Gut, 1965, 6, 225

Number, size, and distribution of Peyer's patchesin the human small intestine

Part I The development of Peyer's patches

J. S. CORNES

From the Department ofPathology, Bristol University

EDITORIAL SYNOPSIS The presence of Peyer's patches is commonly taken for granted but this isthe first serious study of the incidence and development of Peyer's patches before and after birth.

The number of Peyer's patches found in the variousparts of the human small intestine has never beenaccurately determined. Most textbooks of anatomyput their number at 20 to 30 (Gray 1962), and onlyslight variations of these figures are given from onetextbook to another. However, Sappey (1877),Passow (1885), and Gundobin (1892) occasionallyfound 70 or more patches, and Hellmann (1921)in his studies on status thymico-lymphaticusfound as many as 246 patches in young childrenwho had died suddenly and unexpectedly from awide variety of causes.The present study was undertaken to find out how

many patches there are in the normal human gutand to investigate what happens to them before andafter birth.

CASES STUDIED

Specimens of small intestine were obtained from 14necropsies on premature infants who were either stillbornor died shortly after birth, and from 24 necropsies onfull-term infants and children up to the age of 14 years.The investigations were limited to necropsies carried outwithin a few hours of death, and to patients with noclinical history or pathological evidence of diseasereferable to the gastrointestinal tract or reticulo-endo-thelial system.

METHODS OF INVESTIGATION

The specimens were opened along their mesentericborders and washed in running water for at least 24 hoursuntil the washing fluid was free of mucus, blood, andfood residues. Large Peyer's patches were then easilyseen and their number recorded. The duodenum,

jejunum, and ileum were measured, the jejunum beingdefined as the proximal two-fifths of the small intestinebetween the duodeno-jejunal flexure and the ileocaecalvalve.The specimens were next placed in dilute acetic acid

for 24 hours to fix the nuclei. Because Peyer's patchesconsist almost entirely of nuclear material the fixedpatches stand out clearly as white opaque superficialplaques against a semitranslucent greyish background.The follicular content of the patches was made more

apparent by staining with 0 5% polychrome methyleneblue for one minute after washing the fixed specimens inwater. They were rinsed freely to remove excess stain,and left to stand in water for one hour before examinationto permit good differentiation between the Peyer'spatches and the surrounding tissues. The dark bluish-black patches then contrasted with the lighter bluish-green of the rest of the specimen (Figs. 1 and 2). If thecontrast was not sharp further treatment with diluteacetic acid followed by washing in running water for10 minutes produced a satisfactory result.The number of follicles inside a patch were counted

with the help of a dissecting microscope, using trans-illumination and 8 75 x magnification (Fig. 3). Onlythose patches containing more than five follicles werecounted. Separate records were kept of patches containingmore than 25 follicles, and patches measuring more than4 cm. in length.

Finally, blocks were taken for histology from patchesin the duodenum, distal jejunum, and terminal ileum.These were fixed in formol saline, and paraffin sectionswere stained with haematoxylin and eosin to showcellular detail. and impregnated with silver salts todemonstrate reticulin. Initially these sections were madeto confirm that the patches were in fact collections oflymphoid follicles. Because the histological detail wasfound to be remarkably preserved in the majority ofsections examined they were later used to study the

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FIG. 1. Peyer's patches in distal jejunum of case 22. Methylene blue staining and transillumination ( x 0 9).

FIG. 2. Peyer's patches in terminal ileum of case 22. Methylene blue staining and transillumination ( x 2.0).

FIG. 3. Peyer's patch in proximal ileum, showing follicular structure of case 37. Methylene blue staining and trans-illumination (x 1P0).

microscopic anatomy and the follicular content of the lightly, were diffuse, poorly defined, and had blurredpatches. edges.The only difficulty experienced with these methods of

investigation was in the gross differentiation of Brunner's RESULTSglands from Peyer's patches. Peyer's patches staineddarkly, were well localized, sharply defined, and had NUMBER The number of Peyer's patches found in 14smooth, round edges. Brunner's glands, however, stained specimens from premature infants are given in

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Number, size, and distribution ofPeyer's patches in the human small intestine

Table I. The number of patches found in 24 speci-mens from full-term infants and children are givenin Table II. Mean values for selected age groups aregiven in Table III. It will be seen that the number ofpatches varied from 45 at 24 weeks' gestation to305 at 12 years, with mean values varying from 59before 30 weeks' gestation to 239 at puberty.The tables show that there are considerable

numbers of both large and small Peyer's patches inthe human gastrointestinal tract, and that they arewell developed early on in foetal life. Although thereis considerable individual variation there is a generaltendency for the patches to increase in size andnumber with increasing age. The number of patches

found, therefore, bears some relationship toage, body weight, and the length of the small in-testine.

SHAPE The Peyer's patches were generally oval orrectangular in shape and situated on the anti-mesenteric border. In the duodenum and terminalileum, and occasionally in the proximal jejunum, thepatches were situated at random around the gut wall.A few bizarrely shaped patches were invariablyfound in the proximal jejunum and around the ileo-caecal valve. These patches were sometimes serpi-genous in outline, and several had small sidebranches two or three follicles wide.

Case Period ofNo. Gestation (weeks)

234567891011121314

2428282929293031323434343637

TABLE INUMBER OF PEYER'S PATCHES FOUND DURING THE PERIOD OF GESTATION

Sex Body Weight (kg.) Length of Small No. of Patches with More than FiveIntestine (cm.) Follicles

Duodenum Jejunum Ileum Total

FMFMMMFFMMMFFM

0-8171-01-21-31-9131-31-41-12-21-63-41-7

148192192142208147189247119118242182230205

0000

010

00000

00

833151921173517121922224625

3730484644356248413951575073

4563636566539765535873799698

TABLE IINUMBER OF PEYER'S PATCHES FOUND IN INFANCY AND CHILDHOOD

Case No. Age Sex Body Weight (kg.) Length of Small No. ofPatches with More thanIntestine (cm.) Five Follicles

Duodenum Jejunum Ileum

0

0

0

0

0

0

6 days8 wk.8 wk.9 wk.7 mth.9 mth.12 mth.16 mth.20 mth.35 mth.48 mth.56 mth.72 mth.12 yr.12 yr.12 yr.13 yr.14 yr.

FFFFFM

M

M

FM

FM

M

M

FM

FFM

FFM

FM

4-5402-72-32-02-82-62-64-23-17-7

126-6

1511

1635303345395058

397420288278211287165332481470505439427560428558431534548761622805695707

240

0

20

0

0

0

0

544223215645

1111104

504839433023333150436657398449129664954589911811693

71633957648142688037103123806270113577010359148176136152

Total

Total No. of Patcheswith More than 25Follicles

1231157810096104759913080174184123168122244138122161122258305262249

5973415846533367865068795476521066750725095126118125

227

Total No. of Patcheswith More than 25Follicles

33413330335037292142525451

151617181920212223242526272829303132333435363738

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J. S. Cornes

TABLE IIIMEAN VALUE OF NUMBER AND SIZE OF PEYER S PATCHES FOUND IN SELECTED AGE GROUPS

No. of Cases Mean BodyWeight (kg.)

68

10365

1-31-7

3-187

2145

Mean Length ofSmall Intestine (cm.)

172192

333457510718

Mean No. ofPatches

With More than With More thanFive Follicles 25 Follicles

5979

100160161239

3442

576771

103

SIZE AND DISTRIBUTION Duodenal patches werepresent in only five of the first 25specimensexamined.After 9 weeks of age small patches were invariablyfound below the ampulla of Vater. In only two cases(26 and 38) were patches found between the pylorusand the ampulla.Although the ileum usually contained larger and

more numerous patches than the jejunum this wasnot always the case. Five specimens (cases 2, 24, 28,30, 31) contained smaller but more numerouspatches in the jejunum than in the ileum. Bearing inmind that the jejunum is only two-thirds the lengthof the ileum a further nine specimens (cases 13, 15,16, 17, 18, 21, 32, 34, 37) contained smaller butrelatively more numerous patches in the jejunumthan in the ileum.No patch measuring more than 4 cm. in length

was found in specimens from premature infants.After term one or two such patches were found inthe distal jejunum of six specimens, and a variablenumber were found in the ileum of 18 specimens.Although the patches with the largest surface areawere situated close to the ileocaecal valve the longestpatches were usually found in the proximal ileum.The longest patch, found in the proximal ileum ofcase 37, measured 9-9 cm. in length.

FOLLICULAR PATTERN Studies of the follicularcontent of the Peyer's patches showed that theirincreasing size was related to an increase in thenumber of follicles present. The larger the patch thegreater was the number of follicles found within it.Microscopy showed that the patches were only onefollicle thick, the follicles being intimately related tothe overlying epithelium. Occasionally thick patcheswere found in the terminal ileum of well-nourishedinfants and young children and gross examinationsuggested that these patches were two or threefollicles thick. Sections taken for histology, however,showed a papillary appearance similar to that shownin Figure 4. These patches were still only one folliclethick, and the intimate relationship between the

individual follicle and the overlying epithelium waspreserved.

DISCUSSION

The methods used in this study are relatively crudeand give only a rough idea of how much lymphoidtissue is actually present in the human smallintestine. It is clear, however, that there are morePeyer's patches than is generally recognized, andcertainly more than the figures usually quoted intextbooks of anatomy.

FOLLICULAR CONTENT According to Ziegler (1850)the number of follicles in a patch varies from 20 to400. Gundobin (1892) counted 30 to 70 follicles inthe smaller patches and found the number in thelarger patches too difficult to evaluate. In thepresent study the longest patch contained over 980follicles (Fig. 3). The smallest patches generallycontained 10 to 20 follicles, the medium size patches60 to 120 follicles, and the larger ones 180 to 260follicles.

FIG. 4. Histology of Peyer's patch in terminal ileum,showing papillary pattern. Haematoxylin and eosin ( x 5).

Age Group

Before term24-29 weeks30-39 weeks

After term0-10 weeks3-12 months13-72 months12-14 years

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Number, size, and distribution of Peyer's patches in the human small intestine 229

DEVELOPMENT Due to lack of suitable freshmaterial it was not possible to examine any specimenbefore the 24th week of foetal life when 45 well-defined Peyer's patches were found. Lympho-poiesis is, however, found in the wall of the smallintestine as early as the 15th week of foetal life(Eberl-Rothe and Langegger, 1953), and Peyer'spatches are said to be well developed by the end ofthe fourth and the beginning of the fifth month ofgestation (Baginsky, 1882; Cho, 1931).Animal investigations have tended to suggest that

the general pattern of lymphoid tissue in the intestineis laid down early in foetal life. Removal of Peyer'spatches after birth, for example, is not followed bycompensatory new formation of lymphoid tissue atother sites (Sanders and Florey, 1940), but byhypertrophy and hyperplasia of the existinglymphoid tissue (Kelsall and Crabb, 1959). Experi-ments on animals raised in a germ-free environmenthave suggested that the number of patches found isfixed at, or shortly after, birth, the presence ofbacteria being necessary for their full development(Miyakawa, 1959). In the human being this is notthe case. Peyer's patches increase in size and numberthroughout the second half of foetal life, and theycontinue to increase in size and number for at leastthe first 10 years after birth.

TECHNIQUES The most likely explanations for thesmall number of patches recorded in the textbooksare the use of degenerate material and formalinfixation.

In the present study all the material was refriger-ated and obtained within a few hours of death. Aseparate study of refrigerated material obtained twoto five days after death revealed large bile-stainedand necrotic areas in the small intestines of all thecases examined. Dilute acetic acid fixation andmethylene blue staining failed to demonstrate thePeyer's patches in these areas.At the start of these investigations an attempt was

made to demonstrate Peyer's patches in formalin-fixed material. Due to shrinkage of the lymphoidtissue and discoloration of the bowel wall manypatches seen in the post-mortem room were nolonger visible two or three days later when theformalin-fixed specimen was examined. Only largepatches in the ileum could be recognized withcertainty, and small patches in the duodenum andjejunum were obscured altogether. Attempts todistinguish Peyer's patches from the surrounding

tissues by differential staining techniques wereunsuccessful.The simplest way of studying Peyer's patches is to

use fresh material washed in running water. If amore detailed study is required the specimen shouldbe placed in dilute acetic acid and not in formolsaline. The specimen can then be left for severalweeks and the patches actually appear to improvewith keeping.

SUMMARY

Thirty-eight specimens of normal small intestinefrom premature infants and children were examinedfor the presence of Peyer's patches, using aceticacid fixation and polychrome methylene bluestaining.The mean number of patches containing more than

five lymphoid follicles varied from 59 before 30weeks' gestation to 239 at puberty.The mean number of large patches containing

more than 25 follicles varied from over 40 at termto 100 or more at puberty.

Their size and number, although variable, are notfixed at birth.They increase in size and number from early

foetal life to puberty.

REFERENCES

Baginsky, A. (1882). Untersuchungen uber den Darmkanal desmenslichen Kindes. Virchows Arch. path. Anat., 89, 64-94.

Cho, D. (1931). Histological investigation of the digestive tracts of thehuman fetus. II. Development of small intestines. Jap. J.Obstet. Gynec., 14, 324-330.

Eberl-Rothe, G., and Langegger, P. A. (1953). Ober die Entwicklungder Peyerschen Platten. Z, Anat. Entwickl.-Gesch., 117, 26-35.

Gray, H. (1962). Gray's Anatomy, Descriptive and Applied, 33rd ed.,edited by D. V. Davies and F. Davies. p. 1456. Longmans,London.

Gundobin, N. (1892). Uber den Bau des Darmkanals bei Kindern.Jb. Kinderheilk., 33, 439-473.

Hellmann, T. J. (1921). Studien uber das lymphoide Gewebe. IV. ZurFrage des Status lymphaticus. Untersuchungenuber die Mengedes lymphoiden Gewebes, besonders des Darmes beimMenschen mittels einer quantitativen Bestimmungsmethode.Z. menschel. Vererb.-u. Konstit.-Lchre., 8, 191-219.

Kelsall, M. A., and Crabb, E. D. (1959). Lymphocytes and Mast Cells,pp. 294-295. Williams and Wilkins, Baltimore.

Miyakawa, M. (1959). The lymphatic system of germ free guineapigs. Ann. N.Y. Acad. Sci., 78, 221-236.

Passow, A. (1885). Ueber das quantitative Verhalten der Solitarfollikelund Peyers' schen Haufen des Dunndarms. Virchows Arch.path. Anat., 101, 135-155.

Sanders, A. G., and Florey, H. W. (1940). The effects of the removal oflymphoid tissue. Brit. J. exp. Path., 21, 275-287.

Sappey, P. C. (1877). Traite d'Anatomie Descriptive, 3rd ed., vol. 4,p. 239. Delahaye, Paris.

Ziegler, R. 0. (1850). Ueber die solitaren und Peyer'schen Follikel.Inaugural dissertation. F. E. Thein, Wurzburg.

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