| Domain | Established finding | Evidence/recency | Suggested ontology terms |
|---|---|---|---|
| Scope/definition | **Soft-tissue glomus tumor** is the target entity here; it is a **pericytic/glomus-cell neoplasm** and should **not be conflated with glomus jugulare/tympanicum paraganglioma**. ClinicalTrials.gov indexes “Glomus Tumor” under MeSH **D005918**; NOTCH-focused malignant glomus tumor trial eligibility further supports this soft-tissue usage. (pqac-00000004, pqac-00000005) | Clinical registry evidence, updated **2024-01-16**; mechanistic review notes glomus tumors as a subset of **pericytic tumours** with MIR143-NOTCH fusions. (pqac-00000002, pqac-00000004, pqac-00000005) | MeSH: **D005918 Glomus Tumor**; NCIT: *Glomus Tumor*; MONDO: *not confirmed from available context* |
| Typical phenotype | Classic presentation is a **small painful lesion**, often digital/subungual, with marked **tenderness** and often **cold sensitivity**; extradigital and visceral tumors also occur. NF1 guidance specifically mentions **glomus tumours of the digits** in adults. (pqac-00000006) | Mixed evidence base; strong clinical tradition, but only digit localization is directly supported in retrieved context. NF1 surveillance guideline is **2023**. (pqac-00000006) | HPO: **Pain (HP:0012531)**, **Tenderness (HP:0033748)**, **Abnormality of the nail (HP:0001597)**, **Cold-induced pain** *suggested term if curated* |
| Anatomy | Common sites include **digits/finger**, but glomus tumors can also occur in **soft tissue of limbs, trunk, head/neck**, and less commonly **stomach, bone, tongue, lung** in fusion-defined or related pericytic neoplasms. (pqac-00000001) | Molecular pathology review/series context; **2019-2022** evidence indicates broad anatomic spectrum for pericytic tumors with related signaling lesions. (pqac-00000001, pqac-00000002) | UBERON: **finger (UBERON:0002389)**, **nail unit (suggested)**, **soft tissue of upper limb/lower limb (suggested)**, **stomach (UBERON:0000945)** |
| Histology/IHC | Histology typically shows **uniform round/ovoid to epithelioid cells** in nests/trabeculae around a **delicate vascular network**. In related pericytic tumors, **smooth muscle actin (SMA)** and **laminin/collagen IV-type pericellular basement membrane** support pericytic/glomus differentiation; immunophenotype may be variable. (pqac-00000001, pqac-00000002) | Pathology/mechanistic review evidence; **2019-2022**. GLI1-amplified comparator series emphasizes nested epithelioid morphology and variable SMA positivity, useful in differential diagnosis. (pqac-00000001, pqac-00000002) | GO/CL/NCIT suggestions: **vascular smooth muscle cell differentiation (GO:0051146)**, **pericyte (CL:0000669)**, **smooth muscle actin positive** *pathology annotation* |
| Somatic genetics: MIR143-NOTCH | **MIR143-NOTCH1/2/3 fusions** are a major recurrent driver in glomus tumors; review text states these fusions are found in **almost 50%** of glomus tumours. This supports aberrant **NOTCH pathway activation** as an upstream oncogenic mechanism. (pqac-00000002, pqac-00000003) | Mechanistic review **2022** citing primary fusion literature; gene-fusion review **2016** notes MIR143-NOTCH fusions in both **benign and malignant** lesions. (pqac-00000002, pqac-00000003) | HGNC: **MIR143HG**, **NOTCH1**, **NOTCH2**, **NOTCH3**; GO: **Notch signaling pathway (GO:0007219)** |
| Somatic genetics: BRAF | **BRAF-mutant glomus tumors** are a recognized subset, reported in the literature and associated with **malignant histologic characteristics**; however, precise frequency is not available from retrieved full-text context here. | Evidence present only indirectly in retrieved search metadata/unobtainable citation trail; **supportive but not directly quotable from available contexts**. | HGNC: **BRAF**; GO: **MAPK cascade (GO:0000165)** |
| Germline associations | **NF1** is an established predisposition context for **digital glomus tumors**; the 2023 ERN GENTURIS NF1 guideline lists **glomus tumours of the digits** among tumors with increased adult risk. By contrast, **GLMN (glomulin)** classically underlies **glomuvenous malformation/glomangioma**, which is related but **distinct from typical solitary soft-tissue glomus tumor**. (pqac-00000006) | NF1 evidence is directly supported and **2023**. GLMN distinction is standard disease-taxonomy knowledge but **not directly documented in retrieved contexts**, so should be curated cautiously. (pqac-00000006) | HGNC: **NF1**, **GLMN**; MONDO/Orphanet suggestions: **Neurofibromatosis type 1**, **Glomuvenous malformation** |
| Mechanism/pathophysiology | Working model: recurrent **MIR143-driven NOTCH fusion** places a strong smooth-muscle/pericytic regulatory locus upstream of **NOTCH intracellular signaling**, promoting abnormal perivascular cell growth and glomus-tumor phenotype. Reviews frame glomus tumors within **dysregulated vascular NOTCH signaling**. (pqac-00000002, pqac-00000003) | Mechanistic synthesis from review evidence **2016, 2022**. | GO: **Notch signaling pathway (GO:0007219)**, **blood vessel morphogenesis (GO:0048514)**; CL: **pericyte (CL:0000669)** |
| Diagnosis | Diagnosis is usually based on **clinical localization + imaging + excision pathology**. For malignant/unusual cases, **molecular testing** for **NOTCH pathway alterations** can be clinically relevant, as shown by trial enrollment criteria requiring **activating mutation or genetic lesion**. (pqac-00000004) | Direct clinical-trial evidence **2024 registry update**; broader routine diagnostic specifics are not fully captured in available contexts. (pqac-00000004) | NCIT: **Magnetic Resonance Imaging**, **Biopsy**, **Surgical Excision**, **Molecular Diagnostic Testing** |
| Treatment | For typical localized disease, standard care is **complete surgical excision**; no systemic standard is established for most benign tumors. For advanced malignant disease with NOTCH activation, investigational targeted therapy has included the **pan-NOTCH inhibitor CB-103**. (pqac-00000004, pqac-00000005) | Trial evidence current to **2024**; localized surgical management is established practice but not directly detailed in retrieved full text. | NCIT: **Surgical Excision**, **Targeted Therapy**, **CB-103** *if mapped*, **Notch Pathway Inhibitor** |
| Malignant disease/trial | Malignant glomus tumor is **rare** but clinically important. A dedicated phase I/II basket trial (**NCT03422679**) included **“Glomus Tumor, Malignant”** among eligible advanced solid tumors with NOTCH-pathway lesions; trial status was **terminated for business reason**, not efficacy. (pqac-00000004, pqac-00000005) | High-value recent implementation evidence: ClinicalTrials.gov results posted **2024-01-16**. (pqac-00000004, pqac-00000005) | NCIT: **Malignant Glomus Tumor**, **Advanced Solid Neoplasm**, **Clinical Trial** |
| Prognosis | **Benign solitary glomus tumors** generally have excellent outcomes after complete excision; adverse behavior is mainly a concern in **malignant/atypical** lesions. Precise recurrence/metastasis rates are **not available from retrieved contexts**. | Inference from disease class and rarity literature; direct numeric prognosis data **not captured** in available full text. | HPO/NCIT suggestions: **Recurrence**, **Metastatic malignant neoplasm** |
| Prevention | No established **primary prevention** exists for sporadic glomus tumor. In **NF1**, practical prevention is limited to **clinical vigilance/earlier recognition** of symptomatic digital tumors rather than population screening. (pqac-00000006) | NF1 tumor-surveillance framework **2023** supports awareness-based secondary prevention. | NCIT: **Surveillance**, **Genetic Counseling**; HPO: symptom monitoring terms |
| Animal/models | No dedicated, well-established **in vivo glomus tumor model** was identified in the retrieved contexts. Mechanistic inference currently relies more on **human tumor genomics** and broader **vascular NOTCH biology** than on disease-specific models. (pqac-00000002) | Evidence gap, based on absence in retrieved literature and reliance on pathway reviews. | GO: **Notch signaling pathway**; model ontology terms: *not available from current evidence* |
| Evidence gaps | Key gaps from the available evidence set: **validated MONDO/Orphanet mapping**, robust **epidemiology/incidence**, direct **HPO frequency estimates**, standardized **malignancy-risk biomarkers**, disease-specific **QoL** data, curated **GLMN vs glomus tumor** boundary resources, and **animal/model systems**. | Important for curation quality; several requested knowledge-base fields remain under-supported by currently retrieved full text. | MONDO/HPO/UBERON/CL/NCIT mappings require targeted follow-up curation |


*Table: This compact table summarizes core disease-knowledge-base facts for soft-tissue glomus tumor while clearly separating it from paraganglioma terminology. It emphasizes molecular drivers, NF1 association, malignant-disease trial evidence, and current evidence gaps relevant for structured curation.*