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Primary adenocarcinoma of an anal gland with secondary perianal fistulas
H U M A N P A T H O L O G Y - - V O L U M E 12, N U M B E R 11 November 1981
PRIMARY A D E N O C A R C l N O M A OF AN A N A L GLAND WITH SECONDARY PERIANAL FISTULAS SAING H. LEt, M.D.,* MARJORIE ZUCKER, M.D.,t" AND TATStrO SATO, M.D.~c
A case of primary mucinous (colloid) adenocarcinoma associated with multiple perianal fistulas and a supra-anal interglu}eal abscess of a short duration is described. The origin of this tumor has been much debated. Some believe that the tumor occurs primarily in an anal duct or its glands with secondary fistula formation, whereas others claim that the tumor arises in a chronic fistulous tract. The present study substantiates the former concept on the basis of the mode of clinical presentation and the pathologic findings of a large tumor, without involvement of the anorectal mucosa. The residual anal ducts and glands were found in close relationship with the tumor. Hum Pathol 12:1034-1037, 1981. Primary perianal mucinous (colloid) adenocarcinoma is a rare entity. In 1934 Rosser e~ first described a carcinoma associated with chronic fistula in ano~ Since then n u m e r o u s cases o f perianal colloid carcinoma associated with anal fistulas have been r e p o r t e d wittt discussion o f the possible origin o f the ttnnor. 1"4-6'~'12"1~'1s-24"28 Nevertheless, well d o c u m e n t e d cases o f perianal colloid carcinoma o f anal duct or gland origin have been r e p o r t e d in the literature. a'4.6a'm~2,2s-27 Yet the origin o f the t u m o r remains controversial. This neoplasm primarily affects the o l d e r age g r o u p and there is no significant sex p r e p o n d e r a n c e . T h e t u m o r is clinically characterized by a frequent association with anal a n d perianal fistulas o r abscesses o f various durations. It is known to be a slow growing, locally aggressive neoplasm with a low grade histologic a p p e a r a n c e and rarity o f metastasis. O t h e r characteristic features include frequent recurrence following inadeqtmte resection and late development o f metastasis. T h e diagnosis can be made only by open d e e p biopsy o f the gluteal mass or prolonged nonhealing perianal lesions. T r e a t m e n t is a b d o m i n o p e r i n e a l resection with total ablation o f the t u m o r in the gluteal tissue. T h e duration o f survival varies from months to years, with most patients dying o f either surgical complications o r unrelated diseases. T h e purpose o f this r e p o r t is to record a rare case o f p r i m a r y m u c i n o u s a d e n o c a r c i n o m a t h a t was c a r e f u l l y studied at autopsy, with particular emphasis on the origin o f this unique tumor.
was no evidence o f the tract entering the bowel. Light microscopy showed chronic inflammation, fibrosis, microabscesses, and granulation tissue. T h e patient had a stormy conrse in the hospital a n d was finally discharged in October 1978. His final diagnosis at that time was abscess with chronic infection in the lumbosacrococcygeal area secondary to an infected pilonidal cyst with destruction o f the coccyx and osteomyelitis. T h e patient was a d m i t t e d to the Kansas City Veterans Administration Medical Center on February 8, 1979, with progressive ulceration and persistent chronic infection in the sacracoccygeal and perianal area. Examination revealed an ulcerating sacrococcygeal lesion measuring 6 by 8 cm. filled with a p u r u l e n t e x u d a t e attd g r a n u l a t i o n tissue. Proctoscopic examination revealed no mucosal lesion in the anal and rectal canal. A biopsy specimen o f the lesion in the perianal and sacral areas showed adenocarcinoma. A possible a b d o m i n o p e r i n e a l resection was planned, but the patient's condition d e t e r i o r a t e d and the surgery was not done. He became hypotensive and developed p r e r e n a l azotemia and electrolyte imbalance, which did not r e s p o n d to therapy. His condition c o n t i n u e d to deteriorate and he expired on March 15, 1979. A n autopsy was p e r f o r m e d . PATHOLOGY Gross Findings
At autopsy there was a large ulcer with a firm edge in the skin o f the supra-anal intergluteal area measuring
CASE REPORT A 57 year old white male with known alcoholic liver disease entered another hospital in May 1978 for the treatment o f a pilonidal cyst a n d anal infection with draining sinuses for several weeks. Surgery was p e r f o r m e d , with d e b r i d e ~ e n t and excision o f the pilonidal cyst, scraping o f bone, and perianal fistulectomy. An x-ray view o f the pelvic area at the time showed destruction in the coccyx, but there Accepted for publication December 22, 1980. * Assistant Professor of Pathology, College of tleahh Sciences and Hospital, University of Kansas Medical Center, Kansas City, Kansas. Staff Pathologist, Veterans Administration Medical Center, Kansas City: Missouri. ]" Assistant Profesgor of Pathology, College of Health Sciences and Hospital, University of Kansas Medical Center, Kansas City, Kansas. ~t Associate Professor of Pathology, College of Health Sciences and Hospital, University of Kansas Medical Center, Kansas City, Kansas. Chief, Laboratory Service, Veterans Administration Medical Center, Kansas City, Missouri.
1034
Figure 1. Posterior view of tile anal and rectal canal with : large gelatinous tumor in the ischiorectal fossa.
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Mucinous (colloid) adenocarcinoma of anal gland origin. (ltematoxylin and cosin stain. •
9 by 1.5 cm. a n d extending from the superior anal verge to the level o f the coccyx. A large soft gelatinous t u m o r was found involving tile posterior and posterolateral aspects o f the anal and rectal canal. T h e t u m o r was d e e p to the anorectal mucosa and measured 9 by 7 by 5 cm. (Fig. 1). T h e overlying mucosa was not involved by the t u m o r . T h e orifices o f the t h r e e fistulous tracts were noted at the perianal skin and c o m m u n i c a t e d with the tumor. T h e t u m o r completely occupied the ischiorectal fossa a n d e x t e n d e d to the p o s t e r i o r wall o f the pelvis, the coccyx, the gluteal muscles, and soft tissue and had ulcerated throttgh tile supra-anal intergluteal skin to produce the previously described ulcer. T h e r e was no evidence o f metastasis to inguinal o r intral~elvic lymph nodes o r organs elsewhere in the body. O t h e r findings at autopsy were alcoholic micronodular cirrhosis o f the liver with fibrocongestive splenomegaly and massive ascites.
Histologlc Findings Muhiple sections were taken from the rectum and anal canal. Microscopic examination showed invasive mucin p r o d u c i n g adenocarcinoma primarily involving the wall o f the rectum and anal canal and perianorectal soft tissue without involvement o f the mucosa. T h e t u m o r was composed o f various sized spaces filled with a b u n d a n t mucus. Some glafidular spaces were partially lined by mucus secreting c o l u m n a r cells.'In some areas cells o f a signet ring t y p e w e r e n u m e r o u s in pools o f m u t i n o u s m a t e r i a l , whereas o t h e r areas showed well f o r m e d glands lined by similar neoplastic cells (Fig. 2). In m u h i p l e areas pools o f mucus separated the layers o f the anorectal wall and the adjacent soft tissue. T h e r e were microscopic foci o f carcinoma in the coccyx bone. In addition two residual anal ducts anti their glands
were present in the muscular layer o f the anorectal wall. T h e ducts were lined by transitional cells with focal acute and chronic inflammatory infiltrates in the s u r r o u n d i n g tissue. Tile glands were also inflamed but were often lined by tall c o l u m n a r mucus p r o d u c i n g cells and occasional groups o f cells with an eosinophilic g r a n u l a r cytoplasm, p r e s u m ably representing metaplastic cells. In several sections the colloid carcinoma was noted in close proximity to one o f the anal ducts and its gland. T h e fistulous tracts were devoid o f lining e p i t h e l i u m a n d c o n t a i n e d mucus, e x u d a t c , a n d t u m o r cells. T h e walls o f most fistulas revealed acute and chronic focal inflammation as well as t u m o r infiltrate. DISCUSSION Two possible origins o f perianal carcinoma have been proposed: (I) T h e carcinoma arises in a chronic fistulous tract, and (2) it develops from an anal duct o r its gland with secondary fistula formation. Anal ducts and glands have long been known to be present in h u m a n beings, a n d have been well studied in terms o f their embryology, anatomy, and histology by many investigators. 2'4,8,1~ T h e y arise from anal crypts lying in the transitional zone between the rectal mncosa and the anal mucosa. T h e r e are six to eight ducts, which open at the dentate line. T h e y are straight o r spiral tubes with one to six b r a n c h i n g tubules, sometimes f o r m i n g an a c i n a r structure. T h e epithelial lining is usually squamous n e a r the orifice, transitional t h r o u g h o u t most o f the length, and mucus p r o d u c i n g c o l u m n a r epithelium in the terminal acinar structure. In 1934 Rosser 2~ first described a carcinoma associated with chronic fistula in ano. Later his criteria for p r i m a r y perianal carcinomas arising in fistulous tracts included: the fistula antedating the carcinoma, an uninvolved anal and
1035
HUMAN
PATHOLOGY--VOLUME
12, N U M B E R
11
November 1981
r e c t a l mttcosa, a n d t h e o p e n i n g o f tire fistula i n t o t h e a n a l c a n a l o r crypt, n o t i n t o m a l i g n a n t tissue. S k i t ~s s t r e s s e d t h e i m p o r t a n c e o f a l o n g h i s t o r y o f fist u l a in a n o a n d t h e e x c l u s i o n o f a n a n t e c e d e n t c a r c i n o m a to allow d i a g n o s i s o f c a r c i n o , n a a r i s i n g in a b e n i g n f i s t u l a . T i r e r e q u i r e d d u r a t i o n o f s y m p t o m s o f t h e fistula was a r b i t r a r i l y set at I 0 }'ears. Kline e t a l . tz in 1964 s u p p o r t e d R o s s e r 2~ a n d Skir 23 a n d a d d e d five t n o r e cases, lrt t h e i r series t h e d u r a t i o n o f t h e fistula s y m p t o m s r a n g e d f r o m 15 to 4 7 }'ears. Likewise t h e l o n g s t a n d i n g p r e s e n c e o f a n a l fistula in association with c a r c i n o m a is s t r o n g e v i d e n c e in f a v o r o f t h e i r p r e - e x i s t e n c e . H o w e v e r , r e c e n t r e p o r t s f a v o r t h e i d e a t h a t m o s t carc i n o m a s t h a t a l l e g e d l y a r i s e in c h r o n i c fistulas a c t u a l l y o r i g i n a t e in t h e anal dttct, a,4-r.-~ D a v i d 4 claims t h a t a n a l d u c t s play a m o r e p r o n a i n e n t and perhaps even a more determinant role in the p a t h o g e n e s i s o f a n a l fistulas t h a n was p r e v i o u s l y s u s p e c t e d . A r e l a t i o n s h i p b e t w e e n a n a n a l fistula a n d a n a l g l a n d s was first p o i n t e d o u t b y C h i a r i z in 1878. In a l a t e r s t u d y by P a r k s t6 it was f o u n d t h a t 21 o f 30 c o n s e c u t i v e cases o f a n a l fistula ~scre c a u s e d by i u f e c t e d a n a l g l a n d s . R e c e n t l y F e n g e r et al. ~ s t u d i e d e i g h t cases o f colloid c a r c i n o m a a r i s i n g in p r e - e x i s t i n g a n a l fistulas by t h e use o f special m u c i n t t i s t o c h e m i c a l analyses. H e c l a i m e d t h a t in f o u r o f t h e e i g h t cases tire lesions o r i g i n a t e d in t h e a n a l g l a n d s , T h e m u c u s o f t h e a n a l g l a n d s was c h a r a c t e r i z e d by s t r o n g P A S reactivity t h a t was c o m p l e t e l y a b o l i s h e d a f t e r p e r i o d a t e b o r o h y d r i d e s a p o n i f i c a t i o n , ' i n d i c a t i n g t h e scarcity o r a b s e n c e o f 0-acylated sialic acids in t h e a n a l g l a n d m u c u s . T h i s t y p e o f m u c n s is d i f f e r e n t f r o m t h a t p r o d u c e d by globlet cells o f rectal m u c o s a . Now the question remains whether chronic infection h a s a n y causal r e l a t i o n s h i p w i t h t u m o r . It is b e l i e v e d t h a t t h e r e is satisfactory e v i d e n c e t h a t a n a l c a n c e r m a y d e v e l o p in tissne altered by h e m o r r h o i d s , fistulas, o r cicatrices, t~ Since S c a r b o r o u g h 22 in 1941 d e s c r i b e d t h e first p r i m a r y carc i n o m a o f a n a n a l g l a n d , well d o c u m e n t e d s i m i l a r cases h a v e b e e n r e p o r t e d in t h e l i t e r a t u r e . 3.4.6a.tT.e5-z7 R e c e n t l y W i n k e l m a n e t a l . 2r r e p o r t e d a colloid carc i n o m a o f a n a l g l a n d o r i g i n in w h i c h a t r a n s i t i o n f r o m t h e a n a l d u c t orifice to t h e m n c i n o u s p e r i a n a l t u m o r was d e m onstrated. O u r p r e s e n t case s h o w e d m a n ) ' o f t h e typical f e a t u r e s o f a n a n a l g l a n d c a r c i n o m a , m o s t n o t a b l y its exclusively p e r i a n a l i n t r a m u s c u l a r l o c a t i o n with e x t e n s i o n to rite post e r i o r wall o f t h e pelvic cavity a n d i n t e r g l u t e a l soft tissue, without involvement of the rectal or anal mucosa, Other characteristic features included tbe mode of clinical p r e s e n t a t i o n . T h e r e was a s h o r t d u r a t i o n o f t h e anal fistulas, a n d t b r e e o p e n i n g s w e r e i n t o t h e p e r i a n a l skin, n o t i n t o t h e a n a l canal. In a d d i t i o n , s e v e r a l r e s i d u a l a n a l d u c t s a n d g l a n d s w e r e f o u n d in close p r o x i m i t y to t h e t u m o r . O u r p a t i e n t h a d a h i s t o r y o f o n l y a o n e }'ear i n t e r v a l b e t w e e n t h e o n s e t o f t h e a n a l fistula a n d t h e d i a g n o s i s o f c a r c i n o m a . T h i s is too s h o r t a p e r i o d to p o s t u l a t e t h a t t h e c a r c i n o m a d e v e l o p e d in a b e n i g n fistula, especially in view o f t h e l a r g e size o f t h e t u m o r . W e b e l i e v e t h a t it is m u c h m o r e likely t h a t this t u m o r , w h i c h is typically slow growiHg, was p r e s e n t subclinlcally f o r s o m e time~ a n d p r e d a t e d t h e fistnlas. T h e colloid c a r c i n o m a with a b u n d a n t m u c i n p r o d u c t i o n in all likelihood h a d a g r e a t t e n d e n c y to dissect soft t i s s u e p l a n e s , l e a d i n g to t h e s e c o n d a r y d e v e l o p m e n t o f p e r i a n a l fistulas. T h e late d i a g n o s i s o f this t u m o r a n d 9 n g m a l l y n e g a t i v e biopsy studies support the contention that a high index of suspicion and adequate deep biopsies are of great import a n c e in cases o f m u l t i p l e c h r o n i c r e c u r r e n t fistula in ano.
1036
Acknowledgments T h e a u t h o r s wisb to t b a n k A n i t a Y. D i x o n , M.D., a n d S h e r r y R a m p a n t f o r t h e i r assistance in t h e p r e p a r a t i o n o f the manuscript. References 1. Chaos, A., Garrido, H.. Fernandex-Villoria, J. M., Dominquez, J., and Cano, M.C.: Carcinoma associated ~,hh fistula-in-ano. Int. Surg., 58:497-499, 1973. 2. Chiari, H.: Uber die Analen Di~ertikel der Rectumschleimhaut und ihre Beziehung zu den Analfistcln, Med. Jahrb. Wien. 8:419-427, 1878. 3. Close, A.S., and Schwab, R. L: tlistory of anal ducts and anal-duct carcinoma: report of a case- Cancer, 8:979-985, 1955. 4. David, A.: Tumors of the Intestines. Atlas of Tumor Pathology. Washington, D.C., Armed Forces Institute of Pathology, 1967, Section VI, Fascicle 22. 5. Dukes, C. E., and Galvin, C.: Colloid carcinoma arising within fistulae in the anorectal region. Ann. Roy. Coll. Surg. Engl., 18:246-261, 1956. 6. Fcnger, C., and Filipe, M. I.: Pathology of the anal glands with special reference to their mucinons hlstochemistry. Acta Path. Microbiol. Scand. (Sect. A), 85:273-285, 1977. 7. l-tag.ibara, P., Vazquez, M. D., Parker, J. C., and Griffe4~r W. O.: Cartrauma of anal-ductal origin: report of a case. Dis. Col. Rect., 19:594-701, 1976. 8. }tarrison, E. C.: Anal and perianal malignant neoplasms: pathology and treatment. Dis. Col. Reef., 9:255-267, 1956. 9. Heindenreich, A., ColIarini, H. A., Paladino, A. M., Fernande,, J. M., and Calvo, T. O.: Cancer in anal fistulas. Dis. Col. Rect., 9:571-376, 1966. I0. Herrmann, G.: Sur la structure et le d~veloppement de la muqueuse anale. J. Anat. Physiol., 16:434-472, 1880. 11. Johnson, F. P.: The development of the rectum in the human embryo. Am.J. Anat., 16:1-57, 1914. 12. Kline, R.J., Spencer, R.J., and Harrison, E. G.: Carcinoma associated with fistula-in-ano. Arch. Surg., 89:989-994, 1964. 13. Kratzer, G. l., and Dockerty. M. B.: Histopathology of the anal ducts. Surg. Gynecol. Ob~tet., 84:333-338, 1947. 14. McColI, l.: The comparative anatomy and pathology of anal grands. Ann. Roy. Coll. Surg. Engl-, 40:36-67, 1967, 15. Nielsen, O. V., and Koch, F-: Carcinomas of the ano~ectal region of extramucosal origin with special reference to the anal ducts. Acta Chir. Stand., 139:299-305, 1973. 16_ Parks, A. G.: Modern concepts of the anatomy of the anorectal region. Postgrad. *ted. J., 34:360-366, 1958. 17. Pollice, L., and D'Abriceo. V.: On anorectal carcinoma with extramueosal site. Notation of a new case of carcinoma of Hermann's perianal gland. Rev. Anat. Pathol. Oncol., 15:423-441, 1959. 18. Prioleau, P.G., Allen, M.S., and Roberts, T.: Perianal mutinous adenocarcinoma. Cancer, 39:1295-1299, 1977. 19. Rosser, C.: The etiology ofanal cancer. Am.J. Surg., 11:328-333, 193 I. 20. Russet, C.: The relation of fistula-in-ano to cancer of the anal canal. Tr, Am. Proct. Sue., 35:65-71, 1934. 21. Rundle, F.F., and Hales, I. B.: Mncoid carcinoma supervening on fistula-in-ano; its surgical pathology and treatment. Ann. Surg-, 137:215-219. 1953. 22. Scarborough, R. A.: Primary carcinoma of an anal glared. Tr. Am. Proct. Sue., 42:172-176, 1941. 23. Skit, l.: Mucinous carcinoma associated ~'ith fistulas of long-standing. Am.J. Surg., 75:285-289, 194K 24. Stockman, J. M., and Young, V, I.: Carcinom tssociatedwith anorectal fistula. Tr. Am. Proct. Sue.. 54:560-561, 1953. 25. Vicenti, F. A.: Adenocarcinoma arising from an anal gland. J. Florida Med. Assn., 43:254-255, 1956. 26. Wellman, K.F.: Adenocarcinoma of anal duct origin. Can. J. surg., 5:311-318, 1962. 27. Winkelman, J., Grosfeld, J., and Bigelow, B.: Colloid carcinoma of anal-gland origin: report of a case and review of the literature. Am. J. Clin. Patbol., 42:395-401, 1964. 28. Zimberg, Y. H., and Kay, S.: Anorectal carcinomas ofextramucosal origin. Ann. Surg-, 145:344-354, 1957.
Laboratory Service (l 13) Veterans Administration Medical Center 4801 Liuwood Boulevard Kansas City, Missouri 64128 (Dr. Lee)
PRIMARY A D E N O C A R C l N O M A OF AN A N A L GLAND WITH SECONDARY PERIANAL FISTULAS SAING H. LEt, M.D.,* MARJORIE ZUCKER, M.D.,t" AND TATStrO SATO, M.D.~c
A case of primary mucinous (colloid) adenocarcinoma associated with multiple perianal fistulas and a supra-anal interglu}eal abscess of a short duration is described. The origin of this tumor has been much debated. Some believe that the tumor occurs primarily in an anal duct or its glands with secondary fistula formation, whereas others claim that the tumor arises in a chronic fistulous tract. The present study substantiates the former concept on the basis of the mode of clinical presentation and the pathologic findings of a large tumor, without involvement of the anorectal mucosa. The residual anal ducts and glands were found in close relationship with the tumor. Hum Pathol 12:1034-1037, 1981. Primary perianal mucinous (colloid) adenocarcinoma is a rare entity. In 1934 Rosser e~ first described a carcinoma associated with chronic fistula in ano~ Since then n u m e r o u s cases o f perianal colloid carcinoma associated with anal fistulas have been r e p o r t e d wittt discussion o f the possible origin o f the ttnnor. 1"4-6'~'12"1~'1s-24"28 Nevertheless, well d o c u m e n t e d cases o f perianal colloid carcinoma o f anal duct or gland origin have been r e p o r t e d in the literature. a'4.6a'm~2,2s-27 Yet the origin o f the t u m o r remains controversial. This neoplasm primarily affects the o l d e r age g r o u p and there is no significant sex p r e p o n d e r a n c e . T h e t u m o r is clinically characterized by a frequent association with anal a n d perianal fistulas o r abscesses o f various durations. It is known to be a slow growing, locally aggressive neoplasm with a low grade histologic a p p e a r a n c e and rarity o f metastasis. O t h e r characteristic features include frequent recurrence following inadeqtmte resection and late development o f metastasis. T h e diagnosis can be made only by open d e e p biopsy o f the gluteal mass or prolonged nonhealing perianal lesions. T r e a t m e n t is a b d o m i n o p e r i n e a l resection with total ablation o f the t u m o r in the gluteal tissue. T h e duration o f survival varies from months to years, with most patients dying o f either surgical complications o r unrelated diseases. T h e purpose o f this r e p o r t is to record a rare case o f p r i m a r y m u c i n o u s a d e n o c a r c i n o m a t h a t was c a r e f u l l y studied at autopsy, with particular emphasis on the origin o f this unique tumor.
was no evidence o f the tract entering the bowel. Light microscopy showed chronic inflammation, fibrosis, microabscesses, and granulation tissue. T h e patient had a stormy conrse in the hospital a n d was finally discharged in October 1978. His final diagnosis at that time was abscess with chronic infection in the lumbosacrococcygeal area secondary to an infected pilonidal cyst with destruction o f the coccyx and osteomyelitis. T h e patient was a d m i t t e d to the Kansas City Veterans Administration Medical Center on February 8, 1979, with progressive ulceration and persistent chronic infection in the sacracoccygeal and perianal area. Examination revealed an ulcerating sacrococcygeal lesion measuring 6 by 8 cm. filled with a p u r u l e n t e x u d a t e attd g r a n u l a t i o n tissue. Proctoscopic examination revealed no mucosal lesion in the anal and rectal canal. A biopsy specimen o f the lesion in the perianal and sacral areas showed adenocarcinoma. A possible a b d o m i n o p e r i n e a l resection was planned, but the patient's condition d e t e r i o r a t e d and the surgery was not done. He became hypotensive and developed p r e r e n a l azotemia and electrolyte imbalance, which did not r e s p o n d to therapy. His condition c o n t i n u e d to deteriorate and he expired on March 15, 1979. A n autopsy was p e r f o r m e d . PATHOLOGY Gross Findings
At autopsy there was a large ulcer with a firm edge in the skin o f the supra-anal intergluteal area measuring
CASE REPORT A 57 year old white male with known alcoholic liver disease entered another hospital in May 1978 for the treatment o f a pilonidal cyst a n d anal infection with draining sinuses for several weeks. Surgery was p e r f o r m e d , with d e b r i d e ~ e n t and excision o f the pilonidal cyst, scraping o f bone, and perianal fistulectomy. An x-ray view o f the pelvic area at the time showed destruction in the coccyx, but there Accepted for publication December 22, 1980. * Assistant Professor of Pathology, College of tleahh Sciences and Hospital, University of Kansas Medical Center, Kansas City, Kansas. Staff Pathologist, Veterans Administration Medical Center, Kansas City: Missouri. ]" Assistant Profesgor of Pathology, College of Health Sciences and Hospital, University of Kansas Medical Center, Kansas City, Kansas. ~t Associate Professor of Pathology, College of Health Sciences and Hospital, University of Kansas Medical Center, Kansas City, Kansas. Chief, Laboratory Service, Veterans Administration Medical Center, Kansas City, Missouri.
1034
Figure 1. Posterior view of tile anal and rectal canal with : large gelatinous tumor in the ischiorectal fossa.
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.
Mucinous (colloid) adenocarcinoma of anal gland origin. (ltematoxylin and cosin stain. •
9 by 1.5 cm. a n d extending from the superior anal verge to the level o f the coccyx. A large soft gelatinous t u m o r was found involving tile posterior and posterolateral aspects o f the anal and rectal canal. T h e t u m o r was d e e p to the anorectal mucosa and measured 9 by 7 by 5 cm. (Fig. 1). T h e overlying mucosa was not involved by the t u m o r . T h e orifices o f the t h r e e fistulous tracts were noted at the perianal skin and c o m m u n i c a t e d with the tumor. T h e t u m o r completely occupied the ischiorectal fossa a n d e x t e n d e d to the p o s t e r i o r wall o f the pelvis, the coccyx, the gluteal muscles, and soft tissue and had ulcerated throttgh tile supra-anal intergluteal skin to produce the previously described ulcer. T h e r e was no evidence o f metastasis to inguinal o r intral~elvic lymph nodes o r organs elsewhere in the body. O t h e r findings at autopsy were alcoholic micronodular cirrhosis o f the liver with fibrocongestive splenomegaly and massive ascites.
Histologlc Findings Muhiple sections were taken from the rectum and anal canal. Microscopic examination showed invasive mucin p r o d u c i n g adenocarcinoma primarily involving the wall o f the rectum and anal canal and perianorectal soft tissue without involvement o f the mucosa. T h e t u m o r was composed o f various sized spaces filled with a b u n d a n t mucus. Some glafidular spaces were partially lined by mucus secreting c o l u m n a r cells.'In some areas cells o f a signet ring t y p e w e r e n u m e r o u s in pools o f m u t i n o u s m a t e r i a l , whereas o t h e r areas showed well f o r m e d glands lined by similar neoplastic cells (Fig. 2). In m u h i p l e areas pools o f mucus separated the layers o f the anorectal wall and the adjacent soft tissue. T h e r e were microscopic foci o f carcinoma in the coccyx bone. In addition two residual anal ducts anti their glands
were present in the muscular layer o f the anorectal wall. T h e ducts were lined by transitional cells with focal acute and chronic inflammatory infiltrates in the s u r r o u n d i n g tissue. Tile glands were also inflamed but were often lined by tall c o l u m n a r mucus p r o d u c i n g cells and occasional groups o f cells with an eosinophilic g r a n u l a r cytoplasm, p r e s u m ably representing metaplastic cells. In several sections the colloid carcinoma was noted in close proximity to one o f the anal ducts and its gland. T h e fistulous tracts were devoid o f lining e p i t h e l i u m a n d c o n t a i n e d mucus, e x u d a t c , a n d t u m o r cells. T h e walls o f most fistulas revealed acute and chronic focal inflammation as well as t u m o r infiltrate. DISCUSSION Two possible origins o f perianal carcinoma have been proposed: (I) T h e carcinoma arises in a chronic fistulous tract, and (2) it develops from an anal duct o r its gland with secondary fistula formation. Anal ducts and glands have long been known to be present in h u m a n beings, a n d have been well studied in terms o f their embryology, anatomy, and histology by many investigators. 2'4,8,1~ T h e y arise from anal crypts lying in the transitional zone between the rectal mncosa and the anal mucosa. T h e r e are six to eight ducts, which open at the dentate line. T h e y are straight o r spiral tubes with one to six b r a n c h i n g tubules, sometimes f o r m i n g an a c i n a r structure. T h e epithelial lining is usually squamous n e a r the orifice, transitional t h r o u g h o u t most o f the length, and mucus p r o d u c i n g c o l u m n a r epithelium in the terminal acinar structure. In 1934 Rosser 2~ first described a carcinoma associated with chronic fistula in ano. Later his criteria for p r i m a r y perianal carcinomas arising in fistulous tracts included: the fistula antedating the carcinoma, an uninvolved anal and
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PATHOLOGY--VOLUME
12, N U M B E R
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November 1981
r e c t a l mttcosa, a n d t h e o p e n i n g o f tire fistula i n t o t h e a n a l c a n a l o r crypt, n o t i n t o m a l i g n a n t tissue. S k i t ~s s t r e s s e d t h e i m p o r t a n c e o f a l o n g h i s t o r y o f fist u l a in a n o a n d t h e e x c l u s i o n o f a n a n t e c e d e n t c a r c i n o m a to allow d i a g n o s i s o f c a r c i n o , n a a r i s i n g in a b e n i g n f i s t u l a . T i r e r e q u i r e d d u r a t i o n o f s y m p t o m s o f t h e fistula was a r b i t r a r i l y set at I 0 }'ears. Kline e t a l . tz in 1964 s u p p o r t e d R o s s e r 2~ a n d Skir 23 a n d a d d e d five t n o r e cases, lrt t h e i r series t h e d u r a t i o n o f t h e fistula s y m p t o m s r a n g e d f r o m 15 to 4 7 }'ears. Likewise t h e l o n g s t a n d i n g p r e s e n c e o f a n a l fistula in association with c a r c i n o m a is s t r o n g e v i d e n c e in f a v o r o f t h e i r p r e - e x i s t e n c e . H o w e v e r , r e c e n t r e p o r t s f a v o r t h e i d e a t h a t m o s t carc i n o m a s t h a t a l l e g e d l y a r i s e in c h r o n i c fistulas a c t u a l l y o r i g i n a t e in t h e anal dttct, a,4-r.-~ D a v i d 4 claims t h a t a n a l d u c t s play a m o r e p r o n a i n e n t and perhaps even a more determinant role in the p a t h o g e n e s i s o f a n a l fistulas t h a n was p r e v i o u s l y s u s p e c t e d . A r e l a t i o n s h i p b e t w e e n a n a n a l fistula a n d a n a l g l a n d s was first p o i n t e d o u t b y C h i a r i z in 1878. In a l a t e r s t u d y by P a r k s t6 it was f o u n d t h a t 21 o f 30 c o n s e c u t i v e cases o f a n a l fistula ~scre c a u s e d by i u f e c t e d a n a l g l a n d s . R e c e n t l y F e n g e r et al. ~ s t u d i e d e i g h t cases o f colloid c a r c i n o m a a r i s i n g in p r e - e x i s t i n g a n a l fistulas by t h e use o f special m u c i n t t i s t o c h e m i c a l analyses. H e c l a i m e d t h a t in f o u r o f t h e e i g h t cases tire lesions o r i g i n a t e d in t h e a n a l g l a n d s , T h e m u c u s o f t h e a n a l g l a n d s was c h a r a c t e r i z e d by s t r o n g P A S reactivity t h a t was c o m p l e t e l y a b o l i s h e d a f t e r p e r i o d a t e b o r o h y d r i d e s a p o n i f i c a t i o n , ' i n d i c a t i n g t h e scarcity o r a b s e n c e o f 0-acylated sialic acids in t h e a n a l g l a n d m u c u s . T h i s t y p e o f m u c n s is d i f f e r e n t f r o m t h a t p r o d u c e d by globlet cells o f rectal m u c o s a . Now the question remains whether chronic infection h a s a n y causal r e l a t i o n s h i p w i t h t u m o r . It is b e l i e v e d t h a t t h e r e is satisfactory e v i d e n c e t h a t a n a l c a n c e r m a y d e v e l o p in tissne altered by h e m o r r h o i d s , fistulas, o r cicatrices, t~ Since S c a r b o r o u g h 22 in 1941 d e s c r i b e d t h e first p r i m a r y carc i n o m a o f a n a n a l g l a n d , well d o c u m e n t e d s i m i l a r cases h a v e b e e n r e p o r t e d in t h e l i t e r a t u r e . 3.4.6a.tT.e5-z7 R e c e n t l y W i n k e l m a n e t a l . 2r r e p o r t e d a colloid carc i n o m a o f a n a l g l a n d o r i g i n in w h i c h a t r a n s i t i o n f r o m t h e a n a l d u c t orifice to t h e m n c i n o u s p e r i a n a l t u m o r was d e m onstrated. O u r p r e s e n t case s h o w e d m a n ) ' o f t h e typical f e a t u r e s o f a n a n a l g l a n d c a r c i n o m a , m o s t n o t a b l y its exclusively p e r i a n a l i n t r a m u s c u l a r l o c a t i o n with e x t e n s i o n to rite post e r i o r wall o f t h e pelvic cavity a n d i n t e r g l u t e a l soft tissue, without involvement of the rectal or anal mucosa, Other characteristic features included tbe mode of clinical p r e s e n t a t i o n . T h e r e was a s h o r t d u r a t i o n o f t h e anal fistulas, a n d t b r e e o p e n i n g s w e r e i n t o t h e p e r i a n a l skin, n o t i n t o t h e a n a l canal. In a d d i t i o n , s e v e r a l r e s i d u a l a n a l d u c t s a n d g l a n d s w e r e f o u n d in close p r o x i m i t y to t h e t u m o r . O u r p a t i e n t h a d a h i s t o r y o f o n l y a o n e }'ear i n t e r v a l b e t w e e n t h e o n s e t o f t h e a n a l fistula a n d t h e d i a g n o s i s o f c a r c i n o m a . T h i s is too s h o r t a p e r i o d to p o s t u l a t e t h a t t h e c a r c i n o m a d e v e l o p e d in a b e n i g n fistula, especially in view o f t h e l a r g e size o f t h e t u m o r . W e b e l i e v e t h a t it is m u c h m o r e likely t h a t this t u m o r , w h i c h is typically slow growiHg, was p r e s e n t subclinlcally f o r s o m e time~ a n d p r e d a t e d t h e fistnlas. T h e colloid c a r c i n o m a with a b u n d a n t m u c i n p r o d u c t i o n in all likelihood h a d a g r e a t t e n d e n c y to dissect soft t i s s u e p l a n e s , l e a d i n g to t h e s e c o n d a r y d e v e l o p m e n t o f p e r i a n a l fistulas. T h e late d i a g n o s i s o f this t u m o r a n d 9 n g m a l l y n e g a t i v e biopsy studies support the contention that a high index of suspicion and adequate deep biopsies are of great import a n c e in cases o f m u l t i p l e c h r o n i c r e c u r r e n t fistula in ano.
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Acknowledgments T h e a u t h o r s wisb to t b a n k A n i t a Y. D i x o n , M.D., a n d S h e r r y R a m p a n t f o r t h e i r assistance in t h e p r e p a r a t i o n o f the manuscript. References 1. Chaos, A., Garrido, H.. Fernandex-Villoria, J. M., Dominquez, J., and Cano, M.C.: Carcinoma associated ~,hh fistula-in-ano. Int. Surg., 58:497-499, 1973. 2. Chiari, H.: Uber die Analen Di~ertikel der Rectumschleimhaut und ihre Beziehung zu den Analfistcln, Med. Jahrb. Wien. 8:419-427, 1878. 3. Close, A.S., and Schwab, R. L: tlistory of anal ducts and anal-duct carcinoma: report of a case- Cancer, 8:979-985, 1955. 4. David, A.: Tumors of the Intestines. Atlas of Tumor Pathology. Washington, D.C., Armed Forces Institute of Pathology, 1967, Section VI, Fascicle 22. 5. Dukes, C. E., and Galvin, C.: Colloid carcinoma arising within fistulae in the anorectal region. Ann. Roy. Coll. Surg. Engl., 18:246-261, 1956. 6. Fcnger, C., and Filipe, M. I.: Pathology of the anal glands with special reference to their mucinons hlstochemistry. Acta Path. Microbiol. Scand. (Sect. A), 85:273-285, 1977. 7. l-tag.ibara, P., Vazquez, M. D., Parker, J. C., and Griffe4~r W. O.: Cartrauma of anal-ductal origin: report of a case. Dis. Col. Rect., 19:594-701, 1976. 8. }tarrison, E. C.: Anal and perianal malignant neoplasms: pathology and treatment. Dis. Col. Reef., 9:255-267, 1956. 9. Heindenreich, A., ColIarini, H. A., Paladino, A. M., Fernande,, J. M., and Calvo, T. O.: Cancer in anal fistulas. Dis. Col. Rect., 9:571-376, 1966. I0. Herrmann, G.: Sur la structure et le d~veloppement de la muqueuse anale. J. Anat. Physiol., 16:434-472, 1880. 11. Johnson, F. P.: The development of the rectum in the human embryo. Am.J. Anat., 16:1-57, 1914. 12. Kline, R.J., Spencer, R.J., and Harrison, E. G.: Carcinoma associated with fistula-in-ano. Arch. Surg., 89:989-994, 1964. 13. Kratzer, G. l., and Dockerty. M. B.: Histopathology of the anal ducts. Surg. Gynecol. Ob~tet., 84:333-338, 1947. 14. McColI, l.: The comparative anatomy and pathology of anal grands. Ann. Roy. Coll. Surg. Engl-, 40:36-67, 1967, 15. Nielsen, O. V., and Koch, F-: Carcinomas of the ano~ectal region of extramucosal origin with special reference to the anal ducts. Acta Chir. Stand., 139:299-305, 1973. 16_ Parks, A. G.: Modern concepts of the anatomy of the anorectal region. Postgrad. *ted. J., 34:360-366, 1958. 17. Pollice, L., and D'Abriceo. V.: On anorectal carcinoma with extramueosal site. Notation of a new case of carcinoma of Hermann's perianal gland. Rev. Anat. Pathol. Oncol., 15:423-441, 1959. 18. Prioleau, P.G., Allen, M.S., and Roberts, T.: Perianal mutinous adenocarcinoma. Cancer, 39:1295-1299, 1977. 19. Rosser, C.: The etiology ofanal cancer. Am.J. Surg., 11:328-333, 193 I. 20. Russet, C.: The relation of fistula-in-ano to cancer of the anal canal. Tr, Am. Proct. Sue., 35:65-71, 1934. 21. Rundle, F.F., and Hales, I. B.: Mncoid carcinoma supervening on fistula-in-ano; its surgical pathology and treatment. Ann. Surg-, 137:215-219. 1953. 22. Scarborough, R. A.: Primary carcinoma of an anal glared. Tr. Am. Proct. Sue., 42:172-176, 1941. 23. Skit, l.: Mucinous carcinoma associated ~'ith fistulas of long-standing. Am.J. Surg., 75:285-289, 194K 24. Stockman, J. M., and Young, V, I.: Carcinom tssociatedwith anorectal fistula. Tr. Am. Proct. Sue.. 54:560-561, 1953. 25. Vicenti, F. A.: Adenocarcinoma arising from an anal gland. J. Florida Med. Assn., 43:254-255, 1956. 26. Wellman, K.F.: Adenocarcinoma of anal duct origin. Can. J. surg., 5:311-318, 1962. 27. Winkelman, J., Grosfeld, J., and Bigelow, B.: Colloid carcinoma of anal-gland origin: report of a case and review of the literature. Am. J. Clin. Patbol., 42:395-401, 1964. 28. Zimberg, Y. H., and Kay, S.: Anorectal carcinomas ofextramucosal origin. Ann. Surg-, 145:344-354, 1957.
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