Appendiceal neurofibroma and diverticula in a neurofibromatosis type 1 patient with chronic right lower quadrant pain
- 1 Abdominal Surgery, Zuyderland Medical Centre, Heerlen, Limburg, The Netherlands
- 2 Pathology, Zuyderland Medical Centre, Heerlen, Limburg, The Netherlands
- 3 Abdominal Surgery, University Hospitals Leuven, Leuven, Flanders, Belgium
- Correspondence to Dr Sébastien Strypstein; strypstein.md@gmail.com
Abstract
Neurofibromatosis type 1 (NF1, Von Recklinghausen disease) is an autosomal dominant disease with a birth incidence of 1/2500–3000. The most common presentations of NF1 are cutaneous presentations like café-au-lait spots and neurofibromas. 5%–25% of patients with NF1 have gastrointestinal manifestations of the disease. Appendiceal neurofibroma are extremely rare and only a few cases are described in literature. An appendectomy is indicated because of high risk of appendicitis and malignant transformation. We report the case of a 74-year-old male patient with a history of NF1 with chronic right lower quadrant pain. Successive imaging scans showed suspicion of chronic appendicitis. A diagnostic laparoscopy, resulting in a laparoscopic appendectomy was performed without complications. Histopathology showed appendiceal neurofibroma and diverticula. The postoperative course was uneventful. In patients with NF1 with right lower quadrant pain benign appendiceal neurofibroma should be included in the differential diagnosis. A diagnostic laparoscopy should be performed followed by an appendectomy.
Background
Neurofibromatosis type 1 (NF1) is an autosomal dominant hereditary disease with an incidence of 1/2500–3000 births.1–3 The most common presentations are cutaneous presentations like café-au-lait spots and neurofibromas.4 Five to twenty-five per cent of patients with NF1 have gastrointestinal manifestations of the disease of whom 5% are symptomatic.2–4 Eleven per cent of patients with NF1 have neurofibromas in the gastrointestinal tract.5 However, neurofibromas of the appendix are extremely rare and only a few cases are described in literature.1 4 6 Below we present such a case, review the sparsely available literature and make a recommendation for treatment.
Case presentation
A 74-year-old male patient presented to the emergency department with right lower quadrant pain and nausea since 5 days. His medical history included NF1, hypercholesterolemia and bilateral cataract surgery. Physical examination revealed multiple cutaneous neurofibromas and tenderness in the right lower quadrant of the abdomen. The patient had normal vital signs. Laboratory results showed an elevated C-reactive protein of 266 mg/L and white blood cell count of 13.1×109/L. He was admitted and a contrast-enhanced CT was performed. The CT-scan demonstrated a wall thickening of the terminal ileum and cecum as well as the appendix. The most likely diagnosis at that moment was a bacterial/viral enteritis or inflammatory bowel disease. An appendicitis, underlying gastrointestinal stromal tumour or other malignancy also were included in the differential diagnosis. Because of the most likely diagnoses not requiring direct surgery, the longer duration of his complaints and the reassuring clinical situation a conservative treatment with painkillers, anti-emetics and intravenous antibiotics (ceftriaxone/metronidazole) was started. In the following 2 days, the inflammatory parameters decreased, the patient recovered and was discharged with oral antibiotics for a total of 10 days.
Investigations
One month after discharge an MRI scan was performed because of higher prevalence of gastrointestinal tumours in patients with NF1. The MRI showed thickening of the wall of the terminal ileum and a distended appendix with characteristics of chronic appendicitis. Underlying malignancy could not be excluded. An ileocolonoscopy did not show any abnormalities in the whole colon; however, intubation of the terminal ileum was not possible. The case was discussed at our multidisciplinary team meeting. Because of the normal colonoscopy and normal inflammatory parameters in a mildly symptomatic patient, a wait-and-see policy was adopted with follow-up imaging 2 months later. The follow-up CT scan showed a normalised terminal ileum and decreased wall thickening of the retrocecal appendix with low suspicion of malignancy.
Treatment
Due to persisting discomfort in the right lower quadrant, the decision was made to perform an elective diagnostic laparoscopy and appendectomy. Peroperatively the appendix had a retrocecal position. There were no signs of appendicitis but an appendix with multiple lumps was identified (figure 1). The operation was performed without any complications.
Intraoperative findings (left: laparoscopy and right: appendix specimen).
Outcome and follow-up
The postoperative course was unremarkable and the patient was discharged at the day of surgery. At his 2 weeks follow-up, he had complete resolution of his symptoms.
Histopathological analysis of the appendix showed an increase of spindle-shaped cells in the lamina propria and submucosa suggestive of neurofibroma, coexisting with multiple diverticula. No inflammatory signs were observed. Immunohistochemical examination showed positive staining for S100 (figure 2). So the patient was diagnosed with appendiceal diverticula and neurofibroma.
Microscopic image: immunohistochemical stain for S100.
Discussion
The incidence of gastrointestinal manifestations in NF1 varies between 5% and 25% according to the literature.2–4 Different types of gastrointestinal tumours related to NF1 are described like gastrointestinal stromal tumours, neuroendocrine tumours and neurofibroma of which the latter are the most frequent.7 8
Gastrointestinal involvement is mostly asymptomatic. In 5% of the patients, lesions that grow larger over time can cause pain, obstruction, gastrointestinal bleeding and/or perforation.8 An early diagnosis of gastrointestinal manifestations is necessary to prevent serious complications because of an obstructive tumour mass or malignant transformation.1 4 Patients with NF1 have an overall 8%–12% lifetime risk of malignancy.4
Appendiceal neurofibromatosis is an extremely rare entity. To the best of our knowledge only 10 cases are previously described in the English literature.1 4 6 Most of these patients presented with abdominal pain and in all cases a surgical resection (appendectomy or right haemicolectomy) was performed. At histopathological examination the diagnosis of appendiceal neurofibromatosis was made. Surgical resection should be the standard treatment for patients with appendiceal neurofibroma to prevent complications and avoid malignant transformation. The most appropriate surgical procedure remains controversial.4 To our opinion an appendectomy should be enough in appendiceal neurofibroma but in case of malignant transformation an oncologic right haemicolectomy should be performed.
Diverticular disease of the appendix is uncommon but more frequent than appendiceal neurofibroma with reported prevalences in literature up to 4.8%.9 Based on the number of appendiceal layers herniating through the wall, the differentiation is made between a congenital and acquired form.10 Appendiceal diverticulosis can lead to a higher incidence of perforation and therefore a higher mortality rate.10 An association between appendiceal diverticulosis and appendiceal neoplasms has as well been reported. An increased intraluminal pressure due to, for example, proximal tumours pushes the mucosa through a weakening in the appendiceal wall and can lead to the development of appendiceal diverticula.10–13 Due to the possible complications and association with neoplasms prophylactic appendectomy should be performed in patients with incidentally diagnosed appendiceal diverticulosis.13
In our case the patient was diagnosed with appendiceal diverticula combined with neurofibroma. To our knowledge, there is only one case described in the English literature about appendiceal diverticulosis and neurofibromatosis in an NF1 patient.7 Ozaki et al stated that appendiceal diverticulosis may be a complication of appendiceal neurofibroma. In contrast to our case, they describe a case of a ruptured appendiceal diverticulitis with neurofibroma in the absence of severe abdominal pain. This highlights the importance of knowledge about the different gastro-intestinal manifestations of NF1. A quick diagnosis can avoid complications and malignant transformation.
Patient’s perspective
A few years ago I was diagnosed with neurofibromatosis type 1 (NF1). All these years I have been ashamed about these neurofibromas on my skin although they are not that prominent. When I came to the emergency department with right lower quadrant pain I did not know that this had something to do with my NF1. I was glad the doctors finally decided to remove my appendix and hoped that this would help me to get rid of my pain. Before the operation I was really nervous but all the nurses and doctors made me feel comfortable and gave me sufficient information. When I woke up after the operation I felt fine, I had no pain. Postoperatively the surgeon told me she found an appendix with multiple lumps and that this could maybe be associated with my NF1. On my 2 weeks follow-up in the outpatient clinic I was completely pain free and did not had any complications. The histopathology report confirmed neurofibromas and diverticula of the appendix. I was glad the doctors decided to remove my appendix because they explained me I had a higher chance of complications and malignant transformation. I am an artist and to express my gratitude for the operation and the fantastic care I received, I made a painting for all the nurses and doctors who helped me through this journey.
Learning points
-
Diverticular disease of the appendix is uncommon but more frequent than appendiceal neurofibroma with reported prevalences in literature up to 4.8%.
-
Benign appendiceal neurofibromas should be included in the differential diagnosis of right lower quadrant pain in patients known with neurofibromatosis type 1, especially when diverticulosis of the appendix is observed.
-
In such patients a diagnostic laparoscopy followed by appendectomy should be performed to avoid complications and malignant transformation, even in the absence of acute appendicitis.
Footnotes
-
Twitter @seb_strypstein
-
Contributors KVdS designed the paper, reviewed the literature and wrote the paper. RR contributed important ideas. E-JB and SS revised the paper.
-
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
-
Competing interests None declared.
-
Patient consent for publication Obtained.
-
Provenance and peer review Not commissioned; externally peer reviewed.
- © BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.
References
Use of this content is subject to our disclaimer