Page 1108 - Clinical Immunology_ Principles and Practice ( PDFDrive )

1072 ParT EIGhT Immunology of Neoplasia

lymphomas, in which the MYC translocation occurs as a secondary Aggressive NK-cell leukemia is a closely related entity with a
33
event in a more complex karyotype. Most of the translocations similar phenotype, EBV association, and epidemiology. It presents
involve the IGH gene on chromosome 14 and, less commonly, at a younger age than extranodal NK/T-cell lymphoma, is
the light-chain genes on chromosomes 2 and 22. associated with systemic disease, and has a fulminant clinical
Recently, a subset with chromosome 11q alterations that course.
+
morphologically, largely phenotypically, and by GEP resemble There are other EBV T-cell and NK-cell proliferations seen
34
BL but lack MYC translocations has been described as a new mainly in Asian children and in indigenous populations from
provisional entity “Burkitt-like lymphoma with 11q aberration” Central and South Americas and Mexico. These show a broad
in the revised classification. Mutations in the transcription factor range of clinical manifestations from indolent, localized forms
TCF3 or its negative regulator ID3 are present in approximately involving skin, such as hydroa vacciniforme-like lymphoproliferative
70% of sporadic and immunodeficiency-related BL and 40% of disorder (name changed from lymphoma) and mosquito bite
endemic cases. allergy, the latter usually being derived from NK cells, to systemic
+
Few cases show GEP of BL but carry additional BCL2 or EBV T-cell lymphoma (name changed from lymphoproliferative
3
BCL6 cytogenetic abnormalities. These “double-hit” or “triple-hit” disease), a more systemic form characterized by fever, hepato-
lymphomas have an aggressive clinical course and poor prognosis splenomegaly and lymphadenopathy with or without cutaneous
36
and are now reclassified from the previous borderline category manifestations and a fulminant clinical course, and hemophago-
of the 2008 WHO classification now as HGBL with and without cytic lymphohistiocytosis.
MYC and BCL2 or BCL6 translocations (except for those fulfilling
3
the criteria for follicular or lymphoblastic lymphoma). Of note, Nodal T-Cell Lymphoma With T FH Phenotype:
the “double-hit” lymphoma are usually of GCB subtype, whereas Angioimmunoblastic T-Cell Lymphoma
“double expressors” are of the ABC subtype. However, this Recently angioimmunoblastic T-cell lymphoma (AITL) has been
category should not be utilized for otherwise typical DLBCLs grouped under an umbrella category “nodal T-cell lymphoma
with a MYC translocation. with T follicular helper cell (T FH ) phenotype” to highlight a
spectrum of nodal lymphomas with T FH phenotype, including
T-CELL AND NK-CELL NEOPLASMS follicular T-cell lymphoma and other nodal PTCLs with a T FH
phenotype, in addition to AITL. 3
Overview of the Classification of T-Cell Neoplasms AITL presents in adults with generalized lymphadenopathy
Peripheral T-cell lymphomas (PTCLs) are uncommon, representing and prominent systemic symptoms, including fever, weight loss,
fewer than 10% of all non-HLs. The classification of PTCL has and skin rash. Polyclonal hypergammaglobulinemia is usually
always been controversial. The genetic landscape of many entities seen.
has only recently been defined, and immunophenotypic markers Histologically, the nodal architecture is generally effaced,
are less specific for apparently distinct disease entities. For these but peripheral sinuses are often open or dilated. Proliferation
reasons, the WHO classification relied, to a considerable extent, of high endothelial venules (HEVs) is often prominent. Fol-
on clinical presentation to subdivide these tumors. 2 licles are regressed, but a proliferation of dendritic cells (DCs)
often entrapping HEVs is typically seen. The atypical lym-
Extranodal NK/T-Cell Lymphoma, Nasal Type phoid cells have clear cytoplasm and are admixed with small
Extranodal NK/T-cell lymphoma, nasal type, is a distinct clini- lymphocytes, immunoblasts, plasma cells, and histiocytes, with or
copathological entity highly associated with EBV. It affects adults without eosinophils. A relationship to T FH has been confirmed by
(median age 50 years), and the most common clinical presentation GEP. The atypical T cells are usually positive for CD4, CD10, and
is a destructive nasal or midline facial lesion. Palatal destruction, PD-1, a phenotype characteristic of T FH . Chemokine ligand-13
orbital swelling, and edema can be prominent. NK/T-cell lym- (CXCL-13), a chemokine involved in B-cell trafficking into
phomas have been reported in other extranodal sites, including the germinal centers, is also expressed. In keeping with an
skin, soft tissue, testes, the upper respiratory tract, and the GI established derivation from T FH, B-cell proliferation, including
tract. It is much more common in Asians and indigenous popula- marked polyclonal plasmacytosis, is often seen. In some cases, the
+
tions of the Americas than in those of European background, plasma cells may be monoclonal. Background EBV B cells are
+
and this indicates that genetic factors play a role in the patho- almost constant, and progression to EBV B-cell lymphoma may
genesis of these lymphomas. occur. The exact role of EBV in AILT is uncertain; however,
Extranodal NK/T-cell lymphoma, nasal type, is characterized plausible theories include expansion resulting from decreased
by a broad cytological spectrum. Although the cells express some immune surveillance. The majority of cases show clonal rear-
T cell–associated antigens, most commonly CD2, other T-cell rangements of T-cell receptor (TCR) genes, but proliferation of
markers, such as surface CD3, are usually absent. Cytoplasmic B cells also contributes to the histological and clinical picture.
CD3 is positive, but most cases lack clonal T-cell gene rearrange- Patients may initially respond to steroids or mild cytotoxic
ment. In favor of an NK-cell origin, the cells are nearly always chemotherapy, but progression usually occurs. More aggressive
+
CD56 , although CD16 and CD57 are usually negative. EBV is combination chemotherapeutic regimens have led to a higher
invariably positive as shown by in situ hybridization. remission rate, but patients are prone to secondary infec-
The clinical features and treatment response of nonnasal tious complications. The median survival is usually less than
extranodal NK/T-cell lymphoma are different from of those of 5 years.
nasal presentation of this lymphoma in that the addition of New genetic insights have shown recurrent mutations, includ-
radiotherapy in early-stage nasal cases may offer a survival ing TET2, IDH2, DNMT3A, RHOA, and CD28, as well as gene
35
benefit. A hemophagocytic syndrome is a common clinical fusions, such as ITK-SYK or CTLA4-CD28, which affect a sig-
complication and adversely affects survival. Emerging oncogenic nificant proportion of PTCL, NOS cases with a T FH phenotype,
pathways have been identified by GEP. and AITL cases.