Somatic alterations in juvenile polyps from BMPR1A and SMAD4 mutation carriers.

Juvenile polyposis syndrome (JPS) is a rare autosomal dominant disorder predisposing to gastrointestinal hamartomatous polyps and cancer with a pathogenic SMAD4 or BMPR1A germline mutation (1st-hit) being identified in about 40-50% of patients. Little is known, however, about the occurrence and nature of somatic alterations (2nd-hit) in SMAD4-/BMPR1A-related juvenile polyps. In this study, we screened 25 polyps from three patients carrying either a pathogenic SMAD4 (c.1244-1247delACAG) or BMPR1A (c.583C>T; p.Gln195*) germline mutation for somatic alterations. The SMAD4-related polyps were also analyzed for SMAD4 protein expression by immunohistochemistry. Despite comprehensive screening for loss of heterozygosity (LOH), mutations in the coding sequence, chromosomal rearrangements, and promoter methylation, no somatic alterations could be identified in 14 SMAD4-related polyps. SMAD4 protein expression, however, was lost in 8 (57%) of 14 juvenile polyps with 6 showing concomitant loss in both, the epithelial and stromal, compartments. In the BMPR1A-related polyps, five out of nine (56%) displayed LOH. Further analysis of selected polyps revealed that LOH was gene copy number neutral and had occurred in the epithelial compartment. The heterogeneity of genetic mutations and protein expression levels indicates that different modes of gene inactivation can be operational in SMAD4- and BMPR1A-related polyp formation. Our observation, that about half of BMPR1A-related polyps displayed LOH, predominantly in the epithelial compartment, is compatible with BMPR1A acting as a tumour suppressor gene. Still, it remains to be determined whether juvenile polyp development generally requires loss of BMPR1A expression or, as observed in some SMAD4-related polyps, can occur despite normal protein expression.

Solid pseudopapillary neoplasm collides with a well-differentiated pancreatic endocrine neoplasm in an adult man: case report and review of histogenesis.

OBJECTIVES: Solid pseudopapillary neoplasm (SPN) of the pancreas is a rare, clinicopathologically distinct neoplasm with a tendency to affect young women. The histogenesis of SPN is not well defined. Pancreatic endocrine neoplasms (PENs) are also uncommon tumors of the pancreas. METHODS: Our comprehensive review of the literature did not yield any reported cases of collision tumors of the above two neoplasms. We report a case of such a collision tumor in a 45-year-old man. RESULTS: This tumor was an incidental finding on computed tomography, followed by fine-needle aspiration confirmation of a tumor that was initially diagnosed as an SPN only. A histologic examination of a 2.1-cm mass following distal pancreatectomy revealed a 0.7-cm PEN partly engulfed by an SPN. The tumors showed different morphologic and immunohistochemical features, confirming the presence of a collision tumor. CONCLUSIONS: A comparative analysis of immunoprofiles of these tumors yielded interesting findings, enabling us to postulate that SPNs may originate from a multipotential primordial cell that may follow different differentiation pathways, such as endocrine, epithelial, and acinar. The ultrastructures and immunophenotypic characteristics appear to support this hypothesis.

Screening methods for high-grade dysplasia in patients with anal condyloma.

UNLABELLED: Human papilloma virus (HPV) is one of the most common sexually transmitted diseases in the United States. HPV infection can cause anal condylomas and is a risk factor for dysplasia. High-grade dysplasia may progress to squamous cell carcinoma. Currently, biopsy and histological examination are required to grade dysplasia. The purpose of this study is to determine whether anal cytology, morphological characteristics, and/or the presence of high-risk oncogenic HPV-types are effective noninvasive methods to detect high-risk anal condylomas. PATIENTS AND METHODS: From November 2003 to June 2004, all patients with anal condyloma were prospectively evaluated for anal cytology, high-risk oncogenic HPV-types, and tissue biopsies. The Bethesda classification system was used to classify cytologic findings and histological examination, which were grouped as high-risk (HRL) and low-risk (LRL) lesions. Histology results served as true disease for all comparisons. RESULTS: Forty-seven patients with anal condyloma were studied; 43 (91.5%) were men, and the mean age was 39 +/- 11 years. Histology showed 19 (40.5%) patients with HRL, and 28 (59.5%) patients with LRL. Cytology correctly identified 8 patients with HRL and 27 patients with LRL (sensitivity 42% and specificity 96%). High-risk oncogenic HPV-types were found in 84.2% of HRL and 39.3% of LRL (P = 0.0029). Combining cytology with oncogenic HPV-testing, the sensitivity of detecting HRL increased to 89%, and specificity decreased to 42%. CONCLUSION: Anal cytology alone is not accurate for detecting HRL in patients with anal condylomas. Combining oncogenic HPV-testing with cytology is more sensitive in detecting HRL in patients with anal condyloma, and therefore, a more effective screening tool.

Split sample comparison of ThinPrep and conventional smears in endoscopic retrograde cholangiopancreatography-guided pancreatic fine-needle aspirations.

Fine-needle aspiration (FNA) of pancreatic lesions is a common procedure to establish a tissue diagnosis before chemotherapy or surgery. In this study, the authors attempt to compare the diagnostic value of the ThinPrep (TP) method with conventional smears (CSs) in samples obtained by endoscopic retrograde cholangiopancreatography (ERCP)-guided pancreatic FNAs. Material obtained, prospectively, from ERCP-guided pancreatic FNAs was split to prepare CSs (2-5 slides) first, the remainder being rinsed in PreservCyte, and in the laboratory, 1 TP slide was prepared. The diagnostic categories of unsatisfactory, benign, reactive, suspicious for malignancy, and malignant were compared. Fifty-one pancreatic FNAs prepared by split sample method yielded the following results: TP yielded unsatisfactory, 6 cases; benign, 3 cases; reactive, 5 cases; suspicious for malignancy, 11 cases; and malignant, 26 cases; in contrast, CS yielded unsatisfactory, 13 cases; benign, 4 cases; reactive, 3 cases; suspicious for malignancy, 13 cases; and malignant, 18 cases. Histological follow-up was available in 21 cases (reactive, 8 cases; suspicious for malignancy, 1 case, and malignant, 12 cases). The foregoing data indicate a higher sensitivity in detection of pancreatic adenocarcinoma by the TP method (TP, 91% vs. 58% CS) with equivalent specificity (100%). In addition, TP provides better preservation and cytological detail.