| Category | Granular Cell Tumor (GCT) summary |
|---|---|
| Disease name | Granular cell tumor (GCT) |
| MONDO identifiers | MONDO:0006235 granular cell tumor; MONDO:0003250 benign granular cell tumor; MONDO:0002291 cutaneous granular cell tumor; MONDO:0003251 esophageal granular cell tumor; MONDO:0003256 neurohypophysis granular cell tumor (pqac-00000000) |
| Other identifiers | ICD-10 and MeSH were not established in the retrieved evidence set; use MONDO above and site-specific coding in implementation workflows when needed (pqac-00000000) |
| Common synonyms | Abrikossoff tumor; granular cell myoblastoma; granular cell schwannoma; granular cell neurofibroma (historical/alternative usage in literature) (pqac-00000002, pqac-00000006) |
| Evidence source type | Primarily aggregated disease-level reviews plus case series/case reports and tumor sequencing studies; not EHR-derived in the retrieved evidence set (pqac-00000001, pqac-00000002, pqac-00000003) |
| Cell of origin / current understanding | Usually a Schwann-cell-derived neuroectodermal soft tissue neoplasm; neural GCTs are typically S100-positive. Rare non-neural GCTs are described and are often S100-negative/vimentin-positive (pqac-00000001, pqac-00000003, pqac-00000006, pqac-00000009) |
| Frequency / epidemiology | Ultra-rare tumor; estimated at ~0.5% of all soft tissue sarcomas. Most tumors are benign (~98%); malignant tumors are rare (~2%). Female predominance is consistently reported; peak incidence is usually in the 4th-6th decades, though cases occur across ages (pqac-00000002, pqac-00000006) |
| Key genetic alterations | Recurrent loss-of-function alterations in ATP6AP1, ATP6AP2, and ATP6V0C are a major molecular signature; V-ATPase pathway disruption is reported in up to ~72% of GCTs. Oral GCT sequencing also identified ATP6AP1 frameshift c.746_749del p.P249Hfs*4 and ATP6V1A p.D290N, plus variants in lysosomal/autophagosomal genes (pqac-00000001, pqac-00000005, pqac-00000026, pqac-00000028, pqac-00000032, pqac-00000033) |
| Key immunohistochemistry markers | Typical positive markers: S100, SOX10, CD68, inhibin, nestin, calretinin; additional reported positivity includes NSE, CD57, CD63/NKI-C3, vimentin. Myogenic and melanocytic markers are generally negative or only focally positive in rare cases (pqac-00000010, pqac-00000012, pqac-00000013) |
| Histopathology | Non-encapsulated/infiltrative nests or sheets of polygonal cells with abundant eosinophilic granular cytoplasm; PAS-positive, diastase-resistant lysosomal granules; Pustulo-ovoid bodies of Milian; overlying pseudoepitheliomatous hyperplasia may occur (pqac-00000009, pqac-00000010, pqac-00000011) |
| Classification system | Fanburg-Smith criteria: necrosis, mitotic activity >2/10 HPF, spindle cells, nuclear pleomorphism, vesicular nuclei with prominent nucleoli, and high nuclear-to-cytoplasmic ratio. 0 criteria = benign; 1-2 = atypical; ≥3 = malignant. Ki-67 is usually <5% in benign, 5-10% in atypical, and ~10-50% in malignant GCTs (pqac-00000010, pqac-00000023, pqac-00000024) |
| Primary anatomical sites | Can arise almost anywhere; commonly superficial soft tissues, especially skin/subcutis and head and neck. Frequent sites include tongue/oral cavity, gastrointestinal tract (especially esophagus), thoracic wall, upper extremities, breast, and less often internal organs (pqac-00000001, pqac-00000002, pqac-00000003, pqac-00000006) |
| Clinical presentation | Usually a slow-growing, firm, small (often 5 mm-2 cm), painless/asymptomatic nodule or submucosal swelling; lesions are often solitary, but multifocal disease can occur (pqac-00000001, pqac-00000003, pqac-00000006) |
| Treatment options | Standard treatment for localized/resectable disease is complete surgical excision with negative margins. For unresectable/metastatic malignant GCT, evidence is limited; pazopanib is the best-supported systemic option in recent literature. Cytotoxic chemotherapy has generally shown limited activity; isolated reports describe disease control with PI3K inhibitors or pazopanib-based combinations (pqac-00000015, pqac-00000016, pqac-00000017, pqac-00000019, pqac-00000021) |
| Pazopanib data | In the 2023 review of advanced malignant GCT, pazopanib produced disease control in 8/10 reported patients (80%) and objective RECIST response in 4/10 (40%); median time on therapy was ~7 months (pqac-00000016, pqac-00000017) |
| Prognosis: benign GCT | Generally excellent after complete excision; recurrence reported at ~2-8% with clear margins, increasing to ~20% with positive margins in some series/reviews (pqac-00000007, pqac-00000023) |
| Prognosis: malignant/metastatic GCT | Aggressive course. Local recurrence up to ~32%; metastases in about half of malignant cases, often within 2 years; lungs and bone are common metastatic sites. Reported mortality is ~39% within 3 years for malignant GCT, and median overall survival for metastatic disease is ~10 months (pqac-00000004, pqac-00000007, pqac-00000023, pqac-00000024) |


*Table: This table summarizes the core disease characteristics of granular cell tumor, including identifiers, biology, pathology, clinical presentation, treatment, and prognosis. It is useful as a compact reference for disease knowledge base curation.*