Lymphoma and plasma cell neoplasms
T/NK cell disorders
General

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

Revised: 3 April 2017, last major update January 2012

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PubMed Search: T/NK cell disorders

Cite this page: T/NK cell disorders - General. PathologyOutlines.com website. http://pathologyoutlines.com/topic/lymphomanonBTcellgeneral.html. Accessed May 24th, 2017.
Definition / general
  • T/NK cell neoplasms are clonal tumors of mature and immature T cells or natural killer cells at various stages of differentiation (WHO 2008)
  • T and NK neoplasms are considered together because they are closely related and share immunophenotypic and functional properties
Epidemiology
  • Precursor T lymphoid neoplasms (T-ALL / LBL): primarily diseases of children / young adults, 10 - 15% of acute lymphoblastic leukemia (ALL), 85 - 90% of lymphoblastic lymphoma (LBL), male predominance (Pediatr Blood Cancer 2008;51:489)
  • Mature T/NK cell neoplasms: relatively uncommon; 15% of non-Hodgkin lymphomas in U.S. / Western Europe; are usually aggressive with median survival of 10 - 30 months
  • Large international study (Blood 1997;89:3909): 12% of all NHL are T/NK cell (peripheral T cell lymphoma NOS - 25.9%, angioimmunoblastic T cell lymphoma - 18.5%)
  • Significant geographic and racial incidence variation: generally more common in Asia or Asian populations; adult T cell leukemia / lymphoma in endemic HTLV-I areas, enteropathy associated T cell lymphoma in those of Welsh and Irish descent
  • Overall incidence of T cell neoplasms in the U.S. is 2.6 cases / 100,000 persons / year (slight overall increase, mostly in the cutaneous T cell lymphoma category)
Sites
  • Usually mirror the distribution of their normal cellular counterparts
  • Most T cell lymphomas are nodal; most NK cell lymphomas are extranodal
  • Lymphomas of the innate immune system: predominantly extranodal; pediatric and young adult (aggressive NK cell leukemia, systemic EBV+ T-LPD of childhood, hepatosplenic T cell lymphoma, mucosal / cutaneous γδ T cell lymphomas)
  • Lymphomas of the adaptive immune system: mainly nodal, usually adult patients
Pathophysiology
  • Cells of the innate immune system (NK cells, CD3+ CD56+ T cells or NK-like cells, and γδ T cells): first line of defense, primitive response, do not require antigen presentation
  • Adaptive immune system: utilizes specificity and memory
  • T lymphocytes originate from a bone marrow precursor undergoing maturation in the thymus
  • Cortical thymocytes: positive for TdT, CD1a, CD3, CD5, CD7 (immature T cell phenotype); initially CD4 / CD8 double negative, then double positive, then either CD4 or CD8
  • Medullary thymocytes: phenotype similar to mature T cells (could be αβ or γδ); associated with a complete CD3 complex (γ, δ and ε chains)
  • γδ T cells: < 5% of all normal T cells, CD4 / CD8 double negative, usually lack CD5, a subpopulation expresses CD8, restricted distribution (splenic red pulp, intestinal epithelium, other epithelial sites)
  • Two categories of CD4+ T cells: Th1 (secrete IL-2 and interferon γ) and Th2 (secrete IL-4, 5, 6 and 10)
  • Unique subset of CD4+ T cells found in the germinal center: follicular T helper cells (TFH) - positive for BCL6, CD10, CD4, CD57, PD-1, CXCL13
  • Regulatory CD4+ T cells (Treg) with immune suppressing function: positive for CD25, FOXP3 (adult T cell leukemia / lymphoma is associated with marked immunosuppression)
  • NK cells: incomplete T cell receptor complex; positive for cytoplasmic CD3 (not surface), CD2, CD7, CD16, CD56, variably CD57, cytotoxic proteins, sometimes CD8
Etiology
  • EBV associated: extranodal NK/T cell lymphoma, systemic EBV+ T cell lymphoproliferative disorder of childhood, Hydroa vacciniforme-like T cell lymphoma
  • HTLV-I: adult T cell leukemia / lymphoma
Microscopic (histologic) description
  • 99% have diffuse lymphocytic infiltrate with numerous, evenly dispersed, ill defined, small clusters of epithelioid histiocytes, but these may actually be Hodgkin lymphoma or lymphoplasmacytic lymphoma
  • Peripheral T cell lymphomas are, by definition, composed of mature (not precursor) T cells; often misdiagnosed (Mod Pathol 2002;15:420)
  • Most relapses of nodal disease have similar histology, pattern of nodal involvement, immunophenotype (Am J Clin Pathol 2000;114:438)
  • Large B cells present in peripheral T cell disorders may be due to EBV (in immunodeficient patients) or represent clonal populations that develop into diffuse large B cell lymphoma (Am J Clin Pathol 2000;114:236, Am J Clin Pathol 2002;117:368)
Immunohistochemistry
  • Aberrant T cell phenotype (immunophenotypic clusters exhibiting altered expression of T cell antigens relative to normal) usually implies clonality
  • Most common aberrant values are for CD3, CD7, CD5; CD2 is most stable; for CD7, deletion is common (Am J Clin Pathol 2001;116:512)
  • Rarely express B cell markers CD20 and CD79a (Mod Pathol 2001;14:105)
  • NK markers are CD11b, CD11c, CD16, CD56, CD57 and polyclonal CD3 (detects CD3 epsilon)
  • Recommended immunostains include T cell markers (CD3, CD43, CD45RO) and B cell markers (CD20)
  • Granzyme M (suggested role in the effector phase of the innate immune system): NK cells, CD3+ CD56+ T cells and γδ T cells (hepatosplenic T cell lymphoma, cutaneous γδ T cell lymphomas, most intestinal T cell lymphomas)
Molecular / cytogenetics description
  • Must first establish that process is neoplastic
  • Only a few T cell neoplasms have specific genetic abnormalities: anaplastic large cell lymphoma (ALK), HSTL (iso7q)
  • Immunostaining or flow cytometry is useful for classification but usually cannot prove clonality
  • Requires T cell receptor gene rearrangement studies by PCR (can use paraffin)
  • Analysis of KIR receptors in NK cell proliferations is useful (NK cells do not rearrange the T cell receptor genes)