Pathology of colorectal adenomas: colonoscopic · colon); transverse colon; descendingcolon; sigmoid colon; rectum. If indicated as splenic flexure or hepatic flexure, tumours at

J Clin Pathol 1982;35:830-841

Pathology of colorectal adenomas: a colonoscopicsurvey

F KONISHI, BC MORSON

From the Department ofPathology, St Mark's Hospital, City Road, London ECJV 2PS

SUMMARY The size, histological type, and grade of dysplasia of a large series of colorectaladenomas removed by colonoscopic polypectomy were matched against other variables such asanatomical site, age, sex, and number of adenomas per patient. Special emphasis was placed onthe criteria for grading dysplasia in adenomas and the possible significance of severe dysplasia asa selective marker for increased colorectal cancer risk. The results showed that small adenomas(mostly with mild dysplasia) were evenly distributed throughout the colorectum but thatadenomas showing severe dysplasia (mostly the larger tumours, > 10 mm diameter) were concen-trated in the left colon and rectum, particularly the sigmoid part which is also the segment withthe highest risk of colorectal carcinoma in high risk populations.

Severe dysplasia in adenomas appears to be a selective histopathological marker for increasedcolorectal cancer risk. It is closely linked with increasing age and numbers of adenomas perpatient, with the larger adenomas and particularly those with a villous component in their histol-ogy. Severe dysplasia and multiple adenomas could be valuable markers for selecting from thetotal adenoma population those most deserving of close surveillance in follow-up cancer preven-tion programmes.

Conceptually it would appear advantageous to think in terms of the dysplasia-carcinomasequence in the colorectum rather than the polyp-cancer or adenoma-carcinoma sequence. Theimplications of these results in the study of the aetiology of colorectal cancer are discussed.

The increasing role of colonoscopy and polypectomyin the diagnosis and management of colorectaladenomas during the past decade has provided thehistopathologist with an abundance of valuablematerial for study. This material is especially usefulbecause, in most patients subjected to colonoscopy,the entire colorectum has been visualised at oneexamination and all polyps removed for histologicaldiagnosis. Previous studies have relied on adenomasremoved by proctosigmoidoscopy only, and surgicalsegments of bowel usually removed for carcinoma inwhich adenomas were a coincidental finding. There-fore, a colonoscopic survey should provide moredetailed information about their distribution in thelarge bowel matched against other variables such assize, histological type, and grades of dysplasia. Theresults of such a clinical survey can then be com-pared with the figures given in various necropsy

Accepted for publication 16 December 1981

reports. Emphasis in this study is also placed on thesignificance of grade of dysplasia, and especiallysevere dysplasia because the latter has been estab-lished as a valuable marker for increased cancer riskin ulcerative colitis as well as in the study of theepidemiology of adenomas.

Matenal and methods

During the eight-year period 1972 to 1979, 1167adenomas were removed by colonoscopy from 675patients (398 men and 277 women) either by snarepolypectomy or the hot-biopsy-fulguration method.'The histological sections for 28 adenomas weremissing, leaving 1139 adenomas available for study.From the same 675 patients a further 102 adenomaswere removed by other methods, mostly by rigidproctosigmoidoscopy but a few by surgical excision.These were also included in the study, making atotal of 1241 examined. Of these, 54 showing mi-croinvasive carcinoma were excluded thus leaving afinal total of 1187 adenomas for analysis.

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Pathology of colorectal adenomas: a colonoscopic survey

All the removed adenomas were fixed in buffered10% formaldehyde solution; the position of thestalk was identified, if possible, and the specimenswere embedded on their sides in paraffin wax so thatthe tumour and stalk were orientated in their correctanatomical relationship to one another. In smalladenomas (< 0.5 cm diam), only one level was cut;in larger adenomas however two or more levels weretaken, according to the size of the specimen. Mul-tiple semiserial sections were cut only in a minorityof specimens to assess questionable examples of mi-croinvasive carcinoma. All sections were stained byhaematoxylin and eosin.

Size was measured on the histology slides in twodimensions and the arithmetic mean was calculatedto represent the size of the tumours. Comparison ofsize measured in the fresh state and on histologicalslides showed that the size on the section was thesame as, or only slightly smaller than, that in thefresh state because of the method of embedding thetumours. All the sections were examined by one ofthe authors (FK) and graded according to histologi-cal type and grade of dysplasia (see later).The site of adenomas was identified from the col-

onoscopy records. The large bowel was divided intofive segments: right colon (caecum and ascendingcolon); transverse colon; descending colon; sigmoid

colon; rectum. If indicated as splenic flexure orhepatic flexure, tumours at these sites were evenlyallocated to either of the two adjacent segments.Age and sex of the patients were checked in thecolonoscopy records or in the patients' notes.Removal of rectal polyps by rigid proctosig-

moidoscopy is often performed in the OutpatientClinic or operating theatre rather than by colonos-copic polypectomy. In addition, removal ofadenomas by proctosigmoidoscopy may have beenperformed at other hospitals before the patientsattended St Mark's. For these reasons accuratecomparison of the number of rectal and colonicadenomas was not possible. In order to make aproper comparative study of size, histological type,and grades of epithelial dysplasia between rectal andcolonic adenomas a separate consecutive series of270 rectal adenomas removed by rigid proctosig-moidoscopy during the four-year period 1976 to1979 was also studied.Almost all the patients in the colonoscopy series

had barium enema study before colonoscopy eitherat St Mark's Hospital (St Mark's patients) or atother hospitals (cases referred only for colonos-copy). In referred cases when barium enema failedto visualise particular segments of colon (usually theright side), total colonoscopy was carried out but

4.J:f

Fig. 1 Tubularadenoma. Haematoxylinand eosin x IO.

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Fig.....2 Tubuovilu a . Haematoxylin and:eosin x 1..

Fig. 2 Tubulovillous adenoma. Haematoxylin and eosin x 10.

when the barium enema study was of sufficient qual-ity and no polyps were seen in the right colon, totalcolonoscopy was not invariably performed. Usingthis policy total colonoscopy was performed in 60%of the cases and 601 patients were considered tohave had adequate total examination of the largebowel by barium enema study and fibreoptic col-onoscopy. There was no significant difference in thesubsite distribution of colonic adenomas between"referred cases" and St Mark's cases. For thisreason adenomas removed from referred patientsand from St Mark's patients could be analysedtogether.

HISTOLOGY OF ADENOMASIf the tubular pattern occupied more than 80% ofthe tumour it was classified as tubular (Fig. 1); witha villous pattern of more than 80% it was classifiedas villous (Fig. 2); the remainder were classified as

tubulovillous (Fig. 3).Irrespective of histological type all adenomas can

be graded by histological and cytological criteriainto three grades of epithelial dysplasia (atypia)-mild, moderate, and severe, the latter being usedsynonymously with carcinoma-in-situ. However,there are reasons for avoiding the use of this term insurgical reports.2 It is common to see differinggrades of dysplasia within any one adenoma and inthis study individual adenomas have been gradedaccording to the part with the most advanced grade.Sometimes an area with one grade of dysplasia has adistinct boundary with the adjacent area showing adifferent grade but more often there is a gradualtransition. A focus of severe dysplasia in anadenoma often shows an expansive growth patternand a sharp boundary with the adjacent mild tomoderate dysplasia. There have been other studieson grading dysplasia3-6 but it must be emphasised

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Fig. 3 Villous adenoma. Haematoxylin and eosin x 10.

that grading is a subjective assessment taking bothstructural and cytological changes into considera-tion.

GRADING OF DYSPLASIA

Mild dysplasia (Fig. 4)The nuclei are elongated, larger than normal andslightly hyperchromatic with a fine chromatin pat-tern. They are arranged regularly at the base of thecells. Usually nucleoli are not seen. The amount ofmucin is decreased and is confined to the lumenalborder of the cells. The number of mitotic figures isslightly increased. Pleomorphism and loss of polarityof the nuclei are not typical features of this category.The glandular arrangement is irregular with somebranching but there is no further disorganisation ofthe glandular structure. Only occasional reversedgoblet cells (intraepithelial goblet cells) may beseen. The distinction from moderate dysplasia

becomes blurred when the nucleoli begin to becomestratified with some loss of polarity and the amountof mucin is further decreased.

Moderate dysplasia (Fig. 5)This category can be defined as intermediate be-tween mild dysplasia and severe dysplasia. Thenuclei are elliptical rather than elongated and thechromatin is denser and tends to show a clumpingpattern. There is nuclear pseudostratification andminor loss of polarity with some increase in thenuclear-cytoplasmic ratio. The amount of mucin isfurther decreased and reversed goblet cells are seenmore often. An important change is the tendencytowards pleomorphism of nuclei. The interglandularspace is reduced and structural distortion of thecrypts is more manifest, with folding of epithelialcells into the glandular lumen. This is different fromthe true intraglandular budding and bridging whichare the features of severe dysplasia.

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Fig. 4 Mild dysplasia. Nuclei areregularly arranged on the basalside of the glands. There is somebranching ofthe glands. Mucin isrelatively well preserved.Haematoxylin and eosin x 120.

Fig. 5 Moderate dysplasia. Nucleiare larger and showpseudostratification. Mucin isdecreased. There is moderatestructural abnormality.Haematoxylin and eosin x 120.


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Fig. 6 Severe dysplasia.Nuclei are pleomorphic andshow loss ofpolarity. Structuralabnormality is marked,featuring intraglandularbudding and bridging.Haematoxylin and eosin x120.

;k

ZA. '4wa g*s^'*tAs"at awv s,tast.$.~~~~I'

Male

Female

a

z

- 20 25 30 35 40 45 50 55 60 65 70 75 80-Age (yr)

Fig. 7 Age and sex distribution of675 patients.

Severe dysplasia (Fig. 6)The changes are very similar to those of invadingadenocarcinoma. The nuclei are large andpleomorphic with an obvious increase in thenuclear-cytoplasmic ratio. The chromatin pattern is

either diffusely dark or open with clumping of thechromatin and one or more nucleoli can often beseen. The marked pleomorphism is associated withloss of polarity of the nuclei and an obvious increasein the number of mitotic figures. These are the mostimportant features of this category. Little mucin ispresent and cannot be recognised as a clear dropletwith haematoxylin and eosin staining. The glandularstructure is very distorted featuring frequent intra-glandular bridging and budding with obliteration ofthe interglandular space, which gives the impressionof glandular fusion. This condensed growth patternis the so-called "glandular back-to-back" arrange-ment. In some cases, despite little evidence of intra-glandular budding and bridging, the nuclei are largeand show severe pleomorphism and loss of polarity.In many adenomas areas of severe dysplasia have adistinct boundary with adjacent less severe, evenmild, changes.

Results

AGE AND SEX DISTRIBUTIONFigure 7 shows the age and sex distribution of the675 patients in this series. The mean ages were 61-1yr for men and 59-1 yr for women. The peak inci-

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/@S ,o\ -300 O3

V~~~~~~~~

100 - 250 U

050o II V150* / /1 * 100Qo

9;'l1|-150°

a

a0

506n 70 80 90

Age (yr)

Fig. 8 Age distribution ofadenoma patients (this series)and carcinoma patients (South West Thames CancerRegistry).'

4UU

Mate350 -

Female

0 150

- 20 25 30 35 40 45 50 55 60 65 70 75 80-Age (yr)

Fig. 9 Cumulative age and sex distribution.

dence for men is in the age group 60-65 yr and forwomen is in the 55-60 yr group. Compared to theage distribution of large bowel carcinomas,7 thepeak incidence occurs about 10 years younger in ouradenoma patients than in carcinoma patients(Fig. 8), a figure which lends support to the conceptof the adenoma-carcinoma sequence.

Figure 9 shows the cumulative age and sex dis-tribution; the number of younger women patientsslightly predominates, or is about the same as that ofyounger men patients but as age increases from 50yr to over 80 yr, the tendency is for men patients topredominate. This tendency is similar to that of theage-sex distribution of large bowel carcinoma inhigh-risk countries, as reported by Haenszel andCorrea.8

DISTRIBUTION AND Sll-E OF ADF NOMASTable 1 shows the site distribution of 1187adenomas. The number of rectal adenomas shouldnot be compared to the number in the colonbecause, as described previously, rectal adenomasare often treated separately from colonic adenomas.About half (47%) of adenomas removed werelocated in the sigmoid colon, the percentagedecreases from the sigmoid proximally to the rightcolon (8.2%) in striking contrast to the distnrbutionof adenomas in necropsy series.9 '4 The figure forthe right colon could be a slight underestimatebecause of those endoscopically irremovableadenomas not biopsied and subsequently treated byright hemicolectomy. Most reports of necropsystudies show a more or less even distribution with aslightly greater percentage in the right colon. It mustbe remembered, however, that adenomas found innecropsy studies were mostly smaller than those inour colonoscopic series.

Table 2 shows the size of 1187 adenomas by site.Colonic adenomas smaller than 5 mm show a com-paratively even distribution but in striking contrastthose measuring 5 to 10 mm and >10 mm are con-centrated in the left colon; the difference is statisti-cally highly significant. (X2 = 16217, df = 8, p <000 1.)A similar trend has been shown in other

studies." 1" The percentage of rectal adenomasmeasuring 6-10 mm (29%) and >10 mm (23%) areless than those of sigmoid colon adenomas withinthe same size group (approximately 39% for both).However, it should be mentioned that broad-basedadenomas often measuring 3.0 cm across or evenlarger are more common in the rectum than in thesigmoid colon or descending colon. In the rightcolon and in the transverse colon, 67% of adenomaswere


large irremovable ones. Larger adenomas in thesigmoid colon and rectum may be detected morereadily than large adenomas located in other parts ofthe large bowel because of easier accessibility toendoscopic examination.

SITE AND GRADE OF DYSPLASIATable 3 shows the relation between the grade ofdysplasia and the site. The most striking difference isthe high percentage (9.5%) of severe dysplasia inthe left colon; 68% of adenomas with severe dys-plasia are located in this part of the colorectum.Adenomas with moderate dysplasia, although moreoften seen, show a similar subsite distribution asadenomas with severe dysplasia. The difference isstatistically highly significant. (X2 = 44-19, df = 8, p< 0.001.)The percentage of each grade of dysplasia in the

rectum is more or less similar to that obtained fromthe series of all rectal adenomas removed at StMark's Hospital from 1976 to 1979 (Table 4) and inthis series similar to that in the descending colon.The unexpectedly small percentage of severe dys-plasia in the right colon and rectum could be due tobiased selection of patients.

HISTOLOGICAL TYPES OF ADENOMAThe majority of adenomas (81 %) were classified astubular; 16% as tubulovillous (intermediate) andonly 3% as villous adenoma (Table 5). Except forthe percentage of villous adenomas, these figures arenot significantly different when compared with aprevious report from this hospital.6 The smallerpercentage of villous adenomas in this study com-pared to the surgical series reported by Muto et al isprobably due to the fact that in this colonoscopicseries there was a smaller number of rectaladenomas.

It has been stated that villous adenomas arelocated almost exclusively in the rectum.'5 16 In con-trast, our study has shown that both tubulovillousand villous adenomas are more widely distributedwith only a slightly higher incidence in the rectumand in the sigmoid colon. The percentage in the rightcolon, although not significantly different, is slightlyhigher than in the transverse and the descendingcolon. Again, the data for tubulovillous and villousadenomas of the rectum in this colonoscopy series(including adenomas removed by other methods)are similar to those for the previous surgical series ofrectal adenomas removed at St Mark's Hospitalfrom 1976 to 1980 (Table 6).

Table 7 shows the percentage of the three his-tological types related to the age of patients. Thepercentage of tubulovillous and villous adenomas isgreater among patients older than 70 yr compared

Table 3 Percentage grades ofdysplasia by site(1187 adenomas)

Grade Right Trans Desc Sigmoid Rectum Totalcolon colon colon colon

Mild 94 9% 90 7% 86-0% 74-8% 84-5% 81 9%(92) (146) (191) (418) (125) (972)

Moderate 4-1% 8-1% 8 1% 15.7% 10-1% 11-6%(4) (13) (18) (88) (15) (138)

Severe 1-0% 1-2% 5-9% 9-5% 5.4% 6-5%(1) (2) (13) (53) (8) (77)

Table 4 Grades ofdysplasia in rectal adenomas

Mild Moderate Severe

Rectal adenomas in 84-5% 10-1% 54%colonoscopic series (125) (15) (8)

All rectal adenomas 82-2% 12-6% 5-2%(1976-1979) (222) (34) (14)

Table 5 Histological type by site (1187 adenomas)

Type Right Trans Desc Sigmoid Rectum Totalcolon colon colon colon

Tubular 83 5% 89-4% 85 5% 78-8% 69-6% 80.7%(81) (144) (190) (440) (103) (958)

Tubulo- 14 4% 9 9% 11-7% 18-2% 25 0% 16-4%villous (14) (16) (26) (102) (37) (195)

Villous 2 1% 0-6% 2-7% 3 0% 5-4% 2-9%(2) (1) (6) (17) (8) (34)

Table 6 Histological type of rectal adenomas

Tubular Tubulovillous Villous

Rectal adenomas in 69-6% 250% 5.4%colonoscopic sefies (103) (37) (8)

All rectal adenomas 70 7% 23-0% 6.3%(1976-1979) (191) (62) (17)

Table 7 HIistological type and age (1187 adenomas)

Type 7I yr

Tubular 84-6% 81.9% 73-4%(171) (621) (166)

Tubulovillous 12.4% 15.9% 21.7%(25) (121) (49)

Villous 3 0% 2.2% 4.9%(6) (17) (11)

to younger age groups. This difference is statisticallysignificant. (X' = 9 04, df = 4, 0.01 < p < 0.02.)

It may be contributing to the observation that thepercentage of severe dysplasia in patients older than70 yr is greater than that in the younger age groups.

GRADE OF DYSPLASIA AND HISTOLOGICAL TYPEThe percentage of the different histological types inrelation to degree of dysplasia shows that as the his-

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Table 8 Percentage grades ofdysplasia by histologicaltype (1187 adenomas)

Grade Tubular Tubulovillous Villous Total

Mild 88 2% 57 9% 41-2% 81-9%(845) (113) (14) (972)

Moderate 7 7% 26-2% 38.2% 11-6%(74) (51) (13) (138)

Severe 4-1% 15-9% 20-6% 6.5%(39) (31) (7) (77)

Table 9 Grade ofdysplasia (%o) and number ofadenomas(601 patients)

Grade 1 2 3 4

Mild 73 63 59 51Moderate 13 20 24 24Severe 14 17 17 25

Table 10 Multiplicity and age (601 patients)

70 yr Total

Single 56 4% 49.0% 43-8% 49-6%(66) (190) (42) (298)

Multiple 43 6% 51.0% 56 2% 50.4%(51) (198) (54) (303)

tological type becomes more villous severe dysplasiabecomes more common (Table 8). This trend issimilar to that shown in other studies.46

SIZE AND GRADE OF DYSPLASIAThe influence of the size of adenomas on grade ofdysplasia shows a similar trend to that previouslyreported from this hospital.6 As the size ofadenomas increases so does the grade of dysplasia inagreement with previous study.41517 Size is thesimplest and most practical indicator and is closelyrelated to grade of dysplasia.

MULTIPLICITY OF ADENOMASThe numbers of adenomas per patient for this seriesin which there was total examination of the largebowel was 50% with one adenoma, 24% with two,14% with three and 12% with four or more. Inves-tigation of the relationship of size and number ofadenomas per patient showed that with increasingnumber there is a trend towards a greater percen-tage of adenomas with severe dysplasia (Table 9).With increasing age of patient there is also a trendfor the percentage of patients with multipleadenomas to increase (Table 10).

Discussion

Colorectal adenomas can be defined as well demar-cated, circumscribed lumps of epithelial dysplasia(atypia) with or without a stalk, usually polypoid butoccasionally flat, which can be categorised into threehistological types: tubular, tubulovillous and vill-ous.18 The histology of these three types of adenomahas been well documented, but it is important toremember that these are not clear cut categories,being only different manifestations of a spectrum ofabnormal tissue architecture.'9The degree of dysplasia of adenomas can be

graded subjectively into mild, moderate and severe,the latter being closest to invasive carcinoma. Severedysplasia is used synonymously with carcinoma-in-situ. Although there are differences the cellular fea-tures of dysplasia in adenomas have much in com-mon with the dysplasia seen as a consequence oflong-standing ulcerative colitis and the chronic col-itis caused by Schistosoma japonica.2021 Similarchanges of focal or diffuse epithelial dysplasia areseen in the stomach22 and in the squamous mucousmembrane of the oesophagus.23 Moreover, it hasbeen pointed out24 that the word "dysplasia" hasgeneral applicability in the description of histo-pathological precursor lesions for cancer in a varietyof epithelial surfaces both within and without thegastrointestinal tract. Conceptually it now appearsadvantageous to think in terms of the dysplasia-carcinoma sequence in the colorectum rather thanthe polyp-cancer or adenoma-carcinoma sequence.

Kalus25 reported that the incidence of severe dys-plasia in adenomas (he used the term "carcinoma-in-situ") was 6*1% in patients with benign lesionsonly, whereas the incidence rose to 47% inadenomas associated with carcinoma in the samesegment of the colon. From this result he concludedthat the diagnosis of severe dysplasia in an adenomashould be followed by careful search for frankadenocarcinoma in any remaining colon. In anotherstudy of necropsy material in two different com-munities in Japan by Sato et a126 it was shown thatadenomas are more often found in a high colorectalcancer risk community (Akita-30%) than in a lowrisk community (Miyagi-18-3%). These authorsalso showed that the adenomas found in the highrisk community (Akita) more often exhibited severedysplasia than in the low risk community (Miyagi).These studies suggest that severe dysplasia inadenomas might be useful as a selective marker forincreased colorectal cancer risk.

Hill et at27 described an hypothesis for the aetiol-ogy of colorectal cancer in which they suggested thatthree factors operated in the process of car-cinogenesis. Factor El was considered to be the fac-

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tor which produces small adenomas. The second fac-tor E2 makes the smaller adenomas become bigger.The third factor C induces carcinoma in a highproportion of large adenomas. This factor is con-sidered to be ubiquitous and to play no part in de-termining the differences in the risk of developingcarcinoma in large adenomas. Following thishypothesis, we suggest that patients who have smalland only mildly dysplastic adenomas may beexposed to factor El but not E2 and these patientsare considered to have a low cancer risk. On theother hand patients who have adenomas with severedysplasia are considered to have intensified factorE2 and consequently a high cancer risk.Our results have shown that the larger adenomas

with severe dysplasia are mostly concentrated in theleft colon and rectum, but particularly the sigmoidpart. On the other hand, small adenomas with milddysplasia showed a more or less even distributionthroughout the large bowel. It would appear that thefactor which produces small adenomas with milddysplasia operates relatively evenly throughout thecolorectum and that the factor which makes smalladenomas larger and more dysplastic is particularlyconcentrated in the sigmoid part. Haenszel and Cor-rea28 reported that the ratio of sigmoid colon car-cinoma to rectal carcinomas (S/R) increases fromlow-risk countries to high-risk countries. In 1975the same authors reported that the site of rectal car-cinoma was higher in a high-risk community of NewOrleans than in the low cancer risk community ofCali, Colombia.29 There are two other reports fromthe USA which show an increase in the ratio of col-onic carcinomas to rectal carcinomas during the last30 yr.30 31 Although most of the reports of surgicallyremoved carcinomas in high cancer risk countriesshow a higher incidence of carcinomas in the rectumthan in the sigmoid colon,732-34 necropsy studieshave shown that the percentage of sigmoid coloncarcinomas is greater than that of rectal car-cinomas'2 35 36 possibly because the number ofundiagnosed sigmoid colon carcinomas is greaterthan those of rectal carcinomas.34 Since it is prob-able that the true distribution of large bowel car-cinomas is shown in the necropsy studies it can beconcluded that in countries with a high colorectalcancer risk carcinomas are more frequently presentin the sigmoid colon than in the rectum, whichclosely correlates with the site distribution ofadenomas with severe dysplasia as reported here.

There are reports relating increased numbers ofadenomas to increased cancer risk.6 37 For example,Muto et al reported that as the number of adenomasper patient increased so did the percentage ofpatients with invasive carcinoma. If the genesis oflarge bowel carcinoma is considered according to

the hypothesis of Hill et al,27 it can be inferred thatwhen the factor which produces adenomas (El) isintensified, the number of adenomas per patient willincrease. In his epidemiological study published in1978,38 Hill tabulated the prevalence of various fac-tors among countries with various grades of cancerrisk deduced from the incidence of adenomas andcarcinomas. In this Table both factor El and E2 arepresent in high risk countries and both are normallyabsent in low risk countries. In other words thesefactors usually appear together. From this result wecan deduce that if there are multiple adenomaspresent in patients where El is intensified, factor E2would also be intensified, making some adenomaslarger and more dysplastic. Our results on the rela-tion between grades of dysplasia and the number ofadenomas per patient support this theory. Patientswith multiple adenomas tend to have a greater riskof developing severe dysplasia which suggests thatthese patients have a higher cancer risk than thepatients with solitary adenomas. The evidence thatthe greater the number of adenomas per patient thegreater the cancer risk is supported by the exampleof familial polyposis coli in which there arethousands of adenomas per patient, with an almost100% risk of developing carcinoma.

It is well known that there is a higher colorectalcancer risk with increasing age. We have confirmedprevious reports'3 17 39 of a relation between age andsevere dysplasia which, although not statisticallysignificant, demonstrates a trend. Persons over 70 yrold are particularly prone to a high incidence ofsevere dysplasia and consequently can be consideredto be those with the highest cancer risk. Table 10also demonstrates the trend that as age increases thepercentage of patients with multiple adenomasbecomes greater.

Colorectal adenomas are common and most ofthem never become malignant. In other words theadenoma is a very dilute marker of increased col-orectal cancer risk. The objective must be to searchfor more selective markers of especially high cancerrisk by studying the histopathological features ofadenomas. It is already well established that those>10 mm diameter, tumours with a pronounced vill-ous component and adenomas with severe dysplasiahave the greatest malignant potential, but in thisstudy evidence is presented which suggests thatsevere dysplasia per se may be the most selectivemarker of increased cancer risk and that this isclosely linked with the site distribution of colorectalcancers, numbers of adenomas per patient, andincreasing age. Severe dysplasia and multipleadenomas could be valuable markers for selectingfrom the total population of patients with adenomasthose most deserving of close surveillance in

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follow-up cancer prevention programmes, but thiscould only be satisfactorily demonstrated by pros-pective studies.The concentration of severely dysplastic

adenomas in the left colon and rectum suggests thatthe short flexible fibreoptic colonoscope might proveto be especially valuable in the design of cancerdetection and cancer prevention programmesbecause it is easier to use than the long instrumentand theoretically should detect the majority ofadenomas destined to become cancerous. Detectionof lesions in the moTe proximal colon could be left toinvestigation by air contrast barium enema studies.A combination of these endoscopic and radiologicaltechniques might prove to be the most effectivescreening procedure.

This research was made possible by grants to FKonishi from the British Council and to BC Morsonfrom the Cancer Research Campaign, for which weexpress our gratitude. We are also grateful to DrHJR Bussey for invaluable advice, to Dr CB Wil-liams and the staff of the Endoscopy Unit at StMark's Hospital for their co-operation, to Mr LloydSoodeen for technical assistance, to Mr NigelHathaway of the Department of Medical Electronicsat St Bartholomew's Hospital for processing thedata, to Mr Bill Brackenbury for the microphoto-graphs and to Miss DE Harwood for secretarialassistance.

References

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2 Morson BC. The pathogenesis of colorectal cancer. In:Bennington JL, ed, Major problems in pathology Vol 10.Philadelphia, London, Toronto: WB Saunders, 1978.

Wychulis AR, Dockerty MB, Jackman RJ, Beahrs OH. His-topathology of small polyps of the large intestine. SurgGynecol Obstet 1967;124:87-92.

Ekelund G, Lindstrom C. Histopathological analysis of benignpolyps in patients with carcinoma of the colon and rectum. Gut1974;15:654-63.

s Kozuka S. Premalignancy of the mucosal polyp in the large intes-tine: I. Histologic gradation of the polyp on the basis ofepithelial pseudostratification and glandular branching. DisColon Rectum 1975;18:483-93.

6 Muto T, Bussey HJR, Morson BC. The evolution of cancer of thecolon and rectum. Cancer 1975;36:2251-70.

7South Thames Cancer Registry. Report ofthe Executive Commit-tee 1975/76 (incorporating statistics for 1972). London: 1976.

Haenszel W, Correa P. Cancer of the large intestine:epidemiologic findings. Dis Colon Rectum 1973;16:371-7.

Blatt LJ. Polyps of the colon and rectum: incidence and distribu-tion. Dis Colon Rectum 1961;4:277-82.

'0 Chapman I. Adenomatous polypi of large intestine: incidenceand distribution. Ann Surg 1963;157:223-6.

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Requests for reprints to: Dr BC Morson, PathologyDepartment, St Mark's Hospital, City Road, LondonEC1V 2PS, England.

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Documents

Pathology of colorectal adenomas: colonoscopic · colon); transverse colon; descendingcolon; sigmoid colon; rectum. If indicated as splenic flexure or hepatic flexure, tumours at