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J. clin. Path. (1969), 22, 383-395

The histology and cytology of changes in theepithelium of the cervix uteri'

A. D. T. GOVAN, R. M. HAINES, F. A. LANGLEY, C. W. TAYLOR,AND A. S. WOODCOCK2

From the Royal College of Obstetricians and Gynaecologists, London

SYNOPSIS Abnormalities of the cervical epithelium are set out in two main groups: bland lesionswhich are regarded as unrelated to malignancy, and malign lesions which are considered as potentialprecursors of invasive carcinoma. The histological features of each condition and the cytologicalpattern of the corresponding cervical smear are described and correlated.Cone biopsy is advocated as the only satisfactory form of cervical biopsy for both the diagnosis

and evaluation of lesions such as dysplasia and carcinoma in situ. It is emphasized that furtherstudy is necessary to determine their natural history and prognosis in relation to invasive carcinoma.

It is now widely accepted that certain abnormalitiesof structure and arrangement in the cells of cervicalsquamous epithelium may be the precursor ofinvasive carcinoma. These changes within theepithelium are termed mild or severe dysplasiaaccording to their severity, and in their extreme formare described as carcinoma in situ.

Usually these abnormalities produce no signs orsymptoms, and are not detectable at ordinaryclinical examination. Cytology, however, by thestudy of cells scraped or exfoliated from the cervix,provides a routine screening method. The discoveryof cells in the cytological smear suggestive of severedysplasia or carcinoma in situ is an indication forcervical cone biopsy. It is not only in the interestsof the patient that these lesions should be detectedin this way, but it also provides material for furtherstudy of their relationship to invasive carcinoma, asubject on which there is as yet little precise informa-tion. If such a study is to be valid, then there mustbe uniformity in the terminology and histologicalcriteria used in assessing the lesions. This paperattempts to describe and classify abnormalities ofthe cervical epithelium in a manner suited to thispurpose. Many of the views expressed have crystal-lized from the study the authors were asked to makeof histological material in the survey of carcinomain situ being carried out by the Royal College ofObstetricians and Gynaecologists (Govan, Haines,Langley, Taylor, and Woodcock, 1966).'Copies of this paper may be obtained from the Publishing Manager,B.M.A. House, Tavistock Square, London, price 5s each, the envelopemarked, Journal of Clinical Pathology, BROADSHEErs.2The authors of this report are the members of a paniel appointed bythe Royal College of Obstetricians and Gynaecologists.

The paper deals particularly with dysplasia andcarcinoma in situ, but includes other changes which,although unrelated in their natural history, havehistological patterns sometimes confused with theseconditions. Clinically invasive carcinoma is not dis-cussed. The detection of abnormalities in the cervicalsmear is often the first step in the diagnostic sequenceof the more serious lesions; for this reason anattempt is also made at a broad correlation betweenthe histological appearances in the biopsy specimenand the cytological pattern of the correspondingsmear. It is of great practical importance in dis-cussing any abnormality of the cervical epitheliumto decide whether or not it is related to carcinoma.The changes are therefore described in two maingroups: first, bland lesions which are regarded ashaving no proclivities for malignant change, andsecondly malign lesions which are considered to bepotential, though not invariable, precursors ofinvasive carcinoma.

CHANGES IN CERVICAL EPITHELIUM

BLAND LESIONS These are subdivided into squamoushyperplasia (reactive hyperplasia and basal cellhyperactivity), reserve cell proliferation, and meta-plasia incomplete and complete.

MALIGN LESIONS The categories for malign lesionsare dysplasia (mild and severe), carcinoma in situ,and microcarcinoma.

BLAND LESIONS

SQUAMOUS HYPERPLASIA Squamous hyperplasia, an383

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384 A. D. T. Govan, R. M. Haines, F. A. Langley, C. W. Taylor, and A. S. Woodcock

orderly thickening of the squamous epithelium ofthe cervix, occurs in two main forms.

Reactive hyperplasia This form consists in athickening of the whole epithelium. It is seen insome chronic irritative conditions and particularlyas a result of prolapse. The surface usually showshyperkeratosis with parakeratosis of varying degree;the basal layers may be fragmented and the retepegs are often lengthened and broadened. There isno cellular atypism and maturation is normal.

Basal cell hyperactivity This form is of unknownaetiology. The basal layers of the epithelium pro-liferate to form several instead of the usual one ortwo layers. There are only very few mitoses, butthe component cells have rather large nuclei andbasophilic cytoplasm suggesting increased activity.The upper layers of the epithelium are mature andnormally stratified.A regenerating epithelium also may show activity

of its cells. These may be slightly irregular inarrangement and may make up the whole thicknessof the thin re-forming epithelium. There are, how-ever, attempts at maturation, especially towards theedges where the new epithelium merges with thenormal.No disturbing cytological changes occur in the

smear from either form of squamous hyperplasia,for there is no cellular atypism in these variants. Inreactive hyperplasia with hyperkeratosis this will bereflected in the smear by a preponderance of super-ficial squames, some of them anuclear. This patternwill be particularly noticeable when it occurs in the

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FIG. 2. Basal cell hyperactivity: several layers of activebasal cells are covered by squames.

niG. 3. Regenerating epithelium: immature but not undulyactive cells make up most of the epithelium. More maturecells at the right merge into normal epithelium.

FIG. 1. Reactive squamous hyperplasia: an orderly thickeningof the stratified epithelium with keratinization.

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The histology and cytology of changes in the epithelium of the cervix uteri

elderly, postmenopausal patient, whose smear wouldnormally lack this cell type, but who has in thisinstance severe uterine prolapse. In basal cell hyper-activity the smear will as a rule be uninformative,for the Ayre's spatula used to obtain the sample ofcells will not reach the deeper layers. Occasionallya few basal cells may be present and these will haveslightly larger nuclei than is normal. In the smearfrom a regenerating squamous epithelium similarrounded cells with slightly enlarged, bloated nucleimay be found. These cells are sometimes numerous,and if areas of ulceration remain on the cervix theremay also be a considerable number of inflammatorycells including histiocytes. The cytological abnormal-ities, however, are slight and should not producediagnostic difficulties.

RESERVE CELL PROLIFERATION A layer of small cells,patchy in distribution and inconspicuous, is oftenpresent immediately beneath the columnar epith-elium of the cervix. In some conditions, such aserosion or polyp, these cells proliferate to formseveral layers but remain orderly. The clusters ofcells form not only beneath the surface epitheliumbut also around the gland crypt.The degree of proliferation of these so-called

reserve cells varies, and when marked may meritthe term 'reserve cell hyperplasia'. At scanningmagnifications the intricate multilayering may beconfused with the appearances of carcinoma in situ,especially when the process involves gland crypts,but on detailed examination it is distinguished bythe orderly and uniform structure of the componentcells.

FIG. 4. Reserve cellilFpE proliferation: a single layer of

orderly reserve cells liesSriLa beneath the columnarS^It3* epithelium of the endocervix.

FIG. 5. Reserve cell*w < proliferation: reserve cells

have proliferated beneath thecolumnar epithelium ofglandcrypts.

FIG. 6. Reserve cellproliferation: reserve

Ap¢s:;_< cells form a layerbeneath the surface columnar

fr4~~ epithelium and have prolifer-+' ated around a gland crypt.

FIG. 6.

FIG. 4.

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386 A. D. T. Gowan, R. M. Haines, F. A. Langley, C. W. Taylor, and A. S. Woodcock

Reserve cell proliferation produces no character-istic changes in the cervical smear.

METAPLASIA Metaplasia is a change from a colum-nar to a squamous type of epithelium. It usuallystems from a proliferation of the reserve cells and avariety of appearances results according to the stageand extent of the transformation. The process canbe conveniently considered under two headings,incomplete metaplasia and complete metaplasia.

Incomplete metaplasia is a stage at which remnantsof the columnar epithelium are still recognizableas the replacement by squamous epithelium con-tinues. Early in the process layers of proliferatingreserve cells form a sheet of squamoid epitheliumwith a ribbon of columnar cells on its surface. Thesecells may be of typical, well formed endocervicalpattern, but more often they are degenerate, or maybe stunted and peg-shaped without obvious mucoussecretion. As metaplasia proceeds the patternbecomes more confusing. The columnar cells areengulfed by the proliferating reserve cells and a hap-hazard mixture of mucus-secreting and squamoidcells results. The mucous cells degenerate, becomingbloated and distorted; they may burst, leaving onlytiny lacunae, some containing mucus, some poly-morphs, in the depths of the new epithelium. Thebizarre appearances which result can cause difficul-ties in interpretation and may be mistaken forcarcinoma in situ. Careful examination, however,will show that the proliferating reserve cells areorderly as regards the size, shape, and chromatindistribution of their nuclei. The irregularities are dueto degenerative changes in the scattered mucouscells and these may be demonstrated more clearly bythe use of stains such as mucicarmine or alcian blue.

Complete metaplasia, sometimes termed epider-midization, is the state when the columnar cells arereplaced entirely by irregular plaques of newepithelium which is squamous in type, but incom-pletely stratified. The change is usually patchy indistribution but can be extensive. It is not limited tosurface epithelium but may involve gland crypts, andis then particularly liable to be mistaken forcarcinoma. However, the epithelium, although in-completely stratified, is composed of mature cellswithout mitoses or nuclear atypism. In contrast tothe irregular pattern of invasive carcinoma, the meta-plastic epithelium maintains the contours of the sur-face mucosa and the smooth outlines of gland crypts.

In the smear, swollen, distorted endocervical cellsmay be seen in incomplete metaplasia but similarcells occur in other conditions such as erosion,which may indeed coexist. Sometimes a cluster ofthese endocervical cells gives difficulty in interpreta-tion, but as a rule there are occasional cells at the

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FIG. 7. Metaplasia: a sheet of squamoid epithelium, the

result of reserve cell proliferation, lies under an intact

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FIG. 8. Metaplasia: an intricate pattern formed by partialreplacement of the columnar by squamoid epithelium.

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FIG. 9. Metaplasia: on the left, bloated mucous cellsintermingle with squamous cells and distort the patternof the epithelium.



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FIG. 10. Metaplasia: squamous cells occupy the basalportion of the epithelium. The fragmented upper layerscontain mucous cells which could be identified more clearlyby special stains.

FIG. 11. Metaplasia: mature squamoid epithelium com-

pletely replaces the columnar epithelium but the outlineof the crypts remains.

periphery of the cluster which maintain sufficient ofthe characteristic columnar outline for identificationof cell type. Most of the nuclei are of typical, orderly,vesicular pattern with prominent nucleoli. A fewnuclei may be irregular, but the abnormalities aredegenerative, consisting mainly of swelling andblurring due to karyolysis. There are no specificchanges in the smear in complete metaplasia.

MALIGN LESIONS

The changes in the epithelium so far described,although occasionally misinterpreted as malignant,have in fact no known relationship to carcinoma. Incontrast, the lesions now to be discussed are termedmalign because all show in some measure abnormal-ities of cell structure and arrangement which relatethem to malignancy. Nevertheless, mild dysplasiadiffers considerably in clinical significance fromsevere dysplasia and carcinoma in situ, for not infre-quently it results from an inflammatory cause suchas infection with trichomonas and is then usuallyreversible.

Severe dysplasia and carcinoma in situ, on theother hand, carry a far more serious risk of eventualprogression to invasive cancer.

DYSPLASIA The two grades of dysplasia are dis-tinguished histologically by the degree of cellularirregularity.Mild dysplasia The cells do not lose polarity and

stratification is maintained. Maturation and differ-entiation are perverted, however, so that thedysplastic epithelium becomes a caricature of thenormal. The predominant feature of the cells is thatnucleus and cytoplasm are out of step. The cyto-plasm differentiates relatively normally, althoughsometimes individual cells at various levels in theepithelium show premature cornification. In con-trast, the nucleus tends to be large, slightly irregularin outline and may be hyperchromatic. The changesare most evident in the upper layers of the epitheliumwhere many of the cells have a normal cytoplasmiccontent, but enlarged, misshapen nuclei. Super-imposed degenerative changes, such as karyorrhexisand the formation of halo-like clear zones round thenuclei, are a usual feature of dysplasia and accen-tuate the abnormalities. Often pallor and shrinkageof cytoplasm make intercellular bridges con-spicuous.The smear from mild dysplasia mirrors these

epithelial changes. The individual cells are clearlyrecognizable as of superficial, intermediate or basallayer origin, but have the characteristic feature ofan irregular nucleus which is immature in relationto the cytoplasmic content of the cell. Invariably

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FIG. 13.

FIG. 12. Dysplasia: there is a contrast between normaland dysplastic epithelium.

FIG. 13. Mild dysplasia: immature cells with large hyper-chromatic nuclei are scattered through the epithelium butthere is stratification and cells in the upper layers showmaturation.

FIG. 14. Mild dysplasia: pyknosis, karyorrhexis, andperinuclear haloes in the abnormal cells, at higher magni-fication.

FIG. 15: Mild dysplasia: some of the abnormal cells showsevere degenerative changes.

FIG. 16. Severe dysplasia: the epithelium is composed ofpleomorphic cells. Stratification is just discernible in thethin upper layers.

FIG. 17. Severe dysplasia: pleomorphism at higher mag-nification, with both proliferation and degeneration of cells.FIG. 14.

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-o..*>t7-3 !'%v> FIG. 15.

superficial and intermediate squames predominate.The superficial squames have pyknotic nuclei whichare larger than normal and often slightly misshapen.The nuclei of the intermediate squames are enlargedand mildly irregular, but there is little clumping ofchromatin and the upset in nucleo-cytoplasmic ratioproduced by the nuclear enlargement is only slight.Degenerative changes are conspicuous and theremay be perinuclear halos in both superficial andintermediate squames, particularly when the dys-plasia is associated with trichomonas infection. Theterm dyskaryotic has become established to describecells of the above pattern, perhaps to emphasize thatnuclear and not cytoplasmic abnormalities are theircharacteristic. Thus the report of dyskaryotic cells ina smear implies that they arise from an epitheliumwhich is itself dysplastic.

Severe dysplasia The cells are much moreirregular than in mild dysplasia, both in morphologyand arrangement. There is only a poor attempt atmaturation and stratification of the epithelium isbarely discernible. The nuclei are greatly misshapen,usually hyperchromatic and their chromatin iscoarsely clumped. There may be bizarre mitoses atvarying levels in the epithelium. A distinctionbetween severe dysplasia and carcinoma in situ issometimes extremely difficult. A diagnosis of dys-plasia can be made firmly if there is evidence of truestratification, but stratication must not be confusedwith the layer of flattened cells not infrequently seenon the surface of carcinoma in situ. Often theopinion can only be based somewhat arbitrarily onthe impression that there is less crowding of nucleiin the upper than the lower layers. The abnormalepithelium is easily dislodged. If the surface layers

FIG. 16.

FIG. 17.

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A. D. T. Govan, R. M. Haines, F. A. Langley, C. W. Taylor, and A. S. Woodcock

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FIG. 18. Malign epithelium: the epithelium in dysplasiaand in carcinoma in situ is fragile and is easily displaced.

FIG. 19. Carcinoma in situ: undifferentiated cells crowdthe whole thickness of the epithelium and stratificationis lacking.

FIG. 20. Carcinoma in situ: pleomorphic cells with largehyperchromatic nuclei showing an increased nucleo-cytoplasmic ratio.

FIG. 21. Carcinoma in situ: abnormal cells escape fromthe fragmenting epithelium.

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of cells have been lost due to such cause as the recenttaking of smears or swabbing before the biopsy, thenthe distinction from carcinoma in situ may beimpossible.The smear in severe dysplasia contains cells in

which nuclear abnormalities are conspicuous. Thechromatin is clumped and usually hyperchromatic;the nuclear membrane is often irregular andwrinkled. These appearances in the nucleus resemblethose of malignant cells, but, despite their enlargedmisshapen nuclei, the majority of cells maintain anessentially normal outline and cytoplasmic contentso that they can be recognized as dyskaryotic ratherthan malignant. Sometimes, however, when thesmear is from a severe dysplasia barely distinguish-able histologically from carcinoma in situ there maybe a quite considerable upset in nucleocytoplasmicratio. It may then be difficult or impossible to decidewhether the cells are dyskaryotic or malignant.Occasionally a similar difficulty arises when a smearcontains cells from the surface layers of a fairly welldifferentiated invasive carcinoma. These cells mayappear dyskaryotic. In both instances the problemis academic, for such severe abnormalities in a smear,regardless of their precise interpretation, provide aclear indication of the need for cone biopsy.

CARCINOMA IN SITU The characteristic histologicalfeatures of the lesion are complete loss of stratifica-tion and loss of cellular differentiation. The wholethickness of the epithelium is composed of closelypacked, undifferentiated cells, but the basementmembrane is intact and the epithelium is sharplydelineated from the underlying connective tissue.

Rete pegs are rarely seen. There is loss of polarity,cells lying obliquely or at right angles to their usualaxis, often producing a completely haphazardarrangement. There is poor cellular cohesion, sothat the upper layers may appear frayed and incom-plete. Occasionally there are a few flattened cells onthe surface of the epithelium but, as already noted,this does not represent true stratification.The cells are basophilic with an upset in nucleo-

cytoplasmic ratio, so that the nucleus is relativelylarge and the cytoplasm inconspicuous. Generallythe cells are pleomorphic, but on occasion they havea uniformity reminiscent of basal cell carcinoma. Asa rule the nuclei are irregular in shape and hyper-chromatic. Mitoses may be abundant or infrequent;when present a high proportion are bizarre.The smear in carcinoma in situ usually contains a

large number of abnormal cells. Often some of theseare in ribbons or sheets, for the epithelium is fragileand easily removed with the spatula. The cells varyin shape and size. The most characteristic cell,however, is rounded, about the size of a normal

basal cell, but has a much larger nucleus occupyingmore than half the cell. Apart from its greater size,the nucleus differs very much from that of a basalcell in that there is hyperchromasia with coarse,blotchy clumping of the chromatin and indentationand thickening of the nuclear membrane. Nuclei areoften crenated and some are multilobed. Thecytoplasm, unlike that of dyskaryotic cells, is notplentiful, but the cell outlines are usually distinct.Nevertheless it must be emphasized that carcinomain situ and various degrees of dysplasia often coexistin one and the same cervix. Thus the smear in car-cinoma in situ frequently contains an admixture ofdyskaryotic cells.

ENDOCERVICAL GLAND INVOLVEMENT The mucousglands of the cervix are frequently involved incarcinoma in situ and in severe dysplasia, but onlyoccasionally in mild dysplasia. Usually the abnor-malities in the epithelium lining the glands corre-spond to those of the surface epithelium, but thechanges in the glands may appear the more severe.Sometimes this may be due to tangential cutting, andfurther sections should be examined before the lesionis classified. This is particularly important in a conebiopsy when the fragile surface epithelium has beenlost and only the glandular extensions remain forassessment. This may result from manipulationbefore or during operation or in the course oflaboratory processing.

In our opinion the outcome is not affected by thepresence or absence of mucous gland involvement.Such involvement can, however, be mistaken forinvasive carcinoma. This error is especially possiblewhen the plane of section shows no continuitybetween the involved gland and the surface epithe-lium and when the gland lumen appears completelyfilled by the abnormal epithelium. The smoothsymmetrical outlines of the glands help to dis-tinguish this change from true invasion, and thedifficulty may be resolved if additional sectionsreveal remnants of a lumen or of its original colum-nar cell lining.

MICROCARCINOMA We regard microcarcinoma asminimal stromal invasion stemming from carcinomain situ. The clumps and tongues of abnormalepithelial cells which infiltrate the cervical stromain microcarcinoma have not the smooth roundedcontours seen when carcinoma in situ merely involvesgland crypts; in contrast, they have irregular, spikyoutlines. Their cells fray out into the connectivetissues, and often the surrounding collagen iscondensed. A further diagnostic feature is that theinvading cell masses often show at their centres a

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FIG. 22.FIG. 23.

FIG. 22. Malign epithelium in glands:the epithelium in the involved glandsappears to be more abnormal than thaton the surface.

FIG. 23. Gland involvement: carcinomain situ involves glands but their contoursare preserved.

FIG. 24. Microcarcinoma: beneath thecarcinoma in situ there are buds ofmalignant epithelium invading the cervicalstroma.



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The histology and cytology of changes in the epithelium of the cervix uteri 393

FIG. 25. Normal squames: a mixture ofsuperficial (eosin-ophilic) squames with tiny pyknotic nuclei and intermediate(cyanophilic) squames with slightly larger vesicular nuclei.

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FIG. 27. Normal endocervical cells: the cells cluster andmay be seen cither as columnar cells with peg-like pro-

cesses at the lower pole and with basal rounded vesicularnuclei, or as a sheet of closely packed cells with uniformnuclei and prominent nucleoli.

FIG. 28. Dyskaryotic cells: the cells have adequate cyto-

plasm and slightly enlarged nuclei, some with peri-nuclearhaloes; most of the nuclei are smooth and rounded butsome are irregular due to degeneration. The nuclearchromatin may be clumped or granular. A few typicalsquames with small pyknotic nuclei contrast with thedyskaryotic cells. The smear should be related to thehistology seen in Fig. 14, illustrating 'mild dysplasia'.

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FIG. 29. Dyskaryotic cells: the cells have enlargedirregular nuclei with coarsely distributed chromatin; someofthe nuclei arepyknotic. Compare with the normal squamepresent.

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FIG. 30. Dyskaryotic cells: the picture contains a mixtureofnormal and dyskaryotic cells. At the centre the cells withhyperchromatic nuclei are very abnormal and illustrate thedifficulty of distinguishing severe degrees of dysplasia fromcarcinoma in situ. The smear should be related to thehistology seen in Fig. 17, illustrating 'severe dysplasia'.

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FIG. 31. Malignant cells: a cluster of pleomorphicmalignant cells with scanty cytoplasm and coarsely distri

s 2. E9 w buted chromatin in the nuclei. The cells are surrounded byred blood cells. The smear should be related to the histologyseen in Fig. 19, illustrating 'carcinoma in situ'.

FIG. 32. Malignant cells: a higher power picture showingin more detail the bizarre shapes of the cells and thecoarse irregular distribution ofnuclear chromatin typical ofnialignant cells. The smear should be related to the his-tology seen in Fig. 20, illustrating 'carcinoma in situ'.

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degree of differentiation amounting to prickle cellformation.

Microcarcinoma is not distinguishable fromcarcinoma in situ in the cervical smear.

DISCUSSION

Bland and malign lesions are not infrequently bothpresent in the same cervix, but there is no wellestablished evidence that this is other than coinci-dental. As regards malign lesions, it has alreadybeen emphasized that the relationship of dysplasiaand carcinoma in situ to invasive carcinoma requiresmuch further study. There is equal uncertainty aboutthe relation between dysplasia and carcinoma insitu. These lesions may coexist in a cervix, but thecombination is by no means invariable, nor is itestablished that there is a progression from one tothe other. Certainly, follow-up studies suggest thatmild dysplasia quite often regresses, especially when itaccompanies infection with trichomonas or occursin pregnancy. Severe dysplasia is of much moreserious import. Histologically it may be extremelydifficult to distinguish from carcinoma in situ andthere is no proof that it has any less potential fordeveloping into invasive carcinoma.The prime function of cervical cytology is in

bringing to notice epithelial abnormalities whichwould otherwise escape detection because of theirclinical silence. Cytology does not provide a defini-tive diagnosis, for this can only be achieved bybiopsy, especially when more than one lesion ispresent. However, it does give sufficient informationabout the changes in the epithelium for a decisionto be made on the need for biopsy. The area ofmaximum instability in the cervical epithelium is at

the squamo-columnar junction and it is in thisregion that malign lesions usually first appear.Therefore, when cervical biopsy is required, eitherfollowing an abnormal smear or for some clinicalreason, a liberal cone which includes the squamo-columnar junction and adjacent tissues around thewhole circumference of the external os, is the onlyadequate specimen. Ring biopsy often provides in-sufficient material. The whole cone must be examinedby dividing it into multiple blocks and studyingsections from each. When dysplasia or carcinomain situ is found, it is of great importance to be surethat there is not coexistent invasive carcinoma. Anyblock from which the initial slide shows suspiciousareas must be step-sectioned or cut serially. Cytologyis of further value after cone biopsy. Provided thatinvasive carcinoma has been excluded and that thewhole of the abnormal epithelium appears to havebeen removed, a patient may be followed up andsmears can be used to ensure that any residual orrecurrent lesion is detected promptly. Thus cytolo-gical examination and cone biopsy, used as comple-mentary techniques, are not only the main source ofmaterial for elucidating the natural history andprognosis of dysplasia and carcinoma in situ of thecervix, they are also essential to the diagnosis,treatment, and management of these conditions.

Our thanks are due to the Editor of the Journal ofObstetrics and Gynaecology of the British Commonwealthfor permission to reproduce Figures 3, 4, 6, 23, and 24.

REFERENCE

Govan, A. D. T., Haines, R. M., Langley, F. A., Taylor, C. W.,and Woodcock, A. S. (1966). J. Obstet. Gynaec. Brit. Cwlth,73, 883.

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