PART TWO
Diagnostic Cytology
Fig. 30.14 Cyclosporine-induced lymphoproliferative disorder.
The
smear contains polymorphic mononuclear cells including immunoblasts,
plasma cells, and plasmacytoid lymphocytes. Fine-needle aspiration biopsy of
lymph node (Diff-Quik x MP).
C y to lo g y
Fine-needle aspirates contain a m o n o m o rp h ic popu-
la tio n o f large atypical im m unob lasts. The cells have an in te r-
m ediate a m o u n t o f eccentric cytoplasm , o fte n con tain in g sm all
vacuoles. The nuclei are large and noncleaved, w ith vesicular
c h ro m a tin and p ro m in e n t single o r m u ltip le central nucleoli.
A d m ixed w ith the im m un ob la sts are a m in o r p o p u la tio n o f
sm all lym phocytes and plasm a cells.93 Im m u n o p h e n o typ in g
and gene rearrangem ent studies reveal a m o n o c lo n a l o r o lig o -
clonal B-cell p o p u la tio n and a single fo rm o f EBV w ith o u t onco-
gene m u ta tio n s.91,98 T he therapy o f choice is cessation o r change
o f th e im m unosuppressive therapy w ith aggressive antineop las-
tic chem otherapy, ra d ia tio n therapy, o r b oth.
Im m unob lastic lym p h o m a /m u ltip le
m yelom a
(high-grade
PTLD ) is characterized b y the m o n om orp h ic p rolifera tion o f
im m unoblasts a nd /o r atypical plasm a cells. The cells show m ono-
c lo na lity b y gene rearrangements, a single fo rm o f EBV, and
m utations in one o r m ore oncogenes o r tu m o r suppressor genes.
Cessation o f im m unosuppressive therapy and antiviral therapy is
n o t effective in either o f the categories w ith features o f lym phom a.
U terine Cervix
Cervical neoplasia shows a 14-fold increase in the im m unosup -
pressed p o p ulatio n compared w ith the general p op ulatio n.99 The
p red om inant lesion is intraep ithelial. Rarely have invasive neo-
plasms been found. The cytologic features o f the im m un osu p -
pression-induced dysplasia o r cancer are identical to those o f the
cervical neoplasia o f the general pop ulation. A recom m endation
is m ade fo r w om en to have a baseline cervicovaginal smear before
im m unosuppressive therapy and at regular intervals thereafter to
m o n ito r fo r early dysplastic changes. M ost neoplasms respond to
conventional cancer therapy. High-grade m alignancies m ay neces-
sitate a reduction o r cessation o f im m unosuppressive therapy.99
Evaluation of Allograft Transplant Rejection
and immunosuppressive toxicity
Fine-Needle Aspiration of Renal Allograft
Since th e ad vent o f renal a llo g ra ft tra n s p la n ta tio n , core nee-
dle b io p sy has been th e standard in e va lu a tin g h o s t rejec tion ,
im m u n o th e ra p y to xic ity, and ren al fu n c tio n . F N A b io p sy has
Fig. 30.15 Cyclosporine-induced polymorphic B-cell (immunoblastic)
lymphoma.
(A) Large B-cell lymphoma population in fine-needle
aspirate of lymph node, with immunoblasts and apoptotic changes.
(B) CD20+ immunocytochemistry on cell block material from the lymph node
aspiration. (A, Papanicolaou x MP; B, immunocytochemistry— anti-CD20 with
hematoxylin counterstain.)
also becom e an accepted m e th o d fo r m o n ito rin g ren al tra n s-
p la n t rec ip ie nts.100,101 F N A is a less m o rb id procedure, a llo w in g
fo r m o re fre q u e n t sam p lin g o f th e a llo g ra ft w ith less ris k o f
c om p lica tion s. F N A and core needle b io p sy correlate w e ll in
evalu a tin g h o s t re je c tio n .102,103 G raft status d u rin g th e im m e -
d iate p o st-tra n sp la n t p e rio d th a t can be d iffe re n tia te d b y FN A
b io p sy inc lu d e acute tu b u la r necrosis, cyclosp orine to xic ity,
acute c e llu la r rejec tion , in fe c tio n , in fe c tio n w ith p o ly o m a v i-
rus, and g raft necrosis.104,105 These diagnoses can be d iffe re n ti-
ated b y e va lu a tin g th e s u b p o p u la tio n s o f th e in fla m m a to ry
cells using standard cytolog ic stains, such as M a y -G ru n w a ld -
G iem sa, and b y e va lu a tin g th e lym p h o c yte s u b p o p u la tio n s
(T cell and B cell) and ren al tu b u la r H L A -D R antig en expres-
s io n using im m u n o c y to c h e m is try , im m u n o g o ld -im m u n o s il-
ver m arkers, and flo w c yto m e try im m u n o p h e n o ty p in g .101,106,107
A n y e va lu a tio n o f in fla m m a to ry cell p o p u la tio n s m u st take
in to account th e c o n ta m in a tin g elem ents fro m b lo o d . FN A
sam ples m ay be analyzed using a to ta l corrected in c re m e n t
to evaluate increased lym p h oc ytes and m o n o n u c le a r cells
present in rejec tion . O th e r studies am enab le to FN A m ate -
ria l in c lu d e D N A in s itu h y b rid iz a tio n fo r v ira l in fe c tio n s
(cytom eg alovirus, EBV, p o lyo m a viru s, and herp esvirus) and
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