S rectal polyps that show atypia, adenocarcinoma,

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1 HOW RELIABLE IS BIOPSY OF RECTAL POLYPS? A Clinical and Morphological Study of 107 Cases C. ALEXANDER HELLWIG, M.D., AND EDGARD BARBOSA. nr.d. OME OVERLY cautious pathologists call all S rectal polyps that show atypia, adenocarcinoma, Grade I. This attitude is a great injustice to the patient and is misleading to the surgeon. More than 150 cases reported in the literature had such atypical changes and were cured by simple polypectomy (S~inton,~ Mc- Lanahan et a1.,6 Fisher and Turnbull,* Lockhart-Mummery and Dukes,6 Castro et al,l and Welch et al.11). We believe with Swintone that it may require the highest degree of skill and experience to determine the presence, degree, and extent of malignant changes in a clinically benign polyp, and to advise the type of treatment. The purpose of the present paper is to determine how reliable biopsy of rectal polyps is in helping the surgeon decide between abdominoperineal resection and polypectomy, without minimizing the chances of a cancer cure. The gross and microscopic findings for all rectal polyps that had been examined in our laboratory from 1951 to 1957 were reviewed and co-ordinated with the clinical findings, including follow-up observation. There were 142 polyps removed from 107 patients. Eightyseven adenomatous polyps were regarded as benign, 28 as malignant, and 12 as invasive carcinomas. In addition, there were 15 biopsy specimens that were diagnosed as villous papillomas, 5 of them as cancerous. In classifying our material, we made the same subdivisions as Lockhart-Mummery and Dukes;: (I) benign (with goblet cells), 97 cases; (2) active proliferation (with slight atypia and without secretion of mucus), 11 cases; (3) carcinoma in situ, 3 cases; (4) focal intramucosal carcinoma, 19 cases; and (5) invasive carcinoma (spreading to submucosa), 12 cases. In invasivc carcinomas, we determined the grades of malignancy as low (1 case), average (8 cases), and high (3 cases). From the Pathology Department, Hertzler Clinic and Hertzler Research Foundation, Halstead. Kansas. Aided by a pnt from the Kansas Division of the American Cancer Society. Inc. Received for publication July Most of the workers (Lockhart-Mummery & Dukes,5 Helwig,4 McLanahan et a1.,6 Gorsch,s Womackl3) agreed on the importance of removing the whole polyp for careful histolog-, ical examination. Particularly in pedunculated tumors, the necessity of having the whole pedic cle available for microscopic study seems generally recognized. Our own biopsy material was far from ideal with regard to the completeness of the lesions. We more often received small b,its of tissue' than a polyp in its entirety. Seldom did we see a polyp with pedicle intact. Seventy-two biopsy specimens from benign polyps consisted of 1 piece, 21 of 2 or 3 pieces, and 4 had 5 or more fragments. The size of the biopsy specimens from be: nign polyps varied from 1 mm. to 3 cm. Fortyone measured 4 mm. or less, 42 between 5 and 10 mm., and 14 had a diameter of more than 1 cm. Of the 14 polyps with atypia or noninvasive carcinoma, only 2 had a distinct pedicle. Seven specimens consisted of a single piece, 5 of 2 to 4 pieces. The diameter of the biopsy pieces was 4 mm. or less in 5 instances, 5 to 10 mm. in 6 instances, and more than 1 cm. in 3 instances? Of the 19 polyps with focal (intramucosal) carcinoma, only 2 had pedicles. From 1 polyp 3 pieces were obtained for histological study, from 7 polyps 2 pieces, and from the remaining 11 polyps only 1 piece was removed for biopsy. The diameter of the specimens in this, group was 4 mm. or less in 8 instances, between 5 and 10 mm. in 7 instances, and larger than 1 cm. in 4 cases. The largest specimen removed for diagnosis was 5 cm. in diameter. Of the 10 benign villous papillomas, only 1 piece had been removed from each for histological study; the size varied from G to mm. Of the malignant papillomas, we receive& 1 piece from one, 2 from another, while 3 had 3 pieces each removed for histological diagnosis. The size of these specimens varied from 2 mm. to 1.8 cm. Follow-up observations were successful in 90 of our 107 cases (84%). A second specimen was obtained from 37 patients, either as a sec- 620

2 No. 3 How RELIABLE Is BIOPSY OF RECTAL POLYPS? Hellwig 6. Burbosu 621 FIG. 1. Superficial carcinoma in papilloma. Local removal with resulting cure. FIG. 2. Another area of papilloma in Fig. 1. Most of the cells are goblet cells. No evidence of cancer in this. section. FIG. 3. Focal intramucosal carcinoma in centtd portion of papilloma. which is easily missed in superficial biopsy. Local removal of papilloma was ad uate treatment. FIG. 4. Carcinoma in situ. Diagnosed else3ere as adenocarcinoma. No recurrence after polypectomy.

3 FIG. 5. Benign polyp with active proliferation. Diagnosis by other clinic adenocarcinoina. Admitted with request for radical resection. No evidence of cancer. Yrc. 6. Focal carcinoma, Grade 11. in superficial biopsy. The carcinoma is of a higher grade of malignancy and shows the desmoplastic properties stressed by Fisher and Turnbull. There was invasion of the intestinal wall and metastasis in 1 lymph node in the resected specimen. FIG. 7. Invasion of pedicle by adenocarcinoina (Grade 11). Superficial glands have normal epithelium. Resection of rectosiginoid colon. No recurrence. FIG. 8. hlucoid carcinoma in villous papilloma invading intestinal wall.

4 ~ were No. 3 How RELIABLE Is BIOPSY OF RECT AL POLYPS? Hellwig 6. Barbosa 623 ond biopsy or by radical bowel resection. The remaining patients had the polyps removed by electric snare and fulguration of the base. There was complete agreement between biopsy and final diagnosis in 79 of the 90 cases (88%), partial agreement in 7 cases (7.6 %), and dis- 6 agreement in 4 cases (4.4%). Of the 90 patients on whom there was complete follow-up, there were 20 with noninvasive carcinoma who had polypectomy and who did not develop invasive carcinoma.. The results of biopsies in villous papillomas disappointing. In 3 instances, the biopsy specimen showed atypia or carcinoma in situ, - while the examination of the resected specimen revealed carcinoma that had spread to the submucosa. A specimen from one ade-. nomatous polyp was diagnosed as atypia, while a second biopsy and the final specimen showed a highly malignant invasive adenocarcinoma. DISCUSSION Welch et al.11 discussed 3 sources of error of -.- which the pathologist should be aware when examining rectal biopsies. 1. The biopsy specimen submitted to the laboratory may not be representative of the -. lesion. Welch et al. found that in 15 oe 100 consecutive resected cancers of the rectum at Massachusetts General Hospital, the preopera- - tive biopsy had shown a benign lesion. (The difficulty of finding a carcinomatous fociis in villous papillomas in which malig-. nant changes may be present in the central portion of the tumor is well known. We failed to diagnose carcinoma by biopsy in 3 of 5 ma-. lignant papillomas; Scarborough and KleinR missed 10 of 18 malignant papillomas, and 1 Wheat and.4ckerman1 missed the cancerous area in 9 of 35 cases.) 2. Though the biopsy tissue may be obtained from the right area, the microscopic sections may fail to detect the cancerous focus. Therefore, it is imperative to prepare marly microscopic sections from different areas of the specimen Pathologists may disagree in their interpretation of a given specimen. Welch et al.11 recalled a case in which the same microscopic slide of a polyp was sent to 3 eminent pathologists. They received 3 different diagnoses, namely, atypia, cancer in situ, and adenocarcinoma. Ortmayer stated that surgeons are at pres- Frc. 9. Biopsy specimen from part of polyp seen in Fig. 8 showing benign villous papilloma with secretory cells. ent hopelessly confused by what pathologists call metaplastic, atypical, potentially malignant, precancerous, and carcinoma in situ. If one may judge from photomicrographs published in the literature, the criteria of most pathologists regarding cancer in rectal polyps are much too vague to be of practical value to the surgeon. Pseudostratification of nuclei, frequency of mitoses, crowding and elongation of epithelial cells, lack of secretory activity, basophilia, and hyperchromatosis are often wrongly misinterpreted as adenocarcinoma. From the clinical standpoint, only invasion of the submucosa can be accepted as a definite criterion of malignancy to be treated by radical surgery. We agree with Swinton et ai.10 that it is better to request a second biopsy specimen than to make a diagnosis of cancer in a polyp on borderline evidence. SUMMARY AND CONCLUSIONS 1. Atypia, cancer in situ, and intraniucosal focal carcinoma in rectal polyps should not be diagnosed as adenocarcinoma. 2. There are more than 150 cases of non-

5 624 CANCER May-June 1959 VOl. 12 invasive carcinoma in the literature reported cured by simple polypectomy. 3. We followed 20 cases of noninvasive carcinoma after polypectomy; none developed invasive carcinoma. 4. While the pathologist can give a completely valid opinion only if he has the whole tumor available for histological study, he will often receive only small bits of a polyp. Except in cases in which a high grade of malignancy is present, a diagnosis of cancer is not justified when no invasion of the submucosa can be demonstrated. 1. CASTRO, A. F.; AULT, G. W., and SMITH, R. S.: Adenomatous polyps of colon and rectum. Surg. Gynec. 6 ObSf. 92: , FISHER. E. R., and TURNBULL. R. B., JR.: Malignant polyps of rectum and sigmoid; therapy based upon pathologic considerations. Surg. Gynec. 6. Obst. 94: , GORSCH, R. V.: Zn discussion of BINKLEY, G. E., and SUNDERLAND, D. A.: Diagnosis and treatment of papillary adenomas of rectum; and SWINTON, N. W.: Diagnosis and treatment of mucosal polyps of rectum and colon, with early malignant change. Am. J. Surg. 75: , 1948; p HELWIC, F. C.: Role of athologist in diagnosis of polypoid lesions of colon anirectum. Am. J. Surg. 76: , LOCKHART-MUMMERY, H. E., and DUKES, c. E.: Surgical treatment of malignant rectal polyps. Lancet 2: , MCLANAHAN, S.; GROVE, G. P., and KIEFFLR, R. F.. JR.: Conservative surgical management for certain rectal adenomas showing malignant change. J. A. M. A. REFERENCES 5. Biopsy diagnosis of villous papillomas is often unreliable because focal areas of cancer may be present in the center of the lesion, while the peripheral portions are benign. 6. In 4 of our 12 invasive carcinomas, the first biopsy revealed benign or atypical changes, while the second biopsy or the resected specimen showed invasive carcinoma. 7. Small size, or the presence of a pedicle, is no guarantee that a given polyp is benign. Regardless of a clinically benign appearance, every polyp should have an adequate biopsy before it is destroyed by fulguration. 141: , ORTMAYER, M.: Biologic characteristics of nonpalpable, nonsymptomatic, solitary polyps of rectum. J. Nut. Cancer Znst. 7: , SCARBOROUGH, R. A., and KLEIN, R. R.: Polypoid lesions of colon and rectum. Am. J. Surg. 76: , SWINTON, N. W.: Diagnosis and treatment of mucosal polyps of rectum and colon, with early malignant change. Am. J. Surg. 75: , SWINTON, N. W.; HARE, H. F., and MEISSNER, W. A.: Diagnosis of cancer of large bowel. J. A. M. A. 140: , WELCH, C. E.; McK~mrcr. J. B., and BEHRINCER, G.: Polyps of rectum and colon and their relation to cancer. New England J. Mcd. 247: , WHEAT, M. W., JR., and ACKERMAN, L. V.: Villous adenomas of large intestine; clinicopathologic evaluation of 50 cases of villous adenomas with emphasis on treatment. Ann. Surg. 147: , WOMACK, N.: Adenoma of rectum. S. Clin. North America 24:

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