Guidelines on Diagnosis and Treatment of Malignant Lymphomas

Anaplastic Large
Cell Lymphoma
Definition and Incidence
ALCL-ALK+ve is a T cell lymphoma characterised by
translocation involving the ALK gene, expression of the ALK
protein and CD30. Primary systemic ALCL must be distinguished
from Anaplastic large cell lymphoma (ALK negative), primary
cutaneous ALCL and other T and B cell lymphomas with
anaplastic morphology and/or expression of CD30.
ALCL-ALK-ve is a provisional entity defined as a CD30+ T cell
neoplasm, morphologically indistinguishable from ALCL, ALK+,
but lacking ALK protein expression.
ALCL accounts for about 3% of adult NHLs and 10-30% of
childhood lymphomas. It has an incidence of 0.24 new
cases/100,000 population/year. ALK+ve ALCL is most frequent in
the first 3 decades of life and has a M:F ratio of 6:1. ALK –ve
ALCL occurs in older patients with a slight female predominance.
ICD-O code 9714/3
Clinical Presentation
ALCL frequently involves both lymph nodes and extra-nodal sites
including the skin (21%), bone (17%), soft tissue (17%), lung
(11%) and liver (8%). Involvement of the CNS and
gastrointestinal tract is rare. Marrow involvement occurs in 10%
of cases but this increases to 30% if immunohistochemistry for
CD30, EMA and ALK is used.
70% of patients present with stage III or IV disease and most
have B symptoms, particularly high fevers.
Pathology
Pathological appearance is variable. Lymph node/tissue
architecture may be partly effaced and the disease typically grows
within node sinuses. Morphology is variable, ranging from small
cell neoplasms to cases with large anaplastic nuclei. All cases
contain cells with eccentric reniform nuclei known as “hallmark
cells” although the proportion of these cells present is variable.
Morphologic variants include lympho-histiocytic, small cell, and
Hodgkin-like patterns.
Immunophenotype
Cells are CD30+ve with cell membrane and Golgi region pattern.
Most cases are EMA positive. CD2, CD4, CD5 are positive in
70% of cases. Most cases express T cytotoxic associated
antigens including TIA-1, perforin and granzyme B. CD3, CD8,
CD15 are negative in most cases.
ALK protein is positive, most cases demonstrating both nuclear
and cytoplasmic expression. Variant expression patterns,
cytoplasmic, nuclear and membranous, exist.
Genetics
90% of cases show clonal T cell receptor gene rearrangements.
Various ALK translocations are described: the most common,
accounting for >80% of cases, is the t(2;5)(p23;p35)
translocation involving the ALK gene and the nucleophosmin
gene on 5q25 resulting in nuclear and cytoplasmic ALK protein
expression. Variant translocations involving ALK and partner
genes on chromosomes 1,2,3,17,19,22,X occur and are
associated with variable protein expression patterns.
Staging
As for DLBCL.
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