'CHAPTEE 11 SaItpary Gland Pathology
Fortunately, a relatively low percentage of parotid tumors
Tables 11-2 and 11-3 summarize four large series of
prlmary epithelial salivary gland tumors, analyzed by
rites of occurrence and frequency of malignancy, respec-
t~vely.Some variations between studies may represent
differences in diagnostic criteria, geographic differences,
orreferral btas in thecases seen. (Sbmecenters may tend
to see more malignant tumors on referral from other
sources.)
The most common site for salivary gland tumors is the
parotid gland, accounting for 64% to 80% of all cases.
are malignant, ranging from 15% to 3.2%. Overall, if can
bestated that two thirds to three quarters of all salivary
tumors occur in the parotid, and two thirds to three quar-
ters of these parotid tumors are benign,
Table 11-4 summarizes five large, well-known series
of parotid neoplasms. Thepleomorphfcadenomaisover-
whelmingly the most common tumor (33% to 77% of all
cases in the parotidgIand). Warthin tumorsare also fairly
common; they account for 6% to 14% of cases. Avariety
of malignant tumors occur, with the mucoepidermoid
carcinoma appearing to be the most frequent overall.
However, two studies from Great Britain show a signifl-
cantly lower prevalence of this tumor, possibly indtca-
tive of a geographic difference, especially compared with
reports of cases from the United States.
Frnm 1
lranging
frc
Bcomprising
no more than 1 % of all salivary neoplasms. However,
70% to 90% of sublingual tumors are malignant.
Tumors of the various smaller minor salivary glands
make up 9% to 23% of all tumors, which makes this
group the second most common site for salivary neo-
plasia, Table I1 -6 summarizes the findings of three Igge
surveys of minor gland tumors. Unfortunately, a rela-
tively high proporti~n(almost 50%) of these have been
malignant in most studies. Excluding rare sublingual
tumors, it can be stared that the smaller the gland, the
greater the likelihood of malignancy fot a salivary gland
tumor.
As observed in the major glands, thepleornorphic ade-
noma 1s the most common minor gland tumor and
accounts for about 40% of all cases. The mucoepider-
moid carcinoma and adenoid cystic carcinoma generally
have been considered the two most common malignan-
cies, although the recently delineated polymorphous
low-grade adenocarcinoma also is becoming recognized
as one of the more common minor gland tumors.
The palate is the most frequent site for minor salivary
gland rumors, with 42% to 54% of all cases found there
(Table 11-7). Most of these occur on the posterior lateral
hard or soft palate, which have the greatest concentration
ofglands. Table 11 -8 shows the relative prevalenceof var-
ious tumors on the palate. The lips are the second most
1v
408 O R A M MA"W,FACIAL PATHOW

E & %fig&
~f.-. ,. af O c ~ ~ e b ofPriglary
ce L&Sthelial salivary Gland m d r s

(includes all "other

rnonomorphic adenornas")
410
common location for minorgland tumors (21 P/b to 22% of
cases], followed by the buccal murosa (11 % to 15% of
cases). Labial tumors are significantty more common in
the upper lip, which accountg for 77% to 89% of all lip
tumors (Table 11-91. Although mucoeeles are commonly
found on the lower lip, this is a surprisingly rare site for
salivary gland tumors.
Significant differences in the percentage of malignan-
cies and She relative frequency of various tumors can be
noted for different minor salivarygland sites. AS shown in
Table 11-10, 42% to 50% of tumors of the palate and
buccal mucosa sites are malignant, similar to the overall
prevalence of malignancy in all minor salivary gland sites
combined. In the upper l~p,however, only 14% to 25% of
tumors are mal~gnantbecause of the high prevalence of
ORAL % MAXILLOFACIAL F'ATHOUIQ,
m
the canalicular adenoma, which has a special affni
this locanon. In contran, although lower lip tuma
uncommon, 50% to86% aremalignant (mostly
dermoid carcinomas). Up to 91 % of retromolar t
malignanr, also because of a predominance of muc
dermoid carcinomas. Unfortunately, most tumors in
floor of the mouth and tongue are also malignant
PLEOMORPHICADENOMA (BENIGN
MIXED TUMOR)
The pleomorphic adenoma, or benign mixed tu
easily the most common salivary neoplasm. Ita
tor 53%6 to 77% of parotid tumors, 44%to 68%
mandibular tumors, and 38% to 43% of mrnm g
tumors.
 CHNPTER II * Sa7Ivm.v Gfand Pathology
-
.
'Iwmorph'i adsnoma. Slowly gmdhgtuh~ot
of
the p a d ~ gland
d
Pleamorphic adenomas aFe derived f ~ o ma mixture of
ductal and myaepithelial elemen&. A remitrkable micro-
seopic diversly can exist fFom one tumor 'to the next, a s
well as in different areas of the same mmor. The terms
pleomorphic adenoma and mixed tumor both represent
attempts to describe this tumor" unusual histopatho-
loglc features, but neither term is entirely accurate.
Although the basictumor pattern is highly variable, rarely
are the individual cells actually pleomorphla. (However,
focal minor atypia is acceptable.) Likewise, although che
tumor often has a prominent mesenchyme-appearing
Ystromal"compopent, it is not truly a mixed neoplasm
that is derived from more than one germ layer.
clinical and Radiographic Features
Regardless of the site of origin, thepleomorphicadenoma
' typically appears as a painless, slowly growing, firm
mass (Figures 11-33 and 11-34). The patient may be
aware of the lesion for many months or years before
seekinga dfagnosfs. The tumor can occur at any age but
IS most common in young adults between the ages of 30
and 50. There is a slight female predilection.
Most pleomorphic adenomas of the parotid gland
occur in the supedfcial lobe and present a s a swelling
overlying the mandibular ramus in front of the ear. Facial
nerve palsy and pain are rare. initially; thetumor is mov-
411
able bar becomes less mobile a s it gmv& larger. If ne-
glected, the lesion can grow to grotesque propdrtions.
G o u t 10% of paratid mixed tumors develop within the
deep lobe of the gland beneath the facial nerve rF1gure
ii-ssl. sometimes these lesions grow in a medial direc-
tion between the ascending ramus and stylomandlbular
ligament, resulting in a dumbbell-shaped tumor that
appears as a mass of the lateral pharyngeal wall or soft
palate.
The palate is the most common site for minor gland
mixed tumors, accounting for approximately 60% of
inrraoral examples. This is followed by the upper lip
(20%) and buceal mucosa [lo%). Palatal tumars almost
always are found on the posterior lateral aspect of the
palate, presenting a s smooth-surfaced, dome-shaped
masses (Figures 11-36 and 11-37). If the tumor is trau-
matized, secondary ulceration may occur. Beeauseof the
tightly bound nature of the hard palate mucosa, tumors
in this location are not movable, although rhose in the
lip or buccal mucosa frequently are mobile.
Histopamdopic Features
The pleomorphic adenoma is typically a well-circum-
scribed, encapsulated tumor (Figure 11-38]. However,
the capsule may be incomplete or show infiltration by
s of complete encapsulation is more
tumor cells. T h ~ lack
 r t y r e I I -5s rleomorpnlc aaenoma. I I -welgntea, tat-sup-
pressed, contrast-enhanced coronal magnetic resonance image
(MRI) of a tumor of the deep lobe of the parotid gland. (Cour-
tesy of Dr. JoelCur&)

1 .6YI= .,.*, .
mandibular area.
r.NIIIVIJ.IIIC .YCIIYIII.. lYlllYl pterygo-

=.
common for minor gland tumors, especially along the cells are rounded and demonstrate an eccentric nucle

= lial surface.

ithe mesenchyme-like component is highly variab

gmong different tumors. Some tumors may
almost entirely of background "stroma." 0th
-
lhighly cellular with little background alteration.

ductal elements. Such tumors often are called myo-
epltheliomas, although they probably represent one end
of the spectrum of mixed tumors.
matment and Prognosis
Pleomorphic adenomas are best treated by surgical
excision. For lesions in the superfic~allobe of the
parotid gland, superficial parotidectomy with identifi-
cation and preservation of the facial nerve is recom-
mended. Local enucleation should be avoided because
the entlre tumor may not be removed or the capsule
may be violated, resulting in seeding of the tumor bed.
For tumors of the deep lobe of the parotid, total
parotidectomy is usually necessary, also with preser-
vation of the facial nerve, if possible. Submandibular
tumors are best treated by total removal of the gland
-
Figmll-4. - ~ctalstructures (lep)
with arsociated myxoma&us background (nght).
Figure 11-42 r Pleomorphicadenoma. Many of the ducts and
rnyoepithelial cells are surrounded by a hyalin~zed,eosinophilic
background alteration.
with the tumor. Tumors of the hard palate usually are
excised down to periosteum, including the overlying
mucosa. I n other oral sites, the lesion often enucleates
eas~lythrough the incision site.
With adequate surgery, the prognosis is excellent,
with a cure rate of more than 95%. The risk of recur-
rence appears to be lower for tumors of the minor glands.
Conservative enucleation of parotid tumors often results
in recurrence, with management of thesecases madedif-
f~cultas a result of multifocal seeding of the primary
tumor bed. In such cases, multiple recurrences are not
unusual. Malignant degeneration is a potential compli-
cation, resulting in a carcinoma ex pleomorphic ade-
noma (see page 424). The riskof malignant transforma-
tion is probably small, but it may occur in as many as
5% of all cases.
t
414

ONCOCYTOMR (CWPHILCC ADENOMA)

rheancoytamais a Bmi@saliva~@gland ?tumorrom-
ORAL & MAXILI.OFXCIAL PATHOLOGY

I
p ~ of & large epkhelial. EeZIs:kiro@.@ okcoqytes. I t is:
rare neopiasm, represehting approximately 1 % of al
salivary tumors.
Clinical Featam6
The oneocptoma is predominantly a tumor of older
adults, with a peak prevaknce in the eighth decade of
life. A slight female predilmlon has been observed but
may not be signiflcaat. Oncocymmas oeeus prlmasily in
tha major s a l i i t y giaads, espmfally the parotid gland,
whichaccounts forabeut &5% to 90% ofall cases. On@-
cytvmas df the minor ~alivaryglands are exceedingly
rare.
The tumor appears as a firm, slowly growing, pain-
less mass that rarely exceeds 4 cm in diameter. Parotid
oncocytomas usually are found in the superficial lobe
and are clinically indistinguishable from other benign of total removal of the gland, Oneocytomas of the o
tumors. On occasion, bilateral tumors, can occur, minor salivary glands should be removed with a sm@
although these may represent examples of mufrinodular
oncoytte hypefpla,qta iaoneocytosis).
Histopathologic Features
The oncocytoma is usually a well-circumscribed t m o r
that is composed of sheets of large polyhedral cells
(oncocytes), with abundant granular, eosinophilic cyto-
plasm (Figure 11-43]. Sometimes these cells form an
alveolar or glandular pattern. The cells have centrally
located nuclei that can vary from small and hypmhro- ONCOCYTOSIS~NODULARONCOCYTIC
matte to l a w and vesicular. Llttle stroma is present, HYPERPWIA)
'
~6d@~1lt\tfF3 bma of EM^ fibpovas~uktsepta+An ass@- Oncocytic metaplasia is the transformation o
ciared ~ ~ h + r cIMLWate m* ;be nloted. adnar cells to oncowtes. Such cells are
The @&rlM&df' the dQis ewted by an over-
abuiitdehueof mitocbondria, which can be demonstrated
by electron microscopy. Thesegranules also can be iden-
tified on light microscopic examination with a phospho-
tungstic acid-hematoxylin IPTAH) stain. The cells also both the proliferation and accumulation of onco
contain glycogen, as evidenced by their positive staining within salivary gland tissue. It may mimic a tumor,
with the periodicacid-Schiff (PAS) technique but by neg- clinically and microscopically, but it also is consid
ative PAS staining after digestion with diastase. to be a metaplastic process rather than a neoplastic
Qncocytomas may contain variable numbers of cells
with a clear cytoplasm. in rare instances, these clear cells Clinical Features
may compose most of the lesion and create difficulty in
distinguishing the tumor from other clear cell salivary
gland tumors that have a low-grade malignant potential.
Treatment and Prognosis
ancocytomas are best treated by surg~calexcision. in the
parotid gland, this usually entails partial parotidectomy
Uobectomy) to avoidv~olationof the tumor capsule. The
facial nerve should be presewed whenever possible. For most frequently in older adults.
 o k o q k s (BISPWJ in $e parotid gland.

WA~TMIMT U M ~~
~APIMRY=
;
. , ,
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n!Lx,,-r~.
g$**,irumaa ~ ~ ~ @ i ~ & o , @ J : & ~a'mi$gt
~~~'t:t~ul;s
w&&j&y i n t ~ w I p & & e n & . ~ ~& fv~ mw&
~ jess:
efim~m:&n &e g k m ~ g p b &.admi& f$ ~r@pmm&i
tbi &-,: fngg$ ,g@Qm& &$nq+ p~fi@ al
WWO,f,;
a@@@&&:@r@@- I @ $ ,pa~@334ppbpI461~%~
T@e
~~~&,~~&~~&~~~~&&~~$~~$.:b@p.~~~%@~h$~@rna?,,
,*k* -
~ ,,..,c-. +&;,&&$$J&
' - :m'f&b~&&@&;
& fc &@eQ@q-
&s.$&i1p$h0$d::mmpne~m~:may;gk~.Eheemietrikn
tqWz&&
~- . ~ G ~. &*&a'1g&m&a,q$xw,&~p@~ma.
~ ~~. ~ & @ ~ ~ & @ @ g aEsemimattid
,,T~F..... ~ ~ @ mTke:tm
@s
@~i&a';ws$
mm$..@f&eY &pv begre-
..
fc@i$&&$&& x;i-&gp f
6mI&%gMnp@;rQgdJmplj
nodes.. :Hbwevefi,it SLSO: has heei~=su@sfd that €hi*
tum~ra:mey"develo~~om ~prollfm&rfmoSsaliiryglamd
$ u a : l ,epl~&qm;.tha,plsakociated with secendsry fbr-
mati& if l$np:b@idt@sue.~eveialrq?enrpapers have sup-
p~~~~fl~~f$l~@&p~~e~~;jngI~~~ng~@udi~thac W e found
c~nto$en&~..ab~no&ma~~fq:i&Yhe epithem ~%3~p,m&O. A
numberof studies haw dewnstz~teda &ang-wsa@ta-
eon between.the demlnpmentftb~stumorand smokkng.
s q o w h a y e an &&&$!d perrisk!$~r Warthiti kumgr
thm ;q&;mn~tnokefs, ,E.pstein+.rrr vtm also h a s been
impI'ie.d in t&xpaFhogenM$ df Warthin rumor.
FL& -45 Warthii tumor. Mass in the tar1 ofthe parotid
gland. [Courtesy of DI.George Biozis.)
The N A i h W ~ Q usually
T appears as a slowly growing,
paintem, nodular mass d the parotid gland (F~gure
11-4%. 1t may lie f i m or fluctuant tmpalpafmn. The tumor
mest f~equentlyoocws in the tail of the patotid near the of these bilateral tumors do not oceur simultaneously but
angle of the mandible, and it may be noted for many are metachronous (oc~urringat different times).
months before the,patient seeks a diagnash. One unique In rare instances, the Warthin tumor hasbeen reported
fearure i$the tendeney of Wafihin tumor ro occur bilat- within the submandibular gland or minor salivary glands.
erally, whieh has been noted in 5 % to 14% of cases. Most However, because the lymphoid component is often bess
pronoun& in rhese m p a r o t t d sires* the pathalogist
should esetcise caution to SVwLd o%rdiagpbs?$ of a lesion
better classified a s a paplnary! cy6faden~rn.aor salivary
duct cyst with oncocyric ductal meapJasia.
Warthin tumor most often ocrmrs in oIder adwlts, with
a peak prevalence in rhe sixth and aevenrh decades of
life. The observed frequency& this turner is much lower
in blacks than in whlres. Most studies s h m a decided
male predilection, with some early studies demon-
strating a male-to-female ratio up to I0 to 1. However,
more recent investigations show a more balanced se-x
ratio. Because warthin tumors have been associated
with cigarette smoking, thts changing sex ratio may be a
reflection of fhe increased prevalence of smoking in
females over the past few decades. This association with Figure 11-46 Warthin tumor. Low-power view showirga papil-
smoking also may help explain the frequent bilaterality lary cystic tumor with a lymphoid *ma.
of the tumor, because any tumorigeniceffects of smoking
might be manifested in both parotids.

HistoQathologic Features
The \Naithfn t".&qr hasone 6f.the most distifiqtivehisto-
pathologic patterns. of any tumor in the body. Although
the term papillary cystadenama lymphomatosum is
cumbersome, it accurately describes the safient micro-
scopic features.
The tumor is composed of a mixture of ductal epithe-
lium and a lymphoid stroma (Figures 11-46 and 11-47),
The epithelium is oncocytic in nature, forming uniform
rows of ceUs surrounding cystic spaces, The cells have
abundant, finely granular eosinophilic cytoplasm and
,areairawed i n d m olayers. The inner lumfnal l a p con-
@f&i.!l,'- ~-~~ &
s!sYs,..;?.: ,~~.t l i r 9eIl.s
r with centrally pla@A1pal-
i q ~ ~ d 5 ~ , ~ ~ g I ~ : p & ; ~ r & r @ m Wneath ~ d d @ qthis
dei.
is a.s&~@,l&$&f ~~-f&&@~a~i;fi$ ~ @ j @ pce[l$wth
~~l more
~ s i c u l wnudei. Thg linine spithelkn demonstrates
multipkpapilla~rryidoldingsthat pxotrude-hto the cystic ondary tumor sites. Malignant Warthin tumors (c
spares; Focal areas of squarnous metaplasfa o i mucous noma ex papillaty cystadenoma lymphomatosum)
cell prosoplasia may be seen. The epithelium is sup- been reported but are exceedingly rare.
ported by a lymphoid stroma that fwquenily showsger-
minal center formation. MONOMORPHlC ADENOMA
The term monomorphic adenoma was originally used
Treatment and Pragnosis describe a group of benign salivary gland tumors dem
Surgical removal is the treatment of choice for patients strating a more uniform histopathologic pattern than
with Warthin tumor. The procedure usually is easily
accomplished because of the superficial location of the schemes, a variety of tumors were included wn
tumor. Some surgeons prefer local resection with min- broad heading of monomorphic adenoma, in
imal surrounding tissue; others opt for superficial Warthin tumor, oncocytoma, basal cell adenoma,
parotidecromy to avoid violating the tumor capsule and
because a tentative diagnosis may not be known preop-
eratively. A 6% to 12% recurrence rate has been reported.
Many authors, however, believe that the tumor is fre- nature, the term rnonomorphicadenoma proba
quevtly multicentric in nature; therefore, it is difficult to be avoided, and each of the tumors mentioned
determine whether these are true recurrences or sec- referred to by its more specific name.
CHAPTER 11 Salivary ClUnd Pathology 417

CANALKUIAR ADENOMA
The canalicular adenoma is an uncommon tumor that
occurs almost exclusively in the minor salivary glands.
Because of its uniform microscopic pattern, the canalic-
ular adenoma also has been called a "monomorphic ade-
noma." However, because this term also has been
applied to othertumors, its use probably should be dis-
continued. Likewise, the term basal cell adenoma some-
times has been used synonymously for this tumor but
should be avoided because it refers to a separate tumor
with different clinical features (see next topic).

Clinical Features
The canalicular adenoma shows a striking predilection
for the upper lip, with nearly 75% occurring in this loca- 'gum 11-48 Canalicular adenoma. Mass in the upper lip
(Courtesy of Dr. John Fantasia.)
tion. It represents the first or second most common
tumor [along with pleomorphic adenama) of the upper
lip. The buccal mucosa is the second most common
site. Occurrence in other minor salivary glands is
uncommon, and canalicular adenomas of the parotid
gland are rare.
The tumor nearly always occurs in older adults, with
a peak prevalence in the seventh decade of life. There is
a definite female predominance, ranging from 1.2 to 1 .%
females for each male.
The canalicular adenoma appears as a slowly
growing, painless mass that usually ranges from several
millimeters to 2 cm (Figure 11-48), It may be firm or
somewhat fluctuant to palpation. The overlying mucosa
may be normal in color or bluish and can be mistaken
for a mucocele. However, mucoceles of the upper lip are
rare. in some instances, the lesion has been noted to be F ~ r 1e1-49 r Canalicular adenoma. Uniform columnar cells
multifocal, with multiple separate tumors discovered in forming canai-like ductal structures.
the upper lip or buccal mucosa.

HistopathologicFeatures Treatment and Prognosis

The microscopic pattern of canalicular adenoma is
monomorphic in nature. This pattern is characterized by
single-layered cords of columnar or cuboidal epithelial
cells with deeply basophilic nuclei (F~gure11-49), Tn
some areas, adjacent parallel rows of cells may be seen,
resulting i n a bilayered appearance of the tumor cords.
These cells enclose ductal structures, sometimes in the
form of long canals. Larger cystic spaces often are cre-
ated, and the epithelium may demonstrate papillary pro-
jectlons into the cystic lumina. The tumor cells are sup-
ported by a loose connective tissue stroma with
prominent vascularity. Unlike the appearance in pleo-
morph~cadenomas, stromal alterations, such as chon-
droid metaplasia, do not occur. A thin, fibrous capsule
often surrounds the tumor, although incipient foci of
additional tumors sometimes are observed in the sur-
rounding salivary gland tissue.
The canalicular adenoma i s best treated by local surgical
excision. Recurrence is uncommon and actually may rep-
resent cases that are multifocal in nature.
BASAL CELL ADENOMA
The basal cell adenoma is a benign salivary tumor that
derives its name from the basaloid appearance of the
tumor cells. It is an uncommon neoplasm that represents
only 1 % to 2% of all salivary tumors. Because of its uni-
form histopathologic appearance, it often has been clas-
sified as one of the monomorphic adenomas. However,
as mentioned previously, this term probably should be
avoided because of its imprecise and frequently con-
fusingdefin~tion.Also, ultrastructural and immunohisto-
chemical studies have shown that basal cell adenomas
are not necessarily composed of only one cell type but
sometimes of a combination of salivary ductal epithe-
 lium :@rd :g)rceDfehelrd-E@Ge: The basal eeR %denoma
&w~:$6~&hist@pash.q~@~~@ sl'i-ika.tity.mtC?th~canalieular
zl.&efiQ,m&jn the ~ a $ & ; , : t &&&sS ~~& h,aqe
$ ~bzem
~ used
lial cells, The mierosco,pi~app
wf a dermal cylindtnma, one of the Skin rufnors ~i
which it is often &@o@[atgd
~~~

. q m n y m d l p f ~ o m e whtstqpatho\o@e
~ and. iclin@d
di!f&rences.ean be:nore& that warranb:thSrtthey Re: eon- Ttea?ment and'mogoosis
side~eda$!dis@a::eatitie$. .

-- Ctlinrcal .wh€s
.- - Unlikei~e~malis~laradenonra, thebasal erill ad6noma
is p~hnar'lya tumor of &e pamtFd gland, ~ i i *round h 37-76rfixlrrence rate,, ~ P S
~ ~

(heleeHcUye?@rr,;the.m i o r
75% ,of all' cases o r r m r i ~ g nairre.
glands repm.mn%tee'seqond-mos~ c6y:hfoi~sire,specifi- Themalignant counte
c#lI$ t&E~l@&
.~ @Ute .~f@per.Si@ andbuG,ca1ihucosa. The is the basal cell adeno
Pumo,r .- :#c-aut ax^. w~ age but is mwst .common in nocareinomas arBe 'de Wovo, but Some tixamples
rntddlie-a&and otde~~dults,w i t h peak prevalence In from malighant dcgen
theseventh.decade~ofIffaThe.tumor~appeaisto be more adenoma. Fortunately, rhese tumors have
common in females,,with some stud@sshowing as high good prognosis; although local recurrence is mmmo
as ':cjZ:n .fegale-m-.fial@:kafla- the tumor rarely metasta.si%sl'orresults:indeafh.
a;lini~aIl~,~:t~~~b&~al~r~IIadenorna appcarsas a slowly
&io&i',Me1y m9xabIe mass..similarto. a pleamorphtc~
idenoma.. Mast t m r s areless than 3 cm in diamemr.
aucmt PAPILLOMAS fSl~u~Emk.4~
Paratid tumar~mudl%sr&\ac;?tpdw&hinlI?esuperficial PAPIUIFERUM; INTRADUCTALPAPLUMA;
lobe af the gian&. iNVERTEl3 DUCTAL PAPILLOMA)
One subrype, the membranous basal ~ 8 1 1adenoma A number ofsaNvary gland tumors cwn be,
deserves separate mention. This form of the tumor appears
to be hereditary, often occurring in combination withskin
appendage tumors, such as dermal cylindromas and tri-
choepitheliomas. Multiple bilateral tumor. may develop lvltraau~talpapjlloma, and inverted du
=,
- = ,= within the parotids. Because these tumors often Bear a are 'three.rare saliva
htstopathologic re6ealanCe to the skin tumors, t h q also
ha* j b ~ q I l e dermal
d analogue mmars.
eammon squarnous papilldma(seepage316) ofth
mucosa willarise at thesitewhereami
Tbrrbasa41,cellademma B u s z l l l y e m p l a or well cir-
~mse&ed.Themost~ommon subype isthe solid variant,
which comists of mltlple isbands and cords of epithelial
cells that are supported by a small amount of fibrous
stroma. The peripheral cells af these islands are paltsaded
and c u b o j ~to
l columnar in shape, similar to the micro-
scopic appearance of basal cell carcinoma. These periph-
eral cells are frequently hypercfiromatia; the central cells
of the islands tend to have paler staining nuclei. The cen-
tral cells occasionally form eddies or keratin pearls.
Thetrabecular subtype demonstrates narrow cordlik
eptthelial strands (Figure 11-50). The tubular subtype is
characterized by the formation of small, round, ductlike
structures. mquenrly, a mixture of histopathologic sub-
types is seen.
The membranous basal cell adenoma exhibits mul-
tiple large lobular islands of tumor that are molded
- -
toeether in a ,liesaw ouzzle fashion. These islands are
surrounded by a thick layer of hyaline material, wh~ch

1
represenrs reduplicated basement membrane. Similar ngure 11-50 + ~~~l celladenoma, pamtid tumor shodng
hyaline droplets also are often found among the epithe- cords of basalold cells arranged in a trabecular pattern.
CHRPTER 11 + Salivary Gland Pafhology
papillamas."HaYever, it should be emphasizedthatthese
lesions are viral lhuman papillomavirus [HPVI) surface
papillomas and nor primary salivary gland tumors.
--
- show a pitor indentation in the overlying surface mucosa.
&F-lfs&@$; -
The sialadenoma papilliferum most commonly arises
from the minor salivary glands, especially on the palate,
although it also has been repofied in the parotid gland.
~tusually Is seen in older adults and has a 1.5: I male-
to-female ratio. The tumor appears asan exophyric, pap.
illary surface growth that is clinically similar to the
common squamous papilloma.
The intraductal papilloma is an ill-defined lesion that
often has beenconfusedwwtthothersalivarygland lesions,
such as the papillary cystadenoma. It usually occurs i n
adults and is most common in the minor salivary glands,
where it appears as a submucosal swell~ng.
The inverted ductal papilloma is a rare tumor that has
been described only in the minor salivary glands of adults.
tures in the supefic~ailamina propria.
Figus 11-52. Sialadenoma papillifemin. High-power vlew of
cystic areas l~nedby papillary, oncocytlc epithelium.
419
The lower lip and mandibular vestibule are the most
common locations. The lesion usually appears as an
asymptomaticsubmucosal nodule, which sometimesmay
Hiatopatbobgtc Features
At low power, the sialadenomapapilliferum is somewhat
similar to the squamous papilloma, exhibiting multiple
exophytic papillary projections that are covered by strar-
ifiedsquamous epithelium. Thisepithelium is contiguous
with a proliferation of papillomatous ductal epithelium
found below the surface and extending downward into
the deeper connective tissues (Figure 11-51). Multiple
ductal lumina are formed, which characteristically are
lined by a double-rowed layer of cells consisting of a
luminal layer of tall columnar cells and a basiiar layer of
smaller cuboldal cells (Figure 11-52). These ductal cells
often have an oncocytic appearance. An inflammatory
infiltrate of plasma cells, lymphocytes, and neutrophils 1s
.
characteristtcallv, uresent. Because of their microscooic
similarity, this tumor has bcrn considered to be an aAa-
logue uf thccut~ncoussyringocystadcnoma papilliferum.
The intraductal papilloma exhibits a dilated, unicystic
structure that i s located below the mucosal surface. It is
lined by a single or double row of cuboidal or aolumnar
epithelium, which has multiple arborizing papillary pro-
jections Into the cystic lumen. In contrast, the inverted
ductal papilloma is composed primarily of a proliferaflon
of squamoid epithelium with mult~plethlek, bulbous pap-
~ilaryproiections that fill the ductal lumen (Figure 11-53).
1
Figure 11-53 Inverted ductal papilla. Pap~ilaryintraductal pro-
i~ferattonlocated beneath the mucosal surface. Higher-power view
shows both squamous cells and mucous cells (mset). (Courtesy of
Dr. Dean K Whlte.)
 ORAL 8r MAXILLOQACIAL PATHOLOGY
I

~UnicalFeatures
Most studies show that the rnucoepldemoid earcim'ma.
is the most common malignant salivary gland neo@la$m.
 - -

CHAPTER 11 Gand Pathology

Figure 11-55 Mucoepidermoid carcinoma. Mass of the tongue. Figure 11-56. Mucoepidermoidcarcinoma. Low-power view of
a moderately well-differenhated tumor showing ductal and cystic
spaces surrounded by mucous and squamous cells.

Figure 11-9 Mucoepidennoidcarcinoma. This low-grade Figure 11-58 r Mucoepidermoid carcinoma. High-power view
tumor shows numerous large mucous cells surmund~nga cystic showing a sheet of squamous cells with focal mucus-producing
space cells (left).

demonstrate considerable pleomorphism and mitotic Table 11-11 roepidennoid Carcinoma: Grading
actlvlty. Mucus-producing cells may be infrequent, and a n d Point Values
the tumor somettmes can be d~fficultto distinguish from
squamous cell carcinoma.
Intermediate-grade tumors show features that fall
between those of the low-grade and high-grade neo-
plasms. Cyst formarion occurs but is less prominent
than that observed in low-grade tumors. All three major
cell types are present, but the ~ntermediatecells usu-
ally predominate. Cellular atypia may or may not be
observed.
However, some experts have found that tbe reiat~ve
proportion of the three d~fferentcell types does not cor-
relate with prognosis. Instead, they have identified five
sign~ficantmicroscopic parameters, to which relatlve
HPE High power fields
: point values have been assigned
- to determine the grade

I
of the tumor (Table 11-11). From Auelalr PL, Goode RK, Ellls GL. Mucoep~dermo~d carcinoma of
lntraoral salivary glands Evaluarlon and appllcatlon of gradtng crl-
term in 143 cases. Cancer 69'2021 -2030, 1992

-
F i m 11-Zgu Mucoe~idermoidcarcinoma. Clear cell
mucoepidermoid carcinoma.
Reatment and Progm$is
The treatment of mucoepidermo~dcarcinoma is predi-
cated by the location, histopathologicgrade, and clinical
stage of the tumor. Early-stage tumors of the parorid
often can be treated by subtotal parotidectomy with
preservation of the facial nerve. Advanced tumors may
necessitate total removal of the parotid gland, with sac-
rif~ceof the facial nerve. Submandibular gland tumors are
treated by total removal of the gland, Mucoepidermoid
carc~nomasof the minor glands usually are treated by
assured surg~calexcision. For low-grade neoplasms,
only a modest margin of surround~ngnormal tissue may
need l o be removed, but high-grade or large rumors war-
rant wider resection, s~milarto that required for squa-
mous cell carcinomas. If there is underlying bone
destruction, the involved bone must be excised.
Radical neck dissection is indicated for patients with
clinical evidence of metastatic disease and also may be
considered for patients with larger or h~gh-gradetumors.
Postoperat~veradiation therapy also may be used for
more aggressive tumors.
The prognosis depends on the grade and stage of the
tumor. Patients with low-grade tumors generally have a
good prognosis. For most primary sites, local recurrences
or regional metastases are uncommon, and around 90%
to 95% of patients are cured. The prognosis for those
with intermediate-grade tumors is slightly worse than
that for low-grade tumors. The outlook for patients with
high-grade tumors is guarded, with only 30% to 54% of
patients surviving.
For unknown reasons, submandibular gland tumors
are associated with a poorer outlook than those in the
parotid gland. Mucoepidermoid carcinomas of the oral
minor salivary glands generally have a good prognosis,
probably because they are mostly low- to intermedlate-
grade tumors. However, tumors of the tongue and floor
of the mouth are less predictable and may exhibit more
aggress~vebehav~or.
INTRAOSSEOUS MUCOEPIDERMOID
CARCINOMA (CENTRAL MUCOEPIDERMOIP
CARCINOMA)
On rare occasions, salivary gland tumors arise centr
within the jaws, The most common and best-recogni
intrabony salivary tumor is the intraosseous mueoe
dermoid carcinoma. However, other salivary tum
have been reported to develop within the jaws4includ
adenoid cystic carcinoma, benign and malignant mi
tumors, adenocarcinoma, acinic cell adenocarcino
and monomorphic adenoma.
Several hypotheses have been proposed to explain th
pathogenesis of intraosseoussalivary tumors. One the
suggests thatthey may arise from ectopie salivary gla
tissue that was developmentally entrapped withln
jaws. However, the discovery of ectopic salivary tissue i
uncommon in biopsy specimens from the jawsand, the
fore, thisseemsan unlikely sourceformost intrabonysali
vary tumors. Some maxillary tumors may arise fr
glands of the sinuslining, but this is often difficult to pro
or disprove. The most likely source for most intraosseo
tumors is odontogenicepithelium. Mucus-producingce
are Fommon in odontogenlc cyst linings, especially de
tigerous cysts (see page 590). In addition, many intr
osseous mueoepidermoid carcinomas develop in asso
ation with impacted teeth or odontogenlc cysts.
Clinical and Radiographic Raturn
lntraosseous mucoepidermoid carcinomas are m
common in middle-aged adults and demonstrate a sli
female predilection. They are three times more commo
the mandible than in the maxilla and are most often s
in the molar-ramus area. The most frequent presen
symptom is cort~calswelling, although some les~ons
be discovered as incidental findings on radiographs.
trismus, and paresthesia are reported less frequently.
Radiographs usually reveal either a uniiocular or m
tilocular radiolucency with well-defined borders (Figu
11-60). However, some examples are characterized b
more irregular and ill-defined area of bone destructi
Some cases are associated with an unerupted tooth a
therefore, clinically may suggest an odontogenic cys
tumor.
Hbtopathobgic Features
The m~croscopicappearance of intraosseous muco
dermoid carcinoma is similar to that of its soft ti
counterpart. Most tumors are low-grade lesions, altho
high-grade mucoepldermoid carcinomas also have b
reported withln the laws.
Ihatnres~tand P r o p d s
The pr~marytreatment modality for patients w
intraosseous mucoep~dermo~d
carcinoma i s surge

adjunctive radiation therapy also sometimes is used.
Radical surgical resection bffers a better chance for cure
than do more conservative procedures, such as enucle-
ation or curerrage. The local recurrenee rate with con-
servative treatment i,s40%. in contrast to 11% fos more
radical treatment. Metastasis has been reported in about
The overall prognosis is fairly good; around 10% of
patients die, usually as a result of local recurrence of the
ACINIC CELL ADENOCARCINOMA
The acinic cell adenocarcinoma is a salivary gland
malignancy with cells that show serous acinar differen-
tiation. Because many of these tumors aet in a non-
aggressive fashion and are associated with a good prog-
nosis, this neoplasm formerly was called acinic cell
tumor, a nonspecific.designation that did not indicate
whether the lesion was benign or malignant. However,
because some of these tumors do metastasize or recur
and cause death, it is generally agreed today that acinic
cell adenocarcinoma should be considered a low-grade
Clinical Features
Around 85% of all acinic cell adenocarcinomas occur in
the parotid gland, a logical finding because this is the
largest gland and one that is composed entirely of serous
elements. Most surveys have shown that this neoplasm
makes up 1 % to 3 % of all parotid tumors, although one
,study showed it represented 8.6% of all parotid tumors
[see Table 11-4). It is much less common in the sub-
mandibular gland, which is the site for only 2.7% to 4%
of these tumors. About 9% of all acinic cell adenocarci-
nomas develop in the oral minor salivary glands, with
%I-.. -. ..:ink cell adenocarcinoma. Small, nodular mass
of the hard palate. (Courtesy of Dc Rick Canaan.)
the buccal mucosa, lips, and palate being the most
common sltes (Figure 11-61). Overall, around 2% to
6.5% of all minor salivary gland tumors are acinic cell
adenocarcipomas.
The tumor occurs over a broad age range, with a
relatively even peak prevalence stretching from the
second to the seventh decades of life; the mean age is in
the middle 40s. Approximately 60% of cases occur in
women. The tumor usually appears as a slowly growing
mass, and the lesion often is appears for many months
or years before a diagnosis is made. The tumor may be
otherwise asymptomatic, although associated pain or
tenderness sometimes are reported. Facial nerve paral-
ysis 1s an infrequent but ominous sign for parotid tumors.
Histopathologic Featares
Acinic cell adenocam~nomasare highly variable in their
microscopic appearance. The tumor often is well clrcum-
scribed and sometimes may even appear encapsulated;
however, some tumors exhibit an mfiltratlve growth pat-
tern. The most character~sticcell is one with features of
the serous acinar cell, w ~ t h
abundant granular basophilic
cytoplasm and a round, darkly stained eccenrric nucleus.
These cells are fairly uniform in appearance, and mitot~c
activlty i s uncommon. Other cells may resemble interca-
lated duct cells, and some tumors also have cells with a
clear, vacuolated cytoplasm.
Several growth patterns may be seen. The solid
variety consists of numerous well-differentiated acinar
cells arranged In a pattern that resembles normal
parot~dgland tlssue (Figures 11-62 and 11-63), in the
microcystic variety, mult~plesmall cystic spaces are
created that may contain some muclnous or eosino-
philic material. in the papillary-cystic variety, larger
cystic areas are formed that are llned by epithelium
having papillary projections Into the cystic spaces
 I
-
Fimre 11-62 + Acinic cell adenocarcinoma. Parotid tumor
demonstrat~ngsheet of granular, basoph~licserousacinar cells.
F i r e 11-63 Acinic cell adenocarcinoma. Hrgh-power view of
serous cells with basophilic, granular cytoplasm.
(Flgure 11-64). The follicular variety has an appear-
ance similar to that of thyroid tissue. A lymphoid infil-
tmte is not unusual, sometimes with germlnal center
formation.
Rearment and Prognosis
-
Acinic cell adenocarc~nomasconfined to the superficial
lobe of the parotld gland are best treated by lobectomy;
for those in the deep lobe, total parotidectomy is usually
=
-
-
-
P
necessary. The facial nerve may need to be sacrificed if it
isinvolved by tumor. Submandibular tumors are managed
by total removal of the gland, and minor gland tumors are
treated with assured surgical excision. Lymph node dls-
section is not indicated unless there i s clinical evidence
of metastatic disease. Adjunctive radiation therapy may
be considered for uncontrolled local disease.
Theaciniccell adenocarcinoma isassoeiated with one
of the better prognoses of any of the malignant salivary
variant showing proliferation of tumor cells into a large cystic sp
gland tumors. Approximately one third of patients
recurrences locally, and metastases develop in 10
15% of patients. From 6 % to 26% of patients die of
disease. The prognosis for minor gland tumors is b
than that for tumors arising in the major glands.
MALIGNANT MIXED TUMORS (CARCINO
EX PLEOMORPHIC ADENOMA; CARCINO
EX MIXED TUMOR; CARCINOSARCOMA;
METASTASIZING MIXED TUMOR)
Malignant mixed tumors represent malignant cou
parts to the benign mixed tumor or pleomorphic
noma. These uncommon neoplasms constitute 2
6 % of all salivary tumors and can be divided Into r
categories:
I.Carcinoma ex pleomorphic adenoma fcarcin
ex mixed tumor)
2. Carclnosarcoma
3. Metastasizing mixed tumor
The most common of these is the carcinoma ex
morphic adenoma, which is characterized by
nant transformation of the epithelial compone
previously benign pleomorphle adenoma. The car
sarcoma is a rare "mixed" tumor in which both car
matous and sarcomatous elements are present.
metastasizing mixed tumor has histopatholo
tures that are Identical to the common pleo
adenoma (mixed tumor). I n spire of its benign
anee, however, the lesion metastasizes. The meta
tumor also has a benign microscopic appearance,
ally similar to that of the primary lesion.
Clinical Features
 C H A P T E R 11 Salivary Gland Pafhologv
,&e@~flofl~!:r&p,~gs&@~~
m&@&t tra&@rmaflofiwithin
wtiatmiq pmwqcs:I'p+aLjsmgn heoplasm. ~ k gofaj1,;fhet
rn@b q$ ofpetiencs Wtb &~'~rt&ori8 about 1s. yeah
older$&inthat f@rtha henip pleamo.rphica&enoma. It
!ts.mgrstaommon,In m.tddhgetl and aldier aduks wish
a peak pmmience inthe.:slxthro aghth decades of li@
I n i&iionj . . pat1mTS inas fL?gol'tthata mass has Men
pr@enrfofimmany years, $&m&%lm%s undefgoing a recent
rapjld,:j.g,mv$lh'wit$ assaeisted pain: or ul'ceration. How-
'es&~,,smme ~amarsma~have asho;rt duration. The histo-
~pathoI~fc~&sht.res;hieh,.r;e dtscttssed larer, also sup-
pb! matgrant transfdrmmn af ,a benign pleomorphic
adeKImd: has &!ehmred ilia the risk for malignant
cliZn& in. a pleoniap.fik aqenorna increases with the
tdrua%imof the:Tumor.
@ver:80%!ofcases ofi~carcinamaex pleomorphic ade-
noma ate seen ,Wh%n the major gkrnds, primarily $he
.paroiid!glandlSBipre11 -651. Nearly t othirds ofminor
salivary glandrages,oecuf ohtho pal~qte(Mgure11 -66).
Th,& fS a slf@htEmalg pr.edile.&tin.~A~lthough pain or
recent @id growfh is not unu,$uaL,many eases present
sa FI painlees mass that is in&stinguishable from a
i benfgn.mmor. Paraid tumors may produce facial nerve
: paky,
.
F i r e 11-66 Carcinoma ex pleomorphic adenoma. Painfub
ulcerated mass of the palate.
G@l@aSsnrCe&rr,The!earci'no,sa~cama isw.wtremelfl
rii@~@&ez$ Most eases hawbeen repa&d:kn Ihe;p.&,
&an&. but the lesion alsd has been: =en -it&; ,.. - @&w.@I$-
..i. *.
.mdtbxlar @ a d and minos sahya~~&@&*@&
'teal g$@ssarrd. s:g,gpmm~ _ . . ...* C.i.i.l
#@.smf@@f&!&
!azai@i
:$g,p[g@mmapIshSg.&~@m,!~
pre\A&gshj$mTyp7 g w,
plm,wac
a l r ~ @ ~ ~ p h . ~ & t h e r ~ .sfe w,gum,,
~,~~~m~&
~ & d k m a : h m a%e:m~am*f"g-mka
m
tum,rfsalsd guimt,~m, As m
m
m m s , m a ogseg ,onigifi:ateiin tt~aparotid ~ I ~ Y Ebut
I,
the pdmefy tumor alsb. mapoccur in the subma.ndib.ular
g!ena tlr m a r s&vary .g!ands+ hiiletastaa~a:haze. been
idund mPsf fmqu~f1yinLhe'~bnes~~arlun~ hub t h y *lso
:@anmeur1,n @$he?sites, such as:regja.~alljrmph nodes
ar rhe l%m. Mast .pat'its. haye .a hisrdry af a benign
m:&dwmor; wh%h tiimap have been excised mgny years
parlior. Man$ fm:b,$tb%hrima,iy tumn.r ektiibits muiltiple
re.ma@en.cesb&.:ye me@,sta.sisk u r s .
-Hbfapatfiioiogic%awn$
~~~dw~ma.expipomoiphir
ra#art~a4?:
T~?~@?@Q$B
;exp!eamorpfiW .a$~noma6 h W . a vgri@bk& @lai,c?e9pX~1
a-pparance. Areas qf'typial lrenign ~b&@,@M$;BW
kQ!W:Us~llycan he fom$an,d .&Y; cans.riade,:mw~ar
only asmall '~avflonof rhe lesfon.Within.:thetumwr are
areae of malignant .degeneration of the epithelial corn-
pment, :characterized by cellular pleomarphism and
abnormal mifoti6 activity (Figure 11 -67).This change 1s
mostoften in the form of a,poorlydlfferentiated adene-
ca.xcinoma, but a t k r pa5tte~n.salso ean develop;
innluding polymorphous low-grade adenamarchama,
m.ucoepider.moid carcinoma, and adenoid ey$rit carci-
noma. The malignant edmponent @en has an aggres-
sive growth pattern, with capsular invwion a,nd infiltra-
 - - -
- ~ ~ ~ .

F
13*::-
--
,=
,ex>:
j =.
l i

---

- - 'SWf .$-,'a
tf*F ,$the turn&
-~~!*Y,",,".C"~.CU,,,",p.1..
6f.6,.&$,a-*id
6, MaUgnanPportion ofthe turnorihawing.ep&h&-
-"C.

&@&
1 qggniF:,@p f+g
:r@JB:@&gQrQkil*f@&rq@gm
,.:.~.~.*.,.' 3. ,
H@d't@+lg&
i$qLi$&r rQ *~~@$@&figifl 8

mixed tumoror carci~omain Sifu es ia,Wgturn& @&&fi@@g4@5+ '@~&~@~@@~@~~.;&~&.:~~&&d~,~

r&,
,w&& m y he.~m~t~dmni%
rgi-
ichemo~hsm$. %he p t g n a s l s ~ s p n ~

M B f ! mfm@gpb,
eneatme~tf@r~a!t

ADENOID CY4TI.CCARCINOMA

synonym fm this nSoplasm,. HowaVeC, me ,of the qm.

-'IkatnreW and magnosis cylindrdinaprobably Skould be.a\poidedtoileybSc@qx@;@B
cwrlSb@a &pIamh+@&& idWir*e.carci- samd Wrh is' used for a $kin a d ~ e mtuinor
l .&at+v@.gl
noma expfaim:erpJqk a$m~ma:,u.sqallgig he.& tmated by markedly different clinical pre
wide exdsio~~ p e d b 1 ~ia .eon~la.ndiw!with.loaal lymph
no& :drsScction and xdpn:&~ .radiation t h w ~ y The. Clinical and Radiographic Peatuff$
pii?gnV@&?s gk~ar@ed: t h e o ~ w a tfi t - g ~ ~
, c
survival rate
f@bgt&&m13C% fa .6!$%,,but thfs Yated~op$to 10% to
%Bi at '1:s yea^@;. Th,e,pr~@,O$isis fel@Wdto the tiisto- minor
pa.tho;b&ffs
.subtypee8f the malignant ,Camponenk One site:farminorglandturnore IFi
~t~~d~shDwed$hat~~lMiM"emtia~ed.ca~in~mas, such as ,twwors r e found mostly in
pol@orphous low~~de~adenoea~cinoma, hzwnearlya dihular glands, with a klairly
90% %yeasunviva1 rat&m contrast, theo~tlookis much these two sites. On an individual hacis, h'nwe@gb
CHAPTER 11 + Saiivary Gland Pathologv 43 7

FIgure 11-68 *Adenoid cystic carcinoma. Painful mass of the

hard palate and maxillary alveolar ridge. (Courtesy of Dr. George
Bions.)

striking differencecan be seen amongthe variousglands.

In the parotid gland, the adenoid cyst~ccarcmoma is rel-
atively rare, constituting only 2% to 3 % of all tumors. In
the submandibular gland, t h ~ stumor accounts for 12%
to 17% of all tumors and is the most common malig-
nancy. It is also relatively common among palatal sali- Fiflw 71-69 Adenoid cY~*~ccarcinoma- CompuM tomqg
vary neoplasms; it represents 8% to l s o / o of allsuch " P ~ Yr a n of this massive palatal tumor s k s exkrnve destruc-
ken ofthe hard palate with extension of the tumor into the nasal
The lesion Ismost in middle-aged cavity and both maxdlaly sinuses. (Courtesy of Dr. Kevin Ribc)
adults and is rare in people younger than age 20. There
isa fairly equal sex distribution, although some studies
have shown a slight female predilection.
The adenold cystic carcinoma usually appears as a
slowly growing mass. Pain is a common and important
finding, occasionally occurring early in the course of the
disease before there is a noticeable swelling. Patients
often complain of a con$tant, low-grade, dull ache, which
gradually increases i n intensity. Facial nerve paralysis
may develop w ~ t hparotid tumors. Palatal tumors can be
smooth surfaced or ulcerared. mmors arising in the
palate or maxillary 'sinus may show rad~ographicevi-
dence of bone destruction (Figure 11-69).

Histopathalogic Feamres
The adenoid cystic carcinoma i s composed of a mlxture
of myoepithelial cells and ductal cells that can have a
varied arrangement (Figure i1 Three patterns
are recognized: (I) cribriform, (2) tubular, and (31 solid.
Usually a combination of these is seen, and the tumor i s
classified based on the predominant pattern.
The cribriform pattern is the most classic and best-
recognized appearance, characterized by islands of
basaloid epithel~alcells that contain multiple cylindric,
cystl~kespaces resembling Swiss cheese. These spaces
Figun11-JO Adenoid cysticcarcinoma. Islands of hyperchm-
matic cells form~ngcribr~formand tubular structures. inset shows
a high-power vlew of a small crlbriform island.
often contam a mildly basophilic mucoid material, a
hyalinized eosinophilic product, or a combined mucoid-
hyal~nizedappearance. Sometimes the hyalinired mate-
rial also surrounds these cribrlform islands (Figure
11-71), or small strands of tumor are found embedded

.
Figure 11-71 Adanoid cystic carcinoma. The tumor cells are
surrounded by hyalinized material.
within this hyalinized "stroma." The tumor cells are
small and cuboidal, exhibiting deeply basophilic nuclei
and little cytoplasm. These cells are fairly uniform in
appearance, and mitotic activity is rarely seen.
m the tubular pattern, the tumor cells are similar but
occur as multiple small ducts or tubules within a hyalin-
ized stroma. The tubular lumina can be lined by one to
several layers of cells, and sometimes both a layer of
ductal cells and myoepithelial cells can be discerned.
The solid variant consists of larger islands or sheets
of tumor cells that demonstrate little tendency toward
duct or cyst format~on.Unlike thecribriform and tubular
patterns, cellular pleomorphisrn and mitotic activity, as
well as focal necrosis in the center of the tumor islands,
may be observed.
A highly characteristic feature of adenoid cyst~ccar-
cinoma is its tendency to show perineural invaslon
ORAL & MAXILLOEACIAL PATHOLm
(Figure 11 -721, which probably corresponds to the aom-
mon chnical finding of pain in these patients. Sometimes
the cells appear to have a swirling arrangement arounc
nerve bundles. However, perineural invasion is n a
pathognomonic for adenoldcystic carcinoma; italso ma)
be seen in other salivary maltgnancles, especially poly-
morphous low-grade adenocarcinomas.
Beatment and Prognosis
Adenoid cystic carcinoma is a relentless tumor that i a
prone to local recurrence and eventual distant metas-
tasis, Surgical excision is usually the treatment of choice,
and adjunct radiation therapy may slightly improve
patient surviva1 in some cases. Because metasrasis to
regional lymph nodes is uncommon, radical neck dis-
section typically is not indicated. Because of the poor
overall prognosis, regardless of treatment, clinicians
should be cautioned against needlessly aggressive and
mutilating surgical procedures for large tumors or cases
already showing metastases.
Because the tumor is prone to late recurrence and
metastasis, the 5-year survival rate has little significance
and does not equate to a cure. The 5-year survival rate
may be as high as 70%, but this rate continues to
decrease over time. By 2 0 years, only 20% of patients
are still alive. Tumors with a solid histopathologic pat-
tern are associated with a worse outlook than those with
a cribriform or tubular arrangement. With respect to site,
the prognosis is poorest for tumors arising in the maxil-
lary sinus and submandibular gland. Most studies have
shown that microscopic identification of perineural inva-
sion has little effect on the prognos$s.
Death usually results from local recurrence or distant
metastases. Tumorsof thepalateormaxillary sinuseven-
tually may invade upward to the base of the bra~n.
Metastatic spread most commonly occurs to the lungs
and bones.
POLYMORPHOUS LOW-GRADE
ADENOCARC1NOMA (LOBUIAR CARCINOMA;
TERMINAL DUCT CARCINOMA)
The polymorphous low-grade adenocarcinoma is a
recently recognized type of salivary malignancy that was
first described in 1983. Before its identification as a dis-
tinct entity, examples of this tumor were categorized as
pleomorphic adenoma, an unspecified form of adeno-
carcinoma, or sometimes adenoid cystic carcinoma.
Once recognized as a specific entity, however, it was real-
ized that this tumor possesses distinct clinicopathologic
features and IS one of the more common minor salivary
gland mal~gnancies.
C ti A P T E R 1 1 Salivary Gland Pathology 429

~& &!m@ge@q@S&!
a ~ p ~ i8i&@~h1&:qy,m in soma

I
I
$&@: t h e e m qafi &gbibiy~&f&@t@ ? ~ t hp&@&S,z, ',

hence, rhe p@morpbolrs:tmm. The eel16 may &rwim a 1

solid:pa~reriorfh~& eords,dkts, or Sarger~y&tcspares.
in some tusnorsi a cribri%t.mcpamrn .mnbe pra&erd
at^ ~ f ~ @~~~.
. ,.. -~ ~ : @ gqgqc
mimfp&l"a~,aict.uQ~~;-:
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~

.otnmen .
! ! ~ ; @,. '@jjp@

~ < r ~ 1 p ~ ~ , , t ~ e ~ ap:p$&@.wdl.,.g%t-
f,].+&&

@ & . ~ g ~ ; ~ @ Fief611-74 r P ~ l & - q i p h ~ ~ ~ + @ + ~ e ~ w & ~%is

i
m~.
-
&;&,d.,. @w,gsq. $he Rw@hpdl.Ce1f8,aReuSUdtly w e rshawa cfibiIfi,m amtigem6ntrirfurif6cm
m ~ i x m ~ p ~ dew
&&$$j\pe, ;f&adibg &e adfa~ar .a . ~ . ~ & 4 f i 1 ~ twmoiceliswftti pak?dt&ininghirdei.,
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- .~ Emngi@@ &= m&Q<tyiQg::,bdne
or skeletal muscle may be observed. The stroma is often
mucoid in nature, or it may demonstrate hyalinlzation.
Perineural ~nvasionis common-another feature that
mav muse ,&e t ~ m w SD be mistaken for adenoid w t ' w 1

taenf ptdgooses.

u
Treatment and P m"o s i s
The polymorphous low-grade adenocarcinoma is best
treated by wide surgical excision, sometimes including
resection of the underlying bone. Metastasis to regional
lymph nodes is relatively uncommon, occurring in just
under 10% of patients. 'Therefore, radical neck dissec-
lion seems unwarranted unless there is clinical evidence
of cervical metastases, Distant metastasis is rare.
.
fiym 11 -75 po~,,morphous low-mde adcnocarcinoma.
~aje-s@inin~
cells which infiltrate as ;ingle-file mrds.
 --
I 430 ORAL & MAXlLLOPACIAL PATH01

The overall prognosis is relatively good. Recurrent

disease has been reported in 9 % to 17% of all patients,
but this usually can be controlled with reexcision. Death
from tumor is rare but may occur secondary to direct
extension into vital structures. Microscopic identifica-
tion of perineural invasion does not appear to affect the
prognosis.
Figure 11-77 Salivary adenocarcinoma. "Clear cell"adeno
SALIVARY ADENOCARCINOMA, NOT cinoma ofthe submandibulargland.
-
OTHERWISE SPECIFIED
In spite of the w ~ d evariety of salivary gland malignan-
cies that have been specifically identified and cafego-
r~zed,some tumors still defy the existing classification
schemes. These tumors usually are designated as sali-
vary adonocareinomas, not othenvlse specified (NOS).

Clinical and mmpathologlc Features

Because these adenocarcinomas represent such a
diverse group of neoplasms, it is difficult to generalize
about their clinical and microscopic features. Like most
salivary tumors, they appear to be most common in the
parotid gland, followed by the minor glands and the sub-
mandibular gland (Figures 11-77 and 11-78). They may
present as asymptomatic masses or cause pain or facial
nerve paralysis. The microscopic appearance is highly
Figure 11-78 r Salivary adenocarcinoma. Mass of the poster
variable but demonstrates features of aglandular malig- lateral hard palate.
nancy with evidence of cellular pleomorphism, an infil-
trative growth partern, or both, These tumors exhibrt a
wide spectrum of differentiation, ranging from weli-
differentiated, low-grade neoplasms to poorly differen- Weatment and Prognosis
tiated, high-grade malignanc~es. The prognosis for sahvary adenocarcinoma (NOS)
As these tumors are studied more, it should be pos- guarded, but patients with early-stage, well-drfferenti;
sible to classify some of them into separate, specific tumors appear to have a better outcome. The survival
categories and allow more definit~veanalyses of thew is better for tumors of the oral cavity than for those in
clinical and microscopic features. major salivary glands.