PART TWO
Diagnostic Cytology
nuclei m easuring up to 30 p m in diam eter. T o lu id in e b lue
staining is useful in d isting uishing the sm all ring-shaped benign
n uc le oli in th e treated atypical fo llic u la r cells fro m the large
com pact n uc le oli fo u n d in m a lig n a n t fo llic u la r cells. T he large
nuclei are postulated to be p o ly p lo id ow in g to in h ib itio n o f
nuclear d ivisio n.
Radioactive iodine
Radioactive io d in e has been used fo r a b la tio n o f th y ro id tissue
fo r hyp e rth yro id ism . There is no increased incidence o f th y ro id
carcinom a in those patients receiving ablative therapy. T his con-
trasts w ith a hig h percentage o f th y ro id cancer in child ren w h o
have a h is to ry o f ra d ia tio n fo r to n s illitis , th ym ic enlargem ent,
o r acne. The incidence in these child ren is between 4 and 9%.
T he risk is increased in the young, females, and those receiv-
ing h ig h doses. T he h is to ry o f ra d ia tio n is im p o rta n t in patients
w ith nodules, in children, o r in you ng adults.
Thermal Injury
Electrocautery of the Uterine Cervix
Electrocautery is an ab lative therap y causing coagulative "th e r-
m a l" tissue necrosis b y m eans o f a b ite rm in a l hig h-freq uency
electric current. In th e u te rin e cervix, it is used to treat b enign
processes such as erosions, cervicitis, and preneoplastic and
neoplastic lesions. Electrocautery is postulated to cause a h ost
im m u n e response, w ith a ctivatio n o f lym p hocytes th a t are
stim u la te d against th e e p ith e lia l cells in th e lesion. C lin ic a l
in fo rm a tio n in c lu d in g the types o f therap y and th e dates o f the
procedures are essential in e va lu a tio n o f p ost-therap y smears.
B ukovsky and Z id ovsky reported a b no rm a l cells in 4 2% o f
th e cervicovaginal smears o f patients treated b y electrocautery
fo r b enig n cervical lesions.114 T he a b no rm a l cells w ere fo u n d
in th e firs t 8 weeks after th e therap y and persisted fo r up to
20 weeks.
Acute Phase
E arly cytologic features include a necrosis resem bling tu m o r
diathesis and a m arked in fla m m a to ry response com posed o f
n e u tro p h ils and lym phocytes. In neoplastic lesions, a repeat cer-
vicovaginal sm ear is recom m ended 4 -6 weeks after therapy. This
interval allow s the necrotic in fla m m a to ry background to clear
and n o t obscure persistent neoplastic cells. The ab norm al, n o n -
neoplastic cells are m o s tly atypical parabasal and interm ed iate
cells w ith enlarged, coarsely granular nuclear chrom atin. P ro m i-
n e n t n uc le oli, often m u ltip le , are found . These cells have fa irly
abundant, u su ally cyanop hilic cytoplasm . T he nucleocytoplas-
m ic ra tio rem ains close to norm al.
A b n o rm a l endocervical cells are also fo un d . These cells usu-
a lly occur in aggregates. They are enlarged and have nuclei o f var-
ious sizes. The nucleocytoplasm ic ra tio is som etim es m arked ly
increased. T he endocervical cells have coarse c hrom a tin often
condensed at the nuclear m em brane. Koss has described char-
acteristic beading o f the c h ro m a tin in these cells.67 T he n uc le oli
are enlarged; one o r m ore cytoplasm ic vacuoles are found .
Early Healing
B ukovsky and Z id o vsky have rep orted tw o cytolog ic phe-
n o m e n a th a t occur d u rin g th e h e a lin g process after electro-
cautery.114 These are th e "contact-developed lu c id c e ll" and
th e "regression fie ld ." C ontact-developed lu c id cells are firs t
observed at a p p ro xim a te ly th e fo u rth week. T h e y are ro u n d
cells w ith pale, tra nsluc en t cytoplasm and fin e ly granular,
h om og eneous c h ro m a tin . T h e early fo rm s resem ble large
ly m p h o id cells w ith n a rro w rim s o f cytoplasm . A larger cell
w ith a b un d an t tra nsluc en t cytoplasm and a th ic ken ed cyto-
p lasm ic m em b rane is also fo u n d . These cells have one to tw o
p ro m in e n t n u c le o li. C ontact-developed lu c id cells are never
observed alo ne b u t ra th e r are firm ly attached to an a b no rm a l
target cell nucleus in a cell in a cell p attern. As m a n y as 12 con-
tact-developed lu c id cells m ay be ad herent to one target cell.
T he target cells, e p ith e lia l cells s tim u la tin g th e h o s t im m u n e
response, have degenerative cytop lasm ic changes w ith nuclear
s h rin k in g and w rin k lin g . T h e nucleus o f th e target cell assumes
a crescent shape. In th e la te r stages o f th e im m u n e response,
th e contact-developed lu c id cell resem bles a cystic in c lu s io n
w ith in th e target cell.
T he second healing p h en om en on , the regression field , peaks
at a p p ro xim ately the eighth week. T he sm ear background is
granular. T his appearance is secondary to cytoplasm ic debris
fro m destruction o f ab norm al cells. T his background m im ics
the tu m o r diathesis fo u n d in smears w ith invasive carcinom a.
W ith in the regression field , intact and degenerated ab norm al
cells are fo un d . N o rm a l cells are n o t affected. D a rk ro u n d b o d -
ies the size o f red b lo o d cells, representing k ille r lym phocytes,
are fo u n d eith er w ith in o r adherent to target cells. T he nuclei
o f the target cells are h e a vily damaged and m ay even be lysed
o r ejected fro m the cell. A y e llo w -sta in in g "g h o s t" vacuole
rem ains.
Repair
The reparative process starts w ith a single layer o f reparative epi-
th e liu m covering the ulcerated coagulative area 1 w eek after the
therapy is com pleted. By the th ird to eighth week, the treated
area is covered b y a m ature stratified squam ous e p ith e liu m . The
reparative process is postulated to start fro m the c olum na r o r
squam ous cells adjacent to the treated area rather th a n fro m the
reserve cells at the ulcer base, as the basal reserve cells m ay be
gone. N o n h e a lin g areas 2 -3 m o n th s fo llo w in g electrocautery
sho uld be investigated fo r the persistence o f tu m o r. T he cyto-
logic features o f e p ith elial repair in electrocautery damage are
s im ila r to repair due to o th e r causes o f cervical m ucosal d isrup-
tio n and are discussed next.115,116
Cryotherapy
C ryotherapy (freezing) has been used since 1966 in the treat-
m e n t o f chronic cervicitis and p rem alig nant lesions o f the u ter-
ine cervix. The precise m echanism o f cellular in ju ry fo llo w in g
th is fo rm o f therapy is unclear. It m ay be due to the fo rm a tio n
o f extracellular and in tra c e llu la r ice crystals.117 The ice crystals
result in m echanical d isru p tio n o f cell m em branes, dehydra-
tio n o f cells, and increased electrolyte concentrations w ith in
the cells. The m arg in o f the ice b a ll o fte n extends 3 -4 m m
beyond the lesion. As in o th e r u terine cervix ablative therapies,
a clinical h is to ry regarding cryotherapy is needed to evaluate the
cervicovaginal smear. Freeze-associated cytologic changes m ay
sim ula te neoplasia. In te rp re ta tio n o f smears before 6 weeks fo l-
lo w in g cryotherapy o r u n til com plete healing has occurred is
n o t advised. Cancer cells m ay persist in smears fo r several weeks
after cryotherapy. A false-positive sm ear is avoided i f it is taken
after 6 weeks.
966
previous page 954 ComprehensiveCytopathology 1104p 2008 read online next page 956 ComprehensiveCytopathology 1104p 2008 read online Home Toggle text on/off