Clinical, endoscopic, and histologic features of eosinophilic inflammation of the gastrointestinal tract in pediatric liver transplant patients.

Immunosuppression during the post-transplantation period has led to dramatic outcome improvements in PLTR patients. There have been reports describing the development of food allergies and an increased predilection for development of EGI in PLTR. We aimed to identify the clinical, endoscopic and histologic features of EGI in PLTR patients. In this retrospective case series we analyzed medical record of all PLTR who underwent EGD and/or colonoscopy at our institution from 2000 to 2006. From 2000 to 2006, 32 PLTR patients underwent endoscopic evaluation. Seventeen (53%) of 32 patients were diagnosed with EGI. Endoscopic abnormalities were seen in the esophagus, stomach, and small intestine in 11 (65%), 11 (65%), and four (24%) patients, respectively. Eosinophilic inflammation was seen in the esophagus, stomach, and small intestine in 13 (76%), 10 (59%), and five (29%) patients, respectively. Nine of 17 patients underwent colonoscopy and endoscopic abnormalities were seen in four (44%) patients. Five patients (56%) had eosinophilic inflammation. In conclusion, we have characterized the clinical, endoscopic, and histologic features of EGI. Histologic and endoscopic examination reveals that, when present, EGI is often found at multiple segments along the gastrointestinal tract.

Predictors of response to proton pump inhibitor therapy among children with significant esophageal eosinophilia.

OBJECTIVES: To determine predictors of histological response to proton pump inhibitor (PPI) therapy among children with significant esophageal eosinophilia (SEE), defined as >or=15 eosinophils per high powered field (eos/hpf) on esophageal mucosal biopsy (EMB). STUDY DESIGN: Response to PPI therapy among children with SEE treated with PPI who underwent repeat EMB was studied retrospectively. Response was defined as <5 eos/hpf on repeat EMB. Characteristics of responders and nonresponders were analyzed. RESULTS: Of 326 patients (ages 1 through 18 years) diagnosed with SEE over a 7-year period, 43 (mean age, 8.5 years; 67% males) met inclusion criteria. After PPI therapy, 17 patients (40%) were responders. There were no significant differences in demographics, presenting symptoms, endoscopic, or histological findings between responders and nonresponders. Among patients with 15 to 20 eos/hpf on EMB, 50% were responders; among patients with >20 eos/hpf on EMB, 29% were responders. Seven of 17 (41%) patients with abnormal pH monitoring and 5 of 11 (45%) patients with normal monitoring were responders. CONCLUSIONS: Forty percent of patients with SEE demonstrated histological response to PPI therapy. None of the clinical characteristics evaluated predicted response, and response was not dependent on results of pH study. The role of PPI therapy in treating SEE warrants further prospective investigation.

Severity of basal cell hyperplasia differs in reflux versus eosinophilic esophagitis.

OBJECTIVES: Basal cell hyperplasia of the esophageal epithelium is a frequent finding in children with histological evidence of esophagitis. The aim of this study was to compare the severity of basal cell hyperplasia in gastroesophageal reflux vs eosinophilic esophagitis. METHODS: A cohort of pediatric patients who underwent same-day endoscopy with esophageal biopsy and 24-hour esophageal pH monitoring was divided into groups based on endoscopic and pH monitoring findings. Basal cell hyperplasia was defined as normal (< or = 25% of esophageal epithelial height), mild (26%-50%), moderate (51%-75%) or severe (> 75%). The severity of basal cell hyperplasia in patients with abnormal pH monitoring studies, both with and without endoscopic abnormalities of the esophagus, was compared with the severity in patients with eosinophilic esophagitis. RESULTS: Twenty-seven children with abnormal pH monitoring were identified. Of these 27 children, 11 had endoscopic findings consistent with reflux esophagitis. Thirty patients with eosinophilic esophagitis were identified. Patients with eosinophilic esophagitis had significantly increased severity (P < 0.001) of basal cell hyperplasia (87% severe, 3% moderate, 3% mild, 7%, normal) than patients with abnormal esophageal pH monitoring alone (11% severe, 4% moderate, 15% mild, 70% normal) or in combination with endoscopic abnormalities (18% severe, 9% moderate, 18% mild, 55% normal). CONCLUSIONS: Basal cell hyperplasia is more severe in children with eosinophilic esophagitis than in those with reflux esophagitis. The finding of basal cell hyperplasia is a powerful clue into the underlying etiology of pediatric esophagitis and, along with epithelial eosinophil count, can be used as information to guide therapy.

Thyroid transcription factor 1 expression in small cell carcinoma of the urinary bladder: an immunohistochemical profile of 44 cases.

Small cell carcinoma of the urinary bladder is a rare and aggressive tumor resembling small cell carcinoma of the lung. Thyroid transcription factor 1 (TTF-1) expression is common in small cell carcinomas arising in the lung. However, studies of its expression in extrapulmonary small cell carcinomas have yielded varying results. Because information concerning the immunohistochemical profile of small cell carcinoma of the urinary bladder is limited, we investigated the immunoreactivity of this tumor to a battery of antibodies in a series of 44 cases. Using 5-mum sections cut from paraffin-embedded tissue blocks, immunohistochemistry was performed to detect TTF-1, cytokeratin (CK) 7, CK20, and uroplakin antigenicity in 44 cases of small cell carcinoma of the urinary bladder. None of the patients had primary lung tumors. The TTF-1 immunohistochemical stain showed nuclear positivity in 17 cases (39%). Positive immunostaining for CK7 was observed in 26 cases (59%). There was no positive staining with either CK20 or uroplakin. There was no correlation between TTF-1 expression and survival (P = .27). In addition, TTF-1 expression did not correlate with clinicopathological characteristics, including age (P = .74), sex (P = .53), smoking history (P = .96), clinical stage (P = .10), pathological T stage (P = .50), lymph node metastasis (P = .40), and distant metastasis (P = .58). In summary, TTF-1 expression in small cell carcinoma of the urinary bladder was found in 39% of the tumors, demonstrating that this marker is expressed in small cell carcinomas other than those of pulmonary origin. Small cell carcinoma of the urinary bladder is positive for CK7 immunostaining in 59% of cases consistent with its origin from urothelium. Unlike urothelial carcinoma, expression of CK20 and uroplakin in small cell carcinoma of the urinary bladder is consistently negative, and thus, these stains do not appear to be useful in the diagnosis of this neoplasm. TTF-1 positivity is not a significant prognostic factor in small cell carcinoma of the urinary bladder.

Fluorescence in situ hybridization analysis of chromosome 12p in paraffin-embedded tissue is useful for establishing germ cell origin of metastatic tumors.

The over-representation of chromosome 12p sequences is crucial for the development of invasive testicular germ cell tumors. Testicular cancer patients may have metastatic tumors of diverse histologic types, including adenocarcinoma, undifferentiated carcinoma, sarcoma, or other malignancies that lack features of germ cell tumors. We sought to investigate the possible germ cell origin of such tumors using interphase fluorescence in situ hybridization. In all, 10 metastatic malignant somatic-type tumors from patients with histories of testicular cancer, as well as one malignant somatic-type tumor from a patient with primary mediastinal germ cell tumor were studied and included: adenocarcinoma (five cases), poorly differentiated carcinoma (one), sarcoma (four), and neuroendocrine carcinoma (one). The tumors were analyzed using fluorescence in situ hybridization using 12p spectrum green and 12 centromeric spectrum orange probes in paraffin sections. The patients ranged in age from 27 to 55 years (mean, 43). Colon and lung cancers from patients without germ cell tumors were used as controls. Adequate signals were observed in all tumors. Gain of chromosome 12p was seen in six tumors. None of the control tumors showed 12p amplification. Fluorescence in situ hybridization for 12p amplification in routinely processed surgical specimens is a useful adjuvant diagnostic tool in confirming the germ cell origin of metastatic tumors having the histologic appearance of somatic-type neoplasms.

Identical allelic losses in mature teratoma and other histologic components of malignant mixed germ cell tumors of the testis.

Teratomas of the testis in post-pubertal patients are histologically diverse tumors that often coexist with other types of germ cell tumors. Using laser capture microdissection and loss of heterozygosity analysis, we investigated the clonality of mature teratoma and its relationship to other components of malignant mixed germ cell tumors to gain potential insight into the histogenetic relationship of teratoma with other germ cell tumor components. All 16 patients had mature teratoma as one component of their mixed germ cell tumors. The other histological subtypes included immature teratoma, seminoma, embryonal carcinoma, yolk sac tumor, and choriocarcinoma. Laser-assisted microdissection was performed on the formalin-fixed, paraffin-embedded tissue. Polymerase chain reaction was used to amplify genomic DNA at specific loci on chromosome 1p36.2 (D1S508), 2q22-32 (D2S156), 9p21-22 (D9S162), 11p13 (D11S903), 12q22-23 (D12S1051), and 18q21 (D18S46). Fourteen of 16 (88%) cases showed allelic loss in one or more components of the mixed germ cell tumors. Fourteen of 16 mature teratomas showed allelic loss in at least one of six microsatellite polymorphic markers analyzed. The frequency of allelic loss in mature teratoma was 50% (7 of 14) with D1S508, 33% (5 of 15) with D2S156, 58% (7 of 12) with D9S162, 43% (6 of 14) with D11S903, 20% (3 of 15) with D12S1051, and 33% (5 of 15) with D18S46. Completely concordant allelic loss patterns between mature teratoma and all of the other germ cell tumor components were seen in 10 of 14 tumors in which mature teratoma showed loss of heterozygosity. Our data support the common clonal origin of mature teratoma with other components of malignant mixed germ cell tumors of the testis.