Dhungel, Bal M.

Common variable immunodeficiency (CVID) is associated with an increased risk of gastric cancer. The aim of the study was to determine the morphological features of CVID-associated gastric adenocarcinoma (CAGA) and of the background gastritis. The population of gastric cancer patients with CVID of Mayo Clinic in the period 2000-2010 was studied; 6 cases of CVID (2 males, 4 females, average age 47 years, age range 26-71 years) were found in 5793 patients with gastric cancer in the study period. Each patient underwent gastric resection for which histology slides were reviewed. Chronic gastritis variables, CVID-related findings, and features of the adenocarcinoma were recorded. CAGA was of intestinal type, with high number of intratumoral lymphocytes (ITLs). Cancer was diagnosed in younger patients than in the overall population of gastric cancer. Severe atrophic metaplastic pangastritis with extensive dysplasia was present in the background in 4 cases, with features of lymphocytic gastritis in 2 cases. Features of CVID (plasma cells paucity in 4 of 6 cases, lymphoid nodules prominent in four cases) could be detected. In summary, gastric adenocarcinoma at young age with ITLs, accompanied by atrophic metaplastic pangastritis, should alert the pathologist of the possibility of CAGA. It follows that, in presence of those characteristics, the search of CVID-associated abnormalities should be undertaken in the nonneoplastic tissues.

In keeping with the stated goal of providing the surgical pathologist with tools to recognize abnormalities of the gastrointestinal (GI) tract due to drugs (AGIDS), in part II of this review we embark in a more organ-based description of AGIDS. Adequate space is given to the numerous adverse gastrointestinal effects of nonsteroidal anti-inflammatory drugs. Pill esophagitis, esophagitis dissecans, proton pump inhibitors’ effects, diaphragm disease, and the recently described effects of drugs such as olmesartan, mycophenolate, and of compounds such as yttrium-90 are highlighted among several others. The inclusion of drug effects in the differential diagnosis of “conventional” diseases (such as gastric antral vascular ectasia, graft-versus-host disease, ischemic colitis, acute colitis, collagenous enteritis, inflammatory bowel disease) is underscored to avoid sometimes significant diagnostic pitfalls. We reiterate the message of the necessary collaboration between pathologist and clinician in the recognition of these entities to provide the best patient care.

Abnormalities of the gastrointestinal (GI) tract due to drugs (AGIDs) are numerous and have significant impact. The aim of this narrative review is to help the practicing surgical pathologist recognize selected AGIDs. The adverse drug effects presented were chosen with an emphasis on recent and significant pathological and clinical contributions. The selection was based on a thorough review of the PUBMED-based literature and on the authors’ opinions and experience. In the first part of the review, diagnostic abnormalities due to crystals (eg, iron, biphosphonates, nonsystemic drugs), mitosis arresting drugs (colchicine, taxanes), and biological agents, especially ipilimumab, are discussed. Some AGIDs’ histopathologic features can be easily recognized. It is however the clinical correlation that in many cases of AGIDs will provide the necessary support for a drug effect diagnosis. The identification of AGIDs requires heightened awareness of the medical team in which close collaboration of pathologists and clinicians cannot be overemphasized.

Inflammatory cap polyposis (ICP) is a rare nonneoplastic polyposis of the colon of unknown etiology that can be confused with prolapse-induced polyps and hyperplastic polyposis. We contribute a case of ICP from a 59-year-old woman who was affected by severe constipation and hematochezia. Numerous sessile and semipedunculated polyps were found in the colon, all with cap of whitish fibrin. Histology revealed erosion of the surface, superficial dilated crypts filled with mucoid inflammatory exudate, and minimal crypt serration, all findings typical of ICP. Only the largest polyps had smooth muscle in the mucosa. Ki-67 showed modest expansion and irregular distribution of the crypts proliferative areas. Low-degree positivity for p16, similar to that of hyperplastic polyps, was found. CK20 was expressed as in normal mucosa. Distinguishing between ICP and other polyposis is important because of difference in management.

A significant mimicker of malignancy in the esophagus is the presence of atypical/bizarre stromal cells (BSCs). Two patients, a 60-year-old woman and a 59-year-old man, with esophageal polyps at the gastroesophageal junction showed highly atypical/bizarre cells in the polyps’ stroma. BSCs were admixed with inflammatory cells and had large atypical nuclei, prominent nucleoli, and variably abundant amphophilic cytoplasm. Immunohistochemical studies showed that BSCs expressed vimentin whereas S-100, CD68, HMB45, CD45, Pan-cytokeratin, CK5/6, p63, CD10, EMA, MART-1, desmin, smooth muscle actin, CD31, CD34, and CMV were negative. Ki-67 showed low proliferative rate (less than 1% positivity). No evidence of intracellular mucin was found after histochemical stains (AB/PAS and mucicarmine). Follow-up endoscopic mucosal resection was available in both cases and showed benign esophageal mucosa and submucosa with disappearance, in one case, or marked decrease of BSCs. Esophageal BSCs reports in the literature invariably locate them in distal esophagus polyps or masses. Awareness of BSCs, of their location and associations, may help to prevent misdiagnosis of malignancy. The literature of esophageal BSCs is reviewed and the approach to this abnormality is discussed.