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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5186_Библиотеки_им_академика_М_И_Перельмана.pdf
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- •Contributors
- •Preface
- •Contents
- •Sporadic
- •Hereditary
- •Oncogenes
- •Oncogenes
- •Necrosis
- •Autophagy
- •Apoptosis
- •Angiogenesis
- •Biomarkers
- •Immunotherapy
- •Cytokines
- •Excretion
- •Antimetabolites
- •Fractionation
- •Hyperthermia
- •Brachytherapy
- •Palliation
- •Cervix
- •Vagina
- •Melanoma
- •Vulva
- •Adenofibroma
- •Adenosarcoma
- •Carcinosarcoma
- •Ovary
- •Choriocarcinoma
- •Incidence
- •Prevalence
- •Validity
- •Sensitivity
- •Specificity
- •Cervix

Figure 6.25 Fibroepithelial stromal polyp. Atypical stromal cells (inset) may simulate a
malignancy,butthisisabenign,probablyreactiveprocess.Althoughthelesionextendstothe
surfaceepithelium,thereisnocellularcondensation(formingaso-calledcambiumlayer)atthe
surface; the absence of a cambium layer helps to distinguish this lesion from sarcoma
botryoidsonalimitedsampling(seeFig.6.26).Thispolypoccursmostcommonlyinthevagina
butcanalsobeseeninthevulvaandcervix.

VulvarIntraepithelialNeoplasia
Inthevulva,therearetwodifferentpathways—HPV-relatedandHPV-unrelated—thatleadto
thedevelopmentofsquamouscellcarcinoma.Thetwo-tieredCAP-ASCCPLASTProject
terminology applies to HPV-related precursor lesions of the vulva (1). LSIL consists
predominantlyofcondylomaacuminata,whichareassociatedwithlow-riskHPVtypes6and
11(Fig.6.27).Flatcondylomasareuncommoninthevulvabutmaybeassociatedwithhighrisk HPV. Fibroepithelial polyps (skin tags) and hymenal mucosa can be mistaken for
exophyticcondylomas.Nonspecificinflammatoryatypiaorpsoriasiscanbemisdiagnosedas
flatcondylomas.

Figure6.26 Sarcomabotryoids(embryonalrhabdomyosarcoma).Topleft:Botryoidgrowth
patternofcervicalembryonal rhabdomyosarcoma(CourtesyofDr.MatthewQuick).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
punctuatedbylargercellswithmoreabundanteosinophiliccytoplasm.

VulvarHSILcanbequalifiedasVIN2orVIN3.High-riskHPVisidentifiedin53–90%
ofcasesofHSIL(VIN3),withHPV16themostcommontype(32).HPV18,31,33,35,
51,52,and68havebeenisolatedfromcasesofvulvarHSIL(33).
Vulvar HSIL is commonly multicentric, with extension to the perineum and
involvementofthe cervix and vagina. Therearethreepatternsorsubtypes 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,andnumerousmitoticfigures,includingabnormalforms.Dyskeratoticcellsareoften
present, and the dysplastic cells frequently extend down pilosebaceous units, which can
mimicinvasivecarcinoma.
Table6.5TerminologyforPrecursorLesionsofVulvarSquamousCellCarcinoma
LAST2012 WHO2003 ISSVD2004 Synonyms
LSIL Condyloma
acuminatum
Condylomaacuminatum
LSIL VIN1 n/a Flatcondyloma,milddysplasia
HSIL VIN2 VIN,usualtype Moderatedysplasia
HSIL VIN3 Severedysplasia,carcinoma
insitu,Bowendisease,
bowenoidpapulosis,bowenoid
dysplasia
Carcinomainsitu
(simplextype)VIN
3
VIN,differentiatedtype
LAST,LowerAnogenitalSquamousTerminology;WHO,WorldHealthOrganization;ISSVD,InternationalSociety
fortheStudyofVulvarDisease;LSIL,low-gradesquamousintraepitheliallesion;VIN,vulvarintraepithelial
neoplasia;HSIL,high-gradesquamousintraepitheliallesion.
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
clustersofcellswithpalecytoplasminvolvingthesquamousepitheliumofthevulva,andthe
distinctionbetweenthesetwoentitiesrequiresspecialstains.
DifferentiatedorsimplexVINislocalizedtothevulvaandusuallyidentifiedadjacentto

areasofinvasivecarcinomainelderlypatients.Itisrarelyidentifiedprospectively(34).In
contrasttovulvarHSIL,HPVisrarelyidentifiedinsimplexVIN(33). The morphologic
changesofsimplexVINaresubtleandcharacterizedbynuclearatypiaofthebasalcelllayer
and expansion of the basal layer into elongated, narrow,branching rete ridges (Fig. 6.30).
Thenucleicanrangefromrelativelysmall,darkandirregular,toenlargedandpleomorphic.
Maturationisabnormal,as exhibited by the presence of enlarged keratinocyteswithlarge,
pleomorphicnucleiandabundant,markedlyeosinophiliccytoplasminthemid-tosuperficial
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).Thedifferentialdiagnosis for simplex VIN includes lichen sclerosus with
squamous hyperplasia, and other benign dermatologic conditions such as lichen simplex
chronicus,psoriasis,spongioticdermatitis,andcandidavulvitis.
Figure6.27 Condyloma.Exophyticcondylomasarecommoninthevulvaandareassociated
withlow-riskHPVtypes6and11.

Figure6.28 ClassicVIN,warty.Prominentkoilocytosisispresentonthesurfaceandoverlies
severeatypiainvolvingtwo-thirdsoftheunderlyingepithelium.
Lichensclerosusisapotentialriskfactorforthedevelopmentofvulvarsquamouscell
carcinoma. It may play a role in the HPV-independent pathway. Lichen sclerosus is
negativeforHPV and is more frequently identifiedinassociationwith simplex VIN than
withclassicVIN(32,33).

Figure 6.29 Classic VIN, basaloid. Cells with high nuclear-to-cytoplasmic ratios and dark,
irregularnucleiinvolvethefullthicknessofthesquamousepithelium.
SquamousCellCarcinoma
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
associatedwithsimplexVIN(32).

Figure 6.30 Simplex VIN. Abnormal keratinocytes with abundant, markedly eosinophilic
cytoplasminvolvethemidtosuperficiallayersandextendintothe elongated, branchingrete
ridges.
Verrucouscarcinomaisararespecialvariantofsquamouscellcarcinomathatisslow
growing and has minimal metastatic potential. It is typically exophytic, well
circumscribed, and composed of hyperkeratotic fronds of cytologically bland squamous
epithelium.Theinterfacewiththeunderlyingstromacharacteristicallyconsistsofapushing
borderwithassociatedchronicinflammation(Fig.6.32).

Figure 6.31 Conventional keratinizing squamous cell carcinoma of the vulva. Nests of
well-differentiatedtumorcellsjaggedlyinvadeintothestromaonmicroscopicexamination.

Figure 6.32 Verrucous carcinoma of the vulva. Top: Vulvectomy specimen showing
exophyticverrucoustumor.Bottom:Thetumorisexophyticwithhyperkeratoticfrondsofbland
squamousepitheliumandwellcircumscribedwithapushingborderwiththeunderlyingstroma.
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