Lysandra Voltaggio

Sevelamer crystals in the gastrointestinal tract (GIT): A new entity associated with mucosal injury

We report the first description of sevelamer crystals (Renagel and Renvela, Genzyme; phosphate-lowering agents) in the gastrointestinal tract. We prospectively collected cases with novel, histologically identical crystals from 4 major academic centers over a 1-year period and studied pertinent clinicopathologic features. Sevelamer usage in the setting of chronic kidney disease was demonstrated in all cases (n=15 total cases, 7 patients). Sites of involvement included the esophagus (n=2), small bowel (n=2), and colon (n=11). The background mucosa was normal in only 1 case. Notable mucosal abnormality included chronic mucosal damage (n=5), acute inflammation (n=4), inflammatory polyp (n=2), extensive ulceration (n=2), ischemia (n=1), and necrosis (n=1). In general, sevelamer crystals displayed broad, curved, and irregularly spaced “fish scales” with a variably eosinophilic to rusty brown color on hematoxylin and eosin (H&E) staining and violet color on periodic acid-Schiff-alcian special staining with diastase (PAS/D). To validate these findings, sevelamer tablets (Renvela) were crushed and submitted for histologic processing; the findings were identical to those in the patient specimens. The possibility of Kayexalate (sodium polystyrene sulfonate) and cholestyramine had been raised in error. However, Kayexalate has narrow, rectangular “fish scales” and is violet on H&E and magenta on PAS/D; cholestyramine lacks internal “fish scales,” is bright orange on H&E, variably gray or hot pink on PAS/D, and is unassociated with mucosal injury. Further study is required to determine whether sevelamer plays a causal role in these injuries; however, its crystal is an important mimic of both Kayexalate and choleystyramine. As the history of sevelamer administration was not documented in any pathology requisition, awareness of sevelamer’s characteristic morphology is crucial to avoid the diagnostic pitfalls of its mimics.

Syphilitic and lymphogranuloma venereum (LGV) proctocolitis: clues to a frequently missed diagnosis.

A rising incidence of syphilis and lymphogranuloma venereum (LGV) underscores the importance of recognizing these sexually transmitted infections (STI) in routine anocolonic biopsies. To increase awareness of their morphologic manifestations, we undertook a clinicopathologic study of our experience: syphilis (7 patients, 7 specimens), LGV (2 patients, 4 specimens), and syphilis/LGV (1 patient, 3 specimens). The diagnoses of all study specimens were confirmed with pertinent clinical studies. All study patients were human immunodeficiency virus positive, and all 9 with available history were men who have sex with men. The majority presented with bleeding (9), pain (6), and tenesmus (4). Ulcerations were the most common endoscopic abnormality (7), whereas mass lesions were confined to the syphilis group (4). None of the initial impressions included LGV, and syphilis was prospectively suggested only by pathologists (6 of 8) without the knowledge of clinical information and on the basis of morphology. Alternative impressions included condyloma acuminatum (3), inflammatory bowel disease (3), and malignancy (2), among others. All study specimens shared the following histologic core features: an intense lymphohistiocytic infiltrate with prominent plasma cells and lymphoid aggregates, only mild to moderate acute inflammation, minimal basal plasmacytosis and crypt distortion, and only rare granulomas and Paneth cell metaplasia. The spirochetes were focally demonstrated on a Treponema pallidum immunohistochemical stain (1) but not on silver stains (3). All patients with available follow-up data showed resolution of symptoms and imaging abnormalities after STI therapy (6). In summary, we report a unique pattern of STI proctocolitis consistently identified in patients with serologically confirmed syphilis and/or LGV infection; pertinent STI therapy leads to resolution of clinical abnormalities. This histologic pattern is important to recognize for timely treatment, for prevention of onward STI transmission, and to avoid the diagnostic pitfalls of inflammatory bowel disease or malignancy.

A clinical and histopathologic focus on Barrett esophagus and Barrett-related dysplasia.

CONTEXT Barrett esophagus is a metaplastic, premalignant lesion associated with approximately 0.5% annual incidence of progression to esophageal adenocarcinoma. Diagnosis and screening of Barrett esophagus and Barrett-related dysplasia relies on histologic evaluation of endoscopic mucosal biopsies, a process that is burdened with interobserver variability. OBJECTIVES To review the histologic features and classification of Barrett esophagus and Barrett-related dysplasia, to discuss the underlying difficulties in diagnosis and pitfalls, and to provide a brief review of new developments related to therapeutic modalities for patients diagnosed with dysplasia. DATA SOURCES Sources include a review of relevant literature indexed in PubMed (US National Library of Medicine). CONCLUSIONS In spite of interobserver variability, histologic assessment of dysplasia is currently the accepted method of surveillance, and subsequent patient management is dictated by this evaluation. Although not universal, endoscopic therapy is increasingly important in replacing esophagectomy for patients with high-grade dysplasia or early carcinoma.

Celiac disease: clinical, endoscopic, and histopathologic review

Celiac disease, also known as celiac sprue, nontropical sprue, and gluten-sensitive enteropathy, is a chronic immune-mediated disorder that occurs in genetically predisposed populations. Patients affected by the disease may be asymptomatic or manifest classic malabsorption symptoms of abdominal pain, bloating, weight loss, diarrhea, and steatorrhea after gluten ingestion (and related derivatives found in other grains). The astute clinician must be aware of a more subtle GI picture as well as non-GI signs and symptoms (eg, iron-deficiency anemia, abnormal liver function tests, type 1 diabetes mellitus, and gluten ataxia). Diagnosis and screening begin with the use of serologic tests: IgA anti-tissue transglutaminase (tTG), IgA antiendomysial antibodies (EMAs), and serum IgA level. Duodenal biopsy, still considered by many as the criterion necessary for diagnosis, demonstrates the pathologic findings of small intestinal villous atrophy, intraepithelial lymphocytosis, and crypt hyperplasia that occur on exposure to dietary gluten. These changes exhibit improvement after withdrawal of gluten from the diet. Resolution of clinical symptoms after initiation of gluten-free diet is considered to be part of the diagnostic picture. Genetic tests revealing permissive haplotypes may be helpful in confirming the diagnosis as well as identifying susceptible individuals. Celiac disease remains a complex clinicopathologic diagnosis. This review discusses the clinical, endoscopic, and pathologic features of celiac disease, with an emphasis on the importance of clinician and pathologist communication.

Message in a bottle: decoding medication injury patterns in the gastrointestinal tract

Medication injury in the gastrointestinal tract (GIT) is a rapidly evolving topic. Increasing endoscopy together with an ageing population, polypharmacy, and a burgeoning drug industry offer heightened opportunities to observe the unintended side effects of therapeutic ingestants. In this review, we emphasise the most commonly encountered medication injuries involving the GIT, as well as emerging agents and mimics. While topics are organised by organ system, the reader should keep in mind that injury patterns are generally not site-specific. As such, awareness of these major morphologic patterns can be translated to multiple tissue sites to more broadly facilitate the diagnostic process.

Medication-associated lesions of the GI tract

At a Harben Lecture in London in 1908, German scientist Paul Ehrlich described the ideal drug as a “magic bullet” (Zauberkugel). Such a drug would be aimed precisely at a disease site and would not affect healthy tissues. Today, over 3.5 billion prescriptions are dispensed each year in the United States to manage a broad number of health disorders. Although many drugs are aimed more accurately than their predecessors, none of them, as of yet, hit their targets exclusively. Several medications are associated with an increasing incidence of drug-induced (iatrogenic) adverse events, a frequent site of which is the GI tract. In fact, 10% of the drug-induced adverse effects are related to the GI tract. The consequences of such can range from asymptomatic histologic changes in the GI mucosa to fatal adverse events. In some instances, the adverse events are worse than the illness for which the drug was prescribed. However, many drug-induced adverse events are preventable. Therefore, it is becoming increasingly important to recognize both the clinical and pathologic manifestations of GI tract drug-induced injury early, so that the offending drug can be discontinued or replaced. This review uses an organ-based approach to present both clinical information and pathologic findings to increase clinical awareness of the most common druginduced GI conditions. Although each part of the GI tract has been considered separately, some drugs exert a

Gastrointestinal tract spindle cell lesions—just like real estate, it’s all about location

Interpretation of gastrointestinal tract mesenchymal lesions is simplified merely by knowing in which anatomic layer they are usually found. For example, Kaposi sarcoma is detected on mucosal biopsies, whereas inflammatory fibroid polyp is nearly always in the submucosa. Gastrointestinal stromal tumors (GISTs) are generally centered in the muscularis propria. Schwannomas are essentially always in the muscularis propria. Mesenteric lesions are usually found in the small bowel mesentery. Knowledge of the favored layer is even most important in interpreting colon biopsies, as many mesenschymal polyps are encountered in the colon. Although GISTs are among the most common mesenchymal lesions, we will concentrate our discussion on other mesenchymal lesions, some of which are in the differential diagnosis of GIST, and point out some diagnostic pitfalls, particularly in immunolabeling.

Sex, lies, and gastrointestinal tract biopsies: A review of selected sexually transmitted proctocolitides

There are many insults that result in gastrointestinal tract inflammation. Infections can be particularly challenging because (1) only a limited number of organisms provoke a specific endoscopic and/or histologic appearance; and (2) although some organisms may be present on biopsies, the findings may be so subtle or organisms so few that they are easily missed if the reviewer is not performing a specific search for the offender. Sexually transmitted infections (STI) are rarely a consideration at the time of GI biopsy examination and clinicians rarely inquire about sexual behavior at the time of initial patient interview. Although establishing a definitive STI diagnosis is not possible on histology alone, these infections are associated with inflammatory patterns that may help raise this diagnostic possibility. Becoming familiar with these patterns is necessary as worldwide outbreaks of these infections are being reported. This review aims to provide the pathologist with histologic clues associated with the most frequently encountered bacterial pathogens in the setting of STI proctitis, namely, Chlamydia trachomatis, Neisseria gonorrhoeae, and Treponema pallidum.

Autoimmune Metaplastic Atrophic Gastritis: Recognizing Precursor Lesions for Appropriate Patient Evaluation.

Autoimmune metaplastic atrophic gastritis (AMAG) is a significant risk factor for pernicious anemia and gastric neoplasia. Still, the histologic features of AMAG are frequently overlooked, especially in the early stages of the disease. The purpose of our study, therefore, was to catalogue the progression of histologic changes that precede the development of AMAG in affected individuals. Over a 2-year period (2012 to 2014), the diagnosis of AMAG was rendered on material from 113 patients seen at Johns Hopkins Hospital (∼1.8% of “in house” gastric biopsies). Prior gastric body biopsies had been performed on 54 (48%) patients in the cohort, and the majority of these specimens had also shown AMAG. Eighteen of the previous biopsies, however, carried a diagnosis other than AMAG: 13 inactive chronic gastritis, 2 acute Helicobacter pylori gastritis, and 1 each of eosinophilic gastritis, iron pill gastritis, and proton-pump inhibitor–like effect. Upon review of these 18 biopsies, the most common histologic findings were heavy full-thickness or deep lamina propria chronic inflammation (12), inflammatory destruction of oxyntic glands (12), metaplasia (intestinal, pyloric, or pancreatic acinar) (10), prominent lamina propria eosinophils (8), and parietal cell pseudohypertrophy (4). At least 2 of these features were present in the majority (13, 72%) of the biopsies. In addition, 7 (58%) of these patients were also found to have another autoimmune or inflammatory disorder before the diagnosis of AMAG. Although subtle, histologic features of developing AMAG are identifiable in routine gastric body biopsies. When metaplasia, full-thickness chronic inflammation, and/or oxyntic destruction are seen, a note suggesting laboratory testing and/or close clinical follow-up in this subset of patients may be warranted.

Polypoid stromal lesions of the intestines.

Interpretation of intestinal mesenchymal lesions is simplified merely by knowing in which anatomic layer they are usually found. For example, Kaposi sarcoma is detected on mucosal biopsies, whereas inflammatory fibroid polyp is almost always in the submucosa. Gastrointestinal stromal tumours (GIST) are centred generally in the muscularis propria. Schwannomas are essentially always in the muscularis propria. Knowledge of the favoured layer is also most important in interpreting colon biopsies, as many mesenchymal polyps are encountered in the colon. Herein we discuss several mesenchymal lesions and point out some diagnostic pitfalls.