Lymphomas, T-Cell/NK-Cell - T-Cell/NK-Cell Lymphomas

  • Diagnosis
  • Algorithms
  • Background
  • Lab Tests
  • References
  • Related Content

Indications for Testing

  • Adenopathy
  • Fevers/night sweats
  • Recurrent infections
  • Unexplained lymphocytosis or abnormal manual differential

Laboratory Testing

  • Phenotyping by flow cytometry


  • Bone marrow biopsy
    • Goal of ≥2 cm length
    • Classified as “bone marrow involvement” or “no bone marrow involvement”
  • Immunophenotyping to identify lymphoid proliferation and to categorize the lymphoma
    • Flow cytometry testing by identification of aberrant antigen expression patterns (ie, loss of one or more pan-T-cell antigens or coexpression of CD10)
    • T-cell markers – kappa, lambda, CD2, CD3, CD4, CD5, CD7, CD8, CD10, CD16, CD19, CD20, CD23, CD25, CD26, CD30, CD45, CD56, CD57, CD103
  • Immunohistochemistry
    • T-cell stains – CD1a, CD2, CD3, CD4, CD5, CD7, CD8, CD10, CD15, CD20, CD21, CD23, CD25, CD30, CD34, CD43, CD45RO, CD56, CD57, Ki-67, EBER-EBV, ALK, BF-1, Muc-1, TIA-1, granzyme B, TdT
    • Others available – CD20, CD45RA-MT2, CD95, BCL-2, c-Myc
  • Skin biopsy – for mycosis fungoides/Sézary syndrome
    • Immunohistochemistry
    • T-cell receptor gene rearrangements
    • Flow cytometry for Sézary syndrome

Imaging Studies

  • CT/MRI – most useful in assessing where disease is present after diagnosis


  • International Prognostic Index scoring system
    • Based on pretreatment clinical factors of age (≤60 years); tumor stage (I or II); number of extranodal sites (≤1); ECOG performance status (0 or 1); and serum lactate dehydrogenase (LD) (≤1 times normal) – all scored as 0
    • Patients placed in one of four risk groups
    • Limited usefulness in follicular lymphoma, mantle cell lymphoma, NK-cell lymphoma, nasal-type lymphoma, hepatosplenic lymphoma, and enteropathy-type lymphoma
  • Other prognostic systems include
    • Prognostic index for peripheral T-cell lymphoma not otherwise specified – uses bone marrow involvement, age, performance status, LD
    • Bologna score – uses immunohistochemistry (CD15, EBV, Ki76)
    • Korean prognostic NK-cell score – uses β symptoms, LD, lymphoma stage, regional node involvement
    • NK prognostic score – uses stage, performance status, extranodal involvement, nasal type (non vs (+))

Differential Diagnosis

Lymphoma Leukemia Phenotyping Testing Algorithm

T-cell and NK-cell non-Hodgkin lymphomas (NHL) represent a small portion of the lymphomas diagnosed in the U.S.


  • Incidence – 15-20% of all NHL lymphomas
    • >70,000 NHL diagnosed (NCCN, 2014)
  • Age – usually adults (incidence increases with age)
  • Sex – unequal distribution; based on specific type

WHO Classification of Mature T- and NK-cell Neoplasms (2008)

  • T-cell prolymphocytic leukemia
  • T-cell large granular lymphocytic leukemia
  • Chronic lymphoproliferative disorder of NK-cells (provisional entity)
  • Aggressive NK-cell leukemia
  • Systemic Epstein-Barr virus (EBV)-positive T-cell lymphoproliferative disorder of childhood
  • Adult T-cell leukemia/lymphoma (ATLL)
  • Extranodal NK-/T-cell lymphoma, nasal type
  • Enteropathy-associated T-cell lymphoma
  • Hepatosplenic T-cell lymphoma
  • Subcutaneous panniculitis-like T-cell lymphoma
  • Mycosis fungoides
  • Sézary syndrome
  • Primary cutaneous CD30-positive T-cell lymphoproliferative disorders
  • Primary cutaneous gamma-delta T-cell lymphomas
  • Peripheral T-cell lymphoma, NOS (not otherwise specified)
  • Angioimmunoblastic T-cell lymphoma
  • Anaplastic large-cell lymphoma (ALCL), ALK-positive
  • ALCL, ALK-negative (provisional entity)

Risk Factors

  • Viral infection
  • Chromosomal rearrangements
    • Predominantly on T-cell receptor (TCRG) genes
  • Host susceptibility factors – congenital or acquired
    • Gliadin allergy – enteropathy-type T-cell
    • Immunosuppression

Clinical Presentation of Selected Lymphoma Subtypes (based on WHO classification and Gru, 2015)

  • Precursor T-cell neoplasm
  • Mature T-cell and NK-cell neoplasms

Indications for Laboratory Testing

Tests generally appear in the order most useful for common clinical situations.
Click on number for test-specific information in the ARUP Laboratory Test Directory

Leukemia/Lymphoma Phenotyping by Flow Cytometry 2008003
Method: Flow Cytometry

T-Cell Clonality by Next Generation Sequencing 2008409
Method: Massively Parallel Sequencing


Clonal TCRG gene rearrangements below the limit of detection will not be reported

T-Cell Clonality by Flow Cytometry Analysis of TCR V-Beta 0093199
Method: Flow Cytometry


Lacks sensitivity of NGS

Human T-Lymphotropic Virus (HTLV) Types I/II Antibodies by ELISA with Reflex to HTLV-I/II Confirmation by Western Blot 0051164
Method: Qualitative Enzyme-Linked Immunosorbent Assay/Qualitative Western Blot

Epstein-Barr Virus by PCR 0050246
Method: Qualitative Polymerase Chain Reaction

CD2 by Immunohistochemistry 2003505
Method: Immunohistochemistry

CD1a by Immunohistochemistry 2003502
Method: Immunohistochemistry

CD3 by Immunohistochemistry 2003508
Method: Immunohistochemistry

CD4 by Immunohistochemistry 2003511
Method: Immunohistochemistry

CD5 by Immunohistochemistry 2003514
Method: Immunohistochemistry

CD7 by Immunohistochemistry 2003517
Method: Immunohistochemistry

CD8 by Immunohistochemistry 2003520
Method: Immunohistochemistry

CD10 (CALLA) by Immunohistochemistry 2003523
Method: Immunohistochemistry

CD15, Leu M1 by Immunohistochemistry 2003529
Method: Immunohistochemistry

CD19 by Immunohistochemistry 2005114
Method: Immunohistochemistry

CD21 (Dendritic Cell) by Immunohistochemistry 2003535
Method: Immunohistochemistry

CD23 by Immunohistochemistry 2003541
Method: Immunohistochemistry

CD25 by Immunohistochemistry 2003544
Method: Immunohistochemistry

CD30 (Ki-1) by Immunohistochemistry 2003547
Method: Immunohistochemistry

CD34, QBEnd/10 by Immunohistochemistry 2003556
Method: Immunohistochemistry

CD43, L60 (Leu 22) by Immunohistochemistry 2003568
Method: Immunohistochemistry

CD56 (NCAM) by Immunohistochemistry 2003589
Method: Immunohistochemistry

CD57 by Immunohistochemistry 2003592
Method: Immunohistochemistry

Ki-67, MIB-1, by Immunohistochemistry 2004519
Method: Immunohistochemistry

Anaplastic Lymphoma Kinase 1 (ALK-1) by Immunohistochemistry 2003439
Method: Immunohistochemistry

BF-1 by Immunohistochemistry 2003466
Method: Immunohistochemistry

Muc-1 by Immunohistochemistry 2004002
Method: Immunohistochemistry

T-cell Intracytoplasmic Antigen (TIA-1) by Immunohistochemistry 2004148
Method: Immunohistochemistry

Granzyme B by Immunohistochemistry 2007173
Method: Immunohistochemistry

TdT by Immunohistochemistry 2004142
Method: Immunohistochemistry

Additional Tests Available

Hepatic Function Panel 0020416
Method: Quantitative Enzymatic/Quantitative Spectrophotometry


Identify hepatic dysfunction

May provide prognostic information

Panel includes albumin; alkaline phosphatase; aspartate aminotransferase; alanine aminotransferase; bilirubin, direct; protein; bilirubin, total

CBC with Platelet Count and Automated Differential 0040003
Method: Automated Cell Count/Differential


Rule out infectious process; identify lymphocytosis

Lactate Dehydrogenase, Serum or Plasma 0020006
Method: Quantitative Enzymatic


May provide prognostic information

Uric Acid, Serum or Plasma 0020026
Method: Quantitative Spectrophotometry


May provide prognostic information

Assay interference (negative) may be observed when high concentrations of N-acetylcysteine (NAC) are present

Negative interference has also been reported with NAPQI (an acetaminophen metabolite) but only when concentrations are at or above those expected during acetaminophen overdose

CD20, L26 by Immunohistochemistry 2003532
Method: Immunohistochemistry

BCL-2 by Immunohistochemistry 2004513
Method: Immunohistochemistry

Potassium, Plasma or Serum 0020002
Method: Quantitative Ion-Selective Electrode

Calcium, Ionized, Serum 0020135
Method: Ion-Selective Electrode/pH Electrode

Phosphorus, Inorganic, Plasma or Serum 0020028
Method: Quantitative Spectrophotometry


NCCN Clinical Practice Guidelines in Oncology, Non-Hodgkin's Lymphomas. National Comprehensive Cancer Network. Fort Washington, PA [Accessed: Jun 2015]

Protocol for the Examination of Specimens from Patients with Hematopoietic Neoplasms of the Ocular Adnexa. Based on AJCC/UICC TNM, 7th ed. Protocol web posting date: March 2010. College of American Pathologists (CAP). Northfield, IL [Accessed: May 2015]

Protocol for the Examination of Specimens From Patients With Non-Hodgkin Lymphoma/Lymphoid Neoplasms. Based on AJCC/UICC TNM, 7th ed. Protocol web posting date: June 2010. College of American Pathologists (CAP). Northfield, IL [Accessed: Jun 2015]

General References

Foss F. Molecular predictors of response in aggressive T-cell lymphomas. Cancer J. 2011; 17(2): 142-8. PubMed

Good D, Gascoyne R. Classification of non-Hodgkin's lymphoma. Hematol Oncol Clin North Am. 2008; 22(5): 781-805, vii. PubMed

Gru A. Pathology of T-cell lymphomas: diagnosis and biomarker discovery. Cancer Treat Res. 2015; 165: 51-95. PubMed

Hartmann E, Ott G, Rosenwald A. Molecular biology and genetics of lymphomas. Hematol Oncol Clin North Am. 2008; 22(5): 807-23, vii. PubMed

Jaffe E, Harris N, Stein H, Isaacson P. Classification of lymphoid neoplasms: the microscope as a tool for disease discovery. Blood. 2008; 112(12): 4384-99. PubMed

Johnston A, Salles G. Prognostic systems for lymphomas. Hematol Oncol Clin North Am. 2008; 22(5): 839-61, viii. PubMed

Ko C. The new World Health Organization-European Organization for Research and Treatment of Cancer classification of cutaneous lymphomas. Adv Dermatol. 2006; 22: 259-77. PubMed

Rezania D, Sokol L, Cualing H. Classification and treatment of rare and aggressive types of peripheral T-cell/natural killer-cell lymphomas of the skin. Cancer Control. 2007; 14(2): 112-23. PubMed

Skoog L, Tani E. T cell neoplasms. Monogr Clin Cytol. 2009; 18: 38-48. PubMed

Soo K, Shustik D, Yusoff L, Tan L, Tan S. An algorithmic approach to the diagnosis of NK and T cell lymphomas. Pathology. 2011; 43(7): 673-81. PubMed

Vardiman J, et al. Myeloproliferative Neoplasms. In Swerdlow SH, et al. WHO Classification of Tumours of Haematoietic and Lymphoid Tissues, Lyon, France: IARC Press, 2008.

References from the ARUP Institute for Clinical and Experimental Pathology®

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Medical Reviewers

Last Update: January 2016