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Coady LC, Sheahan K, Brown IS, Carneiro F, Gill AJ, Kumarasinghe P, Kushima R, Lauwers GY, Pai RK, Shepherd NA, Slavik T, Srivastava A, Langner C. Esophageal lymphocytosis: exploring the knowns and unknowns of this pattern of esophageal injury. Expert Rev Gastroenterol Hepatol 2024; 18:529-539. [PMID: 39268773 DOI: 10.1080/17474124.2024.2385493] [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: 04/03/2024] [Revised: 05/12/2024] [Accepted: 07/23/2024] [Indexed: 09/15/2024]
Abstract
INTRODUCTION Lymphocyte-rich inflammation of the esophageal mucosa has gained increased awareness among pathologists and clinicians recently. Patients usually present with symptoms of esophageal dysfunction, including dysphagia and food bolus impaction. Endoscopy may show changes similar to eosinophilic esophagitis but may also be entirely normal ('microscopic esophagitis'). Three morphological subtypes or variant forms have been described which include lymphocytic, lichenoid and lymphocyte-predominant esophagitis. These need to be discriminated against other distinct causes of esophageal lymphocytosis, such as gastro-esophageal reflux disease and Candida infection. AREAS COVERED This review provides an overview of diagnostic criteria and clinical associations of the disorder and presents an algorithmic approach to diagnosis. A comprehensive literature review was conducted using PubMed, Medline and Google Scholar databases to identify articles related to lymphocyte-rich esophageal inflammation, published up to March 2024. EXPERT OPINION Lymphocyte-rich inflammation needs to be included in the differential diagnosis and clinical work-up of patients with esophageal dysfunction. There is currently considerable morphological overlap among published subtypes or variant forms. Follow-up studies of affected individuals are needed to formalize diagnostic parameters and identify the clinical course of disease in order to optimize treatment modalities.
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Affiliation(s)
- Laoise C Coady
- Department of Histopathology, St. Vincent's University Hospital, Elm Park, Dublin 4, Ireland
| | - Kieran Sheahan
- Department of Histopathology, St. Vincent's University Hospital, Elm Park, Dublin 4, Ireland
- UCD School of Medicine, University College Dublin, Belfield, Dublin 4, Ireland
| | - Ian S Brown
- Envoi Specialist Pathologists, Brisbane, Queensland, Australia
- Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia
- Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia
| | - Fátima Carneiro
- Ipatimup - Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal
- Department of Pathology, Faculty of Medicine of the University of Porto, Alameda Prof. Hernâni Monteiro, Portugal
- Centro Hospitalar Universitário São João, Alameda Prof. Hernani Monteiro, Porto, Portugal
| | - Anthony J Gill
- Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards, NSW, Australia
- New South Wales Health Pathology, Department of Anatomical Pathology, Royal North Shore Hospital, St Leonards, NSW, Australia
- Sydney Medical School, University of Sydney, Sydney, NSW, Australia
| | | | - Ryoji Kushima
- Department of Pathology, Shiga University of Medical Science, Otsu, Japan
| | - Gregory Y Lauwers
- Department of Pathology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
- Departments of Pathology and Oncologic Sciences, University of South Florida, Tampa, FL, USA
| | - Rish K Pai
- Department of Laboratory Medicine and Pathology, Mayo Clinic Arizona, Scottsdale, AZ, USA
| | - Neil A Shepherd
- Gloucestershire Cellular Pathology Laboratory, Cheltenham General Hospital, Cheltenham, UK
| | - Tomas Slavik
- Ampath Pathology Laboratories, Pretoria, South Africa
- Department of Anatomical Pathology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa
| | - Amitabh Srivastava
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, USA
| | - Cord Langner
- Diagnostic and Research Institute of Pathology, Diagnostic and Research Center for Molecular BioMedicine, Medical University of Graz, Graz, Austria
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Aboona MB, Kosako Yost K, Muńa Aguon P, Fung BM, Nanda R. Lymphocytic Esophagitis Presenting With Food Impaction. Cureus 2023; 15:e42873. [PMID: 37664363 PMCID: PMC10474306 DOI: 10.7759/cureus.42873] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/02/2023] [Indexed: 09/05/2023] Open
Abstract
Lymphocytic esophagitis (LyE) is a rare diagnosis made on esophageal biopsy whose pathogenesis is poorly understood. Since its appearance in the literature 15 years ago, it still remains an enigma due to its low prevalence. In this case report, a 71-year-old male presented with an episode of acute dysphagia due to food impaction. Urgent endoscopy was performed to fragment the food bolus. Repeat endoscopy showed a stricture, and lymphocytic esophagitis was found on esophageal biopsy. A proton pump inhibitor (PPI) was initiated with symptomatic improvement. With its increasing prevalence, lymphocytic esophagitis should be on the differential for causes of dysphagia.
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Affiliation(s)
- Majd B Aboona
- Department of Internal Medicine, University of Arizona College of Medicine, Phoenix, USA
| | - Kelli Kosako Yost
- Department of Internal Medicine, University of Arizona College of Medicine, Phoenix, USA
| | - Paul Muńa Aguon
- Division of Gastroenterology, Department of Internal Medicine, University of Arizona College of Medicine, Phoenix, USA
| | - Brian M Fung
- Division of Gastroenterology, Department of Internal Medicine, University of Arizona College of Medicine, Phoenix, USA
| | - Rakesh Nanda
- Department of Gastroenterology and Hepatology, Carl T. Hayden Phoenix Veterans Administration (VA) Medical Center, Phoenix, USA
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Wojas O, Żalikowska-Gardocka M, Krzych-Fałta E, Szczepankiewicz B, Samel-Kowalik P, Samoliński B, Przybyłkowski A. A case of lymphocytic esophagitis in a woman with multiple allergies. Allergy Asthma Clin Immunol 2021; 17:56. [PMID: 34099042 PMCID: PMC8186211 DOI: 10.1186/s13223-021-00558-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2020] [Accepted: 05/18/2021] [Indexed: 02/08/2023] Open
Abstract
Background Lymphocytic esophagitis is a newly recognized entity of unknown origin. Dysphagia is defined as difficulty swallowing and represents a common symptom in the general population with a prevalence of approximately 20%. Chronic inflammation of the esophageal wall may manifest itself clinically and endoscopically, mimicking inflammation of another origin. However, little is known about the pathogenesis of the disease, as patients are seldom suspected and rarely diagnosed with lymphocytic esophagitis. Case presentation Here, we present a rare case of lymphocytic esophagitis in a patient with multiple allergies and suspected eosinophilic esophagitis. A 28-year-old woman with polyvalent sensitization to food and inhalant allergens presented with intermittent dysphagia, a sensation of a foreign body in the throat, itchiness of the oral cavity after ingesting certain foods, heartburn, and prolonged chewing time. A skin prick test showed positive results for birch-tree, alder, hazel, and rye pollen, as well as house dust mites. Apart from obesity (BMI 30 kg/m2), multiple pustules and excoriations on the skin, her physical examination was insignificant. Esophagogastroduodenoscopy (EGD) was performed revealing full-length but discrete trachealization of the esophagus. A barium swallow test showed slowing of esophageal peristalsis in the recumbent position. No esophageal pathology was observed. A histopathological analysis of mucosal samples revealed slight hyperplasia of the basal layer of the esophagus, and the stomach showed changes typical of chronic gastritis. Conclusions In summary, this clinical case illustrates that lymphocytic esophagitis, as a newly recognized entity, should be considered in the differential diagnosis of chronic dysphagia. Additionally, when treating allergic patients, clinicians should be aware that lymphocytic esophagitis, distinct from eosinophilic esophagitis, should be considered in the diagnosis of patients with atopy and upper gastrointestinal symptoms.
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Affiliation(s)
- O Wojas
- Department of Prevention of Environmental Hazard and Allergology, Medical University of Warsaw, Warsaw, Poland
| | - M Żalikowska-Gardocka
- Department of Gastroenterology and Internal Medicine, Medical University of Warsaw, Warsaw, Poland.
| | - E Krzych-Fałta
- Department of Prevention of Environmental Hazard and Allergology, Medical University of Warsaw, Warsaw, Poland
| | - B Szczepankiewicz
- Department of Pathomorphology, Medical University of Warsaw, Warsaw, Poland
| | - P Samel-Kowalik
- Department of Prevention of Environmental Hazard and Allergology, Medical University of Warsaw, Warsaw, Poland
| | - B Samoliński
- Department of Prevention of Environmental Hazard and Allergology, Medical University of Warsaw, Warsaw, Poland
| | - A Przybyłkowski
- Department of Gastroenterology and Internal Medicine, Medical University of Warsaw, Warsaw, Poland
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Moiseff R, Olson N, Suriawinata AA, Rothstein RI, Lisovsky M. CD8 T-Cell-Predominant Lymphocytic Esophagitis is One of the Major Patterns of Lymphocytic Inflammation in Gastroesophageal Reflux Disease. Arch Pathol Lab Med 2020; 145:1138-1143. [PMID: 33373450 DOI: 10.5858/arpa.2020-0430-oa] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/30/2020] [Indexed: 11/06/2022]
Abstract
CONTEXT.— Published reports have suggested an association of lymphocytic esophagitis (LyE) with gastroesophageal reflux disease (GERD) and primary motility disorders and have also shown that GERD and motility disorders frequently overlap. These findings make it difficult to determine the true relationship between LyE and GERD, which may be confounded by the presence of motility disorders with LyE. OBJECTIVE.— To characterize patterns of lymphocytic inflammation in patients with GERD that have no motility abnormalities. DESIGN.— We identified 161 patients seen at our institution from 1998 to 2014, who were diagnosed with GERD, had normal esophageal motility, and available esophageal biopsies. LyE was defined as peripapillary lymphocytosis with rare or absent granulocytes. CD4 and CD8 immunophenotype of lymphocytes was evaluated using immunohistochemistry. RESULTS.— We found increased intraepithelial lymphocytes in 13.7% of patients with GERD. Two major patterns and 1 minor pattern of lymphocytic inflammation were observed as follows: (1) LyE (in 6.8% [11 of 161] of patients and typically focal), (2) dispersed lymphocytes in an area of reflux esophagitis (in 5.6% [9 of 161] and typically diffuse), and (3) peripapillary lymphocytes in an area of reflux esophagitis (in 1.2% [2 of 161]). CD8 T cells significantly outnumbered CD4 T cells in 91% of patients with lymphocytic esophagitis and 100% of patients with dispersed lymphocytes (9 of 9) or peripapillary lymphocytes (2 of 2) in the area of reflux esophagitis. CONCLUSIONS.— These findings suggest that LyE is one of the major patterns of lymphocytic inflammation in GERD. CD8 T-cell-predominant immunophenotype may be useful as a marker of GERD in the differential diagnosis of LyE.
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Affiliation(s)
- Robin Moiseff
- From the Department of Pathology (Moiseff, Olson, Suriawinata, Lisovsky)
| | - Nicholas Olson
- From the Department of Pathology (Moiseff, Olson, Suriawinata, Lisovsky).,Olson is currently located at Physicians Laboratory in Sioux Falls, South Dakota
| | | | - Richard I Rothstein
- and Section of Gastroenterology and Hepatology (Rothstein), at Dartmouth-Hitchcock Medical Center and Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire
| | - Mikhail Lisovsky
- From the Department of Pathology (Moiseff, Olson, Suriawinata, Lisovsky)
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Patil DT, Hammer S, Langer R, Yantiss RK. Lymphocytic esophagitis: an update on histologic diagnosis, endoscopic findings, and natural history. Ann N Y Acad Sci 2018; 1434:185-191. [PMID: 29797752 DOI: 10.1111/nyas.13710] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2017] [Revised: 03/11/2018] [Accepted: 03/14/2018] [Indexed: 12/14/2022]
Abstract
Lymphocytic esophagitis is a histologic pattern of injury characterized by increased intraepithelial lymphocytes (>20/high-power field) with rare, or absent granulocytes. Lymphocytes tend to be more numerous in the peripapillary epithelium, and are often associated with evidence of mucosal injury, edema, and scattered dyskeratotic cells. More than a decade following its original description, lymphocytic esophagitis remains an enigmatic entity with variable clinical presentations, associated disorders, etiologies, treatment, and natural history. Most of the confusion regarding the clinical significance of this disorder stems from its diagnostic criteria: lymphocytic esophagitis is currently defined based entirely on histologic criteria, despite the common occurrence of lymphocytosis in a variety of unrelated inflammatory conditions of the esophagus. The goal of this review is to summarize the literature regarding lymphocytic esophagitis and focus on key clinicopathologic features that distinguish it from other esophageal disorders that can show increased numbers of intraepithelial lymphocytes.
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Affiliation(s)
- Deepa T Patil
- Department of Pathology, Cleveland Clinic, Lerner College of Medicine, Cleveland, Ohio
| | - Suntrea Hammer
- Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Rupert Langer
- Institute of Pathology, University of Bern, Bern, Switzerland
| | - Rhonda K Yantiss
- Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, New York
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Abstract
PURPOSE OF REVIEW Lymphocytic esophagitis (LE) is an unusual esophageal condition defined by an increased number of lymphocytes in the esophageal epithelium. With few published studies of LE available, it is unclear whether LE is a truly distinct clinical entity or a histological manifestation of other known gastrointestinal disorders. This review summarizes recent studies of lymphocytic esophagitis. RECENT FINDINGS Studies have suggested that LE may be related to eosinophilic esophagitis (EoE) or a manifestation of gastroesophageal reflux disease (GERD). There is an association between LE and Crohn's disease in children, but not in adults. Patients with LE frequently report symptoms of dysphagia and GERD. Treatment options for LE are limited and involve symptom management similar to treatment of EoE or GERD, including proton pump inhibitors (PPI), swallowed topical steroids, and endoscopic dilation. With no formal definition and a variety of clinical presentations and endoscopic findings, diagnosis and management of symptomatic LE patients is challenging for clinicians.
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Affiliation(s)
- Anh D Nguyen
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Texas Southwestern Medical Center, Dallas, TX, 75231, USA
| | - Kerry B Dunbar
- Esophageal Diseases Center, Division of Gastroenterology and Hepatology, Department of Medicine, Dallas VA Medical Center and the University of Texas Southwestern Medical Center, GI Lab-CA 111-B1, Dallas VAMC, 4500 South Lancaster Road, Dallas, TX, 75231, USA.
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Jideh B, Keegan A, Weltman M. Lymphocytic esophagitis: Report of three cases and review of the literature. World J Clin Cases 2016; 4:413-418. [PMID: 28035315 PMCID: PMC5156879 DOI: 10.12998/wjcc.v4.i12.413] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2016] [Revised: 07/20/2016] [Accepted: 09/22/2016] [Indexed: 02/05/2023] Open
Abstract
Lymphocytic esophagitis (LyE) is a rare condition characterised histologically by high numbers of esophageal intraepithelial lymphocytes without significant granulocytes infiltration, in addition to intercellular edema (“spongiosis”). The clinical significance and natural history of LyE is poorly defined although dysphagia is reportedly the most common symptom. Endoscopic features range from normal appearing esophageal mucosa to features similar to those seen in eosinophilic esophagitis, including esophageal rings, linear furrows, whitish exudates, and esophageal strictures/stenosis. Symptomatic gastroesophageal reflux disease is an inconsistent association. LyE has been associated in paediatric Crohn’s disease, and recently in primary esophageal dysmotility disorder in adults. There are no studies assessing effective treatment strategies for LyE; empirical therapies have included use of proton pump inhibitor and corticosteroids. Esophageal dilatation have been used to manage esophageal strictures. LyE has been reported to run a benign course; however there has been a case of esophageal perforation associated with LyE. Here, we describe the clinical, endoscopic and histopathological features of three patients with lymphocytic esophagitis along with a review of the current literature.
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Post-ablation lymphocytic esophagitis in Barrett esophagus with high grade dysplasia or intramucosal carcinoma. Mod Pathol 2016; 29:599-606. [PMID: 26965580 DOI: 10.1038/modpathol.2016.50] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2015] [Revised: 02/05/2016] [Accepted: 02/08/2016] [Indexed: 12/13/2022]
Abstract
In patients who have undergone ablation therapy for treatment of Barrett's esophagus with dysplasia, histologic features of eosinophilic esophagitis, but not lymphocytic esophagitis, have been described. We evaluated for histologic evidence of eosinophilic esophagitis and lymphocytic esophagitis and correlated with endoscopic findings in this population. A single-institution Barrett's esophagus registry was searched for patients who had received radiofrequency ablation, cryotherapy, or both for treatment of Barrett's esophagus with dysplasia. Clinical and endoscopic data were collected and biopsies were reviewed for inflammation and reactive changes at three time points: pre-intervention, first surveillance after ablation therapy, and most recent surveillance. Of the 173 patients initially identified, 102 met the inclusion criteria. Intraepithelial eosinophils were increased at first surveillance (60%, P=0.096) and last surveillance (69%, P=0.048) compared with pre-intervention (50%), although histologic evidence of post-ablation eosinophilic esophagitis was not significant. Prevalence of lymphocytic esophagitis was significantly higher at first surveillance (17%, P=0.02) and at last surveillance (43%, P<0.001), compared with pre-intervention (7%). Smoking, hyperlipidemia, and cryotherapy were identified as independent risk factors for developing histologic lymphocytic esophagitis. This is the first report that histologic evidence of lymphocytic esophagitis increased over time in patients undergoing ablation for Barrett's esophagus with dysplasia. Though the pathophysiology of lymphocytic esophagitis remains unknown, patients in our study with a history of smoking, hyperlipidemia, or cryotherapy were more likely to develop post-ablation lymphocytic esophagitis.
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