J. clin. Path., 1976, 29, 245-249

Lymphoid tissue and lymphoid-glandular complexesof the colon: relation to diverticulosisW. F. KEALY

From the Departments of Morbid Anatomy, King's College Hospital, London and Kingston Hospital,Kingston-on-Thames, Surrey

SYNOPSIS The lymphoid tissue of the normal colon is compared with that of colons with diverticulardisease. Colons with diverticular disease show a significant increase in the number of lymphoidnodules in areas not containing diverticula. Lymphoid-glandular complexes of the colon were

studied in relation to diverticular disease.It is suggested that the lymphoid nodules and the lymphoid-glandular complexes of the colon

constitute weak points in the bowel wall and may play a part in the pathogenesis of diverticula.

Colonic lymphoid-glandular (L-G) complexes are,in all probability, normal structures (Kealy, 1976).However, Clark (1969) and Dyson (1975) raise thepossibility that they may be the forerunners ofdiverticulosis. The relationship of lymphoid-glan-dular complexes and the lymphoid tissue of thecolon to the development of diverticulosis has beenstudied.

Material and Methods

MACROSCOPICAt necropsy colons were taken from subjects over 40years of age. Colons from subjects in whom therewas a possibility of alteration of the lymphoid tissue(eg, due to drugs, lymphoma or primary colonicdisease apart from diverticular disease)were excluded.Each colon included the terminal few centimetres ofileum and was cut opposite the third sacral vertebra.They were washed through with normal saline,distended with 10% formol saline to a pressure ofabout 30 cm of water, and fixed for at least threedays. They were then opened along their mesentericborders and examined. Altogether 100 colons werecollected, 50 with diverticular disease and 50 with noevidence of disease. The number and site of thediverticula were noted together with the age and sexof the patient. Necropsy specimens of colon fromthree Nigerian subjects resident in Nigeria were alsosimilarly examined and these showed no abnorm-ality.

Received for publication 1 September 1975

LymphoidNodule CountSamples about 10 cm2 were taken from the mid-points of the ascending, transverse, descending, andsigmoid parts of each colon. The caecum andareas of colon containing diverticula were ex-cluded. Each specimen was then treated accordingto a method based on that described by Dukes andBussey (1926). Adventitial fat was removed fromeach piece, and the taenia were stripped off ordivided at close intervals in some, in order that themucosa should lie flat. The mucosa was removedfrom the surface of each specimen by light scrapingwith a scalpel under a gentle stream of cold water(fig 1), leaving the muscularis mucosae virtuallyintact. Each piece was blotted dry and placed in a dishcontaining 1% alcoholic methylene blue for threeto five minutes. Differentiation was carried out inwarm running water until the lymphoid nodulesappeared as dark blue dots of variable size on alight blue background (fig 2). A small sheet of plateglass on which was etched an area 6 x 6 cm dividedinto square centimetres was placed on the surface ofthe specimen, and the number of lymphoid nodulesin that area was counted under bright incidentillumination.

MICROSCOPICIt was originally intended to examine sections ofstandard blocks taken from each area ofthe colonbut,because of the autolysis, surgical material wasresorted to. Sections from surgical partial and totalcolectomy and proctocolectomy specimens at King'sCollege Hospital and Kingston Hospital were

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246

:Dk

W

is.¢

Fig Section demonstrating the level to which the colons

were scraped, showing muscularis mucosae and lymphoidnodule (HandE x 26).

examined for the years 1965-74 and 1958-74 res-

pectively.

Results

NECROPSY SPECIMENS

Colons from subjects with diverticular disease

showed an average age of 71 -2 years, range 44-92,sex ratio 27 M :23 F. Diverticula were present mainlyin the descending and sigmoid parts of the colon. In

four specimens they were present throughout, and

in one, they were limited to the ascending colon.

Colons with no evidence of disease had an average

age of 67-5 years, range 40-93, sex ratio 26 M :24 F.

The Nigerian specimens were from two women aged55 and 42 years and from one man aged 38 years.

Lymphoid Nodules

The number of lymphoid nodules counted in each

area was expressed as the average per square centi-

metre. In colons with diverticula the number of

lymphoid nodules per square centimetre, expressed as

W. F. Kealy

an average for the colon as a whole, ranged from2-4 to 9 5; in those without evidence of disease from1P5 to 7-3; and in the Nigerian specimens from 3-1to 3-9.The average numbers of lymphoid nodules per

square centimetre for all areas of colon are shown inthe table.

Colon

Ascending Transverse Dest eniding Signtoid

Diverticular disease 4 2 4 9 5 2 5 8Normalcolon 3-4 3 6 3 5 3 8Increase per cent 23 5 36 1 48 6 52 7Nigerian specimens 3 6 3 4 3 4 3 5

Table Average number oflymphoid nodules persquarecentimetre in allareas ofcolon andpercentage increase indiverticular disease

No correlation was demonstrated between thenumber of diverticula and the number of lymphoidnodules, nor was any increase in the number ofnodules noted with increasing age.

MicroscopicAltogether sections from 1924 partial and totalcolectomy specimens were examined. Diverticulardisease was present in 351 cases, and L-G complexeswere observed in 51 of these. The L-G complexeswere always associated with a lymphoid nodule andprotruded through a gap in the muscularis mucosae(fig 3). The extent of mucosal protrusion through thegaps in the muscularis mucosae was variable, as alsowere the sizes of the lymphoid nodules which wereoften hyperplastic with germinal centres. Lymphoidnodules were often observed at the advancing pointof developing diverticula in the muscle coat situatedinside a gap in the muscularis mucosae (fig 4). Onthe other hand, L-G complexes were seldom seen atthe tip of advancing diverticula within the musclecoat but were occasionally present indiverticulawhichhad penetrated the bowel wall to the serosa (fig 5).

Study of sections from the Nigerian specimensshowed a distribution of lymphoid tissue similar tothat already described for normal colons (Kealy,1976). No L-G complexes were observed in any ofthese sections.

Discussion

The exact mechanism by which diverticula occur isstill not understood (Raia et al, 1973) and no singlefactor explains their origin, but the process probablyresults from a summation of several factors(McGrath, 1912). It is accepted that acquiredcolonic diverticula are pulsion in type associatedwith increased intraluminal pressure (Edwards,

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Lymphoid tissue and lymphoid-glandular complexes ofthe colon: relation to diverticulosis

Fig 2 Plan view ofscraped surface ofcolon showing lymphoid nodules (black dots) (methyleneblue x 15).

..62. 7 '

*S .:

..e.W ...,...

Fig.3.Colon showing L-G complex (HandE x 30).

Fig 3 Colon showingL-G complex (HandE x 30).

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W. F. Kealy

5f .. e | .Ss;.: X.of F

Fig 4 Developing diverticulum with lymphoid nodule at

advancing tip (HandE 26).

1934; Almy, 1965) and a disorder of muscle functionwith increased tone causing shortening of the bowelwith consequent muscle thickening (Williams, 1968;Morson, 1975).The results show that in the colon as a whole there

is a significant (p < 0 001) increase in the number oflymphoid nodules in colons with diverticular diseasecompared to those without disease. The increasednumber is present in those areas of colon which didnot include any diverticula, and this increasebecomes more pronounced from the ascending colonto the sigmoid. Because the lymphoid nodules aredistributed in close apposition to the muscularismucosae and are often situated between its fibres orin gaps in its substance, these foci could be con-sidered as weak points in the bowel wall, and since anincrease in size of the lymphoid nodules is parallelledby an increase in width of the gaps in the muscularismucosae (Kealy, 1976), it is plausible to suggest thatthese points are made weaker by hyperplasia of thelymphoid nodules. In addition, it is possible that theincreased number of lymphoid nodules in colons

Fig 5 Established diverticulum with L-G comlplex in itswallat the serosa, bottom left (HandE , 16).

with diverticular disease may be partly explained bythe presence of diverticula with the associated chronicinflammatory state, but this effect on the nodulecount could be regarded as minimal since the piecesof colon examined did not include any diverticulaand, in the case of the ascending and transversecolons, they were taken from areas of bowel farremoved from the sites of diverticula which in mostcases involved only the descending and sigmoidparts. Also it is conceivable that L-G complexes,which are present at the sites ofgaps in the muscularismucosae, may increase in size when factors such aslymphoid hyperplasia, increased intraluminal pres-sure, and muscle dysfunction are present together.The incidence of diverticular disease in African

countries is rare (Painter and Burkitt, 1971; Hunt,1972) and the Nigerian specimens were included inthis study to see if there existed any gross or micro-scopic differences between them and the otherspecimens. It is interesting to note that the numberof lymphoid nodules in the Nigerian colons is veryclosely similar to that present in the colons showing

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Lymphoid tissue and lymphoid-glandlar complexes of the colon: relation to diverticulosis

no disease. The number of Nigerian colons examinedwas small and because of postmortem autolysis astudy of surgical colectomy specimens from Nigeriais now being undertaken.

It is concluded that the lymphoid nodules inapposition to the muscularis mucosae may constituteweak points in the bowel wall, that the increase intheir number in diverticular disease may represent a

pre-diverticular state, and that these and the L-Gcomplexes may act as the 'thin edge of the wedge' inthe development of diverticula.

I wish to thank Dr M. E. A. Powell, KingstonHospital, for his criticism and advice; ProfessorE. A. Wright, King's College Hospital, and Dr J. H.Earle, Queen Mary's Hospital, Roehampton, foraccess to surgical sections; Dr Ed. 'B. Attah,University of Ibadan, Nigeria, for necropsy material;Mr J. Spicer, Kingston Hospital, for technicalassistance; and Miss B. R. Hume for typing thispaper. The work was supported by a grant from theSouth West Thames Regional Health Authority forthe purchase of photomicrographic equipment.

This paper constitutes part of the work for an

MD thesis to be submitted to the National Universityof Ireland.

References

Almy, T. P. (1965). Diverticular disease ofthe colon-the newlook. Gastroenterol, 49, 109.

Clark, R. M. (1969). Microdiverticula: a possible cause ofgranulomatous ileocolitis. Canad. med. Ass. J., 100,1025-1031.

Dukes, C. and Bussey, H. J. R. (1926). The number oflymphoid follicles of the human large intestine. J. Path.Bact., 29,111-116.

Dyson, J. L. (1975). Herniation of mucosal epithelium intothe submucosa in chronic ulcerative colitis. J. clin. Path.,28,189-194.

Edwards, H. C. (1934). Diverticula of the colon and vermi-form appendix. Lancet, 1, 221-227.

Hunt, T. (1972). Digestive disease: the changing scene. Brit.med. J., 4, 689-694.

Kealy, W. F. (1976). Colonic lymphoid-glandular complex(microbursa): nature and morphology. J. clin. Path., 29,241-244.

McGrath, B. F. (1912). Intestinal diverticula: their etiologyand pathogenesis. Surg. Gynec. Obstet., 15, 429-444.

Morson, B. C. (1975). Pathology of diverticular disease of thecolon. Clin. Gastroent., 4, 37-52.

Painter, N. S. and Burkitt, D. P. (1971). Diverticular diseaseof the colon: a deficiency disease of western civilisation.Brit. med. J., 2,450-454.

Raia, A., Habr-Gama, A., Pinotti, H. W., and Rodrigues,J. J. G. (1973). Diverticular disease in the transposed colonused for oesophagoplasty-a report of 2 cases. Ann. Surg.,177,70-74.

Williams, I. (1968). Diverticular disease of the colon, a 1968view. Gut, 9, 498-501.

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diverticulosis.of the colon: relation tolymphoid-glandular complexes Lymphoid tissue and

W F Kealy

doi: 10.1136/jcp.29.3.2451976 29: 245-249 J Clin Pathol

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