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The pathology of intestinal tuberculosis
June, 1928J
PATHOLOGY OF INTESTINAL TUBERCULOSIS
409
THE PATHOLOGY OJ!' INTESTINAL TUBERCULOSIS.l By M. J. STEWART, M.B., F .R.C.P. Professor of P athology. University nf Leeds,
INFECTION of the alimentary tract with tubercle bacilli may occur by direct invasion from the lumen, by retrograde lymphatic spread from the mesenteric or cooliac lymph glands, or by the blood-stream, There are substantial grounds for believing that the tuberculous ulceration of the intestine which occurs so frequently in the later stages of phthisis is the result of direct infection from swallowed bacilli, and there is equally little doubt that primary ileocracal tuberculosis is also a contact infection from the gut. Miliary tuberculosis rarely attacks the walls of the alimentary tract, and is a phenomenon of very limited interest or importance. Local retrograde extension from tuberculous mesenteric glands is perhaps more common than we suppose. From time to time one meets with cases in which, with an advanced caseous glandular lesion, lines of recent tuberculous lymphatics extending to the gut, and small recent ulcers within the latter, there seems little doubt that the spread has been centrifugal. One can sometimes account in this way for a localised group of ulcers high in the ileum or jejunum with no evidence of a lesion in the more usual sites. Pathologically and clin ically, then, there are onl y two important varieties of intestinal tuberculosis, one secondary, and usually a complication of pulmonary phthisis, the other, h yperplastic tuberculosis, apparently in most cases a primary infection. In typical examples the pathological process in these two lesions varies enormously. (I) SECONDARY INTESTINAL TUBERCULOSIS. Secondary tuberculosis is usually frankly ulcerative, and shows at the ad vancing margin the characteristic histology of the tubercle follicle with abundant giant cell systems and caseation. There is very little reactive fibrosis, and the muscular coat is rarely penetrated completely. As a rule TABLE I.-DISTRIBUTION OF THE LESION IN 500 CAS I1S OF INTESTINAL TUBERCl;iLOSIS FOLI.OWING PUUIONARY PHTHISIS (FENWICK .\ND DODWELL, 1892).
Inchlenct
Duodenum Jejunum Ileum Ascending colon Transverse colon Descending colon
Sigmoid Rectum
3'4 per cent. 28'0 602 61·4 30·6 21'0
Inehlence
a8
pole
inteatinal lesion
1'4 per ceut. 4'4 1'8 1·0
13 IS
14·1
I A paper read at the Provinciall\leeting of the Tuberculosis Society and the Society of Superintendents of Tuberculosis Institutions at Oxford, March 81.
4LO
[June, 192B
'l'UBERCLE
the ulcerati~n is wid.espread, extending upwards and downwards fr.om the seat of election, the ileocsecum. This is well brought out in FenwIck an.d Dodw~ll's (1892) analysis of 500 cases of secondary intestinal tuberc?losls occurrmg at Brompton, in which the ileoceecal region was involved In no less than 85 per cent. The exact distribution is shown in Table 1. Ulceration usually commences in the ileocrecum, and in cases where the disease is widespread, the largest and most advanced lesions are met
TABLE II.-INCIDENCE OF TUBERCULOUS LESIONS, ACTIVE AND OBSOLETE, AT ALL AGES IN A CONSECUTIVE SERIll:S OF 1,000 AUTOPSU:S .AT THE LEEDS GENERAL INFIRMAIlY, (POSTWAR PERIOD.)
Incidence
Incidence of tuberculous lesions, post-mortem, in 100 soldiers most of whom died of
wound_CSt, Ower, 1917)
3 per cent, 1 39
S'6 per cent.
Active tuberculosis .. Tuberculosis the cause of death Gross obsolete lesions Apical scarring only Obliteration of pleural sac only
6'9 23'0 8'3 3'5
Evidence of past or present tuberculosis
43'4 per cent,
" "
11
1 54 per cent.
TABLE IlL-DETAILS OF THE INCIDENCE OF TUBERCULOSIS, ACTIVE AND OBSOLETE, IN CONSECUTIVE AUTOPSIES AT ALL AGES.
1,000
Incidence
'I'horacie glands
Abdominal glands Including lesions in both groups Cervical glands Supra-clavicular •. •, ,. Lungs (grossly caseated, cavitated or calcified) " (apical scarring only) La.rynx Larger bronchi Trachea Tonsils Intestines Ileum Jejunum Colon Duodenum •• Lntracranlal tuberculosis Tuberculous meningitis .. Tuberculomata Meningitis and tuberculomata Peritoneum Liver Kidney Spleen Adrenals Fallopian tube ,, Uterus, bladder, prostate, testis, each ,. .. Seminal vesicles, Bones and joints Skin ..
13'8 per cent, 13'S 2'3 0'5 0'2
14'3
8'3 0-5 0'3
"
0'1 0'2 2'0
1'8 0'9 0'5 0'1 32 2'0 03 0'9 1'7 2'8 2'3 2'1 0'4 0'4 0'2 0'1 0'9 0'1
with in this region. Intraperitoneal perforation is uncommon; it IS estimated by Brown and Sampson (1926) as occurring in 3'7 per cent. of
June, 1928]
PATHOLOGY OF INTESTINAL TUBERCULOSIS
411
cases, and is most common in the lower ileum and ceecum. Even if the whole thickness of the bowel wall should be penetrated, adhesions formed in advance prevent free communication with the general peritoneal sac. More often deep penetration leads to the formation of fistulous tracks between different coils of intestine; rarely a fistula opens on the surface through the anterior abdominal wall. Fistulous intercommunication between adjacent coils of small intestine is of little moment, but the formation of a jejunocolic fistula will naturally be followed by very serious results. Tuberculous ulceration of the intestine is most commonly met with as an accompaniment of the later stages of pulmonary tuberculosis, and is present in at least half the cases which come to autopsy. My own experience of this form of the disease is very limited, as the Leeds General Infirmary rarely admits cases of this kind, and when it does they are soon transferred to a more appropriate institution. I have, however, analysed from the tuberculosis point of view a consecutive series of 1,000 autopsies made by myself during the years 1919 to 1923 inclusive, and the results are shown in Tables II and III. It should be noted that more than a third of the cases were under the age of 30. A more detailed analysis of the 20 cases of intestinal tuberculosis from the point of view of the primary lesion and the proximate cause of death yields results of considerable interest. In 14 cases the primary focus was believed to be in the mesenteric glands, which were in a state of advanced caseation, with calcification in four instances. A primary pulmonary lesion was present in five cases only, and in one case there was a primary hyperplastic tuberculosis of the intestine. On the face of it most of the cases would appear to be examples either of primary tuberculous ulceration of the gut or, more likely, secondary ulceration by extension from the adjacent glandular lesion. It is, perhaps, worthy of note that tuberculous meningitis or gross tuberculoma of the brain was the cause of death in no less than half the total. In one case only, the intestinal ulcers had completely cicatrised, and death was due to gangrenous appendicitis. In contradistinction to the hyperplastic type, secondary intestinal tuberculosis rarely gives rise to serious obstruction. This is due partly to the destructive character of the lesion, partly to the fact that the patients usually die before cicatrisation can take place. Strictures, when they occur, are often multiple, and are usually situated in the small intestine. Healed or healing ulcers are not infrequently met with. in the post-mortem room, but complete healing must be very exceptional. Eisenhardt (1891) found 10 cases with completely healed ulcers in a series of 566 cases studied, and Brown and Sampson (1927) found evidence of healed intestinal tuberculosis in five patients who had died of phthisis. In a series of 463 cases of ulcerative intestinal tuberculosis secondary to phthisis treated with artificial heliotherapy by these authors, 86, or 24 per cent., were apparently cured of their intestinal lesion. This includes a large number of fairly early cases in which the diagnosis of tuberculous enteritis was made by radiological examination.
412
TTTBERCLE
(II)
[June, 1928
PHIMARY HYPERPLASTIC TUm:RCULOSIS OF THE INTESTINE .
This is a comparatively rare type of tuberculous lesion, but is of importance in that it is amenable to surgical treatment. There have been at least 2P cases of this kind treated by radical operation in the Leeds General Infirmary in the last eighteen years; 43 cases were treated in the Edinburgh Royal Infirmary (Caird, 1921), during the twenty-five year period 18\:15 to 1919 inclusive. The disease, fairly prevalent in European countries, is apparently rare in America. and Brown (1927) states that at Trudeau Sanatorium he had seen but two cases. The lesion is essentially proliferative, and ulceration, while often or even usually present, is not, as a rule, the conspicuous feature which it is in the secondary type. The walls of the affected portion of the gut become very greatly thickened and hardened, all the coats being involved. In the mucosa and submucosa there is great overgrowth of lymphoid tissue, with much fibrosis, osdema and lymphocytic infiltration. The muscular coat is hypertrophied, and invaded by fibroblasts and lymphocytes, while the subserosa is also thickened and fibrosed, and in both these sites nodules of lymphoid tissue may make their appearance. As Hartmann (1907) has pointed out, the intestinal enlargement may be continued into a dense, fibre-adipose mass in the mesocolon or mesentery, often with tuberculous glands embedded in its substance. The underlying tuberculous nature of the lesion is usually apparent, tubercle follicles being irregularly scattered, usually in small numbers, throughout the wall of the gut. In other cases tubercles are demonstrated only with difficulty, and in some there may be no histological evidence whatever that the lesion in the intestine is tuberculous. There are good grounds for believing, however, that even cases which are negative histologically may really be tuberculous at bottom . (a) If a large number of blocks are taken from different parts of the lesion it may be found that while most of them show no evidence of tubercle, one or two do ; (b) in a certain proportion of cases where the histology of the gut is negative. the related lymph glands have been actively tuberculous; (c) cases have been described (Mouat, 1925) in which, with a negative histology, positive inoculation results have been obtained. Of the 21 cases in my series, 18 were histologically tuberculous, two showed tubercle follicles only in the associated lymph glands, while one was wholly negative. In three of Mouat's 13 cases, which were negative histologically, positive results were obtained by inoculating guinea-pigs with fresh material from the excised specimens. Besides tuberculous ulceration, or even in its absence, small superficial ulcers of a non-specific kind are often present, or there may be blindending pockets or sinuses, often pus-filled, extending deepl y into the inflammatory mass. 'I'wo obtrusive clinical phenomena are directly dependent on the nature of the pathological process. (a) Owing to the amount of new formation I Specimens from 21 cases were submitted for pathological investi gation; doubtless the total number admitted to hospital was greater than this.
June, 1028]
413
PATHOLOGY OF INT.ESflNAL TUBERCULOSIS
and thickening a large, palpable tumour makes its appearance in the ctecal region, while (b) owing to encroachment on the lumen of the gut signs of intestinal obstruction become manifest. SITE OF THE LESION.
Hyperplastic tuberculosis is a disease of the ileocrecal region. It is usually confined to the last foot of the ileum, the ileocrecal valve, the crecum or the ascending colon, any or all of which may be involved. In my own series, much the commonest site was the last few inches of ileum with the ileocolic valve. In cases where the ascending colon is affected, the contraction of this viscus may drag the crecum upwards towards the liver, the lower ileum then coming into line with the first part of the large intestine. The crecum itself may become flattened out, or converted into a mere subsidiary pouch or diverticulum. Stenosis is most frequent at the lower end of the ileum but occurs also in the ascending colon. The narrowing is brought about partly by the size of the inflammatory mass, partly by cicatricial contraction and partly by a curious polypoidal condition of the mucous membrane which makes its appearance in the later stages. This latter condition, in cases which I have examined, is mainly due to oedema of the submucosa, which in turn depends upon lymphatic obstruction, although it may be in part inflammatory. Occasionally there is much epithelial proliferation, with the formation of true adenomatous polypi. Occasionally the appendix is involved, and again the lesion may or may not be tuberculous histologically. Mummery (1910) has described a case of (?) hyperplastic tuberculosis of the sigmoid occurring in a woman of 27. The polypoidal condition of the mucosa. within the stenosed 4 inches of the gut was most striking, although histological proof of the tuberculous nature of the lesion was lacking. I have myself seen two cases of undoubted tuberculosis occnrring in relation to sigmoid diverticula. Both the patients were males, aged 65 and 53 respectively, and both were rather obese. Radical operations were carried out by my colleagues Mr. Flint and Mr. Chamberlain. In view of some statistics which I have worked out , I should like {or a moment to trespass on the field of the next speaker. TABLE
IV.-AGE
INCIDENCIII AT THill TIllIE OF OPERATION IN (A) CARCINOMA OF THE COLON, AND (B) HYPERPLASTIC ILEOCECAL TOBF.RCULOSIS.
Decades
0- 9 10-19 20-29
3D-89 40-49 150-59 60-69 70-79
A.
n,
Carcinoma coli. 154 cases (Leeds)
Hyperplastic lJeocll'c.1 tuberculosis. I~2 ca". (Caird (1921), COI,rath (18~8), Mouat and St.walt)
g3':ll :g
12'3 0 15 5 21 -5) 33'7
24'7 j"84 '5 4'6
1~:~ f 80 '9
29'6 29'6 10'5 ~ 6'6 2'0
0'0 ,
19'1
414
TUBERCLE
[June, 1928
. (I) Just as. car~inoma of the sigmoid and rectum may be closely
mimicked ,by. diverticulitis, so carcinoma of the csecum or ascending colon
~ay be mIml~ke~ by hyperplastic tuberculosis. The age incidence is an Important point 1D the differential diagnosis ; in carcinoma, 85 per cent. of the cases are over 40, in hyperplastic tubercle 19 per cent. The actual figures of two comparative series are shown in Table IV . .
(2) The value of X-ray examination in the diagnosis of hyperplastic
ileocsecal tuberculosis is not yet fully recognised.
The changes, which of course vary in different cases, may be summarised as followa : (a) ileal stasis witb delay in filling the coocum ; (b) filling defects in crecum and ascending colon ; (c) irregularity of outline of the csecum, and loss of haustral segmentation of the ascending colon; and (d) fixation of the crecum. I should be glad to hear from subsequent speakers whether the ctecocolie hypermotility described by Pirie in 1917, and by Lawrason Brown and Sampson in 1919 as occurring in secondary ceecal tuberculosis is ever met in the hyperplastic variety. ·What is the explanation of this peculiar tuberculous lesion and why does it differ so widely from secondary intestinal tubercle? Three main factors are probably concerned: (1) a fairly high grade of immunity to tuberculous infection; (2) infection by small numbers of bacteria; and (3) infection by bacteria of low virulence, in many cases bovine. These are the exact converse of what takes place in the development of intestinal lesions in phthisis, where resistance is already broken down by previous disease, and massive doses of virulent bacilli, chiefly human, are constantly passing along the gut. The part played by secondary invaders may be of importance especially in explaining the bizarre character of the histological picture. Whether there is such a thing as a hyperplastic entero-colitis of non-tuberculous origin still remains to be seen. I am inclined to think there is, in spite of arguments already put forward . Finally, while I have attempted to make a clear-cut distinction between these two types of intestinal tuberculosis, the hyperplastic and the secondary ulcerative, it must be clearly understood that intermediate grades occur. In practice, however, most of the cases fall definitely into one or other category, an important point in relation to treatment.
REFERENCES. and SAMPSON, H . L. Journ. Amer. Med. Assoc., 1919, 73, 77. "Intestinal Tuberculosis," London, 1926. Journ , Amer. Med. Assoc., 1927,88,1472. CAIRD, P. 1\1. Edi1lburgh Med. JOUTn., 1921, 26, 73. CONRATH, V. Beitr. z, klin, Ohir., 1898, 21, 1. EISENHARDT. loaug. Dissert., Miincheu, 1891. FENWICK, W. S., and DODWELL, P. R. Lancet, 1892, li, 133 and 190. HARTMANN, H. Brit. su«. Journ., 1907, t. 849. LOCKHART-MUMMERY, P. Proc. Roy. S oc. su«, 1910, 3, Pt. 1, Olin. Sect., p. 201. MOUAT, T. B. Thesis for the Degree of Ob.M., Edinburgh, 1925. PIRIE, A. H. Quoted by E . W. Archibald, Trans . Nat. Assoc. for Study and Prevent. of Tuberc., 1917, 13, 117. BROWN, LAWRASON
Idem. Idem.
PATHOLOGY OF INTESTINAL TUBERCULOSIS
409
THE PATHOLOGY OJ!' INTESTINAL TUBERCULOSIS.l By M. J. STEWART, M.B., F .R.C.P. Professor of P athology. University nf Leeds,
INFECTION of the alimentary tract with tubercle bacilli may occur by direct invasion from the lumen, by retrograde lymphatic spread from the mesenteric or cooliac lymph glands, or by the blood-stream, There are substantial grounds for believing that the tuberculous ulceration of the intestine which occurs so frequently in the later stages of phthisis is the result of direct infection from swallowed bacilli, and there is equally little doubt that primary ileocracal tuberculosis is also a contact infection from the gut. Miliary tuberculosis rarely attacks the walls of the alimentary tract, and is a phenomenon of very limited interest or importance. Local retrograde extension from tuberculous mesenteric glands is perhaps more common than we suppose. From time to time one meets with cases in which, with an advanced caseous glandular lesion, lines of recent tuberculous lymphatics extending to the gut, and small recent ulcers within the latter, there seems little doubt that the spread has been centrifugal. One can sometimes account in this way for a localised group of ulcers high in the ileum or jejunum with no evidence of a lesion in the more usual sites. Pathologically and clin ically, then, there are onl y two important varieties of intestinal tuberculosis, one secondary, and usually a complication of pulmonary phthisis, the other, h yperplastic tuberculosis, apparently in most cases a primary infection. In typical examples the pathological process in these two lesions varies enormously. (I) SECONDARY INTESTINAL TUBERCULOSIS. Secondary tuberculosis is usually frankly ulcerative, and shows at the ad vancing margin the characteristic histology of the tubercle follicle with abundant giant cell systems and caseation. There is very little reactive fibrosis, and the muscular coat is rarely penetrated completely. As a rule TABLE I.-DISTRIBUTION OF THE LESION IN 500 CAS I1S OF INTESTINAL TUBERCl;iLOSIS FOLI.OWING PUUIONARY PHTHISIS (FENWICK .\ND DODWELL, 1892).
Inchlenct
Duodenum Jejunum Ileum Ascending colon Transverse colon Descending colon
Sigmoid Rectum
3'4 per cent. 28'0 602 61·4 30·6 21'0
Inehlence
a8
pole
inteatinal lesion
1'4 per ceut. 4'4 1'8 1·0
13 IS
14·1
I A paper read at the Provinciall\leeting of the Tuberculosis Society and the Society of Superintendents of Tuberculosis Institutions at Oxford, March 81.
4LO
[June, 192B
'l'UBERCLE
the ulcerati~n is wid.espread, extending upwards and downwards fr.om the seat of election, the ileocsecum. This is well brought out in FenwIck an.d Dodw~ll's (1892) analysis of 500 cases of secondary intestinal tuberc?losls occurrmg at Brompton, in which the ileoceecal region was involved In no less than 85 per cent. The exact distribution is shown in Table 1. Ulceration usually commences in the ileocrecum, and in cases where the disease is widespread, the largest and most advanced lesions are met
TABLE II.-INCIDENCE OF TUBERCULOUS LESIONS, ACTIVE AND OBSOLETE, AT ALL AGES IN A CONSECUTIVE SERIll:S OF 1,000 AUTOPSU:S .AT THE LEEDS GENERAL INFIRMAIlY, (POSTWAR PERIOD.)
Incidence
Incidence of tuberculous lesions, post-mortem, in 100 soldiers most of whom died of
wound_CSt, Ower, 1917)
3 per cent, 1 39
S'6 per cent.
Active tuberculosis .. Tuberculosis the cause of death Gross obsolete lesions Apical scarring only Obliteration of pleural sac only
6'9 23'0 8'3 3'5
Evidence of past or present tuberculosis
43'4 per cent,
" "
11
1 54 per cent.
TABLE IlL-DETAILS OF THE INCIDENCE OF TUBERCULOSIS, ACTIVE AND OBSOLETE, IN CONSECUTIVE AUTOPSIES AT ALL AGES.
1,000
Incidence
'I'horacie glands
Abdominal glands Including lesions in both groups Cervical glands Supra-clavicular •. •, ,. Lungs (grossly caseated, cavitated or calcified) " (apical scarring only) La.rynx Larger bronchi Trachea Tonsils Intestines Ileum Jejunum Colon Duodenum •• Lntracranlal tuberculosis Tuberculous meningitis .. Tuberculomata Meningitis and tuberculomata Peritoneum Liver Kidney Spleen Adrenals Fallopian tube ,, Uterus, bladder, prostate, testis, each ,. .. Seminal vesicles, Bones and joints Skin ..
13'8 per cent, 13'S 2'3 0'5 0'2
14'3
8'3 0-5 0'3
"
0'1 0'2 2'0
1'8 0'9 0'5 0'1 32 2'0 03 0'9 1'7 2'8 2'3 2'1 0'4 0'4 0'2 0'1 0'9 0'1
with in this region. Intraperitoneal perforation is uncommon; it IS estimated by Brown and Sampson (1926) as occurring in 3'7 per cent. of
June, 1928]
PATHOLOGY OF INTESTINAL TUBERCULOSIS
411
cases, and is most common in the lower ileum and ceecum. Even if the whole thickness of the bowel wall should be penetrated, adhesions formed in advance prevent free communication with the general peritoneal sac. More often deep penetration leads to the formation of fistulous tracks between different coils of intestine; rarely a fistula opens on the surface through the anterior abdominal wall. Fistulous intercommunication between adjacent coils of small intestine is of little moment, but the formation of a jejunocolic fistula will naturally be followed by very serious results. Tuberculous ulceration of the intestine is most commonly met with as an accompaniment of the later stages of pulmonary tuberculosis, and is present in at least half the cases which come to autopsy. My own experience of this form of the disease is very limited, as the Leeds General Infirmary rarely admits cases of this kind, and when it does they are soon transferred to a more appropriate institution. I have, however, analysed from the tuberculosis point of view a consecutive series of 1,000 autopsies made by myself during the years 1919 to 1923 inclusive, and the results are shown in Tables II and III. It should be noted that more than a third of the cases were under the age of 30. A more detailed analysis of the 20 cases of intestinal tuberculosis from the point of view of the primary lesion and the proximate cause of death yields results of considerable interest. In 14 cases the primary focus was believed to be in the mesenteric glands, which were in a state of advanced caseation, with calcification in four instances. A primary pulmonary lesion was present in five cases only, and in one case there was a primary hyperplastic tuberculosis of the intestine. On the face of it most of the cases would appear to be examples either of primary tuberculous ulceration of the gut or, more likely, secondary ulceration by extension from the adjacent glandular lesion. It is, perhaps, worthy of note that tuberculous meningitis or gross tuberculoma of the brain was the cause of death in no less than half the total. In one case only, the intestinal ulcers had completely cicatrised, and death was due to gangrenous appendicitis. In contradistinction to the hyperplastic type, secondary intestinal tuberculosis rarely gives rise to serious obstruction. This is due partly to the destructive character of the lesion, partly to the fact that the patients usually die before cicatrisation can take place. Strictures, when they occur, are often multiple, and are usually situated in the small intestine. Healed or healing ulcers are not infrequently met with. in the post-mortem room, but complete healing must be very exceptional. Eisenhardt (1891) found 10 cases with completely healed ulcers in a series of 566 cases studied, and Brown and Sampson (1927) found evidence of healed intestinal tuberculosis in five patients who had died of phthisis. In a series of 463 cases of ulcerative intestinal tuberculosis secondary to phthisis treated with artificial heliotherapy by these authors, 86, or 24 per cent., were apparently cured of their intestinal lesion. This includes a large number of fairly early cases in which the diagnosis of tuberculous enteritis was made by radiological examination.
412
TTTBERCLE
(II)
[June, 1928
PHIMARY HYPERPLASTIC TUm:RCULOSIS OF THE INTESTINE .
This is a comparatively rare type of tuberculous lesion, but is of importance in that it is amenable to surgical treatment. There have been at least 2P cases of this kind treated by radical operation in the Leeds General Infirmary in the last eighteen years; 43 cases were treated in the Edinburgh Royal Infirmary (Caird, 1921), during the twenty-five year period 18\:15 to 1919 inclusive. The disease, fairly prevalent in European countries, is apparently rare in America. and Brown (1927) states that at Trudeau Sanatorium he had seen but two cases. The lesion is essentially proliferative, and ulceration, while often or even usually present, is not, as a rule, the conspicuous feature which it is in the secondary type. The walls of the affected portion of the gut become very greatly thickened and hardened, all the coats being involved. In the mucosa and submucosa there is great overgrowth of lymphoid tissue, with much fibrosis, osdema and lymphocytic infiltration. The muscular coat is hypertrophied, and invaded by fibroblasts and lymphocytes, while the subserosa is also thickened and fibrosed, and in both these sites nodules of lymphoid tissue may make their appearance. As Hartmann (1907) has pointed out, the intestinal enlargement may be continued into a dense, fibre-adipose mass in the mesocolon or mesentery, often with tuberculous glands embedded in its substance. The underlying tuberculous nature of the lesion is usually apparent, tubercle follicles being irregularly scattered, usually in small numbers, throughout the wall of the gut. In other cases tubercles are demonstrated only with difficulty, and in some there may be no histological evidence whatever that the lesion in the intestine is tuberculous. There are good grounds for believing, however, that even cases which are negative histologically may really be tuberculous at bottom . (a) If a large number of blocks are taken from different parts of the lesion it may be found that while most of them show no evidence of tubercle, one or two do ; (b) in a certain proportion of cases where the histology of the gut is negative. the related lymph glands have been actively tuberculous; (c) cases have been described (Mouat, 1925) in which, with a negative histology, positive inoculation results have been obtained. Of the 21 cases in my series, 18 were histologically tuberculous, two showed tubercle follicles only in the associated lymph glands, while one was wholly negative. In three of Mouat's 13 cases, which were negative histologically, positive results were obtained by inoculating guinea-pigs with fresh material from the excised specimens. Besides tuberculous ulceration, or even in its absence, small superficial ulcers of a non-specific kind are often present, or there may be blindending pockets or sinuses, often pus-filled, extending deepl y into the inflammatory mass. 'I'wo obtrusive clinical phenomena are directly dependent on the nature of the pathological process. (a) Owing to the amount of new formation I Specimens from 21 cases were submitted for pathological investi gation; doubtless the total number admitted to hospital was greater than this.
June, 1028]
413
PATHOLOGY OF INT.ESflNAL TUBERCULOSIS
and thickening a large, palpable tumour makes its appearance in the ctecal region, while (b) owing to encroachment on the lumen of the gut signs of intestinal obstruction become manifest. SITE OF THE LESION.
Hyperplastic tuberculosis is a disease of the ileocrecal region. It is usually confined to the last foot of the ileum, the ileocrecal valve, the crecum or the ascending colon, any or all of which may be involved. In my own series, much the commonest site was the last few inches of ileum with the ileocolic valve. In cases where the ascending colon is affected, the contraction of this viscus may drag the crecum upwards towards the liver, the lower ileum then coming into line with the first part of the large intestine. The crecum itself may become flattened out, or converted into a mere subsidiary pouch or diverticulum. Stenosis is most frequent at the lower end of the ileum but occurs also in the ascending colon. The narrowing is brought about partly by the size of the inflammatory mass, partly by cicatricial contraction and partly by a curious polypoidal condition of the mucous membrane which makes its appearance in the later stages. This latter condition, in cases which I have examined, is mainly due to oedema of the submucosa, which in turn depends upon lymphatic obstruction, although it may be in part inflammatory. Occasionally there is much epithelial proliferation, with the formation of true adenomatous polypi. Occasionally the appendix is involved, and again the lesion may or may not be tuberculous histologically. Mummery (1910) has described a case of (?) hyperplastic tuberculosis of the sigmoid occurring in a woman of 27. The polypoidal condition of the mucosa. within the stenosed 4 inches of the gut was most striking, although histological proof of the tuberculous nature of the lesion was lacking. I have myself seen two cases of undoubted tuberculosis occnrring in relation to sigmoid diverticula. Both the patients were males, aged 65 and 53 respectively, and both were rather obese. Radical operations were carried out by my colleagues Mr. Flint and Mr. Chamberlain. In view of some statistics which I have worked out , I should like {or a moment to trespass on the field of the next speaker. TABLE
IV.-AGE
INCIDENCIII AT THill TIllIE OF OPERATION IN (A) CARCINOMA OF THE COLON, AND (B) HYPERPLASTIC ILEOCECAL TOBF.RCULOSIS.
Decades
0- 9 10-19 20-29
3D-89 40-49 150-59 60-69 70-79
A.
n,
Carcinoma coli. 154 cases (Leeds)
Hyperplastic lJeocll'c.1 tuberculosis. I~2 ca". (Caird (1921), COI,rath (18~8), Mouat and St.walt)
g3':ll :g
12'3 0 15 5 21 -5) 33'7
24'7 j"84 '5 4'6
1~:~ f 80 '9
29'6 29'6 10'5 ~ 6'6 2'0
0'0 ,
19'1
414
TUBERCLE
[June, 1928
. (I) Just as. car~inoma of the sigmoid and rectum may be closely
mimicked ,by. diverticulitis, so carcinoma of the csecum or ascending colon
~ay be mIml~ke~ by hyperplastic tuberculosis. The age incidence is an Important point 1D the differential diagnosis ; in carcinoma, 85 per cent. of the cases are over 40, in hyperplastic tubercle 19 per cent. The actual figures of two comparative series are shown in Table IV . .
(2) The value of X-ray examination in the diagnosis of hyperplastic
ileocsecal tuberculosis is not yet fully recognised.
The changes, which of course vary in different cases, may be summarised as followa : (a) ileal stasis witb delay in filling the coocum ; (b) filling defects in crecum and ascending colon ; (c) irregularity of outline of the csecum, and loss of haustral segmentation of the ascending colon; and (d) fixation of the crecum. I should be glad to hear from subsequent speakers whether the ctecocolie hypermotility described by Pirie in 1917, and by Lawrason Brown and Sampson in 1919 as occurring in secondary ceecal tuberculosis is ever met in the hyperplastic variety. ·What is the explanation of this peculiar tuberculous lesion and why does it differ so widely from secondary intestinal tubercle? Three main factors are probably concerned: (1) a fairly high grade of immunity to tuberculous infection; (2) infection by small numbers of bacteria; and (3) infection by bacteria of low virulence, in many cases bovine. These are the exact converse of what takes place in the development of intestinal lesions in phthisis, where resistance is already broken down by previous disease, and massive doses of virulent bacilli, chiefly human, are constantly passing along the gut. The part played by secondary invaders may be of importance especially in explaining the bizarre character of the histological picture. Whether there is such a thing as a hyperplastic entero-colitis of non-tuberculous origin still remains to be seen. I am inclined to think there is, in spite of arguments already put forward . Finally, while I have attempted to make a clear-cut distinction between these two types of intestinal tuberculosis, the hyperplastic and the secondary ulcerative, it must be clearly understood that intermediate grades occur. In practice, however, most of the cases fall definitely into one or other category, an important point in relation to treatment.
REFERENCES. and SAMPSON, H . L. Journ. Amer. Med. Assoc., 1919, 73, 77. "Intestinal Tuberculosis," London, 1926. Journ , Amer. Med. Assoc., 1927,88,1472. CAIRD, P. 1\1. Edi1lburgh Med. JOUTn., 1921, 26, 73. CONRATH, V. Beitr. z, klin, Ohir., 1898, 21, 1. EISENHARDT. loaug. Dissert., Miincheu, 1891. FENWICK, W. S., and DODWELL, P. R. Lancet, 1892, li, 133 and 190. HARTMANN, H. Brit. su«. Journ., 1907, t. 849. LOCKHART-MUMMERY, P. Proc. Roy. S oc. su«, 1910, 3, Pt. 1, Olin. Sect., p. 201. MOUAT, T. B. Thesis for the Degree of Ob.M., Edinburgh, 1925. PIRIE, A. H. Quoted by E . W. Archibald, Trans . Nat. Assoc. for Study and Prevent. of Tuberc., 1917, 13, 117. BROWN, LAWRASON
Idem. Idem.