CD8-positive indolent T-Cell lymphoproliferative disorder of the gastrointestinal tract: A case report and review of literature.

BACKGROUND: Indolent T-cell lymphoproliferative disorder of the gastrointestinal tract (ITLPD-GI), a primary tumor forming in the gastrointestinal (GI) tract, represents a rarely diagnosed clonal T-cell disease with a protracted clinical course. CASE SUMMARY: This report presented a 45-year-old male patient with a 6-year history of anal fistula and a more than 10-year history of recurrent diarrhea who was not correctly diagnosed until the occurrence of complications such as intestinal perforation. Postsurgical histopathological analysis, combined with hematoxylin-eosin staining, immunohistochemistry and TCRß/γ clonal gene rearrangement test, confirmed the diagnosis of CD8+ ITLPD-GI. CONCLUSION: Individuals with this scarce lymphoma frequently show non-specific symptoms that are hard to recognize. So far, indolent CD8+ ITLPD-GI has not been comprehensively examined. The current mini-review focused on evaluating indolent CD8+ ITLPD-GI cases based on existing literature and discussing future directions for improved differential diagnosis, detection of genetic and epigenetic alterations, and therapeutic target identification.

Case Report: Primary Indolent Epstein-Barr Virus-Positive T-Cell Lymphoproliferative Disease Involving the Central Nervous System.

Background: T-cell lymphoproliferative disease (T-LPD), characterized by primary Epstein-Barr virus (EBV) infection and clonal proliferation of T cells, occurs both in systemic and non-lymphatic organs. However, isolated indolent EBV-positive T-LPD involving the central nervous system has not been reported. Case Presentation: A 48-year-old male who complained of headache, blurred vision, and weakness of the left lower limb for 1 month was hospitalized in our department. Neither neurological deficit nor palpable lymphadenopathy had been found. Bone marrow and laboratory tests had shown no abnormality as well. Enhanced MRI demonstrated enhanced cotton-like lesions up to 20 mm in diameter located in the right frontal, temporal, parietal and left parietal, occipital lobes with perifocal edema. Neuronavigation-assisted mini-craniotomy was performed to achieve total excision of the right temporal superficial lesion and identify the diagnosis. Pathological and EBV analysis described the lesion as indolent EBV-positive T-cell lymphoproliferative disease of the central nervous system (CNS). Then, a therapeutic regimen including whole-brain irradiation, chemotherapy, prednisolone, and aciclovir was given. Serial radiological imaging showed no signal of recurrence at 5 months' follow-up. Conclusion: Primary indolent T-LPD in the central nervous system is quite rare, and it needs to be distinguished from aggressive cerebral T-cell lymphoma, metastatic tumors, and other CNS lesions.

Clinical features of NK/T-cell EBV-associated LPD manifested as gastrointestinal symptoms in patients with normal immunity: a case report and literature review.

BACKGROUND: Epstein-Barr virus (EBV)-associated NK/T-cell lymphoproliferative disorder (LPD) involving the gastrointestinal tract is rarely observed in individuals with normal immunity. The atypical clinical, colonoscopic manifestations often confuse clinicians, leading to misdiagnosis and delays in the treatment. CASE PRESENTATION: Herein, we reported on a single case of a patient with gastrointestinal symptoms. Several colonoscopies showed multiple irregular ulcerations, while biopsies showed colitis with infiltration of neutrophils or lymphocytes. After 2 months follow-up, the patient was diagnosed with the extranodal NK/T-cell lymphoma, nasal type, and was treated with thalidomide. Later on, a second check was performed on his first pathological sample. Immunohistochemistry revealed EBV associated NK/T-cell LPD. CONCLUSIONS: Multiple, multiform, and segmental gastrointestinal ulcers should be an indication for EBV infection, regardless of the presence of fever, lymphadenopathy, and hepatosplenomegaly. If EBV-associated NK/T-cell LPD is considered, serum EBV-DNA should be measured, and the tissue obtained by biopsy should be carefully analyzed for a positive expression of the EBER marker.

Indolent T-Cell Lymphoproliferative Disease of the GI Tract: Insights for Better Diagnosis, Prognosis, and Appropriate Therapy.

Indolent T-cell lymphoproliferative disease of the gastrointestinal tract (indolent GI T-LPD) is a benign neoplasm of CD4+ or CD8+ T cells that form primary tumors in the GI tract. Indolent GI T-LPD has recently been provisionally recognized as a distinct entity by the 2016 revision of the WHO classification of lymphoid neoplasms. Appropriate diagnosis of these cases is challenging as they may be misdiagnosed as T cell lymphoma that has an aggressive clinical course. Consequently, aggressive therapeutic approaches were usually chosen to treat these cases with no obvious benefit for most of the patients and potential side effects. Moreover, inflammatory diseases of the GI tract with similar symptoms may lead to misdiagnosis that leads to delays in administration of proper therapeutics against these cases. Therefore, it is of utmost importance to identify prognostic genetic biomarkers at the time of diagnosis for optimal medical care of these patients. TCR clonality analyses may not be useful for distinguishing these benign neoplasms from aggressive gastrointestinal T cell lymphomas; however, molecular genetic tests may prove useful as recurrent STAT3-JAK2 fusions, which may have diagnostic, prognostic or therapeutic value, have recently been identified. However, there is still lack of comprehensive information on the genetic and epigenetic factors associated with pathogenesis of indolent GI T-LPD. In this mini-review, we focus on the so far reported literature on indolent GI T-LPD cases, and discuss future directions for better differential diagnosis, risk stratification, and therapeutic target discovery with a special focus on the genetic and epigenetic alterations.

Epstein-Barr Virus-Associated T-Cell Lymphoproliferative Disorder Presenting as Chronic Diarrhea and Intestinal Bleeding: A Case Report.

Systemic Epstein-Barr virus-positive T-cell lymphoproliferative childhood disease (EBV+ T-LPD) is extremely rare. Primary acute or chronic active Epstein-Barr virus infection triggers EBV+ T-LPD's onset and the disease involves clonal proliferation of infected T-cells with activated cytotoxic phenotype. The adult-onset EBV+ T-LPD (ASEBV+ T-LPD) is even rarer and needs to be extensively studied. Further, according to literature review, it is a challenge to find patients who are immunocompetent and diagnosed with ASEBV+ T-LPD involving gastrointestinal tract. This case report discusses a previously healthy middle aged woman who presented with unique symptoms mimicking inflammatory bowel disease, and required a total colectomy and terminal ileum rectomy, as reveled by endoscopic examinations, due to severe gastrointestinal bleeding. Post-surgery histopathological findings were confirmatory for the diagnosis of ASEBV+ T-LPD (II: Borderline). This patient died 7 months after the diagnosis.

An adult-onset case of chronic active Epstein-Barr virus infection with fulminant clinical course.

A 56-year-old Japanese male with chronic active Epstein-Barr virus (EBV) infection (CAEBV) who developed systemic gamma-delta T-cell lymphoproliferative disease (LPD) is reported. Although immune cooling therapy was effective, he died of sudden and severe hypoxia and anemia soon after the initiation of cytotoxic chemotherapy that had been previously recommended. There might remain a difficulty to control fulminant adult-onset CAEBV. Additionally, we describe three types of lymphoid cells that were observed in his peripheral blood: morphologically normal lymphocytes, large blastic cells and mature ones with rough granules. Morphological observation appeared to be useful to estimate clinical manifestations. Since CAEBV is extremely rare disease in adult population, it is important to accumulate clinical data to more understand the pathogenesis or to establish treatment strategy.

Clinicopathological categorization of Epstein-Barr virus-positive T/NK-cell lymphoproliferative disease: an analysis of 42 cases with an emphasis on prognostic implications.

Epstein-Barr virus-positive T/NK-cell lymphoproliferative diseases (EBV-T/NK-LPDs) include several overlapping EBV-related conditions with variably aggressive courses. For prognostic categorization, we retrospectively analyzed 42 EBV-T/NK-LPD cases. Male (79% [33/42]), young (≤40 years; 83% [35/42]) patients and T-cell lineage (81% [34/42]; CD8/CD4 = 1.8) were predominant. Clinicopathologically, three systemic and one cutaneous category were developed: hemophagocytic lymphohistiocytosis (HLH; 26% [11/42]), chronic active EBV infection (CAEBV; 31% [13/42]), systemic unclassifiable disease (24% [10/42]), and hydroa vacciniforme/hydroa vacciniforme-like lymphoma (HV/HVL; 19% [8/42]). Prognostically, cutaneous disease (HV/HVL) was better than systemic disease (p = 0.014; median, 285 vs. 10 months). In systemic diseases, HLH was worst (p = 0.002; 3[HLH] vs. 4[unclassifiable] vs. not reached [CAEBV]). Univariate survival analysis (n = 42) revealed cytopenia (≥one lineage; p < 0.001), onset age (>40 years; p = 0.001), T-cell lineage (p = 0.041), hemophagocytic histiocytes (p = 0.031), elevated lactate dehydrogenase (p = 0.020), and liver dysfunction (p = 0.023) predicted shorter survival. In multivariate analysis, T-cell lineage (p = 0.025 [HR =11.3]) and cytopenia (p = 0.028 [HR =5.4]) were independent prognostic factors. Therefore, EBV-T/NK-LPD could be classified into four prognostic categories.

Indolent T-cell lymphoproliferative disease of the gastrointestinal tract after treatment with adalimumab in resistant Crohn's colitis.

We report a case of intestinal indolent T-cell lymphoproliferative disease (TCLPD) occurring after the initiation of tumor necrosis factor-α (TNF-α) inhibitor therapy for resistant Crohn's disease. A prominent T-cell infiltrate positive for CD8, TIA-1, and T-cell receptor-ßF1 was associated with the foci of active inflammation. T-cell receptor gene clonality studies (BIOMED-2) demonstrated monoclonality. After the TNF-α inhibitor treatment was withdrawn, the T-cell infiltrates regressed, but 2 years later, the same monoclonal T-cell infiltrate reappeared at the only site of active inflammation. To the best of our knowledge, this report is the first to show a link between active inflammation and the TCLPD. In addition, it suggests a possible influence of the TNF-α inhibitor treatment on the evolution of the TCLPD. A high degree of suspicion is required in the presence of any unusual lymphoid infiltrate in inflammatory bowel disease to avoid overlooking an indolent TCLPD or misdiagnose an aggressive lymphoma.

TEN-like eruption in setting of EBV positive T-cell lymphoproliferative disease with HLH, in a child.

Haemophagocytic lymphohistiocytosis complicating Epstein-Barr virus positive T-cell lymphoproliferative disease of childhood is a rare and life-threatening entity. We report a child with this condition presenting with a toxic epidermal necrolysis-like eruption.

Cutaneous lymphocyte antigen expression loss and PD1 positivity in early cutaneous lesions of rapidly progressive mycosis fungoides.

KEY CLINICAL MESSAGE: It's important to assess cases both clinically and pathologically for factors potentially predictive of an aggressive clinical course. We concluded that the relative immunosuppressive effects of PD1 may contribute to tumor progression while the lack of staining for cutaneous lymphocyte antigen may be an additional factor facilitating distant extracutaneous migration.

Systemic Epstein-Barr Virus-Positive T-cell Lymphoproliferative Disease of Childhood Presenting as Hemophagocytic Lymphohistiocytosis with Chromosomal Abnormalities / 임상검사와정도관리

Epstein-Barr virus (EBV)-positive T-cell lymphoproliferative disease (EBV+ T-cell LPD) is characterized by a clonal proliferation of T-cells, which may trigger hemophagocytic lymphohistiocytosis (HLH). Chromosomal abnormalities in patients with HLH are usually found in association with underlying malignancies. We report here a case of systemic EBV+ T-cell LPD of childhood initially presenting with HLH. A 19-year-old man was admitted to the hospital with a 2-week history of fever. Laboratory data revealed pancytopenia, hypertriglyceridemia, high ferritin levels, and abnormalities in liver function tests. EBV infection was confirmed by serologic tests and real-time polymerase chain reaction. Examination of the bone marrow showed histiocytic hyperplasia and hemophagocytosis. Further investigation revealed atypical lymphoid cells expressing EBV-encoded RNA, CD3, CD4, and CD8. A chromosomal analysis displayed a complex karyotype. Despite intensive treatment, the patient died 15 days after initial presentation. In conclusion, systemic EBV+ T-cell LPD of childhood presenting with HLH and chromosomal abnormalities may progress rapidly and be fatal. Therefore, a diagnostic workup for chromosomal aberration is essential.