The Relationship Between Polyps and Carcinoma of the Colon and Rectum * ROBERT A. SCARBOROUGH, M.D. San Francisco, California

A RECENT p u b l i c a t i o n by S p r a t t a n d his associates 2 has c h a l l e n g e d some of the gene r a l l y a c c e p t e d concepts in r e g a r d to the relationship between adenomatous polyps a n d c a r c i n o m a . T h i s s t i m u l a t i n g a n d provocative article has caused m e to r e v i e w m y o w n p e r s o n a l e x p e r i e n c e over the p a s t 25 years. T h r e e definite c r i t e r i a were e s t a b l i s h e d for the selection of cases in this s t u d y : (1) T h e i n i t i a l c l i n i c a l diag-nosis m u s t h a v e b e e n t h a t of " p o l y p . " (2) If m i c r o s c o p i c examination revealed carcinoma, there must also be h i s t o l o g i c e v i d e n c e of b e n i g n adeno m a i n the same t u m o r . (3) A l l n o n a d e n o m a t o u s p o l y p s were e x c l u d e d . O n this basis, 1,088 cases were reviewed. E v a l u a t i o n of the p a t h o l o g i c significance of p o l y p s r e q u i r e s m o r e t h a n e x a m i n a t i o n of a p a r t i c u l a r t u m o r a n d its h o s t at a part i c u l a r time. I n the b e l i e f t h a t p o l y p o i d disease is the r e s u l t of a c o n t i n u i n g b i o l o g i c s t i m u l u s to n m l t i c e n t r i c p a t h o l o g i c changes in the mucosa, a p a r t i c u l a r s t u d y was m a d e of 422 p a t i e n t s w h o were f o l l o w e d for a p e r i o d of t h r e e or m o r e years. T h i s phase of the s t u d y provi.ded a t o t a l p a t i e n t - y e a r follow u p of 3,302 years. I n these 422 patients it was f o u n d t h a t 42 (10 p e r cent) u l t i m a t e l y d e v e l o p e d a f r a n k c a r c i n o m a in one a r e a or a n o t h e r of the large bowel. L o n g t e r m follow u p of over 2,000 cancer p a t i e n t s r e v e a l e d a n i d e n t i c a l i n c i d e n c e o£ 10 p e r cent of u l t i m a t e d e v e l o p m e n t of a s e c o n d p r i m a r y c a r c i n o m a of the c o l o n or rectum.

O f p a r t i c u l a r significance is the e v i d e n c e of w h a t h a p p e n e d to a n u m b e r of p a t i e n t s in w h o m t r e a t m e n t of d e m o n s t r a b l e p o l y p s was n o t c a r r i e d o u t for a p e r i o d of f r o m two to 18 years. B r i e f r e c a p i t u l a t i o n of the records of I0 p a t i e n t s is p e r t i n e n t to this discussion. R e p o r t o f Cases Case r: In 1935, a grossly benign pedunculated polyp, 1 cm. in diameter, was observed, 13 cm. above the anus on the left posterior wall of the rectum. This polyp was not removed. In 1953, the patient returned with an annular carcinoma of the upper rectum. Thirteen centimeters above the anus at the site of the original polyp, contiguous with the lower edge of the annular carcinoma, the pathologist demonstrated in the " resected specimen a semispherical area of benign adenomatous tissue. Case 9: In 1942, proctoscopy revealed a sessile polyp, less than 1 cm. in diameter, located 12 cm. above the anus. T h e polyp was not treated. In 1957, the patient returned. There was now an annular carcinoma centering 12 cm. above the anus, overriding the site at which a small polyp had been observed 15 "years before. Laparotomy revealed regional node and liver metastases from which the patient subsequently died. Case 3: A pedunculated polyp 1 cm. in diameter was observed in the rnidampulla of the rectum but was not removed. Two years later a frank carcinoma, 5 cm. in diameter, was present at the same site as the polyp. AbdominoperineaI resection was performed. There was no other polypoid lesion present in the resected specimen and the regional nodes were not involved. Case 4: A pedunculated, grossly benign polyp, 1 cm. in diameter, was observed by proctoscopy but the patient failed to return for treatment until two years later. At that time there was found a frank carcinoma, 2 cm. in diameter,

* Read at the meeting of the American Proctolo~c Society, Houson, Texas, April 25 to 27, 1960. 336

RELATIONSHIP BETWEEN POLYPS AND CARCINOMA at the same site. All evidence of the original small, pedunculated, grossly benign poIyp had disappeared. Case 5: I n 1940, roentgenologic examination of the colon in a 74-year-old man with serious cardiac disease revealed a polyp, 1.5 cm. in diameter, on a long pedicle in the transverse colon, and a similar pedunculated polyp in the proximal portion of the sigmoid. Two years later roentgenologic examination showed that both polyps had doubled in diameter but were still pedunculated. I n 1945, five years after the original demonstration of two pedunculated polyps of the abdominal portion of the colon, barium-air contrast enema examination revealed two irregular tumors, 4 cm. in diameter, without evidence of a pedicle, at the same two sites. Successful surgical renmval was carried out and two broad-based frank carcinomas were found. There were no other polypoid lesions in the colon. Case 6: I n 1952, roentgenotogic examination of the colon of this debilitated man of 82 years revealed a smoothly rounded polyp of the sigmold 1.5 cm. in diameter. No pedicle was demonstrable. I n 1955, repeat roentgenologic examination revealed a filling defect characteristic of carcinoma at the same site. Emergency operation became necessary when the patient developed acute obstruction. The resected specimen contained a frank carcinoma, 4 cm. in diameter, and no other polypoid lesion. Case 7: This patient had four barium-air contrast enema examinations of the colon over a period of two years because of occasional streaking of blood on the stools. The first three examinations were considered normal. The fourth examination revealed a smoothly rounded sessile lesion, 2 cm. in diameter, in the proximal portion of the sigmoid. Review of the films of the examination done two years before disclosed that there hacl been demonstrated, but overlooked, a pedunculated polyp, 1 cm. in diameter, at the same site. Laparotomy revealed a carcinoma 2 cm. in diameter. There was no other polypoid lesion in the resected specimen. Case 8: In 1952, a pedunculated polyp of the sigmoid, 2 cm. in diameter, was demonstrated by roentgenologic examination. It was not removed. I n 1958, laparotomy revealed a carcinoma at the same site, with metastatic carcinoma in the regional nodes and liver. There was no evidence of any other polypoid lesion. Case 9: In 1956, roentgenologic examination revealed a pedunculated polyp of the sigmoid,

337

1.5 cm. in diameter. I n 1958, barium-air contrast enema examination disclosed a polypoid lesion, 2 cm. in diameter, at the same site without a demonstrable pedicle. At operation a 2-cm. frank carcinoma was found w i t h direct extension of the tumor into the mesosig~qaoid. No other polypoid lesion was present in the resected specimen. Case 10: I n 1949, roentgenologic examination of the colon was considered normal. I n 1951 repeat examination revealed a 2-cm. sessile "polyp." Review of the original fihns disclosed in two films definite evidence of a pedunculated polyp, I cm. in diameter, at the same site. At operation a grossly malignant sessile polypoid lesion, 2 cm. in diameter, was resected. Metastatic carcinoma was present in one regional node. T h e a b o v e ten cases are p r e s e n t e d as evidence of the d e v e l o p m e n t of c a r c i n o m a w h e n polyps are n o t removed. I t m i g h t be a r g u e d t h a t some of these lesions were carc i n o m a fl-om the time of t h e i r origin. T h i s possibility c a n n o t be categorically denied, b u t i n every case the earliest a v a i l a b l e evidence justified the diagnosis of a presumably b e n i g n p o l y p of w h i c h e i g h t of t e n were p e d u n c u l a t e d . C o n c l u s i o n s s h o u l d n o t be d r a w n that all polyps will become cancer if they are n o t removed. I n this s t u d y there were an e q u a l n u m b e r of p a t i e n t s i n w h o m d e m o n strable polyps were n o t r e m o v e d u n t i l after a delay of f r o m two to ten years, a n d the polyps were still b e n i g n a d e n o m a s at the time of u l t i m a t e excision. Polyps of the R e c t u m T h e r e have b e e n 837 p a t i e n t s i n w h o m polyps have b e e n f o u n d i n the r e c t u m by proctoscopy. I t has b e e n o u r policy to remove all p e d u n c u l a t e d polyps by diat h e r m y snare, followed by p a t h o l o g i c exa m i n a t i o n of the t u m o r . Sessile polyps m o r e t h a n 7 ram. i n diameter, w i t h the exc e p t i o n of large p a p i l l a r y a d e n o m a s , are s i m i l a r l y r e m o v e d for microscopic e x a m i n a t i o n a n d the base t h e n f u l g u r a t e d . W e thoro u g h l y destroy by electrodesiccation n o n -

338

SCARBOROUGH

TABLE1. Sixty-five Malignant Rectal Polyps Number 4 24 37

Treatment Se~nentalresectima Abdominoperineal resection Local treatment*

Node metastases

Died of carcinoma

0 3 (12.5per cent) --

0 1 1

1--Local recurrence of carcinonla 1--Died of metastatic carcinoma ulcerated sessile lesions less than 7 nnn. in diameter without microscopic examination. It is possible that by such treatment very early carcinomas have not been recognized. But in our experience there has never occurred any subsequent evidence of carcinoma at the site of such treatment or evidence of later metastatic spread from such a lesion. Papillary adenomas with a pedicle are also removed by diathermy snare. But sessile papillary adenomas are removed by complete local surgical excision because of the high incidence of local recurrence observed after apparently adequate electrodesiccation. In the polyps initially removed in these 837 patients the incidence of malignancy was 7 per cent, or 58 patients. In 162 patients who later developed new polyps in the rectum seven had a malignant polyp removed, an incidence in this group of 4.3 per cent. There were, altogether, 65 malignant polyps of the rectum. T h e diagnosis of malignancy has been made only when microscopic examination demonstrates definite invasion through the muscularis mucosa. All polyps which showed "atypism" or "carcinoma in situ" without evidence of invasion were classified as benign and in our experience behaved as benign lesions. Of the 65 malignant polyps of the rectum, four were treated by segmental resection, 24 by abdominoperineal resection, and 37 by local removal of the polyp (Table 1). In four of the 65 patients segmental resection was carried out with restoration of bowel continuity by low pelvic anastomosis or by a Swenson type pull-through technic.

T h e lesions in these four patients were atl sessile, three of the four keing large papillary adenomas with areas of invasive carcinoma, while the fourth was a sessile malignant adenoma, 2 cm. in diameter. In 24 of the 65 patients abdominoperineal resection was performed. All of these patients had sessile lesions. Eleven had areas of malignancy in sessile adenomas from 1 to 3 cm. in diameter, and 13 had areas of malignancy in sessile papillary adenomas from 2 to 6 cm. in diameter. Regional lymph node metastases were demonstrated in one of the 11 patients with a malignant adenoma, and in two of the 13 patients with malignant papillary adenoma. T h e incidence of node metastases in these 24 patients was 12.5 per cent. Of the 24 patients treated by abdominoperineal resection, 23 have shown no evidence of recurrent carcinoma in from one to 14 years. T h i r t e e n of these 23 patients have now been followed more than five years. One patient who had node metastases died of recurrence of carcinoma less than three years after operation.

TABLE2. Size (Centimeters) of 37 Malignant Polyps of Rectum Treated by Local Removal

25--Pedunculated 22--Adenomas 7 0.7 to 1.0 8 1.0tol.5 4 1.5to2.0 1

2.5

2 2.5 to3.0 3--Papillary 1 1 1

2.0 2.5 3.0

12--Sessile 5--Adenomas 1 0.6 1 1.0 2 1.5 1

3.0

7--Papillary 2,5 to 5.0

RELATIONSHIP BETWEEN POLYPS AND CARCINOMA

In 37 of the patients, treatment was by local removal with diathermy snare and adequate fulguration of the base, or by total local surgical excision. Of the 37 malignant polyps so treated, 25 were pedunculated and 12 were sessile lesions. T h e size of these polyps is shown in T a b l e 2. It is noteworthy that eight of the 37 were I cm. or less in diameter. It should be stated that local excision only of 12 sessile lesions was decided u p o n on the basis of the histologic evidence of a relatively small area of invasive carcinoma in an otherwise benign polyp, with the zone of malignancy located superficially, well away from the plane of excision. Thirty-five of these 37 patients have to date exhibited no evidence of local recurrence or metastases. Nineteen of the 35 have been followed more than three years. One patient, a year following removal of a pedunculated malignant adenoma, 1.5 cm. in diameter, developed a frank carcinoma, 2 cm. i n diameter, at the same site. Abdominoperineal resection was performed with no evidence found of metastatic spread of carcinoma, although the primary t u m o r extended through the full thickness of the rectal wall. T h i s patient shows no evidence of recurrent disease after three years. A second patient h a d had a 1.5 cm. sessile malignant adenoma removed by diathermy snare with thorough fulguration of the base. This patient never developed local recurrence of carcinoma, but after three years did have pararectal node metastases and metastases in the chest wail. No other primary site of carcinoma was ever demonstrated in this patient and he died of malignant disease. T h e results of local treatment only in this particular series of malignant polyps of the rectum would appear to justify conservative treatment in carefully selected cases. It should not be forgotten that there is a calculated risk incurred when such local treatment is utilized. Success depends

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upon total removal or destruction of early invasive carcinoma which has not yet metastasized. T h e adequacy of total local removal of the t m n o r is certainly facilitated by the presence of a pedicle. Follow U p E x a m i n a t i o n We have long advocated annual proctoscopic examination for all patients who have had a polyp of the rectum or colon. T h e value of continuing periodic examination is demonstrated in this study. Of the 422 patients followed for more than three years, 162 (38 per cent) have subsequently developed new polyps detectable by proctoscopy. In seven of these 162 patients (4.3 per cent) the new.polyp was malignant. Of particular interest has been our experience with six patients who failed to return for annual proctoscopic e x a m i n a t i o n subsequent to removal of a benign a d e n o m a of the rectum. After several years they returned with frank carcinomas of the rectum. Four of these six patients were lost to follow u p for more than five years and two did not return for more than two years. All six patients had abdominoperineal resection and in three of the six metastatic carcinoma was present in regional nodes. One patient died later of liver metastases which had been observed at the time of resection. Polyps of the A b d o m i n a l Portion of the Colon T h r e e h u n d r e d forty-one patients have been operated u p o n for one or more polyps of the abdominal portion o£ the colon. It has been said 1 that patients with familial polyposis should be excluded in the study of the pathologic significance of polyps, since this is a distinct and separate entity carrying with it its own prognosis and treatment. "vge disagree with this theor/ for a n u m b e r of reasons. A family history of polypoid disease has been lacking in 50 p e r cent of our patients with f r o m 100 to over 2,000 polyps scattered throughout the

SCARBOROUGH

340

TA'P,LE 3. Seventy-five Malignant Polyps of the Abdominal Portton of the Colon Number 54 9 4 8

Pedunculated adenomas 31 Resected 23 Local excision Sessileadenomas--all resected Pedunculated, papillary--resected Sessile,papillary--resected

colon and rectum. We have observed no basic differences in biologic behavior in patients with single polyps or with polyposis, except for the fact that the greater the n u m b e r of polyps the greater the chances are for development of malignancy. We have found no satisfactory answer to the questions: (1) H o w m a n y polyps nmst be present to justify a diagnosis of polyposis? (2) Must the polyps be distributed throughout the entire colon to require the diagnosis of polyposis? For the sake of comparative study and discussion, there have been arbitrarily excluded from this report 36 patients in w h o m abdominal colectomy has been performed for scattered polyps t h r o u g h o u t the colon nflmbering from 11 to over 2,000. Of the remaining 305 patients, 174 (60 per cent) had a single polyp removed at laparotomy. We consider this an erroneous figure, inasmuch as colonoscopy at the time of laparotomy has been utilized for the identification of additional polyps onIy during the past eight years. W i t h the use of this procedure more than 50 per cent of patients have been found to have more than one p o l y p at the time of operation. T h e r e have been 13 patients in w h o m a second laparotomy was performed after more than five years for additional polyps which might have been discovered at the time of the original operation if colonoscopy had been employed. I n these 305 patients, invasive carcinoma was histologically demonstrated in an adenomatous polyp in 75 patients (25 per cent). In the selection of appropriate surgical

Node metastases 5 -0 0 0

Died of carcinoma 1 1

0 0 0

treatment m u c h emphasis has been placed u p o n whether or not the m a l i g n a n t polyp has a pedicle. It has also been said that carcinoma arising in a papillary a d e n o m a is more prone to rnetastasize than carcinoma arising in the ordinary adenoma. W i t h these points in mind, the m a l i g n a n t polyps in this series were subdivided into four groups--pedunculated m a l i g n a n t adenomas, sessile malignant adenomas, p e d u n c u l a t e d papillary adenomas with carcinoma, and sessile papillary adenomas with carcinoma (Table 3). Pedunculated. m a l i g n a n t adenomas occurred most frequently in this series, numbering 54 of 75 patients. I n 31 of these 54 patients radical resection was done. In five of these 31 patients regional node metastases were demonstrated and one of these five patients later died of metastatic carcinoma. It should be stated that in three of the five patients the gross appearance of the polyp was suspicious of carcinoma a n d on histologic e x a m i n a t i o n the m a j o r portion of the p o l y p was malignant. However, all five tumors showed areas of benign adenoma, and in four of the five no microscopic involvement of the pedicle was demonstrable. In 23 of the 54 patier~ts with a pedunculated malignant adenoma local excision only of the m a l i g n a n t p o l y p and its pedicle was performed. One of these 23 patients subsequently died of metastatic carcinoma with no other p r i m a r y carcinoma demonstrable. T h e r e were nine patients with a sessile

RELATIONSHIP BETWEEN POLYPS AND CARCINOMA malignant adenoma. Wide resection was carried out in all nine and none had regional node metastases. All have remained well. T h e r e were four pedunculated papillary adenomas with malignancy and eight sessile papillary adenomas with malignancy. All were resected and none had regional node metastases. All have remained well. It should be pointed out that in every instance here reported the diagnosis of invasive carcinoma has required confirmation by microscopic examination. Patients operated u p o n with a preoperative diagnosis of polyp, but in whom carcinoma has been recognizable by gross inspection and palpation, have been omitted from this study. R e t u r n i n g to the question of the significance of a pedicle, we believe that all polyps begin as sessile lesions which may eventually develop a pedicle by tenting u p of the surrounding normal mucosa as the result o£ peristaltic propulsion of feces against the polyp or, as the polyp increases in size, peristaltic propulsion of the polyp itself. If this is true, one would expect that t h e incidence of pedicle formation would be greatest in the sigmoid flexure, where there is m a x i n m m mass peristaltic propulsion of formed feces through the area of smallest diameter of the large intestine. T h i s has been found to be true in this study. Eightyfive per cent of sigmoidal polyps were

~41

pedunculated, 66 per cent of polyps of the descending colon were pedunculated, 30 per cent of polyps of the transverse colon, and 34 per cent of polyps of the ascending colon had a pedicle. O u r experience has not shown that there is any greater chance of node metastases in the sessile malignant p o l y p than in the pedunculated malignant polyp. I t is true that a pedunculated polyp can be more certainly excised totally than a sessile polyp. We have accepted the experience of others, notably Swinton and T u r n b u l l , with certain reservations, and presently believe that m a n y pedunculated m a l i g n a n t polyps of the abdominal portion of the colon and of the rectum can be excised locally with a high expectation of p e r m a n e n t cure. We also believe that this procedure may be applied to sessile lesions when complete excision with inclusion of adequate margin can be satisfactorily accomplished. However, we also believe that this type of local excision is justifiable only in those patients in w h o m there fs a relatively small area of invasive carcinoma in an otherwise benign lesion, and in w h o m the possibility of metastatic extension to the regional nodes appears definitely less than the surgical risk of more radical operation. T h i s places u p o n the surgeon a great responsibility in regard to clinical j u d g m e n t and technical skill. A comparative study of the relative size of benign polyps and m a l i g n a n t polyps has

TABLE4. Size of Benig*l and Malignant Polyps Number Pedunculated benign adenomas Pedunculated malignant adenomas Sessile benign adenomas Sessile malignant adenomas Pedunculated benign, papillary Pedunculated malignant, papillary Sessile benign, papillary Sessile malignan t, papill ary Total

,819 50 83 7 8 8 18 8 501

Diameter Mean average diameter (centimeters) (centimeters) 0.5 to 4 0.6 to 3 0.2 to 3 1.0 to 4 1.5 to 3 1.5 to4 1.5 to 7 2.0 to 4

1.6 1.7 0.9 2.5 2.3 2.1 3.5 2.3

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SCARBOROUGH

been m a d e in 501 lesions in w h i c h a c c u r a t e m e a s u r e m e n t has been r e c o r d e d ( T a b l e 4). It is n o t e w o r t h y t h a t the m e a n average d i a m e t e r of m a l i g n a n t p e d u n c u l a t e d adenomas was p r a c t i c a l l y the same as t h a t of b e n i g n p e d u n c u l a t e d a d e n o m a s . B o t h the b e n i g n a n d the m a l i g n a n t p a p i l l a r y adenomas were of g r e a t e r size, b u t the presence of invasive c a r c i n o m a c o u l d n o t be p r e d e t e r m i n e d on the basis of size alone.

Summary and Conclusions W e believe t h a t the e x p e r i e n c e h e r e rep o r t e d serves to s u p p o r t the t h e o r y of the close i n t e r r e l a t i o n s h i p b e t w e e n a d e n o m a tous p o l y p s a n d c a r c i n o m a . T h e r e is no way to tell h o w m a n y c a r c i n o m a s b e g i n as c a r c i n o m a , or h o w m a n y b e g i n i n b e n i g n a d e n o m a s . T h e r e is n o way to k n o w h o w many carcinomas have completely replaced a p r e c e d i n g a d e n o m a so t h a t the l a t t e r cann o t be recognized. B u t t h e r e is a b u n d a n t evidence t h a t c a r c i n o m a can a n d does

o r i g i n a t e in b e n i g n a d e n o m a s a n d there is ~urther e v i d e n c e t h a t such a c a r c i n o m a can metastasize a n d cause d e a t h . T h e r e is also e v i d e n c e t h a t i n m a n y instances, in the e a r l y stage of m a l i g n a n t t r a n s f o r m a t i o n , cure can be effected b y c o n s e r v a t i v e r e m o v a l of the e n t i r e lesion b y l o c a l excision. Reco g n i t i o n a n d a p p r o p r i a t e t r e a t m e n t of p o l y p s of the c o l o n a n d r e c t u m c o n s t i t u t e one of the m o s t r e w a r d i n g e n d e a v o r s in the c o n t r o l of cancer. I n the e x p e r i e n c e h e r e r e c o r d e d t h e r e have b e e n n o d e a t h s f r o m o p e r a t i o n s perf o r m e d for p o l y p s .

References 1. Grinnell, R. S. and N. Lane: Benign and malignant adenomatous polyps and papillary adenomas of the colon and rectum: An analysis of 1,856 tumors in 1,335 patients. Internat. Abstr. Surg. 106: 519, 1958. 2. Spratt, J. S., Jr., L. V. Ackerman and C. A. Moyer: Relationship of polyps oE the colon to colonic cancer. Ann. Surg. 148: 682, 1958.