biopsy demonstrated metastatic carcinoma consistent with BCC. Review of medical records from another hospital revealed that four years previously a recurrent BCC had been excised from the left back. One and three years prior to this excision, a skin lesion at this same site had been treated with electrocautery. Review of the skin excision slides demonstrated infiltrating BCC histologically very similar to the metastatic pleural neoplasm. The patient died two months after the pleural biopsy. At autopsy, the cutaneous BCC had not recurred and metastatic BCC extensively infiltrated the pleura bilaterally, with focal involvement of underlying lung parenchyma, subcarinal lymph nodes, diaphragm, and pericardium.

Histologic evolution of basal cell carcinoma recurrence.

The biological behavior and appropriate therapy of recurrent basal cell carcinoma (BCCA) is controversial, with some studies suggesting that this tumor becomes more aggressive with each recurrence, and other studies indicating that the majority are aggressive from the onset. The authors studied the histologic evolution of BCCA by comparing 29 original tumors with their subsequent recurrences to determine if there were any predictable histologic changes. There were borderline statistically significant changes only in degree of fibrosis, prominence of nucleoli, and mitotic frequency. There were no statistically significant changes in any of the other parameters, including those that were shown previously to be predictive of recurrence or aggressive behavior. The results of this study clearly indicate that the majority of recurrent BCCAs are aggressive from the onset, and that in many cases this can be predicted from the histomorphology of the original tumor.