Multilocus Heterotopic Gastric Mucosa
of Ileum Masquerading as VEOIBD in
a Newborn
Livia Lindoso, MD,aCortney R. Ballengee, MD,aKiran P. Patel, MD,b,cRene Romero, MD,a,cShelley Caltharp, MD,c,d Adina L. Alazraki, MD,c,eSubra Kugathasan, MDa,c
abstract
Heterotopic gastric mucosa (HGM) is defined as the presence of gastric mucosa outside of the stomach, which is documented by histologicfinding. HGM is typically a solitary lesion; however, in our Case Report, the patient presented with multilocus HGM, an uncommon form in which the small bowel is extensively involved. We report a unique case of multilocus HGM mimicking very early–onset inflammatory bowel disease with recurrent gastrointestinal bleeding, chronic inflammation, and stricturing in a newborn patient. Histologicfindings from the ileocecal specimen revealed multiple ulcers surrounded by chronic inflammation. Subsequently, a Technetium-99m pertechnetate scan demonstrated an increased tracer uptake in the remaining ileum. This radiologicfinding, in combination with the discovery of gastric mucosa within the remainder of resected ileal specimen, led to the diagnosis of HGM. Omeprazole was initiated, and the patient is now asymptomatic without further gastrointestinal bleeding. Increased awareness of this rare disease and performing a Technetium-99m pertechnetate early can correctly diagnose HGM and prevent disease complication.
Heterotopic gastric mucosa (HGM) is the presence of gastric mucosa outside of the stomach documented by histologic
findings. Literature suggests that HGM can occur throughout various locations in the body, including the esophagus, duodenum, ileum, rectum, gallbladder, and (rarely) outside the gastrointestinal tract in the mediastinum, scrotum, urinary bladder, airways, and spinal cord.1The origin of HGM can be congenital or acquired during the progress of repair of damaged mucosa, although it is typically confined to 1 area.2,3 It commonly occurs in conjunction with other congenital malformations, including Meckel diverticulum and gastrointestinal tract duplication. The clinical presentation of HGM may vary depending on size and location but typically includes abdominal pain, bleeding, perforation, ulceration, and intussusception.
We report a unique case of multilocus HGM mimicking very early–onset inflammatory bowel disease (VEOIBD) in a newborn with recurrent
gastrointestinal bleeding, chronic gut inflammation, and stricturing. This Case Report is a reminder to clinicians to consider HGM in the differential diagnosis of rectal bleeding in newborns. An early Technetium-99m nuclear scan would have led to afirm diagnosis of HGM and avoided the costly workup for VEOIBD and possibly shortened the length of total parenteral nutrition (TPN) in our case.
CASE PRESENTATION
A premature boy born at 33 weeks’ gestation presented with hematochezia, diarrhea, anemia, severe
hypoalbuminemia, and partial bowel
Divisions ofaGastroenterology andbAllergy and Immunology, Departments of Pediatrics,dPathology and Laboratory Medicine, andeRadiology and Imaging Science, School of Medicine, Emory University, Atlanta, Georgia; and cChildren’s Healthcare of Atlanta, Atlanta, Georgia
Dr Lindoso reviewed the patient chart and drafted the initial manuscript; Dr Caltharp did the histological analysis of the specimens and revised the manuscript; Dr Alazraki did the analysis of the magnetic resonance enterography and Technetium-99m nuclear scan and revised the manuscript; Drs Ballengee, Patel, Romero, and Kugathasan critically revised the draft and initial manuscript; and all authors approved thefinal manuscript as submitted.
DOI:https://doi.org/10.1542/peds.2018-2398 Accepted for publication Jan 11, 2019
Address correspondence to Subra Kugathasan, MD, Division of Pediatric Gastroenterology, Department of Pediatrics, Emory University School of Medicine, 1760 Haygood Dr, W427, Atlanta, GA 30322. E-mail: [email protected]
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).
Copyright © 2019 by the American Academy of Pediatrics
FINANCIAL DISCLOSURE:The authors have indicated they have nofinancial relationships relevant to this article to disclose.
FUNDING:No external funding.
POTENTIAL CONFLICT OF INTEREST:The authors have indicated they have no potential conflicts of interest to disclose.
obstruction during thefirst week of life. He was initially presumed to have necrotizing enterocolitis and therefore treated with bowel rest and antibiotics. Recovery was slow, and the patient continued to show partial bowel obstruction despite antibiotic treatment. Ultimately, he required prolonged TPN because of the extended period of bowel rest. An exploratory laparotomy was
performed at 4 weeks of age because of the continued rectal bleeding and bowel obstruction. The surgical specimen revealed severe thickening of the ileum as well as a stricture. The patient consequently underwent ileocecal resection with ileostomy and colonic mucousfistula. Histology revealed chronic organizing and perforating ulcerations surrounded by chronic inflammation. Despite the resection, the patient continued to have an ileal obstruction and underwent repeat ileal segmental resection secondary to recurrent stricture 7 weeks after the initialfirst procedure. Interestingly, the
pathology report from the specimen revealed crypt abscesses and ulceration (Fig 1), which was consistent with VEOIBD. A colonoscopy was performed and revealed macroscopic chronic inflammation of the ileum. A
commercially available targeted gene panel (MM160 Inflammatory Bowel Disease: Sequencing Panel; EGL Genetics, Tucker, GA), which sequences 26 genes known to be
associated with VEOIBD (including IL10RandTTC7a) did not reveal any known pathogenic variants.
Furthermore, an extensive workup for immunodeficiency and infection (including dihydrorhodamine, X-linked inhibitor of apoptosis protein, T-regulatory panel,
antienterocyte antibody, lymphocyte enumeration panel, serum
immunoglobulins, and
cytomegalovirus polymerase chain reaction in blood and urine) was unremarkable. The patient’s clinical course lacked symptoms suggestive of systemic inflammation, multiorgan autoimmunity, recurrent or severe infection, or perianalfistulas, any of which would be consistent with VEOIBD. The patient failed multiple medical therapies, including
corticosteroids and azathioprine, and continued to have intermittent rectal bleeding, poor enteral tolerance, and poor growth. The patient continued to be dependent on TPN at 18 months of age because enteral nutrition advancement was repeatedly delayed by intermittent small-bowel
obstruction.
A magnetic resonance enterography (MRE) was performed and revealed yet another ileal stricture (Fig 2). The patient underwent a third ileal segmental resection given the MRI results and symptoms of bowel obstruction. During this operation, scattered HGM was noted throughout the affected segment of ileum, which
had not previously been observed in the previous 2 resections (Fig 3). Although the patient had 2 previous ileal resections and several
colonoscopies with biopsies, this was thefirst time HGM was found. The patient subsequently underwent a Technetium-99m nuclear scan, which confirmed the presence of multilocus gastric mucosa in the remaining ileal loops, which was evident by the increased tracer uptake (Fig 4). Because of the presence of multilocus HGM, the patient was initiated on high-dose proton-pump inhibitor (PPI) therapy (omeprazole, 20 mg twice per day), and eventually, he was advanced to full enteral nutrition without further need for TPN by the age of 24 months. Because of the significant ileal loss and the risk for vitamin B12 deficiency and bile salt–induced diarrhea, the patient was started on regular vitamin B12injections and cholestyramine. The patient has been doing well with improved growth (height 10th percentile; weight 25th percentile) while on omeprazole with no signs of gastrointestinal bleeding at the age of 30 months.
DISCUSSION
The most common causes of lower gastrointestinal bleeding in the neonatal and infantile period are Meckel diverticulum, polyps, clotting disorders, arteriovenousfistulas, and (uncommonly) VEOIBD.3,4Although
FIGURE 1
Crypt abscesses and ulceration. A, Stricture with circumferential mucosal ulceration (arrows) with focalfissuring ulceration (rectangular) to the muscularis propria. No residual crypts are seen. B, Adjacent acute cryptitis (arrows). C, Crypt abscesses.
rare, HGM should be considered a differential diagnosis for recurrent gastrointestinal bleeding in pediatric populations.3,5Interestingly,
incidentalfindings of asymptomatic HGM in the small bowel occur in
∼0.5% of patients who undergo endoscopy, with boys tending to be slightly more affected than girls.6
Thefirst reported case report of HGM in the small bowel was published in 1912.7Approximately 30 additional reports were published by 1990.8In those cases, the most common presentation was intestinal intussusception, followed by
perforation and intestinal bleeding. Unlike our case, none of the patients in these reported cases presented with multilocus HGM or received PPIs. Eight additional pediatric reports, revealing HGM in the small bowel, were published in the past decade.3,9–16Similar to in our case, in 3 of the 8 cases, Technetium-99m pertechnetate scintigraphy was used to confirm the diagnosis.3,9,10In only 1 case was a patient presented with multilocus HMG and needed 2 jejunum resections and PPI to achieve symptoms relief.9
HGM is most commonly reported to be localized in the esophagus and Meckel diverticulum. It rarely occurs in the ileum without a Meckel diverticulum, as in our case. In addition, HGM may appear polypoidal, nodular, orflat under endoscopic visualization. HGM is usually focal; however, long-segment or multifocal areas have rarely been reported.9,17–21Despite HGM being a rare differential diagnosis, our report reveals that it should be considered when other causes of recurrent lower gastrointestinal bleeding seem unlikely.
The gold standard for diagnosing HGM isfinding the presence of gastric
mucosa outside of the stomach confirmed by histology (Fig 3). These histologicfindings can be divided into type I, consisting of gastric glands and foveolar epithelium, and type II, consisting of only foveolar epithelium.22Type I is thought to have a congenital origin, whereas type II may have originated from metaplastic processes.22Other histologicfindings associated with HGM are foveolar hyperplasia and mild lymphocytic infiltration.22In our case, the patient presented with type I, which according to the literature is the most common histologic
presentation.
Radiologicfindings of HGM are not classic or diagnostic; hence, Technetium-99m pertechnetate scintigraphy is considered to be the diagnostic procedure of choice when HGM is suspected. However, several challenges emerge in the application of the Technetium-99m pertechnetate scintigraphy procedure, mostly pertaining to its low sensitivity and specificity.5For instance, Technetium-99m is taken up by the mucin-producing cells of the gastric mucosa and secreted into the lumen of the intestine. Normal distribution of the tracer includes uptake in the heart, lungs, and thyroid and salivary glands, although these are not usually in thefield of view. It is also seen in vascular organs during uptake and excreted by the urinary tract. However, this radiotracer may be detected outside of the stomach and urinary tract because of anomalies such as bleeding into abdominal or gluteal hematomas, varices, aortic aneurysms, hemangiomas, and active inflammation.
The primary treatment option for extensive HGM is surgical resection of the diseased tissue21; therefore, Technetium-99m pertechnetate scintigraphy plays an important role in characterizing the extent and location of enteric involvement to aid with local staging and surgical planning.21MRE can be useful in FIGURE 2
T2 fat-suppressed coronal image from MRE revealing abnormal wall thickening (arrows) of a distal ileal loop with an upstream ileal stric-ture (arrowheads).
FIGURE 3
Type I gastric heterotopia. Mature gastric cosa completely replaces normal enteric mu-cosa with surface foveolar epithelial lining (arrows) and fundic glands containing chief and parietal cells (asterisk).
FIGURE 4
providing a detailed anatomic assessment; however, it cannot identify the etiology like the
Technetium-99m pertechnetate scan. If residual HGM is present after surgical resection of the most affected tissue, the use of a PPI is
recommended, which provides relief by reducing the acid-secreting capacity of the HGM.23
CONCLUSIONS
Our report demonstrates an unusual case of congenital multilocus HGM of the ileum mimicking VEOIBD in a newborn. HGM should be suspected when symptoms and histologic
findings from resected specimens and biopsies do not correlate. Increased awareness of HGM as a differential diagnosis is vital in newborns presenting with lower
gastrointestinal bleeding. In our case, performing a nuclear scan earlier may have prevented an exhaustive and expensive workup and multiple exploratory surgeries and resections. A nuclear scan may lead physicians to the correct diagnosis of HGM.
ABBREVIATIONS
HGM: heterotopic gastric mucosa MRE: magnetic resonance
enterography PPI: proton-pump inhibitor TPN: total parenteral nutrition VEOIBD: very early–onset
inflammatory bowel disease
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DOI: 10.1542/peds.2018-2398 originally published online March 21, 2019;
2019;143;
Pediatrics
Adina L. Alazraki and Subra Kugathasan
Livia Lindoso, Cortney R. Ballengee, Kiran P. Patel, Rene Romero, Shelley Caltharp,
Newborn
Multilocus Heterotopic Gastric Mucosa of Ileum Masquerading as VEOIBD in a
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DOI: 10.1542/peds.2018-2398 originally published online March 21, 2019;
2019;143;
Pediatrics
Adina L. Alazraki and Subra Kugathasan
Livia Lindoso, Cortney R. Ballengee, Kiran P. Patel, Rene Romero, Shelley Caltharp,
Newborn
Multilocus Heterotopic Gastric Mucosa of Ileum Masquerading as VEOIBD in a
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