Low-Grade Appendiceal Mucinous Neoplasm in an Adolescent Patient With Untreated Crohn's Disease

ABSTRACT

Appendiceal mucinous neoplasms are rarely diagnosed in pediatric patients. We present a 16-year-old adolescent boy with severe Crohn's disease who was not on maintenance medication for his underlying diagnosis. He was referred for nutritional optimization and small bowel obstruction. An emergent laparoscopic ileocecectomy with primary ileocolonic anastomosis was carried out secondary to acute peritonitis. Small bowel pathologic findings were consistent with Crohn's disease with low-grade appendiceal mucinous neoplasm (LAMN) of the appendix.

INTRODUCTION

Appendiceal mucinous neoplasms (AMNs) are rare tumors of the appendix, incidentally discovered in 0.2%–0.7% of all postappendectomy pathology specimens.^1–6 These neoplasms most often affect patients older than 60 years of age, with most pediatric epidemiological data arising from isolated case reports.^1–4 A review including over 3,600 pediatric patients who underwent appendectomy revealed tumors comprised fewer than 0.5% of specimens, none of these being mucinous.^1,7 Despite their rarity, AMNs carry highly variable clinical and prognostic implications for patients, ranging from benign mucinous adenomas to invasive adenocarcinoma with pseudomyxoma peritonei (PMP).^1–4 Low-grade AMNs (LAMNs) are in the middle of this spectrum, typically characterized as well-differentiated adenomas with malignant potential that may lead to low-grade PMP and frequent recurrences even after resection.^1–4

Historically, longstanding appendicular inflammation has been linked to intestinal dysplasia.^5–9 In adults, longstanding inflammatory bowel disease (IBD) has been associated with colorectal adenocarcinoma; however, even in this population, appendiceal tumors are rarely reported. We describe a pediatric patient with Crohn's disease who was incidentally diagnosed with LAMN after ileocecectomy secondary to severe (progressive or chronic inflammatory) colonic obstruction.

CASE REPORT

A 16-year-old adolescent boy presented with abdominal pain and distention for 4 days before admission. Associated symptoms included unintentional 25-lb weight loss and nausea over the previous 3 months. His medical history was significant for 2 lengthy admissions because of partial small bowel obstruction attributed to the narrowing of the distal segment of the terminal ileum. Although the diagnosis was never confirmed histologically, he received a dose of infliximab 5 mg/kg between hospitalizations for suspected IBD.

On arrival to the emergency department, the patient was afebrile and hemodynamically stable. Physical examination revealed a thin, cachectic appearing man with mild right lower quadrant tenderness and absent signs of acute obstruction. Laboratory results revealed normal inflammatory markers, which could be explained by his recent course of oral steroids and the absence of electrolyte derangements. He was admitted to evaluate for suspected IBD and optimization of nutrition because his body mass index and weight had acutely dropped to less than 5% for his age.

The patient was given a bowel preparation regimen in anticipation of endoscopy and colonoscopy. An unprepped colonoscopy was not attempted. The patient subsequently developed abdominal distension, rebound tenderness, severe diffuse abdominal pain in all quadrants, and several episodes of bilious emesis. A decompressive nasogastric tube was placed with minimal relief of symptoms. Abdominal and pelvic computed tomography was performed, revealing markedly dilated bowel loops with a new transition point at the thickened terminal ileum concerning for an acute obstruction. Some free fluid in the pelvis was noted, but there was no pneumoperitoneum or perforation. Despite continued nasogastric tube decompression and the addition of broad-spectrum antibiotics, his physical examination was consistent with acute peritonitis. No infliximab or steroids were given during the admission. Laboratory results showed leukocytosis (15.6×10⁹/L), and his vital signs were concerning for hypothermia. He was taken to the operating room for an emergency laparoscopic ileocecectomy with primary ileocolonic anastomosis. Intraoperatively significant ileitis associated with a 10-cm obstructing terminal ileal stricture and transmural inflammation was grossly observed. There was slight inflammation of the appendix with no appendiceal rupture on extraction, small amounts of free fluid in the pelvis, and no signs of perforation (Figure 1). No intraoperative complications were experienced, and the postoperative course was uneventful.

Figure 1.

Macroscopic view of ileocecal valve and small bowel with adjacent inflamed-appearing appendix.

Pathology findings included cryptitis, crypt abscesses, and epithelialitis in the small bowel changes suggestive of Crohn's disease (Figure 2). Grossly, the appendix was partially dilated and filled with mucin. Microscopic sections of the dilated portion of the appendix showed a lumen filled with mucin that dissected through to the subserosa, with mostly attenuated epithelium with foci of low-grade nuclear atypia. These findings were diagnostic of LAMN (Figure 3). Immunohistochemical stain for CD68 highlighted a few giant cells and scattered histiocytes. Serum biomarkers were normal, CA 125 was 28 U/mL, and CA 19-9 was 11.6 U/mL. Six resected lymph nodes revealed the absence of malignancy, and no extra-appendiceal mucin noted.

Figure 2.

Appendix with crypt abscess.

Figure 3.

Appendix with low-grade appendiceal mucinous neoplasm.

DISCUSSION

Most patients with LAMN are asymptomatic on diagnosis, with right lower quadrant pain being most commonly reported but seen in fewer than 25% percent of affected individuals.¹⁰ LAMN is usually diagnosed incidentally with imaging studies or during surgical interventions for resection of extra-appendiceal tumors.^5,11 Wong et al noted that visualization of a bulging appendiceal orifice during colonoscopy may also be suggestive of the diagnosis.⁵

On an extensive literature review, our group was unable to find any report of concomitant IBD and LAMN in a pediatric patient. However, we discovered a substantial amount of literature regarding appendiceal carcinoids in pediatric and adult patients with IBD.⁵ Previous studies have reported that patients with IBD have increased risk of developing colorectal carcinoma approximately one decade after disease onset, with appendiceal inflammation encountered in up to 86% of colectomy specimens, but appendiceal neoplasms rarely diagnosed.^12,13 Crohn's related inflammation in the appendix is reported in 40%–52% of colectomy specimens. This in addition to disease onset and duration, genotype, and treatment response may play a role in malignancy.¹³

Historically, poor prognostic factors for LAMN include the presence of symptoms at diagnosis, intestinal perforation, and type of surgical technique, open exploratory surgery vs laparoscopic (worse outcomes being described with the first). Another consideration is if the tissue has negative histological margins, which are associated with a decreased likelihood of recurrence, as was the case for our patient.⁵

Best management strategies, as well as time to treatment, are unclear because of the rarity of LAMN.¹⁰ Previous literature reports appendectomy being curative for benign and intact mucinous neoplasms.¹¹ Other studies suggest ileocecectomy or hemicolectomy in patients with unclear margins, some recommending the latter only in the presence of ileocecal valve injury or protruding neoplasm into the cecal lumen. However, there is no standard protocol.^10,11 Because our patient had undergone an ileocecectomy, our strategy included abdominal magnetic resonance imaging every 3 months for the first year and simultaneously monitoring of serological markers, ie, CEA, CA 19-9, and CA 125. In this specific case, we measured markers on pathological diagnosis, finding all of them to be within the reference range for the patient's age. However, other studies have recommended less rigorous pathways with annual imaging and serological monitoring. Our patient has not had a recurrence and is currently only undergoing medical treatment for his IBD.¹⁰ However, there is a risk of PMP syndrome, a disease characterized by deposition of mucin on visceral and parietal peritoneum, which is associated with death 10 years after diagnosis. As a result, a multidisciplinary team should be involved in the care of any affected patient with LAMN.^10,11,14

DISCLOSURES

Author contributions: All authors contributed equally to this manuscript. S. Hernandez Benabe is the article guarantor.

Financial disclosure: None to report.

Informed consent was obtained from the patient's next of kin for this case report.