An Isolated Colonic Neurofibroma Without Systemic Neurofibromatosis: A Rare Case Report and Literature Review

Introduction

Isolated neurofibroma of the gastrointestinal tract was originally described in 1937 and is still an uncommon entity [1]. Neurofibromas are benign tumors of the peripheral nerve sheath and are most frequently encountered in association with neurofibromatosis type 1 (NF1; von Recklinghausen disease), an autosomal dominant disorder characterized by multiple cutaneous, neurologic, and visceral manifestations [2–4]. In patients with NF1, neurofibromas can involve the gastrointestinal tract, most commonly affecting the stomach and small intestine and often present as multiple lesions. In contrast, truly isolated neurofibromas of the colon occurring in the absence of NF1 are exceptionally rare, with fewer than 25 cases reported in the literature to date [5]. This distinction is clinically important, as isolated lesions lack the systemic features of NF1 and may pose a diagnostic challenge due to their nonspecific presentation and resemblance to other submucosal colonic tumors. Sporadic neurofibromas most commonly arise in the skin or subcutaneous tissues of the extremities, while gastrointestinal involvement is uncommon. Although approximately 10% of neurofibromas occur in patients with NF1, most solitary, localized neurofibromas arise sporadically, and their natural history and malignant potential remain poorly defined [6,7].

Here, we report an uncommon case of an isolated colonic neurofibroma in a patient who did not have NF1 characteristics. This case highlights diagnostic and clinical implications associated with such cases.

Case Report

A man in his 70s with benign prostatic hyperplasia presented with recurrent abdominal pain, constipation, and unintentional weight loss of 5 kg over 1 month. He denied vomiting or rectal bleeding. He had no known drug allergies, no family history of cancer, and no prior significant surgical history.

On physical examination, the patient appeared well and in good general condition. Abdominal examination revealed a soft, non-tender, and lax abdomen, with a firm, non-mobile mass measuring approximately 3×3 cm palpable in the right lower quadrant. The rectum showed no masses or blood, and other body systems showed no abnormalities. Furthermore, no pigmented iris hamartomas were present.

A baseline laboratory workup, including complete blood count, renal function tests, liver function tests, and tumor markers, was within normal limits, with the exception of a mildly elevated lactate dehydrogenase of 663 U/L. The preoperative carcinoembryonic antigen (CEA) level was 3.8 ng/mL, which was within the reference range. Computed tomography (CT) showed a cystic mass at the base of the appendix protruding into the cecum (Figure 1). Therefore, magnetic resonance imaging (MRI) was done to evaluate the exact origin of the lesion and the cyst character, which redemonstrated a right cecum oval-shaped cystic mass just at the base of the appendix measuring 4.7×2.2 cm in the longest dimension, bulging within the cecum, which was hyperintense on T2 and hypointense on T1 with diffusion restriction showing progressive enhancement in post-contrast images and subtraction images; correlation with colonoscopy and tissue biopsy was advised (Figure 2). After that, a colonoscopy was done and revealed a large, smooth polypoid tumor on the cecal floor (Figure 3), and biopsies revealed a spindle cell lesion that exhibited no signs of cancer. According to immunohistochemistry, the etiology was neurogenic (schwannoma/neurofibroma) (Figure 4). Final histopathology confirmed a benign isolated colonic neurofibroma, with negative resection margins and no evidence of malignancy. The single mesocolic lymph node was reactive and negative for tumor involvement.

Following histopathology’s confirmation of the final diagnosis, a multidisciplinary team discussed the case and decided to proceed with surgery: a right hemicolectomy with primary ileocolic anastomosis. This decision was justified because the patient was symptomatic and experiencing recurrent abdominal pain and because of the size of the lesion, which can lead to complications such as obstruction. However, these lesions also have the potential to develop malignancy.

The patient underwent an open right hemicolectomy with primary ileocolic anastomosis under general anesthesia. During the procedure, a reddish-purple cecal lesion with a slight yellowish color, measuring 4.5×2×2 cm, firm in consistency with a soft surface, and not mobile was discovered, showing that the appendix was attached to the cecum (Figure 5). The patient recovered without any complications and was discharged home on postoperative day 10. The patient had returned to his regular daily activities and was still asymptomatic at the first follow-up visit 2 weeks after surgery. A structured postoperative surveillance plan was initiated, including tumor markers (CEA and carbohydrate antigen [CA] 19-9), which were examined every 3 months for 2 years, then every 5 months until the fifth year. A colonoscopy was scheduled for 6 months after surgery, followed by 5 years of annual follow-ups. Contrast-enhanced CT of the chest, abdomen, and pelvis was scheduled every 6 months for the first 2 years, then annually for the following 3 years.

At later follow-ups at 3 months, 6 months, and 12 months postoperatively, there were no indications that symptoms associated with neurofibromatosis were emerging. A colonoscopy showed no evidence of recurrence, and tumor markers such as CEA, CA 19-9, and lactate dehydrogenase were within the reference ranges. At the time of this report, he has been followed regularly with tumor markers, imaging, and colonoscopy for over 3 years, and there have been no symptoms or indications of a recurrence. The postoperative surveillance strategy in this case was institution-specific and precautionary because of the initial concern for malignancy.

Discussion

We describe an isolated neurofibroma of the cecum in an older adult man without clinical or family features of NF1. Colon neurofibromatosis associated with NF1 is rare [8–11]. In clinical practice, isolated colonic neurofibromatosis without other NF1-like characteristics is even rarer [5,12]. They typically manifest in numerous ways and belong to a genetic illness that has 2 clinical forms: neurofibromatosis type 2 (also known as central neurofibromatosis or bilateral acoustic neurofibromatosis) and NF1 (also known as von Recklinghausen neurofibromatosis or peripheral neurofibromatosis, NF1). Clinical presentations of these disease entities vary, affecting the skin, gastrointestinal tract, eyes, bones, neurological system, and other body parts. For patients with NF1, the most common causes of death are cardiovascular illness, which might present as hypertension, myocardial infarction, hemorrhage, or cerebral ischemia [13]. Life expectancy in patients with NF1 is reduced by approximately 15 years compared with the general population [14].

Neurofibromas typically originate from the Auerbach (myenteric) plexus in the muscularis propria, the Meissner (submucosal) plexus, or the serosa [5,9]. The lesions are frequently broad-based and sessile, but pedunculated polyps have also been seen [5]. Most of the lesions are found in fourth or sixth decade of life [5,14]. Our patient was diagnosed with isolated colonic neurofibroma at 72 years of age, which exceeds the reported age range in the literature. An isolated colonic neurofibroma rarely causes symptoms prior to puberty and is frequently clinically asymptomatic. NF1 is also linked to the development of various gastrointestinal tract-related neoplasms and has been reported in 25% of individuals with NF1 [5,9,14]. Abdominal pain, palpable masses, mucosal hemorrhage from necrosis or ulceration, obstruction from intussusception or extraluminal pressure, perforation, megacolon, hypertensive ulcer disease, diarrhea, steatorrhea, obstructive jaundice, and obstruction of the pancreatic tract are all part of the clinical picture. There have also been reports of iron deficiency anemia brought on by obscure blood loss [5,15,16]. This relates to our patient, who experienced abdominal pain and constipation with weight loss and had no associated features of von Recklinghausen disease. Numerous neurofibromas have been seen in the gut [2,15]. Additionally, isolated neurofibromas have been seen in different digestive system regions. Eight cases of isolated mesentery neurofibroma have been reported (7 ileal, 1 gastrocolic) [17], and 3 cases of the anal canal, 1 of the esophagus, 1 of the soft palate, 7 of the gallbladder, 1 of the common bile duct, and 1 of ileal isolated neurofibroma [18–23]. In our case, a solitary neurofibroma was discovered in the cecum. Typically, endoscopically discovered colonic neurofibromas are a few millimeters to several centimeters in size and appear as sessile or pedunculated mucosal or submucosal lesions [23–25].

Histopathology is the gold standard for diagnosing colonic polyps, and pathologic testing is a crucial component of the diagnostic workup. Since the patient’s future care depends on a precise pathologic diagnosis, it is critical to distinguish neurofibromas from other spindle cell soft tissue neoplasms, especially gastrointestinal stromal tumors (GISTs). Some investigations have described pathological characteristics of colonic neurofibroma. Axons, fibroblasts, perineurial cells, Schwann cells with wavy, serpentine nuclei with pointed ends, and other peripheral nerve components proliferate in neurofibromas, according to histology. The tumor may have myxoid regions and be infiltrative. Although axons are present throughout the lesion, routine labeling makes it challenging to recognize them. The axons are trapped by silver staining or neurofilament immunostaining. Mitoses are rare [7,14,16,26–35]. CEA is a nonspecific serum marker and is not recommended as a diagnostic tool for an isolated colonic neurofibroma. It can be elevated in several benign and malignant conditions, including smoking, infections, inflammatory bowel disease, pancreatitis, liver disease, and other cancers. In the present case, the CEA level was obtained as part of the initial workup of a colonic mass rather than as a neurofibroma-specific marker.

Inflammatory fibroid polyp, schwannoma, GIST, smooth muscle tumor (leiomyoma/leiomyosarcoma), and ganglioneuroma are among the differential diagnoses for neurofibroma. To differentiate neurofibroma from other spindle cell tumors and to confirm the diagnosis, immunohistochemistry is crucial. Similar to neurofibromas, GISTs can test positive for S100 and CD34. However, GIST exhibits substantial diffuse positivity for CD117 and DOG1, in contrast to neurofibromas that are negative for both markers. The histologic and immunohistochemical findings in our case were as follows: vimentin (V9), diffusely positive; S100 (polyclonal), diffusely positive; CD34 (QBEnd10), positive; GFAP (6F2), negative; EMA (E29), negative; CD117 (c-KIT) (9.7), negative; ALK-1 (ALK01), negative; and Ki-67 (30–9), very low. Alcian blue special stain highlighted myxoid changes in the tumor. This immunophenotype is consistent with a neurofibroma (Figure 6). Grossly, the specimen showed a firm, solid lesion arising at the base of the appendix and measuring 4.5 cm in greatest dimension, with mass effect on the cecal mucosa. A separate fatty lesion was identified in the submucosa of the ileocecal valve (Figure 7). Furthermore, it has been noted that neurofibromas, especially large lesions, can turn cancerous. In one instance, recurrent neurofibroma turned into malignant peripheral nerve tumors (MPNSTs), as reported by Jung et al [36]. However, the prognosis for solitary neurofibromas is generally favorable, and local recurrence and malignant alterations are uncommon [37]. The main treatment is surgical excision with clean margins, and laparoscopic surgery is accepted for colon cancer and colonic neurofibroma. On the other hand, because neurofibromas are uncommon, there is no consensus regarding the management of these cases, and there is disagreement over the precise surgical criteria for tumor size [27,29,31]. In the present case, the patient underwent an open right hemicolectomy with primary ileocolic anastomosis with clear margins and without lymph node dissection. The team was happy about the clinical outcome, and the patient did not need any further intervention or adjuvant therapy, which highlights the effectiveness of surgical excision with clear margins without the need for extensive colectomy. In a previously reported case, the patient had a non-negligible risk of colon cancer and therefore underwent laparoscopic right hemicolectomy with complete mesocolic excision and D3 lymph node dissection. The significance of dissecting lymph nodes for gastrointestinal neurofibroma or malignant peripheral nerve tumors has not been evaluated in any research. However, a precise preoperative diagnosis permits local resection, whereas colectomy with complete mesocolic excision may be excessively invasive for neurofibroma [27]. A single instance of colonic neurofibroma managed by laparoscopic surgery was documented in Japan [38]. No oncological disadvantages have been noted to date. Although laparoscopic surgery for neurofibroma is considered feasible, the long-term results remain to be assessed [27,38].

This case highlights that isolated colonic neurofibroma should be considered in the differential diagnosis of a submucosal or polypoid cecal mass, even in the absence of clinical or family features of NF1. Preoperative endoscopic biopsy may be limited, so histopathology with immunohistochemistry remains essential for definitive diagnosis and for distinguishing neurofibroma from GIST, schwannoma, and other spindle cell tumors.

Table 1 lists isolated gastrointestinal neurofibromas in patients who did not exhibit any systemic symptoms of von Recklinghausen disease. The location of the neurofibromas, sex, and age at diagnosis are provided. Interestingly, most of these patients were women, while our patient was a man. The age range at diagnosis was 45 to 70 years, and there was a minor tendency for the rectum to be involved. In the present case, the lesion was in the cecum. Routine colonoscopies were used to find the majority of cases. A small number of patients showed iron deficiency anemia at presentation, whereas others reported symptoms of constipation, and several had severe lower gastrointestinal bleeding [35].

Regarding postoperative surveillance, our follow-up strategy including CT of the chest in addition to the abdomen and pelvis to rule out potential distant pathology and monitor for recurrence adhered to standard oncological surveillance protocols. Tumor markers were also included, as this patient’s CEA levels were elevated before surgery but returned to normal levels after surgical resection, which supported the completeness of tumor removal and provided a useful baseline for subsequent follow-up. As isolated colonic neurofibroma is so rare, there is limited information on how to standardize postoperative monitoring. Most previously reported cases primarily focus on diagnosis and surgical management, providing minimal details on follow-up surveillance using CT imaging or tumor markers, and their clinical utility remains uncertain [28,30,35].

Few Saudi Arabian cases of solitary colon neurofibroma have been described. To have a better understanding of the occurrence and characteristics of malignant tumors in the Saudi population, more investigation and case reporting are required.

Conclusions

Isolated colonic neurofibroma is an uncommon benign tumor that has no known clinical significance. Although most cases are associated with generalized neurofibromatosis, our patient presented with isolated or solitary neurofibromas of the colon without NF1. This case highlights the importance of maintaining a high index of suspicion when evaluating nonspecific or submucosal colonic masses. Surgical excision with clean margins and without extensive colectomy remains the treatment of choice for symptomatic or large lesions, which can lead to obstruction. Our patient’s postoperative course confirmed the efficacy of surgical excision with clear margins, without the need of lymph node dissection or extensive colectomy, with complete symptom resolution and no perioperative complications. This case is notable for solitary neurofibromas of the colon in the absence of NF1.