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Chapter 6Frozen Section Evaluationof the Appendix
Abstract Appendiceal tumors are rarely diagnosed preopera-tively, and their classification is both challenging and controversialowing to their tendency to disseminate in the peritoneal cavitydespite their frequent low-grade appearance. Frozen section analy-sis may be requested to assess the status of the appendiceal margin,determine whether extra-appendiceal epithelium is present, and toclassify extra-appendiceal disease as low- or high-grade. Othertypes of appendiceal epithelial tumors, such as serrated neo-plasms, should be distinguished from mucinous tumors, sincethey tend to precede overtly malignant peritoneal disease (peri-toneal carcinomatosis). Goblet cell carcinoid tumors often spreadto non-contiguous structures and, thus, may prompt intraoperativeconsultation.
Keywords Appendicitis · Mucinous neoplasm · Extra-appendicealmucin · Endocrine · Goblet cell carcinoid
Introduction
Primary appendiceal tumors are found in less than 2% of sur-gically removed appendices and typically bear a resemblance totheir colonic counterparts. Most epithelial tumors are mucinous orcontain villous projections, and those with serrated architecture
85N.C. Panarelli, R.K. Yantiss, Frozen Section Library: Appendix,Colon, and Anus, Frozen Section Library 4, DOI 10.1007/978-1-4419-6584-4_6,C© Springer Science+Business Media, LLC 2010
86 6 Frozen Section Evaluation of the Appendix
are increasingly recognized. Appendiceal endocrine neoplasmsare relatively common, incidentally discovered lesions that gen-erally do not require intraoperative consultation, although gobletcell “carcinoid” tumors may pose challenges to both surgeonsand pathologists [1]. Unfortunately, the diagnosis of appendicealneoplasia is rarely made preoperatively, since many patients haveclinical symptoms of appendicitis [2, 3]. As a result, intraopera-tive frozen section evaluation is commonly performed to determinethe surgical management of patients with these tumors. Mostimportant issues revolve around the diagnosis and classification ofmucinous neoplasms, as discussed below.
Appendicitis
The acutely inflamed appendix displays serosal hyperemia withor without fibrinopurulent exudates and inflammation (Fig. 6.1).Mucosal necrosis is accompanied by purulent luminal debris andneutrophilic inflammation within the muscularis propria, which
Fig. 6.1 An acutely inflamed appendix displays fibrinous adhesions onthe erythematous serosa. Inflammation in the mesoappendiceal fat reflectsperforation and a periappendiceal abscess
Appendiceal Mucinous Neoplasms 87
may be associated with mesoappendiceal abscesses. A prolongedinterval between the onset of symptoms and surgical resectionmay result in intense eosinophil-rich inflammation in combinationwith granulomas, a foreign body giant cell-rich response to lumi-nal material, and organizing serositis (Fig. 6.2). Sheets of tissuemacrophages laden with ceroid pigment in combination with mult-inucleated giant cells and fat necrosis may prompt a diagnosis of“xanthogranulomatous appendicitis”.
Fig. 6.2 Prolonged acute appendicitis produces a fibroinflammatory appen-diceal mass that simulates a neoplasm. One may observe a mixed inflammatorycell infiltrate with sheets of macrophages associated with fat necrosis andfibrosis
Appendiceal Mucinous Neoplasms
Epithelial neoplasms of the appendix are generally classifiedas mucinous neoplasms and non-mucinous tumors. Appendicealmucinous neoplasms characteristically cause cystic dilatation ofthe appendix, but they may rupture, resulting in accumulationof mucin around the appendix (Fig. 6.3). Mucinous appendicealneoplasms may also disseminate through the peritoneum in the
88 6 Frozen Section Evaluation of the Appendix
Fig
.6.3
Muc
inou
sne
opla
sms
prod
uce
copi
ous
muc
in,r
esul
ting
inst
riki
ngap
pend
icea
ldi
sten
tion
(a).
Rup
ture
dne
opla
sms
may
beas
soci
ated
with
peri
appe
ndic
ealm
ucin
depo
sits
,whi
chsh
ould
beex
haus
tivel
ysa
mpl
edto
excl
ude
the
poss
ibili
tyof
extr
a-ap
pend
icea
lep
ithel
ium
(b)
Appendiceal Mucinous Neoplasms 89
form of mucin deposits, or pseudomyxoma peritonei (Fig. 6.4).They frequently metastasize to the ovary, which may be large andcystic, simulating the appearance of a primary ovarian neoplasm(Figs. 6.5 and 6.6). Pathologists will be called upon to classifyperitoneal tumor deposits in many institutions because immediatetreatment depends upon the degree of atypia present in extra-appendiceal epithelium. Patients with low-grade peritoneal diseasemay be treated with surgical debulking and peritoneal strippingwith the aim of complete cytoreduction either with, or without,intraoperative intraperitoneal chemotherapy. Moderate-to-poorlydifferentiated mucinous carcinomas may also produce gelatinousascites, but they do not respond to cytoreductive surgery, so thesepatients may be offered systemic chemotherapy. Therefore, pathol-ogists should clearly communicate the histologic findings andbiologic implications of their observations at the time of the frozensection.
Mucinous lesions typically display a circumferential growthpattern in the appendiceal mucosa and contain tall columnar muci-nous cells arranged in a single layer, or papillae with low-gradenuclei [4] (Fig. 6.7). When present, extra-appendiceal disease con-sists of pools of mucin containing strips or clusters of neoplasticepithelial cells that usually show bland cytologic features, similarto those of the appendiceal component [5] (Fig. 6.8).
Several groups have proposed a variety of classificationschemes that employ varied, and often confusing, terminology todescribe appendiceal mucinous tumors [6–10] (Table 6.1). Moststudies have shown that mucinous neoplasia confined to the appen-diceal mucosa is essentially cured by excision, regardless of thedegree of dysplasia, whereas peritoneal disease is associated withdisease recurrence and death in nearly half of patients. Emergingdata also suggest that acellular mucin pools limited to the appen-diceal wall and periappendix are associated with an excellentprognosis, provided the entire appendix is submitted for histo-logic evaluation to exclude the possibility of extra-appendicealepithelium. However, any amount of extra-appendiceal epitheliummay be associated with progressive mucinous ascites and death insome cases, even if one identifies only rare clusters of neoplasticepithelial cells surrounding the appendix [5] (Fig. 6.9). Extension
90 6 Frozen Section Evaluation of the Appendix
Fig
.6.
4A
ppen
dice
alm
ucin
ous
neop
lasm
sm
aydi
ssem
inat
ein
the
peri
tone
alca
vity
and
appe
aras
gela
tinou
sde
posi
tsw
ithin
peri
tone
alfa
t(a)
and
onth
ein
test
inal
sero
sals
urfa
ce(b
)
Appendiceal Mucinous Neoplasms 91
Fig. 6.5 Metastatic appendiceal mucinous tumors result in massive ovarianenlargement with multiple loculated cysts filled with mucinous material
beyond the appendix should also be distinguished from herniationsof mucosa through the wall, or diverticula, since this finding has nobiologic implications (Fig. 6.10).
The proposed classification schemes for appendiceal mucinousneoplasia reflect differences of opinion regarding the fundamentalnature of peritoneal disease. At one extreme, some investigatorsfeel that peritoneal dissemination results from appendiceal rup-ture and spillage of both mucin and neoplastic, but non-invasive,epithelium into the peritoneal cavity. Proponents of this hypoth-esis classify tumors limited to the appendiceal mucosa as muci-nous cystadenomas. They consider gelatinous ascites containinglow-grade epithelium to represent disseminated peritoneal ade-nomucinosis but reserve the term “carcinoma” for tumors thatdisplay high-grade cytologic features (Figs. 6.11 and 6.12) [8,10]. Conversely, most authorities, including the World HealthOrganization, now consider pseudomyxoma peritonei to representcarcinoma and grade the cytologic features present in extra-appendiceal epithelium. Low-grade tumors corresponding to “dis-seminated peritoneal adenomucinosis” are classified as low-grade
92 6 Frozen Section Evaluation of the Appendix
Fig
.6.6
App
endi
ceal
muc
inou
sne
opla
sms
that
met
asta
size
toth
eov
ary
prod
uce
larg
em
ucin
-fille
dcy
sts
(a)l
ined
bybl
and
epith
eliu
mth
atm
aysi
mul
ate
apr
imar
yov
aria
ntu
mor
(b)
Appendiceal Mucinous Neoplasms 93
Fig
.6.7
Muc
inou
sne
opla
sms
circ
umfe
rent
ially
invo
lve
the
appe
ndic
ealm
ucos
a(a
)an
dco
ntai
nvi
llous
,or
flat,
low
-gra
dem
ucin
ous
epith
eliu
mw
ithsl
ight
lyen
larg
ed,b
asal
lylo
cate
dnu
clei
(b)
94 6 Frozen Section Evaluation of the Appendix
Fig
.6.8
Peri
tone
alm
ucin
depo
sits
cont
ain
rare
clus
ters
ofep
ithel
ialc
ells
(a)
that
show
low
-gra
decy
tolo
gy(b
)
Appendiceal Mucinous Neoplasms 95
Tabl
e6.
1Pr
opos
edcl
assi
ficat
ion
sche
mes
for
appe
ndic
ealm
ucin
ous
neop
lasm
s
Car
ran
dSo
bin
Mis
draj
ieta
l.Pa
iand
Lon
gacr
eR
onne
ttet
al.
Wor
ldH
ealth
Org
aniz
atio
n
Tum
orco
nfine
dto
appe
ndix
Lim
ited
tom
ucos
aL
ow-g
rade
cyto
logy
Ade
nom
aL
ow-g
rade
appe
ndic
eal
muc
inou
sne
opla
smA
deno
ma
Ade
nom
aA
deno
ma
Hig
h-gr
ade
cyto
logy
Ade
nom
aN
on-i
nvas
ive
muc
inou
scy
stad
enoc
arci
nom
aA
deno
ma
Ade
nom
aA
deno
ma
Posi
tive
surg
ical
mar
gin
Ade
nom
aL
ow-g
rade
appe
ndic
eal
muc
inou
sne
opla
smU
ncer
tain
mal
ig-
nant
pote
ntia
lA
deno
ma
Cel
lula
rm
ucin
inw
all
Inva
sive
muc
inou
sad
enoc
arci
nom
aL
ow-g
rade
appe
ndic
eal
muc
inou
sne
opla
smU
ncer
tain
mal
ig-
nant
pote
ntia
lIn
vasi
vem
ucin
ous
aden
ocar
cino
ma
Tum
orbe
yond
appe
ndix
Low
-gra
deep
ithel
ium
inpe
rito
neal
muc
in
Inva
sive
muc
inou
sad
enoc
arci
nom
aL
ow-g
rade
appe
ndic
eal
muc
inou
sne
opla
smL
ow-g
rade
with
high
risk
ofre
curr
ence
Dis
sem
inat
edpe
rito
neal
ade-
nom
ucin
osis
Low
-gra
dem
ucin
ous
aden
ocar
cino
ma
Hig
h-gr
ade
epith
eliu
min
peri
tone
alm
ucin
Inva
sive
muc
inou
sad
enoc
arci
nom
aIn
vasi
vem
ucin
ous
aden
ocar
cino
ma
Inva
sive
muc
inou
sad
enoc
arci
nom
aPe
rito
neal
muc
inou
sca
rcin
omat
osis
Hig
h-gr
ade
muc
inou
sad
enoc
arci
nom
a
96 6 Frozen Section Evaluation of the Appendix
Fig
.6.
9R
uptu
red
appe
ndic
eal
muc
inou
sne
opla
sms
disp
lay
copi
ous
peri
appe
ndic
eal
muc
inde
posi
ts(a
),w
hich
may
cont
ain
rare
clus
ters
ofex
tra-
appe
ndic
ealt
umor
cells
(b)
Appendiceal Mucinous Neoplasms 97
Fig
.6.
10D
iver
ticul
aar
eco
mm
only
enco
unte
red
inas
soci
atio
nw
ithap
pend
icea
lm
ucin
ous
neop
lasm
san
dre
pres
ent
hern
iatio
nsof
muc
osa
thro
ugh
the
mus
cula
ris
prop
ria
(a).
Rup
ture
ddi
vert
icul
am
aybe
asso
ciat
edw
ithac
ellu
lar
orga
nizi
ngm
ucin
inth
em
esoa
ppen
dix
and
onth
ese
rosa
buts
houl
dno
tbe
inte
rpre
ted
tore
pres
enta
neop
lasm
(b)
98 6 Frozen Section Evaluation of the Appendix
Fig
.6.
11M
ucin
ous
appe
ndic
eal
neop
lasm
sth
atsp
read
toth
epe
rito
neal
cavi
tysh
ould
becl
assi
fied
base
don
the
degr
eeof
cyto
-lo
gic
atyp
iapr
esen
tin
extr
a-ap
pend
icea
lep
ithel
ium
.L
ow-g
rade
lesi
ons
cons
ist
ofm
ucin
pool
s(a
)th
atco
ntai
nsc
ant
stri
psor
clus
ters
ofm
ucin
ous
epith
eliu
mw
ithm
inim
alcy
tolo
gic
atyp
ia(b
).T
hese
lesi
ons
are
cons
ider
edto
repr
esen
tdis
sem
inat
edpe
rito
neal
aden
omuc
inos
isby
som
ean
dlo
w-g
rade
muc
inou
sad
enoc
arci
nom
aby
othe
rs
Appendiceal Mucinous Neoplasms 99
Fig
.6.
12So
me
muc
inou
sne
opla
sms
cont
ain
mor
enu
mer
ous
cell
clus
ters
and
disp
lay
agr
eate
rde
gree
oftis
sue
dest
ruct
ion
and
inva
sion
(a).
The
sele
sion
sty
pica
llysh
owse
vere
lyat
ypic
alcy
tolo
gic
feat
ures
with
enla
rged
,ro
und
nucl
ei,
nucl
eoli,
and
mito
ticfig
ures
(b).
Peri
tone
alin
volv
emen
tpur
sues
anag
gres
sive
cour
se,d
oes
notr
espo
ndw
ellt
osu
rgic
alde
bulk
ing,
and
shou
ldbe
clas
sifie
das
aden
ocar
cino
ma
100 6 Frozen Section Evaluation of the Appendix
Fig
.6.
13C
lust
ered
and
sing
lein
filtr
atin
gce
llsw
ithde
smop
last
ictis
sue
dest
ruct
ion
(a)
repr
esen
thi
gh-g
rade
aden
ocar
cino
mas
,de
spite
the
pres
ence
ofm
ucin
prod
uctio
n(b
).C
linic
ians
shou
ldbe
info
rmed
that
thes
ele
sion
ses
sent
ially
repr
esen
tpe
rito
neal
carc
inom
atos
is,i
nor
der
toav
oid
mis
com
mun
icat
ion
and
over
lyag
gres
sive
surg
ical
man
agem
ento
fth
epa
tient
Non-mucinous Appendiceal Epithelial Neoplasms 101
mucinous adenocarcinomas (Figs. 6.8, 6.9, and 6.11). More cellu-lar lesions that display malignant cytology are considered to rep-resent high-grade mucinous adenocarcinomas [5, 11] (Fig. 6.12).Notably, carcinomas that infiltrate the peritoneal soft tissue assingle cells or cluster associated with desmoplasia are uniformlyclassified as high-grade adenocarcinomas, regardless of the pres-ence of mucin production. They seed the peritoneum in the formof solid tumor nodules, or carcinomatosis, which is not amenableto surgery (Fig. 6.13). The term “mucinous adenocarcinoma” isgenerally avoided when describing such cancers in order to avoidconfusion.
The primary goals of intraoperative examination are to (1)determine whether the mucinous neoplasm is limited to theappendix, (2) assess extra-appendiceal mucin for the presenceof neoplastic epithelium, and (3) grade the severity of cytologicatypia within extra-appendiceal epithelium. Tumors limited to theappendix are treated with appendectomy alone, whereas a rightcolectomy or cecectomy may be considered when the appendixis ruptured, or the neoplasm is present at the appendiceal resectionmargin.
Non-mucinous Appendiceal Epithelial Neoplasms
Non-mucinous adenomas and carcinomas are histologically simi-lar to their colonic counterparts and are commonly referred to as“colonic-type” lesions (Fig. 6.14). Colonic-type appendiceal ade-nomas are relatively uncommon and are generally observed inpatients with familial adenomatous polyposis or represent colonicadenomas that extend to involve the appendiceal mucosa from thececum [4]. More frequently, non-mucinous appendiceal neoplasmsdisplay serrated architecture. They may contain non-dysplastic ordysplastic epithelium and show molecular features similar to thoseof serrated colonic polyps [12] (Fig. 6.15).
Serrated appendiceal lesions are relatively common, but havebeen poorly characterized. They are usually incidentally discov-ered in colectomy specimens obtained for medical indications but
102 6 Frozen Section Evaluation of the Appendix
Fig. 6.14 Colonic-type appendiceal adenomas protrude into the lumen andcontain cells with enlarged pseudostratified nuclei and faintly eosinophiliccytoplasm, reminiscent of tubular or villous adenomas of the colon
may occur in patients with concomitant proximal colon cancers.Importantly, serrated appendiceal lesions occasionally precedeinvasive adenocarcinomas that show overtly malignant featuresand a destructive growth pattern characteristic of colonic cancers(Fig. 6.16a). Although these cancers may contain abundant extra-cellular mucin, peritoneal disease is in the form of solid tumornodules, and pursues a uniformly malignant course (Fig. 6.16b).Therefore, this type of tumor should not be considered within thespectrum of pseudomyxoma peritonei but is simply graded andstaged as invasive adenocarcinoma [12].
Endocrine Neoplasms of the Appendix
The most common appendiceal tumors are well-differentiatedendocrine neoplasms. These tumors have been historically clas-sified as “carcinoid” tumors because they are invasive similar to
Endocrine Neoplasms of the Appendix 103
Fig
.6.
15Se
rrat
edad
enom
asci
rcum
fere
ntia
llyin
volv
eth
eap
pend
icea
lm
ucos
abu
t,un
like
muc
inou
stu
mor
s,th
eyco
ntai
ngo
blet
and
non-
gobl
etep
ithel
ial
cells
with
abun
dant
eosi
noph
ilic
cyto
plas
m(a
).T
hese
rrat
edcr
ypts
are
lined
byce
llsw
ithba
sally
loca
ted,
penc
illat
enu
clei
,sim
ilar
toth
ose
ofco
lore
ctal
serr
ated
aden
omas
(b)
104 6 Frozen Section Evaluation of the Appendix
Fig
.6.1
6C
arci
nom
asde
rive
dfr
omse
rrat
edne
opla
sms
may
disp
lay
conv
entio
nal,
orse
rrat
ed,a
rchi
tect
ure
and
copi
ous
muc
inpr
o-du
ctio
n(a
).H
owev
er,
the
inva
sive
tum
orce
llsha
vehi
gh-g
rade
cyto
logi
cfe
atur
esan
dar
eas
soci
ated
with
desm
opla
stic
stro
ma
(b)
Endocrine Neoplasms of the Appendix 105
carcinomas, but generally pursue an indolent course, even whenmetastases are present. Recently, the World Health Organizationrecommended that such tumors be classified as endocrine, or neu-roendocrine, neoplasms, and abandoned the carcinoid terminology,since the biologic behavior of endocrine tumors varies dependingon anatomic location and other factors.
Appendiceal endocrine neoplasms display a variety of mor-phologic features and vary with respect to their biologic poten-tial. Most are comprised of enterochromaffin cells that expressserotonin in addition to synaptophysin and chromogranin. Theselesions are usually incidentally discovered firm, yellow nodulesthat occur in the distal tip of the appendix (Fig. 6.17). Theycontain nests of bland polygonal cells with abundant faintlyeosinophilic cytoplasm enmeshed within paucicellular collagenousstroma (Fig. 6.18a). The nuclei are monotonous, smooth, andround, without perceptible atypia, and mitotic figures are lacking(Fig. 6.18b). Endocrine neoplasms derived from L-cells are muchless common and express glucagon and peptide YY in addition
Fig. 6.17 Appendiceal endocrine neoplasms form solid tan-yellow nodules inthe distal tip of the appendix
106 6 Frozen Section Evaluation of the Appendix
Fig
.6.1
8E
ndoc
rine
neop
lasm
sge
nera
llysp
are
the
supe
rfici
alm
ucos
abu
tex
pand
the
subm
ucos
aan
dva
riab
lype
netr
ate
the
appe
n-di
ceal
wal
l.N
ests
and
cord
sof
neop
last
icce
llsar
een
mes
hed
with
insl
ight
lyce
llula
rst
rom
a(a
)an
dco
ntai
neo
sino
phili
ccy
topl
asm
and
roun
dnu
clei
with
stip
pled
chro
mat
inan
din
cons
picu
ous
nucl
eoli
(b)
Endocrine Neoplasms of the Appendix 107
to chromogranin and synaptophysin. They also show a predilec-tion for the distal appendix. L-cell endocrine neoplasms containtrabeculae, cords, and, rarely, tubules, of bland endocrine cellswith ovoid nuclei and no mitotic activity. Both enterochromaffinand L-cell endocrine neoplasms are generally benign or pursue anindolent clinical course when metastases are present. Tumors thatspan less than 1 cm are adequately treated by appendectomy, andthe risk of metastases from tumors smaller than 2 cm is proba-bly less than 1%. Extensive resection and regional lymph nodedissection is reserved for larger tumors, or those associated withmetastases, increased mitotic activity, and angioinvasion [1].
Neoplasms that express endocrine markers and contain cyto-plasmic mucin have been termed “goblet cell carcinoid tumors”,although they are more aggressive than other appendicealendocrine neoplasms. They do not form nodular masses but, rather,display circumferential growth in the appendiceal submucosa andmuscularis propria (Fig. 6.19). Goblet cell carcinoid tumors con-tain nests and clusters of tumor cells with large mucin vacuoles that
Fig. 6.19 Goblet cell carcinoid tumors spare the mucosa but diffusely infil-trate the appendiceal wall and extend onto the serosal surface
108 6 Frozen Section Evaluation of the Appendix
Fig
.6.2
0G
oble
tcel
lcar
cino
idtu
mor
sco
ntai
nne
sts
and
clus
ters
ofne
opla
stic
cells
(a)
that
cont
ain
volu
min
ous
cyto
plas
mic
muc
inan
dcr
esce
ntic
,ecc
entr
icnu
clei
(b)
Endocrine Neoplasms of the Appendix 109
Fig. 6.21 Nests of goblet cell carcinoid tumor diffusely infiltrate peritonealfat and are associated with a fibroinflammatory tissue response
compress the nuclei (Fig. 6.20). Neoplasms with these features areoften of advanced pathologic stage at the time of diagnosis. Theypenetrate the serosa, occasionally metastasize to regional lymphnodes, and form tumor deposits in the peritoneal cavity and/orovary, which may prompt frozen section evaluation (Fig. 6.21).Perineural and lymphovascular invasion are frequently observed[13]. In addition, goblet cell carcinoid tumors may precede devel-opment of frank adenocarcinomas, which either form glands orresemble signet ring cell or diffuse-type carcinoma, leading someinvestigators to propose terms, such as “adenocarcinoma ex gobletcell carcinoid” and “mixed goblet cell carcinoid adenocarcinoma”(Fig. 6.22).
110 6 Frozen Section Evaluation of the Appendix
Fig
.6.2
2G
oble
tcel
lcar
cino
idtu
mor
soc
casi
onal
lygi
veri
seto
inva
sive
aden
ocar
cino
mas
that
show
glan
dula
rdi
ffer
entia
tion
(a)
ora
diff
use
grow
thpa
ttern
with
sign
etri
ngce
lls(b
)
References 111
References
1. Carr NJ, Sobin LH (2004) Neuroendocrine tumors of the appendix. SeminDiagn Pathol 21(2):108–119
2. Jordan FT, Mazzeo RJ, Hoshal VL (1983) Primary adenocarcinoma ofthe appendix. Can preoperative or intraoperative diagnosis be made? AmSurg 49(5):278–281
3. Younes M (2005) Frozen section of the gastrointestinal tract, appendix,and peritoneum. Arch Pathol Lab Med 129(12):1558–1564
4. Misdraji J, Young RH (2004) Primary epithelial neoplasms and otherepithelial lesions of the appendix (excluding carcinoid tumors). SeminDiagn Pathol 21:120–133
5. Yantiss RK, Shia J, Klimstra DS, Hahn HP, Odze RD, Misdraji J (2009)Prognostic significance of localized extra-appendiceal mucin depositionin appendiceal mucinous neoplasms. Am J Surg Pathol 33(2):248–255
6. Bradley RF, Stewart JH, Russell GB, Levine EA, Geisinger KR (2006)Pseudomyxoma peritonei of appendiceal origin: a clinicopathologic anal-ysis of 101 patients uniformly treated in a single institution, with literaturereview. Am J Surg Pathol 30(5):551–559
7. Carr NJ, McCarthy WF, Sobin LH (1995) Epithelial noncarcinoid tumorsand tumor-like lesions of the appendix: a clinicopathologic study of184 patients with a multivariate analysis of prognostic factors. Cancer75(3):757–768
8. Misdraji J, Yantiss RK, Graeme-Cooke FM, Balis UJ, Young RH (2003)Appendiceal mucinous neoplasms: a clinicopathologic analysis of 107cases. Am J Surg Pathol 27(8):1089–1103
9. Pai RK, Beck AH, Norton JA, Longacre TA (2009) Appendiceal muci-nous neoplasms: clinicopathologic study of 116 cases with analysis offactors predicting recurrence. Am J Surg Pathol 33(10):1425–1439
10. Ronnett BM, Zahn CM, Kurman RJ, Kass ME, Sugarbaker PH,Shmookler BM (1995) Disseminated peritoneal adenomucinosis and peri-toneal mucinous carcinomatosis: a clinicopathologic analysis of 109cases with emphasis on distinguishing pathologic features, site of ori-gin, and relationship to “pseudomyxoma peritonei”. Am J Surg Pathol19(12):1390–1408
11. Hamilton SR, Aaltonen LA (1999) Tumours of the appendix. WHOclassification of tumours: tumours of the digestive system. WHO Press,Geneva
12. Yantiss RK, Panczykowski A, Misdraji J, Odze RD, Rennert H, Chen Y(2007) A comprehensive study of non-dysplastic and dysplastic serratedpolyps of the vermiform appendix. Am J Surg Pathol 31(12):1742–1753
13. Tang LH, Shia J, Soslow RA, et al (2008) Pathologic classification andclinical behavior of the spectrum of goblet cell carcinoid tumors of theappendix. Am J Surg Pathol 32(10):1429–1443