Page 1109 - Clinical Immunology_ Principles and Practice ( PDFDrive )

ChaPTEr 79 Lymphomas 1073

Peripheral T-Cell Lymphomas, Not Otherwise Specified of implant to lymphoma of about 10 years. Confinement of the
Peripheral T-cell lymphomas, not otherwise specified (PTCL, neoplastic cells to the seroma fluid without capsule invasion
NOS) most often present in adults with generalized lymphade- portends a favorable prognosis.
nopathy, hepatosplenomegaly, and frequent bone marrow Recently GEP studies have shown that ALK-negative ALCLs
involvement. It is a diagnosis of exclusion with most cases being have a signature close to that of ALK-positive counterparts, but
nodal in origin. PTCLs are characterized by cytological and distinct from other NK/T-cell lymphomas. Genetic studies have
phenotypical heterogeneity. Most cases have a mature T-cell shown convergent mutations and kinase fusions leading to
phenotype and express one of the major subset antigens, with constitutive activation of the JAK/STAT3 pathway. The overall
CD4 expression seen more frequently than CD8. These are not survival and disease-free survival are significantly better in
clonal markers, and antigen expression can change over time. ALK-positive cases than in ALK-negative cases. Clinical or
Loss of one of the pan-T-cell antigens (CD3, CD5, CD2, or CD7) prognostic variations exist in ALK-negative ALCLs—a subset
is seen in two-thirds of cases, with loss of CD7 being most with rearrangements at the DUSP22 and IFR4 locus on 6p25
frequent. has a superior prognosis, whereas a small subset with TP63
Recently, GEP has shown a global signature close to one of rearrangements is very aggressive.
the activated T lymphocytes and has identified at least three
subtypes characterized by overexpression of GATA3, TBX21, and Primary Cutaneous ALCL
cytotoxic genes associated with a different clinical behavior and Primary cutaneous ALCL is closely related to lymphomatoid
response to therapy. The clinical course is generally aggressive, papulosis (LyP) and differs at the clinical, immunophenotypic,
especially with a high proliferation signature, with a lower and molecular levels from the systemic form. Indeed, LyP and
response rate than that seen for aggressive B-cell lymphomas. cutaneous ALCL represent a histological or clinical continuum
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of CD30 cutaneous lymphoproliferative diseases. Small lesions
Anaplastic Large-Cell Lymphoma are likely to regress, whereas patients with large tumor masses
Anaplastic large-cell lymphoma (ALCL) is most common in may develop disseminated disease with lymph node involvement—a
children and young adults, and more common in males than in period of observation is usually warranted before the institution
females. Nodal presentations are most common; however, a variety of any chemotherapy for isolated lesions. Most patients with
of extranodal sites can be involved. primary cutaneous ALCL have multiple skin lesions, but it is a
ALCL is characterized by pleomorphic or monomorphic cells more indolent disease compared with other T-cell lymphomas
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that have a propensity to invade lymphoid sinuses. The cells of of the skin. Cutaneous ALCL is CD30 but is usually ALK-1– and
classic ALCL have large, often lobulated nuclei with small EMA-negative, and it also lacks the t(2;5) translocation. More
basophilic nucleoli. In some cases, the nuclei may be round. The recently, LyP variants D-E and LyP with 6p25 have been described;
cytoplasm is usually abundant and amphophilic and has distinct appreciation of these variants is important as they can mimic
cytoplasmic borders, and a prominent Golgi region is generally aggressive T-cell lymphoma histologically but clinically are similar
visible. to other forms of LyP A-C.
The expression of the CD30 antigen is a hallmark of this
disease. However, CD30 expression is not specific for ALCL and Subcutaneous Panniculitis-Like T-Cell Lymphoma
may also be seen in other forms of malignant lymphoma, Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) usually
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including CHL. ALCL-ALK is associated with a characteristic presents with subcutaneous nodules primarily affecting the
chromosomal translocation, t(2;5)(p23;q35), involving the ALK extremities. In its early stages, the infiltrate may appear deceptively
and NPM genes, respectively. A variety of other ALK partners benign, and lesions are often misdiagnosed as panniculitis.
have been identified and monoclonal antibodies to the ALK However, histological progression usually occurs, and subsequent
protein have been able to identify tumor cells regardless of the biopsies show more pronounced cytological atypia.
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underlying translocation. The neoplastic cells show both nuclear The neoplastic cells are CD8 cytotoxic α/β T cells. They are
and cytoplasmic staining in the majority of cases; the presence also positive for the cytotoxic proteins perforin, granzyme B,
of cytoplasmic staining for ALK is suggestive of a variant and TIA-1 that may be responsible for the cellular destruction
translocation. seen in these tumors. EBV is negative. Some PTCL of γ/δ T-cell
Immunohistochemistry is indispensable in the correct diagnosis derivation may show similar features but differ from SPTCL in
of ALCL. The prominent Golgi region usually shows intense their clinical behavior (more aggressive) and histological pattern,
staining for CD30 and epithelial membrane antigen (EMA). The as they are often not confined to the subcutis.
cells exhibit an aberrant phenotype with loss of many of the T Some patients have a history of autoimmune disease, and in
cell–associated antigens. Both CD3 and CD45RO, the most widely particular, the differential diagnosis of SPTCL with lupus pro-
used pan-T-cell markers, are negative in >50% of cases. CD2 and fundus panniculitis can be challenging. Unlike SPTCL, lupus
CD4 are positive in the majority, whereas CD8 is usually negative. panniculitis usually contains abundant plasma cells, a mixture
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ALCL cells, despite the CD4 /CD8 phenotype, often express the of CD4 and CD8 cells, and a relative increase of γ/δ T cells
cytotoxic-associated antigens (TIA-1, granzyme B, and perforin). and plasmacytoid DCs.
In addition, clusterin is generally present in ALCL and represents A hemophagocytic syndrome can be a complication of SPTCL
another useful diagnostic marker. Molecular studies in most cases but is more often associated with γ/δ T-cell lymphomas involving
demonstrate TCR rearrangement, confirming a T-cell origin. the subcutaneous tissue. Patients present with fever, pancytopenia,
Improved criteria now exist for the recognition of ALK- and hepatosplenomegaly. It is most readily diagnosed in bone
negative ALCL as a separate entity. It occurs in an older age marrow aspirate smears, where histiocytes containing erythrocytes,
group compared with the ALK-positive cases. Recently, a unique platelets, and other blood elements may be observed. The
form of ALK-negative ALCL arising in association with breast hemophagocytic syndrome usually heralds a fulminant downhill
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implants has been identified, with a medial interval from time clinical course.