30
Effects of Therapy on Cytologic Specimens
rare b ip o la r naked nuclei, m aking a d istin c tio n fro m m alig n an t
change d iffic u lt.40,41 These cytologic features m arked ly contrast
w ith the histo lo g ic e p ith elial changes described by S c hn itt and
colleagues.39 A clue th a t the changes m ay be rad iation-ind uced
is the h yp o c e llu la rity o f the smears due to the fibrosis. The
presence o f m yo ep ith elial cells o r b ip o la r naked nuclei o r the
tra n s itio n between n o rm a l and h ig h ly atypical cells w ith in an
aggregate o f cells m ay indicate the benign nature o f the lesion.42
It is essential to e lic it a clinical h is to ry o f p rio r ra d ia tio n to
avoid these p itfalls. The sclerotic changes fo llo w in g ra d ia tio n
m ay lim it the n um b er o f cells present in the specim en. Changes
to the chest w a ll and pleura m ay be present. T he p leural meso-
th e lia l cells m ay show changes independent o f the presence o r
absence o f carcinom a.
Prostate
Irra d ia tio n is an accepted m ode o f tre atm e nt fo r lo c a lly advanced,
stage C prostatic adenocarcinom a. F o llo w -u p o f patients w ith an
irrad iated prostate to evaluate ra d ia tio n in ju ry and persistence
o f m alig nancy b y FN A has been in fre q u e n tly studied.
Bostw ick
and
colleagues
studied
histo lo g ic features
o f
n o rm a l and neoplastic prostate tissue after rad iotherap y.43 The
ra d ia tio n in ju ry changes included a trop h y and squam ous m eta-
plasia o f the non-neop lastic glands, w ith o r w ith o u t atypia; stro-
m al fibrosis; and arterial sclerosis. The neoplastic glands were
unaffected, w ith o u t architectural a lte ratio n o r d ed ifferentia-
tio n . C ytologic changes in the neoplastic gland were n o t useful
criteria in d iffe re n tia tin g them fro m non-neop lastic glands w ith
rad iation-ind uced atypia.
Cytology
A sp ira tio n b iop sy o f the irrad iated prostate u su a lly yields a
h yp o ce llu la r specim en because o f fibrosis th a t occurs w ith in a
few days after radiotherapy.44 C ytolog ic changes fo u n d in n o r-
m al and neoplastic g land ular e p ith e liu m consist o f cellular and
nuclear enlargem ent, cytoplasm ic vacuolation, and bizarre giant
nuclear fo rm s (Fig. 30.6) . Squam ous m etaplasia m ay develop.
Fig. 30.6 Radiation change in the prostate. The benign prostatic
glandular cells have nuclear atypia and loss of polarity. Distinguishing these
changes from malignancy may be difficult. Fine-needle aspiration biopsy of
prostate (Diff-Quik x MP).
Degenerative nuclear changes, such as karyorrhexis, karyolysis,
o r pyknosis, are also fo u n d in the m a lig n a n t cells. N u c le o li in
the m a lig n a n t cells m ay s h rin k and m ay no long er be p ro m i-
nent. N o d e fin ite criteria define the v ia b ility o f m a lig n a n t cells.
The presence o f well-preserved nuclei w ith crisp chrom a tin ,
e osin o p hilic nuc le oli, and cellu la r dyshesion suggests a viab le
neop lasm .45
The significance o f persistent m a lig n a n t cells and the value
o f post-therapy b iop sy to assess the tu m o r response are con-
troversial because o f p o o r c orrelation between the biopsy
results and patients' survival. Persistent p ositive b iopsy finding s
1 2 -1 8 m o n th s after therapy m ay indicate residual viab le neo-
plasm .43 Biopsy finding s can convert fro m m a lig n a n t to benign
as late as 1 -2 years after ra d ia tio n .46,47 A fte r 2.5 years, 20% o f
prostate b iop sy samples contain m a lig n a n t cells. A direct cor-
re la tio n w ith prognosis is d iffic u lt to assess because o f problem s
in evaluating the v ia b ility and m etastatic p o ten tial o f the resid-
ual m a lig n a n t cells.43 Serial rectal e xa m in ation and biopsy, Tru -
C ut, o r FNA, s till rem a in the accepted m ethods o f m o n ito rin g a
p atient w ith irradiated prostate carcinom a.
Thyroid
In te rn a l ra d ia tio n b y a d m inistering iodine-131 is used fo r the
tre atm e nt o f Graves' disease and, in som e cases, o f fu n c tio n in g
th y ro id carcinomas. Iodine-131 em its m o s tly beta rays, w h ic h
centrifug ally spread ap p roxim ately 2 m m , thus sparing struc-
tures adjacent to the th yro id . T he effect o f radioactive iod ine
on the th y ro id depends on the dose o f ra d io io d in e per gram o f
th y ro id tissue, the d u ra tion , and the sen sitivity o f the cells to
rad iation.
H isto lo g ic changes are acute and chronic. Acute changes
includ e cytoplasm ic o xyp h ilia , strom a edema, and nuclear
pyknosis. Acute in fla m m a tio n o r necrosis is rare ly fo u n d in
therapeutic doses. By the th ird week, the strom a l edem a has
been replaced b y in te rs titia l fibrosis w ith a decrease in fo llic le
size. C h ro n ic changes, after 6 weeks, includ e in te rs titia l fibrosis,
cytoplasm ic sw e llin g and o xy p h ilia resem bling H u rth le cells,
nuclear atypia w ith hyp erchrom asia and b izarre g iant form s,
sm all follicles, and vascular alterations. T he nuclear changes
are m ost p ro m in e n t in the o xyp h ilic cells and m ay be in d is -
ting u ish ab le fro m m alig nancy.48 A lym p h oc yte in filtra te and
m ultin u clea te d histiocytes w ith the o xyp h ilic cells m ay m im ic
H a shim o to 's th y ro id itis .49 A lth o u g h V ickery reported a 39%
incidence o f H a shim o to 's th y ro id itis in the irrad iated glands,50
it is a re la tive ly u n c o m m o n fin d in g in o th e r series. Regenerative
o r adenom atous nodules m ay develop d uring the long -term
p o stirra d ia tio n period. T he irra d ia tio n received at C h ern o -
byl, Three M ile Island, and irra d ia tio n fo r acne has a ll seen an
increase in th y ro id itis and an increased incidence o f p a p illa ry
carcinom a.
Cytology
C ytolog ic features o f th e irrad iated th y ro id consist o f nuclear
enlargem ent w ith b izarre nuclear form s, c lum p ing o f chro-
m atin , cytoplasm ic sw elling o r e osin o p hilic granularity, and
naked nuclei. Intranuclear inclusions and b lue-black cytoplas-
m ic p ig m ent granules in the fo llic u la r cells have been described
b y K in i.51 These features m ay be ind istin g uisha b le fro m m alig -
nancy, and a h is to ry o f iodine-131 therapy is needed fo r c la rifi-
cation. In the chronic stage, asp iration b iop sy m ay yie ld scant
c e llu la rity ow in g to fibrosis and fo llic u la r atrophy.
957
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