Indolent T-Cell Lymphoproliferative Disorders of the Gastrointestinal Tract (iTLPD-GI): A Review

iTLPD-GI is a low-grade clonal T-cell lymphoproliferative disease arising in GI organs. It is an uncommon disease, and only recently has it been enlisted as a distinct provisional entity in the current WHO Classification. Data from the literature disclose high heterogeneity in terms of pathological and molecular features; on the other hand, establishing an accurate diagnosis of iTLPD-GI is of pivotal importance, since treatment options are different from that of other, more frequent lymphomas that arise in the gastrointestinal tract. In this review, we aimed to better define this novel entity, and to identify useful diagnostic biomarkers; moreover, we provide a biomarker-based approach to the diagnosis and describe the most common issues in differentiating iTLPD-GI from other neoplastic and non-neoplastic disorders.

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Evaluation of a somatostatin analog in the treatment of lymphoproliferative disorders: results of a phase II North Central Cancer Treatment Group trial.

Journal of Clinical Oncology ◽

10.1200/jco.1995.13.8.2012 ◽

1995 ◽

Vol 13 (8) ◽

pp. 2012-2015 ◽

Cited By ~ 28

Author(s):

T E Witzig ◽

L Letendre ◽

J Gerstner ◽

G Schroeder ◽

J A Mailliard ◽

...

Keyword(s):

T Cell ◽

Phase Ii ◽

Partial Remission ◽

Somatostatin Receptor ◽

Lymphoproliferative Disorders ◽

Lymphocytic Leukemia ◽

Somatostatin Analog ◽

Low Grade ◽

Hodgkin's Lymphomas ◽

Mean Time

PURPOSE Malignant cells from non-Hodgkin's lymphomas (NHL) have been shown to express the somatostatin receptor on their cell surface and most NHL are visible on somatostatin radioscintigraphy scans. This provided the rationale to conduct a phase II trial of a somatostatin analog in patients with B- and T-cell lymphoproliferative disorders. PATIENTS AND METHODS Sixty-one patients with measurable or assessable lymphoproliferative disorders (31 stage III or IV low-grade NHL; 21 chronic lymphocytic leukemia [CLL]; and nine cutaneous T-cell NHL [CTCL]) were enrolled. Patients were treated with somatostatin 150 micrograms subcutaneously (SQ) every 8 hours for 1 month. Patients with stable or responding disease received 2 additional months of therapy; those who responded after 3 months were treated for an additional > or = 3 months. RESULTS Sixty patients were assessable for toxicity and 56 for response. There were no complete remissions. In the low-grade NHL group, 36% (10 of 28 patients; 95% confidence interval [CI], 19% to 56%) had a partial remission. Forty-four percent (four of nine; 95% CI, 14% to 79%) of patients with CTCL had a partial response. No patients with CLL had a partial remission. Among 45 patients with stable disease or a partial remission, the mean time to progression (TTP) was 10.9 months (median, 6.2; range, 1.6 to 48.5). The drug was well tolerated, with the most common side effects being diarrhea and hyperglycemia. CONCLUSION Somatostatin at a dose of 150 micrograms every 8 hours is well tolerated and has activity in low-grade NHL.

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Large Granular Lymphocytic Leukemia: A Report of Response to Rituximab

Case Reports in Hematology ◽

10.1155/2017/7506542 ◽

2017 ◽

Vol 2017 ◽

pp. 1-3

Author(s):

Uroosa Ibrahim ◽

Sara Parylo ◽

Shiksha Kedia ◽

Shafinaz Hussein ◽

Jean Paul Atallah

Keyword(s):

T Cell ◽

Cytotoxic T Cells ◽

Treatment Options ◽

Cell Receptor ◽

Lymphocytic Leukemia ◽

Peripheral Blood Flow ◽

Low Grade ◽

Morphological Examination ◽

Purine Analogues ◽

First Line Therapy

Large granular lymphocytic (LGL) leukemia is a rare form of low grade leukemia characterized by large cytotoxic T cells or natural killer cells on morphological examination. Immunosuppressive therapy is employed as first-line therapy. Treatment options in refractory cases include the anti-CD52 antibody alemtuzumab and purine analogues. We report a rare case that responded to the anti-CD20 monoclonal antibody rituximab. A 77-year-old female presented with complaints of fatigue, fever, and chills of 3 months’ duration. A CBC showed that pancytopenia with an absolute neutrophil count (ANC) was 0. Peripheral blood flow cytometry detected increased number of T cell large granular lymphocytes and T cell receptor rearrangement study detected a clonal T cell population. Bone marrow biopsy showed peripheral T cell lymphoma, most consistent with T-large granulocytic leukemia. The patient was treated with prednisone and oral cyclophosphamide for four months with no response. Thereafter, she received four weekly infusions of rituximab with improvement in her blood counts. A response to rituximab in refractory cases such as ours has been reported and may guide us towards exploring other immune-based therapeutics in this rare disease.

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EBV-Driven Lymphoproliferative Disorders and Lymphomas of the Gastrointestinal Tract: A Spectrum of Entities with a Common Denominator (Part 2)

Cancers ◽

10.3390/cancers13184527 ◽

2021 ◽

Vol 13 (18) ◽

pp. 4527

Author(s):

Magda Zanelli ◽

Francesca Sanguedolce ◽

Andrea Palicelli ◽

Maurizio Zizzo ◽

Giovanni Martino ◽

...

Keyword(s):

Gastrointestinal Tract ◽

Epstein Barr Virus ◽

Primary Effusion Lymphoma ◽

Treatment Strategies ◽

Lymphoproliferative Disorders ◽

Common Denominator ◽

Adequate Treatment ◽

Barr Virus ◽

Molecular Features ◽

Epstein Barr

Epstein–Barr virus (EBV) is a common pathogen infecting people primarily early in life. The virus has the ability to persist throughout a person’s life, usually in B lymphocytes. Conditions of immunodeficiency as well as the introduction of immunosuppressive therapies and the advent of transplant technologies has brought immunodeficiency-associated lymphoproliferative disorders into view, which are often driven by EBV. The group of EBV-associated lymphoproliferative disorders includes different entities, with distinct biological features, ranging from indolent disorders, which may even spontaneously regress, to aggressive lymphomas requiring prompt and adequate treatment. These disorders are often diagnostically challenging due to their overlapping morphology and immunophenotype. Both nodal and extra-nodal sites, including the gastrointestinal tract, may be involved. This review, divided in three parts, summarizes the clinical, pathological, molecular features and treatment strategies of EBV-related lymphoproliferative disorders occurring in the gastrointestinal tract and critically analyzes the major issues in the differential diagnosis. In this part of the review, we discuss plasmablastic lymphoma, extra-cavitary primary effusion lymphoma and Burkitt lymphoma.

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Kinetics of T‐cell subset reconstitution following treatment with bendamustine and rituximab for low‐grade lymphoproliferative disease: a population‐based analysis

British Journal of Haematology ◽

10.1111/bjh.15722 ◽

2018 ◽

Cited By ~ 7

Author(s):

Nicolás Martínez‐Calle ◽

Sarah Hartley ◽

Matthew Ahearne ◽

Benjamin Kasenda ◽

Amy Beech ◽

...

Keyword(s):

T Cell ◽

Cell Subset ◽

Population Based ◽

Lymphoproliferative Disease ◽

Low Grade ◽

T Cell Subset ◽

Kinetics Of

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Pathobiology and treatment of lymphomatoid granulomatosis, a rare EBV-driven disorder

Blood ◽

10.1182/blood.2019000933 ◽

2020 ◽

Vol 135 (16) ◽

pp. 1344-1352 ◽

Cited By ~ 4

Author(s):

Christopher Melani ◽

Elaine S. Jaffe ◽

Wyndham H. Wilson

Keyword(s):

B Cell ◽

Immune Modulation ◽

Treatment Options ◽

Bone Marrow Involvement ◽

Immune Surveillance ◽

Lymphoproliferative Disease ◽

Lymphomatoid Granulomatosis ◽

Low Grade ◽

High Grade ◽

Hematopoietic Stem

Abstract Lymphomatoid granulomatosis (LYG) is a rare Epstein-Barr virus (EBV)–driven B-cell lymphoproliferative disease (LPD). This disease is hypothesized to result from defective immune surveillance of EBV, with most patients showing evidence of immune dysfunction, despite no known primary immunodeficiency. Pathologically, LYG is graded by the number and density of EBV+ atypical B cells, and other characteristic findings include an angioinvasive/angiodestructive reactive T-cell infiltrate and various degrees of necrosis. Clinically, LYG universally involves the lungs with other common extranodal sites, including skin, central nervous system, liver, and kidneys. Nodal and/or bone marrow involvement is extremely rare and, if present, suggests an alternative diagnosis. Treatment selection is based on histologic grade and underlying pathobiology with low-grade disease hypothesized to be immune-dependent and typically polyclonal and high-grade disease to be immune-independent and typically oligoclonal or monoclonal. Methods of augmenting the immune response to EBV in low-grade LYG include treatment with interferon-α2b, whereas high-grade disease requires immunochemotherapy. Given the underlying defective immune surveillance of EBV, patients with high-grade disease may have a recurrence in the form of low-grade disease after immunochemotherapy, and those with low-grade disease may progress to high-grade disease after immune modulation, which can be effectively managed with crossover treatment. In patients with primary refractory disease or in those with multiple relapses, hematopoietic stem cell transplantation may be considered, but its efficacy is not well established. This review discusses the pathogenesis of LYG and highlights distinct histopathologic and clinical features that distinguish this disorder from other EBV+ B-cell LPDs and lymphomas. Treatment options, including immune modulation and combination immunochemotherapy, are discussed.

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Indolent T-cell lymphoproliferative disease of the gastrointestinal tract in a renal transplant patient: diagnostic pitfalls and clinical challenges

Pathology ◽

10.1016/j.pathol.2017.03.012 ◽

2017 ◽

Vol 49 (5) ◽

pp. 547-550 ◽

Cited By ~ 4

Author(s):

Gwyneth Soon ◽

Shi Wang

Keyword(s):

Gastrointestinal Tract ◽

T Cell ◽

Renal Transplant ◽

Renal Transplant Patient ◽

Transplant Patient ◽

Lymphoproliferative Disease ◽

Diagnostic Pitfalls

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Relapsing oral and colonic ulcers with monoclonal T-cell infiltration. A low grade mucosal T-lymphoproliferative disease of the digestive tract

Cancer ◽

10.1002/1097-0142(19950401)75:7<1728::aid-cncr2820750727>3.0.co;2-9 ◽

1995 ◽

Vol 75 (7) ◽

pp. 1728-1733 ◽

Cited By ~ 27

Author(s):

Naoto Egawa ◽

Masashi Fukayama ◽

Kenji Kawaguchi ◽

Tsunekazu Hishima ◽

Yukiko Hayashi ◽

...

Keyword(s):

T Cell ◽

Digestive Tract ◽

Lymphoproliferative Disease ◽

Cell Infiltration ◽

Low Grade ◽

T Cell Infiltration

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Genetic and phenotypic characterization of indolent T-cell lymphoproliferative disorders of the gastrointestinal tract

Haematologica ◽

10.3324/haematol.2019.230961 ◽

2019 ◽

Vol 105 (7) ◽

pp. 1895-1906 ◽

Cited By ~ 4

Author(s):

Craig R. Soderquist ◽

Nupam Patel ◽

Vundavalli V. Murty ◽

Shane Betman ◽

Nidhi Aggarwal ◽

...

Keyword(s):

Gastrointestinal Tract ◽

T Cell ◽

Lymphoproliferative Disorders ◽

Phenotypic Characterization

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Characteristic karyotypic pattern in T-cell lymphoproliferative disorders with reactive "angioimmunoblastic lymphadenopathy with dysproteinemia-type" features

Blood ◽

10.1182/blood.v72.2.413.413 ◽

1988 ◽

Vol 72 (2) ◽

pp. 413-421 ◽

Cited By ~ 64

Author(s):

Y Kaneko ◽

N Maseki ◽

M Sakurai ◽

S Takayama ◽

K Nanba ◽

...

Keyword(s):

T Cell ◽

Plasma Cells ◽

Large Population ◽

Lymphoproliferative Disorders ◽

Low Grade ◽

Angioimmunoblastic Lymphadenopathy ◽

T Cell Lymphomas ◽

Abnormal Cells ◽

Chromosome Pattern ◽

Mitotic Cells

Abstract We report the clinical, histological, immunophenotypic, and cytogenetic findings in ten patients with T-cell lymphoproliferative disorders demonstrating reactive “angioimmunoblastic lymphadenopathy with dysproteinemia (AILD)-type” features. Fifteen available specimens were diagnosed as atypical hyperplasias (four) or malignant lymphomas (11). The latter were classified as AILD-type (five), T-zone (four), lymphoepithelioid (one), and low-grade, unclassified lymphoma (one). Despite the histologic differences, all these lesions shared minor nuclear atypicalities and reactive AILD-type features such as prominent vascularity, plasma cells, eosinophils, macrophages, and residual germinal centers. All lesions were immunophenotyped as predominantly T cell. The chromosome pattern was characterized by the frequent presence of karyotypically unrelated abnormal clones and/or cells with nonclonal chromosome abnormalities, a large population of normal mitotic cells, and a high incidence of trisomies 3 and 5. Sequential cytogenetic and histologic studies in five patients revealed that atypical hyperplasia and lymphoma with AILD-type features shared the same cytogenetic characteristics, ie, an unstable coexistence of normal mitotic cells and small-clonal and/or nonclonal abnormal cells, and that histologic transformation from low-grade lymphoma to immunoblastic lymphoma was accompanied by a selective proliferation of abnormal clonal cells. The AILD-type histology and the characteristic karyotypic pattern may be the expression of a specific pathogenesis and may warrant the separation of these neoplasias from other peripheral T-cell lymphomas.

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