Short
communication
Acaseofgastric-typemucinousendocervical
adenocarcinomainpresenceofnabothiancysts
DearEditor,
A group of benign and malignant endocervical glandular
lesionsunrelatedtohumanpapillomavirus(HPV)andshowing
gastricdifferentiation,hasbeendescribedinthelastyears[1].
Minimaldeviationadenocarcinoma(MDA)andlobular
endo-cervical glandular hyperplasia (LEGH) exhibit a gastric
phenotypeandimmunophenotype[2].Gastric-type
adenocar-cinoma (GAS) has been recently described as a subtype of
cervicaladenocarcinoma[3].Theseneoplasmshaveaggressive
clinicalbehavior.ThereisalikelyLEGH-GASsequence,andan
absenceofHPVincasesofLEGH,andMDAsuggestedthatthis
sequencerepresentsanHPV-independentpathwayof
carcino-genesis[1].MorphologicallydefinedGASexhibits
immunore-activityforMUC6and/orHIK1083,representativemarkersfor
pyloric gland differentiation. Notably, GAS is negative for
p16INK4a, a marker for high-risk HPV-driven neoplasm [4].
Clinical manifestations include watery vaginal discharge,
although womencan be asymptomatic [5].Surgery remains
the main treatment for patients with early-stage lesions.
Radiotherapy and/or chemotherapy are recommended for
women with advanced disease.We described a case of
gastric-type mucinous endocervical adenocarcinoma in a
womanwith positive Papsmear tests for atypical glandular
cellsofundeterminedsignificance(AGUS)butnegative
HPV-DNAtest.A 46years oldnulliparous womangave a medical
examination for hydrorrhea. The gynecological examination
showed plentiful mucinous secretions from vagina with
vaginal fornix preserved. The specular examination showed
an eroded and enlarged cervix. The transvaginal ultrasound
(US)scanshowedmultipleNabothcysts,aswellasanuneven
appearanceand aplentifulvascularization ofthe uterus,but
regular ovaries.The lasttwoPap smeartests,performedsix
monthsandoneyearbeforerespectively,showedthepresence
of atypical glandular cells of undetermined significance
(AGUS),sopatientunderwent colposcopythatconfirmedthe
eroded and enlarged aspect of cervix but turned out to be
negativeforHPV-relatedlesions.After3 months,thepatient
redidPapsmeartest whichshowedthepersistenceofAGUS,
whereas HPV-DNA test was negative. For this reason, the
woman underwent a cervical conization: the histologic
examination of cervical sample, measuring 442.5cm,
showedamucinousadenocarcinoma(NOS)moderately
differ-entiated (G2) infiltrating endocervical margin and part of
squamouscervicalepitheliumtissue,withvascularinfiltration.
Her cancer markers (α-FP, CEA, CA 19-9, CA 15-3, CA 125)
turnedouttobeallnegative.AbdomenandPelvicMRIshowed
a tumor thatinvadedthe cervixfor allitsthicknesswithout
involvementofnearbylymphnodes.Thepatientwasreferred
to our institution and underwent a laparotomy procedure.
Uterus and both annexes appeared macroscopically regular.
She underwenta totalhysterectomy,withbilateral
salpingo-oophorectomy and pelvic and obturator lymphadenectomy.
Definitivepathologicexaminationshowedamucinous
adeno-carcinomagastric-type, moderatelydifferentiated (G2),in
fil-tratingcervicalcanalforallitsthickness,withamicroscopic
metastasisinalymphnodeisolatedintherightparametrium
and in two of pelvicand obturatorlymph nodes (pT1B1N1)
(Fig.1A–B). Immunohistochemical analysis turnedout to be
negativeforestrogenreceptor(ER)andprogesteronereceptor
(PR) (Fig.1C) andpositiveforMUC6 (Fig.1D). Thepatientis
currently being treated with pelvic EBRT (external beam
radiationtherapy)andconcurrentchemotherapywith
cisplat-in. The diagnosis of GAS is established primarily based on
morphology: tumor cells with abundant eosinophilic
cyto-plasm,distinctcellborders,andagreaterdegreeofcytological
atypia characterizeit[2,4].However,immunohistochemistry
may contribute to the diagnosis. GAS shows the gastric
phenotype, as demonstrated byHIK1083, MUC6,or carbonic
anhydrase typeIX staining, negativity for p16, as well as a
frequentmutantpatternofp53staining[2].UnlikeMDAand
LEGH,theMRIfindingsofGAShavenotbeenclearlydescribed
yet, although image analysis based on T2-WI have recently
showedatumorshapeclassifiedastypeII,infiltrative[5].GAS
isassociatedwithaggressivebehaviorand a poorprognosis,
including a possible propensity for peritoneal and adnexal
dissemination[5].Indeed,sincethefirstdescriptionofGASin
2007, ithasbeenreporteditspooreroutcomesthan thoseof
usual-type adenocarcinomas (UEA), tipically associated to
high-riskHPVinover90%ofcases.GASisrathercommonin
Japan, accounting for up to 20%–25% of all endocervical
adenocarcinomas while it is considered rare in Western
countries [2]. Kojima et al. showed that GAS had a 5-year
disease-specificsurvivalof30%comparedto77%forUEA[5].
Themeanageofpresentationrangesbetween45–48years.It’s
related to high rate of lymphovascular invasion (LVI) and
regional lymph node metastases [2].Here, we discussed the
diagnosticdifficultiesforendocervicalglandularlesionswith
gastric differentiationand thepossible relationshipwiththe
nabothian cysts. This uncommon entity needs a particular
attentionforitsaggressivebehaviorandbecauseitisnotHPV
related. Screening methods for cancer control for the usual
endocervicaltypelikeHPVDNAtestingareineffectiveandthis
may result in a probable delay in diagnosis and a worse
prognosis.Itwouldbereallyinterestingtoevaluatetheroleof
nabothiancystsinthepathogenesis ofthisparticulartumor.
https://doi.org/10.1016/j.ejogrb.2019.02.024
0301-2115/©2019PublishedbyElsevierB.V.
EuropeanJournalofObstetrics&GynecologyandReproductiveBiologyxxx(2019)xxx–xxx
GModel
EURO10735No.ofPages2
Pleasecitethisarticleinpressas:P. D’Alessandro,et al.,Acaseof gastric-typemucinousendocervicaladenocarcinomainpresenceof
nabothiancysts,EurJObstetGynecol(2019),https://doi.org/10.1016/j.ejogrb.2019.02.024
ContentslistsavailableatScienceDirect
European
Journal
of
Obstetrics
&
Gynecology
and
Reproductive
Biology
Declarationofintereststatement
Theauthorsdeclarethattheyhavenoconflictsofinterestand
nothingtodisclose.
References
[1]ParkCM,KohHM,ParkS,KangHS,ShimSS,KimSY.Gastrictypemucinous
endocervicaladenocarcinomaoftheuterinecervix:veryrareandinteresting
case.ObstetGynecolSci2018;61(January(1)):165–9.
[2]AsakaS,NakajimaT,MomoseM,MiyamotoT,UeharaT,OtaH.Trefoilfactor
family2protein:apotentialimmunohistochemicalmarkerforaidingdiagnosis
oflobularendocervicalglandularhyperplasiaandgastric-typeadenocarcinoma
oftheuterinecervix.VirchowsArch2019;474(January(1)):79–86.
[3]ChungT,DOSI,NaK,KimG,JeongYI,KimYW,etal.Stromalp16overexpression
in gastric-typemucinous carcinomaof theuterine cervix. Anticancer Res
2018;38(January(6)):3551–8.
[4]YamanoiK,IshiiK,TsukamotoM,AsakaS,NakayamaJ.Gastricgland
mucin-specificO-glycanexpressiondecreasesastumorcellsprogressfromlobular
endocervicalglandhyperplasiatocervicalmucinouscarcinoma,gastrictype.
VirchowsArch2018;473(September(3)):305–11.
[5]ParkKJ,KimMH,KimJK,ChoKS.Gastric-typeadenocarcinomaoftheuterine
cervix:magneticresonanceimagingfeatures,clinicaloutcomes,andprognostic
factors.IntJGynecolCancer2018;28(July(6)):1203–10.
PietroD’Alessandro
AntoniaGiudicepietro
LuigiDellaCorte*
BrunoArduino
GabrieleSaccone
DepartmentofNeuroscience,ReproductiveSciencesandDentistry,
SchoolofMedicine,UniversityofNaplesFedericoII,Naples,Italy
AlessandroIacobelli
LuigiInsabato
AnatomicPathologyUnit,DepartmentofAdvancedBiomedical
Sciences,SchoolofMedicine,UniversityofNaplesFedericoII,Naples,
Italy
FulvioZullo
DepartmentofNeuroscience,ReproductiveSciencesandDentistry,
SchoolofMedicine,UniversityofNaplesFedericoII,Naples,Italy
* Correspondingauthorat:DepartmentofNeuroscience,
Repro-ductiveSciencesandDentistry,SchoolofMedicine,Universityof
Naples“FedericoII”,ViaPansini5,Naples,Italy.
E-mailaddress:dellacorte.luigi25@gmail.com(L.DellaCorte).
Received28January2019
Availableonlinexxx
Fig. 1.A–D:A.Highviewoftheadenocarcinomathatresemblethegastricadenocarcinoma,thisparticularfieldhighlightalymphovascularinvasion;B.Itispossibiletonotice theinfiltrativepatternoftheadenocarcinomagastric-type.Theglandsarecomposedbycellswithhighclearcytoplasmanddistinctborders;C.Immunohistochemical analysis:negativityfortheestrogenandprogesteronereceptorsthatarecommonlynegativeinthistypeofcervixadenocarcinoma;positivecontrolsstatedbythefibroblasts inthestroma;D.Immunohistochemicalanalysis:positivityforMUC6.
2 Shortcommunication/EuropeanJournalofObstetrics&GynecologyandReproductiveBiologyxxx(2019)xxx–xxx
GModel
EURO10735No.ofPages2
Pleasecitethisarticleinpressas:P.D’Alessandro,etal.,Acaseofgastric-type mucinousendocervicaladenocarcinomainpresenceof
