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Pneumatosis of the intestine in infancy
P N E U M A T O S I S OF T H E I N T E S T I N E
IN INFANCY
THOMAS W . BOTSFORD, M.D., A~TD CECIL KRAKOWER, M.D. BOSTON, MASSACHUSETTS
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N E U M A T O S I S of the intestine is considered to be a rare pathologic condition. I t was first clearly described in a h u m a n b y Bang ~ in 1876. W i t h the advent of abdominal s u r g e r y in the latter p a r t of the nineteenth century, instances of this disease noted at operation and post m o r t e m have steadily been reported up to the present. T u r n u r e ~ in 1913 collected 50 cases; Mills 3 in 1925, 100 cases; and Memmi 4 in 1934 brought the total to 154. Twenty-one additional eases, not included in the above, have been found. These comprise reports by Silverstone, ~ Lamont, G Sawada, 7 Moore, s T u n g a n d Ngai, 9 Pybus, 1~ Kema], 1~ Nimet, ~2 Bsteh, 13 and E n g l u n d and W a h l g r e n 2 ~ Of these 171 cases, there h a t e been only 5 authentic cases in childhood and infancy. Schnyder ~5 in ]917 observed gas cysts in the intestinal lymphatics, mesentery, and mesenteric glands in a 5-year-old child who died of diphtheria. Moore s in 1929 re'ported four cases in infants of 2 weeks to 14 months of age. Of the six instances t h a t we are reporting, five were observed during the period of a p p r o x i m a t e l y one year. CASE REPORTS
CAS]~ 1.--(A-26-15.) This 4-week-old, white, premature male infant was brought to the hospital because of failure to gain in weight. Subsequently he developed attacks of cyanosis and physical signs of pneumonia. He died two weeks after entry. Necropsy was performed six hours post mortem. The anatomic diagnoses were acute suppurative broachopneumonia, acute bronchial lymphadenitis, and pneumatosis of the colon. Gross Examination.--The upper portion of the ileum was markedly injected, but there were no areas of ulceration. In the descending colon there were many small air blebs, varying from 1 to 3 ram. in diameter. The mucosa was mildly injected in this portion of the large bowel. Microscopic E x a m i n a t i o n . - - J e j u n u m : There was intense vascular congestion throughout the mucosa. The glandular lumina were frequently dilated but free of inspissated mucoid contents. Goblet cells were moderately in excess. There was striking diminution in the number of mitoses. The tunica propria was cellular with excessive numbers of loolymorphonuclear leucocytes~ particularly at the tips of villi. The submucosal blood vessels were greatly dilated and e(/ngested. There were no lymphoid aggregates. The serosa was edematous. There were dilated submucosM lymphatics. I~eum: The sections were similar to the jejunum with the exception that there was somewhat less polymorphonuclear cell infiltration in the tunica propria of the mucosa. There were dilated lymphatics in the submucosa. Colon: The mucosa was moderately tkinned and compressed. There was fairly marked vascular congestion throughout the tunica propria. The glands assumed From the Department of Pathology, the Children's Hospital. 185
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varied a p p e a r a n c e s . I n i n s t a n c e s t h e i r l u m i n a were dilated~ c o n t a i n i n g i n s p i s s a t e d m u c u s or necrotic cellular elements. T h e l i n i n g cells were in places flattened a n d atrophic. Elsewhere, the epithelial cells were tall b u t l a t e r a l l y flattened w i t h v a r i a b l e a m o u n t s of mucus, b u t p r a c t i c a l l y never of t h e full goblet t y p e w i t h flattened b a s a l nucleus. Mitoses in g l a n d u l a r e p i t h e l i u m s were relatively i n f r e q u e n t . T h e r e were occasional m n e o s a l g a s cysts. T h e m u s c u l a r i s m u e o s a e was t h i n n e d , more m a r k e d l y so where f o r m i n g the wall of a d i s t e n d e d s u b m u c o s a l g a s cyst. There were occasional small s u b m u c o s M l y m p h o i d nodules. The whole of t h e s u b m u c o s a otherwise was replaced b y n u m e r o u s g a s cysts. T h e s e possessed no specific endothelial lining. T h e r e were no g i a n t cells. There were dilated p e r l v a s c u l a r . l y m p h a t i e s in the m u s c u l a r a n d serosal coats. CASE 2 . - - ( A - 3 6 - 1 9 . ) T h i s 9-month-old white male i n f a n t was reachnitted because of p e r s i s t e n t e d e m a a n d a n u p p e r r e s p i r a t o r y infection. T h r e e m o n t h s previously a d i a g n o s i s o f n e p h r o s i s h a d been m a d e at his first admission. There h a d been no i m p r o v e m e n t in his condition in t h e interim. F o r t h e first week d u r i n g this second admission, he did f a i r l y well. V o m i t i n g a n d d i a r r h e a t h e n supervened. Ite died a week later.
}eig. 1 . - - C a s e 2. 1, Thoracic d u c t ; 2, cisterna chyli; 3, mesenteric l y m p h nodes. Note m a r k e d e m p h y s e m a of l y m p h nodes a n d distention of cisterna chyli a n d [horaeie duct with gas. N e c r o p s y was p e r f o r m e d one h o u r p o s t m o r t e m . The a n a t o m i c d i a g n o s e s were s u b a c u t e g l o m e r u l o n e p h r i t i s ; b r o n c h o p n e u m o n i a w i t h i n t e r s t i t i a l e m p h y s e m a ; nonobstructive b i l i a r y cirrhosis ( m i l d ) ; acute otitis media, b i l a t e r a l ; a c u t e m e s e n t e r i c l y m p h a d e n i t i s ; p n e u m a t o s i s of ileum, a s c e n d i n g a n d pelvic colons, m e s e n t e r i c l y m p h nodes, c i s t e r n a chyli, a n d thoracic d u c t .
Gross Examination.--The p h a r y n g e a l m u e o s a was reddened a n d thickened. The e s o p h a g u s a n d s t o m a c h were n o t remarkable. The j e j u n u m was d i s t e n d e d w i t h gas~ a n d t h e r e were occasional a r e a s of e m p h y s e m a t o s i s over the m u e o s a l aspect. T h e entire i n n e r s u r f a c e of t h e i l e u m w a s a m a s s of f r o t h y - a p p e a r i n g g a s cysts, dis~ t r i b u t e d i r r e g u l a r l y t o w a r d the ileoeecal valve. N o n e of these c y s t s c o n t a i n e d fluid. There were no f r a n k a r e a s of ulceration. The m u e o s a l s u r f a c e of t h e intestine, part i c u l a r l y in t h e e m p h y s e m a t o u s regions, h a d a d r y g r a n u l a r a n d b r i g h t p i n k i s h a p p e a r a n c e . T h e mucosM aspect of t h e cecum, descending, a n d pelvic colon w a s likewise e m p h y s e m a t o u s . T h e colon w a s d i s t e n d e d with gas. T h e m e s e n t e r i e l y m p h nodes were e n l a r g e d a n d replaced in m a n y i n s t a n c e s b y n u m e r o u s g a s cysts. The c i s t e r n a chyli a n d the p r o x i m a l h a l f of the thoracic duct were d i s t e n d e d w i t h gas. There was, however, no evidence of air embolism. M,icroscopiv Examination.--Esophagus and stomach were normal.
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Duodenum: The tunica propria was cellular but not exceptionally vascular. The glandular lumina were dilated, with occasionally low and atrophic epithelium. There were diminished numbers of mucous-secreting cells. There were moderately frequent mitoses. B r u n n e r ' s glands were normal. J e j u n u m and Ileum: The mucosa was variably thinned. There was glandular atrophy both in areas overlying cysts as well as in uninvolved zones. The glandular lamina were dilated and frequently contained inspissated mucus, desquamated epithe. lial cells, occasional po]ymorphonue]ear leucocytes, and wandering cells. The epithelial cells were to a varied degree atrophic, and occasionally necrotic. Goblet cells and the varied phases of pre- or postsecretory mucous cells were rare. There were fairly frequent mitoses. The stroma was quite markedly hyperemie and cellular, There were increased numbers of polymorphonuc!ear leucocytes and phagocytic monocytes, particularly close to the surface of villar folds and interglandular areas. I n the involved areas, there were occasional mucosal gas cysts. The muscularis mucosae was greatly thinned. There were numerous cysts that distended the submucosa. These infrequently appeared to have an endothelial-like lining; usually they were bordered by collagen alone. There were no giant cells. The adjoining stroma was often edematous and cellular, with rare polymorphonuclear leucocytes and more frequent monocytes, lymphocytes, and plasma cells. There were flattened bands of lymphoid tissue bordering the cysts in juxtaposition to the muscularis mucosae. Nerve cells and fibers were stretched and distorted within the involved portions of submucosa. There were dilated submucosal lymphatics, containing ]ymphocytes and polymorphonuclear leucocytes in instances. There was evidence of dissection of gas throt~gh the muscular coat into the scrosa along the perivascular lymphatics, where endothelial lining membranes were clearly definable. The serosa was generally thin, but there were instances where it was thickened, edematous~ infiltrated by round eells~ and contained occasional gas cysts. Mesenterie Glands: The peripheral lymphatics were dilated. The gas cysts were diffusely disseminated throughout the lymph nodes. There was apparent lymphoid depletion with accentuation of the reticular stroma and perivascnlar fibrosis. The sinusoids revealed endothelial hyperplasia and contain lymphocytes and polymorphonuclear leucocytes. CASE 3.--(A-36-34.) This 7-month-old white male infant was admitted to the hospital for cough and fever of one week's duration. He was cyanotic and presented signs of patchy pneumonia. Two weeks before death he developed persistent vomitii~g and diarrhea. The patient died five weeks after entry. Necropsy was performed four hours post mortem. The anatomic diagnoses were bilateral bronchopneumonia; acute bilateral otltis media; cerebral edema; f a t t y infiltration of the liver; pneumatosls of ileum and mesenteric lymph nodes; and acute mesenteric lymphadenitls.
Gross Examination.--About ]45 cm. from the ileocecal valve there was a raised irregular, frothylike area of emphysematosis, measuring 1.5 by 0.5 cm. Proximal to this area, and continuous with it, there was a column of air terminating in an apical point, where there was seen to be a small pimpoint aperture. The appearance of the whole lesion suggested forceful injection of air through ~ very narrow mucosal aperture which dissected its way in a straight but ever broadening path until it finally broke up into a number of large submucosal cysts. In other areas throughout the length of the small intestine there was diffuse reddening but no ulceration. The colon presented a moderately reddene(1 but nonulcerated mueosa. Mieroscopio Examination.---Esophagus: underlying acute inflammation,. Stomach:
There w e r e small recent ulcers with
There was cystic dilatation of stone of the glands.
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Jejungm and Ileum: I n sections of uninvolved portions of the jejunum and ileum there were evident mucosal changes. These were characterized by thinning in some instances, hyperemia in alt instances, broadening and flattening of the villi and interglandular areas, and increased cellularity and fairly marked polymorphonuclear leucoeytic infiltration, particularly toward the surface. The glandular lumina were dilated and contained inspissated secretion and cellular debris in some areas. Occasionally there was quite marked atrophy of the glandular epithelium with f e w goblet cells. I n some sections there were fairly abundant, incompletely filled, mucous-containing cells. There was decreased mitotic activity. There was very little lymphoid tissue in the submucosa. There were occasional dilated_ submucosal lymphatics.
Fig.
2.--Case
4.
Pneumatosis
of loop
of jejunum,
i.
I n the involved portions of tlle intestine the gas cysts were practically confined to the submucosa. I n areas they appeared to be lined by endothelial cells. There were no giant cells, but in a few areas some polymorphonuclear leucocytes and monocytes were in apposition to tlle inner cyst wall. I n the adjoining stroma there were occasional areas with apparent increase in fibroblasts and rarely some polymerphonuclear reaction.
Mesenter4v Lymph Nodes: There were several small gas cysts. The peripheral and medullary sinusoids were widened and contained many polymorphonuclear leucocytes and proliferated endothelial cells. There was relative depletion of lymphoid tissue.
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CaSE 4.--(A-36~56.) A t 2% months of age this male child was admitted to the hospital for jaundice of two weeks' duration. There were no unusual symptoms accompanying the onset of jaundice. Physical examination revealed a jaundiced infant with liver palpable 3 era. below the costal margin. On the twelfth hospital day he developed diarrhea and vomiting. The diarrhea persisted until the time of death on the twenty-sixth hospital day. Necropsy was performed four and one-half hours post mortem. The anatomic diagnoses were nonobstructive biliary cirrhosis; pulmonary congestion; pneumatosis of jejunum and mesenteric lymph nodes; acute mesenteric lymphadenitis~ rickets, mild; and scurvy, mild. Gross Exa~dnation.--Pharynx and esophagus were not remarkable. The stomach was distended with gas. There was pneumatosis of the jejunum, extending 40 cm. from the pylorus for a distance eaudad of 30 era. The cysts were small, averaging 0,3 to 0.5 era. and were grouped in clusters. There were no areas of ulceration. The mucosa of the small and large intestine elsewhere was pinkish gray. Microscopic Examination.--Esophag~s and stomach were normal.
Fig. 3.--Case 4. Microscopic section of jejunum with emphysema. 1. Note compression and thinning of mueosa with glandular dilatation and epithelial desquamation,
D~odenum: There was moderate mueosal vascular congestion. The glandular lumina were dilated. The epithelium was moderately reduced in height, distinctly atrophi G and ahnost flattened in instances. There were diminished numbers of c0mplete goblet cells and increased numbers of polymorphonnclear leucocytes in areas. Jejunum (nonemphysematous portion) : There was quite mark d mucosai vascular congestion, particularly in the inner third. There was considerable polymorphonuelear leucoeytic infiltration, especially close to the surface and within the villi. The reticular stroma was loose and edematous. Whereas there Was probably some increase in the spacing between glandular bases~ the villi and intervillar areas appeared thick, and cellular. The glands were irregularly tortuous. The lamina were frequently mildly dilated, and a few contained epithelia] debris !and infrequent polymorphonuelear leucocytes. The epithelium in the more dilated glands was low and of irregular shape. There were rare goblet cells, but many with small amounts of mucus of nongoblet form (stages of secretion). Within epithelial cells there were many oval~ slightly basophilie structures surrounded by a halo which resembles an in~ clusion body; but they were probably products of secretion. There were frequent mitoses and necrotic epithelial 6ells. There were a few dilated submucosal lymphatics, but little lymphoid tissue.
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Jeju/aum (emphysematous portion): The mucosal changes resemble those of the nonemphysematous areas and were, in all, less marked. The gas cysts were restricted to the submucosa. There was no clear-cut endothelial lining. There was mild lymphocytic and monocytic reaction with occasional polymorphonuclear leucocytes about, and adjoining the inner membrane of the cyst wall There were dilated lymphatics in the noninvolved portions of the submucosa and in the serosa. Mesenteric Lymph Nodes: The peripheral lymphatics were wide and cystic. One small lymph node was honeycombed with gas cysts. Two others contained one and six cysts, respectively. The sinusoids were wide and active with many phagocytic endothelial ceils, abundant polymorphonuclear leucocytes, and scattered red blood cells. There were many eosinophiles throughout the depleted lymphoid tissue. There was apparent proliferation and, certainly, increase in size and activity of the reticular cells. There was also fibroblastie proliferation within the lymph ,nodes, capsule, and mesenteric tissues.
Fig. 4.--Case 4.
~Viicroscopic section of mesenteric lymph node with emphysema. 1. Note dil~ted peripheral sinusoids. 2.
CASE 5.--(A-36-84). This 31~-month-old male infant was admitted to the hospital because of vomiting and watery diarrhea of eighteen hours' duration. He was one of twins, (The other twin was admitted about the same time with similar complaints. He died a week later, but at autopsy no intestinal emphysema was encountered.) Physical examination revealed a malnourished, irritable i n f a n t with bilateral otitis media. Vomiting and diarrhea continued u n a b a t e d up to the time of death, sixteen days a f t e r entry. Necropsy was performed three hours post mortem. The anatomic diagnoses were bronchopneumonia, mild; nonobstructive biliary cirrhosis, mild; emphysematosis of ileum; acute otitis media, bilateral; and acute mesenteric lymphadenitis.
Gross Examination.--The pharynx was mildly injected. There was vascular congestion and edema of the lower half of the esophagus, but without ulceration. The stomach was distended with gas and its mucosa moderately congested. There was intense vascular congestion of the mucosa of the small intestine, without
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ulceration. Approximately 30 cm. from the ileocecal valve there was an area of emphysema, 3 cm. in length, over the antimesenteric aspect of the ileum. The emphysema was largely limited to the submucosal coat with no appreciable involvemeat of the mucosa. Throughout the large intestine vascular congestion similar to that of the small intestine was noted. The mesenteric lymph nodes were not emphysematous. Microscopic Examination.--Esophagus and: stomach were normal. Duodenum: The mucosa was very cellular with many infiltrating polymorphonuclear leucocytes, especially close to, and within, the villi. The glandular lumina were widened, and in many the epithelium was of lower columnar type than usual. There was desquamated epithelium and debris within the lumina of some glands. There were numerous mitoses and fair numbers of goblet cells. Small Intestine : Here again, there was polymorphonuclear leucocytie infiltration within the mueos% more or less intense in varied sections, with accompanying marked hyperemia. There were either catarrhal epithelial changes with many pregoblet cell forms, fewer mitoses, and epithelial desquamation; or there was a marked scarcity in mucus-secreting cells with epithelial necroses, many mitoses, cystic dilatation of the glandular lumina, and varied atrophy of the epithelium. There was very little submucosal lymphoid tissue. There was moderate edema of the submucosa. I n the te~'minal ileum and colon there were marked catarrhal changes. The glandular lumina were widened, frequently cystic, and filled with mucus and epithelial debris. The lining epithelial cells were of low columnar form and, at times, almost flattened, with poorly defined striate borders. There were abundant mucusfilled cells, and many of these had complete goblet characters. There were fairly frequent mitoses. Ileum (emphysematous): There were mucosal changes similar in character to those of the nonemphysematous portions of bowel, plus pronounced thinning and atrophy over the larger submucosal gas cysts. As in the other eases~ the latter varied in size and were separated by edematous connective tissue with ~ery little evidence of inflammatory reaction. There were no giant cells and practically no specific lining cells. There were, however, distinctly dilated lymphatics within the submucosa. 9 I n addition, there were several gas cysts. Mesenterie L y m p h Nodes: The sinusoids were greatly widened. There was marked endothelial proliferation w i t h very active phagocytosis. There were also fair numbers of polymorphonuclear leucocytes and lymphocytes. There were no microscopic gas cysts. CASE 6.--(A-37-5.) This 2-week-old male infant was admitted to the hospital because of blisters over hands, feet, and body, of twelve d a y s ' duration. Physical examination revealed a poorly developed and poorly nourished, hypertonic infant with large excoriated lesions of feet, hands, face, left groin, and back. The skin lesions failed to respond to a variety of local applications. Intermittent vomiting and diarrhea appeared and persisted, l i e died on the thirty-seventh hospital day. Stool examinations were consistently positive for occult blood. Necropsy was performed one hour post mortem. The anatomic diagnoses were epidermolysis bullosa ; bronchopneumonia, bilateral; acute otitis media; acute mastoiditis, bilateral; acute enteritis, marked; pneumatosis of colon; acute mesenterlc lymphadenitis; and aberrant pancreas in wall of stomach. Gross Examination.--The small intestine was moderately distended with gas. There Were several small areas of mucosal congestion b u t no ulcers. The colon likewise was moderately distended with gas. The mucosal surfaces of the cecum and ascending colon were not very remarkable, although there was C~onsiderable adherent sticky mucus. The wall of the transverse colon was considerably thickened,
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a n d i t s s u b m u e o s a a n d s e r o s a w e r e h o n e y c o m b e d b y n u m e r o u s gas-filled cysts. H e r e too, t h e m u c o s a w a s c o v e r e d b y t e n a c i o u s mucus, which w h e n removed l e f t a n i r r e g u l a r s u r f a c e b o t h s m o o t h a n d g r a n u l a r in character.
Microscopio Examination.--Esophagus: regeneration with subepithelial vascular c o n t r a c t e d n e w l y f o r m e d blood vessels.
There was evidence of recent epithelial d i l a t a t i o n a n d t h e f o r m a t i o n o f small
Stomach: There was a n i s l a n d of a b e r r a n t p a n c r e a s in t h e s u b m u c o s a . Small Intestine: The m u c o s a w a s cellular a n d h e a v i l y infiltrated by polymorp h o n u e l e a r leucocytes, p a r t i e u l a r l y close to the surface. There was r o u n d i n g a n d b r o a d e n i n g of the i n t e r g l a n d u l a r s u r f a c e portions w i t h poorly defined villi. T h e r e was little v a s c u l a r congestion, b u t some of the vessels n e a r t h e s u r f a c e were t h r o m b o s e d . T h e g l a n d s s h a r e d in t h e i n f l a m m a t o r y r e a c t i o n a n d w e r e o f t e n comp r e s s e d . T h e l i n i n g cells w e r e low a n d a l m o s t f l a t t e n e d . H e r e a n d t h e r e t h e l u m i n a were dilated a n d filled w i t h cellular debris. P o r t i o n s of t h e g l a n d u l a r e p i t h e l i u m w e r e e n t i r e l y u l c e r a t e d , a n d t h e r e were i n f l a m m a t o r y cells in t h e l u m e n . T h e e l o n g a t e d , f l a t t e r cells h a d t h e a p p e a r a n c e of b e i n g of r e c e n t r e g e n e r a t i v e character, yet mitoses were rare. T h e r e were f a i r n u m b e r s of goblet cells. T h e r e were rare small l y m p h o i d follicles in t h e submucosa. I n t h e latter, t h e r e were rare vascular thrombi, edema, a n d l y m p h a n g i e c t a s i s . I n the serosa t h e r e were dilated endotheliM-lined l y m p h a t i c s a n d a r e a s of fibrosis, vascularization, edema, a n d round, cell infiltration.
Colon ( n o n e m p h y s e m a t o u s ) : A t h i c k layer of m u c u s covered t h e mucosa. The g l a n d s were p r a c t i c a l l y m a d e up of l a r g e goblet cells w i t h wide c r y p t i c o p e n i n g s where, in particula!', t h e r e was considerable epithelial d e s q u a m a t i o n . The interg l a n d u l a r s t r o m a was f r e e of active i n f l a m m a t o r y reaetion. T h e s u b m u e o s a a n d serosa were of the same c h a r a c t e r as in the ileum, poor in l y m p h o i d tissue in t h e former, fibrosed a n d cellular in the latter, a n d with diIated i r r e g u l a r l y m p h a t i c c h a n n e l s in both. Colon ( e m p h y s e m a t o u s ) : The m u c o s a resembled t h a t of the n o n e m p h y s e m a t o u s p o r t i o n s of t h e l a r g e bowel b u t w a s t h i n n e d over l a r g e r cysts. T h e s u b m u e o s a was riddled b y n u m e r o u s g a s cysts. Occasionally t h e y e x t e n d e d t h r o u g h the m u s c u l a r coat. F r e q u e n t l y t h e y f o r m e d h o n e y c o m b e d areas in t h e serosa. T h e cysts in the s u b m u e o s a possessed no specific l i n i n g except f o r rare, questionable, endothelial cells. I n the serosa t h e smaller ones were more clearly of dilated l y m p h a t i c character. There was no cellular e x u d a t e w i t h i n or a d j o i n i n g the cysts. There were no g i a n t cells. The s u b m u c o s a l s t r o m a was, however, f r e q u e n t l y m i l d l y e d e m a t o u s . T h e m u s c u l a r i s m u e o s a e was i n t a c t a n d thickened in all instances. Mesenteric L y m p h Nodes: T h e r e were g r e a t l y dilated a n d t o r t u o u s p e r i c a p s u l a r l y m p h a t i c s filled w i t h a g r a n u l a r p r e c i p i t a t e . The peripheral and medullary s i n u s o i d s of t h e l y m p h n o d e s w e r e v e r y wide a n d c o n t a i n e d n m n b e r s of polymorp h o n u c l c a r leucocytes a n d p r o l i f e r a t e d endothelial cells. DISCUSSION
The varied factors associated with the production of intestinal emphysema are yet poorly understood. Of the prevailing etiological theories, the mechanical one has gained general acceptance. This theory implies that the gas from the intestinal lumen penetrates the intestinal wall through gross or microscopic mueosal defects. It is believed that the gas may form local cysts or may permeate the intestinal wall and form cystic aggregates at some point distant from the site of entrance.
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Increased intragastric or intraintestinal pressure is probably of importance in initiating, and peristaltic activity in determining, the site of intestinal emphysema. In partial substantiation of this viewpoint is the fact that there have been gastric or duodenal ulcers, often with stenosis, in more than 50 per cent of the cases in adults. I n m a n y of the others there have been ulcers, strictures, or obstruction occasioned b y - i n t r i n s i c or extrinsic factors, in other portions of the intestine. However, experimentally, Tung and Ngai 9 failed to produce local intestinal emphysema in dogs following injection of air into the intestinal wall, although they observed its passage into the mesenteric lymphatics. Likewise, when they produced artificial gastric ulcers and then distended the stomach, air bubbles were found in the serosa] lymphatics of the stomach and omentum but failed to form local or distinct intestinal gaseous cysts. Similarly, we failed to reproduce the condition in healthy rabbits and cats by injection of air into the submucosa. The gas would invariably escape into perivascular, serosal, and mesenteric lymphatics, forming cysts in the mesentery and retroperitoneal tissues but not locally in the intestinal wall. It would seem that under normal conditions the bowel wall can rid itself of the entering gas through patent lymphatics. It is of interest that in the somewhat similar disease in swine there is a constant catarrhal enteritis. I n infancy, enteric symptoms such as diarrhea and vomiting are very common but most often are unaccompanied by anatomic change in the intestine. Intestinal pneumatosis is very rare as f a r as we know. This does not preclude the possibility, however, that enteritis may be an important factor in the pathogenesis of the condition. Very little attention has been paid to the uninvolved portions of the intestine, and it is felt that in these areas there may be functional as well as anatomic changes. In all of Moore's cases there was an intense enteritis and a macroscopic ulcer in one. In five of our patients persistent vomiting and diarrhea, or diarrhea alone, were present. In the intestines of all of these there were glandular changes and inflammatory reactions in the small intestine, but there was no gross ulceration. These findings were constantly present in distant areas, as well as in the emphysematous regions. With these changes present, especially hyperemia and hyposecretion of mucus, minute fissures in a relatively d r y and friable mucous membrane could allow the continued entrance of gas. Certainly disturbances in peristalsis and intraintestinal gaseous pressures could coexist with the enteritis. I n addition, increased or disturbed lymphatic drainage, as evidenced by ~he fairly frequent finding of dilated lymphatics in the intestinal wall and dilated active sinusoids in the mesenteric lymph nodes, would facilitate the diffusion or accumulation of gas. That the latter permeates lymphatic channels is well known. Not only were the mesenteric lymph nodes the seat of
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gas cysts in three of the six cases, but in one the cisterna chyli and thoracic duct were also involved. The presence of giant cells and fibroblastie proliferation about the gas cysts commonly reported in adults is evidence of chronicity, as indicated by the experimental injections of gas into subcutaneous tissues by Wright, 16 where such reactions about gas-filled spaces were noted only after several days. Giant cells were entirely absent in the present cases. There was little evidence of fibrosis, although there were occasional areas of mild inflammation. This would indicate that, in the early establishment of t h e emphysema, the reaction may be m i n i m a l and that here the disease process is quite recent. It is also of interest that in three eases there were evidences of i n j u r y to the liver. In Case 4, a nonobstruetive biliary cirrhosis was the chief anatomic finding. I t is conceivable that, with ulcers or inflammation of the intestinal tract, small amounts of gas" may enter the intestinal wall and rapidly be disposed of by diffusion and absorption. It is true that the condition is overlooked clinically, but there may be temporary symptoms suggesting appendicitis, peritonitis, or intestinal obstruction. It is known that following' laparotomy the gas cysts have disappeared spontaneously. Of recent years Bonnamour, Badolle, and Beaupere 1~ and Graberger is have stressed the possibility of the recognition of the disease by x-ray examination. CONCLUSIONS
Six eases are added to the four examples of intestinal pneumatosis in infancy and childhood reported in the literature. Five of these were observed over the period of approximately one year. It is believed that in the absence of ulcers or obstruction as commonly occur in the adult, enteritis and accompanying functional changes are probably important factors in the initiation and evolution of t h e disease. REFERENCES 1. B a n g : Nor& Med. Ark. 8: 18, 1876 i quoted by Nitch: ]3rit. J. Surg. 11: 714, 1924. 2. Turnure, P . R . : Ann. Surg. 57: 811, 1913. 3. Mills, It. W.: Surg. Gynec. & Obst. 40: 387, 1925. 4. Memmi, 1~.: Pollclinico (sez. chir.) 41: 408, 1934. 5. Silverstone, J . : Lancet 1: 129, 1928. 6. Lamont, D.: Tr. Roy. Med.-Chir. Sot. Glasgow 23: 113, 1928-29. 7. Sawada, ]3.: J. Orient. Med. 9: 66, 1928. 8. Moore, R . A . : Am. J. Dis. Child. 38: 818, 1929. 9. Tung, P. C., and Ngai, S . K . : Chinese M. J. 47: 1-14, 1933. 10. Pybus, F . C . : Brit. J. Surg. 21: 539, 1934. 11. Kemal, M.: Deutsche reed. Wchnschr. 59: 1707, 1933. 12. Nimet, ]3.: Zentralbl. f. Chit. 61: 1986, 3934. 13. BBsteh, O.: Arch. f. klin. Chir. 181: 707, 1935. 14. Englund, F., and Wahlgren, )~.: A c t a chir. Seandlnav. 76: 601, 1935. 15. Sehnyder, K.: Cor.-]31. f. schweiz. Aerzte. 47: 289, 1917; quoted by Mills. 16. Wright, A . W . : Am. J. Path. 6: 87, 1930. 17. ]3onnamour, Bado]le, and Beaupere: J. de. radiol, et d'electrol. 10: 164, 1926. 18. Graberger~ G.: Acta radiol. 16: 439, 1935.
IN INFANCY
THOMAS W . BOTSFORD, M.D., A~TD CECIL KRAKOWER, M.D. BOSTON, MASSACHUSETTS
p
N E U M A T O S I S of the intestine is considered to be a rare pathologic condition. I t was first clearly described in a h u m a n b y Bang ~ in 1876. W i t h the advent of abdominal s u r g e r y in the latter p a r t of the nineteenth century, instances of this disease noted at operation and post m o r t e m have steadily been reported up to the present. T u r n u r e ~ in 1913 collected 50 cases; Mills 3 in 1925, 100 cases; and Memmi 4 in 1934 brought the total to 154. Twenty-one additional eases, not included in the above, have been found. These comprise reports by Silverstone, ~ Lamont, G Sawada, 7 Moore, s T u n g a n d Ngai, 9 Pybus, 1~ Kema], 1~ Nimet, ~2 Bsteh, 13 and E n g l u n d and W a h l g r e n 2 ~ Of these 171 cases, there h a t e been only 5 authentic cases in childhood and infancy. Schnyder ~5 in ]917 observed gas cysts in the intestinal lymphatics, mesentery, and mesenteric glands in a 5-year-old child who died of diphtheria. Moore s in 1929 re'ported four cases in infants of 2 weeks to 14 months of age. Of the six instances t h a t we are reporting, five were observed during the period of a p p r o x i m a t e l y one year. CASE REPORTS
CAS]~ 1.--(A-26-15.) This 4-week-old, white, premature male infant was brought to the hospital because of failure to gain in weight. Subsequently he developed attacks of cyanosis and physical signs of pneumonia. He died two weeks after entry. Necropsy was performed six hours post mortem. The anatomic diagnoses were acute suppurative broachopneumonia, acute bronchial lymphadenitis, and pneumatosis of the colon. Gross Examination.--The upper portion of the ileum was markedly injected, but there were no areas of ulceration. In the descending colon there were many small air blebs, varying from 1 to 3 ram. in diameter. The mucosa was mildly injected in this portion of the large bowel. Microscopic E x a m i n a t i o n . - - J e j u n u m : There was intense vascular congestion throughout the mucosa. The glandular lumina were frequently dilated but free of inspissated mucoid contents. Goblet cells were moderately in excess. There was striking diminution in the number of mitoses. The tunica propria was cellular with excessive numbers of loolymorphonuclear leucocytes~ particularly at the tips of villi. The submucosal blood vessels were greatly dilated and e(/ngested. There were no lymphoid aggregates. The serosa was edematous. There were dilated submucosM lymphatics. I~eum: The sections were similar to the jejunum with the exception that there was somewhat less polymorphonuclear cell infiltration in the tunica propria of the mucosa. There were dilated lymphatics in the submucosa. Colon: The mucosa was moderately tkinned and compressed. There was fairly marked vascular congestion throughout the tunica propria. The glands assumed From the Department of Pathology, the Children's Hospital. 185
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varied a p p e a r a n c e s . I n i n s t a n c e s t h e i r l u m i n a were dilated~ c o n t a i n i n g i n s p i s s a t e d m u c u s or necrotic cellular elements. T h e l i n i n g cells were in places flattened a n d atrophic. Elsewhere, the epithelial cells were tall b u t l a t e r a l l y flattened w i t h v a r i a b l e a m o u n t s of mucus, b u t p r a c t i c a l l y never of t h e full goblet t y p e w i t h flattened b a s a l nucleus. Mitoses in g l a n d u l a r e p i t h e l i u m s were relatively i n f r e q u e n t . T h e r e were occasional m n e o s a l g a s cysts. T h e m u s c u l a r i s m u e o s a e was t h i n n e d , more m a r k e d l y so where f o r m i n g the wall of a d i s t e n d e d s u b m u c o s a l g a s cyst. There were occasional small s u b m u c o s M l y m p h o i d nodules. The whole of t h e s u b m u c o s a otherwise was replaced b y n u m e r o u s g a s cysts. T h e s e possessed no specific endothelial lining. T h e r e were no g i a n t cells. There were dilated p e r l v a s c u l a r . l y m p h a t i e s in the m u s c u l a r a n d serosal coats. CASE 2 . - - ( A - 3 6 - 1 9 . ) T h i s 9-month-old white male i n f a n t was reachnitted because of p e r s i s t e n t e d e m a a n d a n u p p e r r e s p i r a t o r y infection. T h r e e m o n t h s previously a d i a g n o s i s o f n e p h r o s i s h a d been m a d e at his first admission. There h a d been no i m p r o v e m e n t in his condition in t h e interim. F o r t h e first week d u r i n g this second admission, he did f a i r l y well. V o m i t i n g a n d d i a r r h e a t h e n supervened. Ite died a week later.
}eig. 1 . - - C a s e 2. 1, Thoracic d u c t ; 2, cisterna chyli; 3, mesenteric l y m p h nodes. Note m a r k e d e m p h y s e m a of l y m p h nodes a n d distention of cisterna chyli a n d [horaeie duct with gas. N e c r o p s y was p e r f o r m e d one h o u r p o s t m o r t e m . The a n a t o m i c d i a g n o s e s were s u b a c u t e g l o m e r u l o n e p h r i t i s ; b r o n c h o p n e u m o n i a w i t h i n t e r s t i t i a l e m p h y s e m a ; nonobstructive b i l i a r y cirrhosis ( m i l d ) ; acute otitis media, b i l a t e r a l ; a c u t e m e s e n t e r i c l y m p h a d e n i t i s ; p n e u m a t o s i s of ileum, a s c e n d i n g a n d pelvic colons, m e s e n t e r i c l y m p h nodes, c i s t e r n a chyli, a n d thoracic d u c t .
Gross Examination.--The p h a r y n g e a l m u e o s a was reddened a n d thickened. The e s o p h a g u s a n d s t o m a c h were n o t remarkable. The j e j u n u m was d i s t e n d e d w i t h gas~ a n d t h e r e were occasional a r e a s of e m p h y s e m a t o s i s over the m u e o s a l aspect. T h e entire i n n e r s u r f a c e of t h e i l e u m w a s a m a s s of f r o t h y - a p p e a r i n g g a s cysts, dis~ t r i b u t e d i r r e g u l a r l y t o w a r d the ileoeecal valve. N o n e of these c y s t s c o n t a i n e d fluid. There were no f r a n k a r e a s of ulceration. The m u e o s a l s u r f a c e of t h e intestine, part i c u l a r l y in t h e e m p h y s e m a t o u s regions, h a d a d r y g r a n u l a r a n d b r i g h t p i n k i s h a p p e a r a n c e . T h e mucosM aspect of t h e cecum, descending, a n d pelvic colon w a s likewise e m p h y s e m a t o u s . T h e colon w a s d i s t e n d e d with gas. T h e m e s e n t e r i e l y m p h nodes were e n l a r g e d a n d replaced in m a n y i n s t a n c e s b y n u m e r o u s g a s cysts. The c i s t e r n a chyli a n d the p r o x i m a l h a l f of the thoracic duct were d i s t e n d e d w i t h gas. There was, however, no evidence of air embolism. M,icroscopiv Examination.--Esophagus and stomach were normal.
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Duodenum: The tunica propria was cellular but not exceptionally vascular. The glandular lumina were dilated, with occasionally low and atrophic epithelium. There were diminished numbers of mucous-secreting cells. There were moderately frequent mitoses. B r u n n e r ' s glands were normal. J e j u n u m and Ileum: The mucosa was variably thinned. There was glandular atrophy both in areas overlying cysts as well as in uninvolved zones. The glandular lamina were dilated and frequently contained inspissated mucus, desquamated epithe. lial cells, occasional po]ymorphonue]ear leucocytes, and wandering cells. The epithelial cells were to a varied degree atrophic, and occasionally necrotic. Goblet cells and the varied phases of pre- or postsecretory mucous cells were rare. There were fairly frequent mitoses. The stroma was quite markedly hyperemie and cellular, There were increased numbers of polymorphonuc!ear leucocytes and phagocytic monocytes, particularly close to the surface of villar folds and interglandular areas. I n the involved areas, there were occasional mucosal gas cysts. The muscularis mucosae was greatly thinned. There were numerous cysts that distended the submucosa. These infrequently appeared to have an endothelial-like lining; usually they were bordered by collagen alone. There were no giant cells. The adjoining stroma was often edematous and cellular, with rare polymorphonuclear leucocytes and more frequent monocytes, lymphocytes, and plasma cells. There were flattened bands of lymphoid tissue bordering the cysts in juxtaposition to the muscularis mucosae. Nerve cells and fibers were stretched and distorted within the involved portions of submucosa. There were dilated submucosal lymphatics, containing ]ymphocytes and polymorphonuclear leucocytes in instances. There was evidence of dissection of gas throt~gh the muscular coat into the scrosa along the perivascular lymphatics, where endothelial lining membranes were clearly definable. The serosa was generally thin, but there were instances where it was thickened, edematous~ infiltrated by round eells~ and contained occasional gas cysts. Mesenterie Glands: The peripheral lymphatics were dilated. The gas cysts were diffusely disseminated throughout the lymph nodes. There was apparent lymphoid depletion with accentuation of the reticular stroma and perivascnlar fibrosis. The sinusoids revealed endothelial hyperplasia and contain lymphocytes and polymorphonuclear leucocytes. CASE 3.--(A-36-34.) This 7-month-old white male infant was admitted to the hospital for cough and fever of one week's duration. He was cyanotic and presented signs of patchy pneumonia. Two weeks before death he developed persistent vomitii~g and diarrhea. The patient died five weeks after entry. Necropsy was performed four hours post mortem. The anatomic diagnoses were bilateral bronchopneumonia; acute bilateral otltis media; cerebral edema; f a t t y infiltration of the liver; pneumatosls of ileum and mesenteric lymph nodes; and acute mesenteric lymphadenitls.
Gross Examination.--About ]45 cm. from the ileocecal valve there was a raised irregular, frothylike area of emphysematosis, measuring 1.5 by 0.5 cm. Proximal to this area, and continuous with it, there was a column of air terminating in an apical point, where there was seen to be a small pimpoint aperture. The appearance of the whole lesion suggested forceful injection of air through ~ very narrow mucosal aperture which dissected its way in a straight but ever broadening path until it finally broke up into a number of large submucosal cysts. In other areas throughout the length of the small intestine there was diffuse reddening but no ulceration. The colon presented a moderately reddene(1 but nonulcerated mueosa. Mieroscopio Examination.---Esophagus: underlying acute inflammation,. Stomach:
There w e r e small recent ulcers with
There was cystic dilatation of stone of the glands.
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Jejungm and Ileum: I n sections of uninvolved portions of the jejunum and ileum there were evident mucosal changes. These were characterized by thinning in some instances, hyperemia in alt instances, broadening and flattening of the villi and interglandular areas, and increased cellularity and fairly marked polymorphonuclear leucoeytic infiltration, particularly toward the surface. The glandular lumina were dilated and contained inspissated secretion and cellular debris in some areas. Occasionally there was quite marked atrophy of the glandular epithelium with f e w goblet cells. I n some sections there were fairly abundant, incompletely filled, mucous-containing cells. There was decreased mitotic activity. There was very little lymphoid tissue in the submucosa. There were occasional dilated_ submucosal lymphatics.
Fig.
2.--Case
4.
Pneumatosis
of loop
of jejunum,
i.
I n the involved portions of tlle intestine the gas cysts were practically confined to the submucosa. I n areas they appeared to be lined by endothelial cells. There were no giant cells, but in a few areas some polymorphonuclear leucocytes and monocytes were in apposition to tlle inner cyst wall. I n the adjoining stroma there were occasional areas with apparent increase in fibroblasts and rarely some polymerphonuclear reaction.
Mesenter4v Lymph Nodes: There were several small gas cysts. The peripheral and medullary sinusoids were widened and contained many polymorphonuclear leucocytes and proliferated endothelial cells. There was relative depletion of lymphoid tissue.
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CaSE 4.--(A-36~56.) A t 2% months of age this male child was admitted to the hospital for jaundice of two weeks' duration. There were no unusual symptoms accompanying the onset of jaundice. Physical examination revealed a jaundiced infant with liver palpable 3 era. below the costal margin. On the twelfth hospital day he developed diarrhea and vomiting. The diarrhea persisted until the time of death on the twenty-sixth hospital day. Necropsy was performed four and one-half hours post mortem. The anatomic diagnoses were nonobstructive biliary cirrhosis; pulmonary congestion; pneumatosis of jejunum and mesenteric lymph nodes; acute mesenteric lymphadenitis~ rickets, mild; and scurvy, mild. Gross Exa~dnation.--Pharynx and esophagus were not remarkable. The stomach was distended with gas. There was pneumatosis of the jejunum, extending 40 cm. from the pylorus for a distance eaudad of 30 era. The cysts were small, averaging 0,3 to 0.5 era. and were grouped in clusters. There were no areas of ulceration. The mucosa of the small and large intestine elsewhere was pinkish gray. Microscopic Examination.--Esophag~s and stomach were normal.
Fig. 3.--Case 4. Microscopic section of jejunum with emphysema. 1. Note compression and thinning of mueosa with glandular dilatation and epithelial desquamation,
D~odenum: There was moderate mueosal vascular congestion. The glandular lumina were dilated. The epithelium was moderately reduced in height, distinctly atrophi G and ahnost flattened in instances. There were diminished numbers of c0mplete goblet cells and increased numbers of polymorphonnclear leucocytes in areas. Jejunum (nonemphysematous portion) : There was quite mark d mucosai vascular congestion, particularly in the inner third. There was considerable polymorphonuelear leucoeytic infiltration, especially close to the surface and within the villi. The reticular stroma was loose and edematous. Whereas there Was probably some increase in the spacing between glandular bases~ the villi and intervillar areas appeared thick, and cellular. The glands were irregularly tortuous. The lamina were frequently mildly dilated, and a few contained epithelia] debris !and infrequent polymorphonuelear leucocytes. The epithelium in the more dilated glands was low and of irregular shape. There were rare goblet cells, but many with small amounts of mucus of nongoblet form (stages of secretion). Within epithelial cells there were many oval~ slightly basophilie structures surrounded by a halo which resembles an in~ clusion body; but they were probably products of secretion. There were frequent mitoses and necrotic epithelial 6ells. There were a few dilated submucosal lymphatics, but little lymphoid tissue.
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Jeju/aum (emphysematous portion): The mucosal changes resemble those of the nonemphysematous areas and were, in all, less marked. The gas cysts were restricted to the submucosa. There was no clear-cut endothelial lining. There was mild lymphocytic and monocytic reaction with occasional polymorphonuclear leucocytes about, and adjoining the inner membrane of the cyst wall There were dilated lymphatics in the noninvolved portions of the submucosa and in the serosa. Mesenteric Lymph Nodes: The peripheral lymphatics were wide and cystic. One small lymph node was honeycombed with gas cysts. Two others contained one and six cysts, respectively. The sinusoids were wide and active with many phagocytic endothelial ceils, abundant polymorphonuclear leucocytes, and scattered red blood cells. There were many eosinophiles throughout the depleted lymphoid tissue. There was apparent proliferation and, certainly, increase in size and activity of the reticular cells. There was also fibroblastie proliferation within the lymph ,nodes, capsule, and mesenteric tissues.
Fig. 4.--Case 4.
~Viicroscopic section of mesenteric lymph node with emphysema. 1. Note dil~ted peripheral sinusoids. 2.
CASE 5.--(A-36-84). This 31~-month-old male infant was admitted to the hospital because of vomiting and watery diarrhea of eighteen hours' duration. He was one of twins, (The other twin was admitted about the same time with similar complaints. He died a week later, but at autopsy no intestinal emphysema was encountered.) Physical examination revealed a malnourished, irritable i n f a n t with bilateral otitis media. Vomiting and diarrhea continued u n a b a t e d up to the time of death, sixteen days a f t e r entry. Necropsy was performed three hours post mortem. The anatomic diagnoses were bronchopneumonia, mild; nonobstructive biliary cirrhosis, mild; emphysematosis of ileum; acute otitis media, bilateral; and acute mesenteric lymphadenitis.
Gross Examination.--The pharynx was mildly injected. There was vascular congestion and edema of the lower half of the esophagus, but without ulceration. The stomach was distended with gas and its mucosa moderately congested. There was intense vascular congestion of the mucosa of the small intestine, without
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ulceration. Approximately 30 cm. from the ileocecal valve there was an area of emphysema, 3 cm. in length, over the antimesenteric aspect of the ileum. The emphysema was largely limited to the submucosal coat with no appreciable involvemeat of the mucosa. Throughout the large intestine vascular congestion similar to that of the small intestine was noted. The mesenteric lymph nodes were not emphysematous. Microscopic Examination.--Esophagus and: stomach were normal. Duodenum: The mucosa was very cellular with many infiltrating polymorphonuclear leucocytes, especially close to, and within, the villi. The glandular lumina were widened, and in many the epithelium was of lower columnar type than usual. There was desquamated epithelium and debris within the lumina of some glands. There were numerous mitoses and fair numbers of goblet cells. Small Intestine : Here again, there was polymorphonuclear leucocytie infiltration within the mueos% more or less intense in varied sections, with accompanying marked hyperemia. There were either catarrhal epithelial changes with many pregoblet cell forms, fewer mitoses, and epithelial desquamation; or there was a marked scarcity in mucus-secreting cells with epithelial necroses, many mitoses, cystic dilatation of the glandular lumina, and varied atrophy of the epithelium. There was very little submucosal lymphoid tissue. There was moderate edema of the submucosa. I n the te~'minal ileum and colon there were marked catarrhal changes. The glandular lumina were widened, frequently cystic, and filled with mucus and epithelial debris. The lining epithelial cells were of low columnar form and, at times, almost flattened, with poorly defined striate borders. There were abundant mucusfilled cells, and many of these had complete goblet characters. There were fairly frequent mitoses. Ileum (emphysematous): There were mucosal changes similar in character to those of the nonemphysematous portions of bowel, plus pronounced thinning and atrophy over the larger submucosal gas cysts. As in the other eases~ the latter varied in size and were separated by edematous connective tissue with ~ery little evidence of inflammatory reaction. There were no giant cells and practically no specific lining cells. There were, however, distinctly dilated lymphatics within the submucosa. 9 I n addition, there were several gas cysts. Mesenterie L y m p h Nodes: The sinusoids were greatly widened. There was marked endothelial proliferation w i t h very active phagocytosis. There were also fair numbers of polymorphonuclear leucocytes and lymphocytes. There were no microscopic gas cysts. CASE 6.--(A-37-5.) This 2-week-old male infant was admitted to the hospital because of blisters over hands, feet, and body, of twelve d a y s ' duration. Physical examination revealed a poorly developed and poorly nourished, hypertonic infant with large excoriated lesions of feet, hands, face, left groin, and back. The skin lesions failed to respond to a variety of local applications. Intermittent vomiting and diarrhea appeared and persisted, l i e died on the thirty-seventh hospital day. Stool examinations were consistently positive for occult blood. Necropsy was performed one hour post mortem. The anatomic diagnoses were epidermolysis bullosa ; bronchopneumonia, bilateral; acute otitis media; acute mastoiditis, bilateral; acute enteritis, marked; pneumatosis of colon; acute mesenterlc lymphadenitis; and aberrant pancreas in wall of stomach. Gross Examination.--The small intestine was moderately distended with gas. There Were several small areas of mucosal congestion b u t no ulcers. The colon likewise was moderately distended with gas. The mucosal surfaces of the cecum and ascending colon were not very remarkable, although there was C~onsiderable adherent sticky mucus. The wall of the transverse colon was considerably thickened,
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a n d i t s s u b m u e o s a a n d s e r o s a w e r e h o n e y c o m b e d b y n u m e r o u s gas-filled cysts. H e r e too, t h e m u c o s a w a s c o v e r e d b y t e n a c i o u s mucus, which w h e n removed l e f t a n i r r e g u l a r s u r f a c e b o t h s m o o t h a n d g r a n u l a r in character.
Microscopio Examination.--Esophagus: regeneration with subepithelial vascular c o n t r a c t e d n e w l y f o r m e d blood vessels.
There was evidence of recent epithelial d i l a t a t i o n a n d t h e f o r m a t i o n o f small
Stomach: There was a n i s l a n d of a b e r r a n t p a n c r e a s in t h e s u b m u c o s a . Small Intestine: The m u c o s a w a s cellular a n d h e a v i l y infiltrated by polymorp h o n u e l e a r leucocytes, p a r t i e u l a r l y close to the surface. There was r o u n d i n g a n d b r o a d e n i n g of the i n t e r g l a n d u l a r s u r f a c e portions w i t h poorly defined villi. T h e r e was little v a s c u l a r congestion, b u t some of the vessels n e a r t h e s u r f a c e were t h r o m b o s e d . T h e g l a n d s s h a r e d in t h e i n f l a m m a t o r y r e a c t i o n a n d w e r e o f t e n comp r e s s e d . T h e l i n i n g cells w e r e low a n d a l m o s t f l a t t e n e d . H e r e a n d t h e r e t h e l u m i n a were dilated a n d filled w i t h cellular debris. P o r t i o n s of t h e g l a n d u l a r e p i t h e l i u m w e r e e n t i r e l y u l c e r a t e d , a n d t h e r e were i n f l a m m a t o r y cells in t h e l u m e n . T h e e l o n g a t e d , f l a t t e r cells h a d t h e a p p e a r a n c e of b e i n g of r e c e n t r e g e n e r a t i v e character, yet mitoses were rare. T h e r e were f a i r n u m b e r s of goblet cells. T h e r e were rare small l y m p h o i d follicles in t h e submucosa. I n t h e latter, t h e r e were rare vascular thrombi, edema, a n d l y m p h a n g i e c t a s i s . I n the serosa t h e r e were dilated endotheliM-lined l y m p h a t i c s a n d a r e a s of fibrosis, vascularization, edema, a n d round, cell infiltration.
Colon ( n o n e m p h y s e m a t o u s ) : A t h i c k layer of m u c u s covered t h e mucosa. The g l a n d s were p r a c t i c a l l y m a d e up of l a r g e goblet cells w i t h wide c r y p t i c o p e n i n g s where, in particula!', t h e r e was considerable epithelial d e s q u a m a t i o n . The interg l a n d u l a r s t r o m a was f r e e of active i n f l a m m a t o r y reaetion. T h e s u b m u e o s a a n d serosa were of the same c h a r a c t e r as in the ileum, poor in l y m p h o i d tissue in t h e former, fibrosed a n d cellular in the latter, a n d with diIated i r r e g u l a r l y m p h a t i c c h a n n e l s in both. Colon ( e m p h y s e m a t o u s ) : The m u c o s a resembled t h a t of the n o n e m p h y s e m a t o u s p o r t i o n s of t h e l a r g e bowel b u t w a s t h i n n e d over l a r g e r cysts. T h e s u b m u e o s a was riddled b y n u m e r o u s g a s cysts. Occasionally t h e y e x t e n d e d t h r o u g h the m u s c u l a r coat. F r e q u e n t l y t h e y f o r m e d h o n e y c o m b e d areas in t h e serosa. T h e cysts in the s u b m u e o s a possessed no specific l i n i n g except f o r rare, questionable, endothelial cells. I n the serosa t h e smaller ones were more clearly of dilated l y m p h a t i c character. There was no cellular e x u d a t e w i t h i n or a d j o i n i n g the cysts. There were no g i a n t cells. The s u b m u c o s a l s t r o m a was, however, f r e q u e n t l y m i l d l y e d e m a t o u s . T h e m u s c u l a r i s m u e o s a e was i n t a c t a n d thickened in all instances. Mesenteric L y m p h Nodes: T h e r e were g r e a t l y dilated a n d t o r t u o u s p e r i c a p s u l a r l y m p h a t i c s filled w i t h a g r a n u l a r p r e c i p i t a t e . The peripheral and medullary s i n u s o i d s of t h e l y m p h n o d e s w e r e v e r y wide a n d c o n t a i n e d n m n b e r s of polymorp h o n u c l c a r leucocytes a n d p r o l i f e r a t e d endothelial cells. DISCUSSION
The varied factors associated with the production of intestinal emphysema are yet poorly understood. Of the prevailing etiological theories, the mechanical one has gained general acceptance. This theory implies that the gas from the intestinal lumen penetrates the intestinal wall through gross or microscopic mueosal defects. It is believed that the gas may form local cysts or may permeate the intestinal wall and form cystic aggregates at some point distant from the site of entrance.
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Increased intragastric or intraintestinal pressure is probably of importance in initiating, and peristaltic activity in determining, the site of intestinal emphysema. In partial substantiation of this viewpoint is the fact that there have been gastric or duodenal ulcers, often with stenosis, in more than 50 per cent of the cases in adults. I n m a n y of the others there have been ulcers, strictures, or obstruction occasioned b y - i n t r i n s i c or extrinsic factors, in other portions of the intestine. However, experimentally, Tung and Ngai 9 failed to produce local intestinal emphysema in dogs following injection of air into the intestinal wall, although they observed its passage into the mesenteric lymphatics. Likewise, when they produced artificial gastric ulcers and then distended the stomach, air bubbles were found in the serosa] lymphatics of the stomach and omentum but failed to form local or distinct intestinal gaseous cysts. Similarly, we failed to reproduce the condition in healthy rabbits and cats by injection of air into the submucosa. The gas would invariably escape into perivascular, serosal, and mesenteric lymphatics, forming cysts in the mesentery and retroperitoneal tissues but not locally in the intestinal wall. It would seem that under normal conditions the bowel wall can rid itself of the entering gas through patent lymphatics. It is of interest that in the somewhat similar disease in swine there is a constant catarrhal enteritis. I n infancy, enteric symptoms such as diarrhea and vomiting are very common but most often are unaccompanied by anatomic change in the intestine. Intestinal pneumatosis is very rare as f a r as we know. This does not preclude the possibility, however, that enteritis may be an important factor in the pathogenesis of the condition. Very little attention has been paid to the uninvolved portions of the intestine, and it is felt that in these areas there may be functional as well as anatomic changes. In all of Moore's cases there was an intense enteritis and a macroscopic ulcer in one. In five of our patients persistent vomiting and diarrhea, or diarrhea alone, were present. In the intestines of all of these there were glandular changes and inflammatory reactions in the small intestine, but there was no gross ulceration. These findings were constantly present in distant areas, as well as in the emphysematous regions. With these changes present, especially hyperemia and hyposecretion of mucus, minute fissures in a relatively d r y and friable mucous membrane could allow the continued entrance of gas. Certainly disturbances in peristalsis and intraintestinal gaseous pressures could coexist with the enteritis. I n addition, increased or disturbed lymphatic drainage, as evidenced by ~he fairly frequent finding of dilated lymphatics in the intestinal wall and dilated active sinusoids in the mesenteric lymph nodes, would facilitate the diffusion or accumulation of gas. That the latter permeates lymphatic channels is well known. Not only were the mesenteric lymph nodes the seat of
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gas cysts in three of the six cases, but in one the cisterna chyli and thoracic duct were also involved. The presence of giant cells and fibroblastie proliferation about the gas cysts commonly reported in adults is evidence of chronicity, as indicated by the experimental injections of gas into subcutaneous tissues by Wright, 16 where such reactions about gas-filled spaces were noted only after several days. Giant cells were entirely absent in the present cases. There was little evidence of fibrosis, although there were occasional areas of mild inflammation. This would indicate that, in the early establishment of t h e emphysema, the reaction may be m i n i m a l and that here the disease process is quite recent. It is also of interest that in three eases there were evidences of i n j u r y to the liver. In Case 4, a nonobstruetive biliary cirrhosis was the chief anatomic finding. I t is conceivable that, with ulcers or inflammation of the intestinal tract, small amounts of gas" may enter the intestinal wall and rapidly be disposed of by diffusion and absorption. It is true that the condition is overlooked clinically, but there may be temporary symptoms suggesting appendicitis, peritonitis, or intestinal obstruction. It is known that following' laparotomy the gas cysts have disappeared spontaneously. Of recent years Bonnamour, Badolle, and Beaupere 1~ and Graberger is have stressed the possibility of the recognition of the disease by x-ray examination. CONCLUSIONS
Six eases are added to the four examples of intestinal pneumatosis in infancy and childhood reported in the literature. Five of these were observed over the period of approximately one year. It is believed that in the absence of ulcers or obstruction as commonly occur in the adult, enteritis and accompanying functional changes are probably important factors in the initiation and evolution of t h e disease. REFERENCES 1. B a n g : Nor& Med. Ark. 8: 18, 1876 i quoted by Nitch: ]3rit. J. Surg. 11: 714, 1924. 2. Turnure, P . R . : Ann. Surg. 57: 811, 1913. 3. Mills, It. W.: Surg. Gynec. & Obst. 40: 387, 1925. 4. Memmi, 1~.: Pollclinico (sez. chir.) 41: 408, 1934. 5. Silverstone, J . : Lancet 1: 129, 1928. 6. Lamont, D.: Tr. Roy. Med.-Chir. Sot. Glasgow 23: 113, 1928-29. 7. Sawada, ]3.: J. Orient. Med. 9: 66, 1928. 8. Moore, R . A . : Am. J. Dis. Child. 38: 818, 1929. 9. Tung, P. C., and Ngai, S . K . : Chinese M. J. 47: 1-14, 1933. 10. Pybus, F . C . : Brit. J. Surg. 21: 539, 1934. 11. Kemal, M.: Deutsche reed. Wchnschr. 59: 1707, 1933. 12. Nimet, ]3.: Zentralbl. f. Chit. 61: 1986, 3934. 13. BBsteh, O.: Arch. f. klin. Chir. 181: 707, 1935. 14. Englund, F., and Wahlgren, )~.: A c t a chir. Seandlnav. 76: 601, 1935. 15. Sehnyder, K.: Cor.-]31. f. schweiz. Aerzte. 47: 289, 1917; quoted by Mills. 16. Wright, A . W . : Am. J. Path. 6: 87, 1930. 17. ]3onnamour, Bado]le, and Beaupere: J. de. radiol, et d'electrol. 10: 164, 1926. 18. Graberger~ G.: Acta radiol. 16: 439, 1935.