24
Lymph Nodes: Cytomorphology and Flow Cytometry
Fig. 24.29 Blastoid variant of mantle cell lymphoma (MCL). Larger cells
than typical MCL, fine chromatin, numerous mitoses (Papanicolaou x OI).
M C L is generally negative fo r C D 23. A n o th e r help in d iffe re n ti-
ating M C L fro m SLL is th a t im m u n o g lo b u lin and C D 20 expres-
sion is u su ally d im in SLL b u t b rig h t in M C L. A n o th e r useful
m arker is FM C7, w h ic h is expressed in M C L b u t n o t in SLL.147
C D 79a and C D 79b are pan-B-cell antigens th a t are h e lp fu l
m arkers at least in d iffe re n tia tin g M C L fro m the leukem ic phase
o f SLL/CLL. T he y are negative o r d im in CLL b u t are expressed
in hig h levels in M C L.148 M C L is also cyclin D1 (b c l-l)-p o sitiv e
and has a t(11;14).
D iffic u lty in diagnosing M C L can result fro m aberrant phe-
notypes. Rarely M C L m ay be negative fo r C D 5, creating p oten-
tia l confusion w ith M Z L, w h ile som e cases o f M Z L m ay be CD5+
and p o te n tia lly m istaken fo r M CL.
C h ron ic lym p h oc ytic leukem ia/S LL m ay have an atypical
phenotype, w ith an uncharacteristically b rig h te r expression o f
p an-B -cell m arkers and d im in ish e d expression o f C D 23 th a t
m ay correlate w ith atypical m o rp h o lo g y and cytogenetic ab nor-
m alitie s such as triso m y 12.
Because o f these aberrant phenotypes, it is im p o rta n t to use
cytom orp holog ic e xa m in ation and a c o m b in a tio n o f m arkers
as w e ll as cyclin D1 im m u n o s ta in in g o n paraffin-em bedded
cell blocks (fo rm a lin , n o t alcohol fix a tio n ) o r core biopsy, and/
o r FISH analysis fo r the t(11:14) translocation, w h ic h can be
perform ed o n paraffin-em bedded tissue, cytologic smears, o r
Cytospins, to c on firm a suspected diagnosis o f M CL.
Key features of mantle cell lymphoma
• Small- to medium-size irregular lymphoid cells;
• CD5+ CD10- CD- FMC7-positive CD79a+ B cells;
• bcl-1-positive (cyclin Dl-positive);
• Light-chain restriction (bright);
• t(11;14); and
• Important differential diagnosis with SLL/CLL.
Lym phom as Com posed of Predom inantly Large Cells
The p o p u la tio n o f lym p h o m a cells is p re d o m in a n tly large in
LCL, a lth ou g h background sm all b enign lym phocytes can cause
confusion in diagnosis and subclassification. In these situa-
tions, FCM m ay be h e lp fu l i f all sm all cells are T cells and the
large cells are m o n o c lo n a l B cells. LCL m ay be o f B- o r T-cell
o rig in, and the large cells are at least tw o tim es larger th a n a
lym p hocyte and are u su ally ro u n d o r oval b u t occasionally have
indented, irregular, o r even lob u la te d nuclei, p a rtic ularly in
T-cell lym p h o m a o r p leo m o rp hic variants o f LBCL.
Large B-cell Lym phom a (Diffuse Large B-cell/Grade 3
Follicular)
Clinical
D iffu se large B-cell lym p h o m a m ay occur de novo b u t is also a
c om m o n pathw ay o f tra n s fo rm a tio n fo r a variety o f lym p hom as.
The y represent about o n e -th ird o f all N H Ls.112 A lth o u g h the
W o rk in g F o rm u la tio n separates the entities diffuse m ixed sm all-
and large-cell, diffuse large-cell, and im m u n o b la stic B-cell ly m -
phom as, there are no clear survival differences between th e m .149
The W H O classification com bines th em in to the single e n tity o f
DLBCL. T he y are m ore lik e ly to present as either stage com pared
w ith in d o le n t lym p h om a. A b o u t 50% are curable b y aggressive
chem otherap y w ith o r w ith o u t irra d ia tion .
Cytomorphology
T he typical large ro u n d noncleaved centroblasts (as opposed to
centrocytes) in LBCL o r grade 3 FL are som etim es referred to as
large tra nsfo rm e d cells and o fte n have vesicular c h ro m a tin and
one to three p ro m in e n t, p e rip h erally located n uc le oli. There is
a n a rro w rim o f cytoplasm , o fte n b aso p h ilic to a m p h o p h ilic
(Fig. 2 4.3 0 ). A large and central nucleolus w ith surro un d in g
c h ro m a tin clearing is characteristic o f im m un ob la sts, and
there is an im m u n o b la stic va ria n t o f LBCL in w h ic h over 90%
o f the cells are im m u n o b la sts (Fig. 24.31). C entroblasts tend
to be m ore frag ile and in som e preparations m ay n o t be w e ll
preserved. It is im p o rta n t n o t to confuse centroblasts w ith fo l-
lic u la r d e nd ritic re tic u lu m cells th a t tend to be s im ila r in size
to aggregate w ith in the center o f th e neoplastic fo llic le s.20 W e
sh o u ld also d istin g uish large cleaved cells fro m centroblasts.
A lth o u g h there is an overlap in size w ith centroblasts, large cen-
trocytes are m ore irre g ular in shape and lack th e p ro m in e n t
n u c le o li and c h ro m a tin p attern o f centroblasts. D iffe re n tia -
tio n o f centrocytes and centroblasts is discussed in d etail in the
previous section o n FL, as th is process is critical to lym p h o m a
grading.
C ell blocks are very h e lp fu l b y giving a d d itio na l architectural
clues to help d ifferentiate a "lo w grade" o r in d o le n t lym p h o m a
fro m an aggressive LCL. W h e n aggregates o r sheets o f large cells
are present, th ey are as m uch criteria fo r tra n s fo rm a tio n to LCL
in aspirates as in surgical biopsies (Fig. 24.2 0 ).
There is a p leo m o rp hic va ria n t o f D LBC L th a t contains bizarre
p leo m o rp hic nuclei th a t m ay resem ble Reed-Sternberg cells
and m ay grow in a cohesive pattern m im ic k in g carcinom a.150
695
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