L u iz R o b e r t o M e d in a d o s S a n t o s , C la u d io R o b e r t o C e r n e a , L u iz P a u lo K o w a ls k i, P a u lo C a r n e ir o C a r n e ir o , M ir ia m N a k a g a m i S o t o , S u n a o N is h io , F la v ia C a r n e ir o H o ja ij, A u g u s t o D u t r a J r . , G ilb e r t a B r it t o e S ilv a F ilh o , A lb e r t o R o s s e t t i F e r r a z
S q u am o u s-cell carcin o m a o f th e lo w er lip :
A retro sp ectiv e stu d y o f 5 8 p atien ts
Department of Head and Neck Surgery, Department of Pathology, General Hospital of the University of
sao Paulo Medical School. sao Paulo, Brazil
T h e c h a rts o f 5 8 p a tie n ts w ith s q u a m o u s -c e ll c a rc in o m a s o f th e lo w e r lip , tre a te d a t th e G e n e ra l H o s p ita l o f th e U n iv e rs ity o f S a o
P a u lo M e d ic a l S c h o o l fro m J a n u a ry 1 9 8 0 to D e c e m b e r 1 9 8 9 , w e re re tro s p e c tiv e ly a n a ly z e d . In a d d itio n to re g u la r d e m o g ra p h ic d a ta , a ll a v a ila b le in fo rm a tio n w a s c o lle c te d re g a rd in g : s m o k in g a n d d rin k in g h a b its ; s u n e x p o s u re ; c lin ic a l s ta g e ; m a c ro s c o p ic fe a tu re s o f
th e p rim a ry le s io n s ; ty p e o f tre a tm e n t; a n d fo llo w -u p . A m e tic u lo u s p a th o lo g ic a l a n a ly s is , c o m p ris in g th e h is to lo g ic d iffe re n tia tio n g ra d e , m a x im a l tu m o r th ic k n e s s , s u n e la s to s is , p e rin e u ra l s p re a d , v a s c u la r a n d m u s c u la r in v a s io n , s u rg ic a l m a rg in s , p e ritu m o ra l
in fla m m a to ry in filtra te , a n d p o s itiv e ly m p h n o d e s , w ith o r w ith o u t e x tra c a p s u la r s p re a d , w a s u n d e rta k e n a s w e ll. T h e e v a lu a tio n o f th e
o v e r a ll 5 -y e a r s u r v iv a l s h o w e d s ig n ific a n t s ta tis tic a l d iffe re n c e s , w ith p ro g n o s tic im p lic a tio n s , fo r th e fo llo w in g v a ria b le s : m a x im a l tu m o r th ic k n e s s , T -s ta g e a n d p o s itiv e n o d e s .
U N IT E R M S : L ip c a n c e r. L ip n e o p la s m . S q u a m o u s -c e ll c a rc in o m a , p ro g n o s tic fa c to rs . H e a d a n d n e c k c a n c e r.
IN T R O D U C T IO N
A
m o n gs u rg e o n ,th e d is e a s e sc a n c e r is b y fa r th e m o s t im p o rta n t,tre a te d b y th e h e a d a n d n e c kn o t o n ly d u e to th e fre q u e n c y o f its o c c u rre n c e in th is re g io n o f th e h u m a n b o d y , b u t a ls o b e c a u s e o f its p ro g n o s tic im p lic a tio n s . O f a ll m a lig n a n t tu m o rs in th is a re a , lip c a n c e r is th e s e c o n d m o s t fre q u e n t, p re c e d e d o n ly b y s k in c a n c e r, 1 0a n d is a ls o th e m o s t fre q u e n t a m o n g o ra lA d d r e s s f o r c o r r e s p o n d e n c e :
L u iz R o b e r t o M e d in a d o s S a n t o s
R u a D r . H o m e m d e M e lo , 2 3 9 -a p t o . 8 1 -P e r d iz e s S a o P a u lo / S P - B r a s il - C E P 0 5 0 0 7 - 0 0 0
c a v ity tu m o rs .2
.2 0 O w in g to th e lo c a tio n a n d g re a te r
e x p o s u re to s u n lig h t, th e lo w e r lip is a ffe c te d in n e a rly 9 0 p e rc e n t o f a ll c a s e s .1 7.6 3 A m o n g h is to lo g ic ty p e s o b s e rv e d ,
s q u a m o u s -c e ll c a rc in o m a is id e n tifie d in 9 5 p e rc e n t o f a ll c a s e s , w h e re a s b a s a l-c e ll c a rc in o m a , m o re c o m m o n o n th e u p p e r lip , a n d a d e n o c a rc in o m a s a ris in g in m in o r s a liv a ry g la n d s , c o n s titu te th e ra re s t ty p e s .6 4 M o s t a u th o rs a g re e
th a t th e e v o lu tio n , a t tim e s fa v o ra b le , o f s u c h tu m o rs m a y b e c o m p lic a te d b y lo c a l re c u rre n c e , o r ly m p h a tic d is s e m in a tio n , w h e th e r lo c a l-re g io n a l o r d is ta n t, w h ic h m a y le a d to th e p a tie n t's d e m is e Y . 31
T h u s , th e p re s e n t s tu d y w a s u n d e rta k e n to a s s e s s th e tu m o ra l a n d in d iv id u a l fa c to rs w h ic h m a y in flu e n c e a n d d e te rm in e th e m a in p ro g n o s tic a s p e c ts in re g a rd to th e re c u rre n c e a n d ris k o f d e a th c a u s e d b y th e lo w e r lip s q u a m o u s -c e ll c a rc in o m a .
S A N T O S , L .R .M .; C E R N E A , C .R .; K O W A L S K I, L .P . e t a l. - S q u a m o u s -c e ll c a rc in o m a o f th e lo w e r lip : A re tro s p e c tiv e s tu d y o f 5 8 p a tie n ts
F i g u r e 1 - C a s e d i s t r i b u t i o n a t t h e G e n e r a l H o s p i t a l . N u m b e r o f p a t i e n t s t r e a t e d b y D e r m a t o l o g y ( D E R M A ) , O t o r h i n o l a r y n g o l o g y ( E N T ) a n d H e a d a n d N e c k S u r g e r y ( H & N ) .
O u r s tu d y is b a s e d o n th e re tro s p e c tiv e a n a ly s is o f
th e c h a rts o f 5 8 p a tie n ts w ith lo w e r lip s q u a m o u s -c e ll
c a rc in o m a tre a te d a t th e C e n tra l In s titu te o f th e G e n e ra l
H o s p ita l o f th e U n iv e rs ity o f S a o P a u lo M e d ic a l S c h o o l
fro m J a n u a ry 1 9 8 0 to D e c e m b e r 1 9 8 9 .
P a tie n ts in c lu d e d in th e s tu d y w e re th o s e w h o :
a . h a d a h is to lo g ic a lly -c o n firm e d d ia g n o s is o f lo w e r lip
s q u a m o u s -c e ll c a rc in o m a ;
b . h a d n o t b e e n p re v io u s ly tre a te d ;
c . h a d b e e n s u b m itte d to s u rg e ry , a s a firs t tre a tm e n t,
w ith c u ra tiv e in te n t;
d . H a d re c o rd s c o n ta in in g a ll c lin ic a l a n d
a n a to m o p a th o lo g ic a l d a ta re g a rd in g th e tu m o r;
h e n c e , in c o m p le te re c o rd s w e re e x c lu d e d ;'
e . h a d d e m o g ra p h ic d a ta w h ic h w a s a s c o m p le te a s
p o s s ib le .
T h u s , a m o n g th e 1 4 1 p a tie n ts lis te d o n th e c o m p u te r
o f th e G e n e ra l R e g is try a t G e n e ra l H o s p ita l w ith lip c a n c e r
tre a te d d u rin g th e p e rio d m e n tio n e d , w e w e re a b le to s e le c t
5 8 c a s e s . T h e m a in c a u s e s o f re c o rd e x c lu s io n w e re :
a . n o t in d e a d file s
b . im p re c is e tu m o r d a ta
c . th e im p o s s ib ility o f re v ie w in g th e a n a to m o
-p a th o lo g ic a l d a ta .
W e m u s t s tre s s th a t a s th is fa c ility is a g e n e ra l
h o s p ita l, th e c a s e s o f th e p re s e n t s tu d y w e re tre a te d in
th re e d e p a rtm e n ts , a s fo llo w s : D e rm a to lo g y , 2 7 p a tie n ts
P A T I E N T S A N D M E T H O D S (4 6 .5 p e rc e n t); O to rh in o la ry n g o lo g y , 9 (1 5 .5 p e rc e n t); a n d H e a d a n d N e c k S u rg e ry , w h ic h w a s re s p o n s ib le fo r
2 2 p a tie n ts (3 8 .0 p e rc e n t), 4 o f w h o m (6 .9 p e rc e n t) h a d b e e n
re fe rre d b y th e D e rm a to lo g y D e p a rtm e n t, w h e re th e y h a d
b e e n s u b m itte d to th e firs t re s e c tio n (F ig . 1 ).
T h e p ro to c o l o f e a c h c a s e in c lu d e d :
1 . P a tie n t's fu ll n a m e a n d h o s p ita l re g is tra tio n n u m b e r.
2 . S e x .
3 . A g e , in y e a rs .
4 . R a c e : W h ite /o th e r ra c e s .
5 . P la c e o f o rig in : u rb a n /ru ra l a re a .
6 . O c c u p a tio n : o u td o o r/in d o o r a c tiv itie s .
7 . D u ra tio n o f c o m p la in t, in m o n th s .
8 . H a b its : s m o k e r/n o n -s m o k e r; c o n s u m e d a lc o h o l!
c o n s u m e d n o a lc o h o l.
9 . L o c a l p h y s ic a l e x a m in a tio n ; th is c o n ta in e d a c c u ra te
d a ta a b o u t th e tu m o r le s io n , a s w e ll a s le s io n ty p e ,
s iz e in c e n tim e te rs (T ), a n d s ite .
1 0 . T re a tm e n t re c e iv e d : th e d a ta o f th e firs t s u rg e ry w a s
th e b a s is fo r e s tim a tin g e a c h p a tie n t's a c tu a ria l s u rv iv a l,
in m o n th s . T h e ty p e o f h o s p ita l tre a tm e n t re c e iv e d b y
p a tie n ts e n a b le d u s to o rg a n iz e 4 g ro u p s , a s fo llo w s :
G r o u p I - P a tie n ts s u b m itte d to tu m o r re s e c tio n
(R ) w ith p rim a ry c lo s u re (P C ) o f th e s u rg ic a l d e fe c t
( R + P C ) ;
G r o u p II - P a tie n ts s u b m itte d to tu m o r re s e c tio n w ith
s u rg ic a l d e fe c t re c o n s tru c tio n (R E C ) b y m e a n s o f
s o m e k in d o f fla p (R + R E C );
G r o u p III - P a tie n ts s u b m itte d to tu m o r re s e c tio n
c o m b in e d w ith a n y ty p e o f n e c k d is s e c tio n (N D ),
w ith o u t a d ju v a n t ra d io th e ra p y (R + N D );
G r o u p IV - P a tie n ts s u b m itte d to tu m o r re s e c tio n
a n d a d ju v a n t ra d io th e ra p y (R D T ), w ith o r w ith o u t
n e c k d is s e c tio n (S U R + R D T ).
O u r in te n t, w h e n o rg a n iz in g th e fo u r g ro u p s ,
w a s to c o rre la te tre a tm e n t in te n s ity w ith p a tie n t
s u rv i v a l. F i fte e n p a tie n ts (2 5 .9 p e rc e n t) w e re
c la s s ifie d in to G ro u p I; 2 1 (3 6 .2 p e rc e n t) in to G ro u p
II; 7 (1 2 .2 p e rc e n t) in to G ro u p III; a n d th e re m a in in g
1 5 c a s e s (2 5 .9 p e rc e n t) in to G ro u p IV . E le v e n p a tie n ts
(1 9 .0 p e rc e n t) u n d e rw e n t n e c k d is s e c tio n , a n d 4 (6 .9 p e rc e n t) w ith c e rv ic a l m e ta s ta s is w e re g iv e n
ra d io th e ra p y (F ig . 1 ).
1 1 . F o llo w -u p : th is in v o lv e d o b s e rv a tio n s o n th e
d e v e lo p m e n t o f re c u rre n c e s , re g io n a l
m e ta s ta s e s , o th e r m a lig n a n t tu m o rs , o r
e v o lu tio n w ith n o e v id e n c e o f d is e a s e .
1 2 . A n a to m o p a th o lo g ic a l s tu d y : b io p s ie s a n d
s u rg ic a l s p e c im e n s o f th e p a tie n ts in c lu d e d in o u r s tu d y , w h e th e r o f th e p rim a ry tu m o r
H & N
ENT D E R M A
I -
G r o u p I ~ G r o u p I I r im G r o u p I I I ~ G r o u p I Vl
6o 1 6
1 0
2 0 1 8
or recurrences, as w ell as the products of
neck dissection, w ere review ed by tw o
experienced pathologists at the G eneral H ospital.
T hus, w e w ere able to analyze in detail:
12.1.
H istologic grade: according to the classification proposed by B R O D E R S7 in 1926, by w hich theseneoplasm s are divided into four grades, m ainly
considering the cellular differentiation percentage in
the squam ous-cell carcinom a.
12.2.
M axim al tum or thickness: utilizing a 0.1 m m accuracy optical m icrom eter, the m axim al thicknessof each tum or w as m easured vertically, w ith the
exclusion of keratin, from the surface layers of viable
cells, dow n to the deep region of the neoplasm w hich
borders on the corium .
12.3.
S olar elastosis: the alteration of the elastic fiber layer provoked by ultraviolet radiation, causing solaror senile elastosis w as analyzed as present or absent.
12.4.
P erineural invasion: this w as defined as the visualization of a w ell-defined infiltration of theperineural space. T he com pression of nervous fillets
by the neoplasm w as not considered to be an invasion.
12.5.
M uscular invasion: the neoplastic infiltration of the lip m uscles w as also analyzed as present or absent.12.6.
V ascular invasion: the presence of the tum or infiltrating the vascular w all w as analyzed.12.7.
S urgical m argins: the tum or resection m argins on the lip after the cancer excision procedures hadbeen com pleted.
12.8.
Inflam m atory response: the degree of inflam m atory response on the tum or periphery w asassessed through the discreet, m oderate or intense
presence of global reactional cellular infiltrate.
12.9.
A nalysis of cervical lym ph nodes: in order to record data relative to the presence or absence of neoplasticinvolvem ent, rupture and extracapsular tum oral spread,
cervical lym ph nodes w ere divided, in the conventional
fashion, into levels I to V , on both sides.lio
F or the analysis of the different variables exam ined
in the patients, a m icrocom puter (M icrotec X T - I 002) and
specific statistical analysis program s w ere utilized. A ll
data contained in the protocols w ere analyzed in regard to
inform ation coherence, w ith attem pts to select variables
w hich m ight best contribute to the discri m ination of
prognosis-determ ining factors. C um ulative survival rates
and curves w ere generated by the K aplan & M eier m ethod.
C om parisons am ong survival distributions for categories
of the sam e variable w ere m ade using the M antel-C ox test.
T he K M S U R V m icrocom puter program 1 2 w as utilized for
all actuarial analyses relative to overall survival.
RESULTS
T he collection and tabulation of the dem ographic
data concerning the patient group analyzed show ed that
50 (86.2 percent) w ere m en and 18 (13.8 percent) w ere
w om en, and both sexes w ere predom inantly w hite (55
or 94.8 percent). A larger num ber of patients carne from
urban zones (33 or 56.9 percent) rather than rural areas
(25 or 43.1 percent). O utdoor jobs, and consequently,
m ore prolonged exposure to the sun, w ere reported by
30 (51.7 percent) of the patients, w heras the rem aining
28 (48.3 percent) conducted activities indoors, thus
affording greater protection. T he actuarial or overall
survival regarding these four variables did not reveal
statistically significant differences am ong the
categories.
A ges ranged from 18 to 84 and case distribtion w as
as follow s: 10 patients (17.2 percent) w ere under the age
of 40; 21 patients (36.2 percent) w ere aged 41-60, and 27
(46.6 percent) w ere over the age of 61. T he overall 5-year
survival for these thrE :e categories did not reveal a statistical
difference.
T he duration of com plaint varied from 2 to 36
m onths. T his w as shorter than 1 year in 25 cases (43.1
percent), and I or m ore years in 33 cases (56.9 percent).
S urvival at 5 years w as not statistically different betw een
these tw o categories.
A sm oking habit w as reported by 42 patients (72.4
percent). N orm al cigarettes w ere m entioned by 32 (55.2
percent), handrolled cigarettes by 8 (13.8 percent), and
pipes only by 2 of these patients (3.4 percent). T here w ere
no references to sm oking in 12 cases (20.7 percent), and 4
patients (6.9 percent) stated they w ere non-sm okers.
M oderate drinking w as reported by 25 of these
patients (43.1 percent), w hereas 19 (32.8 percent) did not
drink at all, and in 12 cases (20.7 percent) such inform ation
w as lacking. T w o cases (3.4 percent) of alcohol abuse w ere
recorded.
In regard to tum or size, 20 patients (34.5 percent)
exhibited T I lesions; 32 cases (55.2 percent) show ed
T 2; in 5 cases the tum or w as recorded as T 3; and only
1 patient (1.7 percent) had a T 4 tum or. F or patients
w ith T I tum ors, the overall 5-year survi val w as 68.3
percent, w ith a standard error of 10.8. F or T 2 cases,
such survival w as 75.1 percent (S E : 8.3) for T 3 + T 4,
it w as zero, show ing a statistically significant difference
(p=O .O O O O 1).
T he lesion exhibited by 45 patients (77.6 percent)
w as described as uiceroinfiltrative, w hereas verrucose or
vegetating lesions w ere seen in the rem aining 13 (22.4
percent) patients. T he lesion w as noted on the left side in
S A N T O S , L . R . M . ; C E R N E A , C . R . ; K O W A L S K I , L . P . e t a l. - S q u a m o u s - c e ll c a r c in o m a o f t h e lo w e r lip : A r e t r o s p e c t iv e s t u d y o f 5 8 p a t ie n t s
24 of these cases (41.4 percent); on the m id-portion of the
lip in 16 (27.6 percent); and on the right side in an equal
num ber of cases.1 6 It w as described as reaching the left
com m issure in 1 case (1.7 perce~ t), and to have been
inaccurately recorded in only 1 case (1.7 percent). S urvival
values for the type of lesion did not show statistically
significant differences.
T he situation of cervical lym ph.nodes w as carefully
exam ined and no suspicious cervical lym ph nodes w ere
encountered in 44 patients (75.9 percent), w ho w ere
labeled as N O . S ix patients (10.3 percent) w ere classified
as N l; 2 (3.4 percent) as N 2a; 4 (6.9 percent) as N 2b; and
2 (3.4 percent) as N 2c. F or the survival analysis, the
variable w as divided into tw o categories: N O and N + . T hus,
the overall 5-year survival for patients w ith N O
classifications w as 70.4 percent (S E : 7.2) and w as 47.6
. percent (S E : 14.0) for the 14 patients (24.1 percent) w ith
palpable lym ph nodes (N + ), show ing a statistically
significant difference (p= 0.00929).
A s none of the patients presented evidence of distant
m etastasis, they w ere all considered M O . O ur staging by
T N M classification had been com pleted. T hus, there w ere
16 S tage I patients (27.6 percent); 22 S tage II (37.9
percent); 11 S tage III (19.0 percent); and 9 S tage IV (15.5
percent) at initial treatm ent.
T hese patients w ere subm itted to six different form s
of treatm ent, as follow s:
• tum or resection w ith prim ary closure of defect in
15 cases (25.9 percent);
• resection and closure of defect using a regional flap
in 21 cases (36.2 percent);
• tum or resection com bined w ith unilateral neck
dissection in 4 cases (6.9 percent);
• tum or resection associated w ith bilateral neck
dissection in 3 cases (5.2 percent);
• tum or resection w ith neck dissection com bined w ith
postoperative radiotherapy in 11 patients (19.0
percent);
• prim ary tum or resection and neck radiotherapy in
4 cases (6.9 percent).
C onsidering the distribution by treatm ent groups,
the overall 5-year survival for the 15 G roup I patients
(25.9 percent) w as 67.7 percent (S E : 13.3); for the 21
G roup II cases (36.2 percent), survival w as 90.2 percent
(S E : 6.6); for the 7 G roup III cases (12.2 percent), it
w as zero; and for the 15 G roup IV patients (25.9
percent), survival w as 36.0 (S E : 13.2). A highly
significant difference w as evident am ong the categories
(p = 0.00009).
D uring our data collection, w e found that 33 patients
(56.9 percent) w ere still alive, w hereas 25 had died; 12
(20.7 percent) had died because of the lip tum or and 13
patients (22.4 percent) due to other causes.
S urvival varied from 1 to 129 m onths; m ean survival
tim e w as 54 m onths. T here w ere 44 (75.9 percent)
disease-free patients, including those w ho had died, and neoplastic
recurrence in 14 patients (24.1 percent) w as distributed as
follow s:
• 7 cases (12.0 percent) w ith neck recurrence;
• 6 cases (10.3 percent) w ith local and neck
recurrences;
• 1 case (1.7 percent) w ith local, cervical
recurrences, and distant m etastasis.
R ecurrence tim e w as from 3 to 30 m onths and w as
detected w ithin the first postoperative year in 8 patients
(13.8 percent); betw een the first and second year in 5
cases (8.6 percent); and after tw o years in only 1 patient
(1.7 percent) .
T he developm ent of a second tum or w as
docum ented in 7 patients (12.0 percent). It w as located
on the skin in 5 cases (8.6 percent), in the oral cavity
of 1 patient (1.7 percent), and elsew here in the
rem aining case (1.7 percent). O ther clinical ailm ents
w ere recorded during the follow -up of 14 patients (24.1
percent). T here w as 1 patient (1.7 percent) w ith A ID S .
T he accurate histologic analysis of the specim ens on
file at the G eneral H ospital D epartm ent of P athology
revealed interesting and quite im portant data for this study.
T hirty patients (51.7 percent) had G rade 1 tum ors in regard
to cellular differentiation; 22 (37.9 percent) had G rade 2;
and 6 (10.3 percent), G rade 3. S urvival at 5 years show ed
no statistically significant differences am ong these three
categories.
T um or thickness ranged from 0.6m m to 61.8m m ,
w ith m edian thickness approaching 4m m and w as
distributed am ong the patients as follow s (F ig. 2):
F ig u re 2 - C a s e d is trib u tio n a c c o rd in g to tu m o r th ic k n e s s .
F ig u re 3 - C u rve s o f cu m u la tive su rviva l a n d tu m o r th ickn e ss.
• 0.6-4 m m in 30 cases (51.7 percent);
• 4.1-8 m m in 20 cases (34.4 percent);
• > 8 m m in 8 cases (13.9 percent).
T he overall 5-year survival for this variable w as
significantly different:
• 74.5 percent (S E : 8.4) for patients w ith tum ors of
0.6-4m m ;
• 60.9 percent (S E : 11.9) for those w ith tum ors of
4.1-8.0m m ;
• 25.0 percent (S E : 19.8), w ith p= 0.00467 (F ig. 3)
for those w ith tum ors> 8 m m .
S olar elastosis w as present in 44 cases (75.9 percent).
P erineural tum or invasion w as seen in 2I cases (36.2
percent). M uscular invasion w as present in 39 cases (67.2
. percent). N o vascular invasion w as detected in 52 cases
(89.7 percent). T he overall 5-year survival for the three
invasion variables show ed no statistical differences.
T he peritum oral inflam m atory cellular infiltrate w as
intensely evident in 33 cases (56.9 percent), m oderately
evident in 22 (37.9 percent), and discreet in only 3 (5.2
percent). It should be noted that lym phocytes and
plasm ocytes w ere detected in all cases, w hile no
histiocytes, neutrophils or eosinophils w ere present in 8
cases (13.8 percent), 37 (63.8 percent), and 25 cases (43.1
percent), respectively. T he analysis of the overall 5-year
survival relative to inflam m atory infiltrate form s revealed:
• a 60.9 percent (S E : 10.0) m oderate and discreet
infiltrates;
• a 67.1 percent (S E : 8.0) intense infiltrate (p=
0.802 I).
E ighteen (31.0 percent) of the patients treated
underw ent som e form of neck dissection, as already detailed.
1 - 4 n o d e s • 1tEill8 - 88 n o d e s . IilDW N D
I
o1 0
2 0 3 0
60
40
T he analysis of lym ph node involvem ent by
cancer .am ong the different levels of cervical
distributions show ed, as expected, a greater
im plication of levels I, II and III in 15 (25.9
percent), 10 (17.2 percent), and 10 (17.2 percent)
patients, respectively. A m ong the patients
subm itted to neck dissection, there w as no lym ph
node involvem ent in 6 (10.3 percent), w hereas
invasion of Ito 4 lym ph nodes w as detected in.7
patients (12.Ipercent), and 5 to 55 lym ph nodes
positive for carcinom a w ere noted in the
rem aining 5 cases (8.6 percent). N o neck
dissection (N D ) w as perform ed in.40 patients
(69.0 percent) (F ig. 4). T he overall 5-year survival
for patients subm itted to neck dissection and w ith
histologically negative lym ph nodes w as 66.7
percent (S E : 19.2); 34.3 percent (S E : 19.5); for
those w ith involvem ent of 1 to 4 lym ph nodes for
those w ith involvem ent of 5 to 55 lym ph nodes,
such survival w as 40.0 percent (S E : 2 1.9) and,
for those not subm itted to neck dissection, the rate w as
92.5 percent (S E : 4.2). S uch differences w ere statistically
significant (p= 0.0004 I)(F ig. 5).
L ym ph node capsule rupture and extracapsular
neoplastic spread w ere identified in 8 (13.8 percent) of
the 18 patients (3 1.0 percent) w ith neck dissection. F or
this variable, the overall 5-year survi val also show ed
statistically significant results (p= O .O OI I I) am ong the three
categories represented:
• patients w ith no capsular rupture in involved lym ph
nodes had an overall survival of 58.3 percent (S E :
6 .1 );
• patients presenting lym ph node capsule rupture had
an overall survival of 33.3 percent (S E : 18.0);
F ig u re 4 - C a se d istrib u tio n a cco rd in g to th e n u m b e r o f
h isto lo g ica lly-p o sitive lym p h n o d e s.
132
110
MONTHS
88
o
o
22 44 66D 0.6-4 0 4.1-8 1)8
THICKNESS/rnrn
20 40 60 80 100
S A N T O S , L .R .M .; C E R N E A , C .R .; K O W A L S K I, L .P . e t a l. - S q u a m o u s-ce ll ca rcin o m a o f th e lo w e r lip : A re tro sp e ctive stu d y o f 5 8 p a tie n ts
100
oJ
It ~
80
,.. ~ c: j
60
4'l
III ~
40
,.. ~ It
oJ
20 j
t
j tl0
:\ 0 22 44
"
_18 110 '1 2a tt- o 1-4 II H 5 v WND
MONTHS POSiTiVE LiMPH NODES
F ig u re 5 - C u rve s o f cu m u la tive su rviva l a n d th e n u m b e r o f
h isto lo g ica lly-p o sitive lym p h n o d e s.
• p a tie n ts n o t su b m itte d to n e c k d isse c tio n h a d a n
o v e ra ll 5 -y e a r su rv iv a l o f 9 2 .5 p e rc e n t (S E : 4 .2 ).
D IS C U S S IO N
T h e lite ra tu re sh o w s q u ite d iffe re n t fin d in g s w h e n
a n a ly z in g lip c a n c e r in c id e n c e w o rld w id e . In A u stra lia ,
th is in c id e n c e re p re se n ts 1 7 p e rc e n t o f a ll m a lig n a n t tu m o rs
o f th e h e a d a n d n e c k , 3 .2 p e rc e n t o f a ll tu m o rs, a n d 6 2 .1
p e rc e n t o f m o u th c a n c e rs.6 2 In Ita ly , lip c a n c e r c o rre sp o n d s
to 2 5 p e rc e n t o f m o u th c a n c e rs,5 6 in C a n a d a , to th re e
p e rc e n t a ll tu m o rs,5 9 a n d in th e U n ite d S ta te s th is in c id e n c e
v a rie s fro m 0 .6 p e rc e n t2 8 to 2 .2 p e rc e n t4 2 o f c a se s tre a te d
a s c a n c e r in g e n e ra l. In B ra z il, p a rtic u la rly in S a o P a u lo ,
th e a n n u a l in c id e n c e ra te fo r 1 9 7 8 w a s 3 .8 c a se s p e r
1 0 0 ,0 0 0 p o p u la tio n fo r m a le s, a n d 1 .0 c a se p e r 1 0 0 ,0 0 0
fo r fe m a le s.4 4 C a n c e r m o rta lity in S a o P a u lo w a s 0 .1 8 p e r
1 0 0 ,0 0 0 p o p u la tio n 4 3 in 1 9 7 8 .
In re g a rd to d e m o g ra p h ic d a ta , th e lite ra tu re h a s b e e n
q u ite u n a n im o u s in sh o w in g a fa r g re a te r p ro p o rtio n o f
c a se s a m o n g m e n th a n w o m e n . In th e la rg e n u m b e r o f
c a se s d e ta ile d , th e n u m b e r o f m a le p a tie n ts w ith c a n c e r in
th e lo w e r lip v a rie d fro m 7 7 .7 p e rc e n t (2 4 ) to 1 0 0 p e rc e n t.4
In o u r c a se s, c o m p rise d o f 5 0 m a le p a tie n ts (8 6 .2 p e rc e n t),
su c h m a rk e d m a le p re d o m in a n c e w a s a lso fo u n d .
T h e u n a n im ity fo u n d in th e lite ra tu re is re p e a te d
w h e n th e p a tie n ts' e th n ic g ro u p is a n a ly z e d . A ll stu d ie s
c o n su lte d re p o rt a h ig h e r in c id e n c e o f lip c a n c e r a m o n g
w h ite p a tie n ts. B E R N IE R & C L A R K ,5 a m o n g
8 3 5 c a se s c o lle c te d , re p o rte d o n ly 4 (0 .4 7 p e rc e n t)
b la c k p a tie n ts. M O R A & P E R N IC IA R 0 4 6
p u b lish e d a stu d y w ith th e la rg e st n u m b e r o f b la c k
p a tie n ts fo u n d in th e lite ra tu re re v ie w e d : 3 6 ,
tre a te d b e tw e e n 1 9 4 8 a n d 1 9 7 9 . N e v e rth e le ss, n o
ra c e c o m p a riso n is m a d e in th e ir stu d y . S C O P P 's
h y p o th e sis5 4 se e m s p la u sib le , a s it sta te s th e
m e la n in p ig m e n t, m o re a b u n d a n t in b la c k s,
a ffo rd s g re a te r p ro te c tio n fro m th e su n . O u r
p e rc e n ta g e o f w h ite p a tie n ts (9 4 .8 p e rc e n t) a g re e s
w ith th e lite ra tu re .
F o r th e a g e g ro u p o f g re a te r lip c a n c e r
in c id e n c e , d a ta w e re a lso so m e w h a t
u n ifo rm , w ith th e a g e b ra c k 'e t b e tw e e n th e
6 0 's a n d th e 8 0 's b e in g re fe rre d to b y m o st
a u t h o rs. 2 .3 .8 .1 5 .2 2 -2 4 .2 7.3 2 .3 4 .3 8 .4 6 .4 9 .5 0 .6 2B E R N IE R &
C L A R K 5 d e sc rib e d th e lo w e st m e a n a g e fo u n d in
th e lite ra tu re c o n su lte d - 3 7 y e a rs - b a se d o n th e
sa m p le o f p a tie n ts fro m th e a rm y in c lu d e d in th e ir
c a se s. P a tie n ts w ith lip c a n c e r a g e d 1 8 a n d 1 9
y e a rs a re d e sc rib e d . T h e o ld e st p a tie n t, a g e d 9 7 , is
d e sc rib e d in B R O D E R S ' se rie s.8 T h e a g e b ra c k e t in o u r
se rie s re la te s w ith th e lite ra tu re d e sc rib e d ; 4 6 .6 p e rc e n t o f
th e p a tie n ts a re o v e r th e a g e o f 6 1 .
T h e p la c e o f o rig in o f p a tie n ts is a sso c ia te d w ith
th e im p o rta n c e a tta c h e d b y th e a u th o rs to a m o re
p ro lo n g e d su n e x p o su re a s a re le v a n t e tio lo g ic fa c to r
in lo w e ~ lip c a n c e r.8 .1 7 .2 9 .3 4 .5 7A re a s w ith p re d o m in a n tly
su n n y c lim a te s, a s w e ll a s d a ily a c tiv itie s c h a ra c te riz e d
b y su n e x p o su re , w h e th e r a t w o rk o r le isu re , se e m to
p la y a ro le in th e d e v e lo p m e n t o f lo w e r lip c a n c e r. In
th e p re se n t se rie s, 5 6 .9 p e rc e n t o f th e p a tie n ts c a m e
fro m u rb a n a re a s. In a c o u n try w ith a p re d o m in a n tly
tro p ic a l c lim a te lik e B ra z il, su n e x p o su re , e v e n in u rb a n
a re a s, m a y b e m o re p ro lo n g e d w h e n a c tiv itie s a re
c o n d u c te d o u td o o rs (5 1 .7 p e rc e n t o f o u r p a tie n ts).
T h u s, th e c a se d istrib u tio n in o u r stu d y re la te s w ith
th e lite ra tu re . N o n e o f th e v a ria b le s m e n tio n e d a b o v e ,
w h e n stu d ie d in o u r se rie s, p ro v e d to b e sta tistic a lly
im p o rta n t fo r p a tie n t p ro g n o sis.
T h e e a sy e x a m in a tio n o f th e lip , a s p o in te d o u t b y
E L F E N B A U M ,1 9 w h e th e r b y th e in d iv id u a l h im se lf o r b y
d e n tists o r p h y sic ia n s, m a k e s it p o ssib le to o b ta in
d ia g n o stic a n d th e ra p e u tic re so u rc e s a t q u ite a n e a rly sta g e .
T h u s, th e d u ra tio n o f c o m p la in t is n o t lo n g . B R O D E R Sx
h a d m e n tio n e d a m e a n d u ra tio n o f 2 .5 y e a rs, w h e re a s fo r
B E R N IE R ,4 it w a s le ss th a n I y e a r. T h e lo n g e st tim e o f
tu m o ra l c o m p la in t in o u r se rie s w a s 3 6 m o n th s.
A m o n g h a b its c o n sid e re d to b e h a rm fu l to o n e s
h e a lth , sm o k in g is q u ite c o n sta n tly m e n tio n e d b y
authors~u7.21.34 as an im portant
etiologic
factor
in the
developm ent
of lip cancer.
The large num ber
of pipe
sm okers found by BRODERS8 has not been confirm ed by
other authors.29.59 Alcohol abuse did not prove to be an
etiologically
im portant
factor in lip cancer.21 Our study
has not added anything to these data, which are devoid of
prognostic
value.
Few series include
advanced
tum ors.58 In virtually
all publications
dealing
with
treatm ent,
TI
and T2
tum ors
represent
the
m ajority
of
cases.
For
PETROVICH
et aI., 49 93 percent
of a total
of 250
patients
were Tl and T2; M EHREGAN
&ROENIGK41
reported
100 percent
of TI
and T2 in 44 lesions;
ZURRIDA
et al.65 detected
100 percent of TI and T2 in
their group of 131 patients; GROVER
et al.24 found 98.8
percent ofTI
and T2 am ong their 180 cases; and BAKER
&
KRA USE2
reported
81.7
percent
am ong
317
carcinom as.
Such predom inance
of quite early clinical
stages is invariably
accom panied
by high overall survival
rates at 5 years, regardless
of the therapeutic
m ode. Thus,
following
surgical
treatm ent,
survival
was >90 percent
for BAKER
&KRAUSE;2
94.2 percent
for M OHS
&SNOW ;45 and 85 percent
for ZURRIDA
et al.65 TAN62
reported 87.1 percent of overa1l5-year
survival for patients
treated with radiotherapy.
For larger lesions (T3 and T4),
there
was an im pairm ent
in the 5-year
survi val; 71.4
percent for T3, and 50 percent for T4.2 In our series, only
the patients with Tl and T2 tum ors survived 5 years (68.3
percent SE: 10.8, and 75.1 percent SE: 8.3, respectively).
All patients
with T3 and T4 tum ors
died before the
5-year period. The literature seem s to indicate that advanced
or recurrent tum ors and/or positive cervical lym ph nodes
can be m ore effectively
m anaged
by surgical treatm ent.
Advantages,
such as better
assessm ent
of the prim ary
tum or, better and faster healing,
and absence
of local
radiotherapic
com plications,
are cited by BAILEY'
The
author advocates
radiotherapy
only for elderly patients
with sm all,
localized
lesions.
The ulcerous
tum or lesion was the m ost frequently
described. 13.33.35
The sam e occurred
in our series, with no
statistical significance
as to survival rate variation.
According
to the
literature,
the
lym ph
node
involvem ent
at
initial
consultation
was
quite
infrequent.25.49 In our series, this was 34.1 percent,
with
statistical
tests
showing
significant
difference
of
survi val rates of NO and N+ categories.
The presence
or absence
of cervical
m etastases
at
initial consultation
is a relevant factor for the choice of
therapeutic
m ode.
On the basis
of his 2,696
cases,
M AHONEy37
noted
an im portant
decline
in overall
survi val at 5 years
when
com paring
patients
without
m etastasis with patients with positive neck m etastasis (from
97.8 percent to 37.4 percent,
respectively).
HELLER
&SHAH26 detected prim ary m etastases in 10 percent of their
cases, which led them not to indicate the prophylatic
neck
dissection. However, with an overa1l5-year
survival of70
percent,
the authors
recom m ended
the
therapeutic
radical
neck
dissection,
following
a suprahyoid
dissection
which
had
detected
the
presence
of
m etastasis.
The sam e
recom m endation
was m ade
by
others.1.39,64 It m ust be stressed
that PETROVICH
et
al.48 found lym ph node m etastases
in only 5 percent
of
patients
with T I and T2 lesions,
whereas
67 percent
of
T3 and T4 cases
had m etastasized.
EGGERT
et al.
1 xalso reported
a 5-year
survi val of 64.7 percent
am ong
patients
treated
with
elective
neck
dissection,40
as
opposed
to only
10 percent
for patients
subm itted
to
therapeutic
neck dissection.
The significant difference
in the survival of the four
treatm ent groups in our series should not be overestim ated,
as the
present
study
was
not
designed
to analyze
therapeutic form s. Nevertheless,
such difference does help
to reinforce the likelihood of a fatal evolution
of advanced
lip cancer.51
Local or cervical recurrence
is undoubtedly
a factor
of poorer prognosis. DARGENT
et al.16 reported a 5-year
survi val of 60 percent for patients treated for the first ti m e,
and 32 percent
for those treated
for recurrence.
In our
series, neoplastic recurrence
was detected
in 24.1 percent
(14 patients),
with
neck
recurrence
in 7 cases
(12.0
percent). The m ortality rate of recurring patients was 85.7
percent (12 patients), and the 5-year survival rate was 15.3
percent (2 patients).
The purpose of the present study was the analysis of
the factors related to the tum ors in 58 patients.
Although
BRODERS7
and
FRIERSON
&COOPER22
have
encountered
significant
differences
in the prognosis
of
patients with Grade 3 and 4 tum ors, such differences
were
not found in our study. The vascular
invasion
cited by
LUND et al.,36 the nerve invasion described
by BYERS et
al.," in addition to others,42.53all with m arked
influences
on patients'
evolution,
showed no statistical
difference
in
our series, either.
The
peritum oral
Iym phoplasm ocytic
cellular
response, stressed by LUND et al.56 through their tum oral
scores, and by SYRJANEN
et al.,6) who reported that such
scores
correlated
directly
with
the survival
rates
and
inversely
with
the
frequency
of
m etastases,
was
investigated
in our
hi stologic
analysi s. Ou r resul ts
confirm ed
the constant
presence
of lym phocytes
and
plasm ocytes
(100 percent of cases); however, this was not
statistically
significant.
S A N T O S , L . R . M . ; C E R N E A , C . R . ; K O W A L S K I , L . P . e t a l. • S q u a m o u s - c e ll c a r c in o m a o f t h e lo w e r lip : A r e t r o s p e c t iv e s t u d y o f 5 8 p a t ie n t s
M u sc u la r in v a sio n is d e sc rib e d a s q u ite fre q u e n t,
o w in g to th e su p e rfic ia lity o f th e o rb ic u la r m u sc le . In v a sio n
w a s re p o rte d a s p re se n t in 8 4 p e rc e n t o f th e le sio n s
o p e ra te d o n b y M E H R E G A N & R O E N IG K 4 1 . D e sp ite
b e in g p re se n t in 6 7 .2 p e rc e n t o f th e c a se s in o u r se rie s,
m u sc u la r in v a sio n h a d n o p ro g n o stic sig n ific a n c e .
T h e m a x im a l tu m o r th ic k n e ss a n a ly z e d b y
F R IE R S O N & C O O P E R 2 2 a n d b y M E H R E G A N &
R O E N IG K 4 1 w a s e v e n m o re p ro m in e n t in o u r stu d y . T h e
fo rm e r d e sc rib e d th e m in im a l th ic k n e ss o f 6 m m to b e
sta tistic a .Ily sig n ific a n t in te rm s o f p ro g n o sis, w h e re a s th e
la tte r d e sc rib e d th e v a ria tio n in te rv a l o f 0 .3 3 m m to 2 .4 4
m m e n c o u n te re d in .o p e ra te d p a tie n ts, w ith o u t re la tin g
th ic k n e ss to p ro g n o sis. A fte r ta b u la tin g o u r d a ta , w e
o b ta in e d th e v a lu e o f 8 m m , a b o v e w h ic h su rv iv a l is le ss
lik e ly (F ig . 3 ).
T h e ly m p h n o d e in v o lv e m e n t b y th e n e o p la sm w a s
in c lu d e d a s a p ro g n o sis-p re d ic tin g fa c to r b y N O O N E e t a I.4 7
In th e p re se n t se rie s, o v e ra ll su rv iv a l c u rv e s fo r ly m p h n o d e
in v o lv e m e n t sh o w e d sig n ific a n t v a lu e s, e v e n w h e n th e g ro u p
o f p a tie n ts n o t su b m itte d to n e c k d isse c tio n w a s in c lu d e d
(F ig . 5 ). T h e o v e ra llS -y e a r su rv iv a l fo r p a tie n ts w ith p o sitiv e
ly m p h n o d e s w a s 3 4 .3 p e rc e n t. (S E : 1 9 .5 ) fo r I to 4 ly m p h n o d e s, a n d 4 0 .0 p e rc e n t (S E : 2 1 .9 ) fo r 5 to 5 5 ly m p h n o d e s,
a s o p p o se d to 6 6 .7 p e rc e n t (S E : 1 9 .2 ) fo r th o se w ith n o
in v o lv e d ly m p h n o d e s. T h e Iy m p h o n o d e c h a in s m o re
fre q u e n tly in v o lv e d w e re th o se o f le v e ls I,ll a n d IlIo n th e
tu m o r sid e . D isse m in a tio n to o th e r le v e ls is fa r le ss c o m m o n ,
a s d e m o n stra te d b y S H A H e t a I.5 5 in 1 9 9 0 .
N O O N E e t a l.4 7 a lso d e sc rib ~ d th e p re se n c e o f
e x tra c a p su la r sp re a d a s a n im p o rta n t fa c to r o f p o o re r
p ro g n o sis. S A C K & F O R D 5 2 re p o rte d a 3 -y e a r su rv iv a l
ra te a s lo w a s 1 8 p e rc e n t a m o n g p a tie n ts w ith e x tra c a p su la r
in v a sio n . O u r c a se a n a ly sis sh o w e d th e o c c u rre n c e o f
c a p su la r ru p tu re in 1 3 .8 p e rc e n t o f c a se s (8 p a tie n ts), w ith
a 5 -y e a r su rv iv a l sim ila r to th a t fo u n d in p a tie n ts w ith n o
c a p su la r ru p tu re .
T h u s, th e fa c to rs w ith a n a c tu a l p ro g n o stic v a lu e
e n c o u n te re d in th e p re se n t stu d y w e re : tu m o r siz e , m a x im a l
tu m o r th ic k n e ss, a n d h isto lo g ic a lly -p ro v e n ly m p h n o d e
in v o lv e m e n t. F a c to rs su c h a s N , o f th e T N M c lin ic a l sta g e ,
a n d th e ty p e o f tre a tm e n t in stitu te d , m a y b e a tta c h e d g re a te r
sig n ific a n c e in la rg e r se rie s a n d p ro sp e c tiv e stu d ie s. W e
m u st stre ss th a t n o p ro sp e c tiv e ra n d o m iz e d stu d y h a s b e e n
fo u n d in th e lite ra tu re c o n su lte d . T h e re fo re , th e
in fo rm a tio n c o n ta in e d h e re in m a y c o n trib u te to tre a tm e n t
w h e n d e a lin g w ith b o rd e rlin e c a se s.
T h e a n a to m o p a th o lo g ic a l stu d ie s m e n tio n e d m u st b e
c o n sid e re d a s m ic ro sc o p ic h e lp fo r c lin ic a l T N M
c la ssific a tio n in th e c h o ic e o f m o re e ffe c tiv e tre a tm e n t.
A n e v e r-in c re a sin g n u m b e r o f stu d ie s h a v e trie d to a n a ly z e
p ro g n o stic fa c to rs fo r tu m o rs in se v e ra l site s.
L o w e r lip c a n c e r is a n e a sily d ia g n o se d tu m o r w h ic h
g e n e ra lly strik e s lig h t-sk in n e d m a le s in th e ir 6 0 's o r 7 0 's,
p a rtic u la rly th o se w h o a re sm o k e rs a n d h a v e b e e n
e x c e ssiv e ly e x p o se d to th e su n . T u m o rs le ss th a n 4 c m w ith
n o su sp e c te d ly m p h n o d e in v o lv e m e n t c a n b e su c c e ssfu lly
tre a te d b y re se c tio n a n d su rg ic a l re c o n stru c tio n , w ith c u re s
b e in g o b ta in e d in 9 0 p e rc e n t o f c a se s.
A m in im u m fo llo w -u p o f 5 y e a rs w o u ld b e
d e sira b le , w ith a p p o in tm e n ts e v e ry 3 o r 6 ' m o n th s. F o r
p a tie n ts w ith tu m o rs > 4 c m , o r fo r th o se w ith su sp e c te d
c e rv ic a l ly m p h n o d e s, re se c tio n in u st b e c o m b in e d w ith
m o d ifie d n e c k d isse c tio n . S u c h d isse c tio n sh o u ld b e
ip sila te ra l fo r tu m o rs p re d o m in a n t o n o n e sid e , a n d
b ila te ra l fo r m e d ia n tu m o rs.3 0
R e c u rre n t tu m o rs, w h e th e r o n th e lip o r n e c k , sh o u ld
b e tre a te d m o re a g g re ssiv e ly , w ith w id e r re se c tio n s a n d
m o d ifie d6 o r ra d ic a l 1 4n e c k d isse c tio n s. R a d io th e ra p y m a y
b e u se d a s c o m b in e d p o sto p e ra tiv e tre a tm e n t.
RESUMO
E n tr e o s p a c ie n te s p o r ta d o r e s d e c a r c in o m a e s p in o c e lu la r d o la b io in fe r io r , a te n d id o s n o p e r fo d o d e ja n e ir o d e 1 9 8 0 a d e z e m b r o d e 1 9 8 9 , n o H o s p ita l d a s C lfn ic a s d a F a c u ld a d e d e M e d ic in a d a U n iv e r s id a d e d e S a o P a u lo . a n a lis a m o s . r e tr o s p e c tiv a m e n te . 5 8 p r o n tu a r io s . a le m d o s d a d o s d e m o g r a fic o s , a s in fo r m a g 6 e s r e la tiv a s a o s p a c ie n te s fo r a m c o m p le ta d a s c o m a n o ta < ;6 e s s o b r e0u s o d e a lc o o l, fu m o e e x p o s ig a o s o la r . 0 e s ta d io c 1 fn ic o n a e p o c a d a c ir u r g ia , b e m c o m o a s c a r a c te r is tic a s m a c r o s c 6 p ic a s
d o s tu m o r e s , 0 tip o d e tr a ta m e n to in s titu fd o e a s o b s e r v a g 6 e s d o s e g u im e n to p 6 s - o p e r a t6 r io ta m b e m fo r a m a n o ta d o s . F o i,
e n ta o , r e a liz a d a u m a m in u c io s a r e v is a o a n a to m o p a to l6 g ic a d o s e s p e c im e s c ir u r g ic o s . a n a lis a n d o 0 g r a u d e d ife r e n c ia c ;:a o h is to l6 g ic a , e s p e s s u r a , m a x im a tu m o r a l, e la s to s e s o la r , in v a s a o p e r in e u r a l, in v a s a o v a s c u la r . in v a s a o m u s c u la r . m a r g e n s c ir u r g ic a s , in filtr a d o in fla m a t6 r io p e r itu m o r a l e a c o m e tim e n to g a n g lio n a r , c o m o u s e m r o tu r a c a p s u la r . a a n a lis e d a s o b r e v id a
g lo b a l a 5 a n o s d e m o n s tr o u d ife r e n g a s e s ta tis tic a m e n te s ig n ific a tiv a s p a r a a s v a r ia y ie s espessura tumoral, tamanho do tumor
(T)eacometimento ganglionar.
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