Histoputhologu 1992, 21, 447-451
Benign epithelial neoplasms of the appendix: classification and clinical associations G.R.WILLIAMS, C.E.H.DU BOULAY & W.R.ROCHE Department of Pathology, University of Southampton, Southampton General Hospital, Southampton, UK Date of submission 5 November 1991 Accepted for publication 22 April 1992
WILLIAMS G . R . , DU BOULAY C.E.H. & ROCHE W . R .
(1992) Histopathology 21, 447-451
Benign epithelial neoplasms of the appendix: classification and clinical associations The nomenclature of non-carcinoid epithelial proliferations of the appendix is confused and many of the terms used have no histogenetic basis. A classification based on the well-established diagnostic categories of colonic epithelial polyps has been proposed recently. We have applied this classification to 42 benign epithelial lesions of the appendix in order to determine its suitability for routine diagnostic use, and in order to determine the prognosis of patients with these lesions. All lesions could be classified as either hyperplastic, adenomatous, mixed hyperplastic/adenomatous or dilated appendices. Six cases were associated with a synchronous carcinoma of the colon with all types of appendiceal histology being represented. Follow-up of the remainder of the patients revealed two subsequent colonic carcinomas, at 3 and 6 years post-appendicectomyrespectively. In both of these patients, the appendix had shown adenomatous epithelium. We suggest that adenomas of the appendix may have a similar prognostic significance to adenomas elsewhere in the large bowel. Keywords: appendix, epithelial hyperplasia, adenomas. carcinoma of colon
Introduction The classification of benign non-carcinoid epithelial lesions of the appendix has been recognized as unsatisfactory in practice for some time. Terms in current use, such as mucocoele and mucinous cystadenoma, may be used loosely as macroscopic descriptions without reference to the underlying histology. Williams & Whitehead' recently addressed this problem by suggesting that the nomenclature of epithelial lesions elsewhere in the large bowel be applied to the appendix. Thus, they defined adenomatous, hyperplastic and mixed hyperplastic/adenomatous lesions, and assessed the extent of change as localized or diffuse and the pattern of growth as flat, villous or polypoid. The natural history and prognostic significance of benign appendiceal mucosal lesions is unclear. We have Address for correspondence: Dr G.R.Williams.Department of Pathology, University of Southampton. southampton General Hospital, SouthamptonSO9 4XY. UK.
performed a prospective study of the risk of subsequent carcinoma in patients with appendiceal mucosal lesions in order to investigatethe apparent association of benign appendiceal mucosal lesions with carcinoma of the colon. The proposed classification of epithelial lesions has been applied to these appendices to determine if there are specific risk factors for the development of carcinoma.
Materials and methods All appendices coded as mucocoele, mucinous cystadenoma, cystadenoma, adenoma, hyperplasia, metaplasia and villous adenoma were retrieved from the histopathology 6les at Southampton General Hospital. A total of 48 cases were retrieved over a period of 1 5 years. Haematoxylin and eosin stained longitudinal and transverse sections of each appendix were examined by two pathologists, without the knowledge of the patients' clinical details or the nature of the resection specimen. 447
448 G.R.Williams, C.E.H.du Boulay and W.R.Roche
The mucosa was classified as absent, normal with dilatation or inflammation of the appendix, adenomatous, hyperplastic, and mixed hyperplastic/adenomatous. according to the published criteria’. Hyperplasia (used synonymously with metaplasia) was assessed as elongated, serrated crypts showing an increase in the number of absorptive cells compared with goblet cells. None of the cytological abnormalities associated with dysplasia were present and mitotic activity was confined to the cells in the basal half of the glands. Dysplasia was assessed as cellular crowding and stratication, with a decrease in the number of goblet cells: nuclear enlargement, hyperchromatism and pleomorphism: an increased nuclear to cytoplasmic ratio and mitotic activity involving all levels of the crypts including the epithelial surface. Dysplasia was further graded as mild, moderate or severe according to criteria used for similar lesions in the colon2.A consensus diagnosiswas reached in each case. Follow-up information was obtained from hospital case notes, general practice files and, in one case, a death certiticate. The data collected were sex, age at appendicectomy, mode of presentation, subsequent development of malignancy in the colon and time of last medical contact. These data were then correlated with the histological features of the appendix.
ReSLlltS Forty-eight appendices were recovered from the files. Six of these were devoid of epithelium and were excluded from analysis. Follow-up data were available for 30 patients. Ten patients had been lost to follow-up and two had died at presentation. The follow-up period varied from 4 months to 15 years, with a median duration of follow-up of 5 years. Overall, the mean age at appendicectomy was 58 years and the fema1e:male ratio was 1.33 :1. Six cases (14%)were diagnosed at colectomy for
Age (years) median (range) Sex (male:female) Presentation Acute appendicitis Incidental at laparotomy lass Colectomy Unknown Median follow-up (years) Subsequent carcinoma
carcinoma. The indications for appendicectomy are shown in Table 1. Eighteen appendices were classified as adenomatous (Figure 1). These patients had a median age of 64 years at presentation which was significantly older than the patients with simple dilatation of the appendix (MannWhitney U test, P=0.003). One of these patients had a simultaneous carcinoma of the ascending colon. Macroscopically, 11 of the 18 appendices appeared dilated at Iaparotomy. The degree of dysplasia was assessed as mild in 13 cases and moderate in five. No cases of severe dysplasia were seen. Fourteen patients were followed for a median of 5 years (Table 1). Two patients developed colonic carcinoma: a sigmoid carcinoma 6 years after appendicectomy which revealed a moderately dysplastic adenoma of the appendix and a left-sided colonic carcinoma 3 years after appendicectomy for an adenoma with mild dysplasia. Two of the nine patients with hyperplastic lesions of the appendix (Figure 2) had simultaneous carcinoma, of the ascending and sigmoid colon respectively. Macroscopically, none of the hyperplastic appendices was noted to have been dilated. None of the five patients followed for a range of 4 months to 1 0 years developed carcinoma of the colon. Seven patients were found to have mixed adenomatous/hyperplastic lesions. The median age of 66 years at presentation corresponded to that of patients with adenomatous lesions alone (Table 1). Three of these appendices were thought to be dilated macroscopically. The hyperplastic foci were found at the proximal interface between the normal and adenomatous epithelium. All of the appendices showed only mild dysplasia. Two patients from this group had simultaneous colonic carcinomas, of the ascending and transverse colon respectively. Both these patients had associated multiple adenomatous polyps of the colon. Follow-up for
Adenoma
Hyperplasia
Mixed
64 (43-85) 8: 10
53 (22-77) 4: 5
66 (41-82) 2: 5
8 6 1 2 1 5 2
5 2 0 2
.2 1
5 1
1 2 1 3 0
1 1 0
0
2 0
f i l a ~
4 4 (25-65) 4:4
7.5 0
Table 1. Cllnical details of patients studied
Epithelial tumours of the appendix
449
F l a r e 1. a Low and b high power views of adenomatous appendiceai epithelium showing moderate dysplasia.
a median of 3 years (range 1-12 years) showed no subsequent cases of colonic carcinoma, although one patient was treated for multiple adenomatous and hyperplastic colonic polyps subsequent to appendicectomy. The median age of patients with dilated appendices, with or without acute appendicitis, was significantly less than those patients with hyperplastic and/or neoplastic epithelium (Mann-WhitneyU test, P=O.Ol). One of the eight appendices was removed at colectomy for carcinoma of the sigmoid colon. Four of these appendices appeared dilated at laparotomy. The median follow-up period was 5 years. There were no incidences of subsequent colonic adenomas or carcinoma.
Discussion The major reviews of benign non-carcinoid epithelial all lesions of the appendix over the last 20 years’~~-~ highlight recurrent cliiicopathological problems. First, the terminology leads to confusion. The popular term mucocoele is a macroscopic description rather than a
histopathological diagnosis and its limitations are well recognized. favoured discarding mucocoele, Although Higa et it came to be applied to dilated appendices with normal mucosa, while mucinous cystadenoma was applied to lesions with proliferative changes in the epithelium. The disadvantages of the term cystadenoma are two-fold: 1 the prefix ‘cyst-’ suggests that the appendix must be dilated although, as in our study, many of the appendices appear normal macroscopically: and 2 it does not distinguish between hyperplastic and neoplastic epithelial lesions. A variety of other names have persisted including villous adenoma’, papillary adenoma, adenomatous polyp6 and hyperplastic and metaplastic polyp’. The classification as applied by us in this study is based on the conventional classification of epithelial polyps in the remainder of the large bowell. We have found that this classffication, together with the category of dilated appendix with normal or inflamed mucosa, can be used successfully to classify all such lesions which are encountered in the appendix. These lesions are not common and numbers in our
450 G.R.Williams, C.E.H.du Boulay and W.R.Roche
Figure 1. a Low and b high power views of hyperplastic appendiceal epithelium.
study were limited by the relative infrequency of these lesions in surgical practice. The sex ratio for all types of lesions showed a slight female preponderance, in keeping with previous The average age at appendicectomy was significantly higher for adenomatous, hyperplastic and mixed lesions than for dilated appendices. Although not of statistical significance, the patients with hyperplasia alone tended to be younger than those patients with adenomatous or mixed lesions. There was no clear correlation between the macroscopic appearancesof the appendix and the mucosal histology, stressing the unsatisfactory nature of the descriptive terms used previously. We found that mixed hyperplastic and adenomatous lesions had a characteristic distribution of the mucosal changes with the hyperplasla occurring at the proximal junction of the normal and adenomatous epithelium. This may be akin to the hyperplastic mucosa which sometimes accompanies carcinoma of the or may reflect changes due to a common initiating factor.
Although all previous seriesreported an association of appendiceal epithelial lesions with synchronous carcinoma of the colon, between 12 and 21% of cases presenting at c~lectomy’~~-~, the prognostic significance of an appendiceal epithelial lesion in patients without a synchronous carcinoma has not been previously addressed. In accordance with previous studies, six of our 42 cases (14%)presented at colectomy for carcinoma. The site of the carcinoma was not constant and the right side of the colon was not over-represented, two carcinomas occurring in the ascending colon, one at the hepatic flexure, one in the transverse colon and two in the sigmoid colon. There was no particular association between specific lesions of the appendix and a synchronous carcinoma. In contrast, both of the patients who developed carcinoma of the colon subsequent to appendicectomy had adenomatous lesions of the appendix. Although the numbers are too small for statistical analysis, the incidenceis comparable to that reported in patients with
Epithelial tumours of the appendix
solitary colorectal adenomasloJ1,which rises from 1%at 5 years to 5% at 14years. A possible explanation for this observation is that factors which produce colorectal adenomas, and participate in the adenoma-carcinoma sequence, may also act on the mucosa of the appendix. This is in keeping with the involvement of the appendix in familial adenomatous polyposis’2. The subsequent finding of multiple adenomatous and hyperplastic polyps in the colon of one of our patients, who had a mixed hyperplastic/adenomatous lesion of the appendix at appendicectomy, also supports this hypothesis.
References 1. Williams RA. Whitehead R. Non-carcinoid tumours of the appendix-a proposed classification.Pathology 1986; 18; 50-53. 2. Konishi F, Morson BC. Pathology of colorectal adenomas: a colonoscopic survey. 1. Clfn. Pathol. 1982: 5 0 2601-2608. 3. Higa E, Rosai J, Pizambono CA. Wise L. Mucosal hyperplasia, mucinous cystadenoma and mucinous cystadenocarcinoma of the appendix. A reevaluation of the term ‘mucocoele’. Cancer 1973; 32;1525-1541.
451
4. Wolff M, Ahmed N. Epithelial neoplasm of the vermiform appendix (exclusive of carcinoid). I1 Cystadenomas, papillary adenomas and adenomatous polyps of the appendix. Cancer 1976; 37; 2511-2521. 5. Qiziibash AH. Mucocoeles of the appendix. Their relationship to hyperplasticpolyps, mucinous cystadenomasand cystadenocarcinoma. Arch. Pathol. 1975; 99; 548-555. 6. Aranha GV. Reyes CV.Primary epithelial tumours of the appendix and a reappraisal of the appendiceal ‘mucocoele’. Dis. Colon. Rectum 1979: 22;472-476. 7. Lall KS, Mavrells WP. Villous adenoma of the appendix. Report of a case and a review of the literature. Dis. Colon Rectum 1982; 25; 716-719. 8 . Qizilbash AH. Hyperplastic (metaplastic)polyps of the appendix: report of 19 cases. Arch. Pathol. 1974; 97; 385-388. 9. L a m G. Altavilla G. Cavazzini L, Negrini R. Colonic mucosa adjacent to adenomas and hyperplastic polyps-a morphological and histochemical study. Histopathology 1985; 9:.857-873. 10. Kellokumpu I. Hus A. Colorectal adenomas-morphologic features and the risk of developing metachronous adenomas and carcinomas of the rectum. Scan. I. Gastroenterol. 1987: 22;833841. 11. Morson BC. Bussey HJR.Magnitude of risk for cancer in patients with colorectal adenomas. Br. I. Surg. 1985; 72;S23-28. 12. Bussey HJR. Familial Polyposis coli. Baltimore: Johns Hopkins University Press, 1975.
Benign epithelial neoplasms of the appendix: classification and clinical associations G.R.WILLIAMS, C.E.H.DU BOULAY & W.R.ROCHE Department of Pathology, University of Southampton, Southampton General Hospital, Southampton, UK Date of submission 5 November 1991 Accepted for publication 22 April 1992
WILLIAMS G . R . , DU BOULAY C.E.H. & ROCHE W . R .
(1992) Histopathology 21, 447-451
Benign epithelial neoplasms of the appendix: classification and clinical associations The nomenclature of non-carcinoid epithelial proliferations of the appendix is confused and many of the terms used have no histogenetic basis. A classification based on the well-established diagnostic categories of colonic epithelial polyps has been proposed recently. We have applied this classification to 42 benign epithelial lesions of the appendix in order to determine its suitability for routine diagnostic use, and in order to determine the prognosis of patients with these lesions. All lesions could be classified as either hyperplastic, adenomatous, mixed hyperplastic/adenomatous or dilated appendices. Six cases were associated with a synchronous carcinoma of the colon with all types of appendiceal histology being represented. Follow-up of the remainder of the patients revealed two subsequent colonic carcinomas, at 3 and 6 years post-appendicectomyrespectively. In both of these patients, the appendix had shown adenomatous epithelium. We suggest that adenomas of the appendix may have a similar prognostic significance to adenomas elsewhere in the large bowel. Keywords: appendix, epithelial hyperplasia, adenomas. carcinoma of colon
Introduction The classification of benign non-carcinoid epithelial lesions of the appendix has been recognized as unsatisfactory in practice for some time. Terms in current use, such as mucocoele and mucinous cystadenoma, may be used loosely as macroscopic descriptions without reference to the underlying histology. Williams & Whitehead' recently addressed this problem by suggesting that the nomenclature of epithelial lesions elsewhere in the large bowel be applied to the appendix. Thus, they defined adenomatous, hyperplastic and mixed hyperplastic/adenomatous lesions, and assessed the extent of change as localized or diffuse and the pattern of growth as flat, villous or polypoid. The natural history and prognostic significance of benign appendiceal mucosal lesions is unclear. We have Address for correspondence: Dr G.R.Williams.Department of Pathology, University of Southampton. southampton General Hospital, SouthamptonSO9 4XY. UK.
performed a prospective study of the risk of subsequent carcinoma in patients with appendiceal mucosal lesions in order to investigatethe apparent association of benign appendiceal mucosal lesions with carcinoma of the colon. The proposed classification of epithelial lesions has been applied to these appendices to determine if there are specific risk factors for the development of carcinoma.
Materials and methods All appendices coded as mucocoele, mucinous cystadenoma, cystadenoma, adenoma, hyperplasia, metaplasia and villous adenoma were retrieved from the histopathology 6les at Southampton General Hospital. A total of 48 cases were retrieved over a period of 1 5 years. Haematoxylin and eosin stained longitudinal and transverse sections of each appendix were examined by two pathologists, without the knowledge of the patients' clinical details or the nature of the resection specimen. 447
448 G.R.Williams, C.E.H.du Boulay and W.R.Roche
The mucosa was classified as absent, normal with dilatation or inflammation of the appendix, adenomatous, hyperplastic, and mixed hyperplastic/adenomatous. according to the published criteria’. Hyperplasia (used synonymously with metaplasia) was assessed as elongated, serrated crypts showing an increase in the number of absorptive cells compared with goblet cells. None of the cytological abnormalities associated with dysplasia were present and mitotic activity was confined to the cells in the basal half of the glands. Dysplasia was assessed as cellular crowding and stratication, with a decrease in the number of goblet cells: nuclear enlargement, hyperchromatism and pleomorphism: an increased nuclear to cytoplasmic ratio and mitotic activity involving all levels of the crypts including the epithelial surface. Dysplasia was further graded as mild, moderate or severe according to criteria used for similar lesions in the colon2.A consensus diagnosiswas reached in each case. Follow-up information was obtained from hospital case notes, general practice files and, in one case, a death certiticate. The data collected were sex, age at appendicectomy, mode of presentation, subsequent development of malignancy in the colon and time of last medical contact. These data were then correlated with the histological features of the appendix.
ReSLlltS Forty-eight appendices were recovered from the files. Six of these were devoid of epithelium and were excluded from analysis. Follow-up data were available for 30 patients. Ten patients had been lost to follow-up and two had died at presentation. The follow-up period varied from 4 months to 15 years, with a median duration of follow-up of 5 years. Overall, the mean age at appendicectomy was 58 years and the fema1e:male ratio was 1.33 :1. Six cases (14%)were diagnosed at colectomy for
Age (years) median (range) Sex (male:female) Presentation Acute appendicitis Incidental at laparotomy lass Colectomy Unknown Median follow-up (years) Subsequent carcinoma
carcinoma. The indications for appendicectomy are shown in Table 1. Eighteen appendices were classified as adenomatous (Figure 1). These patients had a median age of 64 years at presentation which was significantly older than the patients with simple dilatation of the appendix (MannWhitney U test, P=0.003). One of these patients had a simultaneous carcinoma of the ascending colon. Macroscopically, 11 of the 18 appendices appeared dilated at Iaparotomy. The degree of dysplasia was assessed as mild in 13 cases and moderate in five. No cases of severe dysplasia were seen. Fourteen patients were followed for a median of 5 years (Table 1). Two patients developed colonic carcinoma: a sigmoid carcinoma 6 years after appendicectomy which revealed a moderately dysplastic adenoma of the appendix and a left-sided colonic carcinoma 3 years after appendicectomy for an adenoma with mild dysplasia. Two of the nine patients with hyperplastic lesions of the appendix (Figure 2) had simultaneous carcinoma, of the ascending and sigmoid colon respectively. Macroscopically, none of the hyperplastic appendices was noted to have been dilated. None of the five patients followed for a range of 4 months to 1 0 years developed carcinoma of the colon. Seven patients were found to have mixed adenomatous/hyperplastic lesions. The median age of 66 years at presentation corresponded to that of patients with adenomatous lesions alone (Table 1). Three of these appendices were thought to be dilated macroscopically. The hyperplastic foci were found at the proximal interface between the normal and adenomatous epithelium. All of the appendices showed only mild dysplasia. Two patients from this group had simultaneous colonic carcinomas, of the ascending and transverse colon respectively. Both these patients had associated multiple adenomatous polyps of the colon. Follow-up for
Adenoma
Hyperplasia
Mixed
64 (43-85) 8: 10
53 (22-77) 4: 5
66 (41-82) 2: 5
8 6 1 2 1 5 2
5 2 0 2
.2 1
5 1
1 2 1 3 0
1 1 0
0
2 0
f i l a ~
4 4 (25-65) 4:4
7.5 0
Table 1. Cllnical details of patients studied
Epithelial tumours of the appendix
449
F l a r e 1. a Low and b high power views of adenomatous appendiceai epithelium showing moderate dysplasia.
a median of 3 years (range 1-12 years) showed no subsequent cases of colonic carcinoma, although one patient was treated for multiple adenomatous and hyperplastic colonic polyps subsequent to appendicectomy. The median age of patients with dilated appendices, with or without acute appendicitis, was significantly less than those patients with hyperplastic and/or neoplastic epithelium (Mann-WhitneyU test, P=O.Ol). One of the eight appendices was removed at colectomy for carcinoma of the sigmoid colon. Four of these appendices appeared dilated at laparotomy. The median follow-up period was 5 years. There were no incidences of subsequent colonic adenomas or carcinoma.
Discussion The major reviews of benign non-carcinoid epithelial all lesions of the appendix over the last 20 years’~~-~ highlight recurrent cliiicopathological problems. First, the terminology leads to confusion. The popular term mucocoele is a macroscopic description rather than a
histopathological diagnosis and its limitations are well recognized. favoured discarding mucocoele, Although Higa et it came to be applied to dilated appendices with normal mucosa, while mucinous cystadenoma was applied to lesions with proliferative changes in the epithelium. The disadvantages of the term cystadenoma are two-fold: 1 the prefix ‘cyst-’ suggests that the appendix must be dilated although, as in our study, many of the appendices appear normal macroscopically: and 2 it does not distinguish between hyperplastic and neoplastic epithelial lesions. A variety of other names have persisted including villous adenoma’, papillary adenoma, adenomatous polyp6 and hyperplastic and metaplastic polyp’. The classification as applied by us in this study is based on the conventional classification of epithelial polyps in the remainder of the large bowell. We have found that this classffication, together with the category of dilated appendix with normal or inflamed mucosa, can be used successfully to classify all such lesions which are encountered in the appendix. These lesions are not common and numbers in our
450 G.R.Williams, C.E.H.du Boulay and W.R.Roche
Figure 1. a Low and b high power views of hyperplastic appendiceal epithelium.
study were limited by the relative infrequency of these lesions in surgical practice. The sex ratio for all types of lesions showed a slight female preponderance, in keeping with previous The average age at appendicectomy was significantly higher for adenomatous, hyperplastic and mixed lesions than for dilated appendices. Although not of statistical significance, the patients with hyperplasia alone tended to be younger than those patients with adenomatous or mixed lesions. There was no clear correlation between the macroscopic appearancesof the appendix and the mucosal histology, stressing the unsatisfactory nature of the descriptive terms used previously. We found that mixed hyperplastic and adenomatous lesions had a characteristic distribution of the mucosal changes with the hyperplasla occurring at the proximal junction of the normal and adenomatous epithelium. This may be akin to the hyperplastic mucosa which sometimes accompanies carcinoma of the or may reflect changes due to a common initiating factor.
Although all previous seriesreported an association of appendiceal epithelial lesions with synchronous carcinoma of the colon, between 12 and 21% of cases presenting at c~lectomy’~~-~, the prognostic significance of an appendiceal epithelial lesion in patients without a synchronous carcinoma has not been previously addressed. In accordance with previous studies, six of our 42 cases (14%)presented at colectomy for carcinoma. The site of the carcinoma was not constant and the right side of the colon was not over-represented, two carcinomas occurring in the ascending colon, one at the hepatic flexure, one in the transverse colon and two in the sigmoid colon. There was no particular association between specific lesions of the appendix and a synchronous carcinoma. In contrast, both of the patients who developed carcinoma of the colon subsequent to appendicectomy had adenomatous lesions of the appendix. Although the numbers are too small for statistical analysis, the incidenceis comparable to that reported in patients with
Epithelial tumours of the appendix
solitary colorectal adenomasloJ1,which rises from 1%at 5 years to 5% at 14years. A possible explanation for this observation is that factors which produce colorectal adenomas, and participate in the adenoma-carcinoma sequence, may also act on the mucosa of the appendix. This is in keeping with the involvement of the appendix in familial adenomatous polyposis’2. The subsequent finding of multiple adenomatous and hyperplastic polyps in the colon of one of our patients, who had a mixed hyperplastic/adenomatous lesion of the appendix at appendicectomy, also supports this hypothesis.
References 1. Williams RA. Whitehead R. Non-carcinoid tumours of the appendix-a proposed classification.Pathology 1986; 18; 50-53. 2. Konishi F, Morson BC. Pathology of colorectal adenomas: a colonoscopic survey. 1. Clfn. Pathol. 1982: 5 0 2601-2608. 3. Higa E, Rosai J, Pizambono CA. Wise L. Mucosal hyperplasia, mucinous cystadenoma and mucinous cystadenocarcinoma of the appendix. A reevaluation of the term ‘mucocoele’. Cancer 1973; 32;1525-1541.
451
4. Wolff M, Ahmed N. Epithelial neoplasm of the vermiform appendix (exclusive of carcinoid). I1 Cystadenomas, papillary adenomas and adenomatous polyps of the appendix. Cancer 1976; 37; 2511-2521. 5. Qiziibash AH. Mucocoeles of the appendix. Their relationship to hyperplasticpolyps, mucinous cystadenomasand cystadenocarcinoma. Arch. Pathol. 1975; 99; 548-555. 6. Aranha GV. Reyes CV.Primary epithelial tumours of the appendix and a reappraisal of the appendiceal ‘mucocoele’. Dis. Colon. Rectum 1979: 22;472-476. 7. Lall KS, Mavrells WP. Villous adenoma of the appendix. Report of a case and a review of the literature. Dis. Colon Rectum 1982; 25; 716-719. 8 . Qizilbash AH. Hyperplastic (metaplastic)polyps of the appendix: report of 19 cases. Arch. Pathol. 1974; 97; 385-388. 9. L a m G. Altavilla G. Cavazzini L, Negrini R. Colonic mucosa adjacent to adenomas and hyperplastic polyps-a morphological and histochemical study. Histopathology 1985; 9:.857-873. 10. Kellokumpu I. Hus A. Colorectal adenomas-morphologic features and the risk of developing metachronous adenomas and carcinomas of the rectum. Scan. I. Gastroenterol. 1987: 22;833841. 11. Morson BC. Bussey HJR.Magnitude of risk for cancer in patients with colorectal adenomas. Br. I. Surg. 1985; 72;S23-28. 12. Bussey HJR. Familial Polyposis coli. Baltimore: Johns Hopkins University Press, 1975.
