EBV-positive Mucocutaneous Ulcer Research Articles

Epstein Barr Virus Positive Mucocutaneous Ulcer versus Classic Hodgkin Lymphoma: Challenges in Diagnosis

Abstract Introduction/Objective Epstein- Barr virus positive mucocutaneous ulcer (EBVMCU) is a clinicopathologic entity first identified in 2010. It occurs in patients with immunosuppression and presents as a well circumscribed ulceration on the oropharyngeal mucosa, skin or gastrointestinal tract. Infiltrates of atypical lymphoid cells that may have appearances similar to Diffuse Large B-cell Lymphoma (DLBCL) or Classic Hodgkin Lymphoma (CHL) are seen. Methods/Case Report A 41 year old male patient with history of HIV infection presented with hematochezia and rectal pain, underwent sigmoidoscopy and a large ulcerated mass was present at the anal verge. Polymorphic infiltrates of small lymphoid cells, eosinophils, granulocytes, plasma cells, histiocytes and scattered large atypical lymphoid cells, morphologically mimicking Reed-Sternberg cells were identified. The large atypical lymphoid cells were positive for CD30, MUM-1, BCL-6, EBER (EBV) and negative for CD3, CD15, CD20, CD45, CD79a, SOX-10. Based on lack of B-symptoms, no lymphadenopathy, superficial lesions, reduced CD4/CD8 ratio and specific location, EBVMCU was favored. Eight months later, he presented with night sweats, decreased appetite and inguinal lymphadenopathy. Lymph node excision displayed infiltrates of predominantly small lymphocytes, histiocytes, plasma cells and eosinophils. Foci of scattered large atypical cells morphologically compatible with Hodgkin/Reed Sternberg cells with focal necrosis were noted. The atypical cells were positive for CD30, PAX5 (weak), CD20 (subset), CD15 (focal), MUM-1 and EBV-EBER. CHL, Mixed Cellularity Subtype was diagnosed. Results (if a Case Study enter NA) NA Conclusion As a newer entity, we don’t know if EBVMCU can co-exist with or progress to CHL/DLBCL. Therefore, EBVMCU patients should undergo vigilant screening.

Epstein–Barr virus-positive mucocutaneous ulcer resulting in severe methotrexate intoxication: a case report

BackgroundEpstein–Barr virus-positive mucocutaneous ulcer is one of the mature B-cell lymphoproliferative diseases occurring in patients with immune dysfunction including those with immunosuppressive treatment such as methotrexate.Case presentationA Japanese elderly man in his 80s with rheumatoid arthritis on methotrexate was admitted to our hospital complaining persistent pharyngeal pain. Laboratory tests revealed severe pancytopenia, elevated C-reactive protein, and increased creatinine levels. An otolaryngological examination showed ulceration of the right tonsil, from which diagnostic biopsy was performed. The diagnosis of Epstein–Barr virus-positive mucocutaneous ulcer was made and bone marrow aspiration revealed hypocellularity and megaloblastic changes. Pancytopenia was improved after discontinuing methotrexate, and repeated bone marrow aspiration test revealed recovery of normal cellularity and disappearance of dysplasia, confirming the diagnosis of methotrexate intoxication. Tonsil ulcer was improved only with discontinuation of methotrexate, which strongly supported the diagnosis of EBV-MCU.ConclusionOur case suggested that even this best prognosis form of lymphoproliferative disease could lead to fatal complications if not appropriately managed.

Epstein-Barr virus-related lymphoproliferative disorders of the skin.

Epstein Barr Virus (EBV) is associated both solid (nasopharyngeal carcinoma, non-nasopharyngeal lymphoepithelioma-like carcinoma, gastric carcinoma, leiomyosarcoma) and hematolymphoid malignancies, some of the latter, however, spanning over a spectrum ranging from reactive and self-limiting to severe and life-threatening conditions. This review will focus on the disorder most commonly involving the skin, namely: EBV-positive mucocutaneous ulcer; lymphomatoid granulomatosis; EBV-positive diffuse large B cell lymphoma; plasmablastic lymphoma; post-transplant lymphoproliferative disorder; extranodal NK/T cell lymphoma, nasal type; angoimmunoblastic T cell lymphoma; severe mosquito bite allergy; hydroa vacciniformelike lymphoproliferative disorder. Given the uncommon occurrence of all these infiltrates in the skin, multidisciplinary approach, as well as referral to tertiary care centers are always advisable.

Classifications of cutaneous lymphomas and lymphoproliferative disorders: An update from the EORTC cutaneous lymphoma histopathology group.

The classification of primary cutaneous lymphomas and lymphoproliferative disorders (LPD) is continuously evolving by integrating novel clinical, pathological and molecular data. Recently two new classifications for haematological malignancies including entities of cutaneous lymphomas were proposed: the 5th edition of the WHO classification of haematolymphoid tumours and the International Consensus Classification (ICC) of mature lymphoid neoplasms. This article provides an overview of the changes introduced in these two classifications compared to the previous WHO classification. The main changes shared by both classifications include the downgrading of CD8+ acral T-cell lymphoma to CD8+ acral T-cell LPD, and the recognition of entities that were previously categorized as provisional and have now been designated as definite types including primary cutaneous small or medium CD4+ T-cell LPD, primary cutaneous gamma/delta T-cell lymphoma, primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma, Epstein-Barr virus-positive mucocutaneous ulcer. Both classifications consider primary cutaneous marginal zone B-cell clonal neoplasm as an indolent disease but use a different terminology: primary cutaneous marginal zone lymphoma (WHO) and primary cutaneous marginal zone LPD (ICC). The 5th WHO classification further introduces and provides essential and desirable diagnostic criteria for each disease type and includes chapters on reactive B- or T-cell rich lymphoid proliferations formerly referred as cutaneous pseudolymphomas, as well as histiocyte and CD8 T-cell rich LPD in patients with inborn error of immunity. As already emphasized in previous lymphoma classifications, the importance of integrating clinical, histological, phenotypic and molecular features remains the crucial conceptual base for defining cutaneous (and extracutaneous) lymphomas.

Diagnostic utility of cytology in a patient with Epstein-Barr virus-positive mucocutaneous ulcer in palatine tonsils: A case report.

Epstein-Barr virus-positive mucocutaneous ulcer (EBVMCU) is a newly established immunodeficiency-related disease. Herein, we report a case of EBVMCU and focus on its cytological usefulness for diagnosis. An 82-year-old man manifested pharyngalgia, dysphagia, and oral pain. His medical history included rheumatoid arthritis that had been treated with methotrexate. Clinically, peritonsillar abscess was suspected, but since neoplastic lesions, including malignant lymphoma (ML), could not be excluded, a series of cytohistological examination was attempted. Despite some alarming findings (e.g., frequent mitoses), fine-needle aspiration and touch imprint cytology consistently revealed a heterogeneous population of lymphoid and plasmacytoid cells with mild nuclear atypia. The final diagnosis of EBVMCU was established based on the permanent histologic specimen; however, retrospectively, cytology was more representative of the benign nature of the lesion than histology, helping a great deal to differentiate it from ML. Cytology can be a useful tool for the correct diagnosis of EBVMCU.

Epstein-Barr virus-positive mucocutaneous ulcer in a patient with ulcerative colitis: a recently described entity to take into account.

Epstein-Barr virus-positive mucocutaneous ulcer (EBVMCU) is a new entity recently included in the classification of B-cell lymphoproliferative disorders associated with Epstein-Barr virus (EBV). It is related to immunosuppression and it usually appears in the oropharynx or the skin, being the colon an uncommon location. We present the case of a 31-year-old man with ulcerative proctitis being treated with azathioprine (AZA) and adalimumab (ADA), who was admitted to the hospital due to suspicion of a moderate-severe flare of ulcerative proctitis. Microbiological stool analyses were negative, with a positive fecal calprotectin test (2700 mg/kg). Rectoscopy showed severe endoscopic activity, taking multiple biopsies. Intravenous steroids were started at a dose of 60 mg/day. He presented a favorable clinical and analytical evolution, being discharged from the hospital. The histological results were received at gastroenterology consultation, being compatible with EBVMCU. AZA and ADA were withdrawn, whereas descending steroid regimen and oral and topical mesalazine were continued, being the clinical response adequate.

Sulfasalazine‐Induced Epstein–Barr Virus‐Positive Mucocutaneous Ulcer

Epstein–Barr virus (EBV) may cause a wide spectrum of symptomatology in humans ranging from asymptomatic upper respiratory tract infection to infectious mononucleosis and in more severe cases lymphoproliferative disorders or hemophagocytic lymphohistiocytosis. Its neoplastic potential is higher in immunocompromised individuals. We describe a case of EBV‐positive mucocutaneous ulcer, a more indolent clinical entity on the spectrum of EBV‐driven lymphoproliferative disorders, and are one of the first to put sulfasalazine, an immunomodulatory agent, forward as the possible culprit.

Epstein-Barr virus positive mucocutaneous ulcer – A diagnostic challenge

A significant portion of the global population carries the asymptomatic Epstein-Barr virus (EBV). Transfusions of blood and blood derivatives, organ and tissue transplantation, and oropharyngeal secretions are the main routes of transmission. The World Health Organization recently recognized the EBV mucocutaneous ulcer (EBVMU) as a provisional pathological entity in its classification of hematopoietic and lymphoid tissues. It affects patients who are elderly or immunosuppressed. Histologically, it may be difficult to distinguish from Hodgkin lymphoma (HL). Although skin or mucosa are uncommon sites of HL involvement, diagnosis at these sites should be made with extreme caution. The prognosis for EBVMU is good; cases regress on their own or after immunosuppressive therapy is reduced. We present a 67-year-old woman with a non-healing oral cavity ulcer which was diagnosed as EBV-positive mucocutaneous ulcer.

A Case of Epstein-Barr Virus-Positive Mucocutaneous Ulcer Arising in an Anal Lesion

A Case of Epstein-Barr Virus-Positive Mucocutaneous Ulcer Arising in an Anal Lesion

Epstein-Barr virus-positive mucocutaneous ulcer of the gingiva: A self-limiting disorder of the immune compromised that can present with aggressive clinico-radiological and histomorphological features

Oral ulcerations of the gingiva or mucosa require differential diagnosis. One of these diagnoses may be Epstein-Barr virus (EBV)-positive mucocutaneous ulcer.Epstein-Barr virus (EBV)-positive mucocutaneous ulcer (EBVMCU) is a rare diagnosis and was first described in 2010. It is described as an Epstein-Barr virus (EBV)-mediated B-cell proliferation and occurs in patients with immunosuppression, e.g., therapy with azathioprine, methotrexate, or cyclosporine, but also in patients with age-related immune senescence or chronic diseases/infections such as diabetes and AIDS/HIV. In 2017, EBVMCU was recognized by WHO and included in the classification of tumors.Mucocutaneous ulcerations often present as indolent, sharply demarcated ulcerations of the gingiva. Over 70 % of these ulcerations occur in the oral and pharyngeal cavities. EBV is secreted in saliva and can develop EBVMCU in association with trauma, such as tooth extraction.We present three patient cases with EBVMCU. We describe the clinical presentation, differential diagnosis and diagnosis, treatment, and clinical outcome.

S4127 Spontaneous Regression of a Rare Gastric Epstein-Barr Virus-Positive Mucocutaneous Ulcer, an Entity in Age-Related Immunosenescence

S4127 Spontaneous Regression of a Rare Gastric Epstein-Barr Virus-Positive Mucocutaneous Ulcer, an Entity in Age-Related Immunosenescence

P04 Leg ulceration in a patient with antisynthetase syndrome

Abstract A 42-year-old woman presented with leg ulceration on a background of antisynthetase syndrome and immunosuppression with rituximab, azathioprine and prednisolone. The initial lesion was an erythematous patch on the lower leg, which increased in size with violaceous changes. The area subsequently broke down to form an ulcer. On examination, she had a 7-cm ulcerating lesion with central necrosis. Clinically, the appearance was suspicious of pyoderma gangrenosum; biopsy demonstrated scarring without features of vasculitis, atypia or malignancy. The ulcer did not show improvement as expected after oral and topical steroid treatment, with new fleshy nodular growth. Repeat biopsy showed angiocentric atypical lymphocytes with positive Epstein–Barr virus (EBV)-encoded RNA (EBER) staining. Further incisional biopsy demonstrated large, atypical B lymphocytes with a diffuse sheet-like morphology and a poorly circumscribed base. Immunohistochemistry was positive for CD79a, CD30, CD20, MUM1, BCL6, and EBER. Overall, the findings were consistent with EBV-positive diffuse large B-cell lymphoma (DLBCL). The main differential diagnosis was EBV-positive mucocutaneous ulcer (MCU), another EBV-associated lymphoproliferative disorder, albeit with an indolent course (Dojcinov SD, Venkataraman G, Raffeld M et al. EBV positive mucocutaneous ulcer—a study of 26 cases associated with various sources of immunosuppression. Am J Surg Pathol 2010; 34:405–17). In this case, the diffuse sheet-like morphology and poorly circumscribed base favoured EBV-positive DLBCL. The lesion fully healed with withdrawal of immunosuppression and treatment with rituximab therapy, and involved field radiotherapy. First described in 2003, EBV-positive DLBCL is a rare, classically aggressive lymphoma initially believed to only occur in patients older than 50 years of age (Oyama T, Ichimura K, Suzuki R et al. Senile EBV+ B-cell lymphoproliferative disorders. Am J Surg Pathol 2003; 27:16–26). Since the revision of the World Health Organization classification in 2016, it is also recognized to present in younger patients, with an associated better prognosis. EBV-positive DLBCL occurs in both nodal and extranodal sites. Therefore, cutaneous presentations must complete staging investigations to rule out skin involvement secondary to a nodal lymphoma. Our patient highlights a rare complication of immunosuppression. We illustrate the relevance of considering rare causes of ulceration in patients with autoimmune conditions and immunosuppression and demonstrate the importance of considering malignancy in a nonhealing ulcer. Multiple biopsies may be needed in ulcers that poorly respond to treatment. While EBV-positive DLBCL and EBV-positive MCU can be difficult to differentiate, it is vital for prognostication.

What is new about primary cutaneous B cell lymphomas.

Primary cutaneous B-cell lymphomas (CBCL) are a heterogeneous group of B-cell lymphomas without evidence of extracutaneous disease at the time of diagnosis. The 2022 World Health Organization classification of mature lymphoid neoplasms differentiates the indolent primary cutaneous marginal zone lymphoproliferative disorder, primary cutaneous follicle center lymphoma and Epstein-Barr virus-positive mucocutaneous ulcer, from the more aggressive primary cutaneous diffuse large B-cell lymphoma, leg-type and intravascular large B-cell lymphoma. The new updates in the 2022 classification are based on recent scientific advances in the understanding and characterization of these entities. This article aims to review the main clinical, cellular and molecular features of the five CBCL subsets along with their management and treatment. The exponentially growing evidence for new treatment options for systemic B-cell lymphomas raises expectations for the field of CBCL as well. However, specific prospective high quality research on CBCL is still crucial to further define their management and update international guidelines.

Top Ten Lymphoproliferative Lesions Not to Miss When Evaluating Oral Ulcer Biopsies.

Oral ulcers represent afull thickness lossof the mucosal epithelium leading to exposure of the submucosal connective tissue. These are common and usually self-limited lesions, although they may sometimes result from neoplasms, most commonly squamous cell carcinoma. Lymphoproliferative disorders may be difficult to diagnose in apthous ulcers since they mimic reactive inflammation. This review presents ten rare oral lymphoid proliferations which should not be missed when assessing oral ulcer biopsies. The ten lesions include several with diagnostic cells which look similar to the histiocytes of a reactive inflammatory ulcer, including Rosai-Dorfman disease, reticulohistiocytoma, Langerhans cell histiocytosis, and traumatic ulcerative granuloma. Other lesions, such as EBV-positive mucocutaneous ulcer, extranodal marginal zone lymphoma of mucosal-associated lymphoid tissue, and plasmablastic lymphoma have lymphoid and/or plasma cell differentiation that mimic the reactive lymphocytes and plasma cells foundin reactive ulcers. Two dendritic cell lesions, follicular dendritic cell sarcoma and blastic plasmacytoid dendritic cell neoplasm, both have distinct phenotypes which are required to make an accurate diagnosis. Each of these lesions are diagnosed by evaluating their histology, along with their phenotypic profile, which is sometimes enhanced by pertinent molecular findings.

EBV-positive mucocutaneous ulcer arising in methotrexate-treated rheumatoid arthritis patients: a clinicopathological study of 12 cases with analysis of PD-L1 expression.

Epstein-Barr virus-positive mucocutaneous ulcer (EBVMCU) is a newly recognized disease entity characterized by EBV-positive atypical B-cell proliferation. EBVMCU is a localized self-limited disease that affects mucosa and skin, especially the oral cavity. EBVMCU develops in immunosuppressive patients, such as those with methotrexate (MTX)-administrated rheumatoid arthritis (RA). Here we clinicopathologically analyzed 12 EBVMCU patients in a single institution. All cases were administrated MTX for RA, and five cases occurred in the oral cavity. All cases except one had demonstrated spontaneous regression after withdrawal of the immunosuppressive agent. We found 4 of 5 cases in the oral cavity had preceding traumatic events in the same site within a week before the onset of EBVMCU. Although there is no detailed and large study that has analyzed the trigger of EBVMCU, a traumatic event would indeed be a significant trigger for EBVMCU in the oral cavity. The cases were histologically classified; six cases were diffuse large B-cell lymphoma-type, five were polymorphous-type, and one was Hodgkin-like lesion type due to morphological appearance and immunophenotype. The PD-L1 expression was also examined by two antibodies for PD-L1 (E1J2J and SP142). Both antibodies revealed identical results for PD-L1 expression, and three cases were positive for PD-L1. The application of SP142 for evaluating the immune status of lymphomagenesis has also been proposed. Nine of 12 cases were negative for PD-L1, which implies that most EBVMCU cases may be caused by an immunodeficiency, rather than an immune-evasion, mechanism. However, as three cases were positive for PD-L1, immune escape may underly the pathogenesis in a subset of EBVMCU cases.

A case of EBV-positive mucocutaneous ulcer involving the maxillary gingiva

A case of EBV-positive mucocutaneous ulcer involving the maxillary gingiva

Impact of Epstein-Barr virus infection in patients with inflammatory bowel disease.

A high prevalence of Epstein-Barr virus (EBV) infection in patients with inflammatory bowel disease (IBD) has been reported in many case reports and studies; thus, the association between EBV and IBD has gained increasing attention. Patients with IBD are at an increased risk of opportunistic EBV infection owing to the common use of immunomodulators. EBV infection in IBD patients can cause various complications, including superimposed viral colitis, which is associated with chronicity, exacerbation, and poor prognosis of refractory IBD, and can induce progression to lymphoproliferative disorders, such as EBV-positive mucocutaneous ulcer (EBVMCU), lymphomatoid granulomatosis (LYG), hemophagocytic lymphohistiocytosis (HLH) and diffuse large B-cell lymphoma (DLBCL). It has been suggested to screen for EBV before initiating immunosuppressive therapy and monitor the status of EBV infection in patients with IBD, especially those who are EBV-seronegative and have a risk of primary EBV infection. Clinicians should also be careful of misdiagnosing IBD and EBV-associated lymphoproliferative diseases due to similarities in both clinical symptoms and endoscopic manifestations. Withdrawal of immunosuppressants has been shown to be an effective strategy to achieve remission of disease at the time of EBV diagnosis, but antiviral therapy remains controversial. The present review aims to describe the characteristics of the complications caused by EBV infection and generalize the recent research progress on and challenges caused by EBV infection in IBD patients. The literature for writing this review was collected from 'PubMed' research engine. The keywords 'inflammatory bowel disease and Epstein-Barr virus' or 'ulcerative colitis and Epstein-Barr virus' or 'Crohn's disease and Epstein-Barr virus' were used to collect the literature and relevant papers were collected to help writing this review.

Epstein-Barr virus–positive mucocutaneous ulcer of the stomach

Epstein-Barr virus–positive mucocutaneous ulcer of the stomach

S2724 EBV as a Very Unusual Etiology of Mucocutaneous Ulcer of the Neo-Ileum in a Patient With Crohn's Disease

Introduction: A member of the herpes virus family, Epstein Barr virus (EBV) is one of the most common human viruses. It can cause latent infections in humans, leading to serious health complications, including lymphomas and lymphoproliferative disorders. Mucocutaneous ulcers associated with EBV (EBVMCU) are a recently established entity of the lymphoproliferative disorders in 2010. Case Description/Methods: An 82-year-old male with Crohn's disease s/p right hemicolectomy with the formation of neo-ileum seven years earlier, bladder cancer, lung cancer s/p lobectomy in remission for both cancers. He presented to the hospital complaining of bright red blood per rectum. He reports chronic loose stools attributed to a history of Crohn's disease and right hemicolectomy seven years earlier when 30 cm colon was removed, including terminal ileum to the proximal transverse colon. The patient reports that he believed his Crohn's was never symptomatic and was worried about the side effects of biologic Crohn's treatment, which he refused in the past. Colonoscopy revealed extensive ulceration at the neo-ileum with friable mucosa. The histology shows scattered large atypical EBV-positive cells of B cell lineage in inflamed and ulcerated mucosa with granulation tissue. A definitive diagnosis could not be made, and further biopsies were recommended. PET scan and CT scan were unremarkable for metabolically active malignant lesions or lymphadenopathy. Colonoscopy repeated two months later showed the same ulcerated lesion with the same histological features mentioned earlier. (Figure) Discussion: EBVMCUs manifest as shallow sharply circumscribed ulcers on the mucosa or skin and are histologically distinguished by the proliferation of variable-sized, atypical B-lymphocytes, making the site of the ulcers in the neo-ileum very atypical and unique. The lesion usually develops in individuals with impaired immunity, such as those who are elderly, have iatrogenic immunosuppression, have primary immune disorders, or are HIV/AIDS-infected. The lack of a tumor mass favors an EBV-positive mucocutaneous ulcer, a newly recognized entity that can involve the GIT and occurs as an age-related disease and in immunosuppressed patients. In contrast to other EBV-related lymphoproliferative disorders, such as EBV-positive diffuse large B-cell lymphoma, EBVMCU has a good prognosis. A watch-and-wait approach or reduction in immunosuppressants are usually sufficient to cause EBVMCU patients to achieve remission.Figure 1.: Neo-ileum biopsy: The atypical cells are large with ovoid to irregular nuclear membrane, hyperchromatic nuclei, variable prominent nucleoli, and cytoplasmic clearing.

EPSTEIN-BARR VIRUS–POSITIVE MUCOCUTANEOUS ULCER: A CASE REPORT

Epstein-Barr virus–positive mucocutaneous ulcer (EBVMCU) is a newly recognized clinicopathologic entity included in the group of mature B-cell neoplasms in the 2017 revision of World Health Organization Classification for Lymphoproliferative Disorders. A nonsmoking 92-year-old man presented with an ulcerated lesion on the maxillary alveolar ridge. An incisional biopsy was performed and reported an undifferentiated malignancy composed of cell clusters with scarce cytoplasm and very pleomorphic nuclei. The immunohistochemical profile expressed CD20, CD30, CD15, CD45 and Epstein-Barr virus-encoded latent membrane protein (EBV-LMP) antigens, consistent with EBVMCU. Within 2 weeks, the lesion became painful and the palate was infiltrated. Tomography showed loss of bone tissue and permeative aspect in the right maxilla. After 8 weeks of rituximab, the patient was asymptomatic and presented regression of the lesion, maintaining only the bone exposed area. This case highlights that proper clinical history and ancillary studies can avoid misinterpretation and overtreatment of EBVMCU oral lesions. Epstein-Barr virus–positive mucocutaneous ulcer (EBVMCU) is a newly recognized clinicopathologic entity included in the group of mature B-cell neoplasms in the 2017 revision of World Health Organization Classification for Lymphoproliferative Disorders. A nonsmoking 92-year-old man presented with an ulcerated lesion on the maxillary alveolar ridge. An incisional biopsy was performed and reported an undifferentiated malignancy composed of cell clusters with scarce cytoplasm and very pleomorphic nuclei. The immunohistochemical profile expressed CD20, CD30, CD15, CD45 and Epstein-Barr virus-encoded latent membrane protein (EBV-LMP) antigens, consistent with EBVMCU. Within 2 weeks, the lesion became painful and the palate was infiltrated. Tomography showed loss of bone tissue and permeative aspect in the right maxilla. After 8 weeks of rituximab, the patient was asymptomatic and presented regression of the lesion, maintaining only the bone exposed area. This case highlights that proper clinical history and ancillary studies can avoid misinterpretation and overtreatment of EBVMCU oral lesions.