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Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5186_Библиотеки_им_академика_М_И_Перельмана.pdf
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Figure 6.25 Fibroepithelial stromal polyp. Atypical stromal cells (inset) may simulate a malignancy,butthisisabenign,probablyreactiveprocess.Althoughthelesionextendstothe surfaceepithelium,thereisnocellularcondensation(formingaso-calledcambiumlayer)atthe surface; the absence of a cambium layer helps to distinguish this lesion from sarcoma botryoidsonalimitedsampling(seeFig.6.26).Thispolypoccursmostcommonlyinthevagina butcanalsobeseeninthevulvaandcervix.
VulvarIntraepithelialNeoplasia
Inthevulva,therearetwodifferentpathways—HPV-relatedandHPV-unrelated—thatleadto thedevelopmentofsquamouscellcarcinoma.Thetwo-tieredCAP-ASCCPLASTProject terminology applies to HPV-related precursor lesions of the vulva (1). LSIL consists predominantlyofcondylomaacuminata,whichareassociatedwithlow-riskHPVtypes6and 11(Fig.6.27).Flatcondylomasareuncommoninthevulvabutmaybeassociatedwithhigh­risk HPV. Fibroepithelial polyps (skin tags) and hymenal mucosa can be mistaken for exophyticcondylomas.Nonspecificinflammatoryatypiaorpsoriasiscanbemisdiagnosedas flatcondylomas.
Figure6.26 Sarcomabotryoids(embryonalrhabdomyosarcoma).Topleft:Botryoidgrowth patternofcervicalembryonal rhabdomyosarcoma(CourtesyofDr.MatthewQuick).Top right: Stellate cells set in myxoid stroma are more condensed beneath the surface epithelium, forming a distinct cambium layer. Bottom: Small cells with hyperchromatic nuclei are punctuatedbylargercellswithmoreabundanteosinophiliccytoplasm.
VulvarHSILcanbequalifiedasVIN2orVIN3.High-riskHPVisidentifiedin53–90% ofcasesofHSIL(VIN3),withHPV16themostcommontype(32).HPV18,31,33,35,
51,52,and68havebeenisolatedfromcasesofvulvarHSIL(33).
Vulvar HSIL is commonly multicentric, with extension to the perineum and involvementofthe cervix and vagina. Therearethreepatternsorsubtypes of vulvar HSIL: warty,basaloid, and pagetoid. The warty pattern is characterized by prominent
koilocytosis or warty architecture (Fig. 6.28), whereas the basaloid is more poorly differentiated(Fig.6.29). The atypia involves two-thirds or more of the epithelium and is notable for disorganization, cells with high nuclear-to-cytoplasmic ratios, dark irregular nuclei,andnumerousmitoticfigures,includingabnormalforms.Dyskeratoticcellsareoften present, and the dysplastic cells frequently extend down pilosebaceous units, which can mimicinvasivecarcinoma.
Table6.5TerminologyforPrecursorLesionsofVulvarSquamousCellCarcinoma
LAST2012 WHO2003 ISSVD2004 Synonyms
LSIL Condyloma
acuminatum
Condylomaacuminatum
LSIL VIN1 n/a Flatcondyloma,milddysplasia
HSIL VIN2 VIN,usualtype Moderatedysplasia
HSIL VIN3 Severedysplasia,carcinoma
insitu,Bowendisease, bowenoidpapulosis,bowenoid dysplasia
Carcinomainsitu
(simplextype)VIN 3
VIN,differentiatedtype
LAST,LowerAnogenitalSquamousTerminology;WHO,WorldHealthOrganization;ISSVD,InternationalSociety fortheStudyofVulvarDisease;LSIL,low-gradesquamousintraepitheliallesion;VIN,vulvarintraepithelial neoplasia;HSIL,high-gradesquamousintraepitheliallesion.
The pagetoid subtype is rare but important to recognize because it can closely mimic extramammary Paget disease. Histologically, both are characterized by single cells and clustersofcellswithpalecytoplasminvolvingthesquamousepitheliumofthevulva,andthe distinctionbetweenthesetwoentitiesrequiresspecialstains.
DifferentiatedorsimplexVINislocalizedtothevulvaandusuallyidentifiedadjacentto
areasofinvasivecarcinomainelderlypatients.Itisrarelyidentifiedprospectively(34).In
contrasttovulvarHSIL,HPVisrarelyidentifiedinsimplexVIN(33). The morphologic changesofsimplexVINaresubtleandcharacterizedbynuclearatypiaofthebasalcelllayer and expansion of the basal layer into elongated, narrow,branching rete ridges (Fig. 6.30). Thenucleicanrangefromrelativelysmall,darkandirregular,toenlargedandpleomorphic. Maturationisabnormal,as exhibited by the presence of enlarged keratinocyteswithlarge, pleomorphicnucleiandabundant,markedlyeosinophiliccytoplasminthemid-tosuperficial layers. These abnormal keratinocytes can extend into the basal layer and involve the rete ridges(34). The thickness of the epithelium is variable, and can be atrophic or acanthotic (i.e.,thickened).Thedifferentialdiagnosis for simplex VIN includes lichen sclerosus with squamous hyperplasia, and other benign dermatologic conditions such as lichen simplex chronicus,psoriasis,spongioticdermatitis,andcandidavulvitis.
Figure6.27 Condyloma.Exophyticcondylomasarecommoninthevulvaandareassociated withlow-riskHPVtypes6and11.
Figure6.28 ClassicVIN,warty.Prominentkoilocytosisispresentonthesurfaceandoverlies severeatypiainvolvingtwo-thirdsoftheunderlyingepithelium.
Lichensclerosusisapotentialriskfactorforthedevelopmentofvulvarsquamouscell carcinoma. It may play a role in the HPV-independent pathway. Lichen sclerosus is negativeforHPV and is more frequently identifiedinassociationwith simplex VIN than
withclassicVIN(32,33).
Figure 6.29 Classic VIN, basaloid. Cells with high nuclear-to-cytoplasmic ratios and dark, irregularnucleiinvolvethefullthicknessofthesquamousepithelium.
SquamousCellCarcinoma
Primary invasive squamous cell carcinomas of the vulva can be subdivided into two main types: conventional squamous cell carcinoma and verrucous carcinoma.
Conventional squamous cell carcinomas can exhibit different growth patterns, including warty, basaloid, and keratinizing(Fig.6.31). Invasive squamous cell carcinomas that have warty or basaloid features are typically associated with classic VIN and high-risk HPV, whereas well-differentiated keratinizing squamous cell carcinomas are more commonly associatedwithsimplexVIN(32).
Figure 6.30 Simplex VIN. Abnormal keratinocytes with abundant, markedly eosinophilic cytoplasminvolvethemidtosuperficiallayersandextendintothe elongated, branchingrete ridges.
Verrucouscarcinomaisararespecialvariantofsquamouscellcarcinomathatisslow growing and has minimal metastatic potential. It is typically exophytic, well
circumscribed, and composed of hyperkeratotic fronds of cytologically bland squamous epithelium.Theinterfacewiththeunderlyingstromacharacteristicallyconsistsofapushing borderwithassociatedchronicinflammation(Fig.6.32).
Figure 6.31 Conventional keratinizing squamous cell carcinoma of the vulva. Nests of well-differentiatedtumorcellsjaggedlyinvadeintothestromaonmicroscopicexamination.
Figure 6.32 Verrucous carcinoma of the vulva. Top: Vulvectomy specimen showing exophyticverrucoustumor.Bottom:Thetumorisexophyticwithhyperkeratoticfrondsofbland squamousepitheliumandwellcircumscribedwithapushingborderwiththeunderlyingstroma.