Rectal granular cell tumor treated by endoscopic resection: A case report and review of literature

Abstract

BACKGROUND

Granular cell tumors (GCTs) rarely occur in the gastrointestinal tract and are particularly uncommon in the rectum. We report a 34-year-old woman diagnosed with rectal GCT. In addition, we reviewed the published literature on rectal GCTs to summarize their clinical characteristics, diagnosis, and management.

CASE SUMMARY

The patient underwent a colonoscopy without any symptoms and no remarkable medical or family history of malignancy. A solitary 6-mm polypoid lesion was identified in the rectum and was resected endoscopically, with no additional lesions identified during colonoscopy. The patient had no complications after resection. Histopathological and immunohistochemical examinations confirmed the diagnosis of GCT.

CONCLUSION

The etiology, pathology, and biopsy diagnosis of GCT still require further research.

Key Words: Granular cell tumor; Polypoid lesion; Endoscopic mucosal resection; Literature review; Case report

Core Tip: This article reports a middle-aged female patient with a rectal granular cell tumor (GCT) detected during colonoscopy, who had no remarkable medical or family history. The preliminary biopsy was nondiagnostic, whereas endoscopic resection followed by histopathological examination confirmed the diagnosis. We also review the literature and discuss the diagnosis, clinical and pathological features, and management of rectal GCT.

INTRODUCTION

Granular cell tumor (GCT) was first reported by Abrikossoff[1] in 1926. GCT is currently regarded as a rare soft tissue neoplasm of Schwann cell origin. Its incidence remains unclear because of its rarity. One study published in 1980 reported that GCTs accounted for 0.03% of more than 410000 surgical specimens collected over a 32-years period[2]. However, whether this figure reflects the current incidence of GCT is uncertain given the age of the study. GCT can occur at any age but most commonly affects individuals between 40 years and 60 years of age[3,4]. Most GCTs are benign, with malignant GCTs accounting for fewer than 2% of cases, and whether malignant transformation from benign GCT exists remains controversial[3]. The etiology and behavioral or environmental risk factors for GCTs remain poorly understood. Gastrointestinal (GI) tract GCTs account for approximately 5%-11% of all GCTs[5]. These tumors can occur throughout the GI, including the esophagus, stomach, duodenum, cecum, ileocecal valve, appendix, colon, and rectum. However, rectal GCTs are particularly uncommon, with only a limited number of cases reported in the literature. Most patients with GCT of the intestinal tract are asymptomatic, whereas some may present with abdominal distention or pain, diarrhea, or changes in bowel habits[5]. Definitive diagnosis relies on histopathological and immunohistochemical examination, typically showing positive staining for S-100 protein. Here, we report a case of rectal GCT in a female patient that was resected endoscopically.

CASE PRESENTATION

Chief complaints

A 34-year-old woman was admitted to the Department of Gastroenterology and Oncology, Changsha Hospital of Traditional Chinese Medicine in April for further treatment of a polypoid lesion in the rectum identified 12 days earlier.

History of present illness

Twelve days ago, the patient had undergone colonoscopy as part of routine health examination with no clinical complaints. A 6-mm subpedunculated polypoid lesion with a reddish surface and a slightly depressed center was identified in the rectum, 7 cm from the anus. No other lesion was detected during the first colonoscopy. Histopathological examination of forceps biopsy specimens showed chronic inflammatory changes, focal mild atypical hyperplasia of the glandular epithelium, and fibrous tissue hyperplasia in the lamina propria of polypoid intestinal mucosal tissue.

History of past illness

The patient was diagnosed with atrophic gastritis 12 days earlier based on gastroscopy, conducted as part of routine health examination, with no evidence of Helicobacter pylori infection.

Personal and family history

The patient had no family history of malignant tumors or GI diseases. She did not smoke, consume alcohol, or use drugs.

Physical examination

Vital signs were normal and no significant abnormalities were detected on physical examination.

Laboratory examinations

Routine laboratory investigations, including blood biochemistry, complete blood count, and coagulation tests, were unremarkable.

Imaging examinations

Chest computed tomography (CT) and abdominal ultrasonography revealed no abnormalities.

FINAL DIAGNOSIS

Histopathological and immunohistochemical analyses of resected polypoid lesion showed positive staining for S-100 protein, confirming the diagnosis of GCT. The histopathological findings are shown in Figure 1.

Figure 1 Histopathological and immunohistochemical findings of the rectal granular cell tumor. A: Tumor cells arranged in nests (× 40); B: Tumor cells with abundant eosinophilic granular cytoplasm (× 100); C: Positive immunohistochemical staining for S-100 protein; D: Ki-67 Labeling index of 3%.

TREATMENT

Given the small size and subpedunculated morphology of the lesion, endoscopic mucosal resection (EMR) was performed. After adequate bowel preparation, the polypoid lesion was identified, and methylene blue mixed with glycerol fructose was injected into the submucosa using a single-use mucosal injection needle. The lesion was completely resected with a single-use snare, and the mucosal wound was closed with two titanium clips. The EMR procedures are shown in Figure 2. Patients were requested to fast for 24 hours postoperatively, followed by a liquid diet for 2 days and a semi-liquid diet for 5 days.

Figure 2 Endoscopic findings and treatment of the rectal lesion. A: Endoscopic image showing a 6-mm polypoid lesion in the rectum; B: Submucosal injection of methylene blue and glycerol fructose before resection; C: Post-resection wound surface; D: Wound surface with clips.

OUTCOME AND FOLLOW-UP

The patient was discharged 3 days after the procedure without complications and was advised to undergo follow-up colonoscopy 6 months later. At the two-month follow-up after EMR, the patient reported no abdominal pain, abnormal bowel habits, or other discomfort. The patient’s clinical course is summarized in Supplementary Figure 1.

DISCUSSION

A literature search was conducted in five databases: PubMed, Web of Science for English-language articles, China National Knowledge Infrastructure, VIP, and the WanFang Database for Chinese-language articles. The search terms were included “GCT”, “granular cell tumor”, “rectal”, “rectum”, “gastrointestinal”, and “intestinal”. Articles published up to May 18, 2026, were considered. Eligible studies included case reports and clinical studies of rectal GCT. Studies without specific cases details or involving GCTs at other anatomical sites were excluded. First, titles and abstracts were screened to identify relevant studies. The full texts were then reviewed to confirm eligibility. Finally, the following data were extracted using a standardized Excel spreadsheet: First author, age and sex of patients, presentations, size of tumor, immunohistochemistry markers, and treatment. The results are summarized in Table 1.

Table 1 Summary of reported cases of rectal granular cell tumors.

Ref.	Age/sex	Presentation(s)	Size (mm)	IHC markers (positive)	IHC markers (negative)	Treatment
Wei et al[30]1	NR	Abdominal discomfort, anal heaviness, hematochezia	NR	S-100, CD68, NSE, vimentin	CD117, Dog-1, CD34, SMA, CgA, EMA, CK	Endoscopic resection
Lin et al[31]	56/F	Constipation	6	NSE, nestin, CD68, S-100; Ki-67 < 1%	CK, Cam5.2, CD34, CD117, CgA, CDX2, p53	ESD
Lin et al[31]	66/M	Asymptomatic	7	NSE, nestin, CD68, S-100; Ki-67 < 1%	CK, Cam5.2, CD34, CD117, CgA, CDX2, p53	ESD
Lin et al[31]	47/M	Diarrhea	9	NSE, nestin, CD68, S-100; Ki-67 < 1%	CK, Cam5.2, CD34, CD117, CgA, CDX2, p53	ESD
Li et al[18]	50/M	Altered bowel habits	8	S100, CD68, TFE3	α-inhibin, Dog-1,	ESD
Wu et al[32]	48/M	NR	4.5	CD68, S-100	CKp, Desmin, SMA, CD117, CD34, Dog1, α-inhibin	ESD
Wang et al[33]	NR	NR	NR	CD68, S-100, NSE; Ki-67 < 1%	CK, CD34, SMA, GFAP, NF	NR
Shi and Li[34]	56/M	Asymptomatic	9	Vimentin, S100, Nestin, NSE, Ki-67 1%-2%	CD117, SYN, CD34, CD163, HMB45	EMR
Shi and Li[34]	50/M	Asymptomatic	7	Vimentin, S100, Nestin, NSE, Ki-67 1%-2%	CD117, SYN, CD34, CD163, HMB45	EMR
Yang et al[35]	51/M	Asymptomatic	20	S100		Endoscopic operation
Lee and Kim[36]	47/M	Asymptomatic	10	S100		Endoscopic resection
Sunkara et al[37]	61/M	Asymptomatic	4	S100		CPS
Nakachi et al[38]	47/F	Altered bowel habits	8	S100, NSE	Desmin, vimentin	Radical low anterior resection of rectum
Sunderland et al[39]	56/M	Anal pain	45	CD68, inhibin A, SOX-10, S11	SMA, desmin, CD117, EMA	Laparoscopic abdominoperineal resection with perineum reconstruction
Nakanome et al[40]	60/M	Fecal occult blood positive	8	S100, NSE	chromogranin, synaptophysin, c-kit, CD34	Endoscopic resection
Spinzi et al[41]	47/NR	Hematochezia	NR	NR		NR
Okano et al[42]	67/M	Fecal occult blood positive	8	S100		Electrosurgical snare polypectomy
Na et al[6]	51/M		> 1	S100, CD68, α-inhibin, Calretinin, CD57, CD56, SYP, NSE, Nestin, SOX10, Ki-67 < 1%	CDX2(-), p53(-), CD163(-),	EMR
Na et al[6]	42/M		2	S100, CD68, CD163, Calretinin, CD56, SYP, NSE, Nestin, SOX10, p53, Ki-67 < 1%	CDX2, α-inhibin, CD57	EMR
Shaheen et al[43]	13/M	NR	10	NR	NR	NR
Lack et al[2]1	NR	NR	8-14	NR	NR	NR
Johnston and Helwig[9]	33/M	NR	NR	NR	NR	NR
Johnston and Helwig[9]	32/M	Rectal bleeding	NR	NR	NR	NR
Johnston and Helwig[9]	39/M	Rectal discomfort	NR	NR	NR	NR
Johnston and Helwig[9]	43/M	Diarrhea	NR	NR	NR	NR
Johnston and Helwig[9]	22/NR	Asymptomatic	NR	NR	NR	NR
Johnston and Helwig[9]	42/M	Asymptomatic	NR	NR	NR	NR
Johnston and Helwig[9]	38/F	NR	NR	NR	NR	NR
Johnston and Helwig[9]	43/F	Asymptomatic	NR	NR	NR	NR
Johnston and Helwig[9]	52/F	Asymptomatic	NR	NR	NR	NR
Cohen and Cramm[44]	55/M	Asymptomatic	20	NR	NR	Removed via the transrectal approach
Parfitt et al[45]	45/M	NR	NR	S-100	CD117, CD34, desmin	NR
Take et al[23]	49/M	NR	8	S-100	CD117, CD34, desmin	ESD
Sevilla Ribota et al[46]	59/M	NR	NR	S-100	NR	NR
Qi et al[47]	52/M	NR	9	NR	NR	Endoscopic resection
Kim et al[48]	49/M	NR	7	NR	NR	Endoscopic resection
Payne-James et al[49]	39/F	Asymptomatic	5	NR	NR	excision biopsy

¹These two studies reported 5 and 3 rectal granular cell tumors separately. IHC: Immunohistochemistry; NR: Not reported; ESD: Endoscopic submucosal dissection; EMR: Endoscopic mucosal resection; CPS: Cold polypectomy snare; M: Male; F: Female.

Approximately 5%-11% of GCTs occur in the GI tract. Reported sex distribution varies among studies. Although some reports suggest that GCTs are more common in African-American women, other studies of GI GCTs have shown a male predominance[4,6], which is consistent with our literature review. We identified 45 reported cases of rectal GCTs; 2 cases published in languages other than English or Chinese were not included in Table 1[7,8]. In a study of 98 GI tract GCT cases[4], the mean patient age was 49 years, while another study reported a mean age of 41.8 years[9]. These findings are generally consistent. Our literature review showed that patients with rectal GCT ranged in age from 13 years to 67 years.

Most GCTs are benign, and fewer than 2% are malignant[3,10]. Fanburg-Smith et al[11] proposed histopathological criteria for predicting malignant potential of GCTs, including necrosis, spindling, vesicular nuclei with large nucleoli, increased mitotic activity (> 2 mitoses/10 high-power fields at 200 × magnification), a high nuclear-to-cytoplasmic ratio, and pleomorphism. Tumors exhibiting 3 or more of these features were classified as histologically malignant. Subsequent researchers have proposed modifications to these criteria. Wang et al[12] recommended using a threshold of 5 mitoses per high-power field rather than 2 mitoses per 10 high-power fields. Nasser et al[10] suggested that the presence of necrosis and/or mitoses could be used to differentiate benign from malignant tumors, but the only standard for malignancy is metastasis. Kapur et al[13] reported that increased immunoreactivity for Ki-67 and PHH3 may help identify atypical GCTs. In addition, rapid tumor growth, large size, and Ki-67 > 10% may indicate malignant behavior[3]. Machado et al[3] pointed out that a few malignant GCTs had histologically benign features; thus, classification of GCT should not be based solely on histology, which is thought-provoking and meaningful in clinical practice.

The pathogenesis of GCTs remains poorly understood. Schrader et al[14] reported that multiple GCTs may be associated with mutations in PTPN11. Pareja et al[15] identified mutations in ATP6AP1 and ATP6AP2 that may contribute to the development of GCTs. In addition, Sekimizu et al[16] provided further evidence supporting the hypothesis that dysfunction of the vacuolar ATPase complex may play a role in GCT tumorigenesis. However, the exact mechanisms underlying the development of GCTs remain unclear, and further studies are needed to elucidate their pathogenesis.

Some rectal GCTs are asymptomatic and are discovered incidentally during endoscopic examination. Other patients may present with nonspecific symptoms, such as abdominal pain, diarrhea, altered bowel habits, a positive fecal occult blood test, or hematochezia. Endoscopically, rectal GCTs typically appear as solitary polypoid lesions. Previous reports have described their characteristic appearance as pale yellow or white submucosal elevations with a smooth surface[17]. However, in the present case, the lesion had a reddish surface with a slightly depressed center. This shows that the colonoscopic appearance of GCT may be different, warranting an in-depth diagnostic workup. Review of the literature showed that tumor sizes ranged from 2 mm to 45 mm in diameter. However, due to the limited number of reported cases, no definitive endoscopic features have been established. Endoscopic ultrasonography (EUS) is useful for determining the layer of origin and measuring tumor size. For suspected malignant GCTs, magnetic resonance imaging may help assess tumor extent and local invasion, and CT could be used to assess metastases. Nevertheless, distinguishing GCTs from other subepithelial or polypoid lesions based solely on conventional white-light endoscopy or EUS remains challenging. Histopathological and immunohistochemical examinations therefore remain the gold standards for diagnosis.

Histologically, GCTs cells are composed of polygonal, circular, ovoid, or fusiform cells arranged in nests, sheets, or fascicles. They are typically unencapsulated, and the tumor cells contain abundant eosinophilic granular cytoplasm[18-20]. The growth pattern of GCTs may be either well marginated or infiltrative, with most tumors being well marginated. An infiltrative growth pattern does not necessarily indicate malignancy; however, extensive infiltration may be suggestive of malignancy[4,6]. The histological features of malignant GCT have been discussed in the third paragraph. Common immunohistochemical markers for GI tract GCTs include S-100, CD68, and vimentin. In addition, SOX-10 and neuron-specific enolase may also play important diagnostic roles[18]. Pathologists should differentiate GCTs from GI stromal tumors (GIST), leiomyomas, and other subepithelial tumors. GISTs are typically positive for CD117, Dog-1 and CD34, whereas leiomyomas are characteristically positive for SMA and desmin. However, non-neuronal GCTs that are negative for S-100 have been reported. For example, Kim et al[21] reported a case of S-100-negative malignant GCT. The cellular origin of these tumors remains controversial, particularly regarding whether they arise from Schwann cells. Furthermore, An et al[4] reported that TFE3 and α-inhibin may also be related to GCTs. In this case, positive S-100 staining and a low Ki-67 labeling index supported the diagnosis of a benign GCT.

However, because GCTs are subepithelial tumors and may occasionally result in pseudoepitheliomatous hyperplasia, routine biopsy specimens may not provide a definitive diagnosis because of insufficient tissue, as in the present case. Without subsequent resection, this lesion could have been misdiagnosed. The case highlights the importance of obtaining deeper and adequate tissue samples for the accurate diagnosis of polypoid lesions. Endoscopic ultrasound-guided fine-needle aspiration may help overcome this limitation. Inokuchi et al[22] proposed mucosal incision-assisted biopsy, which can obtain a sufficient amount of tumor tissue for the diagnosis of GCT. Overall, acquisition of an adequate tissue specimen is crucial for accurate diagnosis.

A completely excised polyp or mass serves not only as treatment but also as the ideal specimen for confirming the diagnosis of a GCT. To achieve complete excision, the treatment approach should be selected based on the lesion size and the layer of origin. Currently, most GI tract GCTs are treated endoscopically[23,24], including by EMR, endoscopic submucosal dissection, and endoscopic submucosal excavation. Recently, Michielan et al[25] reported a case of successful endoscopic full-thickness resection of a 2-cm colonic GCT. Some researchers have suggested that endoscopic resection is safe and effective for GCTs measuring ≤ 2 cm in diameter[24]. Periodic endoscopic surveillance may also be an option in selected cases. For malignant GCTs, surgical resection is an effective treatment[26]. The efficacy of radiotherapy and chemotherapy for malignant GCT is still unclear. A few reports have suggested that malignant GCTs may respond to pazopanib therapy[27-29]. The choice of treatment depends largely on tumor size and the depth of invasion. EUS may be particularly useful in determining the most appropriate approach for complete resection. Large prospective studies are needed to establish the optimal management strategy for GCTs.

CONCLUSION

Additional studies and larger case series are needed to better characterize the risk factors, clinical and pathological features, pathogenesis, and optimal treatment of rectal GCTs. We report a case in which the diagnosis of rectal GCT could not be established on biopsy but was confirmed after endoscopic resection. This case highlights that, for polypoid lesions, particularly those originating from the submucosa, complete excision or deep biopsy may be necessary for an accurate diagnosis.

ACKNOWLEDGEMENTS

The authors deeply appreciate Sun Da and Chen Xiang from the Department of Pathology, Changsha Hospital of Traditional Chinese Medicine, for their assistance.