Dipti Mahajan

Grading of gastric foveolar-type dysplasia in Barrett's esophagus

Dysplasia is the gold standard biomarker of cancer risk in Barretts esophagus, but its diagnosis remains difficult. This is due in part to its multitude of histological appearances. One aspect receiving little attention concerns gastric-type Barretts dysplasia, which is distinctly different from the well-established intestinal variant. Recognition of gastric-type dysplasia and development of separate grading criteria are required. The prevalence, diagnostic criteria, and natural history of gastric-type Barretts dysplasia were systematically evaluated in 1854 endoscopic biopsies from a cohort of 200 consecutive Barretts dysplasia patients. Goblet cells were present in all cases, confirming the utility of this defining feature of Barretts esophagus. The prevalence of Barretts gastric-type dysplasia was 15% at the patient level (30 of 200 patients) and 20% at the biopsy level (166 of 852 dysplastic biopsies). Gastric-type dysplasia uniformly showed non-stratified, basally oriented nuclei as the major criterion for distinguishing it from intestinal-type Barretts dysplasia. As such, loss of nuclear polarity, as the most objective criterion to distinguish intestinal-type low- and high-grade dysplasia, cannot be applied to gastric-type dysplasia. Rather, discriminatory features included increased nuclear size with a high-grade dysplasia cutoff by receiver operating characteristic (ROC) analysis approximating 3–4 times the size of a mature lymphocyte, providing an optimal sensitivity, specificity, and area under the curve of 0.78, 0.90, and 0.90 (95% CI: (0.87, 0.93)), respectively. Crowded, irregular glandular architecture (P<0.001) was more common in high-grade lesions (P<0.001), as was eosinophilic and oncocytic cytoplasm relative to the mucinous cytoplasm (P<0.001), prominent nucleoli (P<0.001), mild nuclear pleomorphism (P<0.001), and villiform architecture (P<0.001). During follow-up, 64% (7 of 11) of patients with pure gastric and 26% (5 of 19) with mixed gastric and intestinal dysplasia underwent neoplastic progression. The recognition of Barretts gastric-type dysplasia and use of the proposed grading criteria should promote better diagnostic classification of the Barretts neoplastic spectrum.

Incidental reduction in the size of liver hemangioma following use of VEGF inhibitor bevacizumab

BACKGROUND/AIMS Hepatic cavernous hemangioma is the second most common liver tumor after metastases. Vascular endothelial growth factor (VEGF) is recognized as an essential regulator of blood vessel growth. High VEGF expression leads to increased angiogenic activity in cavernous hemangioma endothelial cells. The use of specific antibodies directed against VEGF abolishes this vascular endothelial growth-promoting activity in vitro. Bevacizumab is a recombinant humanized monoclonal antibody directed against VEGF which is used for the treatment of metastatic colorectal cancer in combination with 5-fluorouracil-based regimens. METHODS We report a patient with invasive colorectal adenocarcinoma and suspected liver metastasis on radiological examination, who showed a significant decrease in the size of his liver lesions after bevacizumab treatment. Histology of the liver lesions revealed hemangioma with a strong staining for VEGF and anti-VEGFr2 antibody in the hemangioma endothelial cells. To date, surgical resection provides the only consistently effective method for treatment of hepatic hemangioma. CONCLUSIONS This is the first documented case of hepatic hemangioma responsive to antiangiogenic therapy, suggesting a possible use for these agents in treating symptomatic patients without surgery. VEGF-signaling blockade including bevacizumab use poses a potential new treatment modality for vascular neoplasms in the liver and other sites.

Lymphocytic colitis and collagenous colitis: a review of clinicopathologic features and immunologic abnormalities.

Lymphocytic colitis (LC) and collagenous colitis (CC), 2 histologic forms of microscopic colitis, were recognized as rare disease entities 4 decades ago. An increasing body of evidence accumulated in the past 40 years reveals increasing incidence and prevalence rates, a wide spectrum of clinical presentations, and several histologic variants. Although several recent randomized clinical trials confirmed the efficacy of oral budesonide in treating LC and CC, disease relapse after a short-duration treatment is common. Despite their common clinical presentations and well-defined histologic diagnostic criteria, there are only few studies on the immunologic abnormalities in colonic tissue. The aim of this review is to (1) familiarize the pathologists in general practice with histomorphology of LC and CC, including the rare histologic variants and the clinical implication associated with these 2 diagnoses, (2) summarize the data from recent randomized clinical trials of oral budesonide, and (3) review immunological studies on colonic tissue. Overall, immunologic abnormalities of colonic tissue seem to explain for the histomorphologic features and the clinical symptomatology of LC and CC. Advances in the understanding of the underlying immunologic abnormalities in the colonic tissue may help develop novel and effective therapies for these 2 diseases.

Acral Soft Tissue Tumors: A Review

Acral soft tissue tumors may present significant diagnostic challenges both for the pathologist and the clinician. This review discusses the most common benign and malignant entities that characteristically present in an acral location. Clinical, histologic, and immunohistochemical features are discussed along with prognosis and differential diagnosis.

Reproducibility of the villous component and high-grade dysplasia in colorectal adenomas <1 cm: implications for endoscopic surveillance.

The presence of high-grade dysplasia (HGD) or villous component (VC) defines an advanced adenoma (AA) in patients with 1 or 2 adenomas <1 cm in size. Current consensus guidelines recommend that patients with AA undergo more intense postpolypectomy surveillance. In these clinical situations, the interobserver reliability in determining VC and HGD would play a major role in the credibility of these consensus guidelines. Therefore, the purpose of this study was to evaluate interobserver variability of VC and HGD in polyps <1 cm before and after the development of consensus criteria among gastrointestinal (GI) pathologists. Five GI pathologists independently evaluated 107 colorectal adenomas <1 cm, and classified them into tubular adenomas or adenomas with a VC (A-VC) and into low-grade dysplasia or HGD. Then a consensus conference was held and consensus criteria for VC and HGD were developed by group review. The same set of 107 slides were rereviewed independently by the same 5 GI pathologists. Interobserver variability using &kgr; statistical analysis before and after the application of consensus criteria was assessed. A 1-sided z-test was used to determine whether &kgr; scores increased after the consensus conference. Interobserver agreement before and after the consensus conference was poor for assessment of A-VC, HGD, and AA. These data calls into question the validity of basing clinical decisions on this distinction.

Repeated Molecular Testing in Gliomas A Retrospective Study of 53 Cases

The value of repeated molecular testing in patients with multiple resections of gliomas is unclear. The purpose of this study was to assess for evidence of molecular changes for chromosome 1p/19q deletions and epidermal growth factor receptor (EGFR) amplification by fluorescence in situ hybridization in 53 glioma cases in which repeated testing was done. Paired results for 1p evaluation demonstrated a change in the profile from intact to loss in 1 (2%) of 50 cases; 19q evaluation demonstrated a change in profile in 4 (10%) of 41 cases. There was no change in the EGFR expression in any of the cases tested. There was no change in the clinical management based on the repeated molecular tests in patients with discrepant repeated results. Hence, there seems to be no indication for reflex repeated 1p/19q or EGFR testing in gliomas at the time of repeated biopsy or resection.

Repeated Molecular Testing in Gliomas

The value of repeated molecular testing in patients with multiple resections of gliomas is unclear. The purpose of this study was to assess for evidence of molecular changes for chromosome 1p/19q deletions and epidermal growth factor receptor (EGFR) amplification by fluorescence in situ hybridization in 53 glioma cases in which repeated testing was done. Paired results for 1p evaluation demonstrated a change in the profile from intact to loss in 1 (2%) of 50 cases; 19q evaluation demonstrated a change in profile in 4 (10%) of 41 cases. There was no change in the EGFR expression in any of the cases tested. There was no change in the clinical management based on the repeated molecular tests in patients with discrepant repeated results. Hence, there seems to be no indication for reflex repeated 1p/19q or EGFR testing in gliomas at the time of repeated biopsy or resection.

Repeated Molecular Testing in GliomasA Retrospective Study of 53 Cases

The value of repeated molecular testing in patients with multiple resections of gliomas is unclear. The purpose of this study was to assess for evidence of molecular changes for chromosome 1p/19q deletions and epidermal growth factor receptor (EGFR) amplification by fluorescence in situ hybridization in 53 glioma cases in which repeated testing was done. Paired results for 1p evaluation demonstrated a change in the profile from intact to loss in 1 (2%) of 50 cases; 19q evaluation demonstrated a change in profile in 4 (10%) of 41 cases. There was no change in the EGFR expression in any of the cases tested. There was no change in the clinical management based on the repeated molecular tests in patients with discrepant repeated results. Hence, there seems to be no indication for reflex repeated 1p/19q or EGFR testing in gliomas at the time of repeated biopsy or resection.