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and irregularly contoured glandular elements, often with internal papillations scattered
throughoutavariablycellularstroma.Thestromaformsacharacteristichypercellularcollar
or cuff (so-called cambium layer) around the glands, often producing irregular, stellate
glandularconfigurations(Fig.6.58).
Approximately 25% of adenosarcomas are myoinvasive. Most patients with uterine
adenosarcomaare curedby hysterectomy.Deep myoinvasion, lymphovascular invasion,
high-gradeheterologousstroma,stromalovergrowth,andextrauterinespread areassociated
with disease recurrence. Stromal overgrowth is defined as pure stromal proliferation
constituting greater than 25% of the tumor. Approximately 10–25% of patients with
uterineadenosarcomadieoftheirdisease.Thisfigurerisesto50%forthosewhosetumors
containstromalovergrowth.
Adenosarcoma often represents a challenge for the pathologist because of a significant
overlapwith adenofibroma and otherformsof benign polyp. Mostadenosarcomasarise in
the uterine corpus, but cervical, vaginal, tubal, ovarian, and primary peritoneal
adenosarcomasalsooccur.Involvementofadditionalextragenitalsitesinwomenislinkedto
endometriosis.
Figure 6.58 Adenosarcoma of uterus. In contrast to adenofibroma, the stroma in
adenosarcoma is cellular and mitotically active. Stromal condensation around the glandular
componentformsacharacteristiccambiumlayer.
Carcinosarcoma
Despite the long-entrenched terminology of “malignant mixed müllerian tumor,”
carcinosarcoma is the preferred designation for mixed neoplasms composed of carcinoma
andsarcoma.Withrareexceptions,carcinosarcomais a diseaseofelderlymenopausal
women,andthereisanassociationwithpriorpelvicradiation.Mostpatientspresentwith
uterine bleeding, and the typical clinical appearance is that of a fleshy, necrotic and
hemorrhagic,polypoidmassthatfillstheuterinecavityandextendsthroughthecervicalos.
The histologic diagnosis of carcinosarcoma requires the presence of a distinct biphasic
neoplasm, composed of separate but admixed malignant-appearing epithelial and
mesenchymal elements (Fig. 6.59). The mesenchymal and epithelial elements should not
mergewithoneanother.Boththehigh-gradenuclearfeaturesandthebiphasicpatternofthis
neoplasm are obvious in the typical case. The stromalcomponents may be homologous
(leiomyosarcoma, stromal sarcoma, fibrosarcoma) or heterologous (chondrosarcoma,
rhabdomyosarcoma,osteosarcoma,liposarcoma).Althoughtraditionholdsthatheterologous
elementsdonotbearonprognosis,a2007studyfromMemorialSloanKetteringsuggested
that surgical stage I uterine carcinosarcoma with heterologous elements may be more
aggressivethanthosewithhomologouselements(59).Prognosisisdependentonthestage,
thesizeofthetumor,andthedepthofmyometrialinvasion.
Ovary
Fourbroad histogenetic categories of ovariantumors areobserved: epithelial tumors
(65–70%), sex cord–stromal tumors (15–20%), germ cell tumors (5–10%), and
metastases(5%).
OvarianEpithelialTumors
Ovarianepithelialtumorsarethe most common neoplasms of theovary (Table 6.10).
Theyconsist of sixtypes:serous,mucinous,endometrioid, clearcell,transitional, and
undifferentiated(60,61).Tumorswith squamousdifferentiationwere historically included
amongtheepithelialtumors,butpuresquamoustumorsarerare;mostariseinteratomas.
SerousTumors
Tumorswithserousdifferentiationrepresent45%ofepithelialovarianneoplasms;they
arecharacterizedbyepithelialcellsresemblingthoseofthefallopiantubeandencompassa
group of three biologically distinct entities: benign serous cystadenofibroma, serous
borderlinetumor(lowmalignantpotential),andserouscarcinoma.
BenignSerousTumors
Benign serous cystadenomas or cystadenofibromas constitute almost one-half of all
serousovarianneoplasms.Benignseroustumorsoccuroverawideagerangebutaremost
common in the reproductive age group. They are often bilateral and composed of varying
amountsoffibrousstromaandcysts.Theyrangeinsizefrom1cmto10cm(rarelyaslarge
as 30 cm). The cysts are unilocular or multilocular and may contain papillary projections.
Surfacepapillomasmaybepresent.Microscopically,thecystsarelinedbyasimplelayerof
epitheliumthatrecapitulatestheciliatedepithelialcellsofthefallopiantube.
Figure6.59Carcinosarcomaofuterus.Biphasiclesioncomposedofmalignantglandsand
stroma (top). Heterologous elements, such as cartilage depicted here, may be present in
carcinosarcoma(bottom).
SerousBorderlineTumors—SerousTumorsofLowMalignantPotential
Serousborderline tumors constituteapproximately15% ofovarian serousneoplasms
andaccountformost oftheborderlineepithelialneoplasms.Theyoccurat aslightly
youngeragethanserouscarcinomas(mean45yearsvs.60years).Theyaremoreoften
bilateral and larger than benign serous tumors and may present with disease beyond the
confines of the ovary.Serous neoplasms in the borderline group are predominately cystic
withvariableamountsofpapillaryepithelialprojections,althoughsolidtumorswithsurface
papillaryexcrescences mayoccur.Microscopically, serousborderline tumorsare composed
ofarchitecturallycomplexbranchingpapillaryandmicropapillarystructures,notunlikethat
oflow-gradeserouscarcinomas,buttheydonotfeaturedestructiveinvasionoftheovarian
stroma. The nuclei are uniform or mildly atypical (Fig. 6.60). Mitotic activity is low.
Psammomabodiesareoftenpresentbutarenotdiagnostic.
Table6.10HistologicClassificationofEpithelialOvarianTumors
HistologicType
a
Total(%)
Serous 46
Mucinous 36
Endometrioid 8
Clear 3
Transitional 2
Undifferentiated 2
Mixed 3
a
Tumorswithsquamousdifferentiationhavealsobeenincludedamongtheepithelialtumors,butpuresquamous
tumorsarerare.Mostariseinanepidermoidordermoidcyst(60,61).
MicropapillaryPattern
Approximately 10% of serous borderline tumors contain foci of significant micropapillary
architecture,defined as nonhierarchical branchingofslender,elongatedpapillae that are at
least five times as long as they are wide (Fig. 6.61), or a sievelike cribriform pattern
occupying a continuous 5-mm extent. The micropapillary variant is more frequently
associated with bilaterality,ovarian surface involvement, and the presence of extraovarian
disease (62). When the extraovarian disease is invasive, serous borderline tumors with
micropapillaryarchitecturehaveapoorerprognosis.
StromalMicroinvasion
Stromalmicroinvasion,defined as 5 mm in linearextent or10 mm2 in area, may be
foundin10–15%ofseroustumorsoflowmalignantpotential.Stromalmicroinvasionis
characterized by eosinophilic cells or small micropapillae lying within stromal spaces
beneathlargerpapillae(Fig.6.62).Itisseenmorefrequentlyduringpregnancy.Althoughthe
overallprognosis isfavorable,stromal microinvasionappears to representa histologic link
betweenserousborderlinetumorsandlow-gradeserouscarcinomaandislikelyabonafide
formofearlyinvasion(63).
ExtraovarianDisease
Approximately 30–40% of serous borderline tumors are associated with similarappearinglesionsinthepelvisandintra-abdominalsites,includinglymphnodes.These
lesions,termedimplants,maybemicroscopicormacroscopic,and aresubclassifiedas
noninvasive or invasive types, based on the presence of destructive infiltration into
underlyingnormaltissuestructures(Fig.6.63).Noninvasive implants aredividedinto
epithelial and desmoplastic types, depending on whether or not there is an associated
stromal response. The distinction between noninvasive and invasive implants is
important, because extraovarian invasive disease is associated with a significantly
poorerprognosis(62).Attimes,itisdifficulttodeterminewhetheranimplantisinvasiveor
not;intheseinstances,theimplantsmaybeclassified asindeterminate. Implantsthat are
indeterminateforinvasionappeartohave a prognosis that is intermediate to that of
noninvasiveandinvasiveimplants(64).
Figure 6.60 Serous borderline tumor (low malignant potential). Papillae are lined by
stratified tubal type epithelium with tufting. Mitotic activity is minimal, and cytologic atypia is
mildtomoderate.Thereisnostromalinvasion.
Figure 6.61 Serous borderline tumor with micropapillary pattern. In this variant, the
papillae are elongated and at least fivefold longer than their width. Ovarian surface
involvement,bilaterality,andextraovarianimplantsaremorecommoninthisvariantthaninthe
usualserousborderlinetumor.
Figure6.62Stromalmicroinvasion in serous borderlinetumor.Small foci of intrastromal
single cells and small, nonbranching papillae may be seen in 10–15% of serous borderline
tumors. Although such foci likely represent early stromal invasion, their presence does not
warranta diagnosis ofcarcinoma, provided theyare small (<5 mm) and show no significant
cytologicatypia.
Figure 6.63 Top: Noninvasive implant of serous borderline tumor. Bottom: Invasive
implantofserousborderlinetumor.Unlikenoninvasiveimplants,invasiveimplantshavean
irregularstromalinterface.
Figure 6.64 Lymph node involvement by serous borderline tumor. Lymph node
involvementbyserousborderlinetumorcanbefloridbutdoesnotconferapoorerprognosis.
Lymphnodeinvolvement(Fig.6.64)occursin20–30%ofovarianseroustumorsoflow
malignantpotential(65),butthepresenceoflymphnodeinvolvementdoesnotconfera
worseprognosisunlessitexhibitsaninvasivepattern.
Endosalpingiosisfrequentlycoexistswithserousborderlinelesionsintheperitoneumand
lymphnodes, butthe presenceof endosalpingiosisalonedoesnotupstage thedisease. The
frequentcoexistenceofendosalpingiosiswith“implants”ofovarianserousborderlinetumor
would seem to support the concept that serous tumors may arise in endosalpingiosis in at
leastasubsetofcases.
Low-GradeSerousCarcinoma
Ovarianserouscarcinomaisgradedusingatwo-tieredsystembasedonthedegreeofnuclear
atypia and the mitotic index (66,67). Low-grade (grade 1) serous carcinomas (Fig. 6.65)
accountforlessthan10%ofserouscarcinomas.Thelow-grade(grade1)serouscarcinomas
exhibitmutationsinKRASandNRAS(68).
Serouspsammocarcinoma,averyrarevariantoflow-gradeserouscarcinoma,isdefinedby
thepresenceofmassivepsammomatouscalcification (at least 75% of the tumor cell nests
contain a psammoma body), predominant extraovarian disease distribution, and low-grade
cytologicatypia.Theprognosisforserouspsammocarcinomaisfavorable(69).