Colitis Cystica Profunda*

j . KIRK MARTIN, JR., M . D . , CLYDE E. CULP, M . D . ,

Louis n . WEILAND, M.D.

Martin JK Jr, Culp CE, Weiland LH. Colitis cystica profunda. Dis Colon Rectum 1980;23:488-491. Colitis cystica profunda is a be- nign disease of the colon. Its importance lies in differentiating it from mucus-producing adenocarcinoma. It has rarely been de- scribed in the surgical literature. A review of records of patients seen at the Mayo Clinic produced 66 clinical cases of localized colitis cystica profunda, and in 21 patients the diagnosis was confirmed histologically. Follow-up, which was available in all patients, ranged from 2 months to 29 years, with a mean follow- up of more than 8 years. The data suggest that local excis ion is the preferred initial therapy. [Key words: Colitis cystica pro- funda; Colon; Cyst(s), submucosal; Polyp(s), rectal]

CoH'r ts CYSTICA PROFUNDA is a benign lesion of the colon. Once cons idered to be rare, it is being diag- nosed with increasing frequency, so the t rue inci- dence and prevalence are unknown. I t is impor t an t tha t the lesion be d i f f e r e n t i a t e d f r o m a m uc us - p roduc ing adenoca rc inoma and that the rectal bleed- ing and d ia r rhea that accompany colitis cystica pro- funda be p roper ly treated. In reviewing the English medical l i terature, we found only 66 cases repor ted . A review of the Mayo Clinic exper ience of 21 patients with histologically p roved lesions forms the basis for this repor t .

M a t e r i a l s a n d M e t h o d s

T h e records of all patients seen at the Mayo Clinic between 1968 and 1979 with colitis cystica p r o f u n d a were retrospectively reviewed. F rom these records, 66 cases were identif ied in which the diagnosis had been made by history, physical examinat ion , and procto- scopic examinat ion, with or without the aid of ba r ium enema study. Between 1968 and 1975, there were 45 cases, and du r ing the final 4 years of the s tudy period, 21 cases were found. To establish a more h o m o g e n e - ous g roup of patients and to eliminate any doubt about the diagnosis, only patients who had histologic p r o o f of colitis cystica p r o f u n d a were chosen for

* Read at the meeting of the American Society of Colon and Rectal Surgeons, Hollywood, Florida, May 11 to 16, 1980.

Address reprint requests to Dr. Martin: Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55901.

From the Department of Surge U, the Section of Colon and Rectal Surge' U , and the Department of

Surgical Patholo~, Ma'r Clinic and M~o Foundation, Rochester, Minnesota

f u r t he r study. This g r o u p consisted of 21 patients, including 2 f rom our early exper ience.

T h e ages of the 21 patients (14 women and 7 men) r anged f rom 14 to 66 years and averaged 39 years. T h e women patients t ended to be slightly youn g e r than the men, 35.9, c o m p a r e d with 45.6 years. Fre- quen t symptoms were rectal b leed ing (81 per cent), mucus discharge (35 per cent), d ia r rhea (30 per cent), and pain, ei ther per ineal or abdomina l (10 per cent). Only one pat ient had associated chronic ulcerative colitis. T h e dura t ion o f symp toms before evaluat ion at ou r clinic r anged f r o m 1 week to 22 years and averaged 37 months . Only, 2 of the 21 patients, both male, were asymptomat ic , and the lesions in both were found incidentally on rout ine examinat ion .

Most of the lesions were descr ibed at proctosig- moidoscopy as f i rm nodules with an over lying ery- thematous mucosa, occasionally with a white "cap" (Fig. 1). In 19 patients, the location of the lesions var ied f rom just above the denta te line to 15 cm above it. In the r emain ing two patients, the nodules were located in the s igmoid colon, without rectal involve- ment . T h e most f r equen t site o f invo lvement was on the anter ior rectal wall be tween 6 and 7 cm above the denta te line. In fact, 60 per cent of the lesions oc- cu r r ed on the anter ior rectal wall, whereas the re- ma inde r occur red with equal f requency on the poste- r ior wall, lateral walls, and sigmoid.

In both patients with s igmoid lesions, colonoscopy was a t t empted . In one, tissue showed an atypical po lyp with areas of mucous gland hyperplas ia and foci o f ulcerat ion and in f lammat ion . In this patient, b a r i um e n e m a s tudy also d e m o n s t r a t e d mucosal in- f l ammatory bowel disease involving the sigmoid colon and rec tum, and a b d o m i n o p e r i n e a l resec t ion was p e r f o r m e d . In the o the r pat ient with s igmoidal in-

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volvement, colonoscopy failed to reach the lesion, so opera t ion was advised, and a sigmoid colotomy with excision of the localized area of colitis cystica pro- funda was per formed.

Pathologic Findings

Grossly, the lesion in colitis cystica p ro funda is a broad-based polyp or nodule covered over by intact mucosa. Cutt ing across the mass reveals mucus-filled cystic spaces in the classic lesion, but only thickening of the submucosa in lesions that are at an earlier stage.

On microscopic examination, several features are prominent . The most impor tan t is the presence of benign colonic epi the l ium benea th the muscularis propria. In some lesions, an actual communica t ion with the overlying mucosa can be seen (Fig. 2B). This ectopic epi thel ium produces mucus that forms cystic spaces. Usually, the mucus escapes and dissects into the loose connective tissue of the submucosa (Fig. 2A). A f requent feature is hyperplasia of the overly- ing mucosa (Fig. 2B). This villous hyperplasia is prob- ably a reactive process related to the submucosal thick- ening; we do not believe that it is related to villous adenoma or o ther neoplasia. It might lead to an er- roneous diagnosis if biopsy specimens are superficial and do not include submucosa.

Treatment and Follow-up

Follow-up was 100 per cent and ranged f rom 2 months to 29 years, With an average of 8.4 years. T r e a t m e n t va r ied f rom excis ional biopsy to ab- d o m i n o p e r i n e a l resect ion. T h e r e were no deaths af ter t reatment.

Of the 21 patients, 19 underwent only biopsy of the rectosigmoid lesions. Just 2 of the 12 patients were asymptomatic at tbllow-up. T h e symptoms ranged f rom inf requent rectal bleeding to more p ronounced diar rhea and bleeding with anemia. Extensive local disease in two patients involved ahnost c i rcumferen- tial rectal nodules and precluded local excision. One patient in this t reatment group died from cancer of the cervix dur ing the follow-up period.

Six patients underwen t excision of the colitis cystica p rofunda , five transanally and one transabdominally. Of these six patients, two with transanal excision were asymptomatic, one 4 months and the o ther 5 years af ter operation. The patient who underwen t sigmoid colotomy and excision was asymptomatic 8 years after ope ra t ion . One asymptomat ic pa t ient t r e a t ed by transanal excision was asymptomatic preoperatively, as was the patient who unde rwen t colotomy. T h e three o ther patients t reated by transanal excision

FIO. 1. Proctoscopic appearance of' colitis cystica profunda.

were all symptomatic: two had rectal bleeding that requi red iron supplementa t ion , and the other had i n f r e q u e n t rec ta l b l e e d i n g that i m p r o v e d post- operatively.

One patient was t rea ted with five fulgurat ions of the lesions, which involved the anter ior two-thirds of the rectal c i rcumference. She continues to have occa- sional rectal bleeding, and the lesions have persisted, unchanged, dur ing the last 3 years. Interestingly, this patient was given corticosteroid therapy for chronic active liver disease and exper ienced a t empora ry im- p rovemen t in rectal bleeding and mucous diarrhea.

T h e two pa t i en t s who u n d e r w e n t a b d o m i n o - per ineal resection were both asymptomat ic 4 and 29 years af ter their p rocedures , the more recent patient undergo ing opera t ion for chronic ulcerative colitis with coexisting colitis cystica p rofunda .

Carcinoma of the colon did not develop in any of ou r patients, and no pat ient in our series died f rom complications directly related to colitis cystica pro- funda. Additionally, no patient had a hemoglobin level of less than 11 g/dl; the average hemoglobin level for the g roup was 13.0 g/dl. O f the patients who complained of mucous diarrhea, none had a total protein value of less than 6.4 g/dl, with the average being 6.9 g/dl. In one patient, rectal stenosis de- veloped after a 4-year history of disease and after multiple biopsy specimens were taken. This patient was considered to have colloid carcinoma and was t reated by abdominoper inea l resection. No patient had rectal prolapse.

Discussion

Although colitis cystica p ro funda was apparent ly f irst descr ibed by Stark , 1'2 la ter desc r ip t ions by

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FIG. 9. Colitis cystica profunda. A. Pools of mucus dissect the loose connective tissues of submucosa. Epithelial cells that produce mucus may be obscure (hematoxylin and eosin; • 60). B. Points of communication from mucosa across muscularis mucosa and into submucosa may occasionally" be seen. Villous hyperplasia of mucosal glands is a frequent finding (hematoxylin and eosin; x 42).

Roki tansky a (1839), Virchow 4 (1863), W o o d w a r d 5 (1879), and Vanzetti 6 (1992) did little to st imulate interest in the disease. Goodal l and Sinclair r (1957), in Britain, reviewed the l i terature and p resen ted two cases, reviving apprec ia t ion of the entity. Epstein and colleagues, s in 1966, p resen ted the first descr ipt ion of the disease in the Uni ted States and discussed four cases seen at Columbia University between 1955 and 1960. T h e largest collected series comes from. Wayte and Helwig ~a at the A r m e d Forces Insti tute of Pathol- ogy. T h e y presented 19 cases of localized colitis cys- tica p r o f u n d a and 5 of the diffuse variety. T o our knowledge, our series is the largest collection of cases o f localized colitis cystica p r o f u n d a f r o m a single institution.

O u r first pat ient was seen 17 years before the first Amer ican descript ion of the disease. This 56-year-old w o m a n had a 4 -yea r h i s to ry o f " u n u s u a l " rectal po lyps , rec ta l b l eed ing , and t e n e s m u s . Mul t ip le b i o p s y s p e c i m e n s were i n t e r p r e t e d as s h o w i n g nonspecific inf lammation�9 Proctoscopy revealed a ses- sile, potypoid lesion 8 cm above the dentate line, ac- compan ied by leukoplakia. T h e biopsy spec imen was in te rp re ted as grade 1 colloid adenocarc inoma, and an abdominoper inea l resection was p e r f o r m e d . Sub- sequent review of the tissue by one of us (L.H.W.)

c o n f i r m e d colitis cystica p ro funda . This pat ient has been followed for 29 years and is included in the p re sen t study. T h e resect ion in 1949 is the only in- stance in which ou r pathologist suspected ca rc inoma f rom biopsy material�9

T h e etiology of colitis cystica p r o f u n d a is unknown. Several theories have been advanced to explain the fo rma t ion o f mucus-conta in ing cysts in the submu- cosa of the bowel wall. Wayte and Helwig 9 ascribed the deve lopmen t to mucosal ulcerat ion and destruc- tion of the muscularis mucosae, as did Goodal l and Sinclair. r Epstein et al. s believed that the lesion proba- bly results f rom hern ia t ion of the mucosa t h r o u g h a weak or d a m a g e d muscular is or f r o m epithelialization o f deep in f l ammato ry ulcers.

We agree with Rut te r and Riddell 1~ that colitis cys- tica p r o f u n d a is likely the end response to in f l amma- tory or traumatic factors and develops f rom a preced- ing rectal ulcer. In 5 o f our 21 patients, s imul taneous rectal u lcera t ion was no ted on initial proctoscopic examinat ion , and in 2 others, subsequen t proctoscopy revealed ulceration.

O t h e r investigators also ascribe the d e v e l o p m e n t of colitis cystica p r o f u n d a to in f lammat ion . Brynjolfsson and Haley it successfully p r o d u c e d lesions histologi- cally similar to colitis cystica p r o f u n d a in rats by ex-

V o i u me 23 .',u~,be~-7 COLITIS CYSTICA PROFUNDA 491

t e r i o r i z i n g a p a t c h o f smal l bowel m u c o s a on the ab- d o m i n a l wall. T h e i n f l a m m a t i o n thus c r e a t e d l ed to the f o r m a t i o n o f s u b m u c o s a l m u c u s - c o n t a i n i n g cysts. H e r m a n a n d N a b s e t h ~e r e p o r t e d a case in wh ich a d i v e r t i n g d e f u n c t i o n a l i z i n g s i g m o i d c o l o s t o m y c a u s e d h e a l i n g o f the les ions in the r e c t u m .

In the ea r ly l i t e r a t u r e , the colitis cystica p r o f u n d a was c o n s i d e r e d to be a r a r e c o m p l i c a t i o n o f c h r o n i c u lce ra t ive colitis, ta O n l y one pa t i en t in o u r ser ies had c h r o n i c u lce ra t ive colitis a n d one o t h e r h a d a h i s to ry o f it.

T h e u s u a l m e t h o d s o f p r o c t o s c o p i c r e m o v a l o f b iopsy t issue f r e q u e n t l y fail to p r o d u c e a s p e c i m e n o f s u f f i c i e n t d e p t h to p r o v i d e a c o n c l u s i v e h i s - t o p a t h o l o g i c d iagnos i s . ~e T h e cons i s t ency o f a f i rm, c y s t i c - a p p e a r i n g n o d u l e is such that w h e n the n o d u l e is g r a s p e d by a b iopsy fo rceps , the jaws o f the i n s t ru - m e n t fail to p e n e t r a t e to the s u b m u c o s a . In fact, 10 o f o u r pa t i en t s h a d p r i o r p roc to scop i c b iopsy tha t d id no t show d i agnos t i c f e a t u r e s o f colitis cyst ica p ro - f u n d a . W e bel ieve tha t su rg ica l exc i s ion o f a n o d u l e is the p r e f e r r e d way to p r o v i d e the p a t h o l o g i s t with a s p e c i m e n for s tudy . Likewise , w h e n recta l les ions a re sugges t ive o f the p r e s e n c e o f colitis cystica p r o f u n d a a n d the b iopsy s p e c i m e n is r e p o r t e d to show a vil lous a d e n o m a , exc i s iona l b iopsy s h o u l d be c o n s i d e r e d to p r o v i d e an a d e q u a t e s p e c i m e n , because the o v e r l y i n g m u c o s a may exh ib i t vi l lous fea tu res .

Resul ts o f t r e a t m e n t in p u b l i s h e d r e p o r t s s eem to i n d i c a t e tha t loca l e x c i s i o n is f a i r ly e f f e c t i v e a n d safe. s, ~e, L4 ,.~ O f the pa t i en t s with loca l ized colit is cys-

t ica p r o f u n d a d e s c r i b e d in the l i t e r a tu r e , 29 h a d been t r e a t e d by local exc i s ion a n d h a d fo l l ow-up d a t a avail- able. In this g r o u p , 23 (79 p e r cent) were f ree o f s y m p t o m s a f t e r the o p e r a t i o n . In W a y t e a n d He lwig ' s ser ies , ~ 12 o f 17 p a t i e n t s with local exc i s ion were s y m p t o m - f r e e .

O u r own e x p e r i e n c e with local exc i s ion has no t b e e n as f avorab le . O n l y t h r e e o f six pa t i en t s were s y m p t o m - f r e e a f t e r local excis ion, a n d only two o f the f ive p a t i e n t s t r e a t e d by t r a n s a n a l e x c i s i o n w e r e s y m p t o m - f r e e . Even less f a v o r a b l e resul t s were n o t e d in t he g r o u p tha t had b iopsy only. In this g r o u p , 2 o f 19 pa t i en t s were a s y m p t o m a t i c when fo l l owed up an a v e r a g e o f 7 ?'ears 4 m o n t h s ( r ange 3~~ to 123A years) . In fact, the on ly t r e a t m e n t tha t was u n i f o r m l y effec- t ive was r e s e c t i o n o f the a f f e c t e d bowel. T h e les ion m u s t be c o m p l e t e l y exc i sed if r e l i e f o f s y m p t o m s is to be o b t a i n e d with any f r e q u e n c y . Excis ion is s o m e w h a t d i f f i cu l t because the s u b m u c o s a mus t be i n c l u d e d . T h e d e g r e e o f s y m p t o m s a n d the d isab i l i ty i n c u r r e d

by t h e p a t i e n t s a l so m i g h t r e q u i r e a g g r e s s i v e t h e r a p e u t i c e f for t s . W h e t h e r t h e r a p y a i m e d at de-

c r e a s i n g i n f l a m m a t o r y r e s p o n s e , such as c o r t i c o - s t e ro ids o r c o r t i s o n e e n e m a s , may have a ro le is u n - known . P e r h a p s t h e i r use in ex t ens ive d i sease m i g h t be i nd i c a t e d . In any event , ha l f to t h r e e - f o u r t h s o f the pa t i en t s were a s y m p t o m a t i c a f t e r local exc is ion , a n d this sugges t s tha t local exc i s ion is the ini t ia l t h e r a p y o f choice . O b s e r v a t i o n o r b iopsy on ly does n o t s e e m to be o f value in the t r e a t m e n t o f colitis cyst ica p ro - f u n d a . I f local i n f l a m m a t i o n o r i r r i t a t i n g fac tors can be i d e n t i f i e d a n d e l i m i n a t e d , t h e n this s h o u l d accom- p a n y any t h e r a p y .

Be c a use colit is cyst ica p r o f u n d a m a y d e v e l o p a f t e r rec ta l u l c e r a t i o n f r o m va r ious fac tors , it m a y no t be a s e p a r a t e d isease ent i ty . O n c e e s t ab l i shed , h o w e v e r , the c o n d i t i o n t e n d s to pe r s i s t (in one o f o u r pa t i en t s , the les ions have b e e n k n o w n to pers i s t for 23 years ) , a n d s p o n t a n e o u s h e a l i n g is r a r e . T h e d e s i g n a t i o n "coli t is cystica p r o f u n d a " p r o b a b l y s h o u l d be r e t a i n e d be c a use the c o n d i t i o n has a c o n s t a n t c l in ica l m a n i f e s - t a t ion a n d m a y r e s p o n d to t r e a t m e n t .

R e f e r e n c e s

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3. Rok tansky Cited by Yeomans FC. Proctology: a treatise on the malformations, injuries and diseases of the rectum, anus and pelvic colon. New York: D Appleton & Co, 1929:460.

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5. Woodward JJ (US Surgeon General's Office). The medical and surgical history of the war of the rebellion. Vol. l, Pt. 2. Washington, DC: Government Printing Office, 1879:511-5.

g. Vanzetti F. Sulla colite cistica. Arch Sci Med 1922;65:43-66. 7. Goodall HB, Sip.clair ISR. Colitis cystica profunda. J Pathol

Bacteriol I957:73:33-42. 8. Epstein SE, Ascari WQ, Ablow RC, Seaman WB. Lattes R.

Colitis cystica profunda. AmJ Clin Pathol 1966;45:186-201. 9. Wayte DM, Helwig EB. Colitis cystica profunda. Am J Clin

Pathol 1967;48: 159-69. 10. Rutter KRP, Ridde[l RH. The solitary ulcer svndrorne of the

rectum. Clin Gastroenterol 1975;4 no. 3:505-30. 1 !. Brynjolfsson G, Haley HB. Experimental enteritis cystica in

rats. Am J Clin Pathol 1967;47:69-73. 12. Herman AH, Nabseth DC. Colitis cystica profunda: localized,

segmental, and diffuse Arch Surg 1973;106:337-41. 13. Morson BC. Pathology. In: Goligher JC, de Dombal FT, Watts

JMcK, Watkinson G, eds. Ulcerative colitis. Baltimore: Wil- liams g: Wilkins Company, 1968:29.

14. Ballas M, Nunez L, Miller EM. Localized colitis cvstica pro- funda. Arch Surg 1971 ; 103:406-8.

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I6. Barcia PJ, Washburn ME. Colitis cystica profunda: an unusual surgical problem. Am Surg 1979;45:61-6.