Histopathology of cervical precursor lesions and cancer

Review

Histopathology of cervical precursor lesions and cancer

Histopathology of cervical precursor lesions and cancer 6/D[

K E Y WORDS cervical cancer, precursor lesions, cytological screening, histomorphology

A

B S T R A C T

The most frequent types of cervical cancer are squamous-cell carcinoma and adenocarcinoma, which develop from the distinctive precursor lesions cervical intraepithelial neoplasia (CIN) / squamous intraepithelial lesion (SIL), and adenocarcinoma in situ (AIS), respectively. Their tumorigenesis is HPV-related. High-risk HPV (e.g., types 16 and 18) is integrated into the genome and leads to tumor progression. Cytological screening leads to detection of precursors and their mimics. P16 and Ki-67 immunohistochemistry assists in the histological differential diagnosis of precursors to reactive and metaplastic epithelium. For invasive cervical carcinoma, stage is the strongest prognostic factor. Per definition, microinvasive (pT1a1 / pT1a2) carcinoma is diagnosed histologically on cone biopsies and treated less radically. The distinction between adenocarcinomas of the cervix and endometrial adenocarcinomas is important and can be supported by immunohistochemistry (e.g., ER, p16, CEA, and vimentin) and HPV in-situ hybridization. The rarer adenoid-basal and neuroendocrine carcinomas are less frequently HPV-related.

Introduction Although invasive cervical carcinoma has become rare in most European countries, from the global per spective it must still be considered a public health bur GHQ,QSDUWLFXODUPDQ\FRXQWULHVLQ$IULFDVRXWKHDVW Asia, and Latin America reveal an incidence that is PRUHWKDQWLPHVDVIUHTXHQWFRPSDUHGWRWKHLQFL GHQFHLQFHQWUDO(XURSH 9DULRXVIDFWRUVVHHPWREH responsible for these epidemiological differences, such DV VRFLRHFRQRPLF VWDQGDUGV LPPXQRGHÀFLHQF\ DQG +39LQIHFWLRQ ,QSDUWLFXODUEHFDXVHWKHSDWKR Acta Dermatoven APA Vol 20, 2011, No 3

genesis has been clearly linked to HPV infection, cer YLFDOFDUFLQRPDKDVEHFRPHDSUHYHQWDEOHGLVHDVH +LVWRORJLFDOO\WKHPRVWIUHTXHQWW\SHRIFHUYLFDO FDUFLQRPD LV VTXDPRXVFHOO FDUFLQRPD IROORZHG E\ adenocarcinoma (3, 4), of which various subtypes are GLVWLQJXLVKHG7DEOH %RWKVTXDPRXVFHOOFDUFLQR ma and adenocarcinoma develop through distinctive SUHFXUVRUOHVLRQV)RUVRPHRIWKHUDUHW\SHVRIFHUYL FDOFDUFLQRPDVXFKDVDGHQRLGF\VWLFDGHQRLGEDVDO DQG VPDOOFHOO FDUFLQRPD QR SUHFXUVRU OHVLRQV DUH NQRZQ 7KH SUDFWLFDO YDOXH RI WKH SUHFXUVRU OHVLRQV

125


Review

is their presence in cervicovaginal smears and the Table 1. WHO classification of malignant tumors of the uterine cervix SRVVLELOLW\RIHDUO\GHWHFWLRQE\F\WRORJLFDOVFUHHQLQJ and their precursors, modified according to (1). 7KH IUHTXHQF\ RI SUHFXUVRU OHVLRQV KDV VLJQLÀFDQWO\ Epithelial tumors increased in most European countries along with the GHFUHDVHLQFHUYLFDOFDUFLQRPDLQFLGHQFH 6TXDPRXVWXPRUVDQGSUHFXUVRUV 6TXDPRXVFHOOFDUFLQRPD126 .HUDWLQL]LQJ 1RQNHUDWLQL]LQJ %DVDORLG Verrucous :DUW\ Papillary Our current understanding of the pathogenesis of /\PSKRHSLWKHOLRPDOLNH VTXDPRXVFHOOFDUFLQRPDFRQVLGHUVLWWRGHYHORSIURP 6TXDPRWUDQVLWLRQDO precursor lesions designated as cervical intraepithe (DUO\LQYDVLYHPLFURLQYDVLYH VTXDPRXVFHOOFDUFLQRPD OLDOQHRSODVLD&,1 &,1LVFDWHJRUL]HGLQWRWKUHH 6TXDPRXVLQWUDHSLWKHOLDOQHRSODVLD grades (CIN1–3) based on the degree of proliferation Cervical intraepithelial neoplasia (CIN3) RIDW\SLFDOEDVDORLGFHOOV 7KHDW\SLFDOEDVDORLGFHOO 6TXDPRXVFHOOFDUFLQRPDLQVLWX proliferation involves the basal third of the epithelium *ODQGXODUWXPRUVDQGSUHFXUVRUV LQ &,1 UHDFKHV WKH PLGGOH WKLUG LQ &,1 DQG H[ Adenocarcinoma WHQGVWRWKHVXSHUÀFLDOWKLUGLQ&,1$PRUHUHFHQW 0XFLQRXVDGHQRFDUFLQRPD DSSURDFK EDVHG RQ WKH %HWKHVGD V\VWHP IRU FHUYLFDO Endocervical cytology distinguishes between two categories with Intestinal GLVWLQFWLYH ELRORJ\ ORZ DQG KLJKJUDGH VTXDPRXV 6LJQHWULQJFHOO LQWUDHSLWKHOLDO OHVLRQV /6,/ DQG +6,/ UHVSHFWLYHO\ 0LQLPDOGHYLDWLRQ /6,/LVFKDUDFWHUL]HGE\H[WHQVLYH+39UHODWHGF\WR Villoglandular logical changes such as koilocytosis and proliferation Endometrioid adenocarcinoma of the basal and parabasal cells with mild atypia and Clear cell adenocarcinoma PLWRVLV ,Q FRQWUDVW +6,/ FRQVLVWV RI VPDOO WR PH Serous adenocarcinoma GLXPVL]HG DW\SLFDO EDVDO FHOOV WKDW PD\ LQYROYH WKH 0HVRQHSKULFDGHQRFDUFLQRPD entire thickness of the epithelium and it often lacks Early invasive adenocarcinoma FOHDUO\ YLVLEOH +39UHODWHG F\WRORJLFDO FKDQJHV ,I Adenocarcinoma in situ FRPSDUHGWRWKH:+2FODVVLÀFDWLRQ&,1UHODWHVWR *ODQGXODUG\VSODVLD /6,/ZKHUHDV&,1DQGDUHUHODWHGWR+6,/7KH Other epithelial tumors YDULRXVFODVVLÀFDWLRQVFKHPHVDUHFRPSDUHGLQ7DEOH $GHQRVTXDPRXVFDUFLQRPD )URP D ELRORJLFDO SRLQW RI YLHZ WKH GXDOLVWLF *ODVV\FHOOFDUFLQRPDYDULDQW %HWKHVGD DSSURDFK LV UHDVRQDEOH EHFDXVH /6,/ DQG Adenoid cystic carcinoma +6,/UHYHDODGLIIHUHQWSDWKRJHQHVLV/6,/LVPRVWO\ Adenoid basal carcinoma DVVRFLDWHG ZLWK ORZ RU LQWHUPHGLDWHULVN +39 VXFK Neuroendocrine tumors DV+39DQGZKHUHDV+6,/KDUERUVFOHDUO\RQ Carcinoid cogenic HPV DNA such as types 16, 18, 31, 33, and Atypical carcinoid 7KHUH DUH DOVR IXQGDPHQWDO GLIIHUHQFHV EHWZHHQ 6PDOOFHOOFDUFLQRPD /6,/DQG+6,/HIIHFWVDWWKHFHOOXODUOHYHO /6,/ /DUJHFHOOQHXURHQGRFULQHFDUFLQRPD LV FKDUDFWHUL]HG E\ LQIHFWLRQ RI WHUPLQDOO\ GLIIHUHQ Undifferentiated carcinoma WLDWHG FHOOV WKDW DUH XQDEOH WR GLYLGH 7KHUHIRUH WKH F\WRORJLFDO FKDQJHV LQYROYH RQO\ WKH VXSHUÀFLDO OD\ HUV RI WKH HSLWKHOLXP 2Q WKH RWKHU KDQG +39 LQ DEOHWRUHSOLFDWHDQGVXUYLYH7KHPHFKDQLVPUHVSRQ fection in HSIL involves the basal and parabasal sible for this process in HSIL is mainly induced by FHOOV ZKLFK DUH VWLOO FDSDEOH RI GLYLGLQJ 7KLV OHDGV WKHYLUDOSURWHLQV(DQG(DQGIXUWKHULQYROYHVKRVW to morphological changes in all or almost all layers UHJXODWRU\SURWHLQVVXFKDVF\FOLQVF\FOLQGHSHQGDQW RI WKH HSLWKHOLXP /6,/ LV W\SLFDOO\ FKDUDFWHUL]HG E\ NLQDVHVDQGF\FOLQGHSHQGDQWNLQDVHLQKLELWRUV7KLV ORZULVN+39²LQGXFHG'1$V\QWKHVLVZLWKRXWDFFX leads to deregulation of the cell cycle and the apop mulation of abnormal DNA, whereas HSIL shows the WRWLF SDWKZD\ ,PSRUWDQW DSRSWRWLF SURWHLQV VXFK DV ODWWHUDVWKHFRQVHTXHQFHRIDGLVUXSWHGFHOOF\FOHE\ SDQG5EORVHWKHLUIXQFWLRQDQGRWKHUVVXFKDVS KLJKULVN+397KLVOHDGVWRDQHXSORLGFHOOVWKDWDUH DUHGHUHJXODWHG+6,/LVIXUWKHUFKDUDFWHUL]HGE\LQ

Pathogenesis and histomorphology of squamous-cell carcinoma and its precursor lesions

126

Acta Dermatoven APA Vol 20, 2011, No 3

Review


Table 2: Comparison of different classification systems of precursor lesions of cervical squamous-cell carcinoma. 7UDGLWLRQDOFODVVLÀFDWLRQ

:+2FODVVLÀFDWLRQ

%HWKHVGDFODVVLÀFDWLRQ

0LOGG\VSODVLD

CIN1

LSIL

0RGHUDWHG\VSODVLD Severe dysplasia Carcinoma in situ

CIN2 CIN3

HSIL

&,1 FHUYLFDOLQWUDHSLWKHOLDOQHRSODVLD/6,/ ORZJUDGHVTXDPRXVLQWUDHSLWKHOLDOOHVLRQ+6,/ KLJKJUDGHVTXDPRXV LQWUDHSLWKHOLDOOHVLRQ

tegration of the viral DNA into the host genome whereas LSIL shows an episomal location of HPV '1$/6,/DVVRFLDWHGZLWKORZULVN+39LVXVX ally polyclonal, whereas those associated with KLJKULVN +39 WHQG WR EH PRQRFORQDO 0RVW HSIL are monoclonal but polyclonality may oc FXU7KHUHLVVRPHHYLGHQFHWKDWSRO\FORQDOOHVLRQV tend to regress whereas monoclonal lesions show SURJUHVVLRQ There is evidence that only a subset of CIN1/ LSIL progresses into CIN2 and 3/HSIL because most LSIL have the potential to regress over some \HDUV ,W LV XQFOHDU ZKHWKHU DOO &,1 GHYHORS IURP &,1 EXW LW KDV EHHQ K\SRWKHVL]HG WKDW &,1RULJLQDWHV´GHQRYRµIURPPHWDSODVWLFVTXD mous epithelium under the transition of atypical VTXDPRXVPHWDSODVLD+RZHYHUWKLVKDVQRWEHHQ SURYHQ DWDOO2QHIXUWKHU SUREOHPLVWKDWDW\SL FDO VTXDPRXV PHWDSODVLD FDQQRW EH HDVLO\ GLVWLQ guished from CIN3 and shows poor interobserver DJUHHPHQWHYHQDPRQJH[SHUWV 7KH KDOOPDUN RI /6,/&,1 LV PRGHUDWHWR marked nuclear atypia on the surface of the epi WKHOLXP .HHSLQJ WKLV LQ PLQG KHOSV DYRLG RYHUGLDJQRVLV ,Q DGGLWLRQ /6,/ LV YHU\ UDUH LQ SRVWPHQRSDXVDO ZRPHQ 1RQDW\SLFDO FHOOV ZLWK SHULQXFOHDU KDORV GR QRW TXDOLI\ IRU NRLORF\WRVLV DQG DUH LQVWHDG GHVLJQDWHG ´SVHXGRNRLORF\WHVµ )XUWKHUPRUH/6,/&,1XVXDOO\GRQRWKDUERUD ORWRIPLWRVLVDQGDEQRUPDOPLWRWLFÀJXUHV7KHUH IRUHOHVLRQVZLWKDKLJKPLWRWLFLQGH[PXVWEHXS JUDGHGWR+6,/:LWKUHVSHFWWR+6,/LWVYDULDEOH KLVWRORJLFDO SUHVHQWDWLRQ PXVW EH VWUHVVHG +6,/ may be associated with marked koilocytosis, hy SHUNHUDWRVLVRUHYHQPHWDSODVWLFIHDWXUHV5HÁHFW ing the multipotential nature of transformation ]RQH FHOOV +6,/ PD\ HYHQ FRPELQH VTXDPRXV DQGPXFLQRXVIHDWXUHV Differential diagnosis includes metaplastic and UHSDUDWLYHSURFHVVHVDVZHOODVDWURSK\ &ULWH ria that help on H&E sections are loss of polarity, Acta Dermatoven APA Vol 20, 2011, No 3

distribution of chromatin, mitosis and, in particu ODU QXFOHDU SRO\PRUSKLVP )XUWKHUPRUH PRVW QRQQHRSODVWLF OHVLRQV WHQG WR VKRZ PDWXUDWLRQ RQWKHHSLWKHOLDOVXUIDFH $PRQJ YDULRXV ELRPDUNHUV S DQG .L seem to be useful for differential diagnosis of in WUDHSLWKHOLDOQHRSODVLDRIWKHFHUYL[ 3RYHU H[SUHVVLRQKDVEHHQOLQNHGWRFRQWLQXHGH[SUHVVLRQ RIWKHYLUDORQFRJHQH(GXHWR+39LQIHFWLRQRI WKHHSLWKHOLXP 7KHUHIRUHDGLIIXVHVWURQJS VWDLQLQJ RI VTXDPRXV HSLWKHOLXP SRLQWV WR LQIHF WLRQE\KLJKULVN+39DQGPD\RFFXULQ+6,/DQG XSWRWRRI/6,/ 7KHGLDJQRVLVRID OHVLRQLVIXUWKHUVXSSRUWHGE\DKLJK.LODEHO LQJLQGH[ZLWKPDQ\.LSRVLWLYHQXFOHLZLWKLQ WKH VXSHUÀFLDO KDOI RI WKH HSLWKHOLXP +RZHYHU it has to be kept in mind that both LSIL/CIN1 and metaplastic epithelium may show focal, patchy VWDLQLQJIRUS

Invasive squamous-cell carcinoma and the significance of microinvasion ,QYDVLYH VTXDPRXVFHOO FDUFLQRPD FRQVLVWVRI nests and irregular clusters of tumor cells, which PD\VKRZHLWKHUDEDVDOOLNHDSSHDUDQFHRUPDWX UDWLRQ RIWHQ ZLWK NHUDWLQL]DWLRQ .HUDWLQ IRUPD WLRQ LV FRQVLGHUHG D VLJQ RI JRRG GLIIHUHQWLDWLRQ 7RGD\ D VXEFODVVLÀFDWLRQ LQWR NHUDWLQL]LQJ DQG QRQNHUDWLQL]LQJ VTXDPRXVFHOO FDUFLQRPD LV recommended, in particular to avoid confusion RI VPDOOFHOO VTXDPRXV FDUFLQRPD DQG VPDOOFHOO FDUFLQRPDRIQHXURHQGRFULQHW\SH1HLWKHUKLVWR SDWKRORJLFDO JUDGLQJ QRU NHUDWLQL]DWLRQ VHHPV WR LQÁXHQFHSURJQRVLV7KHVWURQJHVWSURJQRVWLFIDF WRULVWXPRUVWDJHZKLFKLVSDUWLFXODUO\UHÁHFWHG E\WKHLVVXHRIPLFURLQYDVLYHFDUFLQRPD 0LFURLQYDVLYHFDUFLQRPDLVGHÀQHGE\VL]HLQ

127


Review

Figure 1. Cervical intraepithelial neoplasia 1 (CIN 1) / low-grade intraepithelial lesion (LSIL). The epithelial changes are characterized by significant nuclear atypia in the superficial half due to extensive koilocytosis and proliferation of basal and parabasal cells. The mitotic index is low. HE, 100×.

Figure 2. Cervical intraepithelial neoplasia 3 (CIN 3) / high-grade intraepithelial lesion (HSIL). The epithelium lacks maturation and consists of small highly atypical cells with hyperchromatic nuclei. HE, 100×.

Figure 3. Microinvasive squamous-cell carcinoma of the cervix (pT1a1), diagnosed on a cone biopsy. Small irregular nests of welldifferentiated squamous carcinoma invade the cervical stroma from glands (crypts) (arrows). The surface is covered by CIN3 (asterisks). HE, 20×.

Figure 4. Adenocarcinoma in situ (AIS). Endocervical glandular epithelium is replaced by pseudostratified atypical epithelium with goblet cells. HE, 200×.

WKHDEVHQFHRIDFOLQLFDOO\YLVLEOHWXPRU %\GHÀQL tion, microinvasive carcinoma is diagnosed histologi cally and thus detected through the histopathological DQDO\VLV RI FRQH ELRSVLHV IURP SDWLHQWV ZLWK &,1 7KHFXUUHQW),*2DQG8,&&FODVVLÀFDWLRQIRUFHUYL FDOFDUFLQRPDVWDJLQJ7DEOH GHÀQHVPLFURLQYDVLYH FDUFLQRPDE\DPD[LPXPKRUL]RQWDOGLPHQVLRQRI PPDQGVXEGLYLGHVWZRFDWHJRULHVZLWKDPD[LPXP vertical diameter of 3 mm (Ia1) and 5 mm (Ia2), re VSHFWLYHO\ 7KHPHDVXUHPHQWLVWDNHQIURPWKH

base of the epithelium, either on the surface or within DJODQGFU\SW IURPZKLFKWKHWXPRUVRULJLQDWH 7KH VXEFDWHJRUL]DWLRQ RI PLFURLQYDVLYH FDUFLQRPD has important therapeutic repercussions because cone ELRSV\RUVLPSOHK\VWHUHFWRP\LVXVXDOO\VXIÀFLHQWIRU S7D,DWXPRUV )RU WKH KLVWRORJLFDO GLDJQRVLV RI PLFURLQYDVLYH FDUFLQRPD RI WKH FHUYL[ SHQHWUDWLRQ RI WXPRU FHOOV WKURXJKWKHEDVHPHQWPHPEUDQHLVUHTXLUHG,QYDVLYH IRFLRIWXPRUFHOOVDUHXVXDOO\DUUDQJHGLQDKDSKD]DUG

128


Review


Table 3. TNM and FIGO classification of cervical carcinoma (14). pTNM categories (pT = primary tumor)

FIGO Description stages

PTis

0

Carcinoma in situ (preinvasive)

pT1

I

&HUYLFDOFDUFLQRPDFRQÀQHGWRWKHXWHUXV

pT1a

IA

Diagnosed only by microscopy

PT1a1

IA1

'HSWKPPKRUL]RQWDOVSUHDGPP

PT1a2

IA2

'HSWKPPKRUL]RQWDOVSUHDGPP

pT1b

,%

Clinically visible or microscopic lesion > pT1a2

PT1b1

,%

7XPRUGLDPHWHUFP

PT1b2

,%

Tumor diameter > 4cm

II

7XPRULQÀOWUDWHVEH\RQGWKHXWHUXVEXWQRWWRWKHSHOYLFZDOORUWRWKH lower third of the vagina

pT2a

IIA

No parametrial involvement

PT2a1

IIA1

7XPRUGLDPHWHUFP

PT2a2

IIA2

Tumor diameter > 4cm

pT2b

,,%

,QÀOWUDWLRQRIWKHSDUDPHWULXP

III

7XPRULQÀOWUDWHVWRWKHSHOYLFZDOOWRWKHORZHUWKLUGRIWKHYDJLQDRULV associated with hydronephrosis

pT3a

IIIA

Lower third of the vagina

pT3b

,,,%

,QÀOWUDWLRQWRWKHSHOYLFZDOORUK\GURQHSKURVLV

pN1

,,,%

0HWDVWDVHVLQSHOYLFDQGRUSDUDDRUWLFO\PSKQRGHV

pT4

IVA

7XPRULQÀOWUDWHVPXFRVDRIUHFWXPRUXULQDU\EODGGHURUEH\RQGWUXH pelvis

pT2

pT3 and/or N1

pN – Regional lymph nodes S1[

5HJLRQDOO\PSKQRGHVFDQQRWEHDVVHVVHG

pN0

No metastases in regional lymph nodes

pN1

0HWDVWDVHVLQUHJLRQDOO\PSKQRGHV

pM – Distant metastases S0[

Distant metastases cannot be assessed

S0

No distant metastases

S0

,9%

Distant metastasis (includes inguinal lymph nodes and intraperitoneal GLVHDVHH[FOXGHVLQYROYHPHQWRIYDJLQDDGQH[DHDQGSHOYLFVHURVD

SDWWHUQDQGVKRZLUUHJXODUPDUJLQV7KH\XVXDOO\GLV play better differentiation than the associated CIN by VKRZLQJPDWXUDWLRQ7KHXVHRILPPXQRKLVWRFKHPLV WU\WRGHPRQVWUDWHVWURPDOLQYDVLRQLVRIOLPLWHGYDOXH In particular, disruption of the basement membrane as demonstrated by loss of laminin and collagen IV, re VSHFWLYHO\PD\DOVRRFFXULQQRUPDOFU\SWVDQG&,1 If microinvasive carcinoma occurs multifocally, WKHH[WHQWRIWKHODUJHVWIRFXVLVXVHGIRUFODVVLÀFDWLRQ Acta Dermatoven APA Vol 20, 2011, No 3

This has been challenged by studies that are based on YROXPHWULFPHDVXUHPHQWRIWXPRUVL]H %HFDXVH VPDOO S7E,% FDUFLQRPDV PD\ RFFXU ZLWKRXW D FOLQLFDOYLVLEOHWXPRUDQGEHDVVRFLDWHGZLWKH[FHOOHQW SURJQRVLV H[SDQGLQJ WKH PLFURLQYDVLYH FDUFLQRPD FDWHJRU\KDVEHHQVXJJHVWHG 9DULRXVVSHFLDOW\SHVRIVTXDPRXVFHOOFDUFLQRPD have been described, which are rare and thus of lim LWHGFOLQLFDOYDOXH

129


Pathogenesis and histomorphology of adenocarcinoma and its precursor lesions ,QFRQWUDVWWRVTXDPRXVFHOOFDUFLQRPDWKHSUH cursor lesion of adenocarcinoma, adenocarcinoma LQ VLWX $,6 LV QRW IXUWKHU VXEGLYLGHG $,6 LV FKDUDFWHUL]HG E\ FHOOXODU DW\SLD VLPLODU WR FRORUHFWDO adenoma and may show a variety of cellular differen WLDWLRQ LQFOXGLQJ JREOHW FHOOV 7KH QXFOHL DUH XVXDOO\ FLJDUVKDSHG DQG SVHXGRVWUDWLÀHG VKRZLQJ FRDUVH FKURPDWLQDQGQXPHURXVPLWRVHV*ODQGXODUG\VSOD sia, a lesion with less pronounced changes compared to AIS, has been suggested as a precursor to AIS but has been challenged due to its poor reproducibility DQGLQSDUWLFXODULWVQHJOLJLEOHFOLQLFDOYDOXH 5HFHQWO\ D VFRULQJ V\VWHP ZDV SURSRVHG WR GLVWLQ guish between glandular dysplasia and AIS but due to its limited clinical value it has been suggested that the WHUP ´JODQGXODU G\VSODVLDµ QR ORQJHU EH XVHG LQ WKH FOLQLFDOVHWWLQJ 7KHWHUP&*,1FHUYLFDOJODQGX lar intraepithelial neoplasia), which is subdivided into WKUHH JUDGHV LV XVHG LQ WKH 8. EXW QRW LQ WKH 86 DQGFRQWLQHQWDO(XURSH7KHGLIIHUHQWLDOGLDJQRVLVRI AIS includes reactive changes of the glandular endo FHUYLFDOHSLWKHOLXPDQGWXEDOPHWDSODVLD3DQG.L LPPXQRKLVWRFKHPLVWU\LVXVHIXOEXWLWQHHGVWREH HPSKDVL]HGWKDWWXEDOPHWDSODVLDVKRZVIRFDOO\VWURQJ SLPPXQRUHDFWLYLW\ Cervical adenocarcinoma shows a variety of histo ORJLFDOSDWWHUQV ,IYDULRXVKLVWRORJLFDOFRPSRQHQWV DUHSUHVHQWLQRQHWXPRUWKHFODVVLÀFDWLRQVKRXOGEH based on the predominant pattern, and the other pat WHUQ LI SUHVHQW LQ DW OHDVW RI WKH WXPRU VKRXOG just be mentioned in the report 7KH PRVW IUH TXHQW KLVWRORJLFDO W\SHV DUH WKH HQGRFHUYLFDO W\SH mucinous adenocarcinoma, and endometrioid adeno FDUFLQRPD 7KHUH DUH GLYHUJHQW UHSRUWV RQ WKH distribution of these two histological types, ranging IURPDWZLFHDVIUHTXHQWLQFLGHQFHRIWKHHQGRFHUYL cal type compared to endometrioid adenocarcinoma to a slight predominance of endometrioid adenocar FLQRPD 0RUH VWULNLQJ LV WKH FKDQJH LQ WKH SURSRU WLRQ EHWZHHQ DGHQRFDUFLQRPD DQG VTXDPRXVFHOO FDUFLQRPD RI WKH FHUYL[ &DQFHU UHJLVWULHV RI VHYHUDO countries have reported a relative increase in the ratios RIDGHQRFDUFLQRPDVFRPSDUHGWRVTXDPRXVFHOOFDU FLQRPDV,QVRPHFRXQWULHVWKHLQFLGHQFHRILQYDVLYH FHUYLFDO FDUFLQRPD GHFUHDVHG IURP WKH V WR WKH VE\XSWRRQHWKLUGZKHUHDVWKHLQFLGHQFHRIDG HQRFDUFLQRPDLQFUHDVHGE\XSWR Association with HPV has been found for virtual O\DOOW\SHVRIDGHQRFDUFLQRPDRIWKHFHUYL[DOWKRXJK VRPHGDWDDUHFRQWURYHUVLDO0XFLQRXVDQGHQGRPH

130

Review

WULRLGDGHQRFDUFLQRPDVIUHTXHQWO\KDUERU+39'1$ DQG DQGOHVVIUHTXHQWO\ ,QFRQWUDVWWRSUHYLRXVÀQGLQJV+39'1$ZDVUH cently also found in adenocarcinoma by using new WHFKQRORJLHV

Microinvasive adenocarcinoma A category of microinvasive adenocarcinoma has DOVREHHQHVWDEOLVKHGEXWLQFRQWUDVWWRLWVVTXDPRXV FHOO FRXQWHUSDUW WKH GLDJQRVLV LV PRUH GLIÀFXOW DQG KDVEHHQFRQWURYHUVLDO%DVLFDOO\DOOKLVWRORJLFDOW\SHV of adenocarcinoma may be found in this category but small pT1a/IA tumors are much rarer compared to the VTXDPRXVFHOOFDUFLQRPDJURXS7KHPRVWLPSRUWDQW diagnostic criterion, stromal invasion, is not always XQHTXLYRFDOO\YLVLEOHLQVPDOOJODQGXODUOHVLRQVRIWKH FHUYL[ ,Q SDUWLFXODU ZHOOGLIIHUHQWLDWHG DQG VXSHUÀ FLDOO\ORFDWHGJODQGXODUOHVLRQVPD\EHGLIÀFXOWWRGL DJQRVH$PDUNHGJODQGXODULUUHJXODULW\ZLWKKDSKD] ardly arranged glands is considered an indication for DQLQÀOWUDWLYHJURZWK5HFHQWO\WKHFORVHUHODWLRQVKLS of glands to blood vessels was assessed as a diagnostic WRROIRULQYDVLYHFDUFLQRPDV $GHVPRSODVWLFLQ ÁDPPDWRU\VWURPDOUHVSRQVHPD\EHRIIXUWKHUKHOS DQGWKHSUHVHQFHRIO\PSKYDVFXODULQYDVLRQFRQÀUPV WKHFDUFLQRPDGLDJQRVLV /HVVGLIÀFXOWWRGLDJQRVH LV D FRQÁXHQW JODQGXODU SDWWHUQ ZLWK ORVV RI VWURPD DQGIRUPDWLRQRIFULEULIRUPWXPRUDUHDVRUDFRPSOH[ SDSLOODU\SDWWHUQ7KHYHUWLFDOGLDPHWHURIWKHWXPRU is usually measured from the surface of the lesion, re ÁHFWLQJWXPRUWKLFNQHVVUDWKHUWKDQWKHWUXHGHSWKRI LQYDVLRQ 7KHSURJQRVLVRIPLFURLQYDVLYHDGHQR FDUFLQRPDLVH[FHOOHQW

Adenosquamous carcinoma $GHQRVTXDPRXV FDUFLQRPD GHÀQHG DV D WXPRU ZLWK ERWK VTXDPRXV DQG JODQGXODU GLIIHUHQWLDWLRQ PD\DFFRXQWIRUWRRIDOOFHUYLFDOFDUFLQRPDV EXW LWV GLDJQRVLV YDULHV DQG LV FRQWURYHUVLDO ,W ZDV FDWHJRUL]HGDPRQJPL[HGFDUFLQRPDVEXWWKHUHFHQW :+2 FODVVLÀFDWLRQ FRQVLGHUHG LW D GLVWLQFWLYH W\SH 7KH VTXDPRXV FRPSRQHQW PD\ HYHQ VKRZ NHUD WLQL]DWLRQEXWIRUWKHGLDJQRVLVDVXIÀFLHQWIRUPDWLRQ RIJODQGVPXVWEHSUHVHQW(QGRPHWULRLGDGHQRFDUFL QRPDVZLWKEHQLJQORRNLQJVTXDPRXVHOHPHQWVPXVW QRWEHFDOOHGDGHQRVTXDPRXVFDUFLQRPDV,WLVOLNHO\ that by using strict diagnostic criteria the number of DGHQRVTXDPRXVFDUFLQRPDVPD\GHFUHDVHVLJQLÀFDQW O\'XHWRVLPLODUHSLGHPLRORJLFULVNIDFWRUVDQGSURJ QRVLV DGHQRVTXDPRXV FDUFLQRPD KDV UHFHQWO\ EHHQ UHODWHGWRVTXDPRXVFHOOFDUFLQRPD$VWURQJDVVRFLD WLRQZLWK+39ZDVIRXQG


Review


Distinction between cervical and endometrial adenocarcinoma

Rare types of cervical carcinoma

Determining the site of origin of an adenocar FLQRPD RI WKH FHUYL[ PD\ EH GLIÀFXOW SDUWLFXODUO\ LQ FXUHWWDJHPDWHULDO,QSDUWLFXODUIRUHQGRPHWULRLGDQG endocervical types of adenocarcinomas immunohis tochemistry may be useful in determining the site of RULJLQ (QGRPHWULDO DGHQRFDUFLQRPDV XVXDOO\ H[SUHVV HVWURJHQ UHFHSWRUV (5 DQG YLPHQWLQ EXW ODFN &($ H[SUHVVLRQDQGXVXDOO\GRQRWFRQWDLQ+39'1$,Q contrast, endocervical adenocarcinomas are negative IRU (5 DQG YLPHQWLQ VKRZ SRVLWLYLW\ IRU &($ DQG FRQWDLQ+39'1$7KHUHIRUHDFRPELQDWLRQRI(5 vimentin, and CEA can be applied to determine the VLWH RI RULJLQ +39 LQVLWX K\EULGL]DWLRQ FDQ EH XVHG DV DQ DGGLWLRQDO WRRO 7KH YDOXH RI S LP munohistochemistry has been challenged, in particu ODUEHFDXVHQRQHQGRPHWULRLGDGHQRFDUFLQRPDVRIWKH endometrium, such as mucinous and serous carcino PDV IUHTXHQWO\ H[SUHVV S DV GR PRVW HQGRFHUYLFDO DGHQRFDUFLQRPDV)RUVHURXVDQGFOHDUFHOOFDUFLQRPDV GHWHUPLQLQJWKHVLWHRIRULJLQFDQEHYHU\GLIÀFXOW

$GHQRLGEDVDOFDUFLQRPDDQGQHXURHQGRFULQHFDU FLQRPDDUHHQFRXQWHUHGZLWKLQWKLVJURXS7KHVHWX PRUVDUHUDUHDQGWKXVRIOLPLWHGFOLQLFDOVLJQLÀFDQFH An association with HPV has been found for most W\SHV DOWKRXJK OHVV IUHTXHQWO\ FRPSDUHG WR VTXD PRXVFHOOFDUFLQRPD1RGLVWLQFWLYHSUHFXUVRUOHVLRQV KDYHEHHQIRXQGIRUWKHVHWXPRUV$GHQRLGEDVDOFDU FLQRPD LV VORZJURZLQJ EXW ODFNV D FOLQLFDOO\ YLVLEOH WXPRU 0HWDVWDVHVDUHUDUH Two types of neuroendocrine carcinomas of the XWHULQHFHUYL[DUHGLVWLQJXLVKHGVPDOOFHOOFDUFLQRPD DQG ODUJHFHOO QHXURHQGRFULQH FDUFLQRPD ZKLFK DUH ERWKUDUHDQGDVVRFLDWHGZLWKSRRUSURJQRVLV %RWK H[SUHVV QHXURHQGRFULQH PDUNHUV LQ SDUWLFXODU 1&$0 &' DQG V\QDSWRSK\VLQ OHVV IUHTXHQWO\ FKURPRJUDQLQ$ 2WKHUQHXURHQGRFULQHSHS tides such as serotonin may be produced but do not FDXVHHQGRFULQHV\PSWRPV7KH.LODEHOLQJLQGH[ LVXVXDOO\YHU\KLJK

R EFERENCES 1.

7DYDVVROL)$'HYLOHH3HGLWRUV7XPRXUVRIWKHEUHDVWDQGIHPDOHJHQLWDORUJDQV/\RQ,$5&3UHVV

6FKLIIPDQ0+%DXHU+0+RRYHU51*ODVV$*&DGHOO'05XVK%%HWDO(SLGHPLRORJLFHYLGHQFH VKRZLQJWKDWKXPDQSDSLOORPDYLUXVLQIHFWLRQFDXVHVPRVWFHUYLFDOLQWUDHSLWKHOLDOQHRSODVLD-1DWO&DQFHU ,QVW ±

3.

%ULQWRQ/$7DVKLPD.7/HKPDQ+)/HYLQH560DOOLQ.6DYLW]'$HWDO(SLGHPLRORJ\RIFHUYLFDO FDQFHUE\FHOOW\SH&DQFHU5HV ±

4.

9L]FDLQR$30RUHQR9%RVFK);0XQR]1%DUURV'LRV;0%RUUDV-HWDO,QWHUQDWLRQDOWUHQGVLQ LQFLGHQFHRIFHUYLFDOFDQFHU,,6TXDPRXVFHOOFDUFLQRPD,QW-&DQFHU ±

5.

5LFKDUW50&HUYLFDOLQWUDHSLWKHOLDOQHRSODVLD3DWKRO$QQX±

6.

&YLNR$%ULHP%*UDQWHU653LQWR$3:DQJ7