neuromuscular of the - gut · andvascular hamartoma' are presented. in three of the cases,...

Gut, 1987, 28, 1663-1668

Neuromuscular and vascular hamartoma of the smallintestine: is it Crohn's disease?N A SHEPHERD AND J R JASS

From the Department of Pathology, St Mark's Hospital, City Road, London

SUMMARY Neuromuscular and vascular hamartoma has been described as a specific, if rare,stricturing condition of the small intestine. In this paper four cases with very similar macroscopicand histological features to those described as 'neuromuscular and vascular hamartoma' arepresented. In three of the patients there was an earlier histologically proven diagnosis of Crohn'sdisease of the small intestine. We believe that 'neuromuscular and vascular hamartoma' is not ahamartomatous condition but may be seen as part of the histological spectrum of Crohn's disease,possibly in a chronic and 'burnt out' phase. Indeed the presence of these changes may provideadditional evidence for the diagnosis of Crohn's disease.

In 1982 Fernando and McGovern reported two casesof a previously undescribed small intestinal conditioncalled 'neuromuscular and vascular hamartoma'.The two female patients presented with intestinalobstruction and stricturing lesions were found in thesmall bowel. Histological examination revealedmucosal ulceration and a widened submucosa, whichcontained aberrant fascicles of muscle derived fromthe muscularis mucosae, bundles of non-myelinatednerve fibres with scattered ganglion cells andnumerous blood vessels. They had consideredischaemia as a possible cause, for ischaemic enteritisproduces multiple concentric strictures with hyper-plasia of the muscularis mucosae and incorporationof ganglion cells, but reasoned that the absence offibrosis of the muscularis propria made this diagnosisvery unlikely. The authors therefore interpreted thefindings as a hamartomatous condition.

Smith, Filipe and Owen2 reported a single case of'neuromuscular and vascular hamartoma', with verysimilar macroscopic and histological features as thetwo cases reported by Fernando and McGovern.There were additional pathological features such asmucosal cobblestoning, pyloric metaplasia andgranulomas in local lymph nodes, producing a patho-

Address for correspondence: Dr N A Shcpherd. Dcpartment of Pathology.St Mark's Hospital, City Road. London EC IV 2PS.

Received for publication 4 June 1987.

logical appearance mimicking Crohn's disease. Theclinical features of the presentation had been stronglysuggestive of Crohn's disease.

In this paper four cases with very similar macro-scopic and histological features as 'neuromuscularand vascular hamartoma' are presented. In three ofthe cases, however, a previous clinical and patho-logical diagnosis of Crohn's disease had beenmade and this paper presents evidence whichstrongly suggests that 'neuromuscular and vascularhamartoma' is not a hamartomatous conditionbut it is an unusual histological consequence ofinflammatory bowel disease, predominantly Crohn'sdisease.

Case histories

CASE 1A 34 year old Caucasian woman presented with a oneyear history of central abdominal pain, vomiting andoccasional diarrhoea. Three years before a righthemicolectomy had been carried out for small bowelobstruction. Crohn's disease had been diagnosed inher younger brother at the age of 23. An explorativelaparotomy revealed five discrete 2 cm long strictures,with some proximal dilatation, in both the jejunumand the ileum. The ileocolic anastomosis appearednormal. Each stricture was resected and end-to-endanastomoses carried out. Macroscopic examination

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Fig. 1 Case /. Right hemicolectomy specimen. There isfissuring ulceration and transmural inflammation in theformoflymphoid aggregates. (H & E)

revealed five strictured segments of small intestine,measuring from 4-5 cm to 2-2 cm long. There wasfocal mucosal ulceration and cobblestoning.

Histological sections taken from the right hemi-colectomy specimen were reviewed. There was focalbut extensive surface ulceration with fissuringulceration and pyloric metaplasia was seen in theadjacent mucosa. Transmural inflammation in theform of lymphoid aggregates was present but therewere no granulomas (Fig. 1). There was neuronalhyperplasia, an apparent excess ofganglia and fibrosiswith smooth muscle proliferation associated with thetransmural inflammation. Numerous thin and thickwalled arteries and veins were present in thesubmucosa. The histological features were those ofCrohn's disease.The histological features of the five strictured small

intestinal segments are tabulated in the Table and areshown in Figure 2. There were very occasionallymphoid aggregates in the submucosa adjacent to

Fig. 2 Case I. Section from onernsmall howelstricture. Thereis surface ulceration with pyloric metaplasia oJill/ adjacentmucosa. Upper submucosa contains abundant .smootlhmuscle and hyperplastic nervefibres and thick walled veinsare promineit in the deep sublmucosa. There is no transmuralinflammation. (H & E)

areas of inflammation, but there was no transmuralinflammation. A single poorly formed granulomawith foreign body type giant cells was present in theserosa of one of the strictured segments.

CASE 2A 58 year old Caucasian man presented with an 18month history of discontinuous abdominal p)ain and

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Neulromuscular and vascular hamizartoma ofthe smlall intestine: is it Crohn 's disea.se?

Fig. 3 Case 2. Proximal stricture of'small intestine. There isulceration at the stricture hlt the atljacetnt intestine appearsniorrmlal.

distension, associated with diarrhoea. He had had sixprevious abdominal operations for small intestinalobstruction. A clinical and histological diagnosis ofCrohn's disease had previously been made, but thehistology was not available for review. A small bowelenema revealed a stricture of the terminal ileum withprogressive dilatation of the proximal small intestine.Two strictures were discovered at laparotomy. Browndiscoloration of the bowel was noted. A 29 cmsegment of small intestine, including an ileocolicanastomosis was resected. Macroscopic examinationof the specimen revealed two strictures, one at theileocolic anastomosis and a second stricture of theileum 19 cm proximal to this. There was ulceration ofthe mucosa at the proximal stricture (Fig. 3). Onsectioning the bowel, there was a deep browndiscoloration of the muscularis propria. The histo-logical features of the strictured segments arepresented in the Table. Figure 4 shows the mucosalulceration with marked neuronal hyperplasia,smooth muscle proliferation and thick walledveins. In addition the muscularis propria and themuscle of submucosal arterioles showed extensivelipofuscinosis, indicative of the bowel brownsyndrome.

Table

Case Case 2 Case 3 Case 4

Specimcn Small bowel 11cal Ileocolic llealstricturcs stricturc anastomosis strictures

Granulomas + +Transmural +inflammationUlccration

Focal supcrficial + + + + +Fissuring +

NcuronalhypcrplatsiaNcrvc fibrcs + + + + + + + +Ganglia + + + + + + +

Muscularisation + + + + + + + +of submucosaVatscular changcs

Artcrics MlI MI] Mul MH & AEPVcins*

submucosat + + + + + +scrosa ++ - ++

Mti = medial hypcrtrophy; AEP = asymmctrical cndothcliialproliferation; * vcnous changes wcrc irrcgulair muscular thickcningand cctasia.

CASE 3A 73 year old Caucasian woman presented withrecurrent episodes of colicky abdominal pain.Fourteen years before a right hemicolectomy hadbeen performed for ileal stricturing and she hadundergone an Ivalon rectopexy for complete rectalprolapse 18 months before. A laparotomy was carriedout and a stricture of the ileocolic anastomosis wasresected. Pathological examination revealed asegment of ileum 50 cm long anastomosed to 8 cm ofcolon. There were occasional aphthoid ulcers of the

Fig. 4 Case 2. Section of'stricture shown in Fig. 3. There isulceration with marked neuronal hyperplasia, smoothmuscle proliferation and thick walled veins. (H & E)

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mucosa in the proximal ileum. The distal 12 cm ofileum up to the anastomosis showed stricturing,bowel wall thickening and serpiginous ulceration.Review of the histological sections of the right

hemicolectomy showed the features of Crohn'sdisease. There was focal ulceration without fissuresand there was pyloric metaplasia of the adjacentmucosa. There was transmural inflammation in theform of lymphoid aggregates and a single peri-lymphatic granuloma was present in the serosa. Focalneuronal hyperplasia was seen adjacent to areasof ulceration. Vascular changes included intimalproliferation of submucosal arterioles and ectasia ofvenules and capillaries. The proximal ileum containedtypical aphthous ulcers. The histological features ofthe ileocolic anastomosis specimen are presentedin the Table. The neuromuscular and vascularabnormalities were adjacent to areas of superficialulceration but elsewhere there were fissuring ulcersand occasional lymphoid aggregates in the submocosaand serosa. There were no granulomas.

s] j. * # ~ ~ VK

Fig. 5 Case 4. Section frorm small bowel stric ture. There isfocal ulceration with smooth muscle proliferation and thickwalled veins in the subnmucosa. (H & E)

CASE 4

A 63 year old Caucasian woman presented with a sixweek history of cramping abdominal pain particularlyafter meals. The past medical history included acholecystectomy 19 years before and removal of anephrolith 10 years before. There was no previoushistory of gastrointestinal disease apart from aduodenal ulcer and there had been no other surgicalintervention. Barium studies showed a small bowelstricture with proximal dilatation. A 48 cm segmentof ileum was resected at laparotomy. Pathologicalexamination revealed three strictures of the ileumwith focal ulceration. Since this operation, threeyears ago, there have been no further episodes ofsmall intestinal obstruction although small bowelenema revealed some narrowing of the most distalileum. Two years after her small bowel resection shedeveloped lower back pain and the clinical featureswere suggestive of a sacroiliitis.The histological features of the ileal resection

specimen are presented in the Table and are shownin Figure 5. Arterial changes were particularlyprominent and showed thickening of the media andasymmetrical endothelial proliferation. There wasthrombosis in vessels immediately adjacent to areasof ulceration. There were no granulomas and nofissures were present.

Discussion

The pathological diagnosis of Crohn's disease restson the evaluation of both macroscopic and micro-scopic features. The macroscopic appearances ofsmall intestinal Crohn's disease are not entirelyspecific but include stricturing, serpiginous ulcerationand cobblestoning of the mucous membrane.' Thehistological features of Crohn's disease are equallyvariable. Granulomas and fissuring ulceration arethe hallmarks of the disease but are not alwayspresent. Often the most useful sign is the presence oftransmural inflammation in the form of lymphoidaggregates but, when these are scanty and there is nofissuring ulceration or granulomatous inflammation,the pathological diagnosis becomes more difficult.Fissuring ulceration and transmural inflammation areusually present in severe active Crohn's disease butthe histological features of 'healed' Crohn's diseaseare unknown. It has been suggested that the presenceof granulomas, some undergoing hyalinisation, in theabsence of ulceration and significant inflammation,may represent a resolving phase of Crohn's disease,4but these changes may be seen in macroscopicallynormal intestine adjacent to active Crohn's disease.We have described four cases of small intestinal

strictures and in three of the cases a diagnosis ofCrohn's disease is unavoidable. In each case idcntical

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Neuromuscular and vascular hamartoma ofthe small intestine: is it Crohn 's disease? 1667

features to those described as 'neuromuscular andvascular hamartoma' have been present. All of thepathological features described in this condition maybe seen in Crohn's disease. Neuronal hyperplasia is arelatively common accompaniment of small and largeintestinal Crohn's disease. This includes both anincrease in numbers of ganglion cells5 and enlarge-ment of nerve trunks,6 which have been shown tocontain greatly increased amounts of vasoactiveintestinal polypeptide.7 Muscularisation of thesubmucosa is also not an unusual feature in the smallintestine not only in Crohn's disease but also inischaemic and radiation enteritis, and both of theseconditions may be associated with neuronal hyper-plasia and vascular changes. Although the bundles ofsmooth muscle are often in continuity with theoverlying muscularis mucosae, the submucosalsmooth muscle is not necessarily the result ofproliferation of the muscularis mucosae but may bethe result of muscularisation of a fibrotic submucosa,also a common feature of chronic stricturing diseases.Muscularisation of fibrotic tissues may be seen inother tissues, particularly in the lung in pulmonaryfibrosis.8 Vascular changes are also described inCrohn's disease and these include degenerativearterial lesions, with duplication of the internalelastic lamina and medial hypertrophy, and irregularthickening of the walls of veins as a result ofhyperplasia of fibrous, elastic and muscle tissue.9We have recently reviewed 50 sequential cases of

small intestinal Crohn's disease and, in many cases,histological features identical to those of 'neuro-muscular and vascular hamartoma', namely neuronalhyperplasia and an excess of ganglia, aberrantbundles of smooth muscle, and thickened and ectaticarteries and veins, are not uncommon findings. Thesechanges were associated with fissuring ulceration andtransmural inflammation and therefore the diagnosisof Crohn's disease was not in doubt. In the four caseswe have presented, the histological features presentwere not diagnostic although occasional granulomaswere seen in cases 1 and 2 and there was fissuringulceration in case 3. There was no transmuralinflammation in the first three cases and patchytransmural inflammation in case 4. The histologyfrom the previous resections in cases 1 and 2 bothshowed the classical changes of Crohn's disease. Incase 3 a previous clinical and pathological diagnosisof Crohn's disease had been made. The sections werenot available for review but a history of six previoussmall intestinal resections is certainly much more likeCrohn's disease than a hamartomatous condition.

In their paper Fernando and McGovern' make nomention of the presence or absence of inflammationand presumably no granulomas were present. One oftheir patients was Australian, a country with a high

prevalence of Crohn's disease but the other patientwas of Indonesian extraction. Crohn's disease is rarein eastern Asia and therefore it may be that anotherchronic stricturing disease of the small intestine,possibly tuberculosis or a parasitic infestation,is responsible. Smith et aP describe mucosal cobble-stoning of the strictured segment of small intestineand histologically there were granulomas present inthe local lymph nodes, features which are certainlysuggestive of Crohn's disease. An unusual feature intheir case, and also in our case 4, was the presence ofthrombosis in superficial blood vessels. In both casesthe thrombosis was adjacent to areas of ulceration,however, and is therefore probably a secondaryphenomenon. They describe abnormalities in alllayers of the bowel but the pathology was predomi-nantly mucosal and submucosal. The muscularispropria showed secondary hypertrophy, whichmay be seen in any stricturing condition and theserosa showed ectasia of blood vessels, a commonaccompaniment of active inflammatory boweldisease, particularly in an acute fulminating phase.

In conclusion we believe that 'neuromuscularand vascular hamartoma' is probably not a hamar-tomatous condition, for identical pathologicalfeatures may be seen as part of the histologicalspectrum of Crohn's disease. The absence of fissuringulceration and transmural inflammation in our fourcases suggest that the pathological features may bethose of a chronic, 'burnt out' form of the disease. Wehave, however, seen similar changes in both radiationand ischaemic enteritis, often with. fibrosis of themuscularis propria. Therefore the neuromuscularand vascular abnormalities, in isolation, are arelatively non-specific change. In combination witheither fissuring ulceration, transmural inflammationor granulomas, the changes may provide furtherhistopathological evidence for a diagnosis of Crohn'sdisease.

We thank Dr B C Morson, to whom two of our caseswere referred, for his help and encouragement andMs Jill Maybee for photographic assistance.

References

1 Fernando SSE, McGovern VJ. Neuromuscular andvascular hamartoma of the small bowel. Gut 1982; 23:1008-12.

2 Smith CET, Filipe MI, Owen WJ. Neuromuscular andvascular hamartoma of small bowel presenting as inflam-matory bowel disease. Gut 1986; 27: 964-9.

3 Morson BC, Dawson IMP. Gastrointestinal pathology.Oxford: Blackwell Scientific Publications, 1979: 299.

4 Gray BK, Lockhart-Mummery HE, Morson BC. Crohn'sdisease of the anal region. Gut 1965; 6: 515-24.

5 Davis DR, Dockerty MB, Mayo CW. The myenteric



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plexus in regional enteritis: a study of ganglion cells inthe ileum in 24 cases. Surg Gynecol Obstet 1955; 101:208-16.

6 Whitehead R. Pathology of Crohn's disease. In: KirsnerJB, Shorter RG, eds. Inflammatory bowel disease.2nd ed. Philadelphia: Lea & Febiger, 1980: 296-307.

7 Bishop AE, Polak JM, Bryant MG, Bloom SR, Hamilton

S. Abnormalities of vasoactive intestinal polypeptide-containing nerves in Crohn's disease. Gastroenterology1980; 79: 853-60.

8 Spencer H. Pathology of the lung. 4th ed. Oxford:Pergamon Press, 1985: 797.

9 Morson BC, Dawson IMP. Gastro-intestinal pathology.Oxford: Blackwell Scientific Publications, 1979: 304.



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