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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5186_Библиотеки_им_академика_М_И_Перельмана.pdf
Figure6.19Villoglandularadenocarcinomaofcervix.Slender, elongated villi are lined by
well-differentiatedepitheliumwithanexophyticgrowthpattern.Thistumorisassociatedwitha
good prognosis, provided there is minimal or no cervical stromal invasion. (top, low power;
bottom,highpower)
Figure 6.20 Neuroendocrine carcinoma of cervix. Malignant cells with high mitotic index
are arranged in a sheetlike growth pattern. Necrosis is often present in these clinically
aggressivetumors.
LocalizationofAdenocarcinoma:CervixversusCorpus
Distinction between primary endometrial and primary endocervical adenocarcinoma
maybedifficultinbiopsyandcurettagespecimens,especiallywhennoprecursorlesion
ispresent.Whenclinical and histologic evaluationfails to clearly identifyacarcinoma as
cervical or endometrial in origin, an immunohistochemical panel that includes several
markers, such as estrogen receptor (ER), progesterone receptor (PR), vimentin, and
p16, is often useful (20,25,26). Using this particular panel (Table 6.4), glandular
proliferationsthatareER-positiveandPR-positive,vimentin-positive,andp16-negativeare
almostalwaysendometrialorigin (Fig. 6.22), whereas those that are ER-negative and PRnegative, vimentin-negative, and p16-positive are very likely to be endocervical in origin
(Fig. 6.23). Because the distinction between these two sites of origin may be based on
whether a strong staining pattern with p16 is focal or diffuse in an individual case, this
patternofreactivityismostusefulinwholetissuesections.Inlimitedsamplings,suchasare
encounteredinroutinebiopsyandcurettagespecimens,thesepatternsmaybemisleading.In
addition,overexpression of p16 can occurina variety of other carcinomasindependentof
HPVstatus,includinguterineserouscarcinomas.
MesenchymalTumors
Stromalandsmoothmuscletumorsmayoccurinthecervixwheretheyresembletheirmore
common uterine counterparts. Although the vagina is the more common site, embryonal
rhabdomyosarcoma may occur in the cervix; in contrast to vaginal rhabdomyosarcoma,
whichismorecommoninchildren,cervicalrhabdomyosarcomastendtooccurinyoung
adults. Most are embryonal, but alveolar variants may be seen. Embryonal
rhabdomyosarcomas of the cervix may be associated with DICER1 syndrome, a
pediatriccancerpredispositionconditioncausinga variety oftumortypes inchildren
and young adults, including pleuropulmonary blastoma, cystic nephroma,
rhabdomyosarcoma, multinodular goiter, thyroid carcinoma, ovarian Sertoli–Leydig cell
tumor and other neoplastic conditions (27). Several low-grade sarcomas associated with
NTRK and COL1A1-PDGFB rearrangements have been described in the cervix. These
variablesexpressS100proteinandCD34(28).
MixedEpithelialandMesenchymalTumors
The same mixed epithelial and mesenchymal tumors that occur in the uterine corpus may
occur in the cervix. They tend to exhibit the same patient demographics as their uterine
counterparts,butcervicaladenosarcomasoftenoccuratayoungerage(29).Mostpresent
duringthereproductiveyearswithabnormalbleedingandrecurrentpolyps.Dataarelimited,
butmostappeartohaveamorefavorableprognosis,possiblybecauseoftheearlydetection
oflow-stagediseaseinthemajorityofpatients.Asinuterinecorpustumors,deepinvasion
andsarcomatousovergrowthareadverseprognosticindicators.
Figure6.21Adenoidbasalcarcinoma(epithelioma).This variant of cervical carcinoma is
characterized by nests of bland basaloid and squamoid cells in the cervical stroma. A
squamousintraepitheliallesionis typically presentintheoverlyingmucosa.Thisneoplasm is
oftenreferredtoasadenoidbasalepitheliomabecauseithasaveryfavorableprognosis.(top,
lowpower;bottom,highpower)
Table6.4DistinguishingEndometrialfromEndocervicalAdenocarcinoma
Endocervical Endometrial
ClinicalorRadiologic Dominantmassincervix Dominantmassinuterinefundus
H&E Cancer-containingfragmentsdiffer
fromendometrialfunctionalis
fragments(dimorphicpattern)
Adenocarcinomainsituin
associatedendocervicalglands
Associatedsquamous
intraepitheliallesion
Mergenceofmalignantfragments
withlessatypicalpatternsin
otherfragments(endometrial
hyperplasia/metaplasia)
Stromalfoamcells
Noadenocarcinomainsituin
associatedcervicalfragments
Immunohistochemistry ER-negativeandPR-negative
Vimentin-negative
p16-positive
ER-positiveandPR-positive
Vimentin-positive
p16-negative
HPVinsitu Positive Negative
H&E,hematoxylinandeosin;ER,estrogenreceptor;PR,progesteronereceptor;HPV,humanpapillomavirus.
OtherTumors
A variety of other neoplasmsmayarise in the uterine cervix. Theseincludealveolar soft
partsarcoma, rhabdomyoma,andnerve sheath tumors. Alveolar soft part sarcomas of
thefemalegenitaltractappeartohaveabetterprognosisthantheircounterpartsinothersites.
Yolk sac tumors may occur in the cervicovaginal region. Melanoma, lymphoma, and
leukemia usually involve the cervix secondarily, either as metastases or in the setting of
widespreaddisease(22).
Vagina
SquamousLesionsoftheVagina
SquamousIntraepithelialLesion
TheCAP-ASCCPLASTProjectrecommendationsforstandardizedterminologyapply
across the anogenital tract for HPV-related preneoplastic squamous lesion.
Consequently, preneoplastic lesions of the vagina are termed LSIL or HSIL with the
corresponding vaginal intraepithelial neoplasia (VAIN) terminology in parentheses: LSIL
(VAIN1),HSIL(VAIN2),HSIL(VAIN3).LSILandHSILinthevaginahavethesame
morphologic features as those in the cervix. LSIL can be mimicked by vaginal
papillomatosis, which exhibits papillary architecture, parakeratosis, and cytoplasmic halos.
However, papillomatosis lacks significant acanthosis and nuclear atypia. HSIL can be
mimickedbyatrophyandimmaturesquamousmetaplasiabutcanbedistinguishedbyalack
ofnuclearatypiainthelattertwoentities.
Figure 6.22 Endometrial adenocarcinoma (upper left). Endometrial adenocarcinoma is
typicallyER-positive/PR-positive(upperright),vimentin-positive(lowerright),andp16-negative
(lowerleft).
Figure 6.23 Endocervical adenocarcinoma (upper left). In contrast to endometrial
adenocarcinoma(seeFig.6.22),endocervicaladenocarcinomaistypicallyER-negative/PRnegative(upperright),vimentin-negative(lowerleft),andp16-positive(lowerright).
SquamousCellCarcinoma
Primarysquamous cell carcinomaof thevaginais uncommon. Vaginalsquamous cell
carcinomamorefrequentlyoccurs as a resultof secondary involvement by extension
from the cervix or vulva. The morphologic features are the same as for the cervix. In
patientswith vaginal adenosis, immature squamousmetaplasiainvolving areas of adenosis
canbemistaken for invasive squamous cell carcinoma,butthe two entities can be readily
distinguishedbythelackofcytologicatypiaandthelackofadesmoplasticresponsewiththe
benignprocess.
GlandularLesionsoftheVagina
Clear cell adenocarcinoma is the most common malignant glandular lesion in the
vagina, followed by endometrioid, mucinous, and mesonephric subtypes. The latter
histologicsubtypesoccurpredominantlyinperimenopausalwomen.
ClearCellAdenocarcinoma
Clearcellcarcinomaofthecervicovaginalregionisstronglylinkedtoinuteroexposure
to diethylstilbestrol (DES) and has decreased in incidence with decreased use of this
teratogen.Ittypicallyoccursinassociationwithadenosis.Althoughtheuppervaginaisthe
mostcommonsiteofinvolvementinDES-exposedwomen,thecervixisthemostcommonly
affected site in non-DES–exposed women. The appearance is the same as the ovarian
counterpart(Fig.6.24),andprognosisisdeterminedby tumor size, depth of invasion, and
lymphnodeinvolvement.
Adenosis
Thepresenceofectopicglandularepitheliuminthevaginaistermedadenosis.Adenosis
may exhibit mucinous endocervical-like epithelium or tuboendometrioid epithelium. It is
often asymptomatic but may be detected by colposcopic examination. Atypical adenosis,
whichexhibitsarchitecturalandcytologicatypia,isoftenseeninassociationwithclearcell
adenocarcinoma.
FibroepithelialStromalPolyp
Fibroepithelial stromal polyp is a common, typically small, exophytic polypoid lesion
occurringinreproductive-agedwomen,mostcommonlyinthevagina,butalsointhevulva
andcervix.Almostone-thirdoccurduringpregnancy.Thepolypsoftenoccurintheanterior
wallandrangeinsizefrom0.5cmto4cm.Histologically,theyarecharacterizedbysmall
spindle cells and enlarged, stellate, multinucleated cells in a myxoid stroma (Fig. 6.25).
Mitotic figures can be prominent and may raise suspicion for a malignant process.
Fibroepithelialstromalpolypsaredistinguishedfromsarcomabotryoidesbytheabsenceofa
cambiumlayer.
Figure 6.24 Clear cell adenocarcinoma of vagina. In this solid pattern of clear cell
carcinoma,sheetsofmalignantcellswithclearcytoplasmextensivelyreplacenormaltissue.
SarcomaBotryoides
Embryonalrhabdomyosarcomais themostcommon vaginalsarcoma;it occursalmost
always in infants and children, but rare cases have been reported in young adults and
postmenopausal women. The tumors present as polypoid vaginal masses, often
protruding through the introitus, that may vary in size from 0.2 cm to 12 cm.
Microscopically, the tumor is composed of small, round to oval or spindle-shaped cells
surroundedbyanedematous,myxoidstroma(Fig.6.26).Acharacteristicallydense,cellular
cambium layer can be seen in the subepithelial zone. Rhabdomyoblasts (strap cells) are
presentbutmaybesparseorilldefined.Identificationofrhabdomyoblastscanbefacilitated
byimmunostainingformyogeninorMyo-D1.
Widelocal excision and combination chemotherapy is the preferredtreatmentforsarcoma
botryoides.StaginginchildrenisbasedontheIntergroupRhabdomyosarcomaStudyGroup
classification; adults are staged according to the TNM and FIGO system. Most
rhabdomyosarcomasin thevulvovaginalregion areof the embryonaltype, butraretumors
areofthealveolartype,whichhasaworseprognosis.
Melanoma
Melanoma is the second most common malignancy to occur in the vagina (after
squamouscellcarcinoma).Affectedpatientsaretypicallypostmenopausalandpresentwith
vaginalbleeding.Most,butnotalllesionsarepigmented,nodular,orflat,andmeasure2to3
cminsizeatdiagnosis;ulcerationmaybepresent.Theanteriorwallofthelowerthirdof
the vagina is the most common site. The diagnosis may be difficult on small biopsies
becauseaninsitucomponentorpagetoidspreadisoftenabsent.Epithelioidcelllesionsmay
resemble carcinoma, whereas spindle cell lesions may create confusion with sarcoma.
Immunohistochemical stains for melanoma markers are often required to establish a
diagnosis.Theprognosisispoor.
PostoperativeSpindleCellNodule
Avarietyofreactiveprocessesmayoccurwithinthevagina,particularlyfollowingsurgical
procedures. One such lesion is composed of a cellular, spindle cell proliferation that may
simulateaneoplastic process.Thislesionhasbeen designatedas postoperativespindlecell
nodule.
Vulva
SquamousCellLesionsoftheVulva
Terminology
Similartothecervix,therearemultipleterminologysystemsinusetodescribepreneoplastic
lesionsofthevulva(30)(Table6.5).ThemaindifferenceliesinwhetherVINisgraded.The
2003WorldHealthOrganization(WHO)classificationgradesVINonascaleof1to3,
with VIN 3 further subdivided into classic type and simplex type. In contrast, the
InternationalSocietyfortheStudyofVulvovaginalDisease(ISSVD)decidedin2004to
eliminatethecategoryofVIN1,andtoabolishgradingofVIN.Thisdecisionwasbased
onthelack ofevidencethat condylomas,whichaccountforthemajorityofVIN 1lesions,
progresstocarcinoma,andthelackofinterobserverreproducibilityfordiagnosingVIN1or
for distinguishing between VIN 2 and VIN 3 (31). The ISSVD retained the distinction
betweenclassicVINandsimplex(differentiated)VIN.Giventhevariabilityinterminology,
it is best to determine what terminology system the pathologist is using, especially if the
diagnosisis“vulvarintraepithelialneoplasia(VIN)”withnofurtherspecification.