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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5186_Библиотеки_им_академика_М_И_Перельмана.pdf
High-GradeSerousCarcinoma
High-grade serous carcinoma accounts for 35–40% of all serous ovarian neoplasms
(Fig. 6.66) and approximately 75% of ovarian epithelial carcinomas. Ovarian highgradeserouscarcinomatendstooccurinthesixthtoseventhdecades(mean56years).
Grossly,serouscarcinomaisbilateralin60%ofcases,and issolidandcysticormostly
solid.Microscopically,serouscarcinomasexhibitpapillarystructuresthatcanbecomefused
and form solid sheets of cells with slitlike spaces. Marked nuclear atypia and numerous
mitotic figures, which may be atypical, are characteristic of the high-grade tumors (Fig.
6.66).Psammomabodiesareoftenpresentbutarenotspecific.
High-gradeserouscarcinomasarethemostcommonovarianepithelialcarcinomasand
areassociatedwithp53mutationsandsomaticorgerm-lineabnormalitiesofBRCA1or
BRCA2.High-grade serous carcinoma isthemost common gynecologictumorto occur in
womenwithagermlineBRCA1orBRCA2mutation;serouscarcinomamaydevelopinthe
fallopiantubesandonthesurfaceoftheperitoneum.
SeromucinousTumors
Seromucinoustumorsarebilateralinupto40%ofcases,andhaveastrongassociation
withendometriosis,whichispresentinupto50%ofcases(60).Themeanageofpatients
withmüllerian seromucinousborderlinetumors ismid-30s. These tumorsare composed of
complex papillae, architecturally similar to those of serous borderline tumors, lined by
columnarmucin-secretingepitheliumandciliatedeosinophilicepithelium.Nuclearatypiais
mild to moderate, and mitotic figures may be present. Typically, there is a prominent
neutrophilicinfiltrateinthestromaofthepapillae.Stromalmicroinvasion,similartothatin
serousborderlinetumors,maybepresent.Extraovarianimplantsmaybepresentinasmany
as20%ofcases,buttheirpresenceisnotassociatedwithaworseprognosis.
Figure6.65Low-gradeserous carcinoma of ovary.Simpleandbranchingpapillaeinvade
stromabutshowmoderatecytologicatypiaandlowmitoticactivity.
Figure 6.66 High-grade serous carcinoma of ovary. Sheets and papillae show marked
nuclearpleomorphismandfrequentmitoticfigures.
MucinousTumors
Ovarianepithelialtumorswithmucinousdifferentiationaccountfor15%ofallovarian
neoplasmsintheUnitedStatesandEurope.Thesetumorsarecharacterizedbyepithelial
cellsresemblingthoseofthegastrointestinaltract(enterictype).Liketheseroustumors,they
encompassagroupofthreedistinctentities:benignmucinouscystadenomaoradenofibroma,
mucinous borderline tumor (tumor of low malignant potential), and mucinous carcinoma
(61,70).
BenignMucinousTumors
Almost80% ofall mucinousovarian neoplasmsarebenignunilocularormultilocular
cystadenomas. They occur in a wide age range but are most commonly diagnosed in the
reproductiveage group. Benign mucinoustumorsare typically unilateralandcan reach 30
cmormoreindiameter.Microscopically,thetumorsarecomposedofacolumnarepithelial
liningwithabundant,pale-stainingintracellularmucinthatresemblesendocervicalorgastrictypeepithelium.Gobletcellsmaybepresentbutareuncommoninbenignmucinoustumors
(incontrasttoenteric-typemucinousborderlinetumorsormucinouscarcinomas).
MucinousBorderlineTumors—MucinousTumorsofLowMalignantPotential,
EntericType
Mucinous borderline tumors account for 10–15% of all mucinous ovarian tumors.
Mucinousborderlinetumorsofenterictypeareunilateral,andoftenlargerthanbenign
mucinoustumors.Theyoccurmostcommonlyduringthelatereproductiveyears(mean45
years). Microscopically, the multilocular cysts are lined by variably stratified mucinous
epithelium forming complex papillary folds. The individual cells show mild to moderate
cytologic atypia with increased mitotic figures (Fig. 6.67). Goblet cells are present. The
presence of marked or severe nuclear atypia involving the full thickness of stratified
epithelium(i.e.,notlimitedtothecrypts)isclassifiedasintraepithelialcarcinoma.
Twopatternsof microinvasionare recognized in mucinous borderline tumors of enteric
type.Thefirstpatternconsistsofinfiltrationofstromabyindividualcellsorsmallnests
ofcellsthatarecytologicallysimilartothecellselsewhereintheborderlinetumor.Such
focimustnotexceed5mminlinearextentor10mm2inarea.Thisisanuncommonfinding
inmucinous borderlinetumors (incomparison tothefrequencyofmicroinvasion inserous
borderlinetumors).Thesecond,morecommonpatternconsistsofoneormoresmallfoci
(≤5 mm in linear extent or ≤10 mm2 in area) of nests, individual cells, and glands
exhibiting cytologic features of high-grade carcinoma cells; this latter pattern is
classified as microinvasive carcinoma. Foci of microinvasive carcinoma are of uncertain
prognostic significance, but their presence should prompt a search by the pathologist for
largerfociofinvasivecarcinoma(60).
MucinousCarcinoma,IntestinalType
Mucinous carcinomas account for less than 10% of all mucinous ovarian neoplasms. Two
differentpatternsofinvasion arerecognized, bothofwhich maycoexist inasingle tumor.
The confluent glandular or expansile invasive pattern is recognized by marked glandular
crowding,withlittleinterveningstroma(Fig.6.68).Thedestructivestromalinvasivepattern,
which is less common, is recognized by irregular nests and single cells with malignant
cytologic features infiltrating the stroma (Fig. 6.69). The presence of stromal invasion,
whetherof destructiveor confluenttype, mustexceed 5mminlinearextent or10 mm2in
area in order to be classified as carcinoma; otherwise, a diagnosis of microinvasive
carcinomaiswarranted.
Mostprimarymucinouscarcinomasoftheovaryareconfinedtotheovaryatthetime
of diagnosis. An advanced stage mucinous carcinoma involving the ovary at first
diagnosisshouldbe evaluated as a possible metastasis from anothersite,particularly
thegastrointestinaltract(60).
MucinousTumorwithPseudomyxomaPeritonei
Althoughovarianmucinoustumorsassociatedwithpseudomyxomaperitoneiarelistedasa
distinct category by the WHO, most of these tumors are metastases from primary
mucinous tumors of the vermiform appendix (Fig. 6.70). Rarely, primary ovarian
mucinoustumors of the intestinal typeare associated with pseudomyxoma peritonei;these
tumors typically have an associated teratomatous component in the ovary (71,72). The
naturalhistoryofthesetumorsisnotwellunderstood.
EndometrioidTumors
Ovarianepithelialtumorswithendometrioiddifferentiationexhibittheglandularorstromal
histologic features of endometrial glands and stroma. Ovarian tumors showing
endometrioiddifferentiationaccountforlessthan10%ofallsurfaceepithelial–stromal
tumors.
BenignEndometrioidTumorsandEndometrioidBorderlineTumors—
EndometrioidTumorsofLowMalignantPotential
Benign endometrioid tumors are rare and, when present, typically unilateral.
Borderlineendometrioidtumorsmaybebilateral(30%)andareclinicallybenign. The
tumorsresembletheir uterinecounterpartsandarecomposed ofglandularorvilloglandular
proliferations,whichmayshowcytoplasmicclearingorsecretory-typechangeswithsub-or
supranuclear vacuolization. Squamous metaplasia is common. The changes in borderline
endometrioid tumors are analogous to those seen in complex atypical hyperplasia of the
endometrium,inthattherearecytologicandarchitecturalatypiabutnostromalinvasion.
EndometrioidOvarianCarcinoma
The typical ovarian endometrioid carcinoma is comparable to FIGO grade 1 or 2
endometrioidadenocarcinomaoftheuterus,althoughoccasionaltumorshaveahighergrade,withamoresolidgrowthpattern(Fig.6.71).Squamousmetaplasiaiscommon,as
areothermetaplasticchanges(secretory,ciliatedcell,oxyphilic,ormucinous).Endometrioid
carcinomasoftheovaryexhibitawidearrayofpatternsthatmayposedifferentialdiagnostic
problemsforthepathologist,includingspindled,tubular,insular,trabecular,microglandular,
adenoidbasal,andadenoidcystic.Whenprominent,thesepatternsmaymimicSertolicellor
Sertoli–Leydigcelltumors,carcinoidtumors,orgranulosacelltumors.Metastasesfromthe
gastrointestinaltractmaysimulateaprimaryendometrioidcarcinoma.Anassociationwith
endometriosis,eitherovarianorelsewhereinthepelvis,isobservedinasmanyas40%
ofcases.Simultaneous primary endometrioid carcinomasinthe uterus are presentin
20%ofcases(60).
Figure 6.67 Mucinous borderline tumor, gastrointestinal type. Papillary growth pattern,
stratification, and nuclear atypia distinguish these tumors from cystadenoma. Intestinal
differentiation is exemplified by goblet cells and, in some cases, Paneth cells. There is no
stromalinvasion.(top,lowpower;bottom,highpower)
Figure 6.68 Mucinous adenocarcinoma of ovary. Expansile stromal invasion in a mucinous
ovariantumorisclassifiedasmucinouscarcinoma,butitdoesnotappeartoconferthesame
ominousprognosisasmucinousovariantumors with destructive stromal invasion(Fig. 6.69).
(top,lowpower;bottom,highpower)
Figure 6.69 Mucinous adenocarcinoma of ovary. Destructive stromal invasion in a
mucinousovariantumoris classified as mucinous carcinoma. Metastasis—for example, from
the gastrointestinal tract—should always be considered, especially in the presence of highstagediseaseorbilateralovarianinvolvement.
ClearCellTumors
Ovarianepithelialtumors withclearcelldifferentiationarecharacterized byepithelialcells
containingglycogen-richclearcytoplasm,andhobnailcellswithvaryingdegreesoffibrous
stroma. Previously considered to be of mesonephric origin, clear cell ovarian epithelial
tumorsarerecognized asderivativesofthemülleriantract.Clearcelltumorsaccountfor
only3%ofovarianepithelialtumors,butalmostallaremalignant.
BenignClearCellTumorsandBorderlineClearCellTumors—ClearCell
TumorsofLowMalignantPotential
The benign and borderline clear cell adenofibromatous tumors are extremely rare
(<1%ofclearcelltumors)andpresentinthesecondtoseventhdecadesoflife.
ClearCellOvarianCarcinoma
Clear cell carcinomas tend to occur in the fifth to seventh decades (10% in the fourth
decade). There is an unexplained increased prevalence of clear cell carcinoma in Japan
relative to Western countries. Two-thirds of women with clear cell carcinomas are
nulliparous. More than one-half have associated endometriosis involving the ovary or
other pelvic sites. When associated with endometriosis, mixed clear cell and
endometrioidcarcinoma mayoccur. Patients withclearcell carcinomaare atriskfor
developingparaneoplastichypercalcemia orpelvicvenousthromboses. Most clear cell
carcinomas, even when advanced stage, are unilateral (60). The tumors are composed of
glands, tubules, papillae, or solid sheets of polyhedral cells with optically clear or
eosinophilic granular cytoplasm (Fig. 6.72). Hobnail cells are characteristic. Psammoma
bodiesmaybepresent,andasmanyas25%containeosinophilichyalinebodies.Clearcell
carcinomas of the ovary are not graded (60). Approximately 45% of endometriosisassociatedclearcellcarcinomas(and30%ofendometriosis-associatedendometrioidovarian
carcinomas)harbormutationsinARID1A(73).
TransitionalCell(Brenner)Tumors
Transitional cell tumors are thought to arise through metaplasia of the ovarian surface
epithelium and are analogous to Walthard nests, which are transitional-type epithelial
inclusionsoccurringbeneaththeserosaofthefallopiantubesandinthehilarregionsofthe
ovaries. They are uncommon (3% of all surface epithelial–stromal tumors). Most are
clinicallybenign.
BenignTransitionalCell(Brenner)Tumor
Brennertumorsarethemostcommontypeofovariantransitionalcelltumor.Theyare
often microscopic or incidental findings discovered at laparotomy for unrelated pelvic
conditions. They affect patients during the fourth to eighth decades (mean age 50 years).
Theyaretypicallysolid,unilateraltumorswithsmallcystsoncutsection;mostarelessthan
2cm.Agrittyconsistencymaybepresentbecauseofflecksofcalcification(Fig.6.73).They
may be associated with a mucinous cystic tumor. Microscopically, they contain nests of
cytologically bland cells with a urothelial appearance, surrounded by a prominent
fibromatous stroma. The individual nests may be solid or microcystic, with an inner
mucinousepitheliallining.
