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354 Arch Pathol Lab MedVol 123, April 1999 Pathologic Quiz Case David & Jakate

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Pathologic Quiz CaseOdile David, MD; Shriram Jakate, MD, MRCPath; Chicago, Ill

The patient is a 6-year-old girl with a prenatal historyremarkable for maternal gestational diabetes. The girlwas delivered at term by caesarean section secondary tofailure to progress. Birth weight was 8 lb 5 oz. The peri-natal period was uneventful. At 3 years of age the childwas diagnosed with insulin-dependent diabetes mellitus

and was started on neutral protamine Hagedorn insulin.One year later the child underwent repair of a previouslyundetected atrial septal defect. Recovery was uneventful.

Ten months later the patient presented with abdominalpain, bloody diarrhea, and one episode of emesis. She wasstarted on a course of prednisone without improvementof symptoms. She was admitted 1 week after presentationfor evaluation. Physical examination on admission was re-markable for hepatomegaly and vertical growth delay. Asmall bowel follow-through and x-ray examination of thelower pelvis (KUB) were unremarkable. There was no ev-idence of pneumoperitoneum. The bowel gas pattern wasunremarkable. During the course of hospitalization, en-doscopy and colonoscopy were performed. Gastric antral

and duodenal mucosae appeared unremarkable. Colonos-copy showed severe colitis continuous from mid-trans-verse colon to rectum with sparing of the proximal colon.Random colonic and rectal biopies were taken.

Despite treatment with prednisone and sulfasalazine,the colitis worsened. The patient required admission twicefor evaluation of rectal bleeding. Six months after the ini-tial evaluation, a second colonoscopy with biopsies wasperformed. Sulfasalazine was discontinued and the patientwas started on 6-mercaptopurine. Due to the poor re-sponse to treatment and the parents concern regardinglong-term effects of steroids, the patient underwent total

colectomy with ileoanal pull-through several months laterat 6 years of age.

The initial random biopsies of the colon and rectum allshowed similar histologic features: globally increased cel-lularity in the lamina propria with abundant lymphoplas-macytic and eosinophilic inltrates, disorganized crypts

showing mucodepletion and marked crypt-related inam-matory activity, focal mucosal ulceration and prominentlymphoid nodules, and inammatory atypia (Figure 1).The second set of colonic biopsies taken 6 months lateralso showed active colitis.

The colectomy specimen consisted of a 45-cm-long seg-ment of large bowel with 1.8 cm of ileum at the proximalend (Figure 2, a). The ileum and appendix were unre-markable. The serosal surface was tan-pink, smooth, andglistening. The cecal and ascending colonic mucosa overa distance of 11 cm from the proximal margin was thick-ened and edematous and had palpable crepitance. Sec-tioning revealed cystic spaces in the submucosa through-out this area (Figure 2, b). The transverse, descending, sig-

moid, and rectal mucosae were mildly erythematous withnormal-appearing mucosal folds.Histologically, the colon showed changes mainly on the

left side, where there was crypt disorganization, muco-depletion, and focal crypt-related inammatory activity.The right side was largely quiescent with prominent in-traepithelial lymphocytes. Over the proximal 11 cm fromthe cecum to hepatic exure, there was diffuse plaquelikethickening with edematous mucosa showing prominentsubmucosal air spaces surrounded by giant cell reaction(Figure 3).

What is your diagnosis?

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356 Arch Pathol Lab MedVol 123, April 1999 Pathologic Quiz Case David & Jakate

Pathologic Diagnosis:

Pneumatosis Intestinalis in a 6-Year-Old Girl WithUlcerative Colitis

CommentPneumatosis intestinalis (PI), also known as pneuma-

tosis cystoides intestinalis or pneumatosis coli, is denedas the presence of gas within the bowel wall. Its patho-

physiology and clinical relevance are poorly understood.Although there have been several reported cases of idio-pathic PI, most cases occur in association with underlyingor coexistent diseases. There have been several case re-ports of PI mimicking inammatory bowel disease. 13Pneumatosis intestinalis is classically found in the follow-ing clinical settings: premature infants with necrotizingenterocolitis, children with congenital heart defects, adultswith obstructive pulmonary disease, adults and childrenwith a wide variety of gastrointestinal pathology, connec-tive tissue diseases, transplant, and drug therapy, specif-ically steroids and immunosuppresive agents. 46 Pneu-matosis intestinalis has also been identied incidentallyon radiographs and endoscopic biopsies. 1,3,610 Very littlehas been published regarding the presence of PI in chil-dren beyond the neonatal period, when the risk of nec-rotizing enterocolitis is low and other disease processeshave yet to surface. 6,11 There have been no reported casesof PI in a child with true ulcerative colitis.

Histologically, pneumatosis intestinalis is characterized by empty cysts of varying sizes, usually lined by macro-phages that coalesce to form giant cells. 12 Early cysts may be lined by attened endothelial cells, which are thoughtto be lymphatic in orgin. 13

Both clinically and histologically, PI can be mistaken forinammatory bowel disease. 13 Mild architectural distor-tion of the overlying mucosa was seen in 11 of 13 and 10of 10 cases in 2 studies involving adult patients withoutinammatory bowel disease. 2,3 Also common is the ndingof granulomatous reaction and mutinucleated giant cellsin the vicinity of the cysts, leading in one case to a mis-taken diagnosis of granulomatous colitis. 1 Cryptitis andcrypt abscesses, crypt dilation, and partial crypt rupturewith formation of intramucosal cysts have also been re-ported in association with clusters of small gas cysts inthe lamina propria. 2

Several mechanisms have been proposed over timethroughout the literature to explain the development of PI,including mechanical, bacterial, nutritional, chemical, andneoplastic processes. A familial association has been sus-pected in 2 cases; however, the rarity of this association

has precluded further investigation.5

In the recent litera-ture, the mechanical and bacterial theories of pathogenesishave come to be most widely accepted. The mechanicaltheory postulates that compressed air within the intestinallumen penetrates the mucosa through microscopic or mac-roscopic breaks, dissects down along the mesentery, andreenters the intestinal lumen distally along small vascularand lymphatic channels. Similarly in patients with ob-structive pulmonary disease, air from ruptured alveolidissects retroperitoneally along blood vessels, entering themesentery and eventually nding its way into the intes-tinal lumen. 2,14

The bacterial theory proposes that gas-forming bacillienter the submucosa through breaks in the mucosa andproduce gas in the intestinal wall. However, repeated at-

tempts to culture organisms from the cysts have been un-successful. 5,12

Although the role of steroids in the development of PIis unclear, it has been postulated that lymphodepletion bysteroids creates functional defects in the mucosa, therebypermitting dissection of air into noninamed bowel. 4,6 Itis of note that most of the reported cases of PI associatedwith steroid use occurred in very sick children with a his-tory of autoimmune hemolytic anemia, leukemia, and im-munosuppression therapy following bone marrow or re-nal transplantation. It is difcult to separate the effects of treatment from the effects of underlying disease processin such patients, as it was in the case presented in thispaper.

The patients history of congenital heart defect prior tothe nding of PI is also not unprecedented in the litera-ture. West et al 6 reported 14 cases of PI in children be-tween the ages of 2 months and 8 years. Two of the pa-tients described had complicated cyanotic congenital heartdisease. One developed extensive intestinal necrosis re-quiring small bowel resection. The second was found in-cidentally to have PI and did not require treatment of anykind. A third infant with congenital heart disease devel-oped bloody diarrheal stool and bilious emesis. An ab-dominal radiograph showed intramural air. Stool culturewas positive for rotavirus. Conservative therapy, including broad spectrum antibiotics, uids, and nasogastric drain-age, resolved the symptoms. It has been postulated thatin patients with congenital heart disease, increased bloodviscosity, dehydration, and cardiac catheterization contrib-ute to the development of PI. 15

ConclusionThe authors of this paper believe that this patient had

clinically, endoscopically, and histologically proven ulcer-ative colitis and that the nding of pneumatosis coli wasentirely incidental and without relevance to the course of disease. The patient had multiple conditions associatedwith the presence of PI, namely, a history of congenitalheart defect and repair, steroid use, and mucosal disrup-tion secondary to ulcerative colitis. There have been infre-quent reports of inammatory disease associated with PI,4 in adults with Crohns disease and 2 in adults with se-vere ulcerative colitis and focally necrotic colon. 79 We con-cur with the majority of authors on the subject of pneu-matosis coli that this entity should be taken as a ndingrather than as a diagnosis, particularly in the context of the case presented in this paper.

References

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2. Pieterse AS, Leong AS-Y, Rowland R. The mucosal changes and pathogen-esis of pneumatosis cystoides intestinalis. Hum Pathol . 1985;16:683688.

3. Suarez V, Chesner IM, Price AB, Newman J. Pneumatosis cystoides intes-tinalis: histological mucosal changes mimicking inammatory bowel disease.Arch Pathol Lab Med . 1989;113:898901.

4. Borns PF, Johnston TA. Indolent pneumatosis of the bowel wall associatedwith immune suppressive therapy. Ann Radiol (Parish) . 1973;161166.

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tion of intramural colonic air (pneumatosis coli) as a feature of severe ulcerativecolitis. Gastrointest Radiol . 1987;12:169171.

10. Tobias R, Colman S, Helman CA. Pneumatosis colli stimulating hepato-megaly. Am J Gastroenterol . 1985;80:146149.

11. Mackenzie EP. Pneumatosis intestinalis: review of the literature with reportof 13 cases. Pediatrics . 1951;7:537549.

12. Lewin KJ, Riddell RH, Weinstein WM. Gastrointestinal pathology and itsclinical implications. New York, NY: Igaku-Shoin: 1992.

13. Habouri NY, Honan RP, Hasleton PS, et al. Pneumatosis coli: a case reportwith ultrastructural study. Histopathology . 1984;8:145155.

14. Galandiuk S, Fazio VW. Pneumatosis cystoides intestinalis; a review of theliterature. Dis Colon Rectum . 1986;29:358363.

15. Ghory MJ, Sheldon CA. Newborn surgical emergencies of the gastrointes-tinal tract. Surg Clin N Am . 1985;65:10831089.