T-Cell/NK-Cell Lymphomas

T-cell and NK-cell non-Hodgkin lymphomas (NHL) represent a small portion of the lymphomas diagnosed in the U.S. Laboratory testing methods include flow cytometry and PCR.

Diagnosis

Indications for Testing

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

Laboratory Testing

  • Phenotyping by flow cytometry
  • Genetic testing
    • Genetic variants associated with T-cell lymphomas include TCR, ALK, TP63, and IRF4/DUSP22 rearrangements; TCL1 and TRA translocations; and TET2/IDH1/IDH2/RHOA/DNMT3A and STAT3/STAT5B variants (NCCN, 2019)

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, CXCL13, Ki-67, EBER-EBV, ALK, BF-1, Muc-1, TIA-1, granzyme B, TdT, TCR δ
    • 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

Background

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

Classification

  • Classification of Mature T and NK Neoplasms (World Health Organization [WHO], 2016)
    • 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
    • Hydroa vacciniformelike lymphoproliferative disorder
    • Adult T-cell leukemia/lymphoma (ATLL)
    • Extranodal NK-/T-cell lymphoma, nasal type
    • Enteropathy-associated T-cell lymphoma
    • Monomorphic epitheliotropic intestinal T-cell lymphoma
    • Indolent T-cell lymphoproliferative disorder of the gastrointestinal (GI) tract (provisional entity)
    • Hepatosplenic T-cell lymphoma
    • Subcutaneous panniculitislike T-cell lymphoma
    • Mycosis fungoides
    • Sézary syndrome
    • Primary cutaneous CD30-positive T-cell lymphoproliferative disorders
      • Lymphomatoid papulosis
      • Primary cutaneous anaplastic large cell lymphoma
    • Primary cutaneous gamma-delta T-cell lymphomas
    • Primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma (provisional entity)
    • Primary cutaneous acral CD8-positive T-cell lymphoma (provisional entity)
    • Primary cutaneous CD4-positive small/medium T-cell lymphoproliferative disorder (provisional entity)
    • Peripheral T-cell lymphoma, not otherwise specified (NOS)
    • Angioimmunoblastic T-cell lymphoma
    • Follicular T-cell lymphoma (provisional entity)
    • Nodal peripheral T-cell lymphoma with TFH phenotype (provisional entity)
    • Anaplastic large cell lymphoma (ALCL), ALK positive
    • ALCL, ALK negative
    • Breast implant-associated anaplastic large cell lymphoma (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

  • Clinical presentation of selected lymphoma subtypes (WHO classification, 2016; Gru, 2015)
    • Precursor T-cell neoplasm
    • Mature T-cell and NK-cell neoplasms

ARUP Lab Tests

Aid in evaluation of hematopoietic neoplasms (ie, leukemia, lymphoma)

Specimens include bone marrow, whole blood, tissue, or fluid

Monitor therapy in patients with established diagnosis of hematopoietic neoplasms

Markers selected based on provided clinical history and/or previous test results

Antigens included:

T cell: CD1a, CD2, CD3, CD4, CD5, CD7, CD8, TCR γ-δ, cytoplasmic CD3

B cell: CD10, CD19, CD20, CD22, CD23, CD103, CD200, kappa, lambda, cytoplasmic kappa, cytoplasmic lambda

Myeloid/monocyte: CD11b, CD13, CD14 (Mo2), CD14 (MY4), CD15, CD33, CD64, CD117, myeloperoxidase

Miscellaneous: CD11c, CD16, CD25, CD30, CD34, CD38, CD41, CD42b, CD45, CD56, CD57, CD61, HLA-DR, glycophorin, TdT, bcl-2, CD123, CD138, CD26, CD45, CRLF-2

Aid in the diagnosis of T-cell lymphoproliferative disorders

Aid in histologic diagnosis of T-cell/NK-cell lymphomas

Stained and returned to client pathologist for interpretation; consultation available if needed

Detect IRF4/DUSP22 rearrangements which can contribute to diagnosis and prognosis in B-cell and T-cell lymphomas

Aid in differentiating T-cell leukemias and lymphomas from B-cell leukemias and lymphomas

Stained and returned to client pathologist for interpretation; consultation available if needed

Aid in differentiating T-cell leukemias and lymphomas from B-cell leukemias and lymphomas

Stained and returned to client pathologist for interpretation; consultation available if needed

Detect ALK fusion proteins (IHC) and ALK gene rearrangements (FISH) in solid tumors

Detect IDH1 and IDH2 mutations in whole blood or bone marrow

May have prognostic significance in patients with hematologic malignancies, depending on the clinical and genetic context

Aid in diagnosis of adult T-cell leukemia/lymphoma

Reflex pattern: if HTLV I/II screen is repeatedly reactive, HTLV I/II confirmation by Western blot will be added

Do not use for diagnosis of infectious mononucleosis

Order to detect Epstein-Barr virus (EBV) in individuals suspected of having EBV-related disease

Aid in histologic diagnosis of T-cell/NK-cell lymphomas

Stained and returned to client pathologist for interpretation; consultation available if needed

Aid in identifying some T-cell lymphoblastic lymphomas and leukemias

Stained and returned to client pathologist for interpretation; consultation available if needed

Aid in identifying lymphoblastic lymphoma, Burkitt lymphoma, follicular lymphoma, and CML; aid in differential diagnosis of small B-cell lymphomas and subtyping of lymphoblastic leukemias; helpful in angioimmunoblastic T-cell lymphomas

Stained and returned to client pathologist for interpretation; consultation available if needed

Aid in histologic differential diagnosis of T-cell/NK-cell leukemia/lymphoma

Stained and returned to client pathologist for interpretation; consultation available if needed

Related Tests

Identify hepatic dysfunction

May provide prognostic information

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

Rule out infectious process; identify lymphocytosis

May provide prognostic information

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

 

Medical Experts

Contributor

References

Additional Resources
Resources from the ARUP Institute for Clinical and Experimental Pathology®