Anorectal malignant melanoma has a poor prognosis

Int J Colorect Dis (1993) 8:81-86

Colbi e/al Disease 9 Springer-Verlag 1993

Anorectal malignant melanoma has a poor prognosis P. M. Antoniuk 1, j. j. Tjandra 1, B. W. Webb 2, R. E. Petras 2, j. W. Milsom 1, V. W. Fazio i 1 Department of Colorectal Surgery, Cleveland Clinic Foundation, Cleveland, Ohio, USA 2 Department of Pathology, Cleveland Clinic Foundation, Cleveland, Ohio, USA Received: 30 November 1992; accepted: 10 February 1993

Abstract. Clinicopathologic features and surgical treatment of 15 patients with primary anorectal malignant melanoma were studied retrospectively. There was a female preponderance (2:1). The median age was 66 years. C o m m o n initial symptoms were rectal bleeding (87%) and/or anal pain (33%); 25% of the melanomas were amelanotic. The maximum tumor size ranged between 0.8 and 8.4 cm (median 3.0 cm). Of the tumors evaluated histologically (n = 12), tumor thickness ranged from 0.9 to 11.3 mm (median 6.1 mm). All melanomas invaded at least into the subepithelial tissue (n = 8) and/or the submucosa of the distal rectum (n = 4), with extension into the internal anal sphincter (n = 5) and lamina propria (n = 3). Endoluminal ultrasound accurately demonstrated depth of invasion in 3 of 3 patients. Three (20%) patients with distant metastases at initial presentation had a mean survival of 8 mo; one of these primary melanomas measured 0.8 cm. Of 12 patients undergoing "curative" treatments - - 4 by abdominoperineal resection (APR) and 8 by local excision (LE), the incidence of loco-regional recurrence was similar (2/4 and 5/8). All these 7 patients with loco-regional recurrence developed distant metastases within 3 months. The mean survival was similar between A P R and LE in the total g r o u p (25 mo vs 20 mo), in the decreased (27 mo vs 24 mo) and in those treated with a curative intent (29 mo vs 22 too). There was no long-term survivor but four patients remained tumor-free up to 19 mo after A P R (n = 1) or LE (n = 3). Thus anorectal melanoma has a poor prognosis and, when technically feasible, LE appears to have similar results as APR. R6sum6. Les aspects clinico-pathologiques et le traitement chirurgical de 15 malades pr6sentant un m61anome malin primitif ano-rectal ont 6t6 6tudi6s r6trospectivement. I1 y avait une pr6pond6rance f6minine (2:1). L'fige moyen 6tait de 66 ans. Le premier symptome commun 6tait une rectorragie (87%) et ou une douleur anale (33 %); 25 % de ces m61anomes 6taient achromiques. Le diam~tre maximal de la tumeur 6tait compris entre 0,8 et 8,4 cm (m6diane 3,0 cm). Sur les tumeurs examin6es histologiquement (n = 12), l'6paisseur de la tumeur 6tait comprise entre 0,9 et 11 mm (moyenne 6,1 mm). Tous ces

m61anomes envahissaient au moins le tissu sub-6pith61iai (n = 8) et/ou la sous muqueuse du rectum distal (n = 4), avec une extension dans le sphincter anal interne (n = 5) ou la lamina propria (n = 3). L'6chographie endorectale a montr6 de faqon precise la profondeur de l'invasion chez 3 patients sur 3. Trois patients (20%), avec des m6tastases/t distance lors de l'examen initial, ont eu une moyenne de survie de 8 mois. L'un de ces m61anomes primaires mesurait 0,8 cm. Sur les 12 patients ayant eu un traitement "curatif" - 4 amputations abdomino-p6rin6ales (AAP) et 8 excisions locales (LE) - l'incidence de r6cidive loco-r6gionale fut similaire (2/4 et 5/8). Tousles 7 patients avec une r@idive loco-r6gionale ont d6velopp6 des m~tastases/t distance dans les 3 mois. La moyenne de survie 6tait similaire apr6s AAP ou LE dans le groupe total (25 mois versus 20 mois), chez les malades d~c6d6s (27 mois versus 24 mois), et chez ceux trait6s avec une intention curative (29 mois versus 22 mois). I1 n'y a pas eu de survie /t long terme mais 4 patients demeurent indemmes de r6cidive jusqu'fi 19 mois apr6s AAP (n = 1) ou LE (n = 3). Ainsi le m61anome ano-rectal a un pronostic d6favorable et, lorsque cela est techniquement possible, l'excision locale semble avoir des r6sultats similaires fi l'amputation abdomino-p6rin6ales.

Primary malignant melanoma of the anorectum is rare, comprising less than 1% o f all malignancies at this site [1-3] and accounts for approximately 1% o f all primary melanomas [4]. Since the initial report by Moore [5] in 1857, approximately 500 cases have been reported. Most have appeared as case reports or small series with only a few reports of more than a dozen patients [3, 6-9]. Although the data on anorectal malignant melanoma are sparse, it appears to have a different biological behavior from that of cutaneous melanoma. Although anorectal melanomas are often large, nodular masses at presentation [8], the diagnosis is often delayed [2, 10]. The prognosis in most reports is dismal, with only about 10% of patients surviving beyond 5 years [l, 3, 8, 11, 12]. There is considerable controversy regarding the optimal surgical treatment. Recommended procedures range from

82 posterior pelvic exenteration with concomitant l y m p h a d e n e c t o m y [1, 13], to a b d o m i n o p e r i n e a l r e s e c t i o n [14] to wide local excision [15]. Because o f the p o o r p r o g nosis, i n c r e a s i n g l y there is a swing t o w a r d s p e r f o r m i n g m o r e c o n s e r v a t i v e s u r g e r y [3, 15]. T h e a i m o f this s t u d y was to review o u r experience w i t h a n o r e c t a l m e l a n o m a , e x a m i n i n g clinical a n d histologic features, surgical t r e a t m e n t a n d o u t c o m e .

Patients and methods A review of the surgical pathology records of the Cleveland Clinic Foundation from 1951 through 1991 yielded 15 patients diagnosed with primary malignant melanoma of the anorectum who have undergone surgical treatment at this institution. Melanomas of the perianal skin and lesions regarded as metastases were excluded. There were 10 women and 5 men. The median age was 66 years, with a range of 38 to 81 years. All clinical data were retrieved retrospectively from clinical records and by personal interviews of surviving patients. Chest X-rays, liver scans and CT scans of the abdomen and pelvis were reviewed. The location of the melanoma in relation to the dentate line and the maximum size of the tumor were noted. Endoluminal ultrasound was performed in 3 patients using a Bruel & Kjaer (Naerum, Denmark) scanner, type 1846, with a rotating hand-held endoprobe (type 1850) equipped with a 7-MHz (focal zone, 2 - 5 cm) or 10-MHz (focal zone, 1-4cm) transducer. The techniques of endoluminal ultrasound have been previously described [16]. All ultrasonic studies were performed by the same two investigators (JJT, JWM). The TNM staging system was used in ultrasonic evaluation. Surgical treatment was assumed to be curative if the operation was designed to completely excise the lesion and the surgical margins were free of neoplasm. The techniques of abdominoperineal resection (APR) and wide local excision (LE) have been described in detail elsewhere [17, 18]. Survival time was measured from the date of surgery to either the date of the last follow-up or death. All available pathologic material from 12 patients were reviewed by two gastrointestinal pathologists (BW & REP). The type of epithelium associated with each melanoma was classified as colonic, transitional or non-keratinizing squamous. The presence or absence of junctional activity, defined by the presence of atypical melanocytes within adjacent or overlying mucosal epithelium [19], was noted. Other histologic features observed included morphologic cell type(s), pigmentation, mitotic activity, lymphocytic infiltration, tumor thickness and the deepest extent of invasion. Cell types included polygonal, spindled, small cell and giant multinucleated cell types, as previously described [10, 19, 20]. Mitotic activity was estimated by counting mitotic figures at a magnification of 400X in 10 microscopic fields (total area examined= 1.9 mm2). The degree of lymphocytic response in the form of tumor infiltrating lymphocytes (TILs) was graded as brisk, non-brisk, or absent using the criteria of Clark, et al. [21]. Using the Vernier method [22], maximum tumor thickness was determined from well oriented sections by measuring vertically from the surface of the mucosa or from the base of an ulcer to the deepest extent of invasion [19].

Fig. 1. Endoluminal ultrasound showing a melanoma (T) invading the subepithelial tissue of the anal canal without involvement of the internal sphincter (I). This finding was confirmed by histologic examination

Table 1. Clinical presentations Patient No. (%)

Symptoms Rectal bleeding Anal pain Rectal mass Distant metastases Change in bowel habits Incidental

13 (87) 5 (33) 3 (20) 3 (20) 1 (7) 1 (7)

Tumor site At or above dentate line Below dentate line

7 (47) 8 (53)

a g n o s i s o f m e l a n o m a was initially missed in 11 ( 7 3 % ) p a t i e n t s . T h e m o s t c o m m o n m i s d i a g n o s i s was h e m o r r h o i d s (n = 7) b u t o t h e r s i n c l u d e d p o l y p (n = 1), a n a l fissure ( n = l ) a n d rectal c a r c i n o m a ( n = 2 ) . N o n e o f the patients had cutaneous malignant melanoma. A l l t u m o r s were p a l p a b l e o n digital rectal e x a m i n a t i o n a n d were n e a r l y evenly d i s t r i b u t e d a b o v e a n d b e l o w the d e n t a t e line. T h e m a x i m u m t u m o r size r a n g e d f r o m 0.8 to 8.4 c m ( m e d i a n 3.0 cm). E n d o l u m i n a l u l t r a s o u n d was p e r f o r m e d in 3 p a t i e n t s a n d the d e p t h o f i n v a s i o n (Fig. 1) correlated exactly with subsequent histologic examinat i o n in e a c h case.

Results

Clinical Presentation (Table 1)

Surgical Treatment

T h e m e d i a n d u r a t i o n o f s y m p t o m s was 6 m o n t h s (range, 0 . 5 - 1 8 m o n t h s ) . O n e ( 7 % ) p a t i e n t was a s y m p t o m a t i c a n d d i a g n o s e d o n surveillance c o l o n o s c o p y . T h e c o m m o n e s t initial s y m p t o m was rectal bleeding. T h r e e ( 2 0 % ) p a t i e n t s h a d evidence o f d i s t a n t m e t a s t a s e s at initial pres e n t a t i o n , i n v o l v i n g i n g u i n a l l y m p h n o d e s (n = 3), liver (n = 2), b r a i n (n = 1) a n d j e j u n u m (n = 1). T h e clinical di-

Surgical t r e a t m e n t was i n d i v i d u a l i z e d b a s e d on the p a tient's desires a n d the p h y s i c i a n ' s a s s e s s m e n t (Table 2). P r o p h y l a c t i c i n g u i n a l l y m p h n o d e d i s s e c t i o n was n o t u s e d in a n y cases. F i v e ( 3 3 % ) p a t i e n t s were t r e a t e d b y A P R ; o f these, one p a t i e n t h a d u n d e r g o n e i n c o m p l e t e L E w i t h i n the p r e c e d i n g m o n t h . T h e r e m a i n i n g 10 ( 6 7 % ) p a t i e n t s u n d e r w e n t t r a n s a n a l LE; m a r g i n o f excision was

83 Table 2. Clinical course of 15 patients with anorectal melanoma Patient"

Tumor Size b ( + mesorectal lymph nodes ~)

Disease-Free Interval (Initial Sites of Recurrence)

Status

Survival d

19 mo 5 mo (pelvis) 9 mo (pelvis) 45 mo (lung) Brain mets at presentation (pelvis)

NED Deceased Deceased Deceased Deceased

19 11 15 72 8

mo mo mo mo mo

7 mo 6 mo 11 mo 3 mo (inguinal LN) 6 mo (inguinal LN) 1 mo (local, pelvis) 2 mo (inguinal LN) 53 mo (local, pelvis) Liver mets at presentation (pelvis) Diffuse mets at presentation

NED NED NED Deceased Deceased Deceased Deceased Deceased Deceased Deceased

7 6 11 21 31 7 13 82 7 10

mo mo mo mo mo mo mo mo mo mo

A P R Group ~

1 2 3 4 5

4.0 2.0 2.5 5.0 8.4

cm cm cm cm cm

2.5 4.3 2.3 2.0 3.0 3.0 4.0 1.5 5.0 0.8

cm cm cm cm cm cm cm cm cm cm

(0/15) (11/23) (6/7) (0/5) (8/13)

L E Group

6 7 8 9 10 11 12 13 14 15

a Patient number corresponds to Case number in Table 3 b Maximal tumor size as measured by surgeon and/or pathologist Expressed as the number of involved over the total number of lymph nodes retrieved

d From the date of surgery to the date of last follow up or death e Abbreviations: APR, abdominoperineal resection; mo, months; NED, no evidence of disease (tumor); mets, metastases; LE, local excision; LN, lymph nodes

Fig. 2 A - D . Characteristic histologic appearances of malignant melanoma. A Typical polygonal or epithelioid cells, with large vesicular nuclei and macronucleoli, exhibiting a "nesting" pattern of growth. B Spindled cells arranged in compact fasicles with a stori-

form pattern. C Smaller cells with hyperchromatic and angulated nuclei similar to those of a small cell carcinoma, admixed with typical polygonal melanoma cells. D Giant multinucleated cell with large nucleolated nuclei

84 Table 3. Histologic features Case

Status

Tumor thickness

Adjacent Junctional e p i t h e l i u m activity

Extent of invasion

Cell type

Pigmentation

M i t o s e s / TILs ~ 10 hpf

1

NED a

2.8 mm

colonic

absent

submueosa b

polygonal, small cell

absent

31

absent

2

deceased

4.7 mm

colonic, transitional

present

internal sphincter

polygonal, giant cell

moderate

11

brisk

3

deceased

5.3 mm

colonic, transitional

present

submucosa

polygonal

marked

4

deceased 11.2 mm

colonic, transitional

absent

submucosa

polygonal

slight

50

absent

5

deceased

colonic, transitional squamous

absent

internal sphincter

polygonal, spindled

marked

28

absent

6

NED

7

NED

5.75 mm

colonic, transitional

present

internal sphincter b

polygonal

marked

21

brisk

8

NED

8.6 mm

squamous

present

subepithelial tissue b

polygonal, spindled

moderate

9

absent

9

deceased

4.5 mm'

squamous

present

subepithelial tissue

polygonal

moderate

36

absent

7.0 mm

4

non-brisk

not available

10

deceased not available

11

deceased

8.6 mm

colonic, transitional

absent

internal sphincter

polygonal, small cell

absent

50

non-brisk

12

deceased

6.5 mm

squamous

absent

internal sphincter

polygonal, spindled

slight

31

absent

13

deceased 11.3 mm

colonic

absent

submucosa

polygonal, spindled

slight

4

absent

14

deceased not available

15

deceased

squamous

absent

subepithelial polygonal, tissue giant cell

absent

46

absent

0.9 mm

" NED, no evidence of disease; TIL; Tumor infiltrating lymphocytes Case number corresponds to Patient number in Table 2 not clear in the two patients who had diffuse metastases at presentation. Three patients received adjuvant chemotherapy: two of these patients also received adjuvant radiation therapy to the pelvis.

Histologic Features of the Primary Lesion The pertinent histologic findings o f the twelve cases available for study are presented in Table 3. Tumor thickness ranged from 0.9 to 11.3 m m (median 6.1 mm). Non-keratinizing squamous mucosa alone was identified adjacent to 4 tumors. Colonic type epithelium alone was found adjacent to 2 tumors. O f the remaining six cases, both colonic and transitional types of mucosa were found adjacent to 5 tumors, and 1 tumor was associated with a combination of all three types o f mucosa. Junctional activity was observed in the non-keratinizing squamous mucosa overlying two melanomas and in the transitional type Of epithelium adjacent to 3 others for a total o f 5 cases (42%). Ulceration of the overlying surface mucosa was observed in 9 of 12 cases (75%). Invasion of the subepithelial connective tissue beneath the squamous mucosa was seen in 8 cases, with extension into the smooth muscle of the internal sphincter in 5 cases. Four

b Had endoluminal ultrasound melanomas involved the submucosa of the distal rectum, with extension into the lamina propria in 3 cases. All tumors exhibited characteristic polygonal or epithelioid cells with distinct cell borders, abundant cytoplasm, and pleomorphic nuclei with eosinophilic macronucleoli (Fig. 2A). A nesting growth pattern was seen in seven cases. F o u r cases had a prominent spindle cell component (Fig. 2 B), two cases exhibited cells similar to those of a small cell carcinoma (Fig. 2 C), and two cases contained small populations of giant multinucleated tumor cells (Fig. 2 D), similar to those described by Kantarovsky, et al. [20]. Nine of twelve tumors contained melanin pigment microscopically, with varying degrees of pigmentation frequently present within the same melanoma. Mitotic rates were variable, ranging from 4 to 50 mitotic figures (median 29) per 10 high power fields. Tumor infiltrating lymphocytes were observed in four cases, with only two exhibiting the brisk activity reported to be prognostically favorable by Clark, et al. [21].

Clinical Course The results of patients undergoing different surgical treatments ( A P R vs LE) are shown in Tables 2 and 4.

85 Table 4. Survival data

Survival" - mean (range)

APR b

LE b

Total

Deceased

"Curative" Treatment

n=5 25 mo (8-72 too) n=10 20 mo (6-82 mo)

n=4 27 mo (8-72 too) n=7 24 mo (7-82 mo)

n=4 29 mo (11-72 mo) n=8 22 mo (6-82 too)

" Measured from the date of surgery to the date of the last follow up or death b A b b r e v i a t i o n s : APR, abdominoperineal resection; n, number of patients; mo, months; LE, local excision

Although this is not a randomized study, the tumors in the two groups were similar. All three patients who had distant metastases at initial presentation died within 7 to 10 months (mean survival 8 months), following APR (n = 1) and LE (n = 2). Despite widespread metastases, the size of the primary melanoma of one of these patients measured only 0.8 cm. Twelve patients underwent "curative" treatment - four by APR and eight by LE (Table 2). Of these patients, the incidence of loco-regional recurrence was similar between APR (2/4) and LE (5/8). All seven patients with loco-regional recurrence developed metastases within three months. Overall, 11 (73%) patients died from distant metastases; of these, only six were symptomatic from loco-regional recurrence. The mean survival was similar between A P R and LE in the total group, in the deceased and in those treated with a "curative" intent (Table 4). Only 1 patient in each group (APR vs LE) lived beyond 5 years and they both died 6 to 7 years after surgery from disseminated melanoma. Of those (n -- 8) who succumbed after "curative" surgery, the mean (range) disease-free interval in patients after A P R and LE was /9 months (5 to 45 months) and 14 months (1 to 53 months) respectively. Known metastatic sites at the time of death included liver (n=3), lung ( n = l ) , brain (n=2), bone ( n = l ) , pelvis (n = 5) and inguinal lymph nodes (n = 3). Three o f 9 patients with recurrent or metastatic disease were treated with chemotherapy. In the 6 remaining patients, no further anticancer treatment was given because of the diffuse nature of the metastases. The mean duration from disease recurrence to death was 16 months (6 to 27 months). Four patients remain tumor-free by clinical examination (n=4), CT scan of abdomen and pelvis (n = 1) and intra-rectal ultrasound (n = 3). However, the duration of follow-up for these patients ranges from 6 to 19 months.

Discussion

Malignant melanoma of the anorectum arises from the melanocytes found in either the mucosa of the anal transitional zone above the dentate line, or the non-keratiniz-

ing squamous mucosa below the dentate line [23]. Rare cases may arise from melanocytes reportedly found in true rectal mucosa [24] but this was not observed in any of our patients. The prognosis of malignant melanoma of the anorecrum is clearly dismal. There was no survival beyond 7 years in this study. Of the 500 cases reported in the literature, probably no more than a dozen have survived more than 10 years [10, 20, 25, 26]. These long-term survivors were equally divided between those undergoing A P R and LE. Primary malignant melanoma of the anorectum appears to have a poorer prognosis than cutaneous melanoma. This may be due to delays in diagnosis. Even large anorectal melanomas can be relatively symptom-free and it is c o m m o n to mistake symptomatic anorectal melanomas clinically for such benign conditions as hemorrhoids or adenomas. Furthermore, primary anorectal melanomas frequently lack pigmentation (25% of cases in our study). Delayed diagnosis could result in the larger (median size 3 cm in our patients) and thicker (median thickness 6.1 mm) tumors seen in anorectal melanomas compared to cutaneous melanomas. In addition to large size and delayed diagnosis, certain site-specific characteristics of the anal canal may contribute to the poor prognosis. These include the rich vascular and lymphatic network found in the anorectal mucosa which could facilitate metastatic spread and the susceptibility to trauma and ulceration seen with most lesions involving the anal canal. Ulceration is a recognized poor prognostic factor in cutaneous melanoma [11]. Furthermore, anorectal melanoma may possibly be biologically more agggressive, with a naturally faster growth rate than cutaneous melanoma. There may also be an innate resistance to the host immune response as seen in the lack of lymphocytic response in the form of TILs in most of our cases. The highly malignant nature of anorectal melanoma was manifested in the frequency of distant metastases and loco-regional recurrence. Patients with small [26] and thin [8, 27-31] melanomas seem to be the only ones with any expectation of prolonged survival. However, other series [12, 20] as well as our data have shown exceptions to these generalizations. In contrast to cutaneous melanomas, the relationship of tumor thickness to the presence and extent of nodal metastases in anorectal melanoma is not clear [8], but almost all anorectal melanomas are thicker than 1.7mm, a thickness known to be associated with poor prognosis. Clinical assessment of tumor size and thickness appears unreliable. Furthermore, the poor prognosis in apparently low stage tumors could be due to missed systemic or regional metastases. Most studies have been retrospective in nature and few have been able to utilize recent, more sensitive imaging tools such as CT scan and endoluminal ultrasound. Endoluminal ultrasound has been shown to provide simple and accurate assessment of the depth of tumor invasion, and may allow direct biopsy of pararectal lymph nodes [32]. Together with CT scan, endoluminal ultrasound may further identify a group of patients with localized disease and thus a more favorable prognosis, although few patients will fall in this category.

86 In this s t u d y , the incidence o f d i s t a n t m e t a s t a s e s a n d l o c o - r e g i o n a l r e c u r r e n c e were s i m i l a r l y high after A P R a n d LE. T h e disease-free i n t e r v a l a n d survival are also s i m i l a r l y p o o r b e t w e e n the two g r o u p s . T h e f o l l o w - u p o f o u r 4 ( 2 5 % ) s u r v i v o r s is t o o s h o r t for a n y m e a n i n g f u l assessment. T h u s A P R d o e s n o t a p p e a r to c o n f e r a n y benefit o v e r L E in t e r m s o f local c o n t r o l o r survival. These results a r e in a c c o r d a n c e with several r e p o r t s [3, 19, 33, 34] b u t are in c o n t r a s t to o t h e r s [8, 12, 35, 36] w h i c h h a v e r e p o r t e d h i g h e r local r e c u r r e n c e rates after L E w h e n c o m p a r e d with A P R . T h e r e a s o n for these d i s c r e p a n c i e s are n o t clear. H o w e v e r , A P R is often i n d i c a t e d for technical r e a s o n s b e c a u s e o f the large size o f the t u m o r o r the p r e s e n c e o f l y m p h n o d e m e t a s t a s e s in the pelvis. E n d o l u m i n a l u l t r a s o u n d m a y be a v a l u a b l e a d j u n c t in this assessm e n t b y p r o v i d i n g i n f o r m a t i o n on the e x t e n t o f t u m o r i n v a s i o n a n d the status o r r e g i o n a l l y m p h nodes. It is also p o s s i b l e t h a t m a l i g n a n t m e l a n o m a is o f t e n a systemic disease at the t i m e o f clinical d e t e c t i o n , w h i c h m a y a c c o u n t for the h i g h m o r t a l i t y rates c o m m o n l y rep o r t e d [1 - 1 2 ] . F o r e x a m p l e , the p a t i e n t w i t h the smallest (0.8 cm) a n d t h i n n e s t (0.9 ram) a n o r e c t a l m e l a n o m a in o u r series h a d extensive liver m e t a s t a s e s a t initial p r e s e n t a t i o n . Still, this n e o p l a s m e x h i b i t e d one o f the h i g h e s t m i t o t i c rates in o u r study, a n d l a c k e d a n y l y m p h o c y t i c r e s p o n s e in the f o r m o f T I L s . H o w e v e r , t h e r e is n o effective systemic t h e r a p y to d a t e a n d m a l i g n a n t m e l a n o m a is n o t very r a d i o s e n s i t i v e . F o r the present, o p t i m u m p r i m a r y c a r e r e q u i r e s i n d i v i d u a l i z e d j u d g e m e n t a n d m o s t surgical t r e a t m e n t s s h o u l d be r e g a r d e d as palliative. I n o u r experience, wide local excision w i t h clear m a r g i n s a p p e a r s to p r o v i d e local c o n t r o l c o m p a r a b l e to A P R .

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