T- and NK-Cell Lymphomas and Systemic Lymphoproliferative Disorders and the Immunodeficiency Setting: 2015 SH/EAHP Workshop Report-Part 4

Abstract

Objectives: The 2015 Workshop of the Society for Hematopathology/European Association for Haematopathology aimed to review immunodeficiency-related T- and natural killer (NK)-cell lymphoproliferations.

Methods: The Workshop Panel reviewed 88 T- or NK-cell lymphoproliferations and rendered consensus diagnoses.

Results: Hyperplasias of T-cell subsets may be clonal; retained architecture and the clinical setting support a benign diagnosis. Specific associations include hepatosplenic T-cell lymphoma with iatrogenic immunosuppression and breast implants with an indolent variant of anaplastic large cell lymphoma. Epstein-Barr virus (EBV)-positive T-cell lymphomas rarely occur in the acquired immunodeficiency setting. Systemic T- and NK-cell lymphoma of childhood overlaps with chronic active EBV and reversible hemophagocytic lymphohistiocytosis-related T-cell lymphoproliferations.

Conclusions: Immunodeficiencies predispose to T-cell hyperplasias, which must not be overdiagnosed as lymphoma. Many T-cell lymphomas in the immunodeficiency setting are likely coincidental, with specific exceptions. Systemic T- or NK-cell lymphomas are part of a spectrum of EBV+ T or NK lymphoproliferations and can present in the acquired immunodeficiency setting.

Keywords: Iatrogenic immunodeficiency; NK-cell lymphoma; Posttransplant lymphoproliferative disorder; Systemic T- or NK-cell lymphoma of childhood; T-cell lymphoma.

Image 1

T-cell lymphomas and immunodeficiency. (A) SH2015-225: angioimmunoblastic T-cell lymphoma in a child in the posttransplant setting showing marked paracortical expansion with scattered larger cells, admixed eosinophils, and prominent arborizing high endothelial venules. (B) SH2015-336: γδ hepatosplenic T-cell lymphoma in a patient with Crohn disease chronically treated with cyclosporine. Note the monomorphous lymphoid infiltrate expanding the splenic red pulp. (C) SH2015-126 is a prototypical case of a non-mass-forming, noninvasive breast implant–related anaplastic large cell lymphoma with an excellent prognosis after complete surgical excision despite markedly pleomorphic cytologic features. (D) SH2015-217: secondary Epstein-Barr virus–positive B-cell proliferation resembling a Hodgkin-like immunodeficiency-related lymphoproliferative disorder in the background of a follicular helper-type T-cell lymphoma. (A, H&E, ×40; B-D, H&E, ×20)

Image 2

Immunodeficiency-related T-cell hyperplasia at nodal and extranodal sites can raise concern for lymphoma. (A) SH2015-465: lymphadenopathy in a patient with adult-onset Still disease. The florid immunoblastic infiltrate morphologically mimics an aggressive lymphoma. (B) CD3 immunohistochemistry highlights sheets of morphologically malignant-appearing T cells. (C) SH2015-503: bone marrow γδ lymphocytosis in a patient with Crohn disease and history of tumor necrosis factor α inhibitor use; the infiltrate is subtle and does not result in architectural distortion. (D) SH2015-144 illustrates a reactive γδ T-cell expansion in the splenic red pulp, mimicking hepatosplenic T-cell lymphoma or T-cell large granular lymphocyte leukemia. The infiltrate is monomorphous but cytologically bland and nondestructive, and T-cell gene rearrangement studies are polyclonal. (A, H&E, B, ×40; C, D, H&E, ×20)

Image 3

Epstein-Barr virus (EBV)–associated hemophagocytic lymphohistiocytosis (HLH). (A) The bone marrow contains an interstitial infiltrate of lymphocytes, some showing cytologic atypia. Background histiocytes show marked erythrophagocytosis. (B) Infiltrating lymphoid cells are positive for EBV-encoded small RNA and also positive for CD3 (C) and CD8 (D). Polymerase chain reaction studies for T-cell receptor γ showed a polyclonal pattern, and the patient responded to therapy for HLH (case SH2015-135). (A, B, H&E; A-D, ×40)

Image 4

Chronic active Epstein-Barr virus (EBV) infection of T-cell type, involving the appendix. This 9-year-old girl had acute infectious mononucleosis. Symptoms persisted for more than 10 months. She had persistent fevers, hepatosplenomegaly, and pan-colitis, affecting the gastrointestinal tract. (A) Section of the appendix shows lymphoid hyperplasia, with reactive lymphoid follicles. (B) An EBV-encoded small RNA (EBER) stain shows numerous EBV-positive cells in the perifollicular region. (C) CD3 stains the interfollicular cells, corresponding to the distribution of EBER positivity, while CD20 (D) stains the reactive follicles. T cells were polyclonal by T-cell receptor γ polymerase chain reaction. (A, B, H&E, ×10; C, D, ×20)

Image 5

Systemic Epstein-Barr virus (EBV)–positive T-cell lymphoma, posttransplant. This 57-year-old man developed an aggressive T-cell lymphoma involving the bone marrow 14 years after a cadaveric renal transplant. His presentation was complicated by hemophagocytic lymphohistiocytosis. (A) Bone marrow core biopsy specimen is diffusely infiltrated by atypical lymphoid cells. (B) Lymphoid cells are positive for CD3 and were clonal by T-cell receptor γ polymerase chain reaction. (C, D) Marked hemophagocytic activity in the bone marrow smear (case SH2015-193). (A, H&E, B, ×40; C, D, Giemsa, ×100)