Colorectal cancer anatomic distribution patterns remain the same after sessile serrated adenoma/polyp considered cancer precursor: a 9-year comparison study from community-based endoscopy centers.

BACKGROUND: The overall incidence of colorectal cancer (CRC) in the United States has steadily decreased. However, the incidence of right-sided CRC remains unchanged for the past two decades. The serrated neoplastic pathway (sessile serrated adenoma/polyp, SSA/P) has been considered an important pathway of colorectal carcinogenesis, especially in the right-sided CRC. The aim of this study was to compare CRC anatomic distribution patterns in a 9-year interval in the general population before and after SSA/P was recognized and treated as a CRC precursor. METHODS: The Miraca Life Sciences (MLS) pathology database was queried for all primary CRCs diagnosed between 8/3/2000 to 12/31/2005 (control group) and 1/1/2014 to 12/31/2014 (current group). Patients' demographics, clinical information, and pathology reports were collected and analyzed. RESULTS: A total of 5,602 patients with 5,685 CRCs were identified, of which 2,728 patients with 2,765 CRCs in current group and 2,874 patients with 2,920 CRCs in control group. Overall, there were no statistical differences in the current group in regards to the anatomical distribution patterns of CRCs in the proximal, right-sided, distal, and left-sided colon or genders compared with the control group (all P>0.05). Among the current group, there were 33 (1.2%) patients with 38 (1.4%) CRCs arising in SSA/Ps [serrated carcinomas (SCAs)], of which 33 (86.8%) were in the right-sided colon and 5 (13.2%) in the left-sided colon. Twenty-three (69.7%) SCA patients were female with significant advanced age than male (76.4 vs. 69.6, P=0.023). CONCLUSIONS: The overall current CRC anatomic distribution patterns after SSA/Ps managed as CRC precursor remain the same in the patients' population from the community-based endoscopy centers in the U.S. It is suggested that the current SSA/P management might need to be further modified.

Gene signature distinguishes patients with chronic ulcerative colitis harboring remote neoplastic lesions.

BACKGROUND: Individuals with ulcerative colitis (UC) are at increased risk for colorectal cancer. The standard method of surveillance for neoplasia in UC by colonoscopy is invasive and can miss flat lesions. We sought to identify a gene expression signature in nondysplastic mucosa without active inflammation that could serve as a marker for remote neoplastic lesions. METHODS: Gene expression was analyzed by complementary DNA microarray in 5 normal controls, 4 UC patients without dysplasia, and 11 UC patients harboring remote neoplasia. Common gene ontology pathways of significantly differentially expressed genes were identified. Expression of genes which were progressively and significantly upregulated from controls to UC without neoplasia, to UC with remote neoplasia were evaluated by real-time polymerase chain reaction. Several gene products were also examined by immunohistochemistry. RESULTS: Four hundred and sixty-eight genes were significantly upregulated, and 541 genes were significantly downregulated in UC patients with neoplasia compared with UC patients without neoplasia. Nine genes (ACSL1, BIRC3, CLC, CREM, ELTD1, FGG, S100A9, THBD, and TPD52L1) were progressively and significantly upregulated from controls to nondysplastic UC to UC with neoplasia. Immunostaining of proteins revealed increased expression of S100A9 and REG1α in UC-associated cancer and in nondysplastic tissue from UC patients harboring remote neoplasia compared with UC patients without neoplasia and controls. CONCLUSIONS: Gene expression changes occurring as a field effect in the distal colon of patients with chronic UC identify patients harboring remote neoplastic lesions. These markers may lead to a more accurate and less invasive method of detection of neoplasia in patients with inflammatory bowel disease.

Serrated adenoma: a distinct form of non-polypoid colorectal neoplasia?

Until recently, 2 major forms of colorectal polyp were recognized: the adenoma and the hyperplastic polyp. Adenomas were known to represent a precursor to colorectal cancer, whereas hyperplastic polyps were viewed as nonneoplastic, having no potential for progression to malignancy. We now recognize, however, that the lesions diagnosed as hyperplastic polyps in the past represent a heterogeneous group of polyps, some of which truly are hyperplastic, and others that truly have a significant risk for transformation to colorectal cancer. These polyps have a characteristic serrated architecture, and include not only hyperplastic polyps but also the recently recognized serrated adenomas. Serrated adenomas occur in 2 forms: the traditional serrated adenoma, which is usually a polypoid lesion endoscopically, and the sessile serrated adenoma, a flat or slightly raised, usually right-sided lesion. Serrated adenomas of both types show characteristic molecular alterations not commonly seen in traditional colorectal adenomas, and probably progress to colorectal cancer by means of a different pathway, the so-called serrated neoplasia pathway. The morphologic features of serrated colorectal lesions, the molecular alterations that characterize them, and their role in colorectal cancer development are discussed.

Sessile serrated adenomas strongly predispose to synchronous serrated polyps in non-syndromic patients.

AIMS: To determine the prevalence of various colonic polyps removed during a recent 8-month period; to determine the interobserver agreement in the diagnosis of serrated polyps; and to determine if harbouring a sessile serrated adenoma (SSA) predisposes to the presence of synchronous polyps with similar histology. METHODS AND RESULTS: All polyps resected during an 8-month period at a single tertiary medical centre were analysed. We also analysed all polyps in patients with an SSA or SSA with dysplasia since 2003. SSAs accounted for 4.3% of colonic polyps removed during an 8-month period. A review of 276 serrated polyps by two pathologists revealed good interobserver agreement (kappa = 0.66). Patients with one SSA were more likely to harbour additional serrated polyps. After removal of the index SSA, 18% of their remaining polyps were SSAs, SSAs with dysplasia, and traditional serrated adenomas, contrasting with the approximately 5% prevalence of these polyps in the control population. The hyperplastic polyps in the study population were also twice as likely to occur proximal to the splenic flexure. CONCLUSIONS: These data indicate that there is a strong colonic mucosal field defect in patients with sporadic SSAs that predispose them to develop additional serrated polyps.

Drug-induced Injury of the Gastrointestinal Tract.

The effects of drugs on the gastrointestinal tract are diverse and depend on numerous factors. Diagnosis is centered on histologic findings, with mostly nonspecific patterns of injury that must be interpreted in the correct clinical context. Nonsteroidal antiinflammatory drugs are a common cause of drug-induced gastrointestinal injury, with effects primarily in the gastric mucosa but also throughout the gastrointestinal tract. Another common class of drugs causing a variety of pathologic findings in the gut is chemotherapeutic agents. This article discusses the differential diagnosis of the various patterns of injury, including ischemic damage, and the histologic findings specific for certain drugs.

Update on esophagitis: controversial and underdiagnosed causes.

CONTEXT: Esophagitis is a common cause of symptoms for which patients seek the advice of a physician. Esophagitis of differing etiologies often demonstrate overlapping histopathologic features, making their distinction difficult. This is especially true in esophageal disorders associated with increased numbers of intraepithelial eosinophils, some of which have just recently been recognized. OBJECTIVE: This review discusses the important clinical and pathologic features of the 2 most common disorders associated with esophageal eosinophilic infiltrates--reflux esophagitis and eosinophilic esophagitis--with special emphasis on features that allow the surgical pathologist to distinguish between these disorders. The various forms of drug-induced esophagitis are also discussed because these are frequently underrecognized by pathologists. DATA SOURCES: Data were extracted from articles identified through PubMed-based research. Histologic figures have been taken from the personal case collection of the author. CONCLUSIONS: Reflux and eosinophilic esophagitis demonstrate overlapping histologic features, which may make their distinction difficult. Drug-induced esophagitis is probably a common phenomenon but is underrecognized by pathologists.

Serrated polyps and colorectal cancer: new pathway to malignancy.

Until recently, two major forms of colorectal epithelial polyp were recognized: the adenoma and the hyperplastic polyp. Adenomas were perceived to represent the precursor to colorectal cancer, whereas hyperplastic polyps were viewed as innocuous lesions with no potential for progression to malignancy. We now recognize, however, that the lesions formerly classified as hyperplastic actually represent a heterogeneous group of polyps, some of which have a significant risk for neoplastic transformation. These serrated polyps include not only hyperplastic polyps but also traditional serrated adenomas and sessile serrated adenomas. These polyps demonstrate characteristic molecular alterations not commonly seen in colorectal adenomas, and they probably progress to colorectal cancer by means of a new pathway: the serrated neoplasia pathway. The morphologic features of serrated colorectal lesions, the molecular alterations that characterize them, and their role in colorectal cancer development are discussed herein.

Prostate-specific membrane antigen expression in regeneration and repair.

Prostate-specific membrane antigen is a type II transmembrane glycoprotein, expressed in benign and neoplastic prostatic tissue as well as endothelial cells of neovasculature from a variety of tumors. The expression of prostate-specific membrane antigen in nonneoplastic neovasculature has not been well studied. Therefore, we studied nonneoplastic reparative and regenerative human tissues, as well as preneoplastic tissue, to determine the presence of prostate-specific membrane antigen-expressing neovasculature. Formalin-fixed paraffin-embedded tissue from keloids, granulation tissue from heart valves and pleura, proliferative and secretory endometrium, and Barrett's mucosa with and without dysplasia were stained for the expression of prostate-specific membrane antigen (3E6). Vessels of proliferative, mid-secretory, and late secretory endometrium were consistently strongly positive for prostate-specific membrane antigen expression in all ten cases of each type (100%). Vessels associated with granulation tissue from pleural peels and heart valves were positive in 10 of 12 cases (83%) and 7 of 10 cases (70%), respectively. Keloids had prostate-specific membrane antigen-expressing endothelial cells in 6 of 15 cases (40%). Prostate-specific membrane antigen was not expressed by vessels associated with Barrett's mucosa with low-grade dysplasia (12 foci), high-grade dysplasia (24 foci), or no dysplasia (18 foci). A variety of nonneoplastic neovasculature expresses prostate-specific membrane antigen, including vessels in proliferative endometrium, granulation tissue, and some scars. This is the first study showing that prostate-specific membrane antigen is expressed in neovasculature from physiologic regenerative and reparative conditions. The folate hydrolase activity of prostate-specific membrane antigen may facilitate vasculogenesis and angiogenesis by increasing local availability of folic acid. These findings will enhance our overall understanding of blood vessel development and will enable us to better understand the effects of anti-prostate-specific membrane antigen therapies, which are already being explored in clinical trials.

Immunohistochemical screening of mismatch repair genes hMLH1, hMSH2, and hMSH6 in dysplastic lesions of the colon.

Immunohistochemical decrease in staining for mismatch repair proteins may be seen in either microsatellite instability or inactivation (methylation) of mismatch repair proteins. Both are features of the malignant phenotype in a range of colorectal neoplasms. Expression of mismatch repair proteins in dysplastic lesions in ulcerative colitis (UC) has not been studied extensively. The authors analyzed protein expression of hMLH1, hMSH2, and hMSH6 in 18 cases of dysplasia-associated lesion or mass (DALM) in patients with UC and 10 sporadic adenomas. Immunohistochemical studies revealed adequate staining in almost all of the cases. A significant decrease in protein expression was seen in 2 DALM and 2 sporadic adenomas. The authors conclude that immunohistochemical studies of mismatch repair proteins can be applied to dysplastic lesions in UC with adequate staining results. Decreased wild type expression of hMLH1, hMSH2, and hMSH6 is not a feature of DALM in the setting of UC.