PART TWO
Diagnostic Cytology
present. In its early stages, the changes are noted near centri-
lo b u la r veins. Later, p erip ortal areas are also affected.
Cytology
A c o m b in a tio n o f degenerative, inflam m ato ry, and fa tty changes
are seen. T he degenerative change is represented by the presence
o f M a llo ry bodies (alco h olic hya lin e) in the cytoplasm o f
hepatocytes. They appear as ro u n d o r elongated acid op hilic
clum ps located in a perinuclear p o sition . The in fla m m a to ry
change consists
o f p o lym orp ho n uc le ar in fla m m a tio n ,
and
n e u tro p h ils are seen surro un d in g the degenerated liv e r cells o r
w ith in damaged liv e r cells. Fatty changes o f th e hepatocytes are
a c om m o n finding .
C yto m orp h olog ic features seen in FN A preparations fro m cir-
rhosis, v ira l hepatitis, and a lcoholic hep atitis overlap som ew hat.
However, th e ir overall cytologic find ing s are d ifferent. In FN A
preparations, d iffe re n tia tio n am ong alcoholic hepatitis, c irrho -
sis, and v ira l hep atitis is possible on p u re ly cytom orp holog ic
grounds. The differences in overall cytologic find ing s am ong
these three con d itio ns are sum m arized in Table 2 8.1 .
Cholestasis
Cholestasis im p lie s defective excretion o f b ile by th e liver, w ith
reduced am ounts o f b ile reaching the duod enum . It occurs
in any variety o f jaundice and is a c om p onent o f m an y liv e r
diseases, inc lu d in g those p rim a rily in v o lv in g the b ilia ry tree
and those affecting liv e r cells. However, m uch o f the b iliru b in
present is rem oved in ro u tin e tissue processing, and therefore
intracytop lasm ic b ile granules are n o t read ily appreciated after
tissue processing b u t can be seen in FN A smears. B ile plugs th a t
are m ost c o m m o n ly associated w ith m echanical ob struction
o f the b ilia ry tree are u su a lly recognizable after tissue process-
ing. In histolog ic sections, c e n trilo b u la r cholestasis w ith little
o r no p ortal in fla m m a tio n suggests drug cholestasis o r o the r
fo rm s o f intrahep atic cholestasis. P ortal edema, acute in te r-
lo b u la r in fla m m a tio n , and duct p ro life ra tio n in the absence
o f widespread liv e r cell damage are ind icative o f large b ile duct
obstruction.
Cytology
B ile p ig m ent th a t varies greatly in c olor and texture is noted.
Intracytop lasm ic b ile granules are u su a lly y e llo w o r green
(as a result o f o xid a tio n o f b iliru b in to b iliv e rd in ) and vary con-
siderably in size and density. W ith intrahep atic cholestasis, b ile
pigm ents are u su ally fo u n d in the fo rm o f granules o r clum ps
w ith in hepatocytes and K up ffer cells. A few b ile plugs o r th ro m b i
in u nd ila te d o r m in im a lly d ilated canaliculi m ay be seen
(Fig. 28.2 2 ) , b u t n o p ro life ra tio n o f b ile ducts and n o ductal
e p ith elial hyperplasia are noted.
W ith cholestasis resulting fro m o b struction to m a jo r b ile
ducts w ith in o r outside the liver, b ile is seen in the fo rm o f
p ro m in e n t b ile plugs o r th ro m b i in the d ilated canaliculi
between hepatocytes. O w ing to p ro life ra tio n o f sm a ll b ile ducts
and b ile duct e p ith elial hyperplasia, large sheets and cohesive
groupings o f ductal cells are som etim es seen in FN A smears. The
affected ductal cells m ay be in s lig h tly d isord erly arrangem ents
and show atypical changes. T h e ir nuclei m ay vary in size and
shape.
Focal Nodular Hyperplasia
Focal n o d u la r hyperplasia is fo u n d m a in ly (8 0 -9 5 % ) in females
o f reproductive age,27,28 and 7 -1 5 % o f cases occur in the pediat-
ric age g roup .29 Focal n o d u la r hyperplasia represents hyperplas-
tic response to arterial m a lfo rm a tio n o r o th e r vascular a no m a ly
rather th an a neop lasm .30 Cases o f focal n o d u la r hyperplasia o f
the liv e r are n o t rare, b u t th ey are o fte n undetected because the
lesions in m ost cases are asym ptom atic. The lesions are usually
so lita ry b u t m ay be m u ltip le . T he y are w e ll circum scribed b u t
n o t encapsulated. T he y m easure 1 -8 cm in diam eter and grow
s lo w ly and do n o t becom e m alig nant. The nodules are com -
posed o f liv e r parenchym a intersected b y fib rous septa th a t often
radiate fro m a central stellate scar c on tain in g vascular structures.
The norm al-ap p earing liv e r cells are arranged in sm all pseudo-
lobules. B ile ducts are present.
Fine-needle asp iration smears show a rig id core o f liv e r
d iffic u lt to smear25 and com posed o f n o rm a l hepatocytes th a t
are in te rm in g le d w ith num erous fibroblasts o r embedded in
fragm ents o f fib rous tissue, m im ic k in g cirrhosis (Fig. 2 8.2 3 ) .
However, in the cases o f focal n o d u la r hyperplasia, there is
no p leo m o rp hism o f hepatocytes, n o m ito tic figures, and no
necrotic hepatocytes, as seen in aspirates fro m a c irrho tic liver.
Fatty changes in hepatocytes m ay be seen. In som e instances, the
fib rous elem ent is under-represented in aspirate smears, and the
diagnosis o f focal n o d u la r hyperplasia in such cases is d iffic u lt
on p urely cytom orp holog ic grounds. However, p arallel rows
o f fibrocytes th a t traverse large fragm ents o f liv e r parenchym a
(Fig. 28.2 4 ) can u su ally be fo u n d after a careful search, and this
fin d in g is h e lp fu l in establishing th e diagnosis.
Key features of focal nodular hyperplasia
• C lin ic a l: in c id e n ta l fin d in g in a sy m p to m a tic p atients.
• C T scan: liv e r m ass w ith central ste llate scar w ith enhance-
m e n t in th e a rte ria l phase a nd ra p id w a s h o u t in th e p o rta l
ven ou s phase.
• P hysical features o f th e aspirate: fine -ne ed le cores d iffic u lt
to sm ear.
• N o rm a l hepatocytes th a t are in te rm in g le d w ith n u m e ro u s
fib ro b la sts o r em bedded in fra g m e nts o f fib ro u s tissue.
Table 28.1 Comparison of Cytologic Findings in Cirrhosis, Viral Hepatitis, and Alcoholic Hepatitis
Regenerative
changes
Fibrous stroma
Degenerative changes
Fatty changes
Inflammatory
changes
Cirrhosis
+
+
+ (necrosis)
+
+ (mixed inflammatory
cells)
Viral hepatitis
+
-
+ (ballooning degeneration
and acidophilic bodies)
-
+ (lymphocytes)
Alcoholic hepatitis
-
-
+ (Mallory bodies)
+
+ (polymorphs)
882
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