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

  • Diagnosis
  • Algorithms
  • Background
  • Lab Tests
  • References
  • Related Topics
  • Videos

Indications for Testing

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

Laboratory Testing

  • Phenotyping by flow cytometry

Histology

  • 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

Prognosis

  • 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

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

Epidemiology

  • 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

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

Limitations

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

Limitations

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

Related Tests

Guidelines

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: Mar 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: Oct 2013. College of American Pathologists (CAP). Northfield, IL [Accessed: Jun 2015]

General References

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

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

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

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

Jaffe ES, Harris NLee, Stein H, Isaacson PG. 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 CJ. 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 HD. 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 KL, Shustik D, Yusoff LZ Mohd, Tan L, Tan SY. 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, 4th. Lyon, France: IARC Press, 2008.

References from the ARUP Institute for Clinical and Experimental Pathology®

Bahler DW, Hartung L, Hill S, Bowen GM, Vonderheid EC. CD158k/KIR3DL2 is a useful marker for identifying neoplastic T-cells in Sézary syndrome by flow cytometry. Cytometry B Clin Cytom. 2008; 74(3): 156-62. PubMed

Capriotti E, Vonderheid EC, Thoburn CJ, Wasik MA, Bahler DW, Hess AD. Expression of T-plastin, FoxP3 and other tumor-associated markers by leukemic T-cells of cutaneous T-cell lymphoma. Leuk Lymphoma. 2008; 49(6): 1190-201. PubMed

Chen E, Lim MS, Rosic-Kablar S, Liu J, Jolicoeur P, Dubé ID, Hough MR. Dysregulated expression of mitotic regulators is associated with B-cell lymphomagenesis in HOX11-transgenic mice. Oncogene. 2006; 25(18): 2575-87. PubMed

Chen LC, Delgado JC, Jensen PE, Chen X. Direct expansion of human allospecific FoxP3+CD4+ regulatory T cells with allogeneic B cells for therapeutic application. J Immunol. 2009; 183(6): 4094-102. PubMed

Chen ZWill, Perkins SL, Weiss RL, Bahler DW, Hussong JW, Salama ME. A limited plasma cell flow cytometry panel with reflex CD138 immunohistochemistry is an optimal workflow process for evaluating plasma cell neoplasms in bone marrow specimens Am J Clin Pathol. 2015; 143(1): 78-83. PubMed

Cho H, Reyes-Vargas E, Delgado JC, Celis E. A potent vaccination strategy that circumvents lymphodepletion for effective antitumor adoptive T-cell therapy. Cancer Res. 2012; 72(8): 1986-95. PubMed

Coustan-Smith E, Sandlund JT, Perkins SL, Chen H, Chang M, Abromowitch M, Campana D. Minimal disseminated disease in childhood T-cell lymphoblastic lymphoma: a report from the children's oncology group. J Clin Oncol. 2009; 27(21): 3533-9. PubMed

Florell SR, Cessna M, Lundell RB, Boucher KM, Bowen GM, Harris RM, Petersen MJ, Zone JJ, Tripp S, Perkins SL. Usefulness (or lack thereof) of immunophenotyping in atypical cutaneous T-cell infiltrates. Am J Clin Pathol. 2006; 125(5): 727-36. PubMed

Frazer JK, Meeker ND, Rudner L, Bradley DF, Smith AC H, Demarest B, Joshi D, Locke EE, Hutchinson SA, Tripp S, Perkins SL, Trede NS. Heritable T-cell malignancy models established in a zebrafish phenotypic screen. Leukemia. 2009; 23(10): 1825-35. PubMed

Juenke J, Brown PI, Urry FM, McMillin GA. Drug monitoring and toxicology: a procedure for the monitoring of levetiracetam and zonisamide by HPLC-UV. J Anal Toxicol. 2006; 30(1): 27-30. PubMed

Kadin ME, Pavlov IY, Delgado JC, Vonderheid EC. High soluble CD30, CD25, and IL-6 may identify patients with worse survival in CD30+ cutaneous lymphomas and early mycosis fungoides. J Invest Dermatol. 2012; 132(3 Pt 1): 703-10. PubMed

Lim MS, Elenitoba-Johnson KS J. Mass spectrometry-based proteomic studies of human anaplastic large cell lymphoma. Mol Cell Proteomics. 2006; 5(10): 1787-98. PubMed

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Palomero T, Sulis MLuisa, Cortina M, Real PJ, Barnes K, Ciofani M, Caparros E, Buteau J, Brown K, Perkins SL, Bhagat G, Agarwal AM, Basso G, Castillo M, Nagase S, Cordon-Cardo C, Parsons R, Zúñiga-Pflücker JCarlos, Dominguez M, Ferrando AA. Mutational loss of PTEN induces resistance to NOTCH1 inhibition in T-cell leukemia. Nat Med. 2007; 13(10): 1203-10. PubMed

Raetz EA, Perkins SL, Bhojwani D, Smock K, Philip M, Carroll WL, Min D. Gene expression profiling reveals intrinsic differences between T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma. Pediatr Blood Cancer. 2006; 47(2): 130-40. PubMed

Schumacher JA, Duncavage EJ, Mosbruger TL, Szankasi PM, Kelley TW. A comparison of deep sequencing of TCRG rearrangements vs traditional capillary electrophoresis for assessment of clonality in T-Cell lymphoproliferative disorders. Am J Clin Pathol. 2014; 141(3): 348-59. PubMed

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Medical Reviewers

Last Update: June 2016