Acute Leukemias - Republican Scientific Medical Library

a 7.3 · Diagnosis 115
The vast majority of cases of ALL (~ 85%) are of B
lineage. These have been grouped into further subtypes,
which may correspond to different levels of maturation
in normal B-cell development. However, such differentiation
schemes are not universally agreed upon and
the terminology for the different subtypes is also not
uniform. In fact, due to the lack of conformity, and
the questionable significance of the further subclassification,
the WHO classification scheme simply classifies
cases as “precursor-B” and “precursor-T” ALL without
additional categorization. The most common B-lineage
ALL is the precursor-B phenotype with B-cell markers
(CD19, CD22), TdT, cytoplasmic CD79A, CD34, CD10
(CALLA), and lack of cytoplasmic l (cl) and of surface
immunoglobulin (sIg) expression. This type has variably
been called “common precursor B” ALL, or “early
precursor-B” ALL. A less common type lacks CALLA
and may be at an earlier level of maturation that has
been termed “pro-B” ALL. This type has a worse prognosis.
A type with more maturation than common precursor-B
ALL is characterized by the presence of cl, and
is referred to as “Pre-B”ALL. Reports are conflicting,
but this may be more commonly associated with
t(1;19)(q23;p13). Burkitt leukemia has the immunophenotype
of mature B cells with sIg expression. Whether
rare cases of non-Burkitt ALL also exhibit a mature B
phenotype (sIg+) is questionable, although such cases
have been reported on [31]. B-lineage ALL phenotypes
are listed in Table 7.2 C.
T lineage ALL accounts for only 15–20% of cases
and can also be separated into phenotypic groups
which may correspond to different stages of thymic Tcell
development [32]. As in B-lineage ALL, a type
with intermediate differentiation is the most common.
This “common thymocyte” type shows expression of
the pan T-cell markers, CD2, cytoplasmic CD3 (cCD3),
CD7, and CD5 and distinctively shows coexpression of
CD4 and CD8, and expression of CD1a. A more primitive
type called “prothymocyte” or “immature thymocyte”
type has TdT, cCD3, and variable expression of
CD5, CD2, and CD7, but lacks CD4, CD8, and CD1a. A
more mature phenotype than the “common thymocyte”
type has variable TdT, the pan T-cell markers,
CD4 or CD8 but lacks CD1a. Again, because of lack of
conformity and variability of marker expression, the
WHO classification recognizes only the “precursor-T”
group without further immunophenotypic categorization
[12]. T-lineage ALL phenotypes are listed in Table
7.2 D.
Table 7.3. Scoring system for biphenotypic leukemia
Score
Lineage
B-lymphoid T-lymphoid Myeloid
2 cCD79A cCD3
MPO
cl
cCD22
anti-TCR
1 CD19
CD20
CD10
0.5 TdT
CD24
CD2
CD5
CD8
CD10
TdT
CD7
CD1a
CD117
CD13
CD33
CD65
CD14
CD15
CD64
Greater than 2 points are needed to consider a lineage involved [36]
Coexpression of other nonlymphoid markers is
common on the lymphoblasts in both precursor-B and
precursor-T ALL, and does not necessarily indicate bilineal
potential. The myeloid markers, CD13 and CD33,
are the most frequently expressed [33]. In the past, these
have erroneously been interpreted as indicating a biphenotypic
process and a worse prognosis, but more recently,
this has not been found [34, 35]. Recently, more
strict criteria with a uniform grading system have been
instituted to help define the “biphenotypic” entity, illustrated
in Table 7.3 [36]. Cytoplasmic expression of myeloperoxidase
in ALL has also been reported by flow cytometric
analysis. However, this does not correspond to
the cytochemical detection of enzyme reactivity, and
when identified with a polyclonal antibody, it is of only
questionable significance [37].
Differential diagnostic considerations that have to
be considered in immunophenotyping include hematogones,
thymoma, biphenotypic leukemia, and CML presenting
in lymphoid blast phase. Hematogones have the
same immunophenotype as common precursor B ALL
cells, but the hematogones exhibit a spectrum of maturation
with a continuum of cells from immature to
mature showing loss of CD34, and gain of CD20 and
sIg [38, 39].
Thymoma cells have the phenotype of common thymocytes,
and cannot be distinguished from common T
ALL/lymphoblastic lymphoma by immunophenotype
alone. Correlation with clinical presentation and histology
are important for the correct interpretation. When