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Zeka F, Angori S, Rutishauser D, Moch H, Posovszky C, Amin K, Holtan S, Güngör T, Drozdov D. High Amphiregulin Expression in Intestinal Biopsies of Pediatric Patients with Severe Acute Graft-Versus-Host Disease. Transplant Cell Ther 2025; 31:323.e1-323.e9. [PMID: 40015568 DOI: 10.1016/j.jtct.2025.02.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2024] [Revised: 02/16/2025] [Accepted: 02/21/2025] [Indexed: 03/01/2025]
Abstract
Acute graft-versus-host disease (GvHD) is a major complication of hematopoietic cell transplantation (HCT). Despite of recent advances in prophylaxis, diagnosis and treatment it is still a serious cause of morbidity and mortality after HCT. Amphiregulin (AREG) is an epidermal growth factor receptor ligand known for restoring damaged intestinal tissue. AREG has been studied as a blood biomarker in acute GvHD and was found predictive of steroid response and mortality. However, the expression of AREG in intestinal tissue in pediatric patients with acute GvHD is unknown. The aim of this study is to analyze and evaluate AREG expression in intestinal tissue biopsies of pediatric patients with GvHD, in comparison to patients with inflammatory bowel disease (IBD) and a control group with no pathological findings to provide insights in the biological tissue expression of this potential diagnostic and prognostic biomarker. We performed a retrospective study with pediatric patients who had an intestinal biopsy performed after HCT between 2010 and 2021, patients who had a diagnosis of IBD and patients with normal findings at the University Children's Hospital Zurich. Intestinal biopsies were stained for AREG. We used a semi-quantitative score ranging from 0 (not present) to 3 (intense) to grade the AREG expression. The grading was performed by a pathologist blinded to the group allocation. Lerner scores were also performed. The median AREG scores between the groups were compared using multivariable linear regression with age and sex as confounders. The study protocol was approved by the Ethical committee of Canton Zürich, Switzerland, number 2022-01037. Overall, 59 biopsies were stained for AREG, 20 after HCT (6 patients with severe GvHD, 5 with mild GvHD and 9 without GvHD), 19 with IBD and 20 controls. The median for the AREG overall grade for control group was 2, for the HCT with severe GvHD group 2.5 (P = .060) and for the IBD group 2.5 (P = .007). The results for the AREG epithelium and lamina propria grades were similar. There were no differences in survival between patients with GvHD with overall AREG scores below and greater or equal to the median of 2.5. This study showed that AREG scores were higher in intestinal biopsies from patients with severe GvHD and IBD compared to controls and patients with mild or no GvHD. Consequently, AREG staining could potentially be used as an additional marker for severe inflammation as seen in GvHD and IBD.
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Affiliation(s)
- Fjolla Zeka
- Department of Hematology/Oncology/Immunology, Gene-therapy, and Stem Cell Transplantation University Children's Hospital Zurich - Eleonore Foundation & Children's Research Center (CRC), Zürich, Switzerland; Faculty of Medicine, University of Zürich, Zürich, Switzerland
| | - Silvia Angori
- Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden
| | - Dorothea Rutishauser
- Department of Pathology and Molecular Pathology, University Hospital Zürich and University of Zürich, Zürich, Switzerland
| | - Holger Moch
- Department of Pathology and Molecular Pathology, University Hospital Zürich and University of Zürich, Zürich, Switzerland
| | - Carsten Posovszky
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, University Children's Hospital Zurich, Zürich, Switzerland
| | - Khalid Amin
- Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota
| | - Shernan Holtan
- Division of Hematology, Oncology and Transplant, University of Minnesota, Minneapolis, Minnesota; Transplant and Cellular Therapies, Roswell Park Comprehensive Cancer Center, Buffalo, New York
| | - Tayfun Güngör
- Department of Hematology/Oncology/Immunology, Gene-therapy, and Stem Cell Transplantation University Children's Hospital Zurich - Eleonore Foundation & Children's Research Center (CRC), Zürich, Switzerland
| | - Daniel Drozdov
- Department of Hematology/Oncology/Immunology, Gene-therapy, and Stem Cell Transplantation University Children's Hospital Zurich - Eleonore Foundation & Children's Research Center (CRC), Zürich, Switzerland; Division of Pediatric Hematology and Oncology, Children's Hospital, Kantonsspital Aarau, Aarau, Switzerland.
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Ducloux-Lebon B, Lebon D, Tesson JR, Fumery M, Marolleau JP, Chatelain D. [Recto-colic graft-versus-host disease (GVH). Diagnostic and prognostic criteria in a cohort of patients from Amiens university hospital]. Ann Pathol 2025; 45:205-213. [PMID: 39242243 DOI: 10.1016/j.annpat.2024.08.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2023] [Revised: 08/11/2024] [Accepted: 08/12/2024] [Indexed: 09/09/2024]
Abstract
INTRODUCTION Recto-colic graft-versus-host disease (GVHD) is a frequent and serious complication of hematopoietic stem cell allogeneic transplantation, which is sometimes difficult to diagnose. The aim of our study was to identify histological diagnostic and prognostic criteria for recto-colic GVH. MATERIAL AND METHOD Patients allografted at Amiens university hospital from 2012 to 2017 were retrieved. Those who had a recto-colic biopsy were included and divided into two groups (final diagnosis of GVH and non-GVH), then biopsies were reviewed by 2 pathologists. RESULTS One hundred and nineteen patients were included. Sixty-seven were allocated to the GVH group and 52 to the non-GVH group. In the GVH group, we observed a significantly greater number of apoptotic bodies (AB) on standard HES staining and with the anti-Caspase 3 immunohistochemistry, cryptolytic AB abscesses, atrophy, regenerative glands and glands lined with eosinophilic cells (P<0.001). Anti-Caspase 3 immunohistochemistry revealed more AB than standard HES staining (P<0.005). But to differentiate GVH cases from non-GVH cases, we obtained a threshold value of 3.5 AB per 10 contiguous crypts on standard HE staining and with the anti-Caspase 3 immunohistochemistry. From 4 AB per 10 contiguous crypts, on HES staining and anti-Caspase 3 immunostaining, the diagnosis of GVH became consistent. No non-GVH case had more than 6 AB per 10 contiguous crypts. GVH patients with more than 8 AB per 10 contiguous crypts had a worse prognosis (P<0.001). CONCLUSION We confirm the value of AB and their counting in the diagnosis of GVH, with a diagnostic threshold of 4 AB and a prognostic threshold of 8 AB. Glands lined with eosinophilic cells could be an additional diagnostic criterion in favor of GVH to be confirmed by further studies.
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Affiliation(s)
- Benjamin Ducloux-Lebon
- Service d'anatomie et cytologie pathologiques, CHU Amiens Nord, place Victor-Pauchet, 80000 Amiens, France.
| | - Delphine Lebon
- Service d'hématologie clinique et thérapie cellulaire, CHU Amiens Sud, 1, Rond-Point du Professeur-Christian-Cabrol, 80054 Amiens cedex, France
| | - Jean-René Tesson
- Service d'anatomie et cytologie pathologiques, CHU Amiens Nord, place Victor-Pauchet, 80000 Amiens, France
| | - Mathurin Fumery
- Service d'hépato gastro-entérologie, CHU Amiens Sud, 1, Rond-Point du Professeur-Christian-Cabrol, 80054 Amiens cedex, France
| | - Jean-Pierre Marolleau
- Service d'hématologie clinique et thérapie cellulaire, CHU Amiens Sud, 1, Rond-Point du Professeur-Christian-Cabrol, 80054 Amiens cedex, France
| | - Denis Chatelain
- Service d'anatomie et cytologie pathologiques, CHU Amiens Nord, place Victor-Pauchet, 80000 Amiens, France
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Alkashash A, Bhamidipalli S, Wilkins BJ, Saeed OA, González IA. Validation of a Recently Proposed Histologic Grading System (The Farooq Grade) for Colonic Graft-Versus-Host Disease in the Pediatric Population. Pediatr Dev Pathol 2025:10935266251330159. [PMID: 40183303 DOI: 10.1177/10935266251330159] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/05/2025]
Abstract
BACKGROUND Colonic graft-versus-host disease (GVHD) is rare in children. The goal of this study was to evaluate the Lerner and the Farooq grade in pediatric patients. METHODS Retrospective multicenter study including all biopsies with a diagnosis of GVHD. RESULTS 101 patients were included (median age: 8.9 years) with a male predominance (59%). 71% of patients had extracolonic GVHD. 98% and 54% of cases had apoptotic bodies and >6 apoptotic bodies, respectively. Crypt dropout was seen in 53% of cases and ulceration in 19%. Using the Lerner grade, 47% of cases were grade 1, 13% grade 2, 20% grade 3 and 20% grade 4; and using the Farooq grade, 35% were indeterminate for GVHD, 25% low, 27% intermediate and 14% high grade. There was moderate agreement (K = 0.47) between the system. 67% of the Lerner grade 1 cases were considered indeterminate for GVHD using the Farooq grade. No difference was seen with GVHD-related death and the grading systems. GVHD-related death was associated with extraintestinal involvement (P = .04), and with treatment response (P < .01). CONCLUSIONS Although neither system was associated with GVHD-related death, given the more comprehensive approach, the authors suggest utilizing the Farooq grading system.
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Affiliation(s)
- Ahmad Alkashash
- Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Sruthi Bhamidipalli
- Department of Biostatistics and Health Data Science, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Benjamin J Wilkins
- Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA
| | - Omer A Saeed
- Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Iván A González
- Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
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Pezhouh MK, Lam-Himlin D, Zaheer A, Voltaggio L. Systemic diseases affecting the GI tract: A review of clinical and histopathologic manifestations. Ann Diagn Pathol 2024; 73:152351. [PMID: 39004038 DOI: 10.1016/j.anndiagpath.2024.152351] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2024] [Accepted: 05/31/2024] [Indexed: 07/16/2024]
Abstract
A variety of systemic diseases may affect the gastrointestinal (GI) tract. Since the GI tract responds to injury in limited ways, identifying these processes may be challenging, especially on small endoscopic biopsies. This article reviews the clinicopathologic features of commonly encountered systemic diseases affecting the tubular GI tract: sarcoidosis, graft vs. host disease, mast cell disorders, systemic sclerosis, and IgG-4 related disease. In addition, we offer guidance in differentiating them from their mimics.
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Affiliation(s)
- Maryam K Pezhouh
- University of California San Diego, Department of Pathology, CA, United States of America
| | - Dora Lam-Himlin
- Mayo Clinic, Department of Laboratory Medicine and Pathology, AZ, United States of America
| | - Atif Zaheer
- Johns Hopkins University, Department of Radiology, MD, United States of America
| | - Lysandra Voltaggio
- Johns Hopkins University, Department of Pathology, MD, United States of America.
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Bhowmik S, Mehra L, Ghosh T, Akhtar S, Tiwari A, Dutta R, Kedia S, Yadav R, Makharia GK, Ahuja V, Das P. A Systematic Review and Metaanalysis to Examine the Utility of Histological Parameters Such as Mucosal Basal Plasmacytosis and Eosinophilia for Distinguishing Inflammatory Bowel Disease and Non-IBD-Type Colitis. Int J Surg Pathol 2024:10668969241271352. [PMID: 39300818 DOI: 10.1177/10668969241271352] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/22/2024]
Abstract
Background and aim: Basic differentiation between an inflammatory bowel disease (IBD)-type colitis and a non-IBD type of colitis is the essential histological pre-requisite before further subclassifications are made. The combination of mucosal prominent eosinophilic cell infiltrate along with basal plasmacytosis is supposed to be a useful histological feature that can differentiate between IBD-type and non-IBD-type colitis. Hence, this systematic review and metaanalysis aimed to assess the reliability of mucosal basal plasmacytosis and eosinophilia for histological differentiation of IBD-type versus non-IBD-type colitis. Methods: We searched the PROSPERO, PubMed, Embase, and Scopus from January 1, 2000 to July 30, 2022 for all types of studies (prospective, cross-sectional, or retrospective studies) having histological features (including mucosal basal plasmacytosis, eosinophilia, and neutrophilic infiltration) in IBD and/or non-IBD colitis cases. Two reviewers extracted data, which were aggregated using random-effects models. Results: The 59 selected articles were evaluated for the predecided parameters. Both basal plasmacytosis and lamina propria plasmacytosis did not show any significant correlation between IBD-type and non-IBD-type colitis. The proportions for basal plasmacytosis with 95% CI were 0.50 (0.19-0.82) in IBD-type colitis and 0.46 (0.40-0.52) in non-IBD-type colitis, with a P value of .79. The proportion of lamina propria plasmacytosis with 95% CI was 0.67 (0.42-0.92) in IBD and 0.60 (0.35-0.85) in non-IBD-type colitis, with a P value being .7. Conclusions: This systematic review documented the dearth of published data on key histological features such as basal plasmacytosis and mucosal eosinophilia which are believed to differentiate between IBD-type and non-IBD-type colitis.
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Affiliation(s)
- Shubham Bhowmik
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, DL, India
| | - Lalita Mehra
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, DL, India
| | - Tamoghna Ghosh
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, DL, India
| | - Sagir Akhtar
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, DL, India
| | - Ashok Tiwari
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, DL, India
| | - Rimlee Dutta
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, DL, India
| | - Saurav Kedia
- Department of Gastroenterology All India Institute of Medical Sciences, New Delhi, DL, India
| | - Rajni Yadav
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, DL, India
| | - Govind K Makharia
- Department of Gastroenterology All India Institute of Medical Sciences, New Delhi, DL, India
| | - Vineet Ahuja
- Department of Gastroenterology All India Institute of Medical Sciences, New Delhi, DL, India
| | - Prasenjit Das
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, DL, India
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Feakins RM. Inflammatory disorders of the large intestine. MORSON AND DAWSON'S GASTROINTESTINAL PATHOLOGY 2024:709-857. [DOI: 10.1002/9781119423195.ch35] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Hong N, Wang B, Zhou HC, Wu ZX, Fang HY, Song GQ, Yu Y. Multidisciplinary management of ulcerative colitis complicated by immune checkpoint inhibitor-associated colitis with life-threatening gastrointestinal hemorrhage: A case report. World J Gastrointest Surg 2024; 16:2329-2336. [PMID: 39087117 PMCID: PMC11287687 DOI: 10.4240/wjgs.v16.i7.2329] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2024] [Revised: 05/26/2024] [Accepted: 06/18/2024] [Indexed: 07/22/2024] Open
Abstract
BACKGROUND Programmed cell death 1 (PD-1) inhibitors are immune checkpoint inhibitors (ICI) that have demonstrated significant efficacy in treating various advanced malignant tumors. While most patients tolerate treatment well, several adverse drug reactions, such as fatigue, myelosuppression, and ICI-associated colitis, have been reported. CASE SUMMARY This case involved a 57-year-old male patient with ulcerative colitis complicated by hepatocarcinoma who underwent treatment with tirelizumab (a PD-1 inhibitor) for six months. The treatment led to repeated life-threatening lower gastrointestinal hemorrhage. The patient received infliximab, vedolizumab, and other salvage procedures but ultimately required subtotal colectomy due to uncontrollable massive lower gastrointestinal bleeding. Currently, postoperative gastrointestinal bleeding has stopped, the patient's stool has turned yellow, and his full blood cell count has returned to normal. CONCLUSION This case highlights the necessity of early identification, timely and adequate treatment of ICI-related colitis, and rapid escalation to achieve the goal of improving prognosis.
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Affiliation(s)
- Na Hong
- Department of Gastroenterology, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, Anhui Province, China
| | - Bo Wang
- Department of Gastroenterology, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, Anhui Province, China
| | - Hang-Cheng Zhou
- Department of Pathology, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230036, Anhui Province, China
- Intelligent Pathology Institute, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230036, Anhui Province, China
| | - Zheng-Xiang Wu
- Department of Gastroenterology, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, Anhui Province, China
| | - Hua-Ying Fang
- Department of Gastroenterology, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, Anhui Province, China
| | - Geng-Qing Song
- Department of Gastroenterology and Hepatology, Metro Health Medical Center, Case Western Reserve University, Cleveland, OH 44109, United States
| | - Yue Yu
- Department of Gastroenterology, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, Anhui Province, China
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Arva NC, Bernieh A, Lopez-Nunez O, Pletneva M, Yang GY, Collins MH. Histopathology of Eosinophilic Gastrointestinal Diseases Beyond Eosinophilic Esophagitis. Immunol Allergy Clin North Am 2024; 44:369-381. [PMID: 38575230 DOI: 10.1016/j.iac.2024.01.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/06/2024]
Abstract
Eosinophilic gastrointestinal diseases (EGID), such as eosinophilic gastritis (EoG), eosinophilic enteritis, and eosinophilic colitis (EoC), are chronic inflammatory conditions characterized by persistent gastrointestinal symptoms and elevated levels of activated eosinophils in the gastrointestinal tract. EoG and eosinophilic duodenitis (EoD) are strongly associated with food allergen triggers and TH2 inflammation, whereas EoC shows minimal transcriptomic overlap with other EGIDs. The level of expression of certain genes associated with TH2 immune response is associated with certain histopathologic findings of EoG, EoD, and EoC. Current immune therapy for EoG depletes tissue eosinophilia with persistence of other histopathologic features of disease.
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Affiliation(s)
- Nicoleta C Arva
- Department of Pathology, Nationwide Children's Hospital, 700 Childrens Drive, Columbus, OH 43205, USA.
| | - Anas Bernieh
- Division of Pathology and Laboratory Medicine, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA
| | - Oscar Lopez-Nunez
- Division of Pathology and Laboratory Medicine, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA
| | - Maria Pletneva
- Department of Pathology, University of Utah, 2000 Circle of Hope, Room 3100, Salt Lake City, UT 84112, USA
| | - Guang-Yu Yang
- Department of Pathology, Northwestern University Feinberg School of Medicine, 303 East Chicago Avenue, Chicago, IL 60611, USA
| | - Margaret H Collins
- Division of Pathology and Laboratory Medicine, ML1035, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA
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Zhang T, Hagen CE. Gastrointestinal Biopsies in the Patient Post-Stem Cell Transplant: An Approach to Diagnosis. Surg Pathol Clin 2023; 16:745-753. [PMID: 37863563 DOI: 10.1016/j.path.2023.05.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2023]
Abstract
Graft-versus-host disease (GVHD) is a major complication of hematopoietic stem cell transplantation (SCT), leading to a significant morbidity and mortality. Histologically, gastrointestinal GVHD is characterized by crypt apoptosis and dropout. However, similar histologic features can also be seen in drug-induced injury and opportunistic infection. Knowledge of the timing of biopsy, patient medications, evidence of infection, and presence of GVHD at other organ sites can aid in the correct diagnosis and subsequent management of these patients. This review focuses on the pathologic differential diagnosis of apoptosis in gastrointestinal biopsies obtained from SCT patients.
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Affiliation(s)
- Tao Zhang
- Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 1st Street Southwest, Rochester, MN 55905, USA
| | - Catherine E Hagen
- Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 1st Street Southwest, Rochester, MN 55905, USA.
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Ojukwu K, Cox BK, Larson BK, Guindi M, Waters KM, Hutchings DA. Capecitabine-induced Gastrointestinal Injury Shows a Graft-Versus-Host Disease (GVHD)-like Pattern. Am J Surg Pathol 2023; 47:1160-1167. [PMID: 37493102 DOI: 10.1097/pas.0000000000002093] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/27/2023]
Abstract
Capecitabine is a commonly used oral chemotherapeutic agent. Gastrointestinal (GI) side effects are clinically well-known, however, the histopathologic changes have not been comprehensively studied. This study describes the largest case series (8 patients) characterizing the histopathology of capecitabine-induced GI injury. All patients were adults (median age: 64.5 y, range: 61 to 76 y) and there was gender parity. Patients were receiving treatment for malignancies of the colorectum (n=5), breast (n=1), pancreas (n=1), and appendix (n=1). All had GI symptoms, including 7 with diarrhea and abdominal pain and 1 with melena. Five of 8 (63%) showed graft-versus-host disease (GVHD)-like histologic changes in small intestinal and/or colonic biopsies characterized by crypt disarray and dropout, crypt atrophy, dilated crypts lined by attenuated epithelium, and increased crypt apoptosis. Neuroendocrine cell aggregates were present in 4 of 5 cases. Four of 5 showed patchy prominence in lamina propria eosinophils. One patient receiving concomitant radiation therapy had a small intestinal biopsy showing regenerative changes. Two patients had histologically unremarkable biopsies. On follow-up, capecitabine was discontinued or dose-reduced in all patients. Three of 5 patients with a GVHD-like pattern had clinical improvement, whereas 2 died shortly after biopsy. One with regenerative changes also had radiation dose reduction and improved clinically. Two with unremarkable biopsies improved symptomatically. In summary, capecitabine-related GI injury shows a GVHD-like pattern. Knowledge of this is important to confirm the diagnosis as patients typically improve with dose reduction or discontinuation of the drug.
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Affiliation(s)
- Kenechukwu Ojukwu
- Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA
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Hippe K, Kreft A, Reu-Hofer S, Rosenwald A, Ferrazzi F, Daniel C, Amann K, Kraus S, Holler E, Kandulski A, Hirsch D, Buttner A, Rösler W, Hildner K, Winkler J, Büttner-Herold M. Round-Robin test for the histological diagnosis of acute colonic Graft-versus-Host disease validating established histological criteria and grading systems. Virchows Arch 2023:10.1007/s00428-023-03544-3. [PMID: 37165134 DOI: 10.1007/s00428-023-03544-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2023] [Revised: 04/03/2023] [Accepted: 04/12/2023] [Indexed: 05/12/2023]
Abstract
Histomorpholgy is one of the mainstays of acute Graft-versus-host disease (GvHD) diagnosis. However, concerns about reproducibility and the most appropriate grading system question its usefulness. Our aim was to assess histomorphological parameters and previously reported grading systems for GvHD regarding reproducibility and validity. Moreover, we propose that sum scores, derived by combining separately scored morphological parameters into a total score, might provide a simplified but equally effective means to grade GvHD. A total of 123 colon biopsies were assessed across four pathologists for intestinal GvHD using a Round-Robin test and results were correlated with clinical findings. Interobserver reproducibility was high for histological parameters that were evaluated as indicators of acute GvHD. Published grading systems were moderately reproducible (ICC 0.679-0.769) while simplified sum scores, in comparison, showed better interrater reliability (ICC 0.818-0.896). All grading systems and sum scores were associated with clinical signs of GvHD and in part with therapy response and survival. However, they were not able to stratify patients according to the clinical severity of GvHD. In a hot-spot analysis 1 crypt apoptotic body (CAB) in 10 crypts was a reasonable cut-off value for minimal diagnostic criteria of GvHD. In conclusion, histology can contribute to the diagnosis of GvHD and is reproducible. Published grading systems are able to reflect clinical findings as are simplified sum scores, which showed improved reproducibility and might be easier to handle as they are based on adding up histological parameters rather than transferring histological findings into a separate grading system. Sum scores will have to be further tested in a prospective setting.
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Affiliation(s)
- Katrin Hippe
- Institute of Pathology, University of Regensburg, Regensburg, Germany
| | - Andreas Kreft
- Institute of Pathology, University Medical Center Mainz, Mainz, Germany
| | - Simone Reu-Hofer
- Institute of Pathology, Julius-Maximillians-University Würzburg, Würzburg, Germany
| | - Andreas Rosenwald
- Institute of Pathology, Julius-Maximillians-University Würzburg, Würzburg, Germany
| | - Fulvia Ferrazzi
- Department of Nephropathology, Institute of Pathology, Friedrich-Alexander-University Erlangen-Nuremberg (FAU) and University Hospital, Krankenhausstr. 8-10, 91054, Erlangen, Germany
- Institute of Pathology, Friedrich-Alexander-University Erlangen-Nuremberg (FAU) and University Hospital, Erlangen, Germany
| | - Christoph Daniel
- Department of Nephropathology, Institute of Pathology, Friedrich-Alexander-University Erlangen-Nuremberg (FAU) and University Hospital, Krankenhausstr. 8-10, 91054, Erlangen, Germany
| | - Kerstin Amann
- Department of Nephropathology, Institute of Pathology, Friedrich-Alexander-University Erlangen-Nuremberg (FAU) and University Hospital, Krankenhausstr. 8-10, 91054, Erlangen, Germany
| | - Sabrina Kraus
- Department of Internal Medicine II, University Hospital Wuerzburg, Würzburg, Germany
| | - Ernst Holler
- Department of Internal Medicine III, University Medical Centre, Regensburg, Germany
| | - Arne Kandulski
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious Diseases, University Hospital Regensburg, Regensburg, Germany
| | - Daniela Hirsch
- Institute of Pathology, University of Regensburg, Regensburg, Germany
| | - Anke Buttner
- School of Psychology, College of Life and Environmental Sciences, University of Birmingham, Birmingham, UK
| | - Wolf Rösler
- Department of Medicine 5, Friedrich-Alexander-University Erlangen-Nuremberg (FAU) and University Hospital, Erlangen, Germany
| | - Kai Hildner
- Department of Medicine 1, Kussmaul-Campus for Medical Research and Translational Research Center, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, University Hospital Erlangen, Deutsches Zentrum Immuntherapie (DZI), Erlangen, Germany
| | - Julia Winkler
- Department of Medicine 5, Friedrich-Alexander-University Erlangen-Nuremberg (FAU) and University Hospital, Erlangen, Germany
| | - Maike Büttner-Herold
- Department of Nephropathology, Institute of Pathology, Friedrich-Alexander-University Erlangen-Nuremberg (FAU) and University Hospital, Krankenhausstr. 8-10, 91054, Erlangen, Germany.
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12
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Boulagnon-Rombi C, Dufour C, Chatelain D. [Drug induced gastro-intestinal tract lesions: A pathologist point of view]. Ann Pathol 2023:S0242-6498(23)00045-7. [PMID: 36868901 DOI: 10.1016/j.annpat.2023.02.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2022] [Revised: 01/31/2023] [Accepted: 02/08/2023] [Indexed: 03/05/2023]
Abstract
The number of drugs available to clinicians, especially targeted therapies, grows continuously. Some drugs are known to cause frequent digestive adverse effects, which may affect the gastro-intestinal tract in a diffuse or localized manner. Some treatments may leave relatively pathognomonic deposits, but histological lesions of iatrogenic origin are mostly non-specific. The diagnostic and etiological approach is often complex because of these non-specific aspects and also because (1) a single type of drug may cause different histological lesions, (2) different drugs may cause identical histological lesions, (3) the patient may receive different drugs, and (4) drug-induced lesions may mimic other pathological entities such as inflammatory bowel disease, celiac disease, or graft versus host disease. The diagnosis of iatrogenic gastrointestinal tract injury therefore requires close anatomic-clinical correlation. The iatrogenic origin can only be formally established if the symptomatology improves when the incriminating drug is stopped. This review aims to present the different histological patterns of gastrointestinal tract iatrogenic lesions, the potentially incriminate drugs, as well as the histological signs to look for in order to help the pathologist to distinguish an iatrogenic injury from another pathology of the gastrointestinal tract.
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Affiliation(s)
- Camille Boulagnon-Rombi
- Service de pathologie, centre hospitalier universitaire de Reims, 51092 Reims cedex, France; Université de Reims Champagne Ardenne, CNRS, MEDyC UMR 7369, 51097 Reims, France.
| | - Charlotte Dufour
- Institut de pathologie, centre de biologie pathologie, centre hospitalier universitaire de Lille, 59000 Lille, France
| | - Denis Chatelain
- Service d'anatomie pathologique du CHU d'Amiens, site Nord, 80080 Amiens, France
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13
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Drug-induced digestive tract injury: decoding some invisible offenders. Hum Pathol 2023; 132:135-148. [PMID: 35714837 DOI: 10.1016/j.humpath.2022.06.014] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Accepted: 06/09/2022] [Indexed: 02/07/2023]
Abstract
There is an ever-growing list of pharmacological agents, several of which are attributed to cause clinically significant gastrointestinal (GI) injury. Many patients present with significant but nonspecific symptoms, that in conjunction with the absence of relevant drug history on the requisition slip can make the histopathologic diagnosis challenging. To complicate this, although some drugs have relatively characteristic histopathologic features (such as doxycycline), there exist many other drugs that exhibit wide and varying spectra of histopathologic findings (such as immune checkpoint inhibitors or olmesartan) and have histomorphologic overlap with many other commonly encountered disease entities. This review discusses the histopathologic features of some relatively recently described drugs causing GI tract injury, namely doxycycline, tacrolimus, mycophenolate, immune checkpoint inhibitors, and olmesartan. We also discuss the common mimics in histopathologic differential and some pearls that can help distinguish GI tract injury induced by the aforementioned drugs from its mimics. Awareness of the wide spectra of histopathologic changes associated with these drugs is crucial for practicing pathologists, to avoid misdiagnosis and guiding the clinician for an optimal patient management, which usually involves modifying or discontinuing the offending drug. Needless to say, once a diagnosis of drug-induced injury is suspected, clinicopathologic correlation including corroboration with the drug history is of utmost importance as is the exclusion of dual pathology in these patients.
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14
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Birkness-Gartman JE, Hutchings DA, Montgomery EA, Voltaggio L. Injury patterns and potential diagnostic pitfalls associated with radiation and radio-chemotherapy in the stomach and gastroesophageal junction. Hum Pathol 2023; 131:17-25. [PMID: 36495943 DOI: 10.1016/j.humpath.2022.12.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Revised: 11/30/2022] [Accepted: 12/05/2022] [Indexed: 12/12/2022]
Abstract
Chemoradiation-associated injury may cause marked epithelial and stromal changes in gastric specimens. We characterized these histologic features in a retrospective series of cases. Nineteen cases of radiochemotherapy-associated gastropathy were identified, including 16 from our institution and 3 from consultation material. Patient charts and hematoxylin and eosin-stained slides were reviewed. Most patients were men (79%) with a median age of 66 years. All patients had a documented history of radiation and 15 patients also received chemotherapy. The median time from treatment to biopsy or resection was 2.3 months. Gross and endoscopic findings included erythematous, hemorrhagic, or ulcerated mucosa. Mucosal eosinophilia was seen in 16 cases (84%) while 10 cases (53%) featured acute inflammation including neutrophilic microabscesses. Epithelial changes included increased apoptosis (6 cases, 32%) and marked epithelial atypia (10 cases, 53%), potentially mimicking malignancy in some cases. However, the atypical cells featured voluminous eosinophilic cytoplasm with low nuclear-to-cytoplasmic ratio, a clue to their benign nature. Neuroendocrine cell nests were seen in 4 cases (21%) and loosely aggregated in 1 case, potentially mimicking a well-differentiated neuroendocrine tumor or enterochromaffin-like (ECL) cell hyperplasia in autoimmune gastritis. Eleven cases (58%) featured vascular changes that included vessel dilation, hobnailed endothelial cells, and fibrin thrombi. Stromal changes were seen in 11 cases (58%) and included lamina propria hyalinization, submucosal fibrosis, and myofibroblast atypia. Injury associated with radiochemotherapy is histologically varied and may affect epithelial, stromal, and vascular compartments. Familiarity with these features is important as a subset of these findings may provoke concern for neoplasia.
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Affiliation(s)
- Jacqueline E Birkness-Gartman
- Department of Pathology, Johns Hopkins University School of Medicine, The Harry and Jeanette Weinberg Building, Baltimore, MD 21231-2410, USA
| | - Danielle A Hutchings
- Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
| | - Elizabeth A Montgomery
- Department of Pathology and Laboratory Medicine, University of Miami Miller School of Medicine, Miami, FL 33136-1005, USA
| | - Lysandra Voltaggio
- Department of Pathology, Johns Hopkins University School of Medicine, The Harry and Jeanette Weinberg Building, Baltimore, MD 21231-2410, USA.
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15
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Mehta RS, Saliba RM, Hayase E, Jenq RR, Abraham S, Rashid A, Rondon G, Al-Atrash G, Bashir Q, Hosing CM, Kebriaei P, Khouri I, Marin D, Nieto Y, Olson A, Oran B, Popat UR, Qazilbash MH, Ramdial J, Srour S, Champlin RE, Rezvani K, Shpall EJ, Alousi AM. Mycophenolate Mofetil: A Friend or a Foe with PTCy and Tacrolimus Prophylaxis in HLA-Matched donors? Transplant Cell Ther 2022; 28:500.e1-500.e10. [PMID: 35662592 DOI: 10.1016/j.jtct.2022.05.039] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Revised: 05/02/2022] [Accepted: 05/25/2022] [Indexed: 10/18/2022]
Abstract
Adapted from the haploidentical literature, post-transplantation cyclophosphamide (PTCy) is increasingly being used with HLA-matched donors, generally with a calcineurin inhibitor, such as tacrolimus (Tac) with or without mycophenolate mofetil (MMF). Owing to its immunosuppressive, potentially antitumor, and antimicrobial properties, MMF is an attractive drug; however, it remains unclear how much benefit is gained when used with PTCy/Tac. To assess that, we compared PTCy/Tac (n=242) to PTCy/Tac/MMF (n= 144) in recipients of HLA-matched donors. In multivariate analysis, the PTCy/Tac/MMF group had a significantly higher risk of grade II-IV acute graft-versus-host disease (GVHD; hazard ratio (HR) 2.1, 95% confidence interval (CI) 1.6-2.8, p<0.001), and steroid-refractory/dependent acute GVHD (HR 4.8, 95% CI 2.4-9.6, p<0.001), yet a significantly lower risk of relapse (HR 0.5, 95% CI, 0.3-0.9, p=0.009) and better progression-free survival (PFS; HR 0.7, 95% CI 0.5-0.9, p=0.04). There was no difference in the risk of grade III-IV acute GVHD, chronic GVHD, non-relapse mortality, or overall survival. MMF was associated with prolonged neutrophil engraftment by 2 days, and a higher risk of bacterial infections. In an exploratory stool microbiome analysis (n=16), we noted a higher relative abundance of β-glucuronidase-producing bacteria in the MMF group, which may have a role in the pathogenesis of MMF-related GVHD. Our data suggest that the addition of MMF to PTCy/Tac for HLA-matched donor HCT does not provide any advantage for GVHD prevention. Further studies are needed to decipher this mechanism, and understand its role with PTCy-based prophylaxis.
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Affiliation(s)
- Rohtesh S Mehta
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX.
| | - Rima M Saliba
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Eiko Hayase
- Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Robert R Jenq
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Susan Abraham
- Department of Anatomical Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Asif Rashid
- Department of Anatomical Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Gabriela Rondon
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Gheath Al-Atrash
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Qaiser Bashir
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Chitra M Hosing
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Partow Kebriaei
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Issa Khouri
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - David Marin
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Yago Nieto
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Amanda Olson
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Betul Oran
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Uday R Popat
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Muzaffar H Qazilbash
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Jeremy Ramdial
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Samer Srour
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Richard E Champlin
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Katayoun Rezvani
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Elizabeth J Shpall
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Amin M Alousi
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
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16
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Herlihy N, Feakins R. Gut inflammation induced by drugs: Can pathology help to differentiate from inflammatory bowel disease? United European Gastroenterol J 2022; 10:451-464. [PMID: 35633273 PMCID: PMC9189468 DOI: 10.1002/ueg2.12242] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2021] [Accepted: 04/24/2022] [Indexed: 12/13/2022] Open
Abstract
Drug‐induced mucosal injury (DIMI) in the gastrointestinal tract is important to recognise, partly because cessation of the culprit agent alone may result in resolution of symptoms. An ever‐growing list of medications, including newer immunotherapeutic agents and targeted therapies, can cause gastrointestinal inflammation of varying severity. However, the diagnosis of DIMI is challenging, as a single drug can induce a variety of histopathological patterns of injury including acute colitis, chronic colitis, microscopic colitis, apoptotic colopathy, and ischaemic‐type colitis. An additional consideration is the potential clinical, endoscopic and histological overlap of DIMI with gastrointestinal mucosal injury secondary to other entities such as inflammatory bowel disease (IBD). We discuss DIMI of the gastrointestinal tract with an emphasis on histological patterns that mimic IBD, histological features which may distinguish the two entities, and the diagnostic role and limitations of the pathologist.
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Affiliation(s)
- Naoimh Herlihy
- Department of Cellular Pathology, Royal Free Hospital, London, UK
| | - Roger Feakins
- Department of Cellular Pathology, Royal Free Hospital, London and University College London, London, UK
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17
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Rossi C, Simoncelli G, Arpa G, Stracuzzi A, Parente P, Fassan M, Vanoli A, Villanacci V. Histopathology of intestinal villi in neonatal and paediatric age: main features with clinical correlation - Part I. Pathologica 2022; 114:12-21. [PMID: 34856604 PMCID: PMC9040547 DOI: 10.32074/1591-951x-337] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Accepted: 07/30/2021] [Indexed: 11/30/2022] Open
Abstract
The neonatal and paediatric spectrum of small bowel disorders encompass a wide variety of conditions, ranging from food allergies to life-threatening surgical emergencies or life-long medical conditions and, as such, it comes with a whole set of diagnostic challenges for the non-paediatric pathologist. Histologic examination is a cornerstone of diagnosis in a large number of diseases and may still provide important diagnostic clues in the appropriate clinical context. In this review, divided in two sections, we aim to provide a comprehensive histopathological summary of paediatric small bowel alteration and their differential diagnoses with a reference to the main clinical aspects required for appropriate interpretation. Specifically, in this first part, we describe congenital and metabolic disorders, intestinal lymphangiectasia, immunodeficiencies, GVHD, and necrotising enterocolitis.
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Affiliation(s)
- Chiara Rossi
- Unit of Anatomic Pathology, Department of Molecular Medicine, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy
| | | | - Giovanni Arpa
- Unit of Anatomic Pathology, Department of Molecular Medicine, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy
| | - Alessandra Stracuzzi
- Pathological Anatomy Unit, Department of Diagnostic and Laboratory Medicine, IRCCS Bambino Gesù Children’s Hospital, Rome, Italy
| | - Paola Parente
- Pathology Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
| | - Matteo Fassan
- Department of Medicine (DIMED), Surgical Pathology Unit, University of Padua, Padua, Italy
- Veneto Institute of Oncology, IOV-IRCCS, Padua, Italy
| | - Alessandro Vanoli
- Unit of Anatomic Pathology, Department of Molecular Medicine, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy
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18
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Tang L, Wang J, Lin N, Zhou Y, He W, Liu J, Ma X. Immune Checkpoint Inhibitor-Associated Colitis: From Mechanism to Management. Front Immunol 2021; 12:800879. [PMID: 34992611 PMCID: PMC8724248 DOI: 10.3389/fimmu.2021.800879] [Citation(s) in RCA: 76] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2021] [Accepted: 11/29/2021] [Indexed: 02/05/2023] Open
Abstract
Immune checkpoint inhibitors (ICIs), as one of the innovative types of immunotherapies, including programmed cell death-1 (PD-1), programmed cell death-ligand 1 (PD-L1), and cytotoxic T lymphocyte antigen 4 (CTLA-4) inhibitors, have obtained unprecedented benefit in multiple malignancies. However, the immune response activation in the body organs could arise immune-related adverse events (irAEs). Checkpoint inhibitor colitis (CIC) is the most widely reported irAEs. However, some obscure problems, such as the mechanism concerning gut microbiota, the confusing differential diagnosis with inflammatory bowel disease (IBD), the optimal steroid schedule, the reintroduction of ICIs, and the controversial prognosis features, influence the deep understanding and precise diagnosis and management of CIC. Herein, we based on these problems and comprehensively summarized the relevant studies of CIC in patients with NSCLC, further discussing the future research direction of this specific pattern of irAEs.
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Affiliation(s)
- Liansha Tang
- Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Jialing Wang
- Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Nan Lin
- Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Yuwen Zhou
- Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Wenbo He
- Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, China
| | - Jiyan Liu
- Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Xuelei Ma
- Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
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19
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Hamdeh S, Micic D, Hanauer S. Drug-Induced Colitis. Clin Gastroenterol Hepatol 2021; 19:1759-1779. [PMID: 32360808 DOI: 10.1016/j.cgh.2020.04.069] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2020] [Revised: 03/31/2020] [Accepted: 04/20/2020] [Indexed: 02/07/2023]
Abstract
Drug-induced colitis encompasses a wide spectrum of colon disorders that can manifest microscopically or macroscopically. Patients present with new-onset colitis or exacerbations of inflammatory bowel diseases; in some cases, colitis resolves with discontinuation of medication. Mucosal injury can be focal or extensive, involving the entire colonic mucosa, and sometimes involves other parts of the gastrointestinal tract. It has been a challenge to determine the proportion of new-onset colitis caused by medication and there are few data on the overall prevalence. We review the drugs that have been linked with development of drug-induced colitis and strategies for physicians who believe their patients have this disorder-usually discontinuation of the drug believed to cause colitis and treatment with steroids or immune-modulating therapies. Physicians must be aware of medications that can cause colitis.
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Affiliation(s)
- Shadi Hamdeh
- Department of Internal Medicine, Division of Gastroenterology, Hepatology and Motility, University of Kansas, Kansas City, Kansas.
| | - Dejan Micic
- Department of Internal Medicine, Section of Gastroenterology, Hepatology and Nutrition, University of Chicago, Chicago, Illinois
| | - Stephen Hanauer
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois
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20
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Abstract
Tacrolimus is a common immunosuppressant used in solid organ transplant recipients. Although most patients develop diarrheal symptoms, data regarding patterns of injury in patients taking tacrolimus are limited. We performed this study to characterize tacrolimus-related features of colonic injury. We retrospectively identified colonic samples from 20 patients receiving tacrolimus monotherapy. Records were reviewed for symptoms, endoscopic findings, other medications, and infections. None of the patients had gastrointestinal infections or used other drugs known to cause colonic injury; none had received mycophenolate within 6 months of presentation. Cases were evaluated for the nature and distribution of inflammation and crypt abnormalities, including distortion, destruction, and apoptosis. Eighteen (90%) patients were solid organ transplant recipients. Seventeen (85%) had gastrointestinal symptoms, particularly diarrhea (75%). More than 50% had endoscopic colitis and 15% had ulcers and/or erosions. Most (90%) cases showed regenerative epithelial changes; apoptotic crypt cells were present in 55% and numerous in 10% of cases. Neutrophilic cryptitis was present in 60% of cases; 35% showed crypt destruction. Plasma cell-rich lamina propria inflammation and crypt distortion were observed in 40% and 25% of cases, respectively. There was no correlation between therapy duration and features of chronic injury. We conclude that tacrolimus can cause symptomatic colitis. Histologic abnormalities are often mild, featuring regenerative crypts and scattered apoptotic debris. However, 40% of symptomatic patients have chronic colitis, most likely reflecting drug-induced immune dysregulation. Pathologists should be aware of these associations because colitis often resolves with decreasing drug dosage rather than treatment directed toward inflammatory bowel disease.
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21
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Patil PA, Zhang X. Pathologic Manifestations of Gastrointestinal and Hepatobiliary Injury in Immune Checkpoint Inhibitor Therapy. Arch Pathol Lab Med 2021; 145:571-582. [PMID: 32338534 DOI: 10.5858/arpa.2020-0070-ra] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/24/2020] [Indexed: 02/05/2023]
Abstract
CONTEXT.— Immune checkpoint inhibitors (CPIs), including cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors and the programmed death receptor-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitors, are being increasingly used for treating many advanced malignancies. However, CPI therapy is also associated with gastrointestinal and hepatobiliary adverse effects. OBJECTIVES.— To review the adverse effects of CPI therapy on the gastrointestinal tract and hepatobiliary system. To describe histopathologic patterns and discuss differential diagnostic considerations in the diagnosis of CPI injuries. DATA SOURCES.— Published peer-reviewed literature in the English language and personal experience in the diagnosis of CPI injuries. CONCLUSIONS.— The pathologic manifestations of CPI therapy-induced gastrointestinal and hepatobiliary injury are broad. The patterns of esophageal CPI injury include lymphocytic inflammation and ulcerative esophagitis, while those of gastric injury include chronic active gastritis, lymphocytic gastritis, focal enhancing gastritis, and periglandular inflammation. The duodenal injury may present as duodenitis with villous blunting and granulomas. We also noticed active colitis, microscopic colitis, chronic active colitis, increased apoptosis, ischemic colitis, and nonspecific inflammatory reactive changes in colonic injuries. The reported histologic features of hepatobiliary injuries are panlobular hepatitis, centrilobular necrosis, portal inflammation with bile duct injury, steatosis, nodular regenerative hyperplasia, and secondary sclerosing cholangitis. In summary, we discuss the pathologic features and differential diagnosis of CPI therapy-induced gastrointestinal and hepatobiliary injury. Recognition of CPI injury is important to determine the proper management that often includes cessation of CPI therapy, and administration of steroids or other immunosuppressive agents, based on severity of injury.
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Affiliation(s)
- Pallavi A Patil
- From the Department of Pathology, Yale University School of Medicine, New Haven, Connecticut
| | - Xuchen Zhang
- From the Department of Pathology, Yale University School of Medicine, New Haven, Connecticut
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22
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Wölfl M, Qayed M, Benitez Carabante MI, Sykora T, Bonig H, Lawitschka A, Diaz-de-Heredia C. Current Prophylaxis and Treatment Approaches for Acute Graft-Versus-Host Disease in Haematopoietic Stem Cell Transplantation for Children With Acute Lymphoblastic Leukaemia. Front Pediatr 2021; 9:784377. [PMID: 35071133 PMCID: PMC8771910 DOI: 10.3389/fped.2021.784377] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Accepted: 12/09/2021] [Indexed: 11/13/2022] Open
Abstract
Acute graft-versus-host disease (aGvHD) continues to be a leading cause of morbidity and mortality following allogeneic haematopoietic stem cell transplantation (HSCT). However, higher event-free survival (EFS) was observed in patients with acute lymphoblastic leukaemia (ALL) and grade II aGvHD vs. patients with no or grade I GvHD in the randomised, controlled, open-label, international, multicentre Phase III For Omitting Radiation Under Majority age (FORUM) trial. This finding suggests that moderate-severity aGvHD is associated with a graft-versus-leukaemia effect which protects against leukaemia recurrence. In order to optimise the benefits of HSCT for leukaemia patients, reduction of non-relapse mortality-which is predominantly caused by severe GvHD-is of utmost importance. Herein, we review contemporary prophylaxis and treatment options for aGvHD in children with ALL and the key challenges of aGvHD management, focusing on maintaining the graft-versus-leukaemia effect without increasing the severity of GvHD.
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Affiliation(s)
- Matthias Wölfl
- Pediatric Hematology, Oncology and Stem Cell Transplantation, Children's Hospital, Würzburg University Hospital, Würzburg, Germany
| | - Muna Qayed
- Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Emory University, Atlanta, GA, United States
| | - Maria Isabel Benitez Carabante
- Department of Pediatric Hematology and Oncology, Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain
| | - Tomas Sykora
- Haematopoietic Stem Cell Transplantation Unit, Department of Pediatric Haematology and Oncology, Comenius University Children's Hospital, Bratislava, Slovakia
| | - Halvard Bonig
- Institute for Transfusion Medicine and Immunohematology, Goethe-University Frankfurt/Main, Frankfurt, Germany.,German Red Cross Blood Service BaWüHe, Frankfurt, Germany
| | - Anita Lawitschka
- Department of Pediatrics, St. Anna Kinderspital and Children's Cancer Research Institute, Medical University of Vienna, Vienna, Austria
| | - Cristina Diaz-de-Heredia
- Department of Pediatric Hematology and Oncology, Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain
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23
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Ghouri YA, Tahan V, Shen B. Secondary causes of inflammatory bowel diseases. World J Gastroenterol 2020; 26:3998-4017. [PMID: 32821067 PMCID: PMC7403802 DOI: 10.3748/wjg.v26.i28.3998] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2020] [Revised: 05/15/2020] [Accepted: 07/16/2020] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel diseases (IBD), conventionally consist of Crohn's disease (CD) and ulcerative colitis. They occur in individuals with high risk genotype for the disease in the setting of appropriate environmental factors. The pathogenesis of IBD involves a dysregulated autoimmune response to gut dysbiosis, which in turn is triggered due to exposure to various inciting environmental factors. But there is no clearly defined etiology of IBD and this type of disease is termed as "idiopathic IBD", "classic IBD", or "primary IBD". We reviewed the current medical literature and found that certain etiological factors may be responsible for the development of IBD or IBD-like conditions, and we consider this form of de novo IBD as "secondary IBD". Currently known factors that are potentially responsible for giving rise to secondary IBD are medications; bowel altering surgeries and transplantation of organs, stem cells or fecal microbiome. Medications associated with the development of secondary IBD include; immunomodulators, anti-tumor necrosis factor alpha agents, anti-interleukin agents, interferons, immune stimulating agents and checkpoint inhibitors. Colectomy can in some cases give rise to de novo CD, pouchitis of the ileal pouch, or postcolectomy enteritis syndrome. After solid organ transplantation or hematopoietic stem cell transplantation, the recipient may develop de novo IBD or IBD flare. Fecal microbiota transplantation has been widely used to treat patients suffering from recurrent Clostridium difficile infection but can also causes IBD flares.
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Affiliation(s)
- Yezaz A Ghouri
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Missouri- School of Medicine, Columbia, MO 65201, United States
| | - Veysel Tahan
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Missouri- School of Medicine, Columbia, MO 65201, United States
| | - Bo Shen
- Department of Medicine and Surgery, Interventional IBD Center, Columbia University Irving Medical Center/New York Presbyterian Hospital, New York, NY 10032, United States
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24
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Abstract
Graft-vs-host disease, characteristically a major complication of allogenic hematopoietic stem cell transplantation, is rare after solid organ transplantation. We report a 50-year-old man who presented with abdominal pain, vomiting, and diarrhea shortly after bilateral lung transplantation. Colonoscopy with biopsy revealed diffuse severe active colitis with ulceration and crypt apoptosis consistent with graft-vs-host disease colitis. The diagnosis was confirmed by the presence of donor lymphocytes in the peripheral blood. His symptoms were refractory to corticosteroids but responded to the addition of infliximab and extracorporeal photophoresis. He remained in remission 17 months later.
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25
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Review of Drug-induced Injury in Mucosal Biopsies From the Tubular Gastrointestinal Tract. Adv Anat Pathol 2019; 26:151-170. [PMID: 30870181 DOI: 10.1097/pap.0000000000000230] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
The use of prescription and over-the-counter medications is on the rise in the US population, especially among those aged 65 and over, with over 46% of the population taking at least 1 prescription medication. Given the frequency of medication use, and that the majority of these medications are taken orally, it has become increasingly relevant for pathologist examining endoscopically obtained gastrointestinal tract mucosal biopsies to consider and recognize patterns of mucosal injury associated with various drugs. Reports on injuries associated with certain classes of drugs can be scattered among different sources, making a comprehensive view of various injury patterns and the drugs known to cause them difficult to obtain. Herein, we provide a comprehensive overview of the drugs known to cause mucosal injuries in the tubular gastrointestinal tract organized by the organ involved and the prominent pattern of injury.
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26
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Mourad N, Michel RP, Marcus VA. Pathology of Gastrointestinal and Liver Complications of Hematopoietic Stem Cell Transplantation. Arch Pathol Lab Med 2019; 143:1131-1143. [PMID: 30838881 DOI: 10.5858/arpa.2018-0282-ra] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
CONTEXT.— Despite advances in therapeutic and preventive measures, hematopoietic stem cell transplant recipients remain at risk for a variety of gastrointestinal and liver complications. OBJECTIVE.— To detail the pathologic features of the various gastrointestinal and liver complications occurring after hematopoietic stem cell transplantation in relation to their clinical context. The specific complications covered include graft-versus-host disease, mycophenolate mofetil-induced injury, timeline of infections, neutropenic enterocolitis, gastrointestinal thrombotic microangiopathy, sinusoidal obstruction syndrome, hepatic iron overload, and the controversy around cord colitis syndrome. DATA SOURCES.— The content of this article is based on pertinent peer-reviewed articles in PubMed, relevant textbooks, and on the authors' personal experiences. CONCLUSIONS.— The final histopathologic diagnosis requires the integration of clinical and histologic findings and the exclusion of other competing causes of injury. Review of the clinical data, including the original disease pretransplant, the type of transplant, the timing of the gastrointestinal and/or liver manifestations, the timing of the biopsy after transplant, the presence of graft-versus-host disease in other organs and sites, the list of drug regimens, and the clinical and laboratory evidence of infection, is the key to reaching the proper histologic diagnosis.
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Affiliation(s)
- Nathalie Mourad
- Faculté de médecine, département de biologie moléculaire, de biochimie médicale et de pathologie, Université Laval, Hôpital du Saint-Sacrement - CHU de Québec, Québec, Québec, Canada (Dr Mourad); the Department of Pathology, McGill University and McGill University Health Center, Montreal, Quebec, Canada (Drs Michel and Marcus)
| | - René P Michel
- Faculté de médecine, département de biologie moléculaire, de biochimie médicale et de pathologie, Université Laval, Hôpital du Saint-Sacrement - CHU de Québec, Québec, Québec, Canada (Dr Mourad); the Department of Pathology, McGill University and McGill University Health Center, Montreal, Quebec, Canada (Drs Michel and Marcus)
| | - Victoria A Marcus
- Faculté de médecine, département de biologie moléculaire, de biochimie médicale et de pathologie, Université Laval, Hôpital du Saint-Sacrement - CHU de Québec, Québec, Québec, Canada (Dr Mourad); the Department of Pathology, McGill University and McGill University Health Center, Montreal, Quebec, Canada (Drs Michel and Marcus)
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27
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Wu TT. Other Inflammatory Disorders of Duodenum. SURGICAL PATHOLOGY OF NON-NEOPLASTIC GASTROINTESTINAL DISEASES 2019:239-263. [DOI: 10.1007/978-3-030-15573-5_10] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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28
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Wong M, Larson BK, Dhall D. Neuroendocrine proliferations in inflammatory bowel disease: differentiating neuroendocrine tumours from neuroendocrine cell micronests. Histopathology 2018; 74:415-423. [DOI: 10.1111/his.13769] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2018] [Revised: 09/28/2018] [Accepted: 10/07/2018] [Indexed: 01/17/2023]
Affiliation(s)
- Mary Wong
- Department of Pathology and Laboratory Medicine; Cedars Sinai Medical Center; Los Angeles CA USA
| | - Brent K Larson
- Department of Pathology and Laboratory Medicine; Cedars Sinai Medical Center; Los Angeles CA USA
| | - Deepti Dhall
- Department of Pathology and Laboratory Medicine; Cedars Sinai Medical Center; Los Angeles CA USA
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29
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Karamchandani DM, Chetty R. Apoptotic colopathy: a pragmatic approach to diagnosis. J Clin Pathol 2018; 71:1033-1040. [DOI: 10.1136/jclinpath-2018-205388] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2018] [Accepted: 08/27/2018] [Indexed: 12/17/2022]
Abstract
‘Apoptotic colopathy’ is an umbrella term signifying a pattern of injury where the gastrointestinal biopsy shows a colitic picture with apoptosis as the predominant histological feature. Although the entities within apoptotic colopathy share a common histological feature— ‘apoptosis’, there is a list of varied clinical differential diagnoses that produce this similar histological pattern of injury. These include graft-versus-host disease, drug-induced injury due to multiple drugs (in particular, mycophenolate mofetil, check point inhibitor therapy and some others), infections (particularly cytomegalovirus, adenovirus and some others), immune disorders and other miscellaneous causes. However, the management of these varied differentials is strikingly different, thus necessitating an algorithmic approach for accurate diagnosis and optimal patient management. A definitive diagnosis requires interpretation of varied histological findings in the appropriate clinical context including clinical history, drug history and laboratory findings. This review will focus on the histopathological findings of varied entities that can manifest as ‘apoptotic colopathy’ on assessment of colonic biopsies.
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30
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Bläker H. [Gastrointestinal tract diseases induced by medications]. DER PATHOLOGE 2018; 39:571-575. [PMID: 30171343 DOI: 10.1007/s00292-018-0478-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Gastrointestinal symptoms are common side effects of medical drugs. They are usually mild but sometimes require diagnostic endoscopy and histologic evaluation. Due to the rapidly increasing number of drugs developed especially for cancer treatment, pathologists are faced with a spectrum of different drug-associated histologies in all segments of the gastrointestinal tract. Some medication-induced mucosal damage features may mimic classical pathologies of nondrug-associated diseases, while others result in novel phenotypes. The present article focusses on the histologic presentations of gastrointestinal diseases induced by medications that either compromise or induce immune response.
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Affiliation(s)
- H Bläker
- Pathologisches Institut, Charité Universitätsmedizin, Chariteplatz 1, 10117, Berlin, Deutschland.
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31
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Brincidofovir (CMX001) Toxicity Associated With Epithelial Apoptosis and Crypt Drop Out in a Hematopoietic Cell Transplant Patient: Challenges in Distinguishing Drug Toxicity From GVHD. J Pediatr Hematol Oncol 2018; 40:e364-e368. [PMID: 29846280 PMCID: PMC6059994 DOI: 10.1097/mph.0000000000001227] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Brincidofovir (CMX001) is an oral agent with activity against double-strand DNA viruses undergoing clinical trials in immunocompromised patients. We report a patient clinically diagnosed with brincidofovir-related gastrointestinal (GI) toxicity and his histologic findings. A 2-year-old boy with medulloblastoma undergoing autologous hematopoietic cell transplantation developed adenovirus viremia 9 days posttransplant. After initial treatment with intravenous cidofovir he was started on oral brincidofovir as part of a clinical trial. He developed hematochezia, anorexia, and emesis 11 weeks later. Sigmoid colon biopsy showed marked crypt drop out, moderate epithelial apoptosis, and lamina propria edema. The pathologic diagnosis was drug-related injury versus infection. Brincidofovir toxicity was diagnosed clinically and the drug was discontinued. His GI symptoms improved in 2 weeks with supportive care and octreotide. Brincidofovir causes GI toxicity and histologically demonstrates epithelial apoptosis and crypt injury, similar to graft versus host disease and mycophenolate mofetil toxicity.
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32
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Tayyem O, Saraireh H, Al Hanayneh M, Stevenson HL. Heart transplant recipient with mycophenolate mofetil-induced colitis: the great imitator. BMJ Case Rep 2018; 2018:bcr-2017-224035. [PMID: 29930181 DOI: 10.1136/bcr-2017-224035] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023] Open
Abstract
In this article, we report a case of a 55-year-old male heart transplant recipient who presented with diarrhoea. An extensive workup for infectious diseases was negative. The patient had a colonoscopy with biopsies showing colitis that mimicked graft-versus-host disease on histopathology. After excluding other potential causes and excluding acute cellular rejection, mycophenolate mofetil was discontinued, and the patient had significant clinical improvement with increased appetite and weight gain.
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Affiliation(s)
- Obada Tayyem
- Department of Internal Medicine, University of Texas Medical Branch at Galveston, Galveston, Texas, USA
| | - Hamzeh Saraireh
- Department of Internal Medicine, University of Texas Medical Branch at Galveston, Galveston, Texas, USA
| | - Muhannad Al Hanayneh
- Department of Gastroenterology and Hepatology, University of Texas Medical Branch at Galveston, Galveston, Texas, USA
| | - Heather L Stevenson
- Department of Pathology, University of Texas Medical Branch Institute for the Medical Humanities, Galveston, Texas, USA
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33
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Panarelli NC, Yantiss RK. Inflammatory and infectious manifestations of immunodeficiency in the gastrointestinal tract. Mod Pathol 2018; 31:844-861. [PMID: 29403083 DOI: 10.1038/s41379-018-0015-9] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2017] [Revised: 11/24/2017] [Accepted: 12/11/2017] [Indexed: 12/27/2022]
Abstract
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.
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34
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Moroncini G, Benfaremo D, Mandolesi A, Gabrielli A. Mycophenolate mofetil-induced colitis in a patient with systemic sclerosis. BMJ Case Rep 2018; 2018:bcr-2018-224829. [PMID: 29776943 DOI: 10.1136/bcr-2018-224829] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
Abstract
We present the case of a 44-year-old woman affected by systemic sclerosis (SSc) who was admitted to our department for abdominal pain, nausea, vomiting and fever. Imaging studies showed the presence of a thickened colon wall involving the descending colon and the sigma, while a subsequent endoscopy revealed multiple serpiginous ulcers covered with fibrin and exudates. Under the hypothesis of drug-induced colitis, mycophenolate mofetil (MMF), which she was taking for SSc-related interstitial lung disease (ILD), was readily suspended, with a rapid recovery without further treatment. A follow-up colonoscopy showed the complete resolution of the ulcers. This is the first case of MMF-induced colitis in a patient being treated for SSc-ILD.
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Affiliation(s)
- Gianluca Moroncini
- Dipartimento Scienze Cliniche e Molecolari, Università Politecnica delle Marche, Ancona, Italy.,Clinica Medica, AOU Ospedali Riuniti di Ancona, Ancona, Italy
| | - Devis Benfaremo
- Dipartimento Scienze Cliniche e Molecolari, Università Politecnica delle Marche, Ancona, Italy.,Clinica Medica, AOU Ospedali Riuniti di Ancona, Ancona, Italy
| | | | - Armando Gabrielli
- Dipartimento Scienze Cliniche e Molecolari, Università Politecnica delle Marche, Ancona, Italy.,Clinica Medica, AOU Ospedali Riuniti di Ancona, Ancona, Italy
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35
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Cardona DM, Detweiler CJ, Shealy MJ, Sung AD, Wild DM, Poleski MH, Balmadrid BL, Cirrincione CT, Howell DN, Sullivan KM. Use of the National Institutes of Health Consensus Guidelines Improves the Diagnostic Sensitivity of Gastrointestinal Graft-Versus-Host Disease. Arch Pathol Lab Med 2018; 142:1098-1105. [PMID: 29697275 DOI: 10.5858/arpa.2017-0054-oa] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
CONTEXT - Graft-versus-host disease of the gastrointestinal tract is a common complication of hematopoietic stem cell transplant associated with significant morbidity and mortality. Accurate diagnosis can be difficult and is a truly clinicopathologic endeavor. OBJECTIVES - To assess the diagnostic sensitivity of gastrointestinal graft-versus-host disease using the 2015 National Institutes of Health (NIH) histology consensus guidelines and to analyze histologic findings that support the guidelines. DESIGN - Patients with allogeneic hematopoietic stem cell transplants were identified via a retrospective search of our electronic medical records from January 1, 2005, to January 1, 2011. Endoscopies with available histology were reviewed by 2 pathologists using the 2015 NIH guidelines. The clinical diagnosis was used as the gold standard. A nontransplant set of endoscopic biopsies was used as a control. RESULTS - Of the 250 total endoscopies, 217 (87%) had a clinical diagnosis of gastrointestinal graft-versus-host disease. Use of the NIH consensus guidelines showed a sensitivity of 86% and a specificity of 65%. Thirty-seven of 58 (64%) cases with an initial false-negative histopathologic diagnosis were diagnosed as graft-versus-host disease on our review. CONCLUSIONS - Use of the NIH histology consensus guidelines results in a high sensitivity and specificity, thereby decreasing false-negatives. Additionally, use of the NIH guidelines aids in creating uniformity and diagnostic clarity. Correlation with clinical and laboratory findings is critical in evaluating the differential diagnosis and to avoid false-positives. As expected, increased apoptosis with decreased inflammation was associated with a pathologic diagnosis of graft-versus-host disease and supports the NIH guidelines.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | - Keith M Sullivan
- From the Departments of Pathology (Drs Cardona, Detweiler, Shealy, and Howell) and Internal Medicine (Drs Sung, Wild, Poleski, Balmadrid, and Sullivan), Duke University Medical Center, Durham, North Carolina; and the Department of Biostatistics (Ms Cirrincione), Duke Cancer Institute, Durham, North Carolina
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36
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Abstract
CONTEXT - Patients who receive an upper gastrointestinal endoscopic examination frequently have biopsies taken from the duodenum. Accurate interpretation of duodenal biopsies is essential for patient care. Celiac disease is a common clinical concern, but pathologists need to be aware of other conditions of the duodenum that mimic celiac disease. OBJECTIVE - To review the normal histologic features of duodenal mucosa and describe the clinical and histologic findings in celiac disease and its mimics, listing the differentiating features of biopsies with villous atrophy and epithelial lymphocytosis. DATA SOURCES - The study comprises a literature review of pertinent publications as of November 30, 2016. CONCLUSIONS - Celiac disease is a common cause of abnormal duodenal histology. However, many of the histologic features found in the duodenal biopsy of patients with celiac disease are also present in other conditions that affect the small bowel. Diagnostic precision may be enhanced by obtaining a careful patient history and by ancillary laboratory testing, particularly for the presence of antitissue transglutaminase antibodies.
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Affiliation(s)
- Daniel R Owen
- From the Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada
| | - David A Owen
- From the Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada
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37
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Sun BL, Jain R, Patel C, Bhattacharyya AK. Graft-Versus-Host Disease With Early Cytomegalovirus Infection in Gastrointestinal Tract Biopsies. Int J Surg Pathol 2017; 26:347-352. [PMID: 29207904 DOI: 10.1177/1066896917746745] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Gastrointestinal (GI) graft-versus-host disease (GVHD) and cytomegalovirus (CMV) infection often simulate each other. However, distinction between GVHD and CMV infection is critical in the management of immunosuppression for transplant recipients. This study retrospectively reviewed 16 patients diagnosed with GVHD from 2010 to 2016 and found 4 cases (25%) coinfected with CMV. Two cases were initially diagnosed as GVHD only but found to have CMV infection by serological testing within 3 days after immunosuppression treatment for GVHD. The remarkable histological feature of CMV infection appeared to be significant acute inflammation in addition to apoptotic epithelial injuries, and particularly in an early stage of CMV replication, acute inflammation is possibly the only detectable feature of CMV infection.
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Affiliation(s)
| | - Richa Jain
- 1 Banner-University Medical Center Tucson, AZ, USA
| | - Charmi Patel
- 1 Banner-University Medical Center Tucson, AZ, USA
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38
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Abstract
Every year many new medications are approved for clinical use, several of which can cause clinically significant gastrointestinal tract toxicity. This article emphasizes the histologic features and differential diagnosis of drug-induced injury to the gastrointestinal mucosa. Ultimately, clinical correlation and cessation of a drug with resolution of symptoms are needed to definitively confirm a drug as a causative factor in mucosal injury. Recognizing histologic features in gastrointestinal biopsies, however, can allow surgical pathologists to play a key role in establishing a diagnosis of drug-induced gastrointestinal toxicity.
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Affiliation(s)
- Heewon A Kwak
- Department of Pathology, University of Chicago, 5841 South Maryland Avenue, Chicago, IL, USA
| | - John Hart
- Department of Pathology, University of Chicago, 5841 South Maryland Avenue, MC 6101, Chicago, IL, USA.
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39
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Naymagon S, Naymagon L, Wong SY, Ko HM, Renteria A, Levine J, Colombel JF, Ferrara J. Acute graft-versus-host disease of the gut: considerations for the gastroenterologist. Nat Rev Gastroenterol Hepatol 2017; 14:711-726. [PMID: 28951581 PMCID: PMC6240460 DOI: 10.1038/nrgastro.2017.126] [Citation(s) in RCA: 109] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Haematopoietic stem cell transplantation (HSCT) is central to the management of many haematological disorders. A frequent complication of HSCT is acute graft-versus-host disease (GVHD), a condition in which immune cells from the donor attack healthy recipient tissues. The gastrointestinal system is among the most common sites affected by acute GVHD, and severe manifestations of acute GVHD of the gut portends a poor prognosis in patients after HSCT. Acute GVHD of the gastrointestinal tract presents both diagnostic and therapeutic challenges. Although the clinical manifestations are nonspecific and overlap with those of infection and drug toxicity, diagnosis is ultimately based on clinical criteria. As reliable serum biomarkers have not yet been validated outside of clinical trials, endoscopic and histopathological evaluation continue to be utilized in diagnosis. Once a diagnosis of gastrointestinal acute GVHD is established, therapy with systemic corticosteroids is typically initiated, and non-responders can be treated with a wide range of second-line therapies. In addition to treating the underlying disease, the management of complications including profuse diarrhoea, severe malnutrition and gastrointestinal bleeding is paramount. In this Review, we discuss strategies for the diagnosis and management of acute GVHD of the gastrointestinal tract as they pertain to the practising gastroenterologist.
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Affiliation(s)
- Steven Naymagon
- Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai
| | - Leonard Naymagon
- Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai
| | - Serre-Yu Wong
- Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai
| | - Huaibin Mabel Ko
- Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai.,Lillian and Henry M. Stratton-Hans Popper Department of Pathology and Laboratory Medicine, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, New York, New York 10029, USA
| | - Anne Renteria
- Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai
| | - John Levine
- Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai
| | | | - James Ferrara
- Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai
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40
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Biopsy diagnosis of colitis: an algorithmic approach. Virchows Arch 2017; 472:67-80. [DOI: 10.1007/s00428-017-2274-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2017] [Revised: 11/06/2017] [Accepted: 11/19/2017] [Indexed: 12/17/2022]
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Histologic analysis has a prognostical value in colorectal biopsies assessed for suspicion of graft-versus-host disease. Virchows Arch 2017; 472:213-220. [PMID: 29167990 DOI: 10.1007/s00428-017-2272-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2017] [Revised: 10/21/2017] [Accepted: 11/14/2017] [Indexed: 12/20/2022]
Abstract
Gastrointestinal (GI) graft-versus-host-disease (GVHD) is a common and severe complication of allogeneic hematopoietic stem cell transplantation, but clinical and histological features are unspecific. The aim of this study was to correlate the histological GI GVHD grade with the clinical outcomes. In a retrospective study of 112 patients with clinically suspected GI GVHD, colonic biopsies were reviewed by three pathologists without knowledge of the corresponding clinical data and classified in four scores, according to the NIH Consensus Project recommendations: no GVHD, possible, probable, and unequivocal GVHD. At the end of the study, the histological and clinical data were confronted with the following results: clinical diagnosis of GI GVHD was established for 70 patients (62.5%) and histological scores correlated well with the clinical diagnosis (p < 0.001) and particularly with the prognosis (p < 0.05).When severe lesions were observed, the 1 year overall survival declined to 9%. None of the features reported in the literature to support GVHD diagnosis, eosinophil count, endocrine cells aggregate, immunohistochemical analysis (cytomegalovirus, CD123, chromogranin), did not help us for diagnosis. So routine histopathology alone without immunohistochemistry is a strong and reproducible tool to diagnose GI GVHD with the help of clinical and biological information, and most importantly, histological grading proved to be a powerful prognostic value.
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42
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Differentiating Posttransplant Inflammatory Bowel Disease and Other Colitides in Renal Transplant Patients. Am J Surg Pathol 2017; 41:1666-1674. [PMID: 28786879 DOI: 10.1097/pas.0000000000000921] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Renal transplant recipients who present with gastrointestinal complaints may have symptoms related to their underlying renal disease or secondary to their immunosuppressive regimen. Immunosuppression increases patients' risk for infection and medication-induced injury, and a subset of transplant patients develop a form of inflammatory bowel disease (IBD) despite being immunosuppressed. In this study, we present the spectrum of changes in colonic biopsy histology that occur in the postrenal transplant population, with emphasis on the clinical and histologic features that may allow distinction between several common disorders. Over a 15-year period, 51 postrenal transplant patients underwent colonoscopy with biopsy. Eleven (22%) patients had infectious colitis, and 10 of these had biopsy proven acute colitis. Another 17 (33%) patients were determined to have a medication-related injury based on resolution of symptoms following drug cessation. The majority (53%) of these colonic biopsies demonstrated crypt epithelial cell apoptosis and/or architectural distortion, although 41% were histologically normal. Four (8%) patients were ultimately diagnosed with a form of IBD after exclusion of other etiologies; biopsies from these patients demonstrated chronic active colitis or enteritis with plasma cell-rich expansion of the lamina propria and basal lymphoplasmacytosis. The increased prevalence of IBD in this patient cohort (4/700) compared with that reported in the overall North American population (1 to 2/700) is in line with prior studies and is likely related to the therapeutic regimen and associated immune dysregulation that occurs in solid-organ transplant recipients. We demonstrate that a combination of clinical, endoscopic, and histologic features are useful to distinguish among causes of gastrointestinal symptoms in this high risk population.
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43
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Abstract
Gastrointestinal mucosal biopsies in the hematopoietic stem cell transplantation setting are challenging because histologic features of graft-versus-host disease (GVHD), which is treated by increasing immunosuppression, overlap with those of other conditions, such as infection, which can get worse with GVHD treatment. More than one condition can occur at the same time. It is important to understand the histologic features of GVHD, drug toxicity, infection, and clinical factors surrounding patients, including timing of biopsy in relation to transplantation, medication history, and laboratory data. Rendering a correct diagnosis and generating a pathology report with standard language that can direct clinical management ensure proper management.
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44
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Izower MA, Rahman M, Molmenti EP, Bhaskaran MC, Amin VG, Khan S, Sultan K. Correlation of abnormal histology with endoscopic findings among mycophenolate mofetil treated patients. World J Gastrointest Endosc 2017; 9:405-410. [PMID: 28874961 PMCID: PMC5565506 DOI: 10.4253/wjge.v9.i8.405] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2017] [Revised: 04/23/2017] [Accepted: 05/24/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To describe all abnormal histological findings and their associated endoscopic presentation in patients using mycophenolate mofetil (MMF).
METHODS A retrospective review of all individuals prescribed MMF within 6 mo of a colonoscopy or flexible sigmoidoscopy between 07/2009 and 09/2015 was performed within Northwell Health system. Records were analyzed for age, gender, procedure indication, MMF indication, and both gross and microscopic findings. Only reports with abnormal histology were included.
RESULTS One hundred and eighty-four procedures from 170 patients were found, of which 39 met inclusion criteria. Fifty-one point three percent were female. MMF was used for solid organ transplant in 71.8%. Diarrhea was the indication for 71.8% of colonoscopies. Fifty-nine percent of reports revealed gross and microscopic abnormalities while 41.0% had only microscopic findings. Only 11 patients’ reports (28.2%) indicated a specific histopathology of MMF colitis. Among the entire group, only 23.1% of abnormal histology was isolated proximal to the splenic flexure.
CONCLUSION Our results demonstrate a high rate of left sided disease and microscopic findings without gross mucosal abnormalities among patients using MMF. Also, a broader definition of MMF-colonopathy may be appropriate, with a majority of our abnormal histology falling outside of the more narrowly defined MMF-colitis category. Given the high frequency of isolated microscopic abnormalities and distal disease, sigmoidoscopy with random biopsies may be an appropriate, less invasive initial endoscopic examination in selected MMF patients.
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Graft Versus Host Disease After Liver Transplantation in Adults: A Case series, Review of Literature, and an Approach to Management. Transplantation 2017; 100:2661-2670. [PMID: 27495762 DOI: 10.1097/tp.0000000000001406] [Citation(s) in RCA: 69] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
BACKGROUND Graft-versus-host-disease (GVHD) after liver transplantation (LT) is a deadly complication with very limited data on risk factors, diagnosis and management. We report a case series and a comprehensive review of the literature. METHODS Data were systematically extracted from reports of GVHD after LT, and from the United Network for Organ Sharing database. Group comparisons were performed. RESULTS One hundred fifty-six adult patients with GVHD after LT have been reported. Median time to GVHD onset was 28 days. Clinical features were skin rash (92%), pancytopenia (78%), and diarrhea (65%). Six-month mortality with GVHD after LT was 73%. Sepsis was the most common cause of death (60%). Enterobacter bacteremia, invasive aspergillosis, and disseminated Candida infections were frequently reported. Recipient age over 50 years is a risk factor for GVHD after LT. Hepatocellular carcinoma was overrepresented, whereas chronic hepatitis C was underrepresented, in reported United States GVHD cases relative to all United Network for Organ Sharing database LT cases. Mortality rate with treatment of GVHD after LT was 84% with high-dose steroids alone, 75% to 100% with regimens using dose increases of calcineurin inhibitors, and 55% with IL-2 antagonists. Mortality was 25% in small case series using the CD2-blocker alefacept or TNF-α antagonists. CONCLUSIONS Age older than 50 years and hepatocellular carcinoma appear to be risk factors for GVHD. Hepatitis C may be protective. High-dose steroids and calcineurin inhibitors are ineffective in the treatment of GVHD after LT. CD2-blockers and TNF-α antagonists appear promising. We propose a diagnostic algorithm to assist clinicians in managing adults with GVHD after LT.
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Conner JR, Kirsch R. The pathology and causes of tissue eosinophilia in the gastrointestinal tract. Histopathology 2017; 71:177-199. [DOI: 10.1111/his.13228] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
- James R Conner
- Department of Pathology and Laboratory Medicine; Mount Sinai Hospital; Toronto ON Canada
| | - Richard Kirsch
- Department of Pathology and Laboratory Medicine; Mount Sinai Hospital; Toronto ON Canada
- Department of Laboratory Medicine and Pathobiology; University of Toronto; Toronto ON Canada
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Myerson D, Steinbach G, Gooley TA, Shulman HM. Graft-versus-Host Disease of the Gut: A Histologic Activity Grading System and Validation. Biol Blood Marrow Transplant 2017; 23:1573-1579. [PMID: 28533059 DOI: 10.1016/j.bbmt.2017.05.017] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2017] [Accepted: 05/16/2017] [Indexed: 02/08/2023]
Abstract
The pathologic interpretation of gut biopsies in hematopoietic cell transplant recipients to assess graft-versus-host disease (GVHD) is well accepted and supplements clinical and endoscopic findings. However, the histologic activity grading of GVHD is controversial, with attempts to predict prognosis or response to treatment largely unsuccessful. GVHD is being diagnosed earlier in its course, raising the possibility that the pathologic grading system can be profitably modified. We developed a histologic activity grading system designed to replace the commonly used modified Lerner grading systems. Our system stratifies the low-level Lerner grade I category into 4 activity grade categories, based on the average frequency of apoptotic cells. The results are expressed as ordinal categories: GVHD of minimal, mild, moderate, severe histologic activity, or severe histologic activity with destruction (activity grades 1 to 5). In a retrospective study, we studied 87 consecutive cases with 201 post-transplantation specimens (median, 48 days; range, 18 to 1479 days) of stomach, duodenum, and colorectum, which had been activity graded at the time of the original diagnosis. Most of the biopsies diagnosed as GVHD were low grade-minimal (11%) or mild (71%) histologic activity. We hypothesized that the higher activity grades would be associated with more therapeutic intervention. The odds of increased therapy in the combined all-site specimens were increased as activity grade increased (odds ratio, 2.9 [95% confidence interval {CI}, 1.9 to 4.5]; P = < .0001). Thus, our grading system was validated. To investigate whether the activity grade was associated with therapy within the formerly undivided Lerner grade I category, the analysis was restricted to these 174 all-site specimens. The validation result was similar (odds ratio, 3.1 [95% CI, 1.3 to 7.2]; P = .009). This result interestingly suggests that there is useful information hidden in the Lerner grade I category, which could potentially guide immediately actionable treatment decisions. This histologic activity grade system has been in use at our institution for over 2 years with good acceptance.
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Affiliation(s)
- David Myerson
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; Department of Pathology, University of Washington, Seattle, Washington.
| | - Gideon Steinbach
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; Department of Medicine, University of Washington, Seattle, Washington
| | - Ted A Gooley
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington
| | - Howard M Shulman
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; Department of Pathology, University of Washington, Seattle, Washington
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Abstract
Programmed cell death protein 1 (PD-1) blocking agents are novel immunotherapeutics used for treatment of advanced-stage malignancies. They have shown promise in the treatment of several malignancies, with greater efficacy and better tolerability than cytotoxic T-lymphocyte antigen 4 (CTLA-4) blocking agents. However, as with anti-CTLA-4 agents, clinically significant colitis remains an important complication. Although there is growing awareness of the histopathologic features of anti-CTLA-4 therapy, there is little information on the pathologic features of anti-PD-1 colitis. We describe here the histopathologic findings in 8 patients who developed colitis while on anti-PD-1 monotherapy. The most common pattern of injury observed (5/8 cases) was an active colitis with neutrophilic crypt microabscesses and with prominent crypt epithelial cell apoptosis and crypt atrophy/dropout. These latter features are reminiscent of other colitides with prominent apoptosis such as acute graft-versus-host disease or certain drug-induced colitides. The remainder of cases (3/8) showed a lymphocytic colitis-like pattern, characterized by increased intraepithelial lymphocytes and surface epithelial injury. Apoptosis was also often increased in these cases but crypt atrophy/dropout was not present. In patients who experienced recurrence of anti-PD-1 colitis, histologic features were similar to the initial insult but, in addition, features of chronicity developed that mimicked inflammatory bowel disease (basal lymphoplasmacytosis and crypt architectural irregularity, and Paneth cell metaplasia in 1 case). Awareness of the clinical scenario, however, should allow pathologists to suggest anti-PD-1 colitis. Interestingly, recurrent colitis was observed in patients who had been off anti-PD-1 therapy for many months. As anti-PD-1 agents are increasingly used in oncology, we present this series to increase awareness of anti-PD-1 colitis among pathologists, to facilitate its timely diagnosis and treatment.
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Marginean EC. The Ever-Changing Landscape of Drug-Induced Injury of the Lower Gastrointestinal Tract. Arch Pathol Lab Med 2017; 140:748-58. [PMID: 27472233 DOI: 10.5858/arpa.2015-0451-ra] [Citation(s) in RCA: 53] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
CONTEXT -There is an ever-growing armamentarium of pharmacologic agents that can cause gastrointestinal (GI) mucosal injury, the most common symptoms being diarrhea, constipation, nausea, and vomiting. These are often self-limiting and without serious sequelae, but some symptoms are of greater concern, like drug-induced mucosal ulceration that can manifest as GI hemorrhage, stricture formation, and even perforation. Histologically, there is significant overlap between drug-induced injuries and various disease entities. A single type of medication may cause multiple patterns of injury, which can involve the entire GI tract or just some parts of it. OBJECTIVE -To review the most common drug-induced injury patterns affecting the colon, which may be recognized by the surgical pathologist on colonic mucosal biopsies. This review does not address the injuries occurring in the upper GI tract. DATA SOURCES -A PubMed review of English-language literature, up to December 2015, on drug-induced injury of GI tract was performed. CONCLUSIONS -There are numerous drugs that damage the colonic mucosa. The most common drugs are included in this review according to their histologic pattern of injury. It is important for the pathologist to keep in mind that a single drug type can induce many histologic patterns of mucosal injury that can mimic many disease entities. Although there are some histologic clues helpful in the diagnosis of drug-induced colonic injury, correlation with clinical history and especially medication history is essential to improve diagnostic accuracy.
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Affiliation(s)
- Esmeralda Celia Marginean
- From the Department of Pathology and Laboratory Medicine, University of Ottawa, Ottawa, Ontario, Canada
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Xue Y, Farris AB, Quigley B, Krasinskas A. The Impact of New Technologic and Molecular Advances in the Daily Practice of Gastrointestinal and Hepatobiliary Pathology. Arch Pathol Lab Med 2017; 141:517-527. [PMID: 28157407 DOI: 10.5858/arpa.2016-0261-sa] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
The practice of anatomic pathology, and of gastrointestinal pathology in particular, has been dramatically transformed in the past decade. In addition to the multitude of diseases, syndromes, and clinical entities encountered in daily clinical practice, the increasing integration of new technologic and molecular advances into the field of gastroenterology is occurring at a fast pace. Application of these advances has challenged pathologists to correlate newer methodologies with existing morphologic criteria, which in many instances still provide the gold standard for diagnosis. This review describes the impact of new technologic and molecular advances on the daily practice of gastrointestinal and hepatobiliary pathology. We discuss new drugs that can affect the gastrointestinal tract and liver, new endoluminal techniques, new molecular tests that are often performed reflexively, new imaging techniques for evaluating hepatocellular carcinoma, and modified approaches to the gross and histologic assessment of tissues that have been exposed to neoadjuvant therapies.
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Affiliation(s)
| | | | | | - Alyssa Krasinskas
- From the Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia
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