rectal biopsy as aid to cancer in ulcerative - gut.bmj.com · gut, 1967, 8, 423 rectal biopsy as...

Gut, 1967, 8, 423

Rectal biopsy as an aid to cancercontrol in ulcerative colitis

B. C. MORSON AND LILLIAN S. C. PANG

From the Research Department, St. Mark's Hospital, London

EDITORIAL COMMENT This is a very important paper as it provides the clinician with a new methodof identifying patients with total colitis who may be particularly exposed to the risk of carcinoma.Rectal biopsies of flat mucosa may demonstrate a certain cellular pattern which has been shown tobe particularly associated with carcinoma.

There is general agreement that malignant change inulcerative colitis mostly occurs in those patientswhose large intestine is totally involved and have ahistory of symptoms for more than 10 years. Havingthus defined the population of colitics most at riskthe problem remains of identifying the individualpatient destined to get carcinoma. There is yet noevidence that all the population at risk will eventuallydevelop malignant change. It has been previouslypointed out that some test is required which willdecide that a patient with ulcerative colitis hasentered a precancerous phase (Morson, 1966).The detection of epithelial changes suggestive of

precancer or carcinoma in situ in rectal biopsies frompatients with ulcerative colitis prompted an investiga-tion into the incidence and extent of such changes incolectomy specimens removed for colitis with andwithout malignant change. The results of this enquiryare reported here as well as an analysis of the firstnine patients in whom the diagnosis of precancer wasmade in a rectal biopsy and played an importantpart, together with clinical and radiological observa-tions, in the subsequent decision to perform totalproctocolectomy.

MORPHOLOGY OF PRECANCER IN COLITIS

There are two main types of precancer in ulcerativecolitis: the polypoid variety and precancerouschange in a flat mucosa.

Precancerous polypoid changes in ulcerativecolitis have been described and illustrated byDawson and Pryse-Davies (1959). The appearancesare similar to those found in solitary adenomas andvillous papillomas of the colon and rectum withoutany colitis although there are some significant

differences. The polyps are nearly always multiplealthough few in number compared with inflammatorypolyps. They are sessile, cover a relatively large fieldof mucosa and commonly have a villous or papillarysurface configuration (Figs. 1 and 2) rather than thetypical adenomatous appearance. In our experiencethe circumscribed, adenomatous polyp on a stalk socommon as a solitary lesion and in familial polyposisis seldom seen as part of the precancerous phase ofulcerative colitis. The fact that the villous growthpattern is the commoner type of neoplastic changemay be important, for there is evidence that this ismore prone to produce invasive carcinoma than theadenomatous variety (Grinnell and Lane, 1958).However, many of the precancerous polyps of ulcera-tive colitis have a mixed villous and adenomatousstructure and may be referred to as papillaryadenomas. Another distinctive feature of pre-cancerous polyp formation in ulcerative colitis is thepresence of an obvious inflammatory component.This is in continuity with the inflammation in sur-rounding flat mucosa. The cytological changes foundin these neoplastic or precancerous polyps of ulcera-tive colitis are described below. They are essentiallysimilar to those seen in solitary adenomas and villouspapillomas.

It would appear from our studies that neoplasticor precancerous change in ulcerative colitis morecommonly occurs in a flat rather than a polypoidmucosa. This cannot be detected by macroscopicexamination alone. However, those areas showingprecancerous change at a microscopic level of obser-vation vary in their macroscopic appearance frommucosa which looks almost normal to obviouslyinflamed mucous membrane. Perhaps the commonestchange is a rather thick mucosa with a finely nodularor velvety surface configuration.

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FIG. 1. Case 3 (Table III). Sigmoid colon and rectum. In the upper partof the specimen there is extensive papillary tumour which is partlybenign but contains a malignant stricture about 5 cm. long. In the rectumthere are smaller areas of villous overgrowth of the mucosa.

FIG. 2. Case 7 (Table III). Mucosal surface of colon showing patchypolypoid change which has nodular and papillary surface configuration.

MICROSCOPIC FEATURES The histological and cyto-logical criteria for the diagnosis of precancer incolectomy specimens and rectal biopsies for ulcera-tive colitis are fundamentally the same as those usedfor other precancerous conditions of the intestinesuch as adenomas and villous papillomas. Moreover,they are no different from those used for pre-cancerous lesions or carcinoma in situ in otherorgans such as cervix, bladder, and skin.Precancerous polyps There is adenomatous or

villous overgrowth (Fig. 3) of the intestinal epi-thelium in a polypoid form. The epithelial cells show

loss of goblet cell secretion and the nuclei are strati-fied, hyperchromatic, irregular in shape and size, andshow many mitotic figures. Sometimes there is anexcess of mucin production associated with thevillous type of proliferation, as seen in some solitaryvillous tumours of the colon and rectum. Thesehistological and cytological changes are associatedwith a variable amount of inflammation of thelamina propria, but usually more than that seen inordinary adenomas and villous papillomas.Precancer in flat mucosa (Figs. 4-10) The micro-

scopic features of precancer or carcinoma in situt in a

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Rectal biopsy as an aid to cancer control in ulcerative colitis

FIG. 3. Case 3 (TableIII). Precancerouschange in rectal biopsy;there is villous over-growth of the mucosaand the epitheliumshows loss ofgobletcell secretion andstratification of nucleiwhich are also hyper-chromatic. H. & E. x100.

flat mucosa are of particular importance because thechanges can only be identified at the microscopiclevel of observation. The mucous membrane is intactand either of normal thickness or rather thicker thannormal. The epithelial tubules tend to lose theirnormal parallelism and become irregular in shapeand size. They show lateral budding and frequentlyadopt a vertical or villous growth pattern (Fig. 4).An important characteristic is the tendency to mis-placement of the proliferating epithelial tubulesthrough the muscularis mucosa into the superficialsubmucosa (Fig. 5). Dukes (1954) drew attention tothis feature as important in the pathogenesis of in-vasive carcinoma in ulcerative colitis. However, it issometimes impossible to decide whether the epi-thelium is just misplaced as a result of chronicinflammation or that the appearance is, in fact, anearly stage of invasive carcinoma.The amount of inflammation in the flat pre-

cancerous mucosa of ulcerative colitis is variable butseldom severe. Indeed it may be completely absent.

It usually takes the form of an increase in the in-flammatory cell content of the lamina propria withsomehyperplasiaof lymphoid follicles and occasionalcrypt abscesses. There may be some inflammatoryinfiltration of the superficial submucosa but the deeplayers of the bowel wall are not usually affected. Theabsence of signs of active or acute inflammation, suchas vascular congestion and oedema with mucosaldestruction, is significant because of the clinicalobservation that malignant change in ulcerativecolitis is most commonly found in patients with along history of mild or quiescent disease.The cytological changes of precancer in ulcerative

colitis are identical with those seen in other organs.There is loss of function in the form of a diminutionof the amount of mucus secretion with irregularityin size and shape of the cells which are often largerthan normal. The nuclei are stratified, enlarged,hyperchromatic and vary in shape with prominentnucleoli and a coarse chromatin pattern (Figs. 6 and7). Moreover, the size of the nuclei is considerably

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FIG. 4. Case 3 (Table III).Precancerous change inflat mucosa. The epi-thelial tubules have losttheir normal parallelism,are irregular in shape andsize, and have adopted avillous growth pattern.There is inflammation ofthe lamina propria.H. & E. x 80.

FIG. 5. Precancerous changein flat mucosa with villousgrowth pattern and mis-placement ofproliferatingepithelial tubules through themuscularis mucosa into thesuperficial submucosa. There isinflammation of the laminapropria. H. & E. x 100.



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FIG. 6. Precancerous changein flat mucosa. The epithelialtubules are irregular in shapeand the lining epitheliumshows stratification of nucleiwhich are very hyperchromatic.There is almost completeloss ofgoblet cell secretion;also inflammation of thelamina propria. H. & E. x300.

FIG. 7. Precancerous change inflat mucosa. There is adeno-matous overgrowth of the tubulesand the lining epithelium showsstratification of nuclei which arevery hyperchromatic. Thelamina propria contains chronicinflammation. H. & E. x 180.

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i FIG. 8. Precancerouschange in flat mucosa.There is a transition fromhyperplastic epitheliumto severe precancerouschange with adenomatousovergrowth of the tubules.H. & E. x 25.

I

FIG. 9. Case S (Table III).Precancerous change in flatmucous membrane withunderlying invasion by adeno-carcinoma. There is muchinflammation of the laminapropria. H. & E. x 140.



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FIG. 10. Case 7 (Table III).Precancerous change in rectalbiopsy. There is mild chronicinflammation in the mucosa.The epithelial tubules areirregular in size and shapeand lined by nuclei which arestratified and hyperchromaticwith many mitotic figures.H. & E. x 175.

increased relative to the amount of cytoplasm. Theseverity of precancerous change is variable andstages of transition from relatively normal mucosathrough precancerous epithelium to invasive car-cinoma can be readily demonstrated (Fig. 8). Pre-cancer in flat mucosa is usually a diffuse change andcan affect almost the entire large bowel mucosa.Commonly it occurs in patches and mostly in thedistal parts of the colon and rectum.The criteria for the diagnosis of precancer,

especially in rectal biopsies, must be adhered tostrictly for reactive hyperplasia can produce cyto-logical changes in the epithelial cells which may beconfused with neoplastic transformation. However,reactive hyperplasia is usually associated with amuch greater degree of inflammation, crypt abscessformation, epithelial destruction and ulceration. Theepithelial cells may show nuclear changes, includinga tendency to hyperchromatism and an increase inthe number of mitotic figures, but there is no strati-fication with variation in the size and shape of nuclei.

The lateral budding and villous growth pattern ofthe epithelial tubules mentioned above is also absent.A considerable increase in the number of Paneth

and argentaffin cells has been noted in areas ofprecancerous mucosa. In the absence of any know-ledge of the function of these cells it can only bepresumed that this is a feature of the longstandingchronic colitis rather than the neoplastic change(Watson and Roy, 1960). However, it has beenshown that Paneth cells are common in those polypsof the large intestine which are generally regarded asprecancerous (Gibbs, 1967), and it is thereforepossible that in colitis they are sometimes part of theneoplastic process.

PRECANCER IN COLECTOMY SPECIMENS OF COLITIS ANDCANCER

A retrospective study was made of 27 surgicalspecimens of ulcerative colitis with cancer of thecolon or rectum. Four of these were rejected because

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of inadequate information about the pathology orclinical features. The incidence of precancer in themucosa of the remaining 23 specimens was estimatedtogether with the relationship to length of historyand extent of colitis.The pathological features of precancer were

present in the mucous membrane of all 23 colectomyspecimens removed for colitis in which one or moreinvasive carcinomas were found. The precancerouschanges were very extensive involving large areas ofmucosa away from sites of invasive carcinoma as wellas in their immediate vicinity. It has not been possibleto measure the extent of precancer in these colec-tomy specimens with any precision but it was a verydiffuse process in many cases, as judged by theexamination of many sections from different partsof the colon and rectum. In some specimens theentire mucosa of the large bowel appeared to beaffected although the severity of the changes varied.In general the precancerous changes were morefrequent and extensive in the left colon and rectum.

All 23 specimens of ulcerative colitis with invasivecancer had total colitis as judged by clinical, radio-logical, or pathological evidence. Nineteen patientsgave a history of more than 10 years and nine ofthese for more than 20 years; four had a history ofless than 10 years.

PRECANCER IN COLECTOMY SPECIMENS FOR COLITIS

A consecutive series of 172 colectomy specimens forulcerative colitis were examined retrospectively forthe incidence of precancer together with the relation-ship to extent of colitis and length of history (TableI). In 12 precancer was found but only in patientswith total colitis. The incidence of precancer in the134 patients with total colitis was therefore 9 0 %. Ofthe 12 patients with precancerous change nine had ahistory of colitis exceeding 10 years and three under10 years. The extent of precancer was extremelyvariable ranging from small patches to large areas ofinvolved mucosa.

PRECANCER IN RECTAL BIOPSIES

A retrospective study was made of 148 consecutive

Length of History (yr.)

Under 1010-20Over 20All cases

TABLE IIINCIDENCE OF PRECANCER IN RECTAL BIOPSIES FROM

PATIENTS WHO HAD A SUBSEQUENT COLECTOMY

Length of History (yr.) No. of Cases PrecancerBiopsies

No. of Cases Incidence (%.)Under 1010-20Over 20All cases

26151354

1 409 6006 46116 29-0

rectal biopsies of patients with ulcerative colitis.Ninety-four have had medical treatment only butnone showed any evidence of precancer in the rectalbiopsy. The remaining 54 biopsies were carried outon patients who had a subsequent colectomy(Table II). Sixteen (29%) of these showed the ap-pearances of precancer and similar precancerouschanges were found in the colectomy specimen. Allhad total colitis, but there was no invasive carcinomapresent. Twelve of these are also included in Table I.All but one of the rectal biopsies regarded as pre-cancerous were from patients with a history of colitisfor more than 10 years. Thirty-eight rectal biopsiesnegative for precancer showed no precancerouschange in the subsequent colectomy specimen.During recent years the diagnosis of precancer has

been made by rectal biopsy in nine patients who wereunder clinical and radiological investigation for thestate of their colitis. In these cases the discovery ofprecancer in a rectal biopsy influenced the decisionto carry out surgical treatment. A summary of theclinical history, surgical treatment, and pathology isgiven in Table III.There were seven women and two men. Eight had

a long history of symptoms exceeding 10 years andone for eight years. All nine patients had total colitisconfirmed radiologically or by examination of thecolectomy specimen.

Biopsy of polypoid lesions in the rectum of twopatients showed precancer. The other seven hadprecancer in flat mucosa.One patient (case 1) had an inoperable growth of

the sigmoid at laparotomy. The other eight were alltreated by total proctocolectomy. Invasive car-cinoma as well as extensive precancer were found in

LE IINCIDENCE OF PRECANCER IN COLECTOMY SPECIMENS FOR COLITISTotal Colitis Subtotal Colitis All Cases

No. of Incidence of No. of Incidence of No. of Incidence ofCases Precancer Cases Precancer Cases Precancer

883115

134

3(3*4%)2\ 9(19-6%)

12(9-0%)

227938

NilNilNilNil

1103824172

7 3 (2 7%)

/9 (14 5%)2 12(70%)

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TABLE IIISUMMARY OF CLINICAL FEATURES AND PATHOLOGY

Case Sex Age at Length of ExtentNo. Onset of History of

Colitis (yr.) Colitis

Rectal Biopsy

Type of MucosaShowing Precancer

SurgicalTreatment

Pathology of Colectomy Specimen

Severity Extent ofof Colitis Precancer

23

FF

F

202327

462424

Total FlatTotal FlatTotal Polypoid

4 M 27 18 Total Flat

5 F 46 13 Total Flat6 M 41 8 Total Flat

7

89

FF

F

461824

121727

Total FlatTotal FlatTotal Polypoid

four of these specimens. In four others only pre-cancerous mucosa was found. The invasive car-cinomas were in the descending colon (cases 2 and5) and the sigmoid and rectum (cases 3 and 4). Incase 5 the invasive carcinoma was of microscopicsize, although it had penetrated the full thickness ofthe bowel wall.The extent and severity of the precancerous

changes in the eight proctocolectomy specimensvaried. In one patient (case 5) there was precancer inflat mucosa throughout the colon and rectum. In twoothers (cases 7 and 8) there were large patchesthroughout the large bowel. One of these (case 8)showed widespread precancer of the polypoid typeas well as similar changes in flat mucosa. In cases 4and 6 there was patchy but quite extensive precancerin flat mucosa confined to the left colon and rectum.Case 3 showed patchy polypoid precancer in thesigmoid and rectum, the intervening flat mucosashowing a mild colitis with patchy precancerouschange. In case 9 there was patchy polypoid pre-cancer in the lower rectum only. Case 2 could not beassessed for extent of precancer as the histologicalsections of the bowel were not labelled for site.

Table III also gives an assessment of the severityof the colitis. In only one (case 8) was this at allsevere, showing diffuse chronic inflammation withmuch crypt abscess formation and areas of full-thickness mucosal ulceration. In cases 2, 5, and 7 theseverity of the colitis was graded as moderate and inthree cases (3, 4, and 6) as slight. The inflammationin the latter appeared to be of a residual character.In case 9 the mucosa of the entire large intestineshowed atrophy only with a little increase in theinflammatory cell content of the lamina propria insome areas. Moreover, there was evidence of healedcolitis in the macroscopic examination of the speci-men in the form of extensive submucosal scarring.The following three case reports are representative

Inoperable Not available SigmoidProctocolectomy + + Not available Descending colonProctocolectomy + Sigmoid and Sigmoid

rectumProctocolectomy + Transverse colon Rectum

to rectumProctocolectomy + + Total Descending colonProctocolectomy + Caecum to descend- None

ing colon; rectumProctocolectomy + + Total NoneProctocolectomy + + + Total NoneProctocolectomy + Lower rectum None

of the value of rectal biopsy. The first (case 3) is apatient with a long history of colitis in whomsigmoidoscopic and radiographic opinion was sug-gestive of malignant change. This was reinforced bythe presence of polypoid precancer in the rectalbiopsy. The second (case 5) is a patient with a longhistory of colitis in whom there was no clinical orradiographic evidence of carcinoma, but the biopsyshowed precancer in a flat mucosa. The colectomyspecimen showed only a single small focus of adeno-carcinoma in the descending colon about 1 cm. indiameter. The third (case 7) is a patient with a longhistory of total colitis but no clinical or radiographicevidence of malignancy. Rectal biopsy showed pre-cancer in a flat mucosa. Only extensive precancer wasfound in the operation specimen.

COLITIS AND CANCER (CASE 3, TABLE III) Twenty-fouryears intermittent diarrhoea, sometimes with rectalbleeding. Recent loss of weight and pain in left iliac fossa.Sigmoidoscopy showed proctitis with an area of polypoidmucosa at 8 cm. Barium enema radiographs revealedtotal colitis and narrowing of the sigmoid very suggestiveof carcinoma.

Rectal biopsy (Fig. 3) of the polypoid mucosa showed'villous and adenomatous hyperplasia of the rectalmucosa but no sign of invasion by carcinoma. Theappearances are certainly precancerous'.

Operation Total proctocolectomy in two stages.Pathology of surgical specimens The colon from the

caecum to the descending part is shortened with con-traction of the lumen and a granular atrophic appearanceof the mucous membrane. The sigmoid colon (Fig. 1)shows extensive papilliferous or villous overgrowth of themucosa over a length of 15 cm. in the middle of whichthere is a malignant stricture about 5 cm. long. There isextensive invasion of the pericolic fat by carcinoma. Inthe rectum there is one area of sessile villous overgrowthof the rectal mucosa about 4 cm. in diameter and a secondsmaller area 1 cm. diameter. The remainder of the rectalmucosa is intact but has an atrophic appearance.

InvasiveCarcinoma

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Microscopy shows mild chronic inflammation through-out the mucosa of the large intestine. There is atrophy ofthe mucous membrane in the proximal colon but nodefinite evidence of precancerous change. In the sigmoidthere is extensive villous and adenomatous overgrowth ofthe rectal mucosa with focal invasion by mucus-secretingadenocarcinoma. The rectum shows extensive pre-cancerous change in flat mucosa (Fig. 4) as well as thetwo areas of villous overgrowth, but no sign of invasionby carcinoma. The regional lymphatic glands are notinvolved.

Follow-up Well two years after operation.

COLITIS AND EARLY CANCER (CASE 5) Intermittentdiarrhoea and bleeding per rectum for 13 years. Sigmoido-scopy showed appearances typical of ulcerative colitis.Barium enema radiographs confirmed colitis but therewas no evidence of malignancy.

Rectal biopsy 'Moderate inflammation of the mucosawith some superficial erosion. The epithelial tubules arestrikingly irregular with villous change and the liningepithelium shows bizarre nuclear changes. The appear-ances are those of pre-invasive carcinoma'.

Operation Total proctocolectomy.Pathology of surgical specimen The entire colon and

rectum is shortened with thickening of the bowel wall.The mucous membrane appears abnormal throughoutbut the severity of the changes varies from the caecum tothe rectum. In the right colon the mucosa is intact butthick and slightly granular. In the transverse part it iseven thicker and has a finely nodular surface appearance.Just beyond the splenic flexure is an area about 5 cm.diameter where the mucosa is particularly thick and hasa velvety surface. In the middle of this the cut surface ofthe bowel wall shows a hard white nodule about 1 cm.diameter. The mucosal surface in the sigmoid colon andrectum shows scattered areas ofserpiginous ulceration andthe intervening mucosa is velvety and atrophic.

Microscopy of the caecum and ascending colon showsa slight increase in the chronic inflammatory cell contentof the lamina propria but the epithelial tubules areextremely hyperplastic and have the appearance of earlyprecancerous change. In the transverse colon these pre-cancerous changes are more advanced. In addition thereare occasional crypt abscesses and much distortion of theglandular pattern to produce a low villous and adeno-matous appearance. In the descending colon there areadvanced precancerous changes, particularly marked inthe area of mucosal thickening just below the splenicflexure mentioned above. The hard white nodule is amoderately well differentiated adenocarcinoma of anaverage grade of malignancy invading the deep musclelayers and the serosa (Fig. 9). Other sections taken fromthe region of the descending colon show a tendency tosubmucosal invasion by precancerous epithelium but nofrank carcinoma. In the sigmoid colon and rectum themucosal epithelium is atrophic with a low villous andadenomatous growth pattern. Many Paneth cells arepresent and some crypt abscess formation.

Follow-up Well six months after operation.

COLITIS AND PRECANCER (CASE 7) Diarrhoea and rectal

bleeding for 12 years. Sigmoidoscopy showed a granularproctitis with some contact bleeding. Barium enemaradiographs revealed total colitis, but no sign ofmalignancy. Colectomy advised on clinical evidence.

Rectal biopsy (Fig. 10) 'Mild chronic inflammation ina mucosa which contains significant epithelial changes.The tubules are irregular in size and shape with completeloss of parallelism. They are lined by cells which arestratified, show a diminution in the amount of mucussecretion, and have nuclei varying in shape and size withmany mitoses. The appearances are certainly those ofprecancerous change but there is no sign of invasivecarcinoma in this biopsy'.

Operation Total proctocolectomy.Pathology ofsurgical specimen There is shortening of

the large intestine, particularly on the left side, and themuscle layers are thicker than normal. The mucousmembrane throughout the colon and rectum showspatchy polypoid change which has a nodular and papillarysurface configuration (Fig. 2). Mucosa between thepolypoid areas is thick and has a mucoid appearance.

Microscopy shows intact, but hypertrophic, mucosawith a moderate inflammatory cell infiltration and somecrypt abscess formation. The inflammation does notpenetrate into the submucosa. The epithelial tubules arevery irregular and show horizontal budding in some areas.In others there is a villous or papillary type of prolifera-tion. These adenomatous and villous changes are mostmarked in those areas of polypoid change observedmacroscopically. At a cytological level the entire mucosashows changes of precancer or carcinoma in situ. Inaddition there are many areas where the epithelial tubulesare breaking through the muscularis mucosa, but thisinfiltration does not amount to definite invasion bycarcinoma.

Follow-up Well three months after operation.

DISCUSSION

The diagnosis of carcinoma in ulcerative colitis isoften made at an advanced and incurable stage. It isnot surprising that the prognosis of cancer in colitisis rather poor (Slaney and Brooke, 1959), althoughperhaps not as bad as previously estimated (Hinton,1966). The only way to control the death rate at thepresent time is by earlier diagnosis.

It is well recognized that the detection andtreatment of precancerous lesions is an effectivemethod of cancer control. The progress made inrecent years in the screening of patients by biopsyand exfoliative cytology for precancer of the cervixis perhaps the best example. In the large intestine anotable advance has been made in the prevention ofcancer in polyposis families (Dukes, 1958). In thisdisease the polyposis is a precancerous phase whichis often symptomless and precedes the developmentof invasive carcinoma by many years. Total colec-tomy and ileo-rectal anastomosis in this phase hasconsiderably reduced the incidence of malignantchange (Bussey and Morson, 1967).

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A description of the morphology of precancerouschange in ulcerative colitis is given here making adistinction between the appearances seen in polypoidlesions and in flat mucosa. The recognition ofcarcinoma in situ in flat mucosa is particularly im-portant because there may be no macroscopicevidence of this in colectomy specimens or by sig-moidoscopy and radiographic investigation. Ourstudies indicate that precancer in a flat mucosa ismore common than the polypoid form. The fact thatit can be detected in rectal biopsies from patientswith a long history of total colitis emphasizes theimportance of careful follow-up of such colitics withregular rectal biopsy whatever the state of themucosa as judged by sigmoidoscopy.

It would appear from this study that precancer ispresent in all colectomy specimens removed forcolitis and cancer and can also be found in somepatients who have no invasive carcinoma but have along history of total colitis. Its precise incidence andextent in different parts of the large bowel remainsto be worked out but this study suggests that it ismostly found in the distal large intestine. Althoughinvasive carcinomas in colitis are more evenly dis-tributed in the large bowel than in cancer withoutcolitis the incidence is still greater in the sigmoid andrectum than in the proximal colon (Langman, 1966).

It is obviously desirable that surgical treatmentshould be carried out before the development ofinvasive carcinoma. The problem so far has been toidentify the precancerous phase in the individualpatient before the examination of a colectomy speci-men. It is likely, from experience with precancer inother organs, that the length of the precancerousphase of ulcerative colitis is very variable and it maybe a great many years before invasive carcinomadevelops. Indeed, it is not certain that precancer willinevitably proceed to invasion although the risk mustbe very high.

It would appear that precancerous change inulcerative colitis is usually very diffuse and may eveninvolve the entire mucosa of the large intestine. Theretrospective examination of rectal biopsies reportedhere shows that there is good correlation between thebiopsy diagnosis of precancer and the appearancesin the subsequent colectomy specimen. Moreover,the patients with no precancer in the rectal biopsyshowed no precancer or cancer in the subsequentcolectomy specimen. These operations were mainlyperformed for colitis although the long history ofdisease and the risk of malignancy influenced thedecision to carry out surgical treatment.

Because of the patchy distribution of precancer inthe rectum it is likely that rectal biopsy will some-times fail to be helpful. Negative reports should notbe regarded as excluding the chance that precan-

cerous or cancerous changes may be present in theproximal bowel beyond the reach of the sigmoido-scope. Clinical and radiographic observations bythemselves remain the most valuable means ofassessing the need for surgical treatment. Forexample, one patient with a long history of colitis,not included in this study, was regarded as particu-larly at risk from malignant change. The rectal biopsyreport was equivocal but the subsequent colectomyrevealed a cancer of the ascending colon.

In nine patients the rectal biopsy diagnosis ofprecancer accurately predicted the presence of similarchanges in the subsequent colectomy specimens. Asyet there has been no false diagnosis of precancer ina biopsy. It would appear that rectal biopsy has avaluable part to play in the recognition of the pre-cancerous phase of ulcerative colitis in conjunctionwith clinical and radiographic opinion. However, thedetection of precancer in a rectal biopsy has so farbeen associated with a high incidence of suspectedand unsuspected invasive carcinoma in the moreproximal bowel. Thus, five of the nine patients hadinvasive cancers. In one of these (case 5) the recogni-tion of the patient as a 'high risk colitic' on clinicalevidence together with a rectal biopsy report of pre-cancer led to proctocolectomy at an early and almostcertainly curable stage of the malignant process. Theremaining four patients showed only extensive pre-cancer in the operation specimen. They are examplesof how the development of cancer in colitis may beanticipated and surgical treatment carried out in theprecancerous phase. In all these patients the inten-tion to perform colectomy was much influenced bythe biopsy report although this was, by no means, theonly basis for the decision.

If rectal biopsy can help to detect the patient whohas entered a precancerous phase then it follows thatall patients with a long history of total ulcerativecolitis should have a regular biopsy examination.Once a year should be sufficient. The adoption ofsuch a policy could not only help to prevent orcontrol the death rate from cancer in the populationof colitics at risk, but it would certainly teach usmore about the evolution and fate of the precan-cerous phase.

SUMMARY

Histological changes characteristic of precancer wererecognized by rectal biopsy in nine patients withchronic ulcerative colitis. One or more foci of inva-sive carcinoma, together with widespread pre-cancerous change, were subsequently found in thecolon or rectum of five of these patients. One, how-ever, was at a very early stage of development. In the

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434 B. C. Morson and Lillian S. C. Pang

other four patients the colectomy specimens showedprecancerous changes only.

Rectal biopsy, in conjunction with clinical andradiological studies, may be helpful in the recogni-tion of the patient with ulcerative colitis who hasentered a precancerous phase. However, experienceto date has shown that the recognition of precancerin a rectal biopsy is associated with a high incidenceof suspected or unsuspected invasive carcinoma inthe more proximal bowel.

It is suggested that regular rectal biopsy for allpatients with ulcerative colitis is desirable in orderthat more may be learnt about the evolution of theprecancerous phase. In particular those patients witha long history of total colitis should have a rectalbiopsy at least once a year. Those in a precancerousphase would require total proctocolectomy. Such apolicy should help to control the death rate fromcancer in the population of colitics at risk.

We would like to thank the consultant staff of St. Mark'sHospital for permission to study their cases. The photo-graphs were taken by Mr. Norman Mackie and Mr. LloydSoodeen gave valuable technical assistance. The expenses

of this research were defrayed out of grants from theBritish Empire Cancer Campaign for Research (B.C.M.)and the Medical Research Council (L.S.C.P.).

REFERENCES

Bussey, H. J. R., and Morson, B. C. (1967). Familial Polyposis Coli:The Prevention of Cancer, edited by R. W. Raven and F. J. C.Roe. Butterworth, London.

Dawson, I. M. P., and Pryse-Davies, J. (1959). The development ofcarcinoma of the large intestine in ulcerative colitis. Brit. J.Surg., 47, 113-128.

Dukes, C. E. (1954). The surgical pathology of ulcerative colitis. Ann.roy. Coil. Surg. Engl., 14, 389-400.

(1958). Cancer control in familial polyposis of the colon. Dis.Colon Rect., 1, 413-423.

Gibbs, N. H. (1967). The incidence and significance of argentaffin andPaneth cells in some tumours of the large intestine. J. clin.Path. In the press.

Grinnell, R. S., and Lane, N. (1958). Benign and malignant adeno-matous polyps and papillary adenomas of the colon and rectum:an analysis of 1,856 tumors in 1,335 patients. Int. Abstr. Surg.,106, 519-538.

Hinton, J. M. (1966). Risk of malignant change in ulcerative colitis.Gut, 7, 427-432.

Langman, M. J. S. (1966). Epidemiology of cancer of the large in-testine. Proc. roy. Soc. Med., 59, 132.

Morson, B. C. (1966). Cancer in ulcerative colitis. Gut, 7, 425-426.Slaney, G., and Brooke, B. N. (1959). Cancer in ulcerative colitis.

Lancet, 2, 694-698.Watson, A. J., and Roy, A. D. (1960). Paneth cells in the large intestine

in ulcerative colitis. J. Path. Bact., 80, 309-316.



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