• Immunocytochemistry: CD30-positive, cytotoxic markers
(e.g. granzyme B and TIA-1) positive, T-cell markers often
positive, epithelial membrane antigen sometimes positive,
and ALK protein sometimes positive.
• Cytologic differential diagnosis: seminoma
(CD117-positive and CD30-negative); poorly differenti-
ated non-small-cell carcinomas (cytokeratin-positive
and CD5-positive if thymic origin); primary mediastinal
large B-cell lymphoma (B-cell markers positive, CD30
sometimes positive, and T-cell markers negative); Hodg-
kin's lymphoma (CD30-positive, CD15-positive, and
CD20 focally and weakly positive); metastatic malignant
melanoma (S-100 protein-positive and HMB-45-
Hodgkin's Lymphoma
H od g kin's lym p h o m a o f a n te rio r m ed iastinu m prob ab ly o rig i-
nates fro m postgerm inal center activated B cells; it often affects
patients in the th ird decade and late ad ulthood , w ith fem ale pre-
d ile c tio n .47 M ost cases belong to the n o d u la r sclerosis subtype.
T he lym p h o m a m ay also spread to contiguous lym p h nodes in
the lo w e r cervical region. T u m o r stage rem ains the single m ost
im p o rta n t prognostic factor.
H odgkin's lym p h o m a is diagnosable on the basis o f cytologic
e xa m in ation .103,104 Fine-needle aspiration o f m ediastinal lym p h
nodes harb oring H odgkin's lym p h o m a yields a heterogeneous
p o p u la tio n o f h em a to lym p h o id cells, includ ing the classic Reed-
Sternberg cells
o r "R eed-Sternberg-like"
lym phocytes,
plasm a cells, eosinophils, and histiocytes (Fig. 26.18A ) . The
heterogeneity o f lym p h o id cell p o p ulatio n m ay superficially
resemble a reactive lym p h o id process. Characteristically, classic
Reed-Sternberg cells are binucleated and have a m irro r image
"o w l eye" appearance, w ith large ovoid nuclei, thickened nuclear
m em brane, pale chrom atin, solitary "rod-shaped" eosinop hilic
m acronucleoli, and abundant a m p h o p h ilic cytoplasm . M ore
com m only, m ononuclear variants o f Reed-Sternberg cells w ith
m u ltilo b a te d nuclei, d istinct nucleoli, and pale cytoplasm are
seen. Som etim es m u ltilo b a te d bare nuclei are fo u n d in the back-
ground.39 "Lacunar" cells and perinucleolar clearing o f Reed-
Sternberg cells typ ica lly observed in histolog ic sections (Fig.
26.18B ), however, are n o t appreciated in cytologic preparations.
M oreover, diagnostic Reed-Sternberg cells are n o t always present,
even in cellular aspirates. Also, strom al h ya lin iz a tio n in the nod -
u la r sclerosis subtype o f H odgkin's lym p h o m a m ay som etim es
produce paucicellular fine-needle aspirates, resulting in diag-
nostic p itfa lls.105 A lth o u g h detailed subtyping o f H odgkin's ly m -
p hom a requires histolog ic exam ination, fine-needle aspiration
cytology is useful, especially in diagnosis o f recurrent disease.
Im m u nocytochem ical study shows th a t these m a lig n a n t cells
are p ositive fo r C D 30 and C D 15 in m em branous and som e-
tim es paranuclear "d o t-lik e " staining patterns. There is also focal
w eak staining fo r the B-cell m arker C D 20. F lo w cytom etry often
yields nond iag nostic results and plays little ro le in the im m u n o -
p henotyp ing o f H od g kin's lym p h om a. In -situ h yb rid iz a tio n fo r
E p ste in -B a rr virus early R N A shows p ositive nuclear signals in
ab out 20% o f cases.
As fo r cytologic d iffe re n tia l diagnosis, H od g kin's lym p h o m a
m ay m im ic anaplastic large-cell lym p h o m a , diffuse large B-cell
lym p h o m a (especially T cell-rich B-cell lym p h o m a ), sem i-
nom a, and som etim es th ym o m a . Reed-Sternberg cells m ay be
Fig. 26.18 Hodgkin's lymphoma. (A) A classic Reed-Sternberg
cell is identified (arrow), against a background of small lymphocytes
and some eosinophils. Cytospin preparation of fine-needle aspirate
(Papanicolaou x HP). (B) A binucleated classic Reed-Sternberg cell with
mirror image "owl eye” appearance, large ovoid nuclei, thickened nuclear
membrane, solitary eosinophilic macronucleoli, perinucleolar clearing, and
abundant amphophilic cytoplasm is seen (arrow). Histologic section of
surgical specimen (H&E x HP).
m istaken as cortical e p ith elial cells in th y m o m a on cytologic
e xa m in a tio n .5 In general, th ym ic e p ith elial cells, fo llic u la r
d end ritic cells, and reactive im m un ob la sts never possess "in c lu -
s io n -lik e " m acronucleoli as seen in Reed-Sternberg cells. W h ile
sem in o m a can be excluded by im m unocytochem istry, d istinc-
tio n fro m p rim a ry m ed iastinal large B-cell lym p h o m a m ay n o t
be possible,98 even w ith histo lo g ic assessment o r at m olecular
levels (thus generating the am biguous e n tity o f "grey z o n e " ly m -
p hom a). D e m o n stra tio n o f an E p ste in -B a rr virus association is
in favor o f th e diagnosis o f H od g kin's lym p h om a. S am pling
error, especially in H od g kin's lym p h o m a w ith m u ltilo c u la r
cystic changes o r m arked strom al sclerosis, m ay pose im p o rta n t
p itfa lls in cytologic diagnosis.53
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