Peripheral T-cell Lymphoma, Not Otherwise Specified



Peripheral T-cell Lymphoma, Not Otherwise Specified


James M. You, MD, PhD





Key Facts


Clinical Issues



  • PTCL represents approximately 6.0% of all non-Hodgkin lymphomas


  • Mainly arises in middle-aged adults; rare in children


  • Advanced-stage disease with B symptoms


  • Poor prognosis with frequent relapses


  • Lymphadenopathy; extranodal sites often involved


Microscopic Pathology



  • Paracortical infiltrate or diffuse effacement of lymph node architecture


  • Wide cytological spectrum


  • Background inflammatory cells often numerous


  • ± postcapillary venules in arborizing fashion


  • ± high rates of proliferation and apoptosis


Ancillary Tests



  • Pan-T-cell antigens(+)


  • CD4(+) CD8(−) or CD4(−) CD8(+)


  • Aberrant T-cell immunophenotypes in ˜ 80% of cases


  • CD30 can be positive, exceptionally CD15(+)


  • ± cytotoxic molecules


  • Monoclonal TCR gene rearrangements


  • No consistent chromosomal/molecular abnormality


Top Differential Diagnoses



  • Angioimmunoblastic T-cell lymphoma


  • Adult T-cell leukemia/lymphoma


  • Anaplastic large cell lymphoma


  • Classical Hodgkin lymphoma


  • T-cell/histiocyte-rich large B-cell lymphoma







Peripheral T-cell lymphoma (PTCL) involving lymph node. The neoplastic cells in this case show abundant clear cytoplasm.






PTCL with a “starry sky” pattern indicating a high proliferation rate. The histiocytes corresponding to the “stars” are indicated image. Eosinophils are also present image.


TERMINOLOGY


Abbreviations



  • Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS)


Synonyms



  • Peripheral T-cell lymphoma (PTCL)


  • Peripheral T-cell lymphomas, unspecified



    • Term used in 2001 World Health Organization (WHO) classification


  • Post-thymic T-cell lymphoma


  • Immunoblastic sarcoma of T-cell lineage


Definitions



  • Mature T-cell lymphomas that cannot be classified into specific T-cell categories



    • Heterogeneous group in current WHO classification


    • PTCL is, in part, diagnosis of exclusion


ETIOLOGY/PATHOGENESIS


Etiology and Pathogenesis



  • Evidence that aberrant T-cell signaling drives T-cell lymphoproliferation


  • The specific etiology of PTCL is unknown



    • Once etiology or pathogenesis of a subgroup is defined, this subset is likely to be reclassified


Cell of Origin



  • Activated mature T-lymphocyte, either CD4(+) or CD8(+)


CLINICAL ISSUES


Epidemiology



  • Incidence



    • PTCL represents approximately 6% of all non-Hodgkin lymphomas



      • ˜ 50% of all NK/T-cell neoplasms


  • Age



    • Mainly arises in middle-aged adults; rare in children


  • Gender



    • Male to female ratio ˜ 2:1


Site



  • Lymph nodes are usually involved


  • Involvement of extranodal sites is common, including



    • Bone marrow, spleen, liver, lung, and skin


Presentation



  • Most patients have advanced-stage disease with B symptoms


  • Bulky disease in ˜ 10% of patients


  • Leukemic phase is rare at presentation


  • Cytokine-related paraneoplastic phenomena can occur, including



    • Pruritus &/or eosinophilia


    • Hemophagocytic syndrome


  • Prior to onset of PTCL, immune-mediated disorders can occur, including



    • Hashimoto thyroiditis, rheumatoid arthritis


    • Immune thrombocytopenic purpura


Laboratory Tests



  • Elevated serum lactate dehydrogenase (LDH) level is common


Treatment



  • Aggressive combination chemotherapy ± consolidation therapy



    • Induction combination chemotherapy regimens combine anthracycline with alkylating agent


    • Consolidation therapy



      • Hematopoietic stem cell transplantation


      • Radiation therapy


  • Treatment for refractory or relapsed PTCL



    • Combination chemotherapy but there is no consensus on optimal regimen



    • Participation in clinical trials is encouraged


Prognosis



  • Overall response to therapy is poor with frequent relapses


  • 5-year overall survival and failure-free survival (20-30%)


  • Poor prognosis has been associated with



    • High stage


    • High international prognostic index (IPI)


    • Features suggested but need to be confirmed



      • Epstein-Barr virus (EBV)(+)


      • Gene expression profile showing NF-κB dysregulation or high proliferation signature


      • Cytotoxic immunophenotype


  • Small subset of patients with localized disease and low IPI have better outcome


IMAGE FINDINGS


Radiographic Findings



  • Lymphadenopathy


  • FDG-PET is often positive


MICROSCOPIC PATHOLOGY


Histologic Features



  • Lymph node



    • Paracortical infiltrate or diffuse effacement of architecture


    • Proliferation of postcapillary venules in interweaving (arborizing) fashion can be present


    • High rates of proliferation and apoptosis


    • Background inflammatory cells usually present, including:



      • Eosinophils, plasma cells, small lymphocytes


      • Epithelioid histiocytes, large B cells


    • In subset of cases, there is preferential involvement of T-zones


    • In some cases, neoplasm is associated with fibrosis



      • Fibrous bands can compartmentalize neoplasm, simulating nodular pattern


  • Skin



    • PTCL commonly infiltrates dermis and subcutis; can produce nodules with central ulceration


    • Angiocentricity and adnexal involvement may be seen


    • Epidermotropism is rare


  • Spleen



    • Solitary or multiple fleshy nodules involving white pulp with colonization of periarteriolar sheath


    • Predominant infiltration of red pulp in some cases


Cytologic Features



  • Wide spectrum of neoplastic T-cells of small, intermediate, or large size



    • Numerous intermediate-sized &/or large cells, most common


  • Neoplastic cells have sparse or abundant cytoplasm



    • Clear, eosinophilic, or basophilic


  • Nuclei of neoplastic cells show wide spectrum



    • Vesicular, hyperchromatic, or pleomorphic


    • Multinucleated or Reed-Sternberg-like nuclei can occur


Morphologic Variants of PTCL



  • Lymphoepithelioid (Lennert lymphoma)



    • Diffuse replacement of lymph node architecture


    • Predominantly small lymphoid cells with slight nuclear irregularities


    • Confluent clusters of epithelioid histiocytes


    • Scattered, larger, more atypical cells, including occasional Reed-Sternberg-like cells (usually EBV[+])


    • Occasional admixed inflammatory cells, including eosinophils and plasma cells


    • Neoplastic cells are often CD8(+)


  • PTCL with “follicular” pattern



    • Also reported as perifollicular, intrafollicular, or paracortical nodular variants of PTCL


    • Intrafollicular aggregates of T-cell lymphoma that mimic follicular lymphoma at low-power magnification



    • Enlarged perifollicular zones surrounding hyperplastic follicles mimicking nodal marginal zone B-cell lymphoma


    • Small nodular aggregates of PTCL in background of progressively transformed germinal centers



      • Can mimic nodular lymphocyte-predominant Hodgkin lymphoma


    • Neoplastic cells are T cells, usually CD4(+)


  • T zone



    • Predominantly perifollicular or interfollicular growth pattern


    • Reactive follicles are preserved and can be hyperplastic


    • Small or intermediate-sized neoplastic cells with clear or eosinophilic cytoplasm



      • Minimal nuclear pleomorphism


    • Commonly associated with vascular proliferation and heterogeneous mixture of reactive cells


PTCL with Associated B-cell Proliferation



  • Approximately 10% (or less) of PTCL cases can be associated with numerous B cells


  • B-cells are small mature plasma cells, plasmacytoid large B-lymphocytes, or plasmablasts


  • B cells are often EBV(+)


ANCILLARY TESTS

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Jul 8, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Peripheral T-cell Lymphoma, Not Otherwise Specified

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