Epstein-Barr virus positive post-transplant lymphoproliferative disorder with significantly decreased T-cell chimerism early after transplantation:A case report

BACKGROUND Post-transplant lymphoproliferative disorder(PTLD)is a rare but highly fatal complication occurring after allogeneic hematopoietic cell transplantation(allo-HCT)or solid organ transplantation(SOT).Unlike SOT,PTLD after allo-HCT usually originates from the donor and is rarely accompanied by a loss of donor chimerism.CASE SUMMARY We report a case of Epstein-Barr virus positive PTLD manifesting as diffuse large B-cell lymphoma(DLBCL)with significantly decreased T-cell chimerism early after allo-HCT.A 30-year-old patient with acute myeloid leukemia underwent unrelated allo-HCT after first complete remission.Nearly 3 mo after transplantation,the patient developed cervical lymph node enlargement and gastric lesions,both of which were pathologically suggestive of DLBCL.Meanwhile,the patient experienced a significant and persistent decrease in T-cell chimerism.A partial remission was achieved after chemotherapy with single agent rituximab and subsequent R-CHOP combined chemotherapy.CONCLUSION The loss of T-cell chimerism and the concomitant T-cell insufficiency may be the cause of PTLD in this patient.

Epstein-Barr virus-positive post-transplant lymphoproliferative disordepresenting as hematochezia and enterobrosis in renal transplant recipients in China: A report of two cases

BACKGROUND Post-transplant lymphoproliferative disorder(PTLD) is a rare severe complication after renal transplantation, with an incidence of approximately 0.3%-2.0% in patients undergoing renal transplantation. The clinical manifestations of PTLD are often nonspecific, leading to tremendous challenges in the clinical diagnosis and treatment of PTLD.CASE SUMMARY We report two Epstein-Barr virus(EBV)-positive PTLD cases whose main clinical manifestations were digestive tract symptoms. Both of them admitted to our hospital because of extranodal infiltration symptoms and we did not suspect of PTLD until the pathology confirmation. Luckily, they responded well to the treatment of rituximab. We also discuss the virological monitoring, clinical characteristics, diagnosis, and treatment of PTLD.CONCLUSION PTLD is a deceptive disease and difficult to diagnose. Once patients are confirmed with PTLD, immune suppressant dosage should be immediately reduced and rituximab should be used as first-line therapy.

Epstein-Barr virus-associated monomorphic post-transplant lymphoproliferative disorder after pediatric kidney transplantation: A case report

BACKGROUND Post-transplant lymphoproliferative disease(PTLD)is the most common malignant tumor that occurs after kidney transplantation in children,and is associated with Epstein-Barr virus(EBV).CASE SUMMARY We report a case of PTLD that occurred in a 17-year-old female patient at 5 mo post-transplant.The first symptom was abdominal pain accompanied by fever,nausea,and vomiting.EBV-associated monomorphic PTLD with multiple abdominal nodules was diagnosed by pathology,clinical manifestations,imaging results,and the presence of EB-DNA.After successful treatment with rituximab,the abdominal nodules in the spleen and liver disappeared.CONCLUSION Early pathological biopsy to confirm the diagnosis is critical to treatment and prognosis.Reducing immunosuppression and rituximab therapy are effective methods for treating PTLD,but need to be initiated as early as possible.

Epstein-Barr virus:Silent companion or causative agent of chronic liver disease?

The Epstein-Barr virus(EBV)has an important and multifaceted role in liver pathology.As a member of the herpes virus family,EBV establishes a persistent infection in more than 90%of adults.Besides acute hepatitis during primary infection,many clinical syndromes of interest for the hepatologist are associated with EBV infection.The role of EBV in the evolution of chronic hepatitis from hepatotropic viruses is considered.Chronic EBVassociated hepatitis is suspected in immunocompetent adults with compatible serology,suggestive histology and detection of the viral genome in the liver and/or increase of specific circulating cytotoxic T-lymphocytes.EBV is the main cause of post-transplant lymphoproliferative disorders which occur in up to 30%of cases.EBV-driven lymphoproliferative diseases are also recognized in non-immunocompromised patients and liver is involved in up to a third of the cases.Directly implicated in the pathogenesis of different tumors,EBV has a disputable role in hepatocellular carcinoma carcinogenesis.Further research is required in order to establish or reject the role of EBV in human liver cancer.This paper attempts to discuss the range of EBV-associated chronic liver diseases in immunocompetent patients,from mild,self-limiting mononuclear hepatitis to liver cancer.

Epstein-Barr virus is related with 5-aminosalicylic acid, tonsillectomy, and CD19^+ cells in Crohn's disease

AIM: To study anti-Epstein-Barr virus(EBV) Ig G antibodies in Crohn′s disease in relation to treatment, immune cells, and prior tonsillectomy/appendectomy.METHODS: This study included 36 CD patients and 36 healthy individuals(controls), and evaluated different clinical scenarios(new patient, remission and active disease), previous mucosa-associated lymphoid tissue removal(tonsillectomy and appendectomy) and therapeutic regimens(5-aminosalicylic acid, azathioprine, anti-tumor necrosis factor, antibiotics, and corticosteroids). T and B cells subsets in peripheral blood were analyzed by flow cytometry(markers included: CD45, CD4, CD8, CD3, CD19, CD56, CD2, CD3, TCRαβ and TCRγδ) to relate with the levels of anti-EBV Ig G antibodies, determined by enzyme-linked immunosorbent assay.RESULTS: The lowest anti-EBV Ig G levels were observed in the group of patients that were not in a specific treatment(95.4 ± 53.9 U/m L vs 131.5 ± 46.2 U/m L, P = 0.038). The patients that were treated with 5-aminosalicylic acid showed the highest anti-EBV Ig G values(144.3 U/m L vs 102.6 U/m L, P = 0.045). CD19+ cells had the largest decrease in the group of CD patients that received treatment(138.6 vs 223.9; P = 0.022). The analysis of anti-EBV Ig G with respect to the presence or absence of tonsillectomy showed the highest values in the tonsillectomy group of CD patients(169.2 ± 20.7 U/m L vs 106.1 ± 50.3 U/m L, P = 0.002). However, in the group of healthy controls, no differences were seen between those who had been tonsillectomized and subjects who had not been operated on(134.0 ± 52.5 U/m L vs 127.7 ± 48.1 U/m L, P = 0.523).CONCLUSION: High anti-EBV Ig G levels in CD are associated with 5-aminosalicylic acid treatment, tonsillectomy, and decrease of CD19+ cells.

Hemophagocytic lymphohistiocytosis caused by primary Epstein-Barr virus in patient with Crohn's disease

We present a case of a 19-year-old man with a 6-year history of Crohn's disease(CD), previously treated with 6-mercaptopurine, who was admitted to our department for Epstein-Barr virus(EBV) infection and subsequently developed a hemophagocytic lymphohistiocytosis(HLH). HLH is a rare disease which causes phagocytosis of all bone marrow derived cells. It can be a primary form as a autosomic recessive disease, or a secondary form associated with a variety of infections; EBV is the most common, the one with poorer prognosis. The incidence of lymphoproliferative disorders was increased in patients with inflammatory bowel disease(IBD) treated with thiopurines. Specific EBV-related clinical and virological management should be considered when treating a patient with IBD with immunosuppressive therapy. Moreover EBV infection in immunosuppressed patient can occur with more aggressive forms such as encephalitis and diffuse large B cell lymphoma. Our case confirms what is described in the literature; patients with IBD, particularly patients with CD receiving thiopurine therapy, who present 5 d of fever and cervical lymphadenopathy or previous evidence of lymphopenia should be screened for HLH.

Persistent Epstein-Barr viral load in Epstein-Barr viral na?ve pediatric heart transplant recipients:Risk of late-onset post-transplant lymphoproliferative disease

AIM To examine the risk of late-onset post-transplant lymphoproliferative disorder(PTLD) in the presence of persisting high Epstein-Barr virus(EBV) in EBV na?ve pediatric heart transplant(HT) recipients. METHODS A retrospective review of the medical records of the 145 pediatric HT recipients who had serial EBV viral load monitoring at our center was performed. We defined EBV naive patients whose EBV serology either IgM or IgG in the blood were negative at the time of HT and excluded passive transmission from mother to child in subjects less than 6 mo of age. RESULTS PTLD was diagnosed in 8 out of 145 patients(5.5%); 6/91(6.5%) in those who were EBV seropositive and 2/54(3.7%) in the EBV na?ve group at the time of HT(P = 0.71). We found 32/145(22%) patients with persistently high EBV load during continuing follow-up; 20/91(22%) in EBV seropositive group vs 12/54(22%) in EBV na?ve group(P = 0.97). There was no significant association between pre-HT serostatus and EBV load after transplant(P > 0.05). In the EBV seropositive group, PTLD was diagnosed in 15%(3/20) of patients with high EBV vs 4.2%(3/71) of patients with low or undetectable EBV load(P = 0.14) whereas in EBV na?ve patients 8.3%(1/12) of those withhigh EBV load and 2.3%(1/42) with low or undetectable EBV load(P = 0.41). There was a highly significant association between occurrence of PTLD in those with high EBV load and duration of follow up(4.3 ± 3.9 years) after HT by Cochran-Armitage test for the entire cohort(P = 0.005). At least one episode of acute rejection occurred in 72%(23/32) of patients with high EBV vs 36%(41/113) patients with low or undetectable EBV after HT(P < 0.05). CONCLUSION There is an association between persistently high EBV load during post-HT follow up and the occurrence of late-onset PTLD in pediatric HT recipients irrespective of serostatus at the time of transplant. The occurrence of allograft rejection increased in patients with high EBV load presumably due to reduction in immunosuppression.

Positive correlation between latent Epstein-Barr virus infection and severity of illness in inflammatory bowel disease patients

BACKGROUND Emerging studies indicate the critical involvement of microorganisms,such as Epstein-Barr virus(EBV),in the pathogenesis of inflammatory bowel disease(IBD).Immunosuppressive therapies for IBD can reactivate latent EBV,complicating the clinical course of IBD.Moreover,the clinical significance of EBV expression in B lymphocytes derived from IBD patients’intestinal tissues has not been explored in detail.AIM To explore the clinical significance of latent EBV infection in IBD patients.METHODS Latent EBV infection was determined by double staining for EBV encoded RNA and CD20 in colon specimens of 43 IBD patients who underwent bowel resection.Based on the staining results,the patients were divided into two groups,according to their latent EBV infection states-negative(n=33)and positive(n=10).Illness severity of IBD were assigned according to Crohn’s disease activity index(ulcerative colitis)and Mayo staging system(Crohn’s disease).The clinicpathological data were analyzed between the two different latent EBV groups and also between the mild-to-moderate and severe disease groups.RESULTS Systolic pressure(P=0.005),variety of disease(P=0.005),the severity of illness(P=0.002),and pre-op corticosteroids(P=0.025)were significantly different between the EBV-negative and EBV-positive groups.Systolic pressure(P=0.001),variety of disease(P=0.000),pre-op corticosteroids(P=0.011)and EBV infection(P=0.003)were significantly different between the mild-to-moderate and severe disease groups.CONCLUSION IBD patients with latent EBV infection may manifest more severe illnesses.It is suggested that the role of EBV in IBD development should be further investigated,latent EBV infection in patients with serious IBD should be closely monitored,and therapeutic course should be optimized.

Epstein-Barr virus-associated smooth muscle tumors in immunocompromised patients:Six case reports

BACKGROUND Epstein-Barr virus associated smooth muscle tumor(EBV-SMT)is a rare oncological entity.However,there is an increasing incidence of EBV-SMTs,as the frequency of organ transplantation and immunosuppression grows.EBV-SMT diagnosis relies on histopathology and immunochemical staining to distinguish it from post-transplant lymphoproliferative disorder(PTLD).There is no clear consensus on the treatment of EBV-SMTs.However,surgical resection,chemotherapy,radiation therapy,and immunosuppression reduction have been explored with varying degrees of success.CASE SUMMARY Our case series includes six cases of EBV-SMTs across different age groups,with different treatment modalities,adding to the limited existing literature on this rare tumor.The median latency time between immunosuppression and disease diagnosis is four years.EBV-SMTs present with variable degrees of aggressiveness and seem to have worse clinical outcomes in patients with tumor multiplicity and worse immunocompetency.CONCLUSION It is imperative to continue building on this knowledge and keeping EBV-SMTs on the differential in immunocompromised individuals.

Lymphoma and cerebral vasculitis in association with X-linked lymphoproliferative disease

Lymphoma is seen in up to 30%of patients with X-linked lymphoproliferative disease(XLP),but cerebral vasculitis related with XLP after cure of Burkitt lymphoma is rarely reported.We describe a case of a 5-year-old boy with XLP who developed cerebral vasculitis two years after cure of Burkitt lymphoma.He had Burkitt lymphoma at the age of 3 years and received chemotherapy(non-Hodgkin’s lymphomaBerlin-Frankfurt-Milan-90 protocol plus rituximab),which induced complete remission over the following two years.At the age of 5 years,the patient first developed headache,vomiting,and then intellectual and motorial retrogression.His condition was not improved after anti-infection,dehydration,or dexamethasone therapy.No tumor cells were found in his cerebrospinal fluid.Magnetic resonance imaging showed multiple non-homogeneous,hypodense masses along the bilateral cortex.Pathology after biopsy revealed hyperplasia of neurogliocytes and vessels,accompanied by lymphocyte infiltration but no tumor cell infiltration.Despite aggressive treatment,his cognition and motor functions deteriorated in response to progressive cerebral changes.The patient is presently in a vegetative state.We present this case to inform clinicians of association between lymphoma and immunodeficiency and explore an optimal treatment for lymphoma patients with compromised immune system.

Infectious complications during immunochemotherapy of posttransplantation lymphoproliferative disease–can we decrease the risk? Two case reports and review of literature

BACKGROUND Post-transplant lymphoproliferative disease(PTLD)is a heterogeneous group of diseases that develop after solid organ and hematopoietic stem cells transplantation related to intensive immunosuppression regimen,T-cell depletion and Epstein-Barr virus infection.Despite the improvement in the management of PTLD,the prognosis remains poor.Here we report the management of two transplanted patients with PTLD and infections during immunochemotherapy(ICTH).CASE SUMMARY Of 65-year-old woman 11 years after kidney transplantation(first case)presented with diffuse large B-cell lymphoma(DLBCL)CS III and started ICHT according to R-CHOP protocol.Despite the secondary prevention of neutropenic fever,the patient developed grade 4 neutropenia with urinary and pulmonary tract infections after the fifth cycle.ICTH was continued in reduced doses up to 7 cycles followed by involved-field radiation therapy of the residual disease.The second case presents a 49-year-old man,8 years after liver transplantation due to cirrhosis in the course of chronic hepatitis B,who started ICTH for DLBCL Burkitt-like CS IV.The patient received four cycles of ICTH according to RCODOX/R-IVAC protocol,with reduced doses.In both cases initially undertaken reduction of immunosuppression was ineffective to prevent infectious complications.Despite one incomplete ICHT treatment due to recurrent infections,both our patients remain in complete remission.CONCLUSION Reduction of immunosuppression and the doses of chemotherapeutics may be insufficient to prevent infectious complications during ICTH in PTLD patients.

Epstein-Barr virus-encoded small RNAs in idiopathic orbital inflammatory pseudotumor tissues: a comparative case series

AIM： To investigate the positive rate and types of cells that express Epstein-Barr virus-encoded small RNAs （EBERs） and to determine the distribution of EBER-expressing cells in idiopathic orbital inflammatory pseudotumor （IOIP） tissues. METHODS： We retrospectively examined 40 archived paraffin specimens from two teaching hospitals in Southern China between January 2007 and January 2015 that were pathologically determined to exhibit IOIP. Eleven concurrent paraffin specimens of thyroid-associated ophthalmopathy （TAO） composed the control group. In situ hybridization was performed to detect EBERs. Immunohistochemistry was employed to detect CD3, CD20, Vimentin, and smooth muscle actin （SMA）, and the positive rate, types of positive cells, and distribution and location of EBERs were evaluated. RESULTS： The positive expression rate of EBERs was 47.5% （19/40） in the IOIP group, which was significantly higher than that in the TAO group [0 （0/11）, P=-0.011]. in the IOIP group, the lymphocyte infiltrative subtype, fibrotic subtype, and mixed subtype exhibited EBER-positive rates of 57.1% （12121）, 12.5% （118）, and 54.5% （6/11）, respectively, and no significant differences were found between these subtypes （P=0.085）. Positive signals of EBERs were mainly present in medium-small lymphocytes between or around follicles and in the nuclei of activated immunoblasts （14/19）. CONCLUSION： The positive rate, types, and distribution of EBER-expressing cells in IOIP have been documented.These findings are conducive for a better understanding of the underlying mechanisms of Epstein-Barr virus infection in IOIP pathogenesis.

Fatal septic shock caused by candida myocarditis associated with malignant lymphoma and Epstein-Barr virus mediated disorder

A 60-year-old man with known epilepsy was admitted to our hospital due to hypotension, fever and arrhythmia. He was treated medically and myocardial infarction was ruled out. Treatment of septic shock was established according to the guidelines of the early goal-guided therapy including vasopressors, inotropic agents, mechanical ventilation, and hemofiltration in combination with empirical treatment with antimicrobial drugs and hydrocortisone. The patient’s condition deteriorated rapidly into multiorgan failure resulting in a fatal outcome. Antemortem blood cultures were sterile. Autopsy findings were compatible with Epstein-Barr virus mediated lymphoproliferative disorder, malignant lymphoma, disseminated candidiasis and candida myocarditis. Post-mortem blood and tissue cultures were positive for growth of candida glabrata and candida albicans, respectively. The post-mortem examination documented Epstein-Barr virus mediated lymphoproliferative disorder and malignant small cell lymphoma associated with candida myocarditis. Prior to death, the patient did not receive antiviral or antifungal treatment. Fatal candida myocarditis associated with septic shock secondary to disseminated candidiasis in a 60-years old male patient with prior unknown immune compromised state caused by Epstein-Barr virus mediated lymphoproliferative disorder and malignant lymphoma is described.

Impact of EBV infection and immune function assay for lymphoproliferative disorder in pediatric patients after liver transplantation: A single-center experience

Background:Post-transplant lymphoproliferative disorder(PTLD)is a lethal complication after pediatric liver transplantation,but information regarding risk factors for the development of PTLD remains unclear.This study was to identify characteristics and risk factors of PTLD.Methods:A total of 705 pediatric patients who underwent liver transplantation between January 2017 and October 2018 were studied.Impact of clinical characteristics and Epstein-Barr virus(EBV)infection on the development of PTLD was evaluated.In addition,ImmuKnow assay was adopted in partial patients to analyze the immune status.Results:Twenty-five(3.5%)patients suffered from PLTD with a median time of 6 months(3–14 months)after transplantation.Extremely high tacrolimus(TAC)level was found in 2 fatal cases at PTLD onset.EBV infection was found in 468(66.4%)patients.A higher peak EBV DNA loads(>9590 copies/mL)within 3 months was a significant indicator for the onset of PTLD.In addition,the ImmuKnow assay demonstrated that overall immune response was significantly lower in patients with EBV infection and PTLD(P<0.0001).The cumulative incidence of PTLD was also higher in patients with lower ATP value(≤187 ng/mL,P<0.05).Conclusions:A careful monitoring of EBV DNA loads and tacrolimus concentration might be supportive in prevention of PTLD in pediatric patients after liver transplantation.In addition,application of the ImmuKnow assay may provide guidance in reducing immunosuppressive agents in treatment of PTLD.

Post-transplant lymphoproliferative disorder after liver transplantation: Incidence, long-term survival and impact of serum tacrolimus level

To investigate incidence and survival of post-transplant lymphoproliferative disorder (PTLD) patients after liver transplantation.METHODSA cross-sectional survey was conducted among patients who underwent liver transplantation at Shiraz Transplant Center (Shiraz, Iran) between August 2004 and March 2015. Clinical and laboratory data of patients were collected using a data gathering form.RESULTSThere were 40 cases of PTLD in the pediatric age group and 13 cases in the adult group. The incidence of PTLD was 6.25% in pediatric patients and 1.18% in adult liver transplant recipients. The post-PTLD survival of patients at 6 mo was 75.1% ± 6%, at 1 year was 68.9% ± 6.5% and at 5 years was 39.2% ± 14.2%. Higher serum tacrolimus level was associated with lower post-PTLD survival in pediatric patients (OR = 1.07, 95%CI: 1.006-1.15, P = 0.032). A serum tacrolimus level over 11.1 ng/mL was predictive of post PTLD survival (sensitivity = 90%, specificity = 52%, area under the curve = 0.738, P = 0.035).CONCLUSIONIncidence of PTLD in our liver transplant patients is comparable to other centers. Transplant physicians may consider adjustment of tacrolimus dose to maintain its serum level below this cutoff point.

Recent insights in the pathogenesis of post-transplantation lymphoproliferative disorders

Post-transplant lymphoproliferative disorder(PTLD) is an aggressive complication of solid organ and hematopoietic stem cell transplantation that arises in up to 20% of transplant recipients. Infection or reactivation of the Epstein-Barr virus(EBV), a ubiquitous human herpesvirus, in combination with chronic immunosuppression are considered as the main predisposing factors, however insight in PTLD biology is fragmentary. The study of PTLD is complicated by its morphological heterogeneity and the lack of prospective trials, which also impede treatment optimization. Furthermore, the broad spectrum of underlying disorders and the graft type represent important confounding factors. PTLD encompasses different malignant subtypes that resemble histologically similar lymphomas in the general population. Post-transplant diffuse large B-cell lymphoma(PT-DLBCL), Burkitt lymphoma(PTBL) and plasmablastic lymphoma(PT-PBL) occur most frequently. However, in many studies various EBV+ and EBV- PTLD subtypes are pooled, complicating the interpretation of the results. In this review, studies of the gene expression pattern, the microenvironment and the genetic profile of PT-DLBCL, PT-BL and PT-PBL are summarized to better understand the mechanisms underlying post-transplantation lymphomagenesis. Based on the available findings we propose stratification of PTLD according to the histological subtype and the EBV status to facilitate the interpretation of future studies and the establishment of clinical trials.

Isolated peritoneal lymphomatosis defined as post-transplant lymphoproliferative disorder after a liver transplant: A case report

BACKGROUND Post-transplant lymphoproliferative disorder(PTLD) is a fatal complication of solid organ transplantation or allogenic hematopoietic stem cell transplantation that is associated with immunosuppressive therapy. Potential manifestations are diverse, ranging from reactive lymphoid hyperplasia to high-grade lymphoma.PTLD is usually of B-cell origin and associated with Epstein-Barr virus(EBV)infection. Herein, we describe a case of PTLD involving the peritoneal omentum.There has been only case of PTLD as a diffuse large B-cell lymphoma(DLBCL) in the peritoneum.CASE SUMMARY The patient was a 62-year-old man who had been receiving immunosuppressive therapy with tacrolimus since undergoing a liver transplant 15 years prior. He reported that he had experienced abdominal discomfort and anorexia 1 month prior to the current admission. Abdominal pelvic computed tomography(CT)revealed peritoneal and omental mass-like lesions without bowel obstruction.Ultrasonography-guided biopsy was performed, and he was histologically diagnosed with EBV-negative DLBCL. Positron emission tomography(PET)-CT depicted peritoneum and omentum involvement only, without any lymphadenopathy or organ masses, including in the gastrointestinal tract. Six cycles of chemotherapy with a "R-CHOP" regimen(rituximab-cyclophosphamide, doxorubicin, vincristine, prednisolone) were administered,and PET-CT performed thereafter indicated complete remission.CONCLUSION This is the first report of isolated peritoneal lymphomatosis defined as PTLD in a liver transplant recipient.

Post-transplantation lymphoproliferative disorders:Current concepts and future therapeutic approaches

Transplant recipients are vulnerable to a higher risk of malignancy after solid organ transplantation and allogeneic hematopoietic stem-cell transplant.Posttransplant lymphoproliferative disorders(PTLD)include a wide spectrum of diseases ranging from benign proliferation of lymphoid tissues to frank malignancy with aggressive behavior.Two main risk factors of PTLD are:Firstly,the cumulative immunosuppressive burden,and secondly,the oncogenic impact of the Epstein-Barr virus.The latter is a key pathognomonic driver of PTLD evolution.Over the last two decades,a considerable progress has been made in diagnosis and therapy of PTLD.The treatment of PTLD includes reduction of immunosuppression,rituximab therapy,either isolated or in combination with other chemotherapeutic agents,adoptive therapy,surgical intervention,antiviral therapy and radiotherapy.In this review we shall discuss the prevalence,clinical clues,prophylactic measures as well as the current and future therapeutic strategies of this devastating disorder.

Gastrointestinal manifestations,risk factors,and management in patients with post-transplant lymphoproliferative disorder:A systematic review

BACKGROUND Patients with a history of solid organ transplantation(SOT)or hematopoietic stem cell transplantation(HSCT)are at an increased risk of developing post-transplant lymphoproliferative disorder(PTLD).The gastrointestinal(GI)tract is commonly affected as it has an abundance of B and T cells.AIM To determine typical GI-manifestations,risk factors for developing PTLD,and management.METHODS Major databases were searched until November 2021.RESULTS Non-case report studies that described GI manifestations of PTLD,risk factors for developing PTLD,and management of PTLD were included.Nine articles written within the last 20 years were included in the review.All articles found that patients with a history of SOT,regardless of transplanted organ,have a propensity to develop GI-PTLD.CONCLUSION GI tract manifestations may be nonspecific;therefore,consideration of risk factors is crucial for identifying GI-PTLD.Like other lymphoma variants,PTLD is very aggressive making early diagnosis key to prognosis.Initial treatment is reduction of immunosuppression which is effective in more than 50%of cases;however,additional therapy including rituximab,chemotherapy,and surgery may also be required.

Coexistent Kaposi sarcoma and post-transplant lymphoproliferative disorder in the same lymph nodes after pediatric liver transplantation:A case report

BACKGROUND Kaposi sarcoma and post-transplant lymphoproliferative disorder have been occasionally reported in post-liver transplant patients.However,the simultaneous occurrence of these two diseases in the same lymph nodes is very rare.CASE SUMMARY We report the case of a 19-mo-old boy,who presented with intermittent fever and enlarged cervical lymph nodes after liver transplantation.Six cervical lymph nodes were biopsied,and the histopathological examinations revealed multifocal hyperplasia of spindle cells around small blood vessels,extravasated erythrocytes,and heavy infiltration of plasma cells in the cortex and medulla of the lymph nodes.The immunohistochemical analyses of spindle cells revealed positive expression of CD34,CD31,erythroblast transformation-specific-related gene,friend leukemia integration 1,and human herpesvirus-8.The lymphoproliferative lesions expressed CD38,CD138,and multiple myeloma 1.Epstein-Barr encoded RNA in situ hybridization demonstrated Epstein-Barr virus-positive lymphoid cells.Finally,we diagnosed the coexistence of Kaposi sarcoma and post-transplant lymphoproliferative disorder(plasmacytic hyperplasia)in the same lymph nodes.Treatment strategy included anti-CD20 monoclonal antibody(rituximab)and discontinuation of the immunosuppressant therapies.Lymph node biopsies during follow-up examinations revealed lymphoid hyperplasia.CONCLUSION The rare coexistence of Kaposi sarcoma and post-transplant lymphoproliferative disorder in the same lymph nodes post-liver transplantation possibly associates with immunodeficiency and Epstein-Barr virus and human herpesvirus-8 coinfection.