High interobserver variability and frequent overdiagnosis of dysplasia in fundic gland polyps can be improved by detecting atypia on the surface epithelium and an abrupt transition to non-neoplastic cells.

AIMS: Fundic gland polyps (FGPs) arise sporadically and in combination with familial adenomatous polyposis (FAP). Criteria for distinguishing low-grade dysplasia (LGD) from regenerative atypia in FGPs are not well established. The aims of study were to determine: (i) interobserver variability in diagnosing LGD in FGPs; (ii) bias in diagnosing LGD in FAP patients; and (iii) stringent criteria for LGD in FGPs. METHODS AND RESULTS: Five senior pathologists who were blinded to the clinical history reviewed 72 FAP-associated FGPs and 34 sporadic FGPs. Cases were classified as negative (score = 0) or positive (score = 1) for LGD. Each case was assigned a 'combined dysplasia score' (CDS) ranging from 0 to 5 to reflect all five opinions. Fleiss' kappa showed only moderate interobserver agreement (κ = 0.46). Forty-one FGPs were classified as negative for dysplasia by consensus (CDS = 0-1), including 10 (24%) originally diagnosed as LGD. In contrast, all 37 cases classified as LGD by consensus (CDS = 4-5) were originally diagnosed as LGD, indicating that overdiagnosis of dysplasia is more common than underdiagnosis (P = 0.0012). Cytological atypia in the surface epithelium and an abrupt transition between atypical and normal-appearing epithelium were the most sensitive (97% and 100%, respectively) and specific (100% and 98%, respectively) features of dysplasia (P < 0.0001 for both comparisons). Very good agreement was achieved when a diagnosis of dysplasia was based on the presence of both features (κ = 0.85). CONCLUSIONS: There is high interobserver variability and a tendency to overdiagnose LGD in FGPs. Strict criteria requiring both surface atypia and abrupt transition for LGD in FGPs result in low interobserver variability.

Ocular Myasthenia Gravis Associated With Thymic Amyloidosis.

A 45-year-old woman with ptosis and diplopia was found to have myasthenia gravis (MG) associated with amyloidosis of the thymus gland. Systemic MG is frequently associated with thymomas or thymic hyperplasia but has only once previously been reported in association with amyloidosis of the thymus. This case demonstrates that isolated ocular MG rarely may also be associated with amyloidosis of the thymus.

Cecal diverticulitis as a continuing diagnostic and management dilemma: a report of two cases in children.

Right-sided diverticulitis remains an exceedingly rare condition in the pediatric population. The clinical presentation mimics acute appendicitis, and the correct diagnosis is often difficult to make prior to operative exploration. We report two cases of cecal diverticulitis, and discuss the diagnosis and management of this disease, with a review of the literature.

Radiologic-pathologic correlation in acute appendicitis: can we use it as a quality measure to assess interpretive accuracy of radiologists?

Radiologic-pathologic correlation was evaluated as a quality assurance tool by documenting error rates of 18 radiologists interpreting computed tomographic (CT) scans for acute appendicitis in 763 patients. The departmental error rate was 3.1%. Meaningful individual error rates could be determined in only the seven radiologists who interpreted ≥30 CT scans for acute appendicitis. Radiologic-pathologic correlation is an effective departmental monitor of interpretive accuracy, but individual accuracy can be assessed only for radiologists reading a large number of cases with pathologic proof.

Chromosome X-encoded cancer/testis antigens show distinctive expression patterns in developing gonads and in testicular seminoma.

BACKGROUND: Cancer/testis (CT) antigens are cancer antigens normally expressed in adult testicular germ cells. The expression of chromosome X-encoded CT antigens (CT-X antigens) in human fetal gonads and in testicular seminomas was examined. METHODS: The expression of 10 CT-X antigens (MAGEA, NY-ESO-1, GAGE, CT7/MAGEC1, CT10/MAGEC2, CT45, SAGE1, SSX2, NXF2 and SPANX) was studied immunohistochemically. RESULTS: In adult human testis, SPANX is expressed in late spermatids and spermatozoa, whereas all other CT-X antigens are predominantly expressed in spermatogonia or primary spermatocytes. All CT-X antigens except SPANX are expressed in human fetal germ cells. CT-X-positive germ cells appear as early as 13 weeks after gestation, increase with age and reach a plateau at around 22 weeks. In the fetal ovary, CT-X-positive oogonia are most abundant at around 24 weeks and sharply decrease subsequently. CT-X antigens are almost exclusively expressed in OCT3/4-negative gonocytes and their expression appears to coincide with the loss of pluripotency. Spermatocytic seminoma, a neoplasm derived from adult pre-meiotic germ cells, showed uniform expression of all CT-X antigens except SPANX. In contrast, most seminomas (>80%) express CT7, CT45, GAGE and CT10 but express MAGEA, NXF2 and NY-ESO-1 at lower frequency, and very rarely express SSX2 and SAGE1. CONCLUSIONS: Most CT-X antigens are expressed in human fetal germ cells after they have lost stem cell characteristics, with predominant expression in pre-meiotic germ cells. Spermatocytic seminomas showed expression of all CT-X antigens except SPANX, whereas classical seminomas only express some CT-X antigens, reflecting their different origins from adult versus fetal germ cells.

Preoperative taxane-based chemotherapy and celecoxib for carcinoma of the esophagus and gastroesophageal junction: results of a phase 2 trial.

PURPOSE: The primary objective of this study was to determine the rate of pathological response after preoperative celecoxib and concurrent taxane-based chemotherapy in patients with cancer of the esophagus and gastroesophageal junction. METHODS: Thirty-nine patients were enrolled in this single-arm, phase II clinical trial. Patients were administered daily celecoxib in combination with two to three cycles of carboplatin and paclitaxel with preoperative intent. Levels of cyclooxygenase (COX)-2 expression in resected tumors were analyzed by immunohistochemistry and correlated with clinical outcome measures. Postoperatively, patients were administered daily celecoxib for 1 year or until documented tumor recurrence. RESULTS: All patients received two to three cycles of chemotherapy plus celecoxib 800 mg/d. Toxicities were as expected. A major clinical response (complete response + partial response) was noted in 22 patients (56%); six patients (15%) had a complete clinical response. Thirty-seven patients underwent esophagectomy. Five patients had a major pathological response (12.8%). Four-year overall and disease-free survivals were 40.9% and 30.3%, respectively. Patients with tumors expressing COX-2 demonstrated a higher likelihood of a major clinical response response (62% versus 50%) and an improved overall survival, compared with patients with COX-2-negative tumors. CONCLUSIONS: Preoperative celecoxib with concurrent chemotherapy demonstrated sufficient effect on pathologic response to warrant further study. Patients with tumors expressing COX-2 demonstrated trends toward improved response to preoperative therapy and improved overall survival compared with nonexpressors.

The Association between Childhood Overweight and Reflux Esophagitis.

Background. In adults, it has been shown that obesity is associated with gastroesophageal reflux disease (GERD) and GERD-related complications. There are sparse pediatric data demonstrating associations between childhood overweight and GERD. Objective. To investigate the association between childhood overweight and RE. Methods. We performed a retrospective chart review of 230 children (M : F = 114 : 116) who underwent esophagogastroduodenoscopy (EGD) with biopsies between January 2000 and April 2006. Patient demographics, weight, height, clinical indications for the procedure, the prevalence of BMI classification groups, the prevalence of RE and usage of anti-reflux medications were reviewed. For these analyses, the overweight group was defined to include subjects with BMI>/= 85th percentile. The normal weight group was defined to include subjects with BMI 5th to 85th percentile. Results. Among the 230 subjects, 67 (29.1%) had BMI percentiles above the 85th percentile for age and gender. The prevalence of RE in the overweight group did not differ significantly from that in the normal weight group (23.9% versus 24.5%, resp.). Overweight subjects taking anti-reflux medications clearly demonstrated a higher prevalence of biopsy-proven RE compared to overweight subjects not taking anti-reflux medications (34.1% versus 7.7%, P = .009). Conclusions. There was no significant difference in the prevalence of biopsy-proven RE in the overweight group compared to the normal weight group. However, the prevalence of RE was significantly higher in overweight subjects on anti-reflux medications compared to overweight subjects not taking anti-reflux medications. This finding emphasizes the importance of early recognition and treatment of GERD for the overweight pediatric patients with symptoms in conjunction with weight loss program for this population to reduce long-term morbidities associated with GERD.

Pulmonary blastoma in a neonate: a lesion distinct from pleuropulmonary blastoma with unique cytogenetic features.

Pulmonary blastoma is a rare malignant primary lung neoplasm typically seen in adults that accounts for 0.3-1.3% of lung malignancies. It has been categorized as a subtype of sarcomatoid carcinoma according to the current World Health Organization Classification of Lung Tumours and is distinct from the more common pediatric lung tumor pleuropulmonary blastoma. We report a case of neonatal pulmonary blastoma, illustrating the imaging characteristics of this rare tumor. The subject of pediatric lung masses is confusing because the terms pleuropulmonary blastoma and pulmonary blastoma have been used interchangeably in previously reported cases. We recommend use of the current WHO classification to differentiate these lesions as additional cases are described. Additionally, we discuss distinctive cytogenetic features of this case.

Segmental dilatation of the ileum in a healthy adolescent.

Segmental intestinal dilatation is a rare entity presenting overwhelmingly in infants and young children with congenital malformations, anemia, or history of gastrointestinal pathology, characterized by a focally distended segment of bowel with abrupt transition points without an obstructing barrier. We present a 16-year-old girl with no significant medical history who presented with bowel obstruction clinically. Segmental dilatation of the ileum was evident on a CT scan and small bowel series. Following surgical resection, pathologic examination of the segment revealed the presence of heterotopic gastric mucosa. The girl's symptoms resolved after surgery. Awareness of the imaging presentation of this entity can inform the evaluation of older children with nonspecific symptoms mimicking bowel obstruction.

Positive association between Helicobacter pylori and gastroesophageal reflux disease in children.

OBJECTIVES: The role of Helicobacter pylori (H pylori) in gastroesophageal reflux disease (GERD) remains controversial, particularly in children, because there are limited published data. Adult studies suggested that H pylori infection may protect against GERD by causing atrophic gastritis, which leads to reduced gastric acid secretion. The objective of our study was to determine the role of H pylori infection in the development of GERD in a pediatric population. PATIENTS AND METHODS: A retrospective analysis of 420 patients (M:F = 214:206) who underwent esophagogastroduodenoscopy (EGD) with biopsies between January 2000 and April 2006 was conducted. Patient demographics, clinical indications for EGD and the prevalence of reflux esophagitis (RE), the biomarker for GERD, in 2 groups, H pylori positive and H pylori negative, were reviewed. The prevalence of RE in the H pylori-positive and H pylori-negative groups was further analyzed on the basis of sex and age (<1 year, 1-10 years, >10 years). The mean age of the study population was 8.2 years (range 0-20 years). The clinical indications for EGD were as follows: recurrent abdominal pain (n = 186, 44%), malabsorption (n = 80, 19%), persistent vomiting (n = 80, 19%), suspected eosinophilic gastrointestinal disorders (n = 63, 15%), and others such as upper gastrointestinal bleeding or inflammatory bowel disease surveillance (n = 11, 3%). Statistical analysis was performed by using chi test, Fisher exact test, and multivariate logistical regression analysis. RESULTS: Among the 420 patients, 16 patients (3.8%) were positive for H pylori and 167 patients (39.8%) were found to have RE. Thirteen patients with H pylori were found to have histologic evidence of RE. The prevalence of RE in the H pylori-positive population was 81.3% compared with 38.1% in the H pylori-negative population (P < or = 0.05). There were no patients with H pylori in the youngest age group. In the second age group (1-10 years), 100% of the H pylori-positive patients had RE, whereas 44.6% of the H pylori-negative patients had RE (P < or = 0.05). Both male and female patients with H pylori had a higher prevalence of RE, 77.8% and 85.7%, respectively. On a multivariate logistical regression, for the overall study cohort, H pylori-positive patients had an odds ratio of 5.79 of developing RE compared with H pylori-negative patients (P < or = 0.05). CONCLUSIONS: Our study results indicate that there is a significantly higher prevalence of RE in an H pylori-infected cohort independent of age or sex. The findings suggest that H pylori infection in children is positively associated with RE.

Coexpression of CD43 by benign B cells in the terminal ileum.

Expression of CD43 by B cells is often used as a diagnostic criterion in favor of a B-cell lymphoproliferative disorder, including small lymphocytic lymphoma/chronic lymphocytic leukemia, mantle cell lymphoma, Burkitt lymphoma, precursor B-lymphoblastic lymphoma, and a subset of marginal zone B-cell lymphomas. Benign B cells generally do not coexpress CD43. The authors analyzed 20 biopsies of the terminal ileum for nonneoplastic disease for expression of CD43 and compared them with other sites and with CD20, CD138, and CD3 reactivity. The majority of cases (85%) showed strong coexpression of CD43 by benign perifollicular B cells. The presence of CD43 coexpression in B-cell populations of the terminal ileum, including those of Peyer's patches, should not be used as a diagnostic parameter to differentiate extranodal marginal zone B-cell lymphoma of MALT type from reactive processes.

Congenital infantile hepatic hemangioendothelioma type II treated with orthotopic liver transplantation.

The authors describe a 10-week-old girl with infantile hepatic hemangioendothelioma who initially presented with difficulty feeding, hepatomegaly, and multiple hemangiomas of the skin. Six weeks of steroid therapy and 2 weeks of chemotherapy failed to produce clinical improvement. The patient underwent split liver transplantation. A definitive diagnosis of hemangioendothelioma type II was made. Imaging studies cannot differentiate between hemangioendothelioma and angiosarcoma. Treatment modalities for this condition remain unclear. The patient continues to do well.

Primary Burkitt-like lymphoma presenting as a solitary rectal polyp in a child: case report.

Primary rectal lymphoma in childhood is rare. We report a case in a 10-year-old boy who presented with rectal bleeding and a single rectal polyp. Histologic examination, immunophenotyping and molecular genetic study of the polyp showed a diffuse B-cell lymphoma, Burkitt-like type. The literature on this topic is reviewed and pathologic examination of childhood rectal polyps is emphasized.

Atypical morphologic presentation of biliary atresia and value of serial liver biopsies.

BACKGROUND: Liver biopsy findings are important in diagnosing extrahepatic biliary atresia. Diffuse ductular proliferation is a characteristic finding. We describe four patients with conjugated hyperbilirubinemia in whom the initial liver biopsy findings showed a lack of ductular proliferation, despite subsequent development of biliary atresia. RESULTS: On initial biopsy, paucity of intrahepatic bile ducts was present in three of four patients, with a bile duct to portal space ratio of 0.3 to 0.4 (normal, 0.9-1.8). A normal bile duct to portal space ratio of 1.0 was observed in the fourth patient. Ductular proliferation became apparent in three subjects between 9 and 12 weeks of age, and biliary atresia was noted at the time of a Kasai portoenterostomy. The fourth child had well-developed biliary cirrhosis at liver transplantation. CONCLUSIONS: Changes characteristic of biliary atresia may appear even after 9 weeks of age. Bile duct paucity and normal bile duct to portal space ratio do not preclude the subsequent development of biliary atresia. Infants with unexplained conjugated hyperbilirubinemia and acholic stools should undergo sequential liver biopsies until clinical improvement occurs or until biliary atresia can be excluded from the differential diagnosis.