Lymphoma and plasma cell neoplasms
T / NK cell disorders
Peripheral T cell lymphoma, not otherwise specified

Author: Dragos Luca, M.D. (see Authors page)

Revised: 28 March 2017, last major update August 2011

Copyright: (c) 2002-2017, PathologyOutlines.com, Inc.

PubMed Search: Peripheral T cell lymphoma [title] NOS

See also: Variants
Cite this page: Peripheral T cell lymphoma, not otherwise specified. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/lymphomanonBperipheral.html. Accessed April 27th, 2017.
Definition / General
Terminology
  • Includes lymphoepithelioid (Lennert) lymphoma, follicular T cell, and T zone lymphoma
Epidemiology
  • Among the most common nodal T cell lymphomas (30% of peripheral T cell lymphomas in Western countries)
  • Usually adults, very rare in children
  • M:F ratio 2:1
Sites
  • Peripheral lymph node involvement in most cases but any site may be affected
  • Often generalized, with infiltration of bone marrow, liver, spleen and extranodal tissues
  • Peripheral blood may be involved but leukemic presentation is uncommon
  • Extranodal presentation most commonly in skin and GI tract
  • Less frequently involved sites: lungs, salivary glands and CNS
Diagrams / Tables

Differential diagnosis of nodal peripheral T cell lymphoma, not otherwise specified

Disease

Immunophenotypic features

Peripheral T cell lymphoma, not otherwise specified

CD4 > CD8, antigen loss frequent (CD7, CD5, CD4 / CD8, CD52), CD30-/+, CD56-/+, CD10-, BCL6-, CLCX13-, PD1-

Angioimmunoblastic lymphoma

CD4+ or mixed CD4 / 8, CD10+/-, BCL6+/-, CXCL13+, PD1+, hyperplasia of FDC, EBV+CD20+ B blasts

Adult T cell leukemia/lymphoma

CD4+, CD25+, CD7-, CD30-/+, CD15-/+, FoxP3+/-

Anaplastic large cell lymphoma

CD30+, ALK+/-, EMA+, CD25+, cytotoxic granules+, CD4+/-, CD3-/+, CD43+

T cell rich large B cell lymphoma

Large CD20+ blasts in background of reactive CD3+ T cells

T-zone hyperplasia

Mixed CD4 / CD8, intact architecture, variable CD25 and CD30; scattered CD20+ B cells

+, nearly always positive; +/-, majority positive; -/+, minority positive; FDC, follicular dendritic cells; EBV, Epstein-Barr virus
Clinical Features
  • Usually high stage (III / IV) with skin or lung involvement, generalized lymphadenopathy, B symptoms and often pruritus
  • 30 - 70% have marrow involvement at diagnosis
  • Paraneoplastic features: eosinophilia, pruritus and rarely hemophagocytic syndrome
Case Reports
Prognosis and Treatment
  • More aggressive than most B cell lymphomas; 5 year survival of 25% (20 - 30%)
  • Treatment: chemotherapy, autologous stem cell transplant
  • Usually highly aggressive with poor response to therapy and frequent relapses
  • Factors consistently associated with prognosis: stage and IPI score
  • Other negative prognostic factors: bone marrow involvement, EBV+, NFκB deregulation, high proliferation signature by gene expression, cytotoxic granule expression (Curr Hematol Malig Rep 2010;5:222)
Postulated Normal Counterpart
  • Activated mature T lymphocytes, mostly CD4+ central memory type of the adaptive immune system
Micro Description
  • Paracortical or diffuse effacement by groups of atypical cells of variable sizes separated by delicate PAS+ connective tissue
  • Cells often have clear cytoplasm, resemble Reed-Sternberg cells, with irregular, pleomorphic, hyperchromatic or vesicular nuclei with prominent nucleoli
  • Many mitotic figures; very broad cytologic spectrum from highly polymorphous to monomorphous; eosinophils, small lymphocytes, plasma cells, epithelioid histiocytes or granulomas; often marked vascularity (high endothelial venules)
  • Bone marrow: patterns are small lymphocytic, large cell / immunoblastic or mixed; diffuse or randomly distributed focal infiltrates of variable size with poorly demarcated margins that blend into remaining marrow; large cells have abundant amphophilic cytoplasm and prominent eosinophilic nucleoli resembling Reed-Sternberg cells or its mononuclear varianta; small / medium sized cells have condensed chromatin with normal or irregular nuclear contours; often associated infiltrate of histiocytes, plasma cells, eosinophils and neutrophils; often epithelioid histiocytes, increased vascularity
  • Skin: dermis and subcutis involvement, often nodules with central ulceration; epidermotropism, angiocentricity and adnexal involvement
  • Spleen: solitary or multiple nodules to diffuse white pulp involvement with colonization of the periarteriolar sheath; sometimes predominant red pulp infiltration; may resemble marginal zone lymphoma (Mod Pathol 2002;15:420)
Micro Images

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Lymph nodes

Resembling MALT lymphoma

Positive Stains
  • CD2, CD3, TCR β F1; variable CD4, CD5 and CD7
  • Reticulin in marrow (increased fibers in neoplastic areas that extend into adjacent marrow)
  • Frequent downregulation of CD5 and CD7
  • CD4+ / CD8- predominantly in nodal cases; sometimes double negative or double positive
  • Occasional CD56 and cytotoxic granule expression
  • May be CD15+ / CD30+ and resemble Hodgkin lymphoma (Am J Surg Pathol 2003;27:1513)
  • Occasional aberrant CD20+ or CD79a+
  • Ki67 > 70% associated with worse prognosis
Negative Stains
  • CD1, TdT, CD52 (60%)
  • No follicular T helper phenotype (CD10, bcl6, PD-1 and CXCL13) with the exception of the follicular variant
Molecular / Cytogenetics Description
  • Clonal rearrangements of T cell receptor genes; usually alpha beta phenotype, no specific cytogenetic abnormalities
  • Deletions of 5q, 10q and 12q associated with better prognosis
  • EBV integration reported in some cases
  • Gene expression profile distinct from normal T cells (J Clin Invest 2007;117:823)
Differential Diagnosis
  • Hodgkin lymphoma: classic Reed-Sternberg cells are CD15+, CD30+, no atypia in lymphocytes
  • Systemic mastocytosis: tryptase+
  • Reactive lymphoid hyperplasia: usually no marked atypia, no T cell receptor clonality
  • Angioimmunoblastic T cell lymphoma: follicular T helper phenotype, different gene signature
  • Follicular B cell lymphoma
  • Anaplastic large cell lymphoma: different immunophenotype, different gene signature