This review summarizes our current understanding of lymphocytic esophagitis (LE), a novel form of chronic esophagitis that incorporates distinctive histologic, clinical, and endoscopic features. ...First described as a histologic entity, a diagnosis of LE requires intraepithelial lymphocytosis without significant granulocytic inflammation and some evidence of epithelial damage; the rationale for and studies supportive of these histologic criteria are discussed within. Clinically, the majority of patients who present with histologically confirmed LE are older women or patients with underlying immunologic abnormalities, such as Crohn disease, rheumatologic disorders, or common variable immunodeficiency. The most common presenting symptom of LE is dysphagia, and the endoscopic findings can vary from normal mucosa to mucosal changes that resemble eosinophilic esophagitis: edema, rings, furrows, and plaques. The incidence of luminal strictures and the persistent dysphagia and/or lymphocytosis present in some patients provide evidence that LE is a chronic inflammatory disorder, at least within a subset of individuals. Several histologic mimics of LE are examined, as are disagreements surrounding the LE diagnosis.
Most cancers in humans are large, measuring centimetres in diameter, and composed of many billions of cells. An equivalent mass of normal cells would be highly heterogeneous as a result of the ...mutations that occur during each cell division. What is remarkable about cancers is that virtually every neoplastic cell within a large tumour often contains the same core set of genetic alterations, with heterogeneity confined to mutations that emerge late during tumour growth. How such alterations expand within the spatially constrained three-dimensional architecture of a tumour, and come to dominate a large, pre-existing lesion, has been unclear. Here we describe a model for tumour evolution that shows how short-range dispersal and cell turnover can account for rapid cell mixing inside the tumour. We show that even a small selective advantage of a single cell within a large tumour allows the descendants of that cell to replace the precursor mass in a clinically relevant time frame. We also demonstrate that the same mechanisms can be responsible for the rapid onset of resistance to chemotherapy. Our model not only provides insights into spatial and temporal aspects of tumour growth, but also suggests that targeting short-range cellular migratory activity could have marked effects on tumour growth rates.
Colorectal carcinoma screening programs have shown success in lowering both the incidence and mortality rate of colorectal carcinoma at a population level, in part because this carcinoma is ...relatively slow growing and has an identifiable premalignant lesion. Still, many patients do not undergo the recommended screening for colorectal carcinoma, and of those who do, a subset may be over- or under-diagnosed by the currently available testing methods. The primary purpose of this article is to review the data regarding currently available colorectal cancer screening modalities, which include fecal occult blood testing, direct colonic visualization, and noninvasive imaging techniques. In addition, readers will be introduced to a variety of biomarkers that may serve as stand-alone or adjunct tests in the future. Finally, there is a brief discussion of the current epidemiologic considerations that public health officials must address as they create population screening guidelines. The data we provide as laboratory physicians and scientists are critical to the construction of appropriate recommendations that ultimately decrease the burden of disease from colorectal carcinoma.
- Invasive pancreatic ductal adenocarcinoma has a greater than 90% mortality rate at 5 years. Understanding noninvasive, curable precursor lesions gives us the best hope for reducing mortality from ...pancreatic ductal adenocarcinoma. The 3 pancreatic precursor lesions that have been well studied include intraductal papillary mucinous neoplasm, mucinous cystic neoplasm, and pancreatic intraepithelial neoplasia.
- To give an update on the latest clinical, molecular, and pathologic advances in intraductal papillary mucinous neoplasm, mucinous cystic neoplasm, and pancreatic intraepithelial neoplasia for the general surgical pathologist.
- The current literature was analyzed and the authors' experiences with institutional and consult material were incorporated.
- Our understanding of the molecular alterations that lead from pancreatic precursor lesion to invasive carcinoma continues to evolve. These advances aid clinicians in their treatment decisions and researchers in their search for actionable, druggable targets.
Lymphocytic esophagitis is a well-known manifestation of Crohn disease among children but is not considered to be an immune-mediated mucositis in adults. We hypothesize that adult-onset ...lymphocyte-predominant esophagitis is also an immune-mediated inflammatory pattern, the nature of which has been masked by other conditions that feature esophageal lymphocytosis and occur in older patients. We performed this study to consolidate diagnostic criteria for lymphocyte-predominant esophagitis and determine its clinical significance. We identified 61 patients with lymphocyte-rich inflammation in the mid or proximal esophagus, none of whom had another explanation for esophageal lymphocytosis. Affected patients were usually older adults and 72% were women. Most (56%) presented with dysphagia and 34% had eosinophilic esophagitis-like changes with rings, exudates, and/or edematous mucosa and linear furrows. Intraepithelial lymphocytosis was accompanied by mucosal injury featuring edema, basal zone hyperplasia, and scattered dyskeratotic cells. Some cases displayed occasional neutrophils or even superficial microabscesses; eosinophils were consistently infrequent. Most (67%) patients had at least 1 systemic immune-mediated disorder, particularly Crohn disease (30%) and connective tissue diseases (23%); only 1 had mucocutaneous lichen planus. We conclude that mild mucosal lymphocytosis (ie, ≥20 lymphocytes/HPF) alone is a frequent and nonspecific finding; criteria for lymphocyte-predominant esophagitis should include evidence of mucosal injury and allow for more than the occasional neutrophil. When this diagnosis is limited to cases that feature lymphocytosis unattributed to acid reflux, motility disorders, or infection, lymphocyte-predominant esophagitis may represent an immune-mediated disorder with characteristic clinical manifestations and a predilection for middle-aged women.
Background & Aims A long duration of inflammatory bowel disease (IBD) increases the risk for colorectal cancer. Mutation analysis of limited numbers of genes has indicated that colorectal tumors that ...develop in patients with IBD differ from those of patients without IBD. We performed whole-exome sequencing analyses to characterize the genetic landscape of these tumors. Methods We collected colorectal tumor and non-neoplastic tissues from 31 patients with IBD and colorectal cancer (15 with ulcerative colitis, 14 with Crohn’s disease, and 2 with indeterminate colitis) and performed whole-exome sequencing analyses of the microdissected tumor and matched nontumor tissues. We identified somatic alterations by comparing matched specimens. The prevalence of mutations in sporadic colorectal tumors was obtained from previously published exome-sequencing studies. Results Two specimens had somatic mutations in the DNA proofreading or mismatch repair genes POLE , MLH1 , and MSH6 and the tumor cells had a hypermutable phenotype. The remaining tumors had, on average, 71 alterations per sample. TP53 was the most commonly mutated gene, with prevalence similar to that of sporadic colorectal tumors (63% of cases). However, tumors from the patients with IBD had a different mutation spectrum. APC and KRAS were mutated at significantly lower rates in tumors from patients with IBD than in sporadic colorectal tumors (13% and 20% of cases, respectively). Several genes were mutated more frequently or uniquely in tumors from patients with IBD, including SOX9 and EP300 (which encode proteins in the WNT pathway), NRG1 (which encodes an ERBB ligand), and IL16 (which encodes a cytokine). Our study also revealed recurrent mutations in components of the Rho and Rac GTPase network, indicating a role for noncanonical WNT signaling in development of colorectal tumors in patients with IBD. Conclusions Colorectal tumors that develop in patients with IBD have distinct genetic features from sporadic colorectal tumors. These findings could be used to develop disease-specific markers for diagnosis and treatment of patients with IBD and colorectal cancer.
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