Granular cell tumor (GCT) is a rare, typically benign neoplasm that demonstrates neuroectodermal differentiation (1). Malignant transformation of the tumor has been described but it is quite rare (2). Granular cell tumor was first described by Abrikossoff in 1926 in the skeletal muscle of the tongue. He considered GCTs to be of muscular origin and, on the basis of their morphology and frequent localization in the tongue, coined the term “myoblastic myomata” (3, 4). Current evidence strongly suggests that GCT is derived from Schwann cells, a finding supported by its consistent positivity for the S-100 protein (1, 5). GCTs can occur in virtually any site of the body, with the most common locations being the head and neck region (particularly the tongue), skin, subcutaneous tissue, breast, and gastrointestinal tract (GIT), with less than 1% developing in the biliary tract (1).

A 37-year-old female patient presented to the emergency department in early August 2025 due to persistent biliary colic that did not respond to symptomatic treatment. An ultrasound of the abdomen revealed a previously known hyperechoic mass, suspected to be a polyp, measuring 5 mm with normal wall thickness and gallbladder size. The patient was evaluated by an abdominal surgeon, who indicated the need for emergency surgical intervention. On the day of admission, a laparoscopic cholecystectomy was performed, and the excised tissue was sent for pathological analysis. Examination of the gallbladder revealed a polypoid lesion measuring 0.5 cm in diameter located at the fundus, with no other focal changes observed in the mucosa (Figure 1A). Histologically, the surface of the polyp exhibited a normal columnar epithelium. Within the lamina propria of the described polyp, clusters of cells were identified, characterized by abundant cytoplasm, some of which displayed mild to pronounced eosinophilia, alongside small, uniform nuclei without atypia (Figure 1B). No mitotic figures or necrosis were observed. Immunohistochemical analysis revealed that the described cells were positive for S-100 and SOX10, and focally positive for CD68 (Figure 2), while negative for CKAE1/AE3, Melan A and HMB 45. The histopathological analysis suggested the presence of a benign granular cell tumor of the gallbladder, which was completely excised. The postoperative course was uneventful.

GCT is a rare soft-tissue tumor that most probably has neural origin. This origin is strongly supported by immunohistochemical positivity for Schwann-like mesenchymal cell related antigens, such as S-100 protein, neuron-specific enolase, myelin-specific protein, CD68, protein gene product 9.5, inhibin alpha protein and negative for desmin and smooth muscle actin (2, 5-7). GCT is typically a solitary lesion, usually measuring less than 3 cm in diameter, and behaves predominantly in a benign fashion (1). However, a small percentage of cases, accounting for only 1-2% of all GCTs, exhibit malignant behavior and may metastasize, which significantly limits survival (8).

Epidemiology. GCTs can occur in patients of all ages but are most frequently diagnosed in adults in their 40s and 50s and show a slight female predominance (F:M=5:4) (2). The most common site for GCT is the head and neck region, accounting for 45%-65 % of cases, followed by the skin and subcutaneous tissue. In contrast, GCT of the biliary tract is exceptionally rare, accounting for 1% of all GCTs (1). The first case of biliary tract GCT was reported in 1952 (9). Interestingly, the epidemiology for biliary tract GCT shows a marked difference from general GCTs, it is more prevalent in younger Black females (F:M=5.3:1 with median age of presentation 34 years). The younger age at presentation might reflect a spatial problem due to a narrow lumen of the biliary tract (1). To our knowledge, this represents the tenth reported case of a granular cell tumor arising in the gallbladder (6, 10, 11).

Symptoms. The clinical presentation depends on location. GCT of the gallbladder and cystic duct usually present with biliary colic or symptoms of acute cholecystitis and rarely with thickened gallbladder wall as a suspect of carcinoma (1, 10). Since GCTs of the gallbladder and biliary tract are predominantly benign, the definitive treatment is complete surgical excision (2, 6, 12).

Histology. GCT is composed of large, uniform polygonal cells arranged in clusters, sheets, or nests that often appear to infiltrate the surrounding stroma. These cells are characterized by abundant eosinophilic and granular cytoplasm. The characteristic granular appearance is due to the accumulation of secondary lysosomes within the cytoplasm. These cytoplasmic granules stain positive with the periodic acid-Schiff (PAS) stain and are diastase-resistant. The tumor cells possess relatively small, central, and vesicular nuclei with dense chromatin. Benign GCTs typically show an absence of both necrosis and mitoses. A common finding that may predispose to local recurrence after incomplete excision is perineural infiltration, where the tumor cells diffusely infiltrate along the nerves within the surrounding structures (1, 2, 13). Immunohistochemical (IHC) studies provide strong evidence supporting the neural (Schwann cell) origin of GCT. The majority of GCTs show strong positivity for a panel of markers associated with Schwann cells, including S-100, neuron-specific enolase (NSE), vimentin, Protein Gene Product 9.5 (PGP 9.5), inhibin alpha and SOX10. Most GCTs express S-100, but some rare variants termed “non-neural GCT” may be S-100 negative. The tumor cells are typically negative for epithelial and endothelial markers such as cytokeratin, desmin, CD31, CD34, and Melan-A, helping to exclude other soft tissue neoplasms. Atypical or malignant GCTs can mimic malignant melanoma, particularly when the melanoma exhibits granular cell change. Immunohistochemical staining is necessary to distinguish between the two. While HMB-45 is 100% specific for melanoma in this setting, Melan-A is slightly less specific, as rare cases of GCT may demonstrate focal reactivity (1, 5, 6, 14-16).

Prognosis. While GCT is overwhelmingly benign, rare reports of malignant transformation exist, highlighting the importance of careful histological assessment. Currently, there are no reports of malignant GCT specifically within the biliary tract. Fanburg-Smith et al. proposed a widely accepted classification system to differentiate benign, atypical, and malignant GCTs based on six specific histopathological criteria: presence of necrosis, presence of spindle-shaped tumor cells, vesicular nuclei with prominent nucleoli, increased mitotic activity (≥2 mitoses per 10 high-power fields), a high nuclear-to-cytoplasmic ratio and marked cellular pleomorphism. Based on this system, tumors lacking all six features are classified as benign. Tumors meeting one or two criteria are classified as atypical. Tumors exhibiting three or more criteria are classified as malignant. In challenging cases, the Ki-67 labeling index (LI) can serve as an important adjunctive tool (13). However, metastases remain the sole definite criterion for malignancy (8). In the present case, no histopathological evidence of malignancy was detected, consistent with a benign GCT.

GCT of the gallbladder is an exceptionally rare entity, however, it should be recognized as a noteworthy cause of biliary colic, particularly in younger patients, since they mimic more common conditions such as cholecystitis. Furthermore, because these tumors can present with symptoms of biliary obstruction, they may raise clinical concern for cholangiocarcinoma. Consequently, GCT should be included in the differential diagnosis of gallbladder tumors despite its extremely low incidence.

Author Kristina Lalić declares a dual role as both a contributing author and the patient in this case report. As a medical professional and colleague of the clinical team, she contributed substantially to the drafting and literature review of the manuscript. However, to ensure diagnostic objectivity and mitigate potential bias, the pathohistological diagnosis and clinical evaluations were performed independently by the other co-authors and the pathology department. Informed consent for the publication of this case was obtained from the author-subject. All other authors declare no competing interests.

The surgical intervention was performed by the abdominal surgeon (DV) on the patient, who is also an author (KL). The histological and immunohistochemical evaluations were conducted by the pathologists (AP, KK, AS). Each author participated in the review of the clinical data and the data regarding the granular cell tumor diagnosis. All Authors participated in drafting the manuscript and have reviewed and approved the final version for submission.

The Authors would like to thank the entire laboratory staff of the Department of Pathology at University Hospital Dubrava, Zagreb, for their technical expertise in preparing the histological slides and for their assistance with the immunohistochemistry analysis presented in this report.

During the preparation of this manuscript, a large language model (Google Gemini) was used solely for language editing and stylistic improvements in select paragraphs. No sections involving the generation, analysis, or interpretation of research data were produced by generative AI. All scientific content was created and verified by the authors. Furthermore, no figures or visual data were generated or modified using generative AI or machine learning–based image enhancement tools.