Gut, 1972, 13, 260-269

Pathology of intestinal tuberculosis and its distinctionfrom Crohn's diseaseH. D. TANDON AND A. PRAKASH

From the Departments ofPathology and Surgery, All-India Institute of Medical Sciences, New Delhi-16,India

SUMMARY Intestinal lesions of 212 cases presenting with symptoms of intestinal obstruction were

studied. Of these, 159 cases were diagnosed as tuberculosis and 10 as Crohn's disease. Forty-threecases could not be classified into any of these entities and are excluded from this account. Theamount of chemotherapeutic diugs received by each patient preoperatively was recorded. Casesproved as tuberculosis at the first operation were put on antituberculosis chemotherapy. Thirteen ofthese cases were operated on a second time, and tissue reactions under the influence of chemo-therapy were studied. Fresh diseased tissue was studied for acid-fast organisms by culture andanimal inoculation.

Morphological features of the tuberculosis group are described in detail. Although the cases were

broadly classified into the ulceiative and ulcerohypertrophic varieties, a distinction was not alwayssharp and the two types of lesions were at times found to coexist. The macroscopic features presenteda very wide range, and at times distinction fiom Crohn's disease, especially in the ulcerohypertrophicvariety, was difficult. Microscopically, however, they could be distinguished without much difficulty.Caseation, although a characteristic feature of tuberculous granulomas may, albeit rarely, beabsent. Granulomas which are characteristically confluent may be present only in the mesentericlymph nodes. Acid-fast organisms are not grown consistently from diseased tissues; where grown,

they are of human type. Reparative changes during chemotherapy are described in detail; thesefollow a non-specific pattern.

In the group of Crohn's disease, transmural cracks and fissures were consistently observed in allcases. Distinguishing features between the two diseases are discussed in detail.

After the classical description by Crohn, Ginzburg,and Oppenheimer (1932) of regional enteritis theterm 'hypertrophic ileocaecal tuberculosis' was allbut discarded (Taylor, 1945; Anand, 1956; Bruce,1959; Rhoades, Klein, and Welsh, 1960; Chandraand Basu, 1967), and its authenticity began to bedoubted (Paustian and Brockus, 1959). In its over-enthusiastic acceptance, even workers in countrieswhere tuberculosis is still prevalent claimed thatcicatrizing lesions in the ileocaecal region were infact Crohn's disease (Mangalik and Misra, 1952;Gupta, Chatterjee, Roy, and Ghosh, 1962). Figuresfor the incidence of the two diseases from the samecountry show a wide variation (Tribedi and Gupta,1941; Anguli and Menon, 1950; Banerjee, 1950;Mangalik and Misra, 1952; Anand, 1956). This isReceived for publication 20 January 1972.

perhaps due to relatively inadequate studies made onsmall series of one to 15 cases (Ashken and Baron,1962; Amerson and Martin, 1964; Howell andKnapton, 1964; Lee and Roy, 1964; Winter andGoldman, 1966) and difficulty in distinguishing themorphological features of tuberculosis and Crohn'sdisease (Taylor, 1945; Cattell and Mosely, 1946;Warren and Sommers, 1948; Hoon, Dockerty, andPemberton, 1950; Anand, 1956; Brenner, Annes,and Parker, 1970).

Perhaps the most detailed account of the pathologyof ileocaecal tuberculosis has been given in the oftenquoted paper by Hoon et al (1950). Among the 58cases studied by them, they described the entity of'non-caseating tuberculated enterocolitis' whichresembled tuberculosis, but neither showed caseationin the granulomas nor yielded organisms on culture.

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The terminology has created considerable confusionand has not been accepted by subsequent workers.

While investigating a large series of cicatrizingintestinal lesions of inflammatory origin, the clinicaland radiological features of which have been reportedearlier (Prakash, Tandon, Nirmala, Wadhwa,Prakash, and Kapur, 1970), we have been impressedby the protean anatomical manifestations of in-testinal tuberculosis. The present communication isa detailed account of our experience with thesepathological features and their differentiation fromCrohn's disease.

Material and Methods

Two hundred and twelve patients presenting withsymptoms of chronic or subacute intestinal obstruc-tion were studied. The amount and type of chemo-therapy received by each patient was recorded. Theoperation consisted generally of resection of thediseased segment of the intestine with the mesentericlymph nodes, or, where this was not possible, abiopsy of the diseased tissue. In many cases, freshbiopsy material from the diseased tissue was sub-mitted for bacteriological examination and culture,and a tissue homogenate was used for a guinea piginoculation test. Patients diagnosed histologicallyas tuberculous were put on a course of antitubercu-losis chemotherapy consisting usually of strepto-mycin 1 g and isonicotinic acid hydrazide (INH) 300mg daily for 90 days followed by para-aminosalicylicacid (PAS) 9 g and INH 300 mg daily for four tofive months.The present paper is based on a study of 169 cases

which were diagnosed as tuberculosis (159 cases) orCrohn's disease (10 cases); the remaining 43 casescould not be classified as either of these diseases andare excluded from this account. Among the 159cases of tuberculosis, 39 had only a biopsy at thefirst operation. These were put on chemotherapy and13 of them had to be operated on a second time forrecrudescence of obstructive symptoms, when asegment of intestine was resected after an intervalranging from one month to three years and twomonths. Thus a total of 133 specimens of resectedintestine were available from the group. In the groupof Crohn's disease, resected intestine was availablein all the 10 cases.

Macroscopic examination was conducted after24-hour fixation of the opened intestine. Tissueblocks were taken from the entire circumferentialwidth of the ulcerated lesions, sliced at 5 mm inter-vals, and the mesenteric nodes. Histological sectionswere stained with haematoxylin and eosin, and wherenecessary, for acid-fast bacilli, reticulin, and con-nective tissue.

Observations

The sex distribution was predominantly female inthe tuberculosis group, the female: male ratio beingapproximately 2:1, whereas in Crohn's diseasemales predominated 4: 1. The commonest age groupaffected in both the groups was 20-39 years (105 outof 159 cases for tuberculosis and six out of 10 casesfor Crohn's disease). Four cases in the tuberculosisgroup belonged to the first decade.The commonest site of the lesion in both the

groups was the lower ileum and ileocaecal region (90out of 159 cases in tuberculosis and four out of 10cases in Crohn's disease). Colon alone was involvedin five cases of tuberculosis and one case of Crohn'sdisease; when considered in combination with theileocaecal region and terminal ileum, it was involvedin 18 and three cases respectively of tuberculosis andCrohn's disease. Duodenum and/or jejunum wasinvolved in two cases of tuberculosis.

Tuberculosis

MACROSCOPIC CHANGESThe active lesions can be described under thefollowing broad categories of ulcerative and ulcero-hypertrophic types.

The ulcerative typeThe diseased segment is moderately indurated and ismarked by a conspicuous increase in mesenteric fatand the circumference is studded with nodules ofvariable size. Mesenteric lymph nodes are usuallyenlarged. Characteristic caseation may be foundonly after examining numerous lymph nodes.The ulcers may be single or multiple, in the latter

case variable lengths of uninvolved mucosa beingpresent in between (Fig. 1). Characteristically, theestablished lesion consists of an annular ulcerinvolving the entire circumference affecting a segmentgenerally less than 3 cm in length (Fig. 1). The lumenin this region is narrowed, sometimes measuring lessthan 1 cm in diameter, resulting in a napkin-ringtype of stricture (Fig. 1).

Ulceration is relatively superficial and does notordinarily penetrate the muscularis propria. Theulcers present a variable appearance. The ulcer bed iscovered with a necrotic slough. It may be coarselygranular, often showing small pseudopolyps, or themucosal folds may be replaced by a mamillatedsurface. Sometimes, the mucosal folds are evenedout and scattered with irregularly disposed mucosalerosions. Where the ulcers are well defined, themargins may be undermined or sloping, or flush withthe surface. In an occasional case, the ulcer presentsa stellate appearance with a deep excavation

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Fig. 1 Tuberculous enteritis ofthe ulcerative type showingmultiple lesions with skippedareas.

Fig. 2 Tuberculous enteritisaffecting the caecum andascending colon showing extensiveulceration of the mucosa, whichappears ragged. There is extensivemucosal bridging andpseudopolyposis.

bordered by sharply overhanging hypertrophicmucosal shelves which are intensely hyperaemic. Theulcer in such cases tends to be disposed along thelongitudinal axis and the neighbouring mucosalfolds tend to converge upon the ulcer. The thicknessof the wall underlying the ulcer bed is variable; itmay be thinned or may appear hypertrophic andscarred, streaked with yellowish areas of necrosis.

In one case the entire mucosal surface of thecaecum and the adjacent ascending colon wasreplaced by a ragged appearance with extensivepseudopolyposis, mucosal bridging, and deep,gutter-like ulcers running along the longitudinal axis(Fig. 2).

Ulcero-hypertrophic varietyThis variety commonly affects the ileocaecal region,

the patient presenting with a large lump in the rightiliac fossa. The ileocaecal region, mesenteric fat, andtheir constituent lymph nod-s are seen to constitutea large mass with extensive adhesions. The ileocaecalangle is distorted and often obtuse. On opening, thewall is seen to be markedly thickened, occasionallyin a tubular form, measuring up to 3 cm in thickness.The mucosal changes are quite variable. There maybe a prominent 'cobblestoning' or pseudopolyposis(Fig. 3) or the mucosal folds may be flattened andthe surface shows irregularly disposed furrowsmostly converging upon the constriction.

It may be mentioned here that there are no sharpdifferences in the two varieties described above, andthe two types of lesion may coexist.Among all the cases, including both varieties,

seven had perforation of the bowel and two hadfaecal fistulae.

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Fig. 5 Active tuberculous enteritis showing namerousconfluent, non-caseating granulomas in the mucosa.

H&Ex 105.

Fig. 3 Tuberculous enteritis ofthe ulcerohypertrophic varietyshowing tubular narrowing andpronounced 'cobblestoning'.

Fig. 4 Healed tuberculousenteritis. The mucosa is completelyregenerated, and the area showingsmoothed folds represents the siteof the old lesion. The nodularprojections are prominent Peyer'spatches.

Healed tuberculosisFive cases were diagnosed as healed tuberculosis onthe basis of a previous history of active tuberculosis,proved at surgery, and followed by a period of anti-biotic chemotherapy, resulting in a completedisappearance of specific morphological features oftuberculosis. In such cases, the mucosa was com-pletely regenerated and smooth, and often studdedwith nodules 2 to 3 mm wide representing hyper-trophic Peyer's patches (Fig. 4).

MICROSCOPIC CHANGESMicroscopic features of the two varieties do notdiffer significantly, the mass in the hypertrophicvariety being principally contributed by exuberantgranulomatous tissue extending onto the serosa, andalso by mesenteric fat, enlarged lymph nodes,fibrosis, and hypertrophy of the muscularis. Thefirst appearance of the granulomas seems to takeplace in the mucosa or the Peyer's patches (Fig. 5).The structure of the caseating granulomas, which isconsidered a diagnostic finding, is well known. Theperipheral part of the granuloma contains a zone of

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Fig. 6A Characteristic tuberculous granulomatous lesions showing caseous necrosis in the centre, and a prominent cuffof lymphocytes and plasma cells at the periphery. The esion appears to have resultedfrom the confluence of two tothree granulomas. H & E x 60.

Fig. 6B Sarcoid granulomas of Crohn's disease in the lymph node. The epithelioid cells have an irregular disposition;there is no central necrosis. The granulomas are approximately the same size and remain discrete despite being closelyadjacent. H & E x 160.

infiltration by an admixture of lymphocytes, plasmacells, and giant cells of the Langhans variety (Fig.6a). The granulomas are often large and usuallyshow marked variation in size. Characteristically,they tend to be confluent and the initial focus seemsto enlarge by expansion of individual granulomas orby confluence of numerous satellite granulomas (Fig.6b).The ulcers do not usually penetrate beyond the

muscularis and are mo3tly lined by non-specificinflammatory granulation tissue, with the infiltrateabounding in polymorphs and often extending intothe submucosa as microabscesses. Granulomas areoften seem in the immediate lining of the ulcer bed.There is no appreciable widening of the submucosaalthough a variable degree of oedema may beobserved in the vicinity of the ulcer beds withdilatation of the lymphatics. The oedema is never assevere as in Crohn's disease. Transmural cracks and

fissures are generally not a conspicuous feature; if atall present, they do not extend beyond the submucosa(Fig. 7A). Such fissures are often lined by character-istic granulomas. In longstanding lesions there maybe a variable degree of fibrosis which extends fromthe submucosa into the muscularis. The transitionto the grossly uninvolved areas is gradual, wellformed granulomas being observed in the wall inadjacent areas.Many established lesions show variable degrees of

reparative changes, even in cases which have notreceived antituberculosis chemotherapy as describedlater. Pyloric gland metaplasia is common andextensive, and often observed in cases with activeiprflammation.A point of special emphasis is that often numerous

sections of the intestinal wall show an entirely non-specific picture and the granulomas may be seen onlyin the regional lymph nodes. This phenomenon was

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Fig. 7A Tuberculous enteritis. A fissure runs superficially through the submucosa, and is lined by characteristicgranulomas. H & E x 80.

Fig. 7B Crohn's disease. A transmuralfissure is seen to extend deep into the muscularis,almost up to the serosa.H&Ex 90.

Fig. 8 Healed tuberculousgranuloma in the mesentericlymph node. H & E x 200.

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observed in nine cases. Five patients had received noantituberculosis chemotherapy and the remainingfour had received 7-40 g of streptomycin. Thereverse, ie, the presence of granulomas in the intestineand no granulomas in the lymph nodes, has not beenobserved in any case. Characteristic granulomas maybe seen only in a few lymph nodes, the rest showingonly a non-specific reaction associated with variableamounts of para-amyloid. Healed granulomata havebeen observed only in the lymph nodes. The granu-lomas undergoing healing tend first to be circum-scribed by hyalinized connective tissue and later arecompletely replaced by it (Fig. 8).

TISSUE CHANGES OBSERVED IN HEALINGPathological material before and after the adminis-tration of antituberculosis chemotherapy wasavailable only from 13 patients who were operatedon twice. This material is not sufficiently large forany definite conclusions regarding the length oramount of antituberculosis chemotherapy and itsrelationship with the degree of tissue healing.However, five patients who had active lesions at thefirst operation healed completely; the ulcers had re-epithelialized, and no active granulomas wererecognized in the intestine or the lymph nodes. Theyhad received antibiotic treatment consisting of 90-200 g streptomycin in addition to PAS and INH as inthe regimen stated above. The rest continued toshow activity of lesions in the form of active granu-lomas. Among them one had received 150 g andothers 30-75 g of streptomycin.The first evidence of healing is seeen as mucosal

regeneration which begins at the ulcer margins, firstas a single layer ofmucosal cells with hyperchromaticnuclei which are seen to creep along the surface fromboth sides bridging over a part of the entire surface.The mucosa is reconstituted by the epitheliumdipping down to form tubular glands. Later, ittends to be thrown into simple folds complete withtheir own muscularis mucosae and the acini dis-persed in irregular axes. This accounts for thecobblestoning which is not produced by submucousoedema. In the final stages the villous pattern is moreor less completely re-established. It has been seen,however, that even in such instances, occasional gapsof unbridged ulcers still remain which continue to belined by inflammatory granulation tissue. There is avariable degree of fibrosis involving the submucosaas well as the muscularis. The intensity of the in-flammatory reaction steadily diminishes. However,unlike the lymph nodes, there are no rounded scarssuggestive of healed individual granulomas.

In some instances, mucosal crypts were seenembedded deep in the hypertrophic scarred muscu-laris. These crypts of misplaced epithelium are

distended with mucin or even inflammatory infil-trates, which may be seen bursting.The healing reaction in the lymph nodes is more

precise and the pattern more predictable as describedearlier.

BACTERIOLOGICAL STUDIESOrganisms were grown from 15 cases, of which threehad shown no positive microscopic findings charac-teristic of the disease either in the bowel or theregional lymph nodes on initial examination. Asubsequent examination of further tissue blocksrevealed characteristic granulomas in one case. Inthree other cases no caseation was observed in thegranulomas. One patient had received 150 g ofstreptomycin before the resection of the specimenwhich yielded a positive culture. A guinea-piginoculation test was also positive in one of theselatter three patients. All organisms were of thehuman type.

Crohn's Disease

The morphological features of this disease are wellknown and have been exhaustively described(Lockhart-Mummery and Morson, 1960, 1964;Comes and Stecher, 1961; Williams, 1964; Hawk,Turnbull, and Farmer, 1967; McGovern andGoulston, 1968; Lennard-Jones, Lockhart-Mummery, and Morson, 1968; Morson, 1968). The-lesions were all chronic, and the inflammatoryreaction was characteristically transmural. Irregu-larly disposed cracks and fissures penetrating thewall, many times through the muscularis propria,emphasized by Morson (1968) as a characteristic-feature, were present in all cases (Fig. 7B). Sarcoidgranulomas were observed in two cases. Figures 6and 7 illustrate the morphological differencesbetween the granulomas and the cracks and fissures-respectively between tuberculosis and Crohn's.disease.

Discussion

From the above account it is evident that tuberculosis.still constitutes the most important single aetiologicalfactor in ulceroconstrictive lesions of the intestine inIndia, as also indicated in earlier reports from this.country (Anguli and Menon, 1950; Banerjee, 1950;Anand, 1956; Chandra and Basu, 1967; Hancock,1968).Many workers (Paustian and Bockus, 1959;

Hamandi and Thamer, 1965; Anscombe, Keddie,.and Schofield, 1967; Bentley and Webster, 1967).have attempted to classify the lesions into ulcerative,.

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ulcerohyperplastic, and hyperplastic varieties,following the classification of Hoon et al (1950).Such a strict classification is not always possiblealthough admittedly the lesions in the ileocaecalregion are often of the ulcerohypertrophic variety(Howell and Knapton, 1964).By far the commonest site of involvement in the

bowel is the terminal ileum and the ileocaecal region,as shown by the high incidence of involvement ofthese regions in the series (Hancock, 1958; Abramsand Holden, 1964; Bentley and Webster, 1967;Bockus, 1964). This study also confirms the beliefthat tuberculous colitis is by itself an uncommondisease entity, and that in the colon the mostfrequently observed site is the caecum, followed by theascending and descending colon (Abrams andHolden, 1964).Our experience with tuberculosis indicates that the

clinical and gross morphological manifestations ofthis disease are protean, and can mimic a number ofdiseases. This point is emphasized with regard to themacroscopic appearance of tuberculosis, particularlyaffecting the ileocaecal region where it may produce atubular narrowing, longitudinal furrowing, andoccasional 'cobblestoning' of the mucosa and it maybe difficult to distinguish it from Crohn's disease(Fig. 3).Hoon et al (1950) emphasize two criteria for

diagnosing tuberculosis: the presence of caseatinggranulomas in the bowel of lymph nodes, and apositive demonstration of acid-fast organisms intissues or in culture or a positive animal inoculationtest. Undoubtedly, these criteria should be fulfilledbefore a lesion can be objectively accepted astuberculosis. In the experience of the authors, all theabove criteria are rarely ever satisfied in all cases.Caseation appears to bear no relationship to positivecultures (Taylor, 1945; Rappaport, Burgoyne, andSmetana, 1951; Anand, 1956; Hancock, 1958;Abrams and Holden, 1964; Howell and Knapton,1964; Lee and Roy, 1964). It may not always bepresent and often one has to study a large number ofsections or numerous deep cuts in the tissue blockbefore it is seen. In three cases no evidence ofcaseation was found in the multiple sections ex-amined, and in another three initial microscopicexamination of the lesion was not diagnostic of thedisease, yet bacterial cultures were positive in allcases. The experience of Sweany (1947), Hoon et al(1950), Ashken and Baron (1962), Howell andKnapton (1964), Chandra and Basu (1967), andHawley, Woolfe, and Fullerton (1968) has beensimilar. Organisms grown were all of the human typeas in the previous studies, with the exception of thatof Hamandi and Thamer (1965) from Iraq.A tubercular granuloma, the hallmark of diagnosis

of tuberculosis, may at times not be evident at theinitial examination, especially in the sections fromthe intestine, and an examination of mesentericlymph nodes is often more rewarding. In nine cases adiagnosis of tuberculosis was made only by thepresence of characteristic granulomata in the lymphnodes, none of the several sections, including deepcuts into the tissue blocks of the intestinal lesions,having shown any. Such was also the experience ofBockus, Tumen, and Kornbloom (1940), Hoon etal (1950), Hancock (1958), and Chandra and Basu(1967). In cases undergoing chemotherapy, thecharacteristic granulomata had often disappeared inthe intestine but were present in active or healedforms only in the mesenteric lymph nodes.

MORPHOLOGICAL DISTINCTION FROM CROHN SDISEASEThe difficulties of distinguishing Crohn's diseasefrom tuberculous enteritis have been repeatedlyemphasized (Taylor, 1945; Cattell and Mosely,1946; Hoon et al, 1950; Anand, 1956; Brenner et al,1970). Asdescrib-d and illustrated above, in tubercu-losis the luminal narrowing may be tubular, as alsowas observed by Howell and Knapton (1964). Themucosal changes may also show a striking resem-blance to Crohn's disease (Hancock, 1958) withprominent cobblestoning and pseudopolyposis. Thecharacteristic girdle ulcer spanning the circumferenceand resulting in a sharply outlined stricture, whilestill the most common presentation in the ulcerativevariety, may not always be present. In the series ofHoon et al (1950), they were present in only four outof the 22 cases of the ulcerative type.

After our experience with a large series it isadmitted that a clear distinction may sometimes bedifficult, especially on macroscopic observationsalone, but certain features help to make such adistinction. These are listed in the Table. None of thedistinguishing features except caseation in thegranulomas are absolute but a careful examinationof the specimen and an overall consideration of theabove features will help to distinguish most cases.Granulomas are a feature common to both the

diseases. It is not unusual to find them in themesenteric lymph nodes, while the bowel shows nonein tuberculosis, whereas in Crohn's disease lymphnodes do not show granulomas, if none are seen inthe intestine (Morson, personal communication).Caseation, which is considered an essential criterionin the diagnosis of tuberculosis, may often bedifficult to demonstrate. Yet, there are severalfeatures which help to distinguish the non-caseatingtuberculous granulomas from those of Crohn'sdisease, as indicated in the Table. Of special signifi-cance is their tendency to confluence in the former

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Features Tuberculosis Crohn's Disease

MacroscopicAnal lesions Rare CommonMiliary nodules on serosa Conspicuous and common RareLength of strictures Generally less than 3 cm Usually longInternal fistulae Very rare FrequentPerforation Uncommon RareUlcers(a) Location Circumferential More prominent along mesenteric attachment(b) Direction in relation to long axis Generally transverse Longitudinal or serpiginous

MicroscopicGranulomasPresence Always present Absent in at least 25% casesIncidence in intestine in relation to lymph May be absent in the intestine but usually Not seen in lymph nodes when absent in thenodes present in mesenteric nodes intestineSize Often large Usually smallCaseation Usually present AbsentShape Often confluent Usually discreteSurrounding fibrosis Common RareHyalinization Common RarePeripheral collar of inflammatory cells Usually present Usually absentAssociated paramyloid May be present Absent

Other FeaturesSubmucosal widening Generally absent Generally presentFissures Generally absent; do not penetrate the Common; penetrate deep

muscularisTransmural follicular hyperplasia Absent Usually presentFibrosis of muscularis propria Prominent UncommonPyloric gland metaplasia Common, extensive Less common, patchyEpithelial regeneration Common Uncommon

Table Distinguishing differences between tuberculosis and Crohn's disease

(Figs. 5 and 6A), as also is emphasized by Howelland Knapton (1964) and Hawley et al (1968), whichaccounts for a greater variability in size and stage ofevolution. In contrast, the granulomas in Crohn'sdisease remain discrete, even if lying adjacent to eachother (Fig. 6B), and represent the same stage ofevolution, as was also observed by Comes andStecher (1961). They too have a 'punched-out'appearance, lacking a peripheral zone of inflam-matory cell infiltration.The cracks and fissures, emphasized by Lockhart-

Mummery and Morson (1964), Williams (1964),and Morson (1968) as an important diagnostic featurefor Crohn's disease, were specially looked for in allour cases. They have been observed in but a few casesof tuberculosis, especially of the hypertrophic variety,as angular or linear tears originating from the ulcer-ated surface, but were never seen to penetrate deeperthan the muscularis propria (Fig. 7A), unlike Crohn'sdisease in which they extend deep, through themuscle coat almost up to the serosa (Fig. 7B).

Inflammation in both these conditions has atransmural spread, and penetrates through themuscle coat, although relatively less often in Crohn'sdisease. In the latter, it is seen mostly as a non-specific inflammatory infiltrate extending betweenthe muscle planes on the serosa, whereas in tubercu-losis it is comprised of characteristic granulomas.

EFFECTS OF CHEMOTHERAPYThe morphological pattern of healing responsesunder the influence of chemotherapy observed inproven cases of tuberculosis does not differ signifi-cantly from those described by Rappaport et al (1951)in Crohn's disease, or those which may occurspontaneously. Unlike the lung (Denst, 1953; Poppede Figuerido and de Paola, 1955; Puzik and Uvavova,1959), there are no specific morphological featureswhich are associated with the tissue healing undersuch a regimen. It is notable that although granu-lomas had disappeared from the intestinal lesions,some of them continued to show ulceration, at leastin parts. Whether the ulcers continue to be perpetu-ated due to secondary infection by other organismsor to some other factors is not understood. It ispossible that it may represent recurrent ulcerationdue to factors other than tuberculosis. It is alsointeresting that no evidence of healed granulomaswas seen in the intestines, although the mesentericlymph nodes did show a progressive hyalinization ofsuch lesions.

H. D. Tandon is grateful to Sir Francis Avery Jonesfor his interest in this study, and The WellcomeTrust, London, provided a travel grant to him tovisit the United Kingdom. Part of the material wasstudied jointly with Dr Basil Morson, of St Mark's

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Pathology of intestinal tuberculosis and its distinction from Crohn's disease 269

Hospital, in London. His help in drawing up thedistinguishing criteria from Crohn's disease isgratefully acknowledged.We are grateful to the late Professor Om Prakash,

Department of Microbiology, All-India Institute ofMedical Sciences, for his assistance in processingthe bacterial cultures.

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