Neurofibromatosis Type I Presenting with Incomplete Ileal Volvulus in a Pediatric Patient

Background

Neurofibromatosis type I (NF1) is a well-documented neurocutaneous disorder with protean manifestations. It is well known that this disease is caused by mutation of the gene responsible for neurofibromin, an important cell-signaling and growth-regulating protein coded within the long arm of chromosome 17 [1]. Mutations of the NF1 gene result in altered signal transduction within the Ras oncogene pathway, and the resulting decreased negative regulation results in increased cell proliferation [2].

Classically, the clinical manifestations of NF1 include benign soft-tissue tumors of the skin (neurofibromas) as well as multiple neurocutaneous manifestations such as café au lait spots and Lisch nodules. However, manifestations are multisystemic. Within the central nervous system, findings may include white matter/basal ganglia focal areas of increased signal intensity (FASI) as well as a propensity for central nervous system malignancies, notably CNS astrocytomas. Musculoskeletal findings may include decreased muscle mass and muscle work capacity/performance as well as malformations of skeletal structures.

In some instances, atypical presentations of NF1 may be the trigger to identify and diagnose this condition in patients in whom the diagnosis has been delayed. In this case, we present a juvenile patient with a previously unknown diagnosis of NF1 presenting to the emergency room with incomplete ileal volvulus. An imaging diagnosis of volvulus secondary to a mesenteric neurofibroma was made with subsequent histopathological confirmation. To the best of our knowledge, only 3 cases of mesenteric neurofibroma secondary to NF1 have been reported in the literature, of which 2 cases demonstrated mesenteric involvement by a plexiform neurofibroma [3–5]. This is the second case reported in the literature where a mesenteric plexiform neurofibroma resulted in volvulization of the intestine [6]. Our case elegantly demonstrates the adage in medicine that proper history taking and physical exam results in a more certain diagnosis. Furthermore, this case highlights that in patients with presumed or known diagnosis of NF1 presenting with abdominal pain, mesenteric neurofibromatosis should be considered in the differential diagnosis as a potential complication of this multisystemic disorder.

Case Report

Our case details a 15-year-old white Hispanic male whose main clinical concern was long-standing, persistent, nonspecific abdominal pain, whose prior medical history was significant for gastritis, gastroesophageal reflux (GER), attention deficit hyperactivity disorder, and learning disabilities.

Initially, the patient was taken from school to the nearest emergency room due to acute onset of periumbilical pain of 7/10 intensity associated with nausea. The patient had an unremarkable physical examination and laboratory test results and was discharged home with subjectively decreased pain. The patient continued to have intermittent bouts of abdominal pain for the following days, unrelieved by bed rest.

Seven days prior to admission, the patient was taken again to the emergency room. Routine laboratory tests and X-rays were once again unremarkable. However, the patient’s persistent pain prompted transfer to our institution. An abdominal sonogram was performed and was unremarkable. Soon after, the patient was discharged home with a diagnosis of gastritis.

The patient continued to have abdominal pain for the following week with loss of appetite and poor oral intake while remaining afebrile. Two days prior to admission, the patient’s abdominal pain worsened and he was taken to another medical institution, where laboratory test results were normal and X-rays failed to reveal any abnormal findings. A CT scan of the abdomen and pelvis was performed and was remarkable at that time for “edema of the small bowel,” “multiple nodes,” and a “twisting of the mesenteric layer” but otherwise without obstruction. At this point, he was transferred to our institution.

Further history taking yielded significant findings of prior admission to our institution for GER and poor weight gain, as well as a brain tumor in a 14-year-old maternal cousin diagnosed at 2 years of age.

On physical exam, the patient had normal vital signs and was in the 11th and 3rd percentile for height and weight, respectively. Multiple café au lait spots were noted, the largest on his right upper arm (Figure 1).

Examination of the abdomen revealed hyperactive bowel sounds and right lower-quadrant tenderness to palpation, with an otherwise soft and depressible abdomen.

The patient was admitted to our institution for pain management and further workup of abdominal pain. He was consulted to our Radiology Department, where review of history and prior imaging was performed. It was determined that the patient needed a follow-up abdominal and pelvic CT scan, in light of findings on prior imaging, to assess interval changes and/or resolution.

CT scans performed at our institution demonstrated a persistent swirling of the mesentery at the right lower quadrant (Figure 2A) and additional findings pointed to a low-grade partial small-bowel obstruction. Furthermore, a confluent, nodular soft-tissue density mass was seen throughout the mesentery with a perivascular distribution and showing extensive confluence, particularly at the most distal portions of the mesentery (Figure 2B). Finally, thickening of the lumbosacral nerve roots was noted (Figure 2C, 2D), and a prospective diagnosis of type I neurofibromatosis with mesenteric and lumbosacral manifestations was made; specifically, mesenteric neurofibromatosis.

The patient was taken to the operating room for an exploratory laparotomy, and intraoperative findings revealed a confluent, dense nodular mass diffusely scattered throughout the distal mesentery and extending to the mesenteric root (Figure 3A), with twisting of a portion of the distal small bowel, compatible with imaging findings. Manual untwisting of the bowel was then performed. The untwisted portion of the distal small bowel showed thickened, edematous walls and a dilated lumen along an amotile bowel segment. In addition to this affected small bowel segment, there was additional infiltrative involvement of a significant portion of the remaining mesentery and small bowel. Separating the mass from the mesentery was determined impossible without significantly risking the associated mesentery and bowel. It was also determined that the extent of the mass throughout the mesentery made it prohibitive to excise as a whole due to the amount of viable bowel that would necessarily be resected. It was thus determined that partial tumor debulking via partial resection of the affected, symptomatic bowel would be performed, and 36 cm of small bowel, associated mesentery, and mass were removed (Figure 3B). Primary small bowel anastomosis was then performed with subsequent conclusion of surgical procedure.

Surgical gross pathologic inspection of the mesenteric mass disclosed diffuse infiltration of the mesentery by a nodular mass with macroscopic appearance reminiscent of a “bag of worms.” Microscopic evaluation demonstrated a myxoid matrix, containing a network of bundles of Schwann cells with hyperchromatic nuclei, impinging upon and distorting the adjacent intestinal microarchitecture, consistent with a plexiform neurofibroma (Figure 4).

Our patient recovered adequately without complications within the next few days and was discharged home 5 days after his exploratory laparotomy. Eight months after the procedure, the patient denied recurrence of symptoms.

Discussion

NF1 is a multisystemic disease of variable penetrance. As such, it remains a clinical challenge to accurately predict the true extent of disease.

Patients such as ours presenting without the diagnosis of NF1 and with limited cutaneous stigmata are particularly challenging because prospective diagnosis complications of the disease necessitate prior diagnosis of the disease causing the complications. Our patient presented a particular scenario in which relevant clinical information was sought by and made available to our interpreting radiologists and, coupled with imaging findings, allowed our team to not only provide a prospective diagnosis of NF1, but also one of its uncommon complications, mainly incomplete volvulus with resulting low-grade partial small bowel obstruction. As such, we propose that in patients with known, recent, or presumptive diagnosis of NF1 presenting with acute or chronic abdominal pain, the clinician should consider the diagnosis of a MPN, including, and not limited to, obstructive etiology that may include a secondary volvulus of the small intestine.

Although the differential diagnosis for small-bowel obstruction is extensive, CT findings can help narrow down the list. Our patient presented with an extensive, nodular soft-tissue density mass throughout the mesentery. Fukuya et al suggested that these soft-tissue density nodularities actually represent cross-sectional images of enlarged peripheral nerves. Because these nerves tend to form an interconnecting network, they trap normal peripheral fat among their entangled network. These findings are absent in other retroperitoneal and mesenteric masses [3].

Surgical resection is the preferred treatment for MPNs [7]. As our case demonstrates, MPNs are prone to mechanical complications; these include ulceration and bleeding, obstruction, intussusception, and volvulus, manifestations that increase the risk of subsequent perforation [4]. Mesenteric vessel encasement may also predispose to vascular and lymphatic obstruction, impaired gastrointestinal absorption and systemic manifestations such as failure to thrive in pediatric patients [5]. Furthermore, transformation of plexiform neurofibromas (PNs) into malignant peripheral nerve-sheath tumor (MPNST) is a well-established complication contributing to significant mortality in this patient population [8]. There are no characteristic clinical, laboratory, or imaging findings that distinguish PNs from other MPNSTs. Rather, distinction is solely based on pathologic examination of the specimen, in which benign PNs are diffusely positive for S-100 protein, whereas MPNSTs are negative or focally positive [9]. However, imaging findings that may suggest malignant transformation include sudden enlargement of a previously stable mass, marked inhomogeneities in MR signal intensity, infiltrative margins, and irregular bone destruction [10]. Therefore, in anticipation of these complications and malignant transformation, prophylactic surgical removal should be considered in asymptomatic NF1 patients with incidental findings that suggest MPNs on imaging.

Our case also highlights an important clinical aspect regarding the clinical history, progression, and eventual treatment of patients with MPNs. Slow, insidious tumor growth results in periods of asymptomatic clinical status, eventually followed by nonspecific signs and symptoms such as vague abdominal pain. As such, the resulting delay in diagnosis contribute to tumor growth with extensive internal organ involvement, and surgical options may be limited to partial resection and/or debulking in cases where surgery is still a viable treatment option. In our patient, complete resection was limited not only by the infiltrative nature of the tumor (preventing separation of tumor from bowel and mesentery), but also by the amount of bowel that could be resected without compromising digestive function due to a shortened digestive and absorptive surface area.

Several different atypical gastrointestinal presentations of NF1 have been previously reported on literature. Our literature review included querying the PubMed archive with combinations of the keywords “Neurofibromatosis Type I,” “pediatric,” “volvulus,” “mesenteric,” and “plexiform;” combining all these terms returned zero (0) results. Nonetheless, refining our search by omitting 1 or more of the above keywords, we found that our case is the second in which a plexiform mesenteric neurofibroma presented as a small-bowel volvulus [6]. Given that our case report is the second instance in the literature in which mesenteric neurofibromatosis resulted in intestinal volvulization, this suggests that although rare, intestinal volvulus from disease burden is a distinct clinical complication of NF1 [10].

Furthermore, in contrast to other case reports, the etiologic source of the volvulus identified on imaging, and thereafter confirmed on pathologic examination of the specimen, enabled a retrospective diagnosis of NF1. It was only after radiologic diagnosis and confirmatory pathology that physical examination findings of classical skin manifestations of NF1 were retrospectively recognized, since the clinicians performing the physical examination at time of admission visualized and documented the patient’s café au lait spot, yet (understandably) failed to diagnose the patient with NF1 based on this single, isolated cutaneous finding.

Conclusions

This case report presented a unique and uncommon initial presentation of NF1, specifically that of a partial small-bowel obstruction resulting from an incomplete ileal volvulus secondary to an underlying plexiform neurofibroma. We stress the importance of accurate, relevant history taking and physical examination in providing an accurate diagnosis. Finally, we propose that in patients presenting with a history of NF1 (or presumptive diagnosis of NF1) and with acute or chronic abdominal concerns, the diagnosis of mesenteric neurofibromatosis should be considered early, not only for treatment of the patient’s symptoms, but also to anticipate potentially morbid and/or fatal sequelae that at the time of this publication remain incompletely characterized in the literature.