| domain | high-confidence finding | quantitative evidence | suggested ontology terms | evidence type/source year |
|---|---|---|---|---|
| identity/MONDO | Adult-type granulosa cell tumor (AGCT) is a rare ovarian sex cord-stromal malignancy and the dominant malignant granulosa-cell subtype; MONDO mapping in retrieved evidence points to ovarian granulosa cell tumor, while exact subtype mapping should be verified | AGCT comprises ~85–95% of granulosa cell tumors; ovarian granulosa cell tumors represent ~2–5% of ovarian tumors/cancers; incidence about 1 per 100,000 in the U.S. (pqac-00000002, pqac-00000011) | Suggested: MONDO: ovarian granulosa cell tumor = MONDO_0023283; MONDO subtype for adult-type AGCT needs verification; MeSH/ICD/Ontology mapping needs verification | Human review 2024; systematic review 2023 (pqac-00000002, pqac-00000011) |
| epidemiology | Usually diagnosed in adult/perimenopausal women; many cases present early stage | Median diagnosis age 46 years in review; typical age 50–55 years in large IHC cohort; 50–80% detected at FIGO IA (pqac-00000002, pqac-00000009, pqac-00000011) | Suggested: HP:0003596 Adult onset; NCIT: Perimenopausal; FIGO stage terms need verification | Human review/cohort 2023–2024 (pqac-00000002, pqac-00000009, pqac-00000011) |
| core phenotypes | Common manifestations include abdominal/pelvic symptoms and endocrine manifestations, but not all tumors are estrogenic | Iranian cohort: abdominal pain 56%; menopause in 69.2%; review notes up to 30% do not produce estrogen (pqac-00000001, pqac-00000002) | Suggested: HP:0002027 Abdominal pain; HP:0000132 Abnormality of female internal genitalia; HP:0000857 Menstrual irregularity; HP:0008222 Precocious puberty/endometrial effect terms may apply case-by-case and need verification | Human cohort/review 2024 (pqac-00000001, pqac-00000002) |
| anatomy | Primary site is ovary, arising from granulosa cells within sex cord-stromal tissue; recurrent/metastatic disease can involve abdomen/pelvis | Ovarian tumors in 81.3% of cohort; recurrences often abdominal in case literature; model tumors obliterate ovarian tissue (pqac-00000001, pqac-00000018) | Suggested: UBERON:0000992 ovary; CL:0000501 granulosa cell; UBERON female gonad-associated stroma terms need verification | Human cohort 2024; mouse model 2023 (pqac-00000001, pqac-00000018) |
| FOXL2 genomics | Somatic FOXL2 c.402C>G (p.C134W) is the central driver lesion in most AGCTs | Present in ~95–97% of AGCTs; 223/225 tested tumors positive in the 290-case IHC/molecular cohort; Open Targets links FOXL2 to ovarian granulosa cell tumor (pqac-00000001, pqac-00000002, pqac-00000009, pqac-00000000) | Suggested: HGNC:FOXL2; Sequence variant FOXL2 p.C134W; MONDO_0023283 association | Human cohort/review 2024; disease-target association resource (pqac-00000001, pqac-00000002, pqac-00000009, pqac-00000000) |
| secondary genomics | Recurrent secondary alterations occur in a subset, especially in recurrent/advanced disease, but AGCT remains genomically relatively homogeneous | Review of 423 samples: TERT promoter 56%, KMT2D 16.8%, CDKN2A/B deletions 10.2%, TP53 8.3%, MTAP deletion 5.8%, PIK3CA 5.4%; independent 93-case study: KMT2D 10/93 (10.8%); whole-genome study found chromosome 12 and 14 gain and chromosome 22 loss; TP53-mutant high-grade subgroup in 3 patients (pqac-00000002, pqac-00000011, pqac-00000003) | Suggested: HGNC:TERT, KMT2D, CDKN2A, CDKN2B, TP53, MTAP, PIK3CA; CNV gain chr12/14, loss chr22; NCIT somatic mutation/CNV terms | Human genomic studies/review 2020–2024 (pqac-00000002, pqac-00000003, pqac-00000011) |
| pathways | Strongest mechanistic support centers on FOXL2-mutant interaction with TGFβ/SMAD signaling; PI3K/AKT and hormone signaling are also implicated | FOXL2C134W binds SMAD4/SMAD2/3 and induces EMT-like gene expression; mouse FOXL2 C134W tumors showed transcriptomic changes consistent with gain-of-function affecting TGFβ signaling; recurrent tumors altered LHCGR, INSL3, CYP19A1 and showed immune/hormone pathway enrichment (pqac-00000004, pqac-00000015, pqac-00000014) | Suggested GO: TGF-beta receptor signaling pathway; epithelial to mesenchymal transition; PI3K-AKT signaling; steroid hormone biosynthetic process; CL granulosa cell/fibroblast/macrophage | Human mechanistic study 2020; mouse causal model 2023; human transcriptomics 2023 (pqac-00000004, pqac-00000015, pqac-00000014) |
| pathology/IHC | Diagnosis relies on morphology plus sex cord-stromal markers; large 2024 cohort defines a practical immunophenotype | In 290 AGCTs: SF1 100%, FOXL2 98%, PR 94%, CD99 90%, AR 82%, inhibin A 78%, calretinin 45%, ER 41%; PD-L1 uniformly negative; HER2 negative; p53 aberrant in 1%; CTLA4 ~70% (pqac-00000009) | Suggested: NCIT Immunohistochemistry; HGNC/NCIT markers SF1/NR5A1, FOXL2, PR/PGR, AR, CD99, INHA, CALB2, ESR1, CTLA4, PD-L1/CD274, HER2/ERBB2 | Human pathology cohort 2024 (pqac-00000009) |
| biomarkers | Inhibin and AMH are the best-supported circulating biomarkers for diagnosis/follow-up; endocrine activity is variable | Review: inhibin A/B produced in almost all patients and correlates with disease activity; AMH sensitivity 89% and specificity 93%; up to 30% of tumors are non-estrogenic (pqac-00000001) | Suggested: CHEBI/NCIT inhibin A, inhibin B, anti-Mullerian hormone, estradiol; LOINC assay mappings need verification | Human review 2024 (pqac-00000001) |
| imaging/diagnostics | MRI often shows cystic, solid, or cystic-solid ovarian masses with hemorrhagic features; pathology confirmation remains required | 10-case AGCT with normal estrogen: ages 28–81, mean 54±16; metastatic lesions all cystic; described “honeycomb” and “Swiss cheese” signs; high DWI signal in solid components (pqac-00000012 not applicable, pqac-00000001 not imaging; evidence from retrieved study summarized in search output) | Suggested: NCIT Magnetic Resonance Imaging; RadLex ovarian mass/cystic lesion terms need verification | Human imaging series 2024 (source retrieved in search results; no citeable context ID available) |
| natural history/prognosis | Prognosis is often favorable initially but late recurrence is a defining feature; very long follow-up is needed | Recurrence about 20% in reviews; one-third relapse between 4–8 years in 2021 review; latency typically 5–10 years and can exceed 20 years; recurrence rates across series 10–64%; average relapse 48–57 months; 10-year survival ~90% stage I vs 17–33% stage III–IV (pqac-00000001, pqac-00000002, pqac-00000011) | Suggested: NCIT recurrent neoplasm; HP recurrent ovarian neoplasm term needs verification; FIGO stage ontology terms need verification | Human reviews 2021–2024 (pqac-00000001, pqac-00000002, pqac-00000011) |
| prognostic factors | Prognostic biomarker evidence is limited and heterogeneous; some IHC markers correlate with worse outcomes | Review found worse prognosis associated with CD56, GATA-4, and SMAD3 expression; ER, AMH, and inhibin were not prognostic; Ki-67, p53, β-catenin, HER2 inconsistent (pqac-00000010, pqac-00000011) | Suggested: HGNC/NCIT NCAM1(CD56), GATA4, SMAD3, MKI67, TP53, CTNNB1, ERBB2 | Systematic review 2023 (pqac-00000010, pqac-00000011) |
| standard treatments | Surgery is the cornerstone; systemic therapy is used for advanced/recurrent disease, but evidence is mostly retrospective/small-series | Review notes surgery is standard; CAP response rate 60% and PVB 66% in small series; systemic chemotherapy remains standard for advanced disease (pqac-00000001, pqac-00000002) | Suggested NCIT: Oophorectomy, Hysterectomy, Cytoreductive Surgery, Adjuvant Chemotherapy, Cyclophosphamide, Doxorubicin, Cisplatin, Vinblastine, Bleomycin, Etoposide, Paclitaxel, Carboplatin | Human review 2024; historical clinical evidence summarized therein (pqac-00000001, pqac-00000002) |
| endocrine/targeted therapy | Hormonal and precision approaches are increasingly used in recurrent disease; evidence remains early | Review reports long partial responses with temozolomide+TRC102 (>12 months in 2 AGCT patients) and paclitaxel+nilotinib (>5 years in 2 AGCT patients); JNK inhibition reduced growth in patient-derived xenografts; TILs from 11 patients showed 100% autologous tumor reactivity and 57% reactivity to FOXL2 peptides in vitro (pqac-00000003) | Suggested NCIT: Aromatase inhibitor, letrozole, exemestane, leuprolide acetate, temozolomide, nilotinib, JNK inhibitor, tumor-infiltrating lymphocyte therapy | Human review 2024 summarizing case/preclinical evidence (pqac-00000003) |
| experimental trials | Multiple modern interventional studies are testing endocrine, NOTCH/gamma-secretase, and TGFβ/activin-axis strategies | NCT06169124 phase 2 darolutamide + leuprolide acetate + exemestane, active-not-recruiting, planned n=17; NCT05872204 phase 2 abemaciclib + letrozole, recruiting, planned n=100 rare ER+ ovarian cancers; NCT05348356 phase 2 nirogacestat, completed, n=53, 150 mg BID; NCT06254781 luspatercept single-patient completed study, n=1 (pqac-00000005, pqac-00000006) | Suggested NCIT: Clinical Trial, Darolutamide, Leuprolide Acetate, Exemestane, Abemaciclib, Letrozole, Nirogacestat, Luspatercept | ClinicalTrials.gov evidence 2022–2025 (pqac-00000005, pqac-00000006) |
| prevention | No established primary prevention or population screening strategy is supported by retrieved evidence; management focuses on surveillance after treatment | No validated population screening biomarker or prevention intervention identified in gathered evidence; long-term follow-up emphasized because relapse may occur decades later (pqac-00000002, pqac-00000011) | Suggested NCIT: Surveillance, Follow-Up; secondary prevention/screening mappings need verification | Human reviews 2023–2024 (pqac-00000002, pqac-00000011) |
| environmental/inherited risks | Evidence for environmental causes, protective factors, or common hereditary predisposition is currently limited/unclear in retrieved data | No consistent environmental risk factor identified in gathered evidence; AGCT is primarily characterized as a somatic FOXL2-driven neoplasm; isolated hereditary reports exist for sex cord-stromal tumors but not enough for routine AGCT risk assignment here (pqac-00000002, pqac-00000011) | Suggested: Etiology unknown/nonhereditary in most cases; germline predisposition terms need verification | Review-level evidence; evidence gap noted (pqac-00000002, pqac-00000011) |
| tumor microenvironment | Recurrent AGCT shows stromal depletion and myeloid enrichment, suggesting relapse-associated microenvironment remodeling | 24 tumors analyzed (8 primary, 16 recurrent); 31 DEGs; recurrent tumors had increased neutrophils/macrophages and decreased CAFs/endothelial cells; CAF depletion validated in independent datasets (pqac-00000012, pqac-00000013, pqac-00000015) | Suggested GO/CL: macrophage, neutrophil, endothelial cell, fibroblast/cancer-associated fibroblast, hormone signaling, immune response | Human transcriptomic/TME study 2023 (pqac-00000012, pqac-00000013, pqac-00000015) |
| models | The best current causal model is the Foxl2 C134W knock-in mouse; additional PI3K/PTEN/FOXO and other models support pathway biology but do not fully recapitulate human AGCT | In Foxl2+/C134W mice, all females developed ovarian tumors before 18 months; 50% of mutant females produced offspring after 6 months with WT males; primordial follicles markedly reduced; no recurrent driver beyond C134W identified in tumors; review of models notes existing mouse models do not completely recapitulate human molecular phenotype (pqac-00000018, pqac-00000021, pqac-00000022, pqac-00000016) | Suggested: NCBITaxon:10090 mouse; CL granulosa cell; GO TGF-beta signaling, follicle development, PI3K-AKT signaling | Mouse causal model 2023; prior mouse model review 2015 (pqac-00000018, pqac-00000021, pqac-00000022, pqac-00000016) |


*Table: This compact table summarizes high-confidence, evidence-backed facts for adult-type ovarian granulosa cell tumor across disease identity, biology, diagnosis, prognosis, treatment, and models. It is designed for rapid knowledge-base population and flags ontology mappings that need verification.*