Malignant Melanoma of the Rectal Ampulla: R e p o r t of a C a s e a n d R e v i e w o f t h e L i t e r a t u r e * RICHARD M . ALEXANDER, M.D., t LA~VRENCE A . CONE, M.D. S From the Eisenhower Medical Center, Palm Desert, California
necessitating anticoagulation. T h e search for a p r i m a r y m e l a n o m a was delayed, b u t u l t i m a t e l y a survey of the gastrointestinal tract disclosed a 3.5 • 4.0 cm polypoid t u m o r , 10 c m above the crypt level of t h e anal canal. Histologic e x a m i n a t i o n of the biopsy specimen confirmed t h e suspected diagnosis of a melanotic m e l a n o m a (Fig. 2). T h e rect u m a n d sigmoid colon were resected a n d colostomy performed. T h e residual rectal s e g m e n t was left in place. P a t h o l o # c review of the specimen disclosed p e n e t r a t i o n of t h e lesion t h r o u g h the m n s cularis a n d no l y m p h - n o d e metastases. I m m u n o therapy with BCG {bacillus Calmette-Guel-in) h a d been initiated prior to the snrgical procedure a n d was continued. A p u l m o n a r y infarction occurred i n c l u d i n g computerized axial tomog-raphy scan, shortly after operation, h u t the p a t i e n t otherwise r e m a i n e d welt for a n a d d i t i o n a l three m o n t h s , u n t i l right h e m i p l e g i a a n d a p h a s i a a n d neurologic findings consistent with recurrence of the cerebral lesion s u d d e n l y developed. C o m b i n a t i o n chemotherapy with C C N U (1-[2-chloroethyl]-3-cyclohexyl1-nitrosurea) a n d D T I C (5-[3,3 dimethyl-l-triazene] imidazole-4-carboxamide) was instituted, with imp r o v e m e n t of the patient's condition, only m i n i m a l right-sided weakness r e m a i n i n g . A year after t h e onset of his illness, in N o v e m b e r 1975, n u m b n e s s of
T H E INFREQUENT OCCURRENCE o f m a l i g n a n t
m e l a n o m a of the anus and rectum has been well established. A p p r o x i m a t e l y 180 cases have been r e p o r t e d since the first description of its occurrence in man by Moore in 1857.16 Of these, 16 cases have involved the rectal a m p u l l a or rectosigmoid colon without evidence of a melanotic lesion of the anus or anal canal ( T a b l e 1)Y T h e 16 patients were 11 men and five women. T i l e lesion was most often discovered when the patients were between 50 and 65 years of age. Five patients were less than 50 years old. Distances of the lesion from the anus ranged from 3 to 15 cm. A l t h o u g h the m e a s u r e m e n t in each case might be questioned for accuracy, there is no d o u b t that none of the lesions involved the a n o d e r m or anal canal. T h i s p a p e r has been p r e p a r e d to document the seventeenth known p r i m a r y occurrence of a m a l i g n a n t m e l a n o m a above the anal canal.
TABLE 1.
Reference
Report of a Case A 56-year-old white m a n h a d enjoyed good h e a l t h u n t i l the s u d d e n onset of slurred speech, headache, a n d n a u s e a in November 1974. Right-sided weakness, u n s t e a d y gait, and sensory deficits in the r i g h t u p p e r a n d lower extremities then developed. Brain scan a n d cerebral a n # o g r a p h y confirmed a solitary left parietal mass lesion. T h e lesion was excised by craniotomy in J a n u a r y 1975. T h e pathologic diagnosis was metastatic m a l i g n a n t m e l a n o m a (Fig. I). T h e postoperative course was complicated by" extensive a n d repeated p u l m o n a r y embolization, * Read at the m e e t i n g of the American of Colon a n d Rectal Surgeons, New Orleans: ana, May 2 to 6, 1976. i - C h a i r m a n , D e p a r t m e n t of Surgery. ++C h a i r m a n , D e p a r t m e n t of Medicine. Address r e p r i n t requests to Dr. Alexander: hower Medical Center, 39-000 Bob Hope P a l m Desert, California 92260.
Society Louisi-
EisenDrive,
Summary of Reported Cases
Patient's Age (Years), Sex
Bacon a n d Penal B e h r e n d a n d B e h r e n d 2" Consiglio a n d MullerS Chalier a n d Bonnet4 Delaney et al.7 F e r r a n d a n d ElbazS Kallet a n d Saltzsteinn Kraskel-~ L a u m o n i e r et at.Is Mason a n d HelwlglS Braasted et al.3 Q u a n et aLZ7 RamazanogIuIS G u i v a r c ' h et al.9 W e s t o n a n d Marren2O
61, 53, 55, 48, 50, 43, 47, 45, 45, 61, 59, ?, 56, 68, 52,
M M F M M F F M M F F M M M M
A l e x a n d e r et al. H a m b r i c k et al.lO
56, 57,
M M
Distance from Anus 7 cm Rectosigwnoid 6 cm m~ 9 3 cm 6 cm Rectum 5 cm 6 cm 15 cm 4 cm ? 6-8 cm 4-5 cm 8 cm, 12.5 cm 10 cm 6 cm
53 Dis. Col. & Rect. Jam-Feb. 1977
Volume 20 Number 1
54
ALEXANDER AND CONE
Dis. Col. & Rect. Jan,-Feb. 1977
Fro. 1. Metastatic malignant melanoma of tile brain.
the right arm recurred. Neurologic examination, failed to confirm recurrence of the cerebral neoplasm. Fourteen months after the onset of initial symptoms, severe pancytopenia suddenIy deveIoped, and the patient became febrile and died with gramnegative sepsis despite appropriate antibiotic and supportive therapy. At atttopsy, a 1 • 1 cm metastatic nodule of malio~nant melanoma was found in the right parietal area of the brain, but no
Fro. 2.
residual lesion in the left parietal area or anywhere else could be found. Comment Many theories have been advanced in an effort to e x p l a i n the p r i m a r y o c c u r r e n c e of malignant melanoma in the mid-rectum and
Malignant melanoma of the rectosigmoid colon.
Volume 20 Number 1
MALIGNANT MELANOMA OF T H E RECTAL AMPULLA
o t h e r a r e a s o~ t h e g a s t r o i n t e s t i n a l tract. I t is p o s t u l a t e d t h a t s u c h t u m o r s r e p r e s e n t metastases from undetected primary melan o m a s e l s e w h e r e . 6 T h e a u t h o r s are convinced that the rectal lesion described in this case r e p o r t was i n d e e d a p r i m a r y t u m o r d e s p i t e t h e fact t h a t a s a t i s f a c t o r y e x p l a n a t i o n f o r its o r i g i n in t h a t l o c a t i o n is l a c k i n g . T h e use of B C G in the t r e a t m e n t of pat i e n t s w h o h a v e m e l a n o m a is w e l l k n o w n , e s p e c i a l l y as a n i n t r a l e s i o n a l i n j e c t i o n in cutaneous tumors. T h e d e v e l o p m e n t of i n b r e d s t r a i n s of l a b o r a t o r y a n i m a l s in t h e m i d - 1 9 5 0 ' s c o n t r i b u t e d to t h e s t u d y of tumor-specific antigens and tumor-specific immunity. C o n s i d e r a b l e e v i d e n c e has acc u m u l a t e d to i n d i c a t e t h a t b o t h a n i m a l a n d human cancers have tumor-specific antigens a n d t h a t t h e h o s t c a n p r o d u c e an i m m u n e r e a c t i o n to these a n t i g e n s . T h i s i m m u n e r e s p o n s e is n o t always effective in i n d i viduals who have clinically evident tumors. T h e o b j e c t i v e o[ u s i n g B C G is to s t i m u l a t e t h e h o s t ' s i m m u n e r e a c t i o n to b r i n g it i n t o t h e r a p e u t i c effectiveness. T h e m e c h a n i s m of a c t i o n of C C N U a n d D T I C , by w h i c h t h e y p r o d u c e a c a r c i n o s t a t i c state, is n o t w e l l u n d e r s t o o d . T h e y a r e b e i n g u s e d o n t h e basis of m a n y years of c l i n i c a l trial14, 19 in w h i c h s i g n i f i c a n t activity against tumors previously resistant to o t h e r c h e m o t h e r a p e u t i c a g e n t s has b e e n d e m o n s t r a t e d . T h e p r i m e d i s a d v a n t a g e of t h e s e m e d i c a t i o n s is t h e i r t o x i c i t y to b o n e marrow with delayed recovery.
3.
4.
5. 6.
7.
8. 9.
10.
11.
12.
13.
14.
15. 16.
Summary D o c u m e n t a t i o n of t h e s e v e n t e e n t h case of m e l a n o m a of t h e r e c t u m is p r e s e n t e d . T h e w o r l d l i t e r a t u r e is r e v i e w e d . The e f f e c t i v e n e s s of i m m u n o t h e r a p y w i t h B C G or BCG in combination with CCNU and D T I C r e m a i n s to b e e s t a b l i s h e d .
17.
18.
19. References 1. Bacon HE, Pena E: ~Lalignant melanoma of the anorectum: Report of two cases. Clinics 3: 457, 1944 2. Behrend M, Behrend A: Melanosarcoma (malig-
20.
55
nant melanoma) of the rectosigmoid: Report of a unique case. Gastroenterology 12: 142, 1949 Braasted FW, Dockerty MB, Dixon CF: Melanoepithelioma of the anus and rectum: R e p o r t of cases and review of the literature. Surgery 25: 82, 1949 Chalier A, Bonnet P: Les tumeurs mflaniques primitives du rectum. Rev Chir Paris 46: 914, 1912; 47: 64, 1913 Consiglio L, Muller I: I1 melanoma primitivo del retto. Chir GastroenteroI 4:307, 1970 Das Gupta TK, Brasfield RD: Metastatic melanoma of the gastrointestinal tract. Arch Surg 88: 969, 1964 Delaney LT, Scudamore HH, Waugh JM: Malignant melanoma of the rectum: Report of case. Mayo Clin Proc 29: 416, 1954 Ferrand J, Elbaz C: Les m~lanomes primitifs du rectum. J Chit (Paris) 71: 391, 1955 Guivarc'h M, Nathan G, Mouchet A, et al: Un cas de m6lanome malin primitif de l'ampoule du rectum. Arch Fr blal App Dig 62: 613, 1973 Hambrick E, Abearian H, Smith D, et al: Malignant melanoma of the rectum in a Negro man: Report of a case and review of the literature. Dis Colon Rectum 17: 360, 1974 Kallet HI, Saltzstein HC: Sarcoma, melanoma and leukosarcoma of the rectum. Arch Surg 26: 633, 1933 Kraske P: Erfahrungen uber den mastdarmkrebs. Sammlung klinischer vortrage. Neue Folge 52: 771, 1897 Laumonier R, Cornillot R, Boutxy P, et al: Melanomes malins du rectum glandulaire. Arch Fr Mal App Dig 51: 700, 1962 Luce JK, Thurman WG, Isaacs BL, et al: Clinical trials with the antitumor agent 5-(3,3dimethyl-l-triazeno) imidazole-4-carboxamide (NSC-45388). Cancer Chemother Rep 54: 119, 1970 Mason JK, Helwig EB: Ano-rectal melanoma: Cancer 19: 39, 1966 Moore R: Recurrent melanosis of the rectum, after previous removal from the verge of the anus, in a man aged sixty-five. Lancet 1: 290, 1857 Quan SH, White JE, Deddish MR: Malignant melanoma of the anorectum. Dis Colon Rectum 2: 275, 1959 Ramazanoglu M: A propos d'un cas de m~lanoblastome du rectum. Rev Meal Moyen Orient 18: 188, 1961 Skibba JL, Ramirez G, Beal DD, et al: Preliminary clinical trial and the physiologic disposition of 4(5)-(3,3-dimethyl-l.triazeno) imidazole-5 (4)-carboxamide in man. Cancer Res 29: 1944, 1969. Weston SD, Marren M: Malignant melanoma of the rectum. J Int Coll Surg 17: 403, 1952
necessitating anticoagulation. T h e search for a p r i m a r y m e l a n o m a was delayed, b u t u l t i m a t e l y a survey of the gastrointestinal tract disclosed a 3.5 • 4.0 cm polypoid t u m o r , 10 c m above the crypt level of t h e anal canal. Histologic e x a m i n a t i o n of the biopsy specimen confirmed t h e suspected diagnosis of a melanotic m e l a n o m a (Fig. 2). T h e rect u m a n d sigmoid colon were resected a n d colostomy performed. T h e residual rectal s e g m e n t was left in place. P a t h o l o # c review of the specimen disclosed p e n e t r a t i o n of t h e lesion t h r o u g h the m n s cularis a n d no l y m p h - n o d e metastases. I m m u n o therapy with BCG {bacillus Calmette-Guel-in) h a d been initiated prior to the snrgical procedure a n d was continued. A p u l m o n a r y infarction occurred i n c l u d i n g computerized axial tomog-raphy scan, shortly after operation, h u t the p a t i e n t otherwise r e m a i n e d welt for a n a d d i t i o n a l three m o n t h s , u n t i l right h e m i p l e g i a a n d a p h a s i a a n d neurologic findings consistent with recurrence of the cerebral lesion s u d d e n l y developed. C o m b i n a t i o n chemotherapy with C C N U (1-[2-chloroethyl]-3-cyclohexyl1-nitrosurea) a n d D T I C (5-[3,3 dimethyl-l-triazene] imidazole-4-carboxamide) was instituted, with imp r o v e m e n t of the patient's condition, only m i n i m a l right-sided weakness r e m a i n i n g . A year after t h e onset of his illness, in N o v e m b e r 1975, n u m b n e s s of
T H E INFREQUENT OCCURRENCE o f m a l i g n a n t
m e l a n o m a of the anus and rectum has been well established. A p p r o x i m a t e l y 180 cases have been r e p o r t e d since the first description of its occurrence in man by Moore in 1857.16 Of these, 16 cases have involved the rectal a m p u l l a or rectosigmoid colon without evidence of a melanotic lesion of the anus or anal canal ( T a b l e 1)Y T h e 16 patients were 11 men and five women. T i l e lesion was most often discovered when the patients were between 50 and 65 years of age. Five patients were less than 50 years old. Distances of the lesion from the anus ranged from 3 to 15 cm. A l t h o u g h the m e a s u r e m e n t in each case might be questioned for accuracy, there is no d o u b t that none of the lesions involved the a n o d e r m or anal canal. T h i s p a p e r has been p r e p a r e d to document the seventeenth known p r i m a r y occurrence of a m a l i g n a n t m e l a n o m a above the anal canal.
TABLE 1.
Reference
Report of a Case A 56-year-old white m a n h a d enjoyed good h e a l t h u n t i l the s u d d e n onset of slurred speech, headache, a n d n a u s e a in November 1974. Right-sided weakness, u n s t e a d y gait, and sensory deficits in the r i g h t u p p e r a n d lower extremities then developed. Brain scan a n d cerebral a n # o g r a p h y confirmed a solitary left parietal mass lesion. T h e lesion was excised by craniotomy in J a n u a r y 1975. T h e pathologic diagnosis was metastatic m a l i g n a n t m e l a n o m a (Fig. I). T h e postoperative course was complicated by" extensive a n d repeated p u l m o n a r y embolization, * Read at the m e e t i n g of the American of Colon a n d Rectal Surgeons, New Orleans: ana, May 2 to 6, 1976. i - C h a i r m a n , D e p a r t m e n t of Surgery. ++C h a i r m a n , D e p a r t m e n t of Medicine. Address r e p r i n t requests to Dr. Alexander: hower Medical Center, 39-000 Bob Hope P a l m Desert, California 92260.
Society Louisi-
EisenDrive,
Summary of Reported Cases
Patient's Age (Years), Sex
Bacon a n d Penal B e h r e n d a n d B e h r e n d 2" Consiglio a n d MullerS Chalier a n d Bonnet4 Delaney et al.7 F e r r a n d a n d ElbazS Kallet a n d Saltzsteinn Kraskel-~ L a u m o n i e r et at.Is Mason a n d HelwlglS Braasted et al.3 Q u a n et aLZ7 RamazanogIuIS G u i v a r c ' h et al.9 W e s t o n a n d Marren2O
61, 53, 55, 48, 50, 43, 47, 45, 45, 61, 59, ?, 56, 68, 52,
M M F M M F F M M F F M M M M
A l e x a n d e r et al. H a m b r i c k et al.lO
56, 57,
M M
Distance from Anus 7 cm Rectosigwnoid 6 cm m~ 9 3 cm 6 cm Rectum 5 cm 6 cm 15 cm 4 cm ? 6-8 cm 4-5 cm 8 cm, 12.5 cm 10 cm 6 cm
53 Dis. Col. & Rect. Jam-Feb. 1977
Volume 20 Number 1
54
ALEXANDER AND CONE
Dis. Col. & Rect. Jan,-Feb. 1977
Fro. 1. Metastatic malignant melanoma of tile brain.
the right arm recurred. Neurologic examination, failed to confirm recurrence of the cerebral neoplasm. Fourteen months after the onset of initial symptoms, severe pancytopenia suddenIy deveIoped, and the patient became febrile and died with gramnegative sepsis despite appropriate antibiotic and supportive therapy. At atttopsy, a 1 • 1 cm metastatic nodule of malio~nant melanoma was found in the right parietal area of the brain, but no
Fro. 2.
residual lesion in the left parietal area or anywhere else could be found. Comment Many theories have been advanced in an effort to e x p l a i n the p r i m a r y o c c u r r e n c e of malignant melanoma in the mid-rectum and
Malignant melanoma of the rectosigmoid colon.
Volume 20 Number 1
MALIGNANT MELANOMA OF T H E RECTAL AMPULLA
o t h e r a r e a s o~ t h e g a s t r o i n t e s t i n a l tract. I t is p o s t u l a t e d t h a t s u c h t u m o r s r e p r e s e n t metastases from undetected primary melan o m a s e l s e w h e r e . 6 T h e a u t h o r s are convinced that the rectal lesion described in this case r e p o r t was i n d e e d a p r i m a r y t u m o r d e s p i t e t h e fact t h a t a s a t i s f a c t o r y e x p l a n a t i o n f o r its o r i g i n in t h a t l o c a t i o n is l a c k i n g . T h e use of B C G in the t r e a t m e n t of pat i e n t s w h o h a v e m e l a n o m a is w e l l k n o w n , e s p e c i a l l y as a n i n t r a l e s i o n a l i n j e c t i o n in cutaneous tumors. T h e d e v e l o p m e n t of i n b r e d s t r a i n s of l a b o r a t o r y a n i m a l s in t h e m i d - 1 9 5 0 ' s c o n t r i b u t e d to t h e s t u d y of tumor-specific antigens and tumor-specific immunity. C o n s i d e r a b l e e v i d e n c e has acc u m u l a t e d to i n d i c a t e t h a t b o t h a n i m a l a n d human cancers have tumor-specific antigens a n d t h a t t h e h o s t c a n p r o d u c e an i m m u n e r e a c t i o n to these a n t i g e n s . T h i s i m m u n e r e s p o n s e is n o t always effective in i n d i viduals who have clinically evident tumors. T h e o b j e c t i v e o[ u s i n g B C G is to s t i m u l a t e t h e h o s t ' s i m m u n e r e a c t i o n to b r i n g it i n t o t h e r a p e u t i c effectiveness. T h e m e c h a n i s m of a c t i o n of C C N U a n d D T I C , by w h i c h t h e y p r o d u c e a c a r c i n o s t a t i c state, is n o t w e l l u n d e r s t o o d . T h e y a r e b e i n g u s e d o n t h e basis of m a n y years of c l i n i c a l trial14, 19 in w h i c h s i g n i f i c a n t activity against tumors previously resistant to o t h e r c h e m o t h e r a p e u t i c a g e n t s has b e e n d e m o n s t r a t e d . T h e p r i m e d i s a d v a n t a g e of t h e s e m e d i c a t i o n s is t h e i r t o x i c i t y to b o n e marrow with delayed recovery.
3.
4.
5. 6.
7.
8. 9.
10.
11.
12.
13.
14.
15. 16.
Summary D o c u m e n t a t i o n of t h e s e v e n t e e n t h case of m e l a n o m a of t h e r e c t u m is p r e s e n t e d . T h e w o r l d l i t e r a t u r e is r e v i e w e d . The e f f e c t i v e n e s s of i m m u n o t h e r a p y w i t h B C G or BCG in combination with CCNU and D T I C r e m a i n s to b e e s t a b l i s h e d .
17.
18.
19. References 1. Bacon HE, Pena E: ~Lalignant melanoma of the anorectum: Report of two cases. Clinics 3: 457, 1944 2. Behrend M, Behrend A: Melanosarcoma (malig-
20.
55
nant melanoma) of the rectosigmoid: Report of a unique case. Gastroenterology 12: 142, 1949 Braasted FW, Dockerty MB, Dixon CF: Melanoepithelioma of the anus and rectum: R e p o r t of cases and review of the literature. Surgery 25: 82, 1949 Chalier A, Bonnet P: Les tumeurs mflaniques primitives du rectum. Rev Chir Paris 46: 914, 1912; 47: 64, 1913 Consiglio L, Muller I: I1 melanoma primitivo del retto. Chir GastroenteroI 4:307, 1970 Das Gupta TK, Brasfield RD: Metastatic melanoma of the gastrointestinal tract. Arch Surg 88: 969, 1964 Delaney LT, Scudamore HH, Waugh JM: Malignant melanoma of the rectum: Report of case. Mayo Clin Proc 29: 416, 1954 Ferrand J, Elbaz C: Les m~lanomes primitifs du rectum. J Chit (Paris) 71: 391, 1955 Guivarc'h M, Nathan G, Mouchet A, et al: Un cas de m6lanome malin primitif de l'ampoule du rectum. Arch Fr blal App Dig 62: 613, 1973 Hambrick E, Abearian H, Smith D, et al: Malignant melanoma of the rectum in a Negro man: Report of a case and review of the literature. Dis Colon Rectum 17: 360, 1974 Kallet HI, Saltzstein HC: Sarcoma, melanoma and leukosarcoma of the rectum. Arch Surg 26: 633, 1933 Kraske P: Erfahrungen uber den mastdarmkrebs. Sammlung klinischer vortrage. Neue Folge 52: 771, 1897 Laumonier R, Cornillot R, Boutxy P, et al: Melanomes malins du rectum glandulaire. Arch Fr Mal App Dig 51: 700, 1962 Luce JK, Thurman WG, Isaacs BL, et al: Clinical trials with the antitumor agent 5-(3,3dimethyl-l-triazeno) imidazole-4-carboxamide (NSC-45388). Cancer Chemother Rep 54: 119, 1970 Mason JK, Helwig EB: Ano-rectal melanoma: Cancer 19: 39, 1966 Moore R: Recurrent melanosis of the rectum, after previous removal from the verge of the anus, in a man aged sixty-five. Lancet 1: 290, 1857 Quan SH, White JE, Deddish MR: Malignant melanoma of the anorectum. Dis Colon Rectum 2: 275, 1959 Ramazanoglu M: A propos d'un cas de m~lanoblastome du rectum. Rev Meal Moyen Orient 18: 188, 1961 Skibba JL, Ramirez G, Beal DD, et al: Preliminary clinical trial and the physiologic disposition of 4(5)-(3,3-dimethyl-l.triazeno) imidazole-5 (4)-carboxamide in man. Cancer Res 29: 1944, 1969. Weston SD, Marren M: Malignant melanoma of the rectum. J Int Coll Surg 17: 403, 1952
