post-mortem the - gut · post-mortem examination ofasmallintestine in the coeliac syndrome fig. 1....

Gut, 1965, 6, 466

Post-mortem examination of a small intestine in thecoeliac syndrome

B. CREAMER AND P. LEPPARD

From the Gastro-Intestinal Laboratory, St Thomas's Hospital, London

EDITORIAL SYNOPSIS This is an illustrated account of the post-mortem appearances of the smallintestine from a patient with a secondary coeliac syndrome. It shows the value of the dissectingmicroscope in the examination of such material.

Histological examination of the small intestine afterdeath is almost invariably valueless because ofautolysis. This is the reason why the lesion of idio-pathic steatorrhoea or coeliac syndrome has onlybeen recognized in recent years with the introductionof peroral biopsy. These biopsies can be profitablyexamined under the dissecting microscope (Rubin,Brandborg, Phelps, and Taylor, 1960; Holmes,Hourihane, and Booth, 1961) but as yet there havebeen no reports of post-mortem material examinedin this way.

This paper describes and illustrates the post-mortem changes in the small intestine from a patientwho died with a coeliac syndrome secondary toreticulum cell sarcoma (Hindle and Creamer, 1965).The material also shows the difference between theante-mortem and post-mortem appearances of theintestine as viewed through the dissecting micro-scope.

METHODS

The whole small intestine of a man with secondarycoeliac syndrome was available for study. Specimensabout 2 cm. square were taken every 8 in. from the upperduodenum to the terminal ileum; there were 23 speci-mens. They have been numbered 1 to 23 from duodenumto ileum. They were pinned flat without obliterating themucosal folds and stained with 5% alcoholic eosin andcleared in xylol. Each specimen was examined under thedissecting microscope and several areas photographed,always recording separately appearances on the crests ofthe mucosal folds and in the troughs between them.

CASE HISTORY

The patient was a man of 55 who developed diarrhoea,weight loss, oedema, tetany, and a sore tongue and wasadmitted in September 1963 after an illness of fivemonths. He presented with the typical appearances ofmalabsorption and had a faecal fat excretion of 26-1 g.

per day. Investigations showed a megaloblastic anaemiawith folic acid deficiency, low serum calcium, hypo-proteinaemia, and positive evidence of exudative entero-pathy. A small bowel meal showed an abnormal appear-ance compatible with steatorrhoea and jejunal biopsyshowed a flat mucosa.He was treated on a gluten-free diet and improved

remarkably but two weeks after starting this, spon-taneously perforated in the mid-ileum. Eight inches ofileum were resected and he made an uninterruptedrecovery. Examination of the specimen showed a simpleperforation without any tumour mass but histology re-vealed a small area on the edge of the perforation whichlooked like reticulum cell sarcoma. Under the dissectingmicroscope the mucosa showed a convoluted pattern onthe crests of the mucosal folds and a leafy appearance inthe troughs. Histology confirmed this showing a markeddifference between the crests and the troughs. The patientcontinued to respond to the diet and regained normalhealth and weight. In April 1964 diarrhoea and wastingreappeared and he was readmitted. This time his appear-ance was similar to that on the first admission exceptthat he had enlarged glands in an axilla and one groin.Biopsy of these showed reticulum cell sarcoma. He againhad a full malabsorption syndrome and a flat jejunalmucosa. He was treated with chlorambucil, 5 mg. t.d.s.,and the remaining glands shrank and disappeared in onemonth. During this time two further jejunal biopsiesshowed no significant change except for some diminutionin mitosis. However, he went steadily downhill and diedwith gross emaciation. Necropsy was carried out twenty-four hours after death. There was no evidence of lymph-oma in any part of the body. The small intestine wasopened and fixed in formalin.

RESULTS

The structure of the mucosa, as viewed under thedissecting microscope, was excellently preservedthroughout the whole small intestine. Histologicalsections, however, showed an appearance thatwould be dismissed as autolysis because almost all

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Post-mortem examination of a small intestine in the coeliac syndrome

FIG. 1. Peroral jejunal biopsy taken one month beforedeath.

FIG. 3. Specimen no. 2: trough between mucosalfolds.

the epithelial cells covering the surface were missingand those in the crypts were extremely degenerate.When the post-mortem mucosa was compared withthe ante-mortem biopsies the explanation of thisdiscrepancy was immediately apparent (Figs. 1 and2). The visibly stained structures were the nakedstroma of the epithelium; in fact the basementmembrane was now the surface. Thus the orificesin the jejunum were large in the post-mortemmaterial but like buttonholes in the biopsies. In

FiG. 2. Specimen no. 2: crest of mucosalfold.

FIG. 4. Specimen no. 5: crest of mucosalfold.

these post-mortem orifices cell debris could be seen.Similarly in the lower parts of the small intestine theconvolutions and leaves were thinner when comparedwith the surgically resected specimen and werenaked structures.

OVERALL PICTURE The specimens showed a com-plete gradation from a flattening in the duodenumand upper jejunum to a nearly normal appearance inthe terminal ileum (Figs. 2-16). With the exception

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of differences due to site on the mucosal folds therewas little irregularity in the gradual change fromtop to bottom of the small intestine. As the mucosalstructure became more complicated in the ileumthe range of variations seen at any one level becamegreater.

MUCOSAL FOLDS In every specimen there was adifference between the structure on the crests of themucosal folds compared with the troughs in between,



but this was more marked in the mid and lowerintestine than in the upper. On the crests thestructures were always flatter and simpler than thosein the troughs (Figs. 2-12). Where ridges and leaveswere present these were orientated so they rantransversely across the folds, that is, along theluminal axis of the intestine (Fig. 11). Finger-shapedvilli were not seen on the crests of the folds exceptin the terminal ileum, where the folds were scantyand small.

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Post-mortem examination of a small intestine in the coeliac syndrome

FIG. 9. Specimen no. 10: trough between mucosalfolds. FIG. 10. Specimen no. 13: trough between mucosalfolds.


TRANSITION FROM NORMAL TO FLAT APPEARANCE Inthe lower ileum there were easily recognizablefinger-shaped villi (Fig. 16). There was, however,often a profusion of appearances with finger villi,leaves, and doughnut-like structures with a cryptopening in the centre. In between the villi of what-ever shape crypt orifices could be seen. A littlehigher leaf-shaped structures predominated butthere were also some interconnecting convolutions(Fig. 15). In the upper ileum there was an obviously

. 12. S i n. : t,_FS Mr e _ E . . _ _iv

FIG. 12. Specimen no. 18: trough between mucosal folds.

convoluted pattern with a maze of ridges joiningand dividing with the openings of crypts clearlyvisible between them and occasionally opening in themiddle of a ridge (Fig. 10). At slightly higher levelsthe ridges became larger and were usually orientatedso that most ran in one direction with slenderconnecting cross ridges. Higher in the jejunum theridges became lower structures and holes betweenthem more circular; these orifices were much largerthan the crypt openings in the ileum (Fig. 6). In the

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FIG. 13. Specimen no. 20: trough between mucosalfolds. FIG. 14. Specimen no. 21: trough between mucosalfolds.

FIG. 15. Specimen no. 22: trough between mucosa folds.

upper jejunum and duodenum the mucosa on thecrests of the mucosal folds, which were larger thanthose in the ileum, was completely flat with largeorifices giving a pigskin-like appearance and at thebottom of these orifices the openings of two or threecrypts could be seen (Fig. 2). In the troughs themucosa was also flat but about the orifices thestructure was slightly raised looking more like a

honeycomb (Fig. 3). Over this area a crazy-pavingpattern was present, more prominent on the crests


of the folds (Fig. 17). This pattern delineated areascontaining from five to 50 orifices.

CUT SURFACE OF MUCOSA When the specimens werecut vertically the mucosa could be examined as in ahistological section. The detail here was not asgood as on surface inspection but the relation oforifices to crypts could be seen. In the duodenum andupper jejunum there were more crypts than orificesand crypts appeared to join to form an orifice. In the

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Post-mortem examination ofa small intestine in the coeliac syndrome 471

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FIG. 17. Specimen no. 5: low-power view showing crazypaving pattern.

lower parts of the small intestine the crypts couldbe seen to open directly onto the surface. The outlineof the crazy paving appeared to be gutters of thesame depth as the orifices and were thus orificesextended in one direction.

DISCUSSION

In this case the whole small intestine obtained at aroutine necropsy 24 hours after death was entirelysatisfactory for examination by the dissectingmicroscope although histology showed markedautolysis. The lack of enzymes in the abnormalmucosa may have favoured the preservation but wehave so far found that many other cases can besimilarly examined at necropsy (Loehry andCreamer, 1965). The structure differs from biopsyand surgical specimens in that it is denuded ofsurface epithelium and it is the stroma which isbeing examined. This, however, gives a vivid viewof the mucosal architecture. Although the patientwas treated with chlorambucil in life it seems unlikelyto have caused much change in the mucosa, asbiopsies before death showed little change.From this study certain points emerge. The

mucosal abnormality is most marked in the duo-denum and upper jejunum and gradually changes toa near normal appearance in the lower ileum. Thisis in accord with the studies where the ileum has

been biopsied (Rubin et al., 1960). The gradualchange from a flat to normal appearance passesthrough a variety of structures with a graduallyincreasing surface area. This can be better appreci-ated from the illustrations than from any writtendescription. It is clear that a flat mucosa must be avery stable structure while convolutions, leaves, andfinger villi represent a change to increasingly vulner-able and unstable projections. This is emphasizedby the marked difference between the mucosa on thecrests of folds and that in the more shelteredtroughs. This would seem to be due to traumaand any theory of the genesis of the abnormal mucosamust take this into account.The findings also show that abnormal mucosal

structures are moulded by certain factors, presumablymainly by the intestinal movements and flow ofcontents. Thus the ridges on the crests of the foldsalways ran across the fold and not along it. Also thecrazy paving pattern seen in the upper small intestineis a guttering dividing up the mucosa into smallareas and would seem to be again the result ofintestinal movement, allowing for buckling andstretching.

This method of examining the small intestinegives a vivid picture of the relation of crypts tovillous structures. In the upper small intestine theorifices opening onto the surface appear to becommon channels for more than one crypt while inthe ileum the crypts open directly at the base ofvilli.

SUMMARY

The whole small intestine of a patient who diedfrom a secondary coeliac syndrome due to reticulumcell sarcoma has been examined by the dissectingmicroscope. This report illustrates the spectrum ofchange from the flat upper intestinal mucosa to thealmost normal lower ileum. The mucosal structuresare naked of epithelial cells and represent thestromal architecture.

REFERENCES

Hindle, W., and Creamer, B. (1965). The significance of a flat smallintestinal mucosa. Brit. med. J., 2, 455-458.

Holmes, R., Hourihane, D. O'B., and Booth, C. C. (1961). Themucosa of the small intestine. Postgrad. med. J., 37, 717-724.

Loehry, C. A., and Creamer, B. (1965). Unpublished observations.Rubin, C. E., Brandborg, L. L., Phelps, P. C., and Taylor, H. C. Jr.

(1960). Studies of celiac disease. I. The apparent identical andspecific nature of the duodenal and proximal jejunal lesion inceliac disease and idiopathic sprue. Gastroenterology, 38, 28-49.



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