Detection of Invasive Cervical Cancer By Exfoliative Cytology

DETECTION OF INVASIVE CERVICAL CANCER BY EXFOLIATIVE CYTOLOGY CHARLES

,J.

\VROBEL,

M.D.,

BEVERLY HILLS, CALIF.

THERE ~s ,general. ag;·eenwnt at Tres~~l~~ ~}:at it ~s, feasihl.e, t.o ~l.('t~c.'l c•an·t.1. noma ot tne <'Pl'YIX ny means ot PXlonanvc· eytowgy wnnm nmns c1f ae·· <'llracy entirely aeeeptable fm· dinieal praetic·e. Houtine screening !'X
At

pre:-~ent. a substantial pet·eputngp of tit!' <'t'tTieal lesions now ]i(·ing

cletectecl lJy eyt.ologie Pxamination c·on:-~ists uJ so-eall<'cl '' f·an•inoma in situ.'' ··preinvasive enreinoma, '' or· "rwninfilt.rtHlent on wlwth('l' in-llitu careinoma of t.lw ('('t'\·ix i:-; dd<·t·JttinPd to h!' a pl·ogTeSiliY<' Iii' r·eg-ressi\l· lt•siotl.''

1t was f!'lt that stndi('t-> direded at the c·xn<"t natun• of the lt•sion !wing' eu nently cletretecl by l'ytologir S<·rt•enin g might :-~lwd light on t hi~; funrlanH•n1al C[UPstion. The materi<11 following haH ]wen aeewnulated with this end i11 dew, and is eonqwsrcl of data on -1-,200 patients spc•n in a eiinie-type pradiee.'"' 'rlu:ose were all examitwcl with vaginal smpar·s ;Js a ser<'Prling pt·ne<·chJr·c•. :'\o ;Jtternpt ut seleetion

011

any basi:-~ hn:-~ lwen mach·

fu this study 18 ea:-~t·s in whieh a histologi(' diagnosi:-; of <·areinotlla was ultimately made are recorded in Tahlt-> l. Jn eal'h of thesr C'HSE'!-i th<· initial elinieal impre:->sion was other· than c'at·c•incmw. the first positive~ inclieation of malignancy ht.•ing the result of cytolog·i<, t>xaminatiou. Three east'S of elini(~ally evi(lr11t eareinoma with po~;itivt• smt.•ar·:-; have lwc·n exeln<1(•cl frum this study as immaterial. The physician making the initial smtoar· in eaeh <·ase pi·o,·icled tho data listed in an~;wet· to a qnestionnait·c• whieh i1wlnd0d tlw following·:

1. In what clinic WPJ'<' ihf' smean; takc·n~ 2. Did the patient havcc a speeifie gyw•c•ologic• <·om plaint"! (11' .n's, sTwc·i t'y hl'icfty.) :3. \Vas there a visiblt> lesion ol' thl' <'('J'Yix at tht• tint<' thP snwars wt>n' taken! (If so, give clinieal impres~;ion.) -t \Yas there a biopsy taken nt the tinu' of stllt>
histologic diagnosis?) 5. T..Jist any subsequent histolog-iC' di
Pl~rrnanente

F'oundation Clink to revert

402

thE-~::>e

data i:3 gratefully

Volume 71

Number 2

lJE'l'ECTION OP INVASIVE CERVICAL CANCER BY CY'l'OLOOY

403

(If the final histologic diagnoses of eancer llHlde, lU of JB pt'oved to lw early invasive carcinoma in the opinion of two independent pathologists. Extension into the necks of the endocervical glands was not consideted to be true invasion in this study. Eight of these 10 patients were seen in the gyneeolog,v ~·linic by a qualified physician. Six (Nos. 1, JO, 11, 13, 16, and 18) had complaints commonly associated with cerviral earcinoma. Three of the 10 had no clinical lesion of the cervix. while 7 lesions were described varionslv as "cervicitis'' or "cerdcal erosion.:' In 8 of the 10 eases no biopsy was p'erformed at the time the initial positive smear was made. In 2 of the 8, the eervix was actually hy-passerl in favor of endomet1·ial biopsy. 'i'Al:II,E

PATIENT

AGJ<

<'LI:-
2. J.B.

4A

Gyn.

Irrrgular period;;

Gyn.

~ot

Gyn.

Not

CUMPLAJ:-.IT

1

1Ml'J>ES8HJK OJ<' CERVIX A'l' l'IM~: 01!' SMEAR

A'r TIME OF' INI'l'IAL SMEAR

BIOPSY

~'INA!,

HISTOLOGIC DIAGNOSIS

earcinomn

3. I. W.

4. D. A.

-15

~ormal

\ EndomPtrial biopsy)

Carcinoma in situ

given

Chroni<·. crrviei! is

Chronir o•rrvicitis

Carcinoma in situ

g·[y(~ll

Chrmli<'

l11vasivc ran·inoma

Invasivr carc.inoma

••f•rvl(~,itis

5. H. B.

3ii

Oyn.

PI'! vie pain

HypertrOJ>hic rnvi<:itiR

None

Carcinoma in 8itu

6. A.S.

±a

Gyn.

'' J\.1enopaus(•''

Normal

None

Invasive earcinon1a

7. L.P.

51

Hyn.

•'Vulvar itrh"

(:I'I'Vl\\ttl

'.None

Carcinomn in situ

8. A.P.

31

Oyn.

Vaginal discharge

Ct>rvhonl

Cervititis

Carcinoma in situ

{'ro:qiou ero~i011

!l. 8.0.

:JR

Gyu.

None

Normal

)!one

Carcinoma in ~itn

10. V.N.

:111

nyn.

Metrorrhagia

Cnvieal l'l"osion

Nont>

] nva;;ive rarcirwma

11. L.M.

±:i

Mt><1.

1\Ietrorrhagia

('ervical <>roRion

None

Invasive

19 D. K.

;1:l

None

('hrnnie eefvf('.i tiH

n,•rvlr:it.l~

Invasive

Dyspareunia

Bullous

Carcinoma in ~itu

Invasive carcinoma

Me
flart<.inon1:1

eareiTUIUlH

Vl. R. K.

:.~3

H. F. II.

38

Me d.

None

Chronie cerviPitis

None

Careinonm in situ

15. M.H.

63

Me d.

None

Normal

None

lm·a~ivr

1 Endometrial

Invasive

rPrviciti~

rarrinom:c

Hl. L.H.

33

Gyn.

M<>norrhagia

Ct>rvi('itis

17. D. G.

41

!\led.

V:tginal discharge

Nornml

None

C:n rr1-ino1na

Ct>rvil'itis

(Endometrial

Invasive rarcinoma

lR. A. F.

43

Gyn.

Menorrhagia

biopsy)


in 8ilu

404-

:\m J. Ot-r.. t. & l3yuu

\V HO H 1·: I.

f't·hrue~ry, 191\r,

Jn cliseussiou of this latter datum with the physicians invohed. tlw qll\'s tion arose as to whethet· in a large pt·opol'tion of thes<· H cases no biopsy w;J.-.: JWrformerl lwr·an~>t• thr· <·linieian i·p]ied (Ill l'ytnlog·ir· acenra<•y. lt \\'as ngt·<·Pd thai this fador
Comment l)U!llt:! hHS l'~IJ!'rHeHf.t•d Rehrtnati(•gjh· fliP n:lfhn.O'Ptlf·~i~

in wllieh a vreiilYasivc stng<· is prPsrnt

11.1

A ·:lill,

l: n n•eognizable

earcinogenesis

On~Pt

nf

:ll 1'{1.1){~~!1'

tl;;: f;)jj;;~vi~I,g·~;;;~flll-J~~·~,J;r·t:: t•f'J'\·il 1

1\

I

-or;;;, rr{noma-( >nsr;i-ofTilvasiV{•

r;er\~i··

in situ

lJ~\mrtime-·nf (liagtHJSiR nf

symptomatic and/or ,•Jini cal canci'r

Let us use a silllilnr sch<'llJe fm· 111\' ('l'tTi<·aJ <·anc~t·r in whieb it iii assUIH<'d that no preinvasive stag(• takt>s pla<~r. ('

A

IIIII l' nrecognizable

carcinogenesis

-

\'so a!

--on:setofiil\:;~j,.,.

•·•·rvi,·al

' !1 me ;;f -diagrlo~i~-;){ syrnp

tomati.~

ea11<'Pr

and/or clinical

~ancer

\Y<> may now consider- the cytologic eoutribution to the over-all problern of <'<'t'\'lcal eanc<·I· in thrsr· -t200 iiHlividuals in terms of two fignrrs, of whieh one is known and the other i~ a percentage of a known. Tho first figure consists of 10 cases of invasive carcinoma whieh may h(' desi!!natecl ns those nrevailin!" in the interval hetween B :md C in either Di
r.

ti~!

.

Volume 71 Number 2

DETECTION OF INVASIVE CERVICAL CANCER BY CYTOLOGY

405

In order to compare the type of lesion detected by cytologic means in private practice as opposed to clinic practice, a review' of' 1,000 consecutive vaginal cytology examinations performed by the author on privately referred patients was made. Six carcinomas of the cervix were detected all clinically ummspected. Of this number, 3 proved to be already invasiv~. \Vhile th.l' nnmher of eases is not large, there is at least a strong suggestion that a comparable percentage of early invnsive eareinnmas will he detected in pdvat(' a.nd clinic practice. 'l'o return to the question regarding the nature of carcinoma in situ nwntionecl at the beginning of this paper, it might h€' well to summarize present enncepts briefly. Dunn 2 has stat<>n this prohl<>m very fully in the form of thP following three questions: A. \Vhat percentage, if not all, of carcinomas in situ ultirnatelv become in· vasive carcinoma? B. \Vhat percentage of invasive carcinomas arise as carcinoma in situ"! C. Assuming that all, or a substantial proportion of, carcinomas in situ become invasive carcinoma, what is the average duration of carcinoma in situ, and how much time variation is there arounfl this mean duration~ He points out that no study based on indivitlual cases of cervical carcinoma can provide information on the second of these questions. Purtberrnore, direct evidence related to the first and third questions is not abundant because of the long time period involved in individual case follow-up. Despite this fact, several noteworthy contributions to these questions arc already available. No definitive answers to these three questions may be forthcoming :for another· ten years, but there can be little doubt that the prohlt'm will in time yield to the combined efforts now being made. Carson and GalP r·c-cxamined 718 cervical biopsies in which a diagnosiF: of chronic cervicitis or squamous metaplasia had originally been rendered. In 13 of these, changes compatible with the diagnosis of carcinoma in situ were found. Follow-up studies of these individuals showed 5 cases of invasive carcinoma diagnosed shortly after the first biopsy, 3 cases of invasive carcinoma diagnosed after intervals of 2, 5, and 12 years, respectively, one inc1ividual free from disease after 10 years, and 4 patients not located. They also
Evidence gained by a similar approach has heen presented by Galvin . •Tunes, and Te Uncle. Seven hundred forty cases of clinical invasive careinoma W('l"e reviewed to determine whether cervical biopsy had been performed on thr illllivi(luals some timE' prior to the diagnosis of invasivE' carcinoma. ThirtN•n sue h eases were found. and in all but one instance the previous biopsy tissue rt>Hn.le(l carcinoma in situ. Hertig and Younge 5 have assembled the following arguments favoring the thesis that carcinoma in situ is actually true carcinoma in a preinvasive stage: 1. 'l'he general prevalence of one lesion is comparable to that of: the other, while the mean age of incidence of carcinoma in situ is lower than that of invasive carcinoma. 2. The prevalence of both conditions in ,Jewish women is almost the same, as compared to the prevalence in non~J ewish women (one to six and one to fivf', respectively, for preinvasive carcinoma and invasive carcinoma). ~. They cite a number of f•ases of eareinoma in sitn obs0rved to progr0Sf-l from this status to invasion,

Arn. J,

406

4.

Oh~t.

& Gyw'1.

Frhr1JJry, l9Sf

nhserve that inereasing- dt~g'!'PPS ~~r ~·eJ!ulai' atypisrn f!!'e t~h ....;er\~(.iJ aH the ill ~-;itn le~-;imr h<·t·onH's in l'asi 1'<'. :i. The pattern of in Hitu l'arrinoma is rleH<~rilwd as nrarl;r always pr·est•i11 at the periphery of inyasin• <~areinoma, !L Both lesions arc ohsrrvrd to exhibit idt•nti<·nl lig·ht.-ahsorption pat1<'1'Jts when examined hy ultraviolet illumination. by

'Jlhe~yr

cytologi<~ method~-;

!~vidence against the rrlationHhip between <•an·inoma in sitn and i111 asiw

is offerc·ll hv Kottm\'iPt',n who followed +I individuals with untreated t•arcinoma in situ for' a ten-yPar Jwriogarding the lr•sion whirh has hrt·om<' invasin• m· whieh is i11vnsivP ft'ollr ineeption, lW disagT<'f'lll<'ld (•xist" thai Parly
Conclusions I. Data af•eumulatrd ft·om a serif's of S!•.n•ening· <'Xatninations for <'<'l'l'it•:tl eanr·er are pr!•sent<•d. 2. Eviclen<~(· is offerer] that eytologie S<'l'erning iH oi' l1istinct valrw i11 1lPt<',.,. tion of rarly iJlYasivc carcinoma of the <~<·t-vix in the pr·cclinical state, as well as in detection of t'ar·cinomn in sitn, mnt'P than half the cases deteded in this series bring already invasin. :). A partial snmm;u-y of the tlllT<'IIt opinion
References l. McDonald, .1. H.: i\n1 .. J. Clin. !'a til. 24: !iF:::, ]!l;i~. :.l. Dunn, .T. E., .Jr.: Cancer 6: .~73, 1!lfi:). 3. Carson, R. P., and Gall, Ei!wan1 A.: A111 .• J. l'ath. 30: !;), I!I!J-l. 4. Galvin, Gerald A., .Tones, H. W., .rr., ancl 'J'r LindP, R. W.: .J. A. M. A. 49: 74-~, 1!1;):.). 5. Hertig, Arthur .T., aml YoungP, Paul A.: A:11. .J. Ons·r. ii: OYNEC. 64: H07, Hl52. 6. Kottmeier, H. L.: Trans. InternaL & Fourth Am. ('ongr""~ on Oh~t. & GvnN•, r An 1 • • r. Ohst. & Gynec. Rnpp.) 61A: 1::).!, 1Hfi 1. · 'i. 1viorton, D. G., and Dignam, ·w.: AM . •T. 0BS'l'. c1: t~YN};C. 64: H9H, ifl53. 441 NORTH

CAMDEN DRTvto;