The Incidence and Significance of Villous Change in Adenomatous Polyps

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1 The Incidence and Significance Villous Change in Adenomatous Polyps CHRISTOPHER H. K. FUNC, M.D., AND HARVEY GOLDMAN, M.D. Department Pathology, Harvard Medical School and Beth Israel Hospital, Boston, Massachusetts Abstract. Fung, Christopher, H. K., and Goldman, Harvey: The incidence and significance villous change in adenomatous polyps. Am. J. Clin. Path. 53: 21-25, A retrospective review 108 colonic adenomatous polyps revealed focal villous change in 6% solitary lesions, 15% polyps with coexisting adenocarcinoma, 33% those with coexisting villous adenoma, and 64% polyps with carcinomatous transformation. However, a subsequent prospective analysis 67 colonic polypoid lesions, using a dissecting microscope and more sections, indicated that the incidence focal villous change had been underestimated. This feature was found in 35% solitary adenomatous polyps and appeared to be directly related to the size the polyps, reaching 75% in lesions larger than 1 cm. in diameter. The dissecting microscopic interpretations provided the correct estimate a villous pattern in 96% cases. Although morphologically the adenomatous polyp with focal villous change appears to represent an intermediate form between the pure adenomatous polyp and the villous adenoma, evidence for obligatory transformation and increased malignant potential this form is inconclusive. The difficulty that may be encountered in the interpretation a villous area in a small biopsy is discussed. A PRECISE histologic distinction between adenomatous polyp is characterized by a adenomatous polyps and villous (or papil- coarsely-lobulated structure with minimal lary) adenomas is desirable in view the or no detectable villous areas, whereas the pronounced difference between the malig- villous adenoma is defined simply by the nant potentials the two forms. Whereas presence a predominant villous or papilthe occurrence carcinoma in adenoma-, i i i i i i, lar >' pa"ern. ligible, tous polyps - s or has at been most considered less than to 1%, be neg- the _.,..,,..,!, i lny i ever, Difficulties have ten in been exact encountered, classification, ' 18 how and recorded incidence malignancy in villous adenomas has ranged from 35 to the possible existence intermediate 7(w.i, io, i3, i4,17 Since no essential differ- forms has been proposed by numerous indices in cytologic detail " 10. 1S or mucin vestigators. 5 - "' " " " 15 The present study, content" have been demonstrated in these which includes observations made with the two lesions, the established criterion for dissecting microscope, was conducted in their separation has been limited to the order to determine the frequency occurdegree villous pattern present. The rence 0f villous areas in various groups adenomatous polyps and to consider these Received lime lfi, 19G9; accepted for publication r, i t. i r - i August ustf. 6, 1009, ifjjjo. i i findings in relation to the genesis vil- 21

2 22 FUNG AND GOLDMAN Vol. 53 Fie. 1. Low-power photomicrograph o adenomatous polyp with focal villous change. The predominant component (left and top) is adenomatous, but a distinct villous area is present on the right. Hematoxylin and eosin. X 12. lous adenomas and to overall malignant potential. Fin. 2. Higher-power view villous area noted in Figure 1. Hematoxylin and eosin. X HO. Material and Methods The study, in which we employed surgical material exclusively, consisted two parts: 1) a retrospective study, in which 108 selected adenomatous polyps the human colon, alone or in association with other lesions, were reviewed, and 2) a prospective study, in which 67 colonic polypoid lesions (including adenomatous polyps, villous adenomas, carcinomas, hyperplastic polyps, 0 inflammatory polyps and mucosal tags) were examined initially with the dissecting microscope. For both, paraffin-embedded sections formal in-fixed tissues were stained with hematoxylin and eosin. Whereas the number sections each polyp available in the retrospective survey was generally one to two, usually more than four sections each lesion in the prospective study were examined. Standard histologic criteria as outlined by Dukes 4 were employed to distinguish the adenomatous and villous areas, and the designations adenomatous polyps

3 January 1970 VILLOUS CHANGE IN ADENOMATOUS POLYPS 23 and villous adenomas depended solely on the predominant pattern present. For each adenomatous polyp, the presence focal villous change, i.e., involving less than half the lesion, was noted as well. Accordingly, pure adenomatous polyps, adenomatous polyps with focal villous change (Figs. 1 and 2), and villous adenomas were recognized. The diagnosis carcinoma within the polyp was determined by the demonstration invasion or extreme cytologic atypicality, usually the former; metastases were not observed in any these cases. Results Retrospective Study. The relative incidences focal villous change observed within the various subgroups adenomatous polyps examined in the retrospective study are listed in Table 1. Villous change appeared to be distinctly more common in cases with carcinoma in the polyp or in those with a coexisting villous adenoma. Prospective Study. The 67 colonic lesions examined with the dissecting microscope were described as villous, leafy, lobulated, cobblestoned, pitted, granular, firm, or mucinous in appearance. Except for the villous pattern, however, there were no consistent histologic counterparts for these features. A precise correlation between the gross impression the presence or absence a villous pattern and the histologic confirmation was achieved in all but three cases (96%). Jn two cases, a villous pattern was anticipated but not confirmed by histologic study, and in one instance, the villous appearance was missed. Adenocarcinoma was suspected in 11 cases on the basis induration or excessively mucinous appearance, but was confirmed in only five; the remaining six lesions, four were villous adenomas and two, inflammatory polyps. In addition, there was one carcinoma arising in a polyp which was not grossly apparent. TABLE 1. Incidence Focal Villous Change in Adenomatous Polyps {Retrospective Study) Number Villous Change Type Lesion Polyps Number % Adenomatous polyps with out associated villous adenoma or carcinoma Adenomatous polyps with coexisting adenocarcinoma the colon Adenomatous polyps with coexisting villous adenoma the colon Adenocarcinoma arising in adenomatous polyps In Table 2, the incidences histologically-demonstrated villous patterns, either focal or more diffuse, are listed for the lesions examined in the prospective study. Comparison with the retrospective study (Table 1) reveals that the occurrence a focal villous area in solitary adenomatous polyps is a common feature (35%) which may be missed in examinations employing random or few sections (6%). Furthermore, TABLE 2. Incidence Villous Pattern in Colonic Polypoid Lesions {Prospective Study) Number Villous Pattern Type Lesion Lesions Number % Adenomatous polyps only Adenomatous polyps with 0 0 coexisting adenocarcinoma colon Adenomatous polyps with 2 2 coexisting villous adenoma colon Adenomatous polyp with 1 1 carcinoma arising in it Villous adenomas Villous adenomas with 2 2 carcinoma arising in them Adenocarcinomas, de novo 3 0 Miscellaneous (hyperplas tic and inflammatory polyps and mucosal tags)

4 24 FUNG AND GOLDMAN Vol. 53 TABLE 3. Relation Focal Villous Change to Size Adenomatous Polyp {Prospective Study) Size Polyp 0-5 mm mm. >10mm. TOTAL Number Polyps Villous Change Number % there appears to be a distinct relation between the size the adenomatous polyp and the presence a focal villous change, as indicated in Table 3. Thus, 75% the solitary adenomatous polyps larger than 1 cm. in diameter exhibited a focal villous area. Discussion The presence focal villous change in otherwise typical adenomatous polyps appears to be common, especially in lesions larger than 1 cm. in diameter. The much higher incidence observed in solitary adenomatous polyps in the prospective study (35%), as compared with the retrospective study (6%), is due in part to the use the dissecting microscope, which clearly aided in the selection the appropriate area for histologic study. In fact, the estimation a villous pattern by the dissecting microscope was accurate in all but three the 67 lesions examined. However, the greater number sections taken routinely in the prospective study may also have contributed to the higher incidence villous change noted, and suggests further that the total incidence this feature may be largely underestimated. The occurrence focal villous change in adenomatous polyps and its relation to the size the lesion have been noted previously. Ferraro and Ross 5 detected villous features in 45% adenomatous polyps, and observed that this was more common in larger polyps and in older age groups. The lower overall incidence 7.5%, noted by Jackman and Beahrs, 7 reflects the small size the majority the polyps examined in that series; it is noteworthy, however, that in polyps larger than 1 cm. in diameter, a villous pattern was found in 43%. This relation to size the polyps is supported by the present study, in which the incidence focal villous change was found to be even greater than that previously recorded. The precise significance focal villous change within an adenomatous polyp has not been established. Thus, the retrospective study revealed an increased incidence focal villous change in adenomatous polyps associated with villous adenomas and carcinomas, as compared with solitary lesions (Table 1). However, in the subsequent prospective study employing adequate and selective sections (Tables 2 and 3), this feature was detected in the majority solitary adenomatous polyps larger than 1 cm. in diameter. Because adenomatous polyps this size are, in general, much more common than villous adenomas, and possess a very low malignant potential, the presence villous change in these polyps must at present be considered to be limited importance as a sign a biologically more significant lesion. Whether the appearance focal villous change represents an abortive attempt at transformation and whether some villous adenomas are derived by successful transformation pre-existing adenomatous polyps cannot be established from the results the present study. In view the apparent difference in behavior between polyps with focal villous change and those with diffuse or predominantly villous patterns, i.e., villous adenomas, an accurate histologic distinction is essential. Ideally, this can be accomplished when the entire lesion is available for study by simply assessing the degree the villous area present. Difficulties, however, may be encountered when small mucosal biopsy specimens are examined.

5 January 1970 VILLOUS CHANGE IN ADENOMATOUS POLYPS 25 Thus, if the biopsy reveals a villous area, it may be derived not only from a villous adenoma but also from an adenomatous polyp with focal villous change. Since from the present study the latter appears to be so common, especially in the larger polyps which may have an initial biopsy before excision, there exists the danger overestimating the significance the villous feature, resulting in an erroneous diagnosis and incorrect therapy. Clearly, the histologic study a biopsy must at all times be correlated with the gross appearance the lesion as viewed by sigmoidoscopy or operative colostomy; if any disparity exists between the gross and microscopic impressions, definitive diagnosis should await examination the entire lesion References 1. Bacon, H. E., Lowell, E. J., Jr., and Trimpi, H. 1).: Villous papillomas the colon and rectum. Surgery, 35: 77-87, Castleman, B., and Krickstein, H.: Do adenomatous polyps o the colon become malignant? New Engl. J. Med., 267: , 1962.!. Castleman, 15., and Krickstein, H.: Carcinoma arising in adenomatous polyps the colon is greatly exaggerated. In lngelfinger, F. J., Relman, A. S., and Finland, M. (eds.): Controversy in Internal Medicine. Philadelphia, W. B. Saunders Co., 1966, pp Dukes, C. E.: An explanation the difference between a papilloma and an adenoma the rectum. Proc. Roy. Soc. Med., 40: , Ferraro, L., and Ross, S.: Evaluation villous patterns in tumors the colon and rectum. Dis. Colon Rectum, 8: , Goldman, H., and Ming, S. C: Mucins in normal and neoplastic gastrointestinal epithelium. Arch. Path., 85: , Jackman, R., and Beahrs, O.: Tumors the Large Bowel. Philadelphia, W. B. Saunders Co., 1968, pp Lane, N., and Kaye, G.: Pedunculated adenomatous polyp the colon with carcinoma, lymph node metastasis, and suture-line recurrence. Am. J. Clin. Path., 48: , Lane, N., and Lev, R.: Observations on the origin adenomatous epithelium the colon. Cancer, 16: , Mackie, J. A., Jr., Miller, L. D., and Fills, W. T., Jr.: Polyps and polypoid lesions the large bowel: Surgical considerations. Surg. Clin. N. Amcr., 42: , Morson, B. C: Precancerous lesions the colon and rectum. J.A.M.A., 179: , Spjut, H. J., and Navarrete, A.: Adenomatous polyps and polyps familial polyposis: A. morphological study the contrasts and similarities. Am. J. Path., 48: 5a-6a, Sunderland, D. A., and Binkley, G. E.: Papillary adenomas the large intestine. Cancer, 1: , Swinton, N. VV., Meissner, W. A., and Soland, W. A., Jr.: Papillary adenomas the colon and rectum. Arch. Int. Med., 96: , Turrell, R., and Haller, J.: A re-evaluation the malignant potential colorectal adenomas. Surg. Gynec. Obslet., 119: , Welch, C. E., McKittrick, J. B., and Rehringer, C: Polyps rectum and colon and their relation to cancer. New Engl. J. Med., 247: , Wheat, M. W., and Ackerman, L. V.: Villous adenomas the large intestine. Ann. Surg., 147: , Wood, D.: Tumors the intestine. Atlas Tumor Pathology, Section VI Fascicle 22. Washington, D. C, Armed Forces Institute Pathology, 1967, pp Requests for reprints should be addressed to: Harvey Goldman, M.D., Department Pathology, Beth Israel Hospital, 330 Brookline Avenue, Boston, Massachusetts