Publications by authors named "Rhonda K Yantiss"

117 Publications

Exogenous and Endogenous Sources of Serine Contribute to Colon Cancer Metabolism, Growth, and Resistance to 5-Fluorouracil.

Cancer Res 2021 Feb 1. Epub 2021 Feb 1.

Department of Medicine, Weill Cornell Medical College, New York, New York.

Serine is a nonessential amino acid generated by the sequential actions of phosphoglycerate dehydrogenase (PHGDH), phosphoserine aminotransferase (PSAT1), and phosphoserine phosphatase (PSPH). Increased serine biosynthesis occurs in several cancers and supports tumor growth. In addition, cancer cells can harness exogenous serine to enhance their metabolism and proliferation. Here we tested the relative contributions of exogenous and endogenous sources of serine on the biology of colorectal cancer. In murine tumors, status was identified as a determinant of the expression of genes controlling serine synthesis. In patient samples, PSAT1 was overexpressed in both colorectal adenomas and adenocarcinomas. Combining genetic deletion of with exogenous serine deprivation maximally suppressed the proliferation of colorectal cancer cells and induced profound metabolic defects including diminished nucleotide production. Inhibition of serine synthesis enhanced the transcriptional changes following exogenous serine removal as well as alterations associated with DNA damage. Both loss of PSAT1 and removal of serine from the diet were necessary to suppress colorectal cancer xenograft growth and enhance the antitumor activity of 5-fluorouracil (5-FU). Restricting endogenous and exogenous serine augmented 5-FU-induced cell death, DNA damage, and metabolic perturbations, likely accounting for the observed antitumor effect. Collectively, our results suggest that both endogenous and exogenous sources of serine contribute to colorectal cancer growth and resistance to 5-FU. SIGNIFICANCE: These findings provide insights into the metabolic requirements of colorectal cancer and reveal a novel approach for its treatment. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/00/0/000/F1.large.jpg.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/0008-5472.CAN-20-1541DOI Listing
February 2021

Dietary Interventions to Prevent High Fructose Diet-associated Worsening of Colitis and Colitis-associated Tumorigenesis in Mice.

Carcinogenesis 2021 Jan 29. Epub 2021 Jan 29.

Departments of Medicine, Weill Cornell Medicine, New York, NY.

Diet is believed to be an important factor in the pathogenesis of Inflammatory Bowel Disease. High consumption of dietary fructose has been shown to exacerbate experimental colitis, an effect mediated through the gut microbiota. This study evaluated whether dietary alterations could attenuate the detrimental effects of a high fructose diet (HFrD) in experimental colitis. First, we determined whether the pro-colitic effects of a HFrD could be reversed by switching mice from a HFrD to a control diet. This diet change completely prevented HFrD-induced worsening of acute colitis, in association with a rapid normalization of the microbiota. Second, we tested the effects of dietary fiber, which demonstrated that psyllium was the most effective type of fiber for protecting against HFrD-induced worsening of acute colitis, compared to pectin, inulin or cellulose. In fact, supplemental psyllium nearly completely prevented the detrimental effects of the HFrD, an effect associated with a shift in the gut microbiota. We next determined whether the protective effects of these interventions could be extended to chronic colitis and colitis-associated tumorigenesis. Using the azoxymethane/dextran sodium sulfate model, we first demonstrated that HFrD feeding exacerbated chronic colitis and increased colitis-associated tumorigenesis. Using the same dietary changes tested in the acute colitis setting, we also showed that mice were protected from HFrD-mediated enhanced chronic colitis and tumorigenesis, upon either diet switching or psyllium supplementation. Taken together, these findings suggest that high consumption of fructose may enhance colon tumorigenesis associated with long-standing colitis, an effect that could be reduced by dietary alterations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/carcin/bgab007DOI Listing
January 2021

The Frontiers of Appendiceal Controversies: Mucinous Neoplasms and Pseudomyxoma Peritonei.

Am J Surg Pathol 2021 Jan 6;Publish Ahead of Print. Epub 2021 Jan 6.

Department of Pathology, University of Michigan, Ann Arbor, MI Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY.

Appendiceal mucinous neoplasms show a range of morphologic features and biological risk. At one end of the spectrum, high-grade adenocarcinomas are cytologically malignant with infiltrative invasion, lymph node metastases, and behavior similar to that of extra-appendiceal mucinous adenocarcinomas. At the other end, mucinous neoplasms confined to the mucosa are uniformly benign. Some cases lying between these extremes have potential risk to metastasize within the abdomen despite a lack of malignant histologic features. They show "diverticulum-like," pushing invasion of mostly low-grade epithelium through the appendix with, or without, concomitant organizing intra-abdominal mucin. The latter condition, widely termed "pseudomyxoma peritonei," tends to pursue a relentless course punctuated by multiple recurrences despite cytoreductive therapy, culminating in death for many patients. The combination of bland histologic features and protracted behavior of peritoneal disease has led some authors to question whether these metastatic tumors even represent malignancies. The World Health Organization and its cadre of experts widely promote usage of "low-grade appendiceal mucinous neoplasm" as an umbrella term to encompass benign and malignant conditions, as well as those that have uncertain biological potential. Although this practice greatly simplifies tumor classification, it causes confusion and consternation among pathologists, clinical colleagues, and patients. It also increases the likelihood that at least some patients will undergo unnecessary surveillance for, and treatment of, benign neoplasms and non-neoplastic conditions. The purpose of this review is to critically evaluate the relevant literature and discuss a practical approach to classifying appendiceal mucinous neoplasms that more closely approximates their biological risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/PAS.0000000000001662DOI Listing
January 2021

Histopathology annual review edition for 2021.

Histopathology 2021 Jan;78(1):2-3

Weill Cornell Medicine, Department of Pathology and Laboratory Medicine, New York, NY, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/his.14293DOI Listing
January 2021

Epithelial-Stromal Polyps of the Colon Are Not Perineuriomas.

Am J Clin Pathol 2020 Dec 14. Epub 2020 Dec 14.

Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY.

Objectives: Some colorectal polyps contain serrated or tubular crypts surrounded by whorls of spindle cells that expand the mucosa. These epithelial-stromal polyps have been termed benign fibroblastic polyps or, more commonly, perineuriomas. We hypothesized that these lesions are pathogenetically heterogeneous polyps that share in common exuberant fibroblastic proliferations derived from the pericryptal sheath.

Methods: Forty-six epithelial-stromal polyps containing serrated crypts (n = 21) and nonserrated crypts (n = 25) were evaluated with epithelial membrane antigen and BRAF V600E immunohistochemical stains, and a subset was subjected to next-generation sequencing for BRAF mutations. Polyp morphology and immunohistochemical results were correlated with clinical information.

Results: Epithelial-stromal polyps containing serrated crypts were significantly associated with other sessile serrated polyps (43%, P = .01) and hyperplastic polyps (29%, P = .006). They also showed BRAF V600E abnormalities (95%) and strong, patchy epithelial membrane antigen staining of spindle cells (95%). In contrast, polyps with nonserrated crypts lacked BRAF alterations and infrequently showed robust EMA staining of stromal cells (16%, P < .01).

Conclusions: Benign epithelial-stromal polyps with serrated epithelium are biologically similar to sessile serrated polyps and should be classified as such to ensure appropriate clinical surveillance. The nature of polyps without serrated crypts is less clear, but evidence that they are perineuriomas is circumstantial at best.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ajcp/aqaa210DOI Listing
December 2020

Autopsy Findings in 32 Patients with COVID-19: A Single-Institution Experience.

Pathobiology 2021 17;88(1):56-68. Epub 2020 Sep 17.

Weill Cornell Medicine, New York, New York, USA,

Background: A novel coronavirus, SARS-CoV-2, was identified in Wuhan, China in late 2019. This virus rapidly spread around the world causing disease ranging from minimal symptoms to severe pneumonia, which was termed coronavirus disease (i.e., COVID). Postmortem examination is a valuable tool for studying the pathobiology of this new infection.

Methods: We report the clinicopathologic findings from 32 autopsy studies conducted on patients who died of COVID-19 including routine gross and microscopic examination with applicable special and immunohistochemical staining techniques.

Results: SARS-CoV-2 infection was confirmed by nasopharyngeal RT-PCR in 31 cases (97%) and by immunohistochemical staining for SARS-CoV-2 spike-protein in the lung in the remaining 1 case (3%). The ethnically diverse cohort consisted of 22 males and 10 females with a mean age of 68 years (range: 30-100). Patients most commonly presented with cough (17 [55%]), shortness of breath (26 [81%]), and a low-grade fever (17 [55%]). Thirty-one (97%) of the patients had at least 1 comorbidity (mean = 4). Twenty-eight patients (88%) had widespread thromboembolic disease, as well as diffuse alveolar damage (30 [94%]), diabetic nephropathy (17 [57%]) and acute tubular injury. Patterns of liver injury were heterogeneous, featuring 10 (36%) with frequent large basophilic structures in sinusoidal endothelium, and increased immunoblast-like cells in lymph nodes.

Conclusion: This series of autopsies from patients with COVID-19 confirms the observation that the majority of severely affected patients have significant pulmonary pathology. However, many patients also have widespread microscopic thromboses, as well as characteristic findings in the liver and lymph nodes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000511325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7573917PMC
February 2021

Clinicopathologic Features of Varicella Zoster Virus Infection of the Upper Gastrointestinal Tract.

Am J Surg Pathol 2021 02;45(2):209-214

Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York Presbyterian Hospital.

Reactivation of latent varicella zoster virus (VZV) may be limited to a dermatome or involve multiple organs, including the gastrointestinal tract. Although gastrointestinal manifestations of disseminated zoster have been likened to those of herpes simplex virus (HSV), histologic features of VZV-related injury to the tubular gut are not well-documented. We performed this study to describe the clinicopathologic features of VZV-related gastrointestinal injury. We identified 6 such patients with VZV infection. All involved the upper gastrointestinal tract, affecting the esophagus (n=3), stomach (n=2), or both (n=1). All patients were immunocompromised adults with hematologic malignancies (n=5) or a heart transplant (n=1); 3 with hematologic malignancies had received stem cell transplants. Five patients had cutaneous and gastrointestinal zoster; 1 had gastrointestinal disease alone. When compared with 14 HSV-related esophagitis controls, there were several notable differences. VZV caused hemorrhagic ulcers with nodularity or erythema, whereas HSV produced round, shallow ulcers on a background of nearly normal mucosa (P=0.01). VZV-related ulcers featured fibrin-rich, pauci-inflammatory exudates compared with the macrophage-rich exudates of HSV (P=0.003). The cytopathic changes of VZV were present at all levels of the squamous epithelium, especially in a peripapillary distribution. In contrast, HSV inclusions were located in the superficial layers (P=0.003) and detached keratinocytes. Unlike HSV, VZV involved the stomach, producing hemorrhage accompanied by striking apoptosis in the deep glands. We conclude that VZV produces unique patterns of gastrointestinal injury that facilitate its diagnosis. Recognition of gastrointestinal VZV infection is important because it heralds potentially life-threatening disseminated disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/PAS.0000000000001576DOI Listing
February 2021

Histology of Colorectal Carcinoma: Proven and Purported Prognostic Factors.

Surg Pathol Clin 2020 Sep 9;13(3):503-520. Epub 2020 Jul 9.

Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, 525 East 68th Street, New York, NY 10065, USA. Electronic address:

Although tumor stage has a profound influence on prognosis, several histologic features are also important. These parameters predict biological behavior and can be used by clinicians to determine whether patients are at high risk for disease progression and, thus, are candidates for adjuvant therapy, particularly when they have localized (ie, stage II) disease. This article summarizes the evidence supporting the prognostic values of various histologic parameters evaluated by pathologists who assign pathologic stage to colorectal cancers. Criteria to be discussed include histologic subtype, tumor grade, lymphatic and perineural invasion, tumor budding, and host immune responses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.path.2020.05.008DOI Listing
September 2020

Next-generation sequencing of residual cytologic fixative preserved DNA from pancreatic lesions: A pilot study.

Cancer Cytopathol 2020 11 29;128(11):840-851. Epub 2020 Jun 29.

The Leopold G. Koss Division of Cytology, The Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, New York.

Background: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is a sensitive and specific tool in the risk stratification of pancreatic lesions, including cysts. The sensitivity and specificity of EUS-FNA has been shown to improve when cytology is combined with next-generation sequencing (NGS). Ideally, fresh cyst fluid is used for NGS. In this pilot study, we explore the possibility of sequencing DNA derived from residual alcohol-fixed pancreatic aspirates.

Methods: Residual cytologic fixatives (n = 42) from 39 patients who underwent EUS-FNA for pancreatic lesions were collected along with demographics, imaging, and laboratory studies. Samples were designated as nonneoplastic/nonmucinous benign (NB), mucinous cyst (MC), pancreatic ductal adenocarcinoma (PDAC), or well-differentiated neuroendocrine tumor (NET) on the basis of cytopathologic evaluation and sequenced on the Oncomine platform (ThermoFisher Scientific, Waltham, Massachusetts).

Results: Ten of 14 (71.4%) MCs exhibited clinically significant variants, including KRAS, GNAS, and TP53. Ten of 15 (66.7%) PDACs had KRAS alterations, and 9 of 15 (60%) showed variants in TP53. No variants were detected in any NETs. Only 1 of 9 (11.1%) NB aspirates showed variants in KRAS and MAP2K. Sequencing of formalin-fixed, paraffin-embedded tissue revealed variants identical to those detected in fixative-derived DNA in 4 of 5 cases (80%).

Conclusion: Residual DNA from alcohol-fixed aspirates are an underutilized source for NGS. Sequencing residual fixative-derived DNA has the potential to be integrated into the workup of pancreatic aspirates, possibly impacting management.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cncy.22315DOI Listing
November 2020

Smooth muscle tumors of the gastrointestinal tract: an analysis of prognostic features in 407 cases.

Mod Pathol 2020 07 12;33(7):1410-1419. Epub 2020 Feb 12.

University of Utah, Salt Lake City, UT, USA.

Smooth muscle tumors represent the second most common mural mesenchymal neoplasm in the gastrointestinal tract, but established criteria for prognostic assessment of these tumors are lacking. A large cohort of surgically resected intramural gastrointestinal smooth muscle tumors from 31 institutions was analyzed to identify potential prognostic features. Pathologic features were assessed by expert gastrointestinal and/or soft tissue pathologists at each center. Immunohistochemical confirmation was required. A total of 407 cases from the esophagus (n = 97, 24%), stomach (n = 180, 44%), small bowel (n = 74, 18%), and colorectum (n = 56, 14%) were identified. Patients ranged in age from 19 to 92 years (mean 55 years), with a slight female predominance (57%). Mean tumor size was 5.4 cm, with the largest tumor measuring 29 cm. Disease progression following surgery, defined as local recurrence, metastasis, or disease-related death, occurred in 56 patients (14%). Colorectal tumors were most likely to progress, followed by small bowel and gastric tumors. None of the esophageal tumors in this series progressed. Receiver operator characteristic analysis identified optimal cutoffs of 9.8 cm and 3 mitoses/5 mm for discriminating between progressive and non-progressive tumors. Histologic features strongly associated with progression by univariate analysis included moderate-to-severe atypia, high cellularity, abnormal differentiation (defined as differentiation not closely resembling that of normal smooth muscle), tumor necrosis, mucosal ulceration, lamina propria involvement, and serosal involvement (P < 0.0001 for all features). Age, sex, and margin status were not significantly associated with progression (P = 0.23, 0.82, and 0.07, respectively). A risk assessment table was created based on tumor site, size, and mitotic count, and Kaplan-Meier plots of progression-free survival for each subgroup revealed progression-based tiers. Based on our findings, it appears that nonesophageal gastrointestinal smooth muscle tumors measuring >10 cm and/or showing ≥3 mitoses/5 mm may behave aggressively, and therefore close clinical follow-up is recommended in these cases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41379-020-0492-5DOI Listing
July 2020

The diagnosis of clinically significant oesophageal Candida infections: a reappraisal of clinicopathological findings.

Histopathology 2020 Apr;76(5):748-754

Department of Pathology, University of Michigan, Ann Arbor, MI, USA.

Aims: Distinguishing true oesophageal Candida infections from oral contaminants is a common diagnostic issue. Historically, histological features believed to indicate true infection included epithelial invasion by pseudohyphae and intraepithelial neutrophils. Whether or not these features correlate with endoscopic lesions, symptoms and response to therapy has never been tested in a large cohort. The aim of this study was to determine whether specific histological features correlate with clinical and endoscopic findings when Candida is found in oesophageal biopsies.

Methods And Results: We reviewed 271 biopsies in which Candida was detected. Cases were evaluated for the presence of desquamated epithelial cells, location/type of fungal forms, neutrophils, and ulceration. Medical records were reviewed for clinical history, endoscopic lesions, and response to antifungal therapy. Statistical analysis was used to determine whether any histological features significantly correlated with clinical variables. There were 120 males and 151 females with a mean age of 42 years. Fifty-nine per cent had symptoms referable to the oesophagus, particularly dysphagia (36%). Most (73%) patients had abnormal endoscopic findings, with plaques, ulcers, or macroscopic evidence of oesophagitis. Seventy-one per cent of patients with documented antifungal therapy showed symptomatic improvement. Overall, there was no statistically significant correlation between any histological feature and presenting symptoms, endoscopic findings, or response to therapy. Importantly, the lack of pseudohyphae, demonstrable invasion of intact epithelium or neutrophilic infiltrates did not exclude clinically significant infection.

Conclusions: We conclude that detection of Candida in oesophageal biopsies is always potentially clinically significant. Treatment decisions should be made on the basis of an integration of clinical, endoscopic and histological findings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/his.14063DOI Listing
April 2020

Post-inflammatory mucosal hyperplasia and appendiceal diverticula simulate features of low-grade appendiceal mucinous neoplasms.

Mod Pathol 2020 05 19;33(5):953-961. Epub 2019 Dec 19.

Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, 10065, USA.

Post-inflammatory mucosal hyperplasia and appendiceal diverticulosis simulate mucinous neoplasms, causing diagnostic confusion. Distinction between neoplasia and its mimics is particularly important since many authorities now consider all appendiceal mucinous neoplasms to be potentially malignant. The purpose of this study was to identify clinicopathologic and molecular features that may distinguish appendiceal mucinous neoplasms from non-neoplastic mimics. We retrospectively identified 92 mucinous lesions confined to the right lower quadrant, including 55 non-neoplastic examples of mucosal hyperplasia and/or diverticulosis and 37 low-grade neoplasms. Presenting symptoms, radiographic findings, appendiceal diameter, appearances of the lamina propria, non-neoplastic crypts, and epithelium, as well as mural changes were recorded. Twenty non-neoplastic lesions were subjected to KRAS mutational testing. Non-neoplastic appendices were smaller (p < 0.05) and more likely to present with symptoms of appendicitis (p < 0.05) than neoplasms. While post-inflammatory mucosal hyperplasia and diverticula often showed goblet cell-rich epithelium, extruded mucin pools, and patchy mural alterations with fibrosis, they always contained non-neoplastic crypts lined by mixed epithelial cell types and separated by lamina propria with predominantly preserved wall architecture. On the other hand, mucinous neoplasms lacked normal crypts (p < 0.05) and showed decreased lamina propria (p < 0.05) with diffusely thickened muscularis mucosae and lymphoid atrophy. Six (30%) non-neoplastic lesions contained KRAS mutations, particularly those containing goblet cell-rich hyperplastic epithelium. We conclude that distinction between neoplastic and non-neoplastic mucinous appendiceal lesions requires recognition of key morphologic features; KRAS mutational testing is an unreliable biomarker that cannot be used to assess biologic risk or confirm a diagnosis of neoplasia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41379-019-0435-1DOI Listing
May 2020

American registry of pathology expert opinions: Evaluating patients with eosinophilic esophagitis: Practice points for endoscopists and pathologists.

Ann Diagn Pathol 2019 Dec 23;43:151418. Epub 2019 Oct 23.

Center for Esophageal Diseases, Baylor University Medical Center, the Center for Esophageal Research, Baylor Scott & White Research Institute, Dallas, TX, United States of America.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.anndiagpath.2019.151418DOI Listing
December 2019

Lymphocyte-predominant Esophagitis: A Distinct and Likely Immune-mediated Disorder Encompassing Lymphocytic and Lichenoid Esophagitis.

Am J Surg Pathol 2020 02;44(2):198-205

Departments of Pathology and Laboratory Medicine.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/PAS.0000000000001394DOI Listing
February 2020

Acellular mucin in pseudomyxoma peritonei of appendiceal origin: what is adequate sampling for histopathology?

J Clin Pathol 2020 Apr 13;73(4):220-222. Epub 2019 Oct 13.

Department of Pathology, Peritoneal Malignancy Institute, Basingstoke and North Hampshire Hospital, Basingstoke, UK.

Introduction: Acellular intra-abdominal mucin is associated with a favourable prognosis in pseudomyxoma peritonei. There are no current guidelines on how many blocks are needed to classify the mucin as acellular with confidence.

Methods: Specimens from cytoreductive surgery for mucinous appendiceal neoplasia, in which acellular mucin was found on initial histopathological examination, were prospectively identified. Additional tissue blocks were then taken to include either all residual visible intra-abdominal mucin or a maximum of 30 blocks. We also sent a questionnaire to pathologists in other centres.

Results: Twelve patients were identified. In two cases, neoplastic epithelial cells were found on taking additional blocks. The questionnaire results suggested considerable variation in block-taking practice.

Conclusion: Taking additional tissue identified neoplastic cells in 2 of 12 cases. We recommend that sampling additional material should be considered when only acellular mucin is found on initial histology. Further work to determine the optimum sampling protocol is indicated.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/jclinpath-2019-206213DOI Listing
April 2020

Challenges with colorectal cancer staging: results of an international study.

Mod Pathol 2020 01 5;33(1):153-163. Epub 2019 Aug 5.

Department of Pathology and Laboratory Medicine, Western University and London Health Sciences Centre, London, ON, Canada.

Challenges exist with standardized colorectal cancer reporting despite adoption of the American Joint Committee on Cancer-Staging Manual 8th edition. We performed this study to gauge current practice patterns among a diverse group of surgical pathologists. A web-based questionnaire depicting problematic issues and images related to colorectal carcinoma staging was circulated among 118 surgical pathologists and their responses were correlated with their geographic location (North America vs. Europe vs. others), nature of practice (academic vs. community), the sign-out model (gastrointestinal subspecialty vs. general surgical pathology), and years of professional experience. We found that a substantial number of practicing pathologists ignore recommended-staging criteria in specific settings, particularly with respect to assessment of advanced T stage. Tumors that communicated with the serosa through inflammatory foci were staged as pT3 (49%) or pT4a (51%) by nearly equal numbers of pathologists regardless of level of experience, the sign-out model, or geographic location. Only 65% assigned T stage and margin status based on extent of viable tumor in the neoadjuvant setting. One-third of pathologists, particularly those in Europe (p = 0.015), classified acellular mucin deposits as N1 disease when detected in treatment-naive cases. Nearly 50% of pathologists classified isolated tumor cells (i.e., deposits <0.2 mm) in lymph nodes as metastatic disease (i.e., pN1, p = 0.02). Our results suggest that pathologists ignore recommendations that are based on insufficient data and apply individualized criteria when faced with situations that are not addressed in the American Joint Committee on Cancer Staging Manual 8th edition. These variations in practice limit the ability to compare outcome data across different institutions and draw attention to areas that require further study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41379-019-0344-3DOI Listing
January 2020

Cytomegalovirus reactivation in inflammatory bowel disease: an uncommon occurrence related to corticosteroid dependence.

Mod Pathol 2019 07 5;32(8):1210-1216. Epub 2019 Apr 5.

Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.

Cytomegalovirus promotes mucosal injury in patients with inflammatory bowel disease, historically affecting 10-25% of ulcerative colitis patients with refractory disease. Viral reactivation is likely related to long-term corticosteroid therapy, which is no longer central to maintenance of patients with inflammatory bowel disease. We hypothesize that viral detection rates have decreased in the modern era, reflecting widespread use of immunomodulatory agents to control inflammation. We performed this study to evaluate the relationships between medical regimens and cytomegalovirus detection rates among patients with inflammatory bowel disease. We searched our database for all patients with established inflammatory bowel disease and severe flares diagnosed from 2002 to 2017. Patients maintained with corticosteroid therapy were considered to be corticosteroid-dependent and those treated with other agents were classified as corticosteroid-independent, provided they had not received corticosteroids within 6 months of colonoscopy. Biopsy samples were reviewed for viral inclusions and subjected to cytomegalovirus immunohistochemistry, and rates of viral detection were compared between groups. There were 135 corticosteroid-dependent patients; most had ulcerative colitis flares occurring during the 2002-2009 period. Patients with ulcerative colitis and Crohn disease were equally represented in the corticosteroid-independent group (n = 133) and most were evaluated for disease flares during the 2010-2017 interval. Cytomegalovirus was detected in 13 (8%) cases; 9 (69%) were diagnosed from 2002 to 2009 and all were obtained from corticosteroid-dependent patients (p = < 0.001). We conclude that rates of cytomegalovirus-related enterocolitis are declining among inflammatory bowel disease patients, reflecting a shift away from corticosteroid-based maintenance therapy in favor of more effective agents that do not promote viral reactivation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41379-019-0258-0DOI Listing
July 2019

Malformations, choristomas, and hamartomas of the gastrointestinal tract and pancreas.

Semin Diagn Pathol 2019 Jan 16;36(1):24-38. Epub 2018 Nov 16.

Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.

Congenital and hamartomatous lesions of the gastrointestinal tract cause diagnostic challenges for surgical pathologists. Many of these are merely histologic curiosities, whereas others have substantial clinical implications because they herald cancer syndromes or associated anomalies. Although a comprehensive discussion of all developmental abnormalities that can occur in the gastrointestinal tract is beyond the scope of a single manuscript, some entities are more likely to be encountered by surgical pathologists, have important clinical consequences, or pose diagnostic difficulties. The purpose of this review is to discuss the more common malformations and choristomas, as well as hamartomatous lesions that may be clinically important due to their risk for cancer development, frequent associations with heritable cancer syndromes and other anomalies, or potential to simulate other entities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1053/j.semdp.2018.11.004DOI Listing
January 2019

Portal Cavernoma Cholangiopathy: Histologic Features and Differential Diagnosis.

Am J Clin Pathol 2019 02;151(3):255-262

Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY.

Objectives: Portal cavernoma cholangiopathy (formerly portal biliopathy) is a type of biliary injury that occurs in association with a portal vein thrombus or cavernoma. Although the radiographic features of portal cavernoma cholangiopathy have been enumerated in the literature, its histologic features have not been described in detail.

Methods: We describe the histologic findings in liver specimens from three patients with radiologically confirmed portal cavernoma cholangiopathy.

Results: Of the three patients, one underwent surgical resection due to a clinical suspicion for cholangiocarcinoma, one had a liver biopsy sample obtained for evaluation of possible cirrhosis, and one had a clinically suspicious "hilar mass" at the time of orthotopic liver transplant. Histologic features common among the three liver specimens included portal venous abnormalities, where the portal veins were obliterated or small relative to the portal tract size, and obstructive biliary changes, such as ductular reaction and reactive epithelial atypia accompanied by a mixed inflammatory cell infiltrate with neutrophils.

Conclusions: This case series provides clinicopathologic characteristics of portal cavernoma cholangiopathy. Histologic changes are reminiscent of hepatoportal sclerosis and/or bile duct obstruction. Attention to portal veins can provide helpful diagnostic clues, especially when biopsy samples are obtained from patients with a known portal vein thrombus or cavernoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ajcp/aqy132DOI Listing
February 2019

Tumor Grade Is Prognostically Relevant Among Mismatch Repair Deficient Colorectal Carcinomas.

Am J Surg Pathol 2018 12;42(12):1686-1692

Department of Pathology and Laboratory Medicine.

Intestinal-type colorectal adenocarcinomas are graded based on extent of glandular differentiation, although mucinous, signet-ring cell, and solid cancers are, by convention, classified as high grade. Mismatch repair-deficient tumors frequently show high-grade histologic features, yet the World Health Organization classifies them as low grade to reflect their favorable prognosis compared with mismatch repair-proficient cancers. Although some mismatch repair-deficient colorectal cancers behave aggressively, few authors have identified features that predict their behavior. We performed this study to determine which histologic features, if any, predicted outcome among mismatch repair-deficient colorectal carcinomas. We identified 116 mismatch repair-deficient colorectal carcinomas, including 77 localized (stage I to II) and 39 advanced (stage III to IV) tumors, and evaluated them for extent of gland formation, extracellular mucin, signet-ring cell differentiation, solid growth, nuclear grade, tumor-infiltrating lymphocytes and tumor budding. Relationships between these features, pathologic stage, and disease-free survival were assessed. We found that high-grade mismatch repair-deficient tumors were more often of advanced stage than low-grade tumors (46% vs. 23%, P=0.01). Disease-free survival was inversely associated with the presence of a dominant high-grade component and tumor budding (P=0.01 and 0.04, respectively). Predominantly solid tumors, in particular, were significantly associated with decreased disease-free survival compared with low-grade tumors (P=0.001). Nuclear grade and tumor-infiltrating lymphocytes were not associated with pathologic stage or outcome. We conclude that low-grade mismatch repair-deficient carcinomas present at an earlier stage and pursue a more favorable course than those mostly composed of high-grade elements. These findings suggest that mismatch repair status should not supplant histologic grade in the assessment of colorectal carcinomas.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/PAS.0000000000001145DOI Listing
December 2018

Treatment Effects Can Mimic Recurrent Extramammary Paget Disease in Perianal Skin.

Am J Surg Pathol 2018 11;42(11):1472-1479

Department of Pathology and Laboratory Medicine.

The histologic differential diagnosis of perianal Paget disease includes malignant melanoma, pagetoid spread of squamous cell carcinoma, and secondary involvement by colorectal carcinoma. While consideration of these entities is useful when establishing a diagnosis, it does not apply when patients with Paget disease undergo surveillance for recurrent disease. Treatment of perianal Paget disease consists of a combination of surgical excision with skin grafts and topical chemotherapeutic agents that induce cytologic alterations in benign cells and simulate recurrent malignancy. To evaluate the therapy-related changes and possible diagnostic pitfalls in patients with Paget disease, we reviewed 412 posttreatment tissue samples from 3 women with primary perianal Paget disease who underwent wide excision, skin grafting, and topical 5-fluorouracil therapy. Biopsy samples from engrafted skin often displayed single and clustered cells with hyperchromatic nuclei dispersed in the deep epidermis. Similar cells were scattered throughout all levels of the epidermis in biopsy samples following topical chemotherapy. The abnormal cells were negative for cytokeratin 7 (CK7) and mucicarmine in both situations. Disease ultimately recurred in all patients; some Paget cells showed classic features with eosinophilic or mucinous cytoplasm and eccentric nuclei, whereas others were smaller with less conspicuous atypia. All Paget cells showed strong, membranous CK7 staining. In short, treatment of perianal Paget disease can elicit cytologic abnormalities in benign epithelial cells that simulate the cytologic features of recurrent disease, and can diminish the atypia of Paget cells. Immunohistochemical stains for CK7 can be helpful when evaluating surveillance samples from these patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/PAS.0000000000001130DOI Listing
November 2018

Are Enterocolic Mucosal Mast Cell Aggregates Clinically Relevant in Patients Without Suspected or Established Systemic Mastocytosis?

Am J Surg Pathol 2018 10;42(10):1390-1395

Department of Pathology and Laboratory Medicine, Weill Cornell Medicine.

The World Health Organization considers enterocolic mast cell aggregates with atypical morphologic and/or immunohistochemical features diagnostic of systemic mastocytosis mostly because published data are heavily influenced by inclusion of symptomatic patients with systemic disease. We occasionally encounter atypical mast cells in gastrointestinal biopsy samples from patients in whom systemic mastocytosis is not suspected. The aim of this study was to describe the clinicopathologic features and implications of atypical enterocolic mast cell aggregates in 16 patients without suspected or established systemic mastocytosis. Mast cell infiltrates were assessed for morphology, distribution, associated inflammatory cells, and CD117 and CD25 immunoexpression. Most (63%) patients were women; 15 underwent endoscopic examination for screening (n=7), abdominal pain (n=3), diarrhea (n=3), changing bowel habits (n=1), and dysphagia (n=1). Mast cell aggregates were detected in 1 colectomy specimen for cancer. Colonic involvement was most common (n=14) and resulted in polypoid (n=10), edematous (n=2), or normal (n=3) mucosae. All cases featured CD117/CD25, ovoid mast cells concentrated beneath the epithelium, or diffusely involving the entire mucosal thickness. Eosinophils were numerous and obscured mast cells in 63% of cases. Spontaneous resolution of symptoms occurred in all patients (mean follow-up: 54 mo), and asymptomatic patients remained symptom-free (mean follow-up: 17 mo). Of 4 patients evaluated for systemic mastocytosis, 3 had negative bone marrow biopsies and one lacked a KIT mutation in peripheral blood. We conclude that, although careful clinical assessment of patients with incidental enterocolic mast cell aggregates is reasonable, labeling them with a systemic hematologic disorder may not be justified.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/PAS.0000000000001126DOI Listing
October 2018

Assessing colorectal cancer mismatch repair status in the modern era: a survey of current practices and re-evaluation of the role of microsatellite instability testing.

Mod Pathol 2018 11 28;31(11):1756-1766. Epub 2018 Jun 28.

Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York, NY, 10065, USA.

Results of DNA mismatch repair testing are used to detect Lynch syndrome and have prognostic and therapeutic implications among patients with sporadic colorectal carcinomas. Immunohistochemistry for mismatch repair proteins (MLH1, PMS2, MSH2, MSH6) and PCR for microsatellite instability are two established methods for assessing mismatch repair function. Older literature suggested a discordance rate of approximately 5% between these assays, leading some institutions to perform dual testing on all cases. Although universal mismatch repair testing is now recommended by multiple professional organizations, none provide guidelines regarding preferred assays. We surveyed 96 academic and nonacademic institutions to assess Lynch syndrome screening practices and evaluated discordance rates between immunohistochemistry and PCR among 809 colorectal cancers tested in our own institution. Our survey demonstrated no significant differences between academic and nonacademic practices with respect to testing strategies. Eighty six percent performed universal screening, and usually (76%) employed immunohistochemistry on initial biopsy samples. Only 20% employed PCR; these were mostly academic practices that used both immunohistochemistry and PCR (p < 0.01 compared with the nonacademic groups). Loss of MLH1/PMS2 staining was often (90%) followed by either BRAF mutational analysis or MLH1 methylation assays. Only 24% adhered to WHO recommendations to assign histologic grade based on mismatch repair status. We found only 3 cases (0.4%) with discordant immunohistochemistry and PCR results in our own practice: 1 reflected decreased MSH-6 staining in a neoadjuvantly treated microsatellite stable tumor, 1 MLH1-deficient tumor showed diminished MLH1/PMS2 in the tumor compared with internal control, and 1 case reflected an error in the molecular laboratory. Overall, our results showed extremely low discordance between methods assessing mismatch repair status and would suggest immunohistochemistry as the preferred single screening test. PCR can be reserved for cases that show equivocal immunostaining patterns.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41379-018-0094-7DOI Listing
November 2018

Statement on Best Practices in the Use of Pathology as a Diagnostic Tool for Celiac Disease: A Guide for Clinicians and Pathologists.

Am J Surg Pathol 2018 09;42(9):e44-e58

North American Society for the Study of Celiac Disease (NASSCD).

Small intestinal biopsy interpretation has been the cornerstone for the diagnosis of celiac disease for over 50 years. Despite the existence of sensitive and specific serological tests, duodenal mucosal biopsies continue to be obtained in the vast majority of patients in whom a diagnosis of celiac disease is being considered. The accurate evaluation of these biopsies requires coordination and information sharing between the gastroenterologist, laboratory, and pathologist in order to optimize tissue sampling, preparation and interpretation. This document, a collaboration between the Rodger C. Haggitt Gastrointestinal Pathology Society and the North American Association for the Study of Celiac Disease, is intended to provide clinicians and pathologists with a summary of best practices in the use of endoscopy and biopsy for patients with suspected celiac disease. The authors present a comprehensive and critical appraisal of the literature with respect to the topics of endoscopic findings, best methods for the obtaining biopsies, completing the pathology form and pathologic assessment, including evaluating intraepithelial lymphocytes and villous architecture. A discussion of conditions with overlapping pathologic findings in duodenal mucosal biopsies is presented. In order to provide additional guidance for challenging situations, the authors include an appendix containing practical suggestions. This review may be utilized in interdisciplinary discussions to optimize care for patients with possible celiac disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/PAS.0000000000001107DOI Listing
September 2018

Lymphocytic esophagitis: an update on histologic diagnosis, endoscopic findings, and natural history.

Ann N Y Acad Sci 2018 12 24;1434(1):185-191. Epub 2018 May 24.

Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, New York.

Lymphocytic esophagitis is a histologic pattern of injury characterized by increased intraepithelial lymphocytes (>20/high-power field) with rare, or absent granulocytes. Lymphocytes tend to be more numerous in the peripapillary epithelium, and are often associated with evidence of mucosal injury, edema, and scattered dyskeratotic cells. More than a decade following its original description, lymphocytic esophagitis remains an enigmatic entity with variable clinical presentations, associated disorders, etiologies, treatment, and natural history. Most of the confusion regarding the clinical significance of this disorder stems from its diagnostic criteria: lymphocytic esophagitis is currently defined based entirely on histologic criteria, despite the common occurrence of lymphocytosis in a variety of unrelated inflammatory conditions of the esophagus. The goal of this review is to summarize the literature regarding lymphocytic esophagitis and focus on key clinicopathologic features that distinguish it from other esophageal disorders that can show increased numbers of intraepithelial lymphocytes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/nyas.13710DOI Listing
December 2018

The microscopic anatomy of the esophagus including the individual layers, specialized tissues, and unique components and their responses to injury.

Ann N Y Acad Sci 2018 12 15;1434(1):304-318. Epub 2018 May 15.

Department of Pathology, University of Michigan, Ann Arbor, Michigan.

The esophagus, a straight tube that connects the pharynx to the stomach, has the complex architecture common to the rest of the gastrointestinal tract with special differences that relate to its function as a conduit of ingested substances. For instance, it has submucosal glands that are unique and have a specific protective function. It has a squamous lining that exists nowhere else in the gut except the anus and it has a different submucosal nerve plexus when compared to the stomach and intestines. All of the layers of the esophageal wall and the specialized structures including blood and lymphatic vessels and nerves have specific responses to injury. The esophagus also has unique features such as patches of gastric mucosa called inlet patches at the very proximal part and it has a special sphincter mechanism at the most distal aspect. This review covers the normal microscopic anatomy of the esophagus and the patterns of reaction to stress and injury of each layer and each special structure.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/nyas.13705DOI Listing
December 2018

Frozen Sections of the Liver.

Surg Pathol Clin 2018 Jun 26;11(2):453-466. Epub 2018 Mar 26.

Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, 525 East 68th Street, Starr 10, New York, NY 10065, USA.

Intraoperative consultation requires skills in gross examination and histologic diagnosis, as well as an ability to perform rapid interpretations under time constraints. The aim of this review is to provide surgical pathologists with a framework for dealing with hepatic specimens in the frozen section area by covering common clinical scenarios and histologic findings. Differential diagnoses are considered in relation to primary hepatic neoplasia and metastatic diseases. Benign mimics of malignancy and other pitfalls in frozen section diagnosis of lesional tissue are covered. Finally, assessment of donor liver biopsy for organ transplant evaluation is discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.path.2018.02.012DOI Listing
June 2018

Findings in exudates can help distinguish benign gastric ulcers from ulcerated adenocarcinomas.

Histopathology 2018 Aug 3;73(2):215-219. Epub 2018 May 3.

Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.

Aims: Most gastric carcinomas develop in association with mucosal atrophy and hypochlorhydria, whereas benign peptic ulcers are acid-related. Given that acid sterilises the gastric contents, we hypothesised that ulcerated gastric cancers may be associated with increased numbers of luminal microorganisms as compared with peptic ulcers, and that this feature may represent a helpful diagnostic clue to the presence of malignancy. We performed this study to determine whether the features of luminal debris, including microorganisms, from ulcerated gastric cancers were significantly different from those of debris associated with benign ulcers.

Methods And Results: We retrospectively identified 50 ulcerated adenocarcinomas and 50 site-matched peptic ulcers. Luminal debris was evaluated for the nature of inflammation, necrosis, and the presence of mixed bacterial colonies or yeasts. Non-lesional mucosa was assessed for chronic gastritis, Helicobacter pylori, chemical gastropathy, and intestinal metaplasia. Patients in both groups were adults (mean age: 69 years and 62 years, respectively) with similar amounts of inflammation and cellular necrosis in biopsy material. However, 76% of ulcerated cancers harboured non-H. pylori bacterial colonies, as compared with only 22% of peptic ulcers (P < 0.01). Filamentous bacteria and fungi were highly specific for carcinoma (98% and P = 0.02 for both comparisons). Background intestinal metaplasia was more common among gastric cancers than among peptic ulcers (50% versus 26%, P = 0.02), whereas chemical gastropathy was more commonly associated with the latter (50% versus 10%, P < 0.01).

Conclusion: Gastric cancers may be colonised by non-H. pylori microorganisms. Detection of numerous bacterial colonies, filamentous bacteria or fungi in biopsy material obtained from ulcerated gastric lesions should raise suspicion for underlying malignancy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/his.13510DOI Listing
August 2018

Gastric Carcinomas With Lymphoid Stroma: An Evaluation of the Histopathologic and Molecular Features.

Am J Surg Pathol 2018 04;42(4):453-462

Departments of Pathology and Laboratory Medicine.

Gastric carcinoma with lymphoid stroma is an uncommon variant enriched for mutually exclusive Epstein-Barr virus (EBV) positivity and mismatch repair (MMR) deficiency. We performed this study to evaluate molecular alterations in this morphologically homogeneous subtype and compare them with 295 conventional gastric cancers analyzed in The Cancer Genome Atlas study. We identified 31 study cases and subjected them to in situ hybridization for EBV-encoded RNAs and assessment for MMR status. Immunostains for PD-L1, β-catenin, and HER2 were performed; extracted DNA was sequenced with a Comprehensive Cancer Panel. Most study patients were older adult men with stage I or II disease (76%). Tumors were classified as EBV/MMR-proficient (MMR-P) (n=7), EBV/MMR deficient (n=12), and EBV/MMR-P (n=12). EBV/MMR-P tumors were usually located in the proximal stomach (83%) and showed heterogenous growth patterns with glandular differentiation (83%). Tumors in all groups showed numerous tumor infiltrating lymphocytes and PD-L1 expression, infrequent nuclear β-catenin accumulation (10%), and lacked both membranous HER2 staining and HER2 amplification. EBV/MMR-deficient tumors showed significantly higher tumor mutation burden (P=0.001) and KRAS alterations (56%) compared with EBV/MMR-P tumors (9%, P=0.05). TP53 variants were more common among EBV/MMR-P tumors (82%) compared with EBV/MMR proficient (0%, P=0.01) and EBV/MMR-deficient (11%, P<0.01) tumors. Alterations in KRAS, ARID1A, PIK3CA, and TP53 followed similar patterns of distribution compared with The Cancer Genome Atlas dataset. We conclude that gastric carcinomas with lymphoid stroma show a spectrum of molecular changes and frequent PD-L1 expression, raising the possibility that this subgroup of tumors may be susceptible to checkpoint inhibitors and/or agents that target receptor tyrosine kinase-mediated signaling.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/PAS.0000000000001018DOI Listing
April 2018

Inflammatory and infectious manifestations of immunodeficiency in the gastrointestinal tract.

Mod Pathol 2018 06 5;31(6):844-861. Epub 2018 Feb 5.

Weill Cornell Medicine, New York, NY, USA.

Immune compromise may result from genetic abnormalities, HIV/AIDS, or consequences of therapy for neoplastic and autoimmune diseases. Many immunocompromised patients develop severe gastrointestinal symptoms, particularly diarrhea, accompanied by non-specific or mild endoscopic abnormalities; mucosal biopsy with pathologic interpretation has a major role in the diagnosis and management of these patients. Immunocompromised individuals are at risk for all the diseases that affect those with a healthy immune system, but they are also prone to other illnesses that rarely affect immunocompetent patients. This review discusses the gastrointestinal manifestations of primary and acquired immunodeficiency, chemotherapy-related injury, and infections that show a predilection for immunocompromised patients. Key histologic features and relevant differential diagnoses are emphasized.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41379-018-0015-9DOI Listing
June 2018