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Heterotopic gastric mucosa and reduplications of the intestinal tract
HETEROTOPIC ARTHUR
R.
GASTRIC MUCOSA AND REDUPLICATIONS OF THE INTESTINAL TRACT* KIMPTON,
M.D.
AND
Surgeon-in-Chief, First SurgicaI Service, Boston City Hospital
D.
REYNOLDS CRANE,
M.D.
Assistant Pathologist, MaIIory Institute of PathoIogy, Boston City Hsopital
BOSTON, MASSACHUSETTS HILE the occurrence of gastric mucosa in ectopic foci throughout the body may be responsibIe for severe cIinica1 signs and symptoms and may even Iead directIy to the death of the patient, it is aIso true that proper surgica1 treatment may produce a compIete cure. In view of these facts we shouId Iiketo caII attention to the occurrence of this type of congenita1 abnormahty in various portions of the gastrointestina1 tract and reIated structures and report three unusual cases which nevertheIess iIIustrate we11 its more common pathoIogic effects. The presence of isIands of gastric mucosa in the esophagus and in remnants of the viteIIine duct (MeckeI’s diverticuIum) is common. NichoIsonl states that there is an incidence as high as 75 per cent in the upper portion of the esophagus. In a report of thirty-two cases of Meckel’s divertic&m, Hudson and KopIik2 found gastric mucosa in 52 per cent. This corresponds very cIoseIy with the figures from the surgica1 and autopsy records of the MaIIory Institute of PathoIogy where, of the Iast twenty Meckel’s diverticuIa examined histoIogicaIIy, ten, or 50 per cent, showed isIands of ectopic gastric mucosa. Aside from these two Iocations the occurrence of ectopic gastric mucosa is extremeIy rare. It has, however, been reported in the duodenum by TayIor,3 in the jejunum by Bart6k4 and by Kimpton and Crane,5 in the iIeum by Poindecke# and by TayIor,3
W
and in the pancreas, gaII-bIadder and coIon by NichoIson. l Its occurrence in the umbihcus in remnants of the viteIIine duct has been described by Stone7 and by NichoIson.* IsIands of ectopic gastric mucosa produce no typica or pathognomonic cIinica1 signs or symptoms, these depending to a Iarge extent upon the site of their occurrence. However, the one sign which they may have in common, regardIess of their Iocation, is hemorrhage into the gastrointestina1 tract. The cause of the bIeeding is the frequent presence of typica peptic uIcers either adjacent to or invoIving the ectopic mucosa, with uIceration of bIood vesseIs which may actuaIIy Iead to death from exsanguination. The importance of uIceration and hemorrhage in connection with MeckeI’s diverticuIa has been emphasized by previous writers2*gs10 and Hudsonl’ states that 31 per cent of MeckeI’s diverticuIa may show hemorrhage on this basis. In considering the various possibIe causes of intestina1 hemorrhage this condition shouId be remembered, particuIarIy when deaIing with intestina1 hemorrhage in chiIdren. The uIcerations associated with this anomaIy may aIso Iead to perforation with peritonitis or mediastinitis. The heterotopic mucosa may be of sufficient size or may proliferate to suff&ient size to produce the cIinica1 picture of a tumor with a paIpabIe mass, obstruction, voIvuIus or intussuscep-
* From the First SurgicaI Service and the MalIory Institute of PathoIogy, Boston City HospitaI. 342
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tion. The folIowing three unusua1 cases wiII serve to illustrate some of these possible dangers of heterotopic gastric mucosa.
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Iaxative; this was invariably followed by a watery defecation, but at no time were the stooIs abnormaIIy
dark or bloody.
The attacks
FIG.I.Case 1. Cross specimen showing tumor nodule in jejunum. The gross resrmblance of the mucosal surface of the tumor nodule to gastric mucosa is striking. About two times actual size.
CASE
REPORTS
CASE I. .J.B., a 7 year old girl, was seen in consultation by one of us (A. R. K.) because of recurrent attacks of severe paraumbiIi~aI pain associated with nausea and vomiting since the age of 3. She was born at ful1 term after a norma pregnancy, the fifth chiId of a family of nine. Her weight at birth was 894 pounds and no physicaI abnormalities were noted. Her parents and siblings were entireIy normal, and there were no pertinent factors in her past history other than those associated with her present iIIness. The first abdomina1 complaint occurred at the age of 3 and was manifested by severe pain about the umbiIicus, not Iocalized, and marked by a continuous ache with occasional attacks of excruciating pain causing her to cry out. After two or three hours the chiId vomited and the pain was reIieved. SimiIar attacks occurred subsequently three to six times a year. They lasted from one to three days, and began during the night as frequently as during the day. Following each attack the child appeared perfectly normal except for a sense of weakness. Fever never developed during any of the attacks. The mother aIways gave the chiId a
gradually became more frequent. and severe, but no definite inducing factor was ever noted. TWO years after the onset of this condition a physician was consulted for the first time and a diagnosis of intestina1 worms was made. Three weeks Iater a second physician was consuIted and for the first. time an abdominal mass was paIpated; the mother stated that a mass could be seen especially when the pain was severe. At this time a diagnosis of voIvuIus was made, the abdomen was tightly strapped with tape, and abdominal massage and shaking the child in an upside-down position by hoIding the feet were advised. FoIlowing this the attacks were much Iess frequent. One year later, because of a severe attack, the patient was referred to a hospital, where .+rays of the intestinal tract reveaIed nothing abnormal. During the year preceding the present examination she had had attacks of varying severity every four or five weeks. She was seen in consultation on June 21, 1937, ha\:ing just suffered an acute attack of abdominal pain. PhysicaI examination was negative save for the abdomen, where an elongated tumor couId be felt extending diagonaIIy across the abdomen from left to right. It was IO or 12 cm. in length, 2 or 3 cm. in width, soft, smooth and non-
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tender. The center of the mass Iay just beneath the umbilicus. The appearance was quite typica of intussusception. WhiIe Iying quietIy
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7 by 5 by 0.4 cm. The serosa was measuring negative but the entire waII was thickened and edematous, aIthough not otherwise remarkabIe.
FIG. 2. Case 1. High-power field of the tumor mucosal ceIIs, showing Iarge, round parieta1 ceIIs (indicated by arrows). HematoxyIin and eosin. X gro.
on the examining table, the chiId suddenly screamed, doubled up, holding her abdomen, became pallid and perspired profuseIy. This lasted for about ten minutes and was foIIowed in a few minutes by a simiIar attack. The abdomina1 tumor became very prominent through the chiId’s thin abdomina1 waI1 while the pain was most severe. At operation, the abdomen was exposed by a left paraumbiIica1 midrectus incision and a large intussusception of the jejunum was found starting about 15 cm. beIow the Iigament of Treitz. The bowel was edematous but entireIy viable, and the intussusception was reduced with ease. When it was compIeteIy reduced, a soft, dough-Iike tumor mass was found fiIIing the entire Iumen of the jejunum 20 cm. below the Iigament of Treitz. This was resected with12 cm. of jejunum, out diffIcuIty by removing and a side-to-side anastomosis was done. The abdomen was closed in Iayers without drainage. The immediate postoperative course was uneventfu1. Eighteen months after the operation the chiId was heaIthy and had had no recurrence of her previous symptoms. Pathologic Report. The gross specimen consisted of a piece of smaI1 intestine (jejunum)
3 cm. in The mucosa in one area measuring diameter was redundant, being eIevated 0.4 cm. above the surrounding tissue to form a definite tumor noduIe with a broad base. There was no evidence of infiItration of the underIying tissues. HistoIogic sections through the redundant portion of mucosa showed it to be composed of Iong mucous gIands of the gastric type in some of which numerous Iarge, round, eosinophilic parietal ceIIs couId be readiIy identified. At the margin of the noduIe there was an abrupt transition to a mucosa of the jejunal type, with many Iarge pIicae circulares and numerous gobIet ceIIs. The tumor noduIe itself lay entireIy on the mucosa1 side of the muscuIaris mucosa, and the redundancy of the mucosa noted in gross examination was due to the numerous gastric gIands of which the tumor was composed. There were occasiona mitotic figures in the epitheIium, but the ceIIs were perfectIy differentiated into adult chief and parieta1 ceIIs, as found in the mucosa of the muscuIaris and stomach. The submucosa, serosa were norma save for evident interceIIular edema.
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This case is essentially but
intussusception,
interest
because
is
a typical unusual
of the embryologic
FIG. 3. Case
Crane-Gastric one of of anom-
and
C. C., a g months old baby boy, to the Boston City Hospitai because of bleeding by rectum. He was the first chiId of a 28 year oId white housewife and was born at term. It was noted in the CASE
II.
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hospitaI after his birth that he vomited frequently, but his parents never returned him to the hospital for study as advised. There were
II. Drawing to demonstrate the abnormahty of redupIication the ileum. Cecum and appendix are on left.
afy which was responsibIe for the intussusception. The r61e of tumors in the production of intussusception, particularIy in the adult, has been emphasized by recent investigators,1~~13~14 although the association of the two lesions has Iong been recognized. Roan,13 in reporting a series of cases of intussusception, states that tumors are a negligible factor in chifdren up to the age of 3, Since benign tumors are much commoner than malignant ones in the smaII intestine, they predominate in any analysis of tumors causing intussusception. Nevertheless, the polypoid nature of many benign intestinal neoplasms renders them even more potent factors in the genera1 etiology of intussusception. In all reported series the commonest types of tumors encountered are myomas and adenomas, akhough instances of fibroma, Iipoma, hemangioma and other benign tumors are not infrequent. was admitted
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no other pertinent factors in his past history other than those associated with his present iIIness. The first appearance of recta1 bIeeding occurred at the age of 3 months about three weeks after the onset of pertussis. At that time the child had three red to tarry stooIs. He was admitted to the South Department of the Boston City HospitaI because of the pertussis and rectal bleeding, but was taken home against advice before he could be properly studied. There had been no recurrences of the recta1 bIeeding up until the day of the Iast admission when his mother noted the presence of bIack tarry stools and fresh blood in his diapers twice within a period of two hours. The physicai examination showed marked pallor of the skin, a hard round mass about the size of a lemon in the Ieft upper quadrant of the abdomen, distention of the abdomen and the presence of blood in the rectum. In addition he showed some beading of the ribs and enrargement of the head with prominent fronta bosses. The physical examination was otherwise negative. The only laboratory data gathered were a hemogiobin of 25 per cent, a red bIood count of 2,060,000, and a white brood count of 17,200 with 80 per cent poIynucIear ceIIs.
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A Iaparotomy was performed and a giant diverticuIum of the iIeum was found. The iIeum became doubIe-barreIed at a point about
FIG. 4. Case II. Cyst after cross section showing the rugose gastric-Iike appearance of the lining and a typica “punched-out” peptic uIcer. About actuaI size.
25 cm. from the iIeoceca1 vaIve. This doubIe iIeum continued proximaIIy for about g5 cm., the inner or faIse bowe1 Iying in the mesentery of the outer or true bowe1 but in cIose approximation to it. The faIse segment then dipped towards the base of the mesentery penetrated the mesentery and ended in a round cystic structure about 6 cm. in diameter, apparentIy corresponding to the mass noted cIinicaIIy in the Ieft upper quadrant of the abdomen. It was felt that the cyst and an uIcer which couId be paIpated at the bifurcation of the iIeum were the main sources of the bIeeding and therefore the cyst, about 5 cm. of the diverticuIum with the cyst and about 5 cm. of iIeum at the point of bifurcation were resected. A side-to-side anastomosis was then done between the termina1 iIeum and a portion of iIeum overIying the diverticulum. Pathologic Report. The gross specimen consisted of three parts. The first was a piece of intestine from the bifurcation of the iIeum 5 by 4.2 by 0.3 cm., the surface of which was grayred and edematous. In the middIe of the mucosa1 surface of this fragment were three punched-out ulcers, the largest I cm. in diameter and 0.3 cm. in depth, the others being but
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sIightIy smaIIer. The other two portions of the specimen were a piece of intestine measuring 5 by I by 0.3 cm. and somewhat resembIng an appendix and a cystic structure 6 cm. in diameter fiIIed with partiaIIy digested bIack bIood and showing a rugose gastric-Iike mucosa. It contained approximately eight punched-out uIcers, the Iargest measuring I by I by 0.6 cm. HistoIogicaIIy a11 three of these segments showed typica gastric mucosa with both chief and oxyntic ceIIs the Iatter being extremeIy abundant. The muscle Iayers of the segments were those of smaI1 bowe1 save for that of the cyst which showed interIacing muscle bundIes simiIar to those seen in the norma stomach. The uIcers were sharply defined, in some areas extended deeply into the muscuIaris and showed a moderate foca1 Iymphocytic reaction. FoIIowing the operation the patient showed progressive elevation of temperature and puIse and died within twenty-four hours. The onIy important autopsy findings were those reIated to the intestina1 tract. The Iarge bowe1 was not remarkabIe, and 23 cm. proxima1 to the iIeoceca1 valve there was a side-to-side anastomosis between two closed and sutured ends of iIeum. The ileum proxima1 to the anastomosis was double, being composed of two distinct tubes which were inseparabIy fused at their adjacent surfaces. The inner intestina1 tube was greatIy distended as it Iay in the mesentery of the outer or norma iIeum. The mesenteric vesseIs to the true bowel circumscribed this inner bowel. These intestina1 tubes ran paraIIe1 for a distance of go cm. at which point the inner tube became detached and ran for a short distance towards the base of the mesentery. The outer intestine continued on proximaIIy to join a norma jejunum, duodenum and stomach. HistoIogic sections showed this inner segment of bowe1 to be Iined throughout by gastric mucosa with numerous oxyntic ceIIs. The muscuIaris was incompIete, being entirely Iacking in the portion where the two tubes were adjacent aIthough the remainder of the muscularis of each segment was normaI. CASE III. F. W., a 77 year oId white male, was admitted to Boston City HospitaI because of edema and dyspnea of increasing severity. Because of his poor condition no reIiabIe history was obtained. On physica examination he showed an enIarged heart, bIood pressure of r~o/go and marked dependent edema. Labora-
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tory data were not significant. The patient did well for a few days and then showed increasing signs of cardiac failure and died twenty days after admission.
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portions of this diverticuIum connecting directly with the bowel lumen. It would seem that autodigestion by the local concentration of hydrochloric acid in the sac
FE<;. 5. Case 11. Cross section through normaI bowel and redupfication at point indicated in Figure 3. Gastric mucosa lining reduplication above; lumen of true bowe1 with norma mucosa below. Note the absence of the muscularis between the two lumens on the right of the photograph. Hematoxylin and eosin. x 30.
Autopsy showed ulceration in the esophagus about 4 cm. from the cardia and measuring about 3 cm. in diameter, with an irreguIar edge and a green sIoughing base extending into the walI for about 0.2 cm. In addition signs of cardiac deconlpensation and a biIateraJ bronchopneumonia were apparent. HistoIogicaIIy at the margin of the uIcer a few gIands simiIar to those of the stomach couId be identified. These gIands showed onIy chief cells, however, no oxyntic ceIIs being seen. At the base of the ulcer there was compIete destruction and fibrous repjacement of the normaI muscuIaris of the esophagus, and in addition there was a marked chronic inflammatory reaction throughout the waI1 of the ulcer with a moderate diffuse Iymphocytic and pIasma ceI1 infiltration. These two cases serve to show the association of ulcer and bfeeding with ectopic gastric mucosa. Th e explanation of the SymptomatoIogy of Case II is clear enough smce there were bleeding uIcers in various
and at the opening of the d~~~erticuIum may have been a most important factor in the deveIopment of the ulcers. It is unfortunate that a more pertinent history was not availabIe in the third case, but LyaI115 states that the common clinica symptoms of uIcer of the esophagus are pain, dysphagia and hematemesis. In regard to peptic uIcers of the esophagus Jackson’” Iists the foIIo~~ing causes: focal infection, retrograde flow of gastric juice, cardiospasm, insuffIciency of the cardia, insufficiency of the diaphragmatic pinchcock, and ectopic gastric mucosa. He points out that the occurrence of gastric mucosa in the esophagus may be an active factor by the secretion of gastric juice or passiveIS by supplying a tissue that may be sensitive to concentrated gastric juice. The role of ectopic gastric mucosa in this type of uIcer of the esophagus is aIso emphasized by LyaII and by HurstI who fee1 the most
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important factor is the active secretion of hydrochIoric acid by the ectopic tissue and the trapping of this acid in the Iower
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in various ways. This, however, carries us no cIoser to the pathogenesis of such Iesions, beyond removing the necessity of expIain-
FIG. 6. Case II. High tower fieId of gastric mucosa shown in Figure 5. Note the Iarge round parietal ceIIs. HematoxyIin and eosin. X 1200.
portion of the esophagus by cardiospasm. The commonest compIications of peptic uIcer of the esophagus are perforation and hemorrhage. The extensive damage evident in Case III shows how such uIcers may we11go on to perforation and mediastinitis. ETIOLOGY
The reasons for the deveIopment or existence of ectopic gastric mucosa are entireIy unknown aIthough numerous theories have been suggested. We agree with NichoIson’s* who concIudes that the deveIopmenta1 heteromorphoses indicate that the origina prospective potencies of ceIIs are wider than their prospective vaIues; and that the accidenta heteromorphoses suggest that the origina prospective potencies are not entirely Iost during deveIopment, since they are sometimes accidenta y reveaIed in pathoIogic states in oId age. In other words, one must bear in mind the common origin of the intestina1 epitheIium and reaIize that each ceI1 may differentiate
ing a11 such findings on the basis of embryoIogic rests. Curd18 reviews the various theories of origin and deveIopment of ectopic gastric mucosa. Briefly stated, these are: I. The presence of a substance in the intestines which stimuIates the formation of intestina1 mucosa, and the Iack of which is necessary for the formation of gastric mucosa. This substance was thought to be biIe. 2. An inffammatory process in the endoderm during some stage of embryoIogic deveIopment. 3. MispIaced feta1 incIusions or rests. 4. The rapid growth of the intestines does not aIIow the differentiation of ceIIs into the gastric type, whiIe the smaIIer size and sIower growth of the stomach aIIow for compIete differentiation of the gastric mucosa. The first theory has been proved incorrect and is further disproved by the first case reported here. The theory of rapid
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development of the intestines is ruled out by our second case. It is impossible to conclude what mechanism governs the
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6. The nodules of Lewis and Thyng.20 These authors noted noduIes of epithelia! cells occurring along the course of the
FIG. 7. Case III. Section of esophageal ulcer showing extensive scarring and compIetc destruction of the muscularis and marked chronic inflammatory reaction extending through to the adventitia. h~ucosal surface is above. Hematoxylin and eosin.
development of ectopic gastric mucosa in the Iight of our present knowledge. Case II showed an unusual deformity in addition to the ectopic gastric mucosa. Hudson collected eighteen such cases from the literature and reported three of his own under the title of “Giant Diverticula or Reduplications of the IntestinaI Tract.” The pathogenesis of this type of anomaly is likewise entireIy unknown. Hudsonlg lists the foIIowing theories : or reversion to an earIier I. Atavism phylogenetic form. 2. Twinning, in which case “the stimulation to redupIication, although acting at an early stage of cel1 division has affected a certain section only of the embryo.” 3. Through the deveIopment of a median septum. 4. Sequestration of a segment of the intestinal tube. 5. Persistence and alterations of the vitelIine duct.
gastrointestina1 tract in pig, rabbit and human embryos. Normally these disappear or coaIesce to form a part of the Iumen of the digestive tube but they may persist. The evidence is not concIusive for any single theory, but Hudson concludes that the evidence favors the beIief that the nodules of Lewis and ThyngzO are antecedents of those cysts and diverticuIa not associated with remnants of the omphalomesenteric duct. TREATMENT
The only satisfactory treatment of islands of heterotopic gastric mucosa regardless of the Iocation or form of their occurrence is complete surgical remova where possible. RedupIications of the intestina1 tract shouId aIso be compIeteIy excised since they may be whoIIy or partiaIIy Iined with gastric mucosa. At this point we should also Iike to emphasize the importance of a thorough surgical explora-
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tion in individuaIs, and especiaIIy chiIdren, presenting vague or unusua1 but persistent intestina1 symptoms particularly when associated with gastrointestina1 hemorrhage. In the case of the esophagus Jackson16 recommends remova of foci of infection. cauterization of uIcers with weak siIver nitrate and a dietetic rkgime such as would be advised for a patient with a gastric uIcer of the stomach with especia1 attention to the avoidance of rough, harsh and buIky foods. SUMMARY I. Three instances of heterotopic gastric mucosa are reported (esophagus, jejunum and giant diverticuIum of iIeum), two of which were known to have been responsibIe for cIinica1 symptoms. 2. The dangers of uIceration, hemorrhage and perforation have been emphasized in connection with ectopic gastric mucosa. 3. The theories of origin of heterotopic gastric mucosa and giant diverticuIa of the intestine are presented. REFERENCES I. NICHOLSON, G. W. Heteromorphoses (metapIasia) of the aIimentary tract. J. Patb. H Bact., 26: 3gg417, 1923. 2. HUDSON, H. W., and KOPLIK, L. H. Meckel’s diverticulum in chiIdren: a cIinica1 and pathoIogic study, with report of 32 cases. New England J. Med., 206: 827-840, 1932. 3. TAYLOR, A. L. The epitheIia1 heterotopias of the alimentary tract. J. Path. @ Bact., 30: 415-449, 1927. 4. BARTOK, F. 0 het_erotopiich sIiznice zaIudne&i v tenkern streve. Casop. lhk. Eesk., 71: 1070, 1107, 1932.
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5. KIMPTON, A. R., and CRANE, A. R. Heterotopic gastric mucosa. New England J. Med., 218: 627-629, ‘938. 6. POINDECKER, H. Ueber einen Fall heterotoper MagenschIeimhaut im Diinndarm. Zentralbl. f. allg. Path. u. patb. Anat., 23: 481-486, 1912. 7. STONE, E. Aberrant gastric mucosa: report of 2 cases-an umbiIica1 poIyp and a Meckel’s diverticulum. Surg., Gynec. H Obst., 37: 51-56, ‘923. 8. NICHOLSON, G. W. Gastric glands in the extroverted dista1 end of the viteIIine duct. J. Patb. Ed Bact., 25: 201-206, 1922. g. KLEINSCHMIDT, K. Das UIcus pepticum des MeckeI’schen Divertikels. Beitr. z. klin. Cbir., 138: 715-720, 1927. LO. SCHULLINGER, R. N., and STOUT, A. P. Meckel’s diverticulum: report of a case of hemorrhage in the bowe1 associated with a MeckeI’s diverticulum that presented an adenoma composed of gastric and duodenal gIands. Arch. Surg., 28: 440-466, 1934. I I. HUDSON. H. W.. JR. MeckeI’s diverticulum in children. New England J. Med., 208: 525, 1933. 12. KOSTER, H. Intussusception. Am. J. Surg., 22: 465-475, 1933. 13. ROAN, 0. Intussusception due to benign tumors of the smaI1 intestine. Texas State J. Med., 27: 782786, 1932. 14. RANKI’N, F. W., and NEWELL, C. E. Benign tumors of the smaI1 intestine; report of 24 cases. Surg., Gynec. ti Obst., 57: 501-507, 1933. 15. LYALL, A. Chronic peptic uIcer of the esophagus. Brit. J. Surg., 24: 534-547, 1937. 16. JACKSON, C. Peptic uIcer of the esophagus. J. A. M. A., 92: 369-372, 1929. 17. HURST, A. F. Some disorders of the esophagus. J. A. M. A., 102: 582-587, 1934. 18. CURD, H. H. A histologic study of Meckel’s diverticuIum with specia1 reference to heterotopic tissue. Arch. Surg., 32: 506-523, 1936. I). HUDSON, H. W., JR. Giant diverticuIa or redupIications of the intestina1 tract. New England J. Med., 213: 1123-I 131, 1935. 20. LEWIS, F. J., and THYNG, F. W. The regular occurrence of intestina1 diverticuIa in embryos of the pig, rabbit and man. Am. J. Anat., 7: 505, IgoT-Igo8.
R.
GASTRIC MUCOSA AND REDUPLICATIONS OF THE INTESTINAL TRACT* KIMPTON,
M.D.
AND
Surgeon-in-Chief, First SurgicaI Service, Boston City Hospital
D.
REYNOLDS CRANE,
M.D.
Assistant Pathologist, MaIIory Institute of PathoIogy, Boston City Hsopital
BOSTON, MASSACHUSETTS HILE the occurrence of gastric mucosa in ectopic foci throughout the body may be responsibIe for severe cIinica1 signs and symptoms and may even Iead directIy to the death of the patient, it is aIso true that proper surgica1 treatment may produce a compIete cure. In view of these facts we shouId Iiketo caII attention to the occurrence of this type of congenita1 abnormahty in various portions of the gastrointestina1 tract and reIated structures and report three unusual cases which nevertheIess iIIustrate we11 its more common pathoIogic effects. The presence of isIands of gastric mucosa in the esophagus and in remnants of the viteIIine duct (MeckeI’s diverticuIum) is common. NichoIsonl states that there is an incidence as high as 75 per cent in the upper portion of the esophagus. In a report of thirty-two cases of Meckel’s divertic&m, Hudson and KopIik2 found gastric mucosa in 52 per cent. This corresponds very cIoseIy with the figures from the surgica1 and autopsy records of the MaIIory Institute of PathoIogy where, of the Iast twenty Meckel’s diverticuIa examined histoIogicaIIy, ten, or 50 per cent, showed isIands of ectopic gastric mucosa. Aside from these two Iocations the occurrence of ectopic gastric mucosa is extremeIy rare. It has, however, been reported in the duodenum by TayIor,3 in the jejunum by Bart6k4 and by Kimpton and Crane,5 in the iIeum by Poindecke# and by TayIor,3
W
and in the pancreas, gaII-bIadder and coIon by NichoIson. l Its occurrence in the umbihcus in remnants of the viteIIine duct has been described by Stone7 and by NichoIson.* IsIands of ectopic gastric mucosa produce no typica or pathognomonic cIinica1 signs or symptoms, these depending to a Iarge extent upon the site of their occurrence. However, the one sign which they may have in common, regardIess of their Iocation, is hemorrhage into the gastrointestina1 tract. The cause of the bIeeding is the frequent presence of typica peptic uIcers either adjacent to or invoIving the ectopic mucosa, with uIceration of bIood vesseIs which may actuaIIy Iead to death from exsanguination. The importance of uIceration and hemorrhage in connection with MeckeI’s diverticuIa has been emphasized by previous writers2*gs10 and Hudsonl’ states that 31 per cent of MeckeI’s diverticuIa may show hemorrhage on this basis. In considering the various possibIe causes of intestina1 hemorrhage this condition shouId be remembered, particuIarIy when deaIing with intestina1 hemorrhage in chiIdren. The uIcerations associated with this anomaIy may aIso Iead to perforation with peritonitis or mediastinitis. The heterotopic mucosa may be of sufficient size or may proliferate to suff&ient size to produce the cIinica1 picture of a tumor with a paIpabIe mass, obstruction, voIvuIus or intussuscep-
* From the First SurgicaI Service and the MalIory Institute of PathoIogy, Boston City HospitaI. 342
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tion. The folIowing three unusua1 cases wiII serve to illustrate some of these possible dangers of heterotopic gastric mucosa.
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Iaxative; this was invariably followed by a watery defecation, but at no time were the stooIs abnormaIIy
dark or bloody.
The attacks
FIG.I.Case 1. Cross specimen showing tumor nodule in jejunum. The gross resrmblance of the mucosal surface of the tumor nodule to gastric mucosa is striking. About two times actual size.
CASE
REPORTS
CASE I. .J.B., a 7 year old girl, was seen in consultation by one of us (A. R. K.) because of recurrent attacks of severe paraumbiIi~aI pain associated with nausea and vomiting since the age of 3. She was born at ful1 term after a norma pregnancy, the fifth chiId of a family of nine. Her weight at birth was 894 pounds and no physicaI abnormalities were noted. Her parents and siblings were entireIy normal, and there were no pertinent factors in her past history other than those associated with her present iIIness. The first abdomina1 complaint occurred at the age of 3 and was manifested by severe pain about the umbiIicus, not Iocalized, and marked by a continuous ache with occasional attacks of excruciating pain causing her to cry out. After two or three hours the chiId vomited and the pain was reIieved. SimiIar attacks occurred subsequently three to six times a year. They lasted from one to three days, and began during the night as frequently as during the day. Following each attack the child appeared perfectly normal except for a sense of weakness. Fever never developed during any of the attacks. The mother aIways gave the chiId a
gradually became more frequent. and severe, but no definite inducing factor was ever noted. TWO years after the onset of this condition a physician was consulted for the first time and a diagnosis of intestina1 worms was made. Three weeks Iater a second physician was consuIted and for the first. time an abdominal mass was paIpated; the mother stated that a mass could be seen especially when the pain was severe. At this time a diagnosis of voIvuIus was made, the abdomen was tightly strapped with tape, and abdominal massage and shaking the child in an upside-down position by hoIding the feet were advised. FoIlowing this the attacks were much Iess frequent. One year later, because of a severe attack, the patient was referred to a hospital, where .+rays of the intestinal tract reveaIed nothing abnormal. During the year preceding the present examination she had had attacks of varying severity every four or five weeks. She was seen in consultation on June 21, 1937, ha\:ing just suffered an acute attack of abdominal pain. PhysicaI examination was negative save for the abdomen, where an elongated tumor couId be felt extending diagonaIIy across the abdomen from left to right. It was IO or 12 cm. in length, 2 or 3 cm. in width, soft, smooth and non-
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tender. The center of the mass Iay just beneath the umbilicus. The appearance was quite typica of intussusception. WhiIe Iying quietIy
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7 by 5 by 0.4 cm. The serosa was measuring negative but the entire waII was thickened and edematous, aIthough not otherwise remarkabIe.
FIG. 2. Case 1. High-power field of the tumor mucosal ceIIs, showing Iarge, round parieta1 ceIIs (indicated by arrows). HematoxyIin and eosin. X gro.
on the examining table, the chiId suddenly screamed, doubled up, holding her abdomen, became pallid and perspired profuseIy. This lasted for about ten minutes and was foIIowed in a few minutes by a simiIar attack. The abdomina1 tumor became very prominent through the chiId’s thin abdomina1 waI1 while the pain was most severe. At operation, the abdomen was exposed by a left paraumbiIica1 midrectus incision and a large intussusception of the jejunum was found starting about 15 cm. beIow the Iigament of Treitz. The bowel was edematous but entireIy viable, and the intussusception was reduced with ease. When it was compIeteIy reduced, a soft, dough-Iike tumor mass was found fiIIing the entire Iumen of the jejunum 20 cm. below the Iigament of Treitz. This was resected with12 cm. of jejunum, out diffIcuIty by removing and a side-to-side anastomosis was done. The abdomen was closed in Iayers without drainage. The immediate postoperative course was uneventfu1. Eighteen months after the operation the chiId was heaIthy and had had no recurrence of her previous symptoms. Pathologic Report. The gross specimen consisted of a piece of smaI1 intestine (jejunum)
3 cm. in The mucosa in one area measuring diameter was redundant, being eIevated 0.4 cm. above the surrounding tissue to form a definite tumor noduIe with a broad base. There was no evidence of infiItration of the underIying tissues. HistoIogic sections through the redundant portion of mucosa showed it to be composed of Iong mucous gIands of the gastric type in some of which numerous Iarge, round, eosinophilic parietal ceIIs couId be readiIy identified. At the margin of the noduIe there was an abrupt transition to a mucosa of the jejunal type, with many Iarge pIicae circulares and numerous gobIet ceIIs. The tumor noduIe itself lay entireIy on the mucosa1 side of the muscuIaris mucosa, and the redundancy of the mucosa noted in gross examination was due to the numerous gastric gIands of which the tumor was composed. There were occasiona mitotic figures in the epitheIium, but the ceIIs were perfectIy differentiated into adult chief and parieta1 ceIIs, as found in the mucosa of the muscuIaris and stomach. The submucosa, serosa were norma save for evident interceIIular edema.
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This case is essentially but
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is
a typical unusual
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FIG. 3. Case
Crane-Gastric one of of anom-
and
C. C., a g months old baby boy, to the Boston City Hospitai because of bleeding by rectum. He was the first chiId of a 28 year oId white housewife and was born at term. It was noted in the CASE
II.
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hospitaI after his birth that he vomited frequently, but his parents never returned him to the hospital for study as advised. There were
II. Drawing to demonstrate the abnormahty of redupIication the ileum. Cecum and appendix are on left.
afy which was responsibIe for the intussusception. The r61e of tumors in the production of intussusception, particularIy in the adult, has been emphasized by recent investigators,1~~13~14 although the association of the two lesions has Iong been recognized. Roan,13 in reporting a series of cases of intussusception, states that tumors are a negligible factor in chifdren up to the age of 3, Since benign tumors are much commoner than malignant ones in the smaII intestine, they predominate in any analysis of tumors causing intussusception. Nevertheless, the polypoid nature of many benign intestinal neoplasms renders them even more potent factors in the genera1 etiology of intussusception. In all reported series the commonest types of tumors encountered are myomas and adenomas, akhough instances of fibroma, Iipoma, hemangioma and other benign tumors are not infrequent. was admitted
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no other pertinent factors in his past history other than those associated with his present iIIness. The first appearance of recta1 bIeeding occurred at the age of 3 months about three weeks after the onset of pertussis. At that time the child had three red to tarry stooIs. He was admitted to the South Department of the Boston City HospitaI because of the pertussis and rectal bleeding, but was taken home against advice before he could be properly studied. There had been no recurrences of the recta1 bIeeding up until the day of the Iast admission when his mother noted the presence of bIack tarry stools and fresh blood in his diapers twice within a period of two hours. The physicai examination showed marked pallor of the skin, a hard round mass about the size of a lemon in the Ieft upper quadrant of the abdomen, distention of the abdomen and the presence of blood in the rectum. In addition he showed some beading of the ribs and enrargement of the head with prominent fronta bosses. The physical examination was otherwise negative. The only laboratory data gathered were a hemogiobin of 25 per cent, a red bIood count of 2,060,000, and a white brood count of 17,200 with 80 per cent poIynucIear ceIIs.
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A Iaparotomy was performed and a giant diverticuIum of the iIeum was found. The iIeum became doubIe-barreIed at a point about
FIG. 4. Case II. Cyst after cross section showing the rugose gastric-Iike appearance of the lining and a typica “punched-out” peptic uIcer. About actuaI size.
25 cm. from the iIeoceca1 vaIve. This doubIe iIeum continued proximaIIy for about g5 cm., the inner or faIse bowe1 Iying in the mesentery of the outer or true bowe1 but in cIose approximation to it. The faIse segment then dipped towards the base of the mesentery penetrated the mesentery and ended in a round cystic structure about 6 cm. in diameter, apparentIy corresponding to the mass noted cIinicaIIy in the Ieft upper quadrant of the abdomen. It was felt that the cyst and an uIcer which couId be paIpated at the bifurcation of the iIeum were the main sources of the bIeeding and therefore the cyst, about 5 cm. of the diverticuIum with the cyst and about 5 cm. of iIeum at the point of bifurcation were resected. A side-to-side anastomosis was then done between the termina1 iIeum and a portion of iIeum overIying the diverticulum. Pathologic Report. The gross specimen consisted of three parts. The first was a piece of intestine from the bifurcation of the iIeum 5 by 4.2 by 0.3 cm., the surface of which was grayred and edematous. In the middIe of the mucosa1 surface of this fragment were three punched-out ulcers, the largest I cm. in diameter and 0.3 cm. in depth, the others being but
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sIightIy smaIIer. The other two portions of the specimen were a piece of intestine measuring 5 by I by 0.3 cm. and somewhat resembIng an appendix and a cystic structure 6 cm. in diameter fiIIed with partiaIIy digested bIack bIood and showing a rugose gastric-Iike mucosa. It contained approximately eight punched-out uIcers, the Iargest measuring I by I by 0.6 cm. HistoIogicaIIy a11 three of these segments showed typica gastric mucosa with both chief and oxyntic ceIIs the Iatter being extremeIy abundant. The muscle Iayers of the segments were those of smaI1 bowe1 save for that of the cyst which showed interIacing muscle bundIes simiIar to those seen in the norma stomach. The uIcers were sharply defined, in some areas extended deeply into the muscuIaris and showed a moderate foca1 Iymphocytic reaction. FoIIowing the operation the patient showed progressive elevation of temperature and puIse and died within twenty-four hours. The onIy important autopsy findings were those reIated to the intestina1 tract. The Iarge bowe1 was not remarkabIe, and 23 cm. proxima1 to the iIeoceca1 valve there was a side-to-side anastomosis between two closed and sutured ends of iIeum. The ileum proxima1 to the anastomosis was double, being composed of two distinct tubes which were inseparabIy fused at their adjacent surfaces. The inner intestina1 tube was greatIy distended as it Iay in the mesentery of the outer or norma iIeum. The mesenteric vesseIs to the true bowel circumscribed this inner bowel. These intestina1 tubes ran paraIIe1 for a distance of go cm. at which point the inner tube became detached and ran for a short distance towards the base of the mesentery. The outer intestine continued on proximaIIy to join a norma jejunum, duodenum and stomach. HistoIogic sections showed this inner segment of bowe1 to be Iined throughout by gastric mucosa with numerous oxyntic ceIIs. The muscuIaris was incompIete, being entirely Iacking in the portion where the two tubes were adjacent aIthough the remainder of the muscularis of each segment was normaI. CASE III. F. W., a 77 year oId white male, was admitted to Boston City HospitaI because of edema and dyspnea of increasing severity. Because of his poor condition no reIiabIe history was obtained. On physica examination he showed an enIarged heart, bIood pressure of r~o/go and marked dependent edema. Labora-
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tory data were not significant. The patient did well for a few days and then showed increasing signs of cardiac failure and died twenty days after admission.
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portions of this diverticuIum connecting directly with the bowel lumen. It would seem that autodigestion by the local concentration of hydrochloric acid in the sac
FE<;. 5. Case 11. Cross section through normaI bowel and redupfication at point indicated in Figure 3. Gastric mucosa lining reduplication above; lumen of true bowe1 with norma mucosa below. Note the absence of the muscularis between the two lumens on the right of the photograph. Hematoxylin and eosin. x 30.
Autopsy showed ulceration in the esophagus about 4 cm. from the cardia and measuring about 3 cm. in diameter, with an irreguIar edge and a green sIoughing base extending into the walI for about 0.2 cm. In addition signs of cardiac deconlpensation and a biIateraJ bronchopneumonia were apparent. HistoIogicaIIy at the margin of the uIcer a few gIands simiIar to those of the stomach couId be identified. These gIands showed onIy chief cells, however, no oxyntic ceIIs being seen. At the base of the ulcer there was compIete destruction and fibrous repjacement of the normaI muscuIaris of the esophagus, and in addition there was a marked chronic inflammatory reaction throughout the waI1 of the ulcer with a moderate diffuse Iymphocytic and pIasma ceI1 infiltration. These two cases serve to show the association of ulcer and bfeeding with ectopic gastric mucosa. Th e explanation of the SymptomatoIogy of Case II is clear enough smce there were bleeding uIcers in various
and at the opening of the d~~~erticuIum may have been a most important factor in the deveIopment of the ulcers. It is unfortunate that a more pertinent history was not availabIe in the third case, but LyaI115 states that the common clinica symptoms of uIcer of the esophagus are pain, dysphagia and hematemesis. In regard to peptic uIcers of the esophagus Jackson’” Iists the foIIo~~ing causes: focal infection, retrograde flow of gastric juice, cardiospasm, insuffIciency of the cardia, insufficiency of the diaphragmatic pinchcock, and ectopic gastric mucosa. He points out that the occurrence of gastric mucosa in the esophagus may be an active factor by the secretion of gastric juice or passiveIS by supplying a tissue that may be sensitive to concentrated gastric juice. The role of ectopic gastric mucosa in this type of uIcer of the esophagus is aIso emphasized by LyaII and by HurstI who fee1 the most
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important factor is the active secretion of hydrochIoric acid by the ectopic tissue and the trapping of this acid in the Iower
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in various ways. This, however, carries us no cIoser to the pathogenesis of such Iesions, beyond removing the necessity of expIain-
FIG. 6. Case II. High tower fieId of gastric mucosa shown in Figure 5. Note the Iarge round parietal ceIIs. HematoxyIin and eosin. X 1200.
portion of the esophagus by cardiospasm. The commonest compIications of peptic uIcer of the esophagus are perforation and hemorrhage. The extensive damage evident in Case III shows how such uIcers may we11go on to perforation and mediastinitis. ETIOLOGY
The reasons for the deveIopment or existence of ectopic gastric mucosa are entireIy unknown aIthough numerous theories have been suggested. We agree with NichoIson’s* who concIudes that the deveIopmenta1 heteromorphoses indicate that the origina prospective potencies of ceIIs are wider than their prospective vaIues; and that the accidenta heteromorphoses suggest that the origina prospective potencies are not entirely Iost during deveIopment, since they are sometimes accidenta y reveaIed in pathoIogic states in oId age. In other words, one must bear in mind the common origin of the intestina1 epitheIium and reaIize that each ceI1 may differentiate
ing a11 such findings on the basis of embryoIogic rests. Curd18 reviews the various theories of origin and deveIopment of ectopic gastric mucosa. Briefly stated, these are: I. The presence of a substance in the intestines which stimuIates the formation of intestina1 mucosa, and the Iack of which is necessary for the formation of gastric mucosa. This substance was thought to be biIe. 2. An inffammatory process in the endoderm during some stage of embryoIogic deveIopment. 3. MispIaced feta1 incIusions or rests. 4. The rapid growth of the intestines does not aIIow the differentiation of ceIIs into the gastric type, whiIe the smaIIer size and sIower growth of the stomach aIIow for compIete differentiation of the gastric mucosa. The first theory has been proved incorrect and is further disproved by the first case reported here. The theory of rapid
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development of the intestines is ruled out by our second case. It is impossible to conclude what mechanism governs the
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6. The nodules of Lewis and Thyng.20 These authors noted noduIes of epithelia! cells occurring along the course of the
FIG. 7. Case III. Section of esophageal ulcer showing extensive scarring and compIetc destruction of the muscularis and marked chronic inflammatory reaction extending through to the adventitia. h~ucosal surface is above. Hematoxylin and eosin.
development of ectopic gastric mucosa in the Iight of our present knowledge. Case II showed an unusual deformity in addition to the ectopic gastric mucosa. Hudson collected eighteen such cases from the literature and reported three of his own under the title of “Giant Diverticula or Reduplications of the IntestinaI Tract.” The pathogenesis of this type of anomaly is likewise entireIy unknown. Hudsonlg lists the foIIowing theories : or reversion to an earIier I. Atavism phylogenetic form. 2. Twinning, in which case “the stimulation to redupIication, although acting at an early stage of cel1 division has affected a certain section only of the embryo.” 3. Through the deveIopment of a median septum. 4. Sequestration of a segment of the intestinal tube. 5. Persistence and alterations of the vitelIine duct.
gastrointestina1 tract in pig, rabbit and human embryos. Normally these disappear or coaIesce to form a part of the Iumen of the digestive tube but they may persist. The evidence is not concIusive for any single theory, but Hudson concludes that the evidence favors the beIief that the nodules of Lewis and ThyngzO are antecedents of those cysts and diverticuIa not associated with remnants of the omphalomesenteric duct. TREATMENT
The only satisfactory treatment of islands of heterotopic gastric mucosa regardless of the Iocation or form of their occurrence is complete surgical remova where possible. RedupIications of the intestina1 tract shouId aIso be compIeteIy excised since they may be whoIIy or partiaIIy Iined with gastric mucosa. At this point we should also Iike to emphasize the importance of a thorough surgical explora-
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tion in individuaIs, and especiaIIy chiIdren, presenting vague or unusua1 but persistent intestina1 symptoms particularly when associated with gastrointestina1 hemorrhage. In the case of the esophagus Jackson16 recommends remova of foci of infection. cauterization of uIcers with weak siIver nitrate and a dietetic rkgime such as would be advised for a patient with a gastric uIcer of the stomach with especia1 attention to the avoidance of rough, harsh and buIky foods. SUMMARY I. Three instances of heterotopic gastric mucosa are reported (esophagus, jejunum and giant diverticuIum of iIeum), two of which were known to have been responsibIe for cIinica1 symptoms. 2. The dangers of uIceration, hemorrhage and perforation have been emphasized in connection with ectopic gastric mucosa. 3. The theories of origin of heterotopic gastric mucosa and giant diverticuIa of the intestine are presented. REFERENCES I. NICHOLSON, G. W. Heteromorphoses (metapIasia) of the aIimentary tract. J. Patb. H Bact., 26: 3gg417, 1923. 2. HUDSON, H. W., and KOPLIK, L. H. Meckel’s diverticulum in chiIdren: a cIinica1 and pathoIogic study, with report of 32 cases. New England J. Med., 206: 827-840, 1932. 3. TAYLOR, A. L. The epitheIia1 heterotopias of the alimentary tract. J. Path. @ Bact., 30: 415-449, 1927. 4. BARTOK, F. 0 het_erotopiich sIiznice zaIudne&i v tenkern streve. Casop. lhk. Eesk., 71: 1070, 1107, 1932.
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5. KIMPTON, A. R., and CRANE, A. R. Heterotopic gastric mucosa. New England J. Med., 218: 627-629, ‘938. 6. POINDECKER, H. Ueber einen Fall heterotoper MagenschIeimhaut im Diinndarm. Zentralbl. f. allg. Path. u. patb. Anat., 23: 481-486, 1912. 7. STONE, E. Aberrant gastric mucosa: report of 2 cases-an umbiIica1 poIyp and a Meckel’s diverticulum. Surg., Gynec. H Obst., 37: 51-56, ‘923. 8. NICHOLSON, G. W. Gastric glands in the extroverted dista1 end of the viteIIine duct. J. Patb. Ed Bact., 25: 201-206, 1922. g. KLEINSCHMIDT, K. Das UIcus pepticum des MeckeI’schen Divertikels. Beitr. z. klin. Cbir., 138: 715-720, 1927. LO. SCHULLINGER, R. N., and STOUT, A. P. Meckel’s diverticulum: report of a case of hemorrhage in the bowe1 associated with a MeckeI’s diverticulum that presented an adenoma composed of gastric and duodenal gIands. Arch. Surg., 28: 440-466, 1934. I I. HUDSON. H. W.. JR. MeckeI’s diverticulum in children. New England J. Med., 208: 525, 1933. 12. KOSTER, H. Intussusception. Am. J. Surg., 22: 465-475, 1933. 13. ROAN, 0. Intussusception due to benign tumors of the smaI1 intestine. Texas State J. Med., 27: 782786, 1932. 14. RANKI’N, F. W., and NEWELL, C. E. Benign tumors of the smaI1 intestine; report of 24 cases. Surg., Gynec. ti Obst., 57: 501-507, 1933. 15. LYALL, A. Chronic peptic uIcer of the esophagus. Brit. J. Surg., 24: 534-547, 1937. 16. JACKSON, C. Peptic uIcer of the esophagus. J. A. M. A., 92: 369-372, 1929. 17. HURST, A. F. Some disorders of the esophagus. J. A. M. A., 102: 582-587, 1934. 18. CURD, H. H. A histologic study of Meckel’s diverticuIum with specia1 reference to heterotopic tissue. Arch. Surg., 32: 506-523, 1936. I). HUDSON, H. W., JR. Giant diverticuIa or redupIications of the intestina1 tract. New England J. Med., 213: 1123-I 131, 1935. 20. LEWIS, F. J., and THYNG, F. W. The regular occurrence of intestina1 diverticuIa in embryos of the pig, rabbit and man. Am. J. Anat., 7: 505, IgoT-Igo8.