Liver and Pancreas
am ong d iffe re n t parts o f a c irrho tic liver, the cytologic finding s
in various samples fro m the same liv e r m ay be q uite different.
Recent advances in liv e r im aging, surgery, and transplanta-
tio n have draw n a tte ntion to a variety o f lesions th a t are fo un d
in c hronically diseased, u su ally cirrhotic, livers. In 1993, a m u l-
tin a tio n a l panel o f five expert liv e r pathologists reviewed such
nodules and were able to reach a consensus o n the diagnostic
criteria and to devise a standard nom enclature to describe these
lesions.33 They proposed th a t benign nodules show ing little h is-
tolog ic difference fro m c irrho tic nodules be classified as "m ac-
roregenerative" nodules, and nodules w ith atypical features n o t
diagnostic o f carcinom a be classified as "b o rd e rlin e ." In addi-
tio n , the absence o r m arked decrease in re tic u lin is considered
an im p o rta n t c riterion fo r m alignancy. The proposed nom encla-
ture was endorsed tw o years later b y an in te rn a tio n a l w orking
C lin ica lly, the presence o r absence o f cirrhosis is m ost im p o r-
ta n t.26 In the setting o f cirrhosis, hep atocellular carcinom a is a
m ore lik e ly find ing . M acroregenerative and b o rd e rline nodules
th a t occur in cirrhosis m ay have the characteristic o f hepato-
cellular carcinom a o n im aging studies. In th is setting, the size
o f the n od u le is im p o rta n t. A hep atocellular n od u le o f > 2 cm
occurring in c irrh o tic liv e r is h ig h ly suspicious o f hepatocellu-
la r carcinom a unless proven otherwise. S m alle r nodules m ay
be b o rd e rlin e o r m acroregenerative in nature. In a liv e r w ith -
o u t cirrhosis, liv e r cell adenom a o r focal n o d u la r hyperplasia
is m ore likely. In a d d itio n, a lm ost all fib ro la m e lla r variants o f
hep atocellular carcinom a and 1 5 -2 0 % o f the usual hepatocel-
lu la r carcinom as occur in n o n c irrh o tic liver.26
Macroregenerative Nodule
This term refers to benign nodules show ing little histologic d iffer-
ence fro m cirrhotic nodules.33,34 It is also called low-grade dysplasia,
large-cell dysplasia, large-cell change, and adenom atous hyperpla-
sia.35 Macroregenerative nodules have abundant cytoplasm and
relatively n o rm a l N /C ratio and n orm al retic ulin n etw ork w ith
m aintenance o f n o rm a l live r plate architecture.33-36 FN A smears
show a c om b ination o f regenerative changes, fibrosis, degenera-
tive changes, and fa tty m etam orphosis. Regenerative changes are
Fig. 28.29 Borderline hepatocellular nodule. The aspirate from a
1.5 cm liver nodule was granular and showed trabecular groupings. FNA
smear (Papanicolaou x LP).
represented by p leom orp hism o f hepatocytes, an increase in the
num b er o f m ito tic figures, and an increase in the num b er o f b in u -
cleate hepatocytes. The nuclei o f hepatocytes often show variation
in size and have p ro m in e n t nucleoli (Fig. 28.28) .
Key features of macroregenerative nodule
• P hysical features o f th e aspirate: fine -ne ed le cores d iffic u lt
to sm ear.
• H epatocytes w ith v a ria tio n in n u c le a r size. Regenerated
hepatocytes appear p le o m o rp h ic w ith large n u c le i and
p ro m in e n t n u c le o li.
Borderline Nodule
B ord erline n od u le is also called high-grade dysplasia, sm all-cell
dysplasia, sm all-cell change, and atypical adenom atous hyper-
plasia. This lesio n is a precursor to hep atocellular carcinom a.
This term refers to atypical hepatic nodules th a t are n o t yet fu lly
diagnostic o f carcinom a.33,34 B ord erline nodules are present in 5 -
15% o f c irrho tic livers. B ord erline nodules are fre q ue ntly m u lti-
ple. The size o f the n od u le is u su a lly < 2 cm. It is characterized by
increased N /C ra tio fro m reduced cytoplasm . R eticulin fibers are
decreased o r absent.26,33 In FN A smear, the sm ear pattern is in d is-
ting uishab le fro m w ell-d ifferentiated hep atocellular carcinom a,
except the size is < 2 cm. The case illustra ted in Figs 28.29 and
28.30 was aspirated fro m a 1.5-cm, solid, hypervascular nod ule
in a p atient w ith cirrhosis and p rio r to liv e r transplant. The h is-
tologic fo llo w -u p in the liv e r explant 12 m on ths later was h ig h -
grade (sm all cell) dysplasia.37 The smears were fin e ly granular
grossly and show num erous m icrotrabeculae w ith m o n o to n o u s
sm all hepatocytes w ith p ro m in e n t nucleoli. R eticulin fibers were
m arked ly decreased. However, the size o f the n od u le was o n ly
0.9 cm in the liv e r explant and had n o in filtra tiv e border.
Key features of borderline nodule
• C T scan: s m a ll liv e r n o d u le (< 2 cm ).
• P hysical features o f th e aspirate: g ra n u la r sm ear.
• M o n o to n o u s p o p u la tio n o f s m a ll hepatocytes w ith h ig h
N /C ra tio (n o rm a l nuc le ar size b u t c ytop lasm is reduced).
Fig. 28.30 Borderline hepatocellular nodule. The cytologic features are
indistinguishable from hepatocellular carcinoma, but the final diagnosis was
0.9 cm "small cell dysplasia". FNA smear (Papanicolaou x HP).
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