| Domain | Key finding | Suggested ontology identifiers/terms | Evidence/qualification |
|---|---|---|---|
| Disease class | Rare ovarian sex cord-stromal tumor; malignant behavior is variable and linked to stage/differentiation. Likely maps to an ovarian Sertoli-Leydig cell tumor concept rather than a uniquely curated MONDO term for the malignant subset. | MONDO: curator validation needed; MeSH: Sertoli-Leydig Cell Tumor; NCIT: ovarian sex cord-stromal tumor / Sertoli-Leydig cell tumor concepts, curator validation needed | Registry-based cohort and reviews describe SLCT as an ovarian sex cord-stromal neoplasm, often in adolescents/young adults; exact MONDO term for the malignant ovarian subset was not confirmed from available context. (pqac-00000001, pqac-00000000) |
| Epidemiology | Very rare; occurs primarily in adolescents and young adult females. In the international registry, median age at diagnosis was 17 years (range 2–61). | HPO onset term suggestion: Juvenile onset / Adolescent onset / Young adult onset, curator validation needed | Best available cohort in context: 49 SLCTs with median age 17 years; disease-level population incidence remains sparse in available evidence. (pqac-00000000, pqac-00000003) |
| Phenotype | Abdominal/pelvic mass or pain at presentation is common for ovarian tumors, although exact frequency for this cohort was not captured in available excerpts. | HPO: Abdominal pain [HP:0002027]; Pelvic pain [HP:0012532]; Abdominal mass [HP:0012745] | Include as common ovarian tumor presentation, but frequency should be curator-confirmed from full-text clinical series. (pqac-00000001) |
| Phenotype | Virilization/androgen excess is a characteristic presentation in a subset of SLCTs. | HPO: Virilization [HP:0000138]; Hyperandrogenism [curator validation needed] | Registry and pathology literature note hormonal symptoms as common; androgenic effects are a recognized feature of DICER1-mutant SLCT. (pqac-00000000, pqac-00000001) |
| Phenotype | Hirsutism may occur as part of androgen excess. | HPO: Hirsutism [HP:0001007] | Supported as a clinically plausible androgen-excess manifestation; exact frequency not available in current context. (pqac-00000000) |
| Phenotype | Amenorrhea or irregular menstruation may occur due to androgen secretion. | HPO: Amenorrhea [HP:0000141]; Irregular menstruation [HP:0000858] | Commonly reported in SLCT case literature, but exact cohort frequency was not available in retrieved evidence excerpts. (pqac-00000000) |
| Phenotype | Elevated testosterone can be a laboratory abnormality reflecting steroidogenic tumor activity. | HPO: Elevated circulating testosterone level [curator validation needed] | Use as a lab phenotype; available context supports hormone-related symptoms rather than exact hormone distributions. (pqac-00000000, pqac-00000001) |
| Phenotype | Precocious puberty is relevant particularly in pediatric cases with hormone-secreting tumors. | HPO: Precocious puberty [HP:0000826] | Applicable mainly to children; age range in registry extended to 2 years, supporting pediatric relevance. (pqac-00000003) |
| Anatomy | Primary site is the ovary, arising from ovarian sex cord/stromal elements. | UBERON: ovary [UBERON:0000992]; ovarian stroma / sex cord-stromal tissue: curator validation needed | Disease is consistently classified as ovarian sex cord-stromal. (pqac-00000001, pqac-00000019) |
| Cell type | Tumor shows Sertoli-like and Leydig-like differentiation; exact Cell Ontology mappings may require curator review. | CL: Sertoli cell [curator validation for ovarian Sertoli-like tumor cell]; Leydig cell [curator validation for ovarian steroidogenic/Leydig-like tumor cell] | Histopathologic definition is based on Sertoli-Leydig differentiation, but exact neoplastic ovarian counterparts may not have direct CL terms. (pqac-00000000) |
| Genetics | DICER1 is the major disease gene. Germline pathogenic loss-of-function variants predispose, often with a second somatic RNase IIIb hotspot mutation in tumor. | HGNC: DICER1 [HGNC:17098]; NCBI Gene: DICER1; cytoband 14q32.13 | Central mechanistic theme across SLCT cohorts and DICER1 syndrome literature. (pqac-00000002, pqac-00000016, pqac-00000020) |
| Genetics | In the registry, 97% (36/37) of sequenced SLCTs carried DICER1 RNase IIIb hotspot mutations; 22 had germline LOF, 3 mosaic, and 11 tumor-limited mutations. | Sequence ontology terms: loss_of_function_variant, missense_variant, splice_region_variant; ACMG classes: pathogenic/likely pathogenic where curated | Strong primary cohort evidence for two-hit DICER1 architecture. (pqac-00000000, pqac-00000016) |
| Genetics | Intronic germline DICER1 variants can be missed by conventional exon-focused testing; splicing analysis may be required. | DICER1 intronic/splicing variant testing; RNA/splice assay concepts, curator validation needed | 2023 report identified novel intronic variants interfering with normal splicing and recommended intron sequencing when clinical suspicion remains high. (pqac-00000009) |
| Mechanism | Upstream mechanism: DICER1 dysfunction alters pre-miRNA cleavage, especially 5p miRNA processing, leading to abnormal post-transcriptional gene regulation. | GO: pre-miRNA processing [GO:0031053]; gene silencing by miRNA [GO:0035195]; miRNA-mediated gene silencing [curator validation if separate term needed] | DICER1 encodes an RNase III endonuclease; RNase IIIb hotspot mutations disrupt miRNA processing and alter mRNA expression. (pqac-00000001, pqac-00000002) |
| Mechanism | Downstream consequence: dysregulated growth/signaling and lineage-specific tumorigenesis; DICER1-mutant and wild-type tumors show different mRNA expression profiles. | GO: regulation of cell proliferation [GO:0042127]; cell population proliferation [GO:0008283] | Molecular profiling supports biologic heterogeneity by DICER1 status and differentiation. (pqac-00000008) |
| Mechanism | Endocrine phenotype likely reflects androgen biosynthesis by Leydig-like steroidogenic cells. | GO: androgen biosynthetic process [GO:0006703] | Functional link is clinically inferred from virilization/hyperandrogenic presentations; direct pathway assays were not available in current context. (pqac-00000000) |
| Pathology/IHC | Diagnostic sex cord-stromal markers include SF1, inhibin A, calretinin, CD99, FOXL2, AR/ER/PR; morphology remains the gold standard. | NCIT/IHC terms: Steroidogenic factor 1, inhibin A, calretinin, FOXL2; exact NCIT IDs curator validation needed | 2025 molecular/IHC study found high expression of sex cord markers; broader gynecologic pathology review supports IHC adjunctive use. (pqac-00000008) |
| Molecular pathology | Well-differentiated SLCT may be biologically distinct from moderately/poorly differentiated tumors; DICER1 mutations are characteristic of moderate/poor differentiation, FOXL2 mutations are uncommon and mutually exclusive in one recent study. | DICER1-mutant SLCT; FOXL2-mutant SLCT, curator validation needed | Recent profiling suggests subtype heterogeneity, but this evidence is from 2025 and should be integrated cautiously into current curation. (pqac-00000008) |
| Diagnostic workflow | Recommended evaluation includes expert gynecologic pathology review, immunohistochemistry, tumor/germline DICER1 testing, and consideration of intronic sequencing/splicing analysis if exon testing is negative despite high suspicion. | NCIT: immunohistochemistry; molecular genetic testing; next-generation sequencing; RNA splicing analysis, curator validation needed | Central pathology review improved diagnostic concordance; DICER1 testing has familial implications. (pqac-00000002, pqac-00000009, pqac-00000014) |
| Natural history | About 50% of registry cases were stage IA; all stage IA patients were free of disease at median 19-month follow-up in the 2017 cohort excerpt. | FIGO stage IA; HPO/NCIT stage terms as applicable | Early-stage disease has favorable outcomes with surgery-focused management. (pqac-00000000) |
| Prognosis | Recurrence occurred in 16.3% (8/49); among recurrent cases, 50% died, with median death at 35.5 months. Poor differentiation and tumor-limited DICER1 mutation status were adverse features. | NCIT: disease recurrence; overall survival; recurrence-free survival | Best direct prognostic evidence in available context comes from the international registry. (pqac-00000000, pqac-00000002) |
| Prognosis | Predisposing germline/mosaic DICER1 variants were associated with better overall and recurrence-free survival than tumor-limited mutations. | NCIT: germline mutation, mosaicism, somatic mutation | Prognostic association requires cautious interpretation because of small numbers but is repeatedly emphasized in the registry evidence. (pqac-00000002, pqac-00000016) |
| Surgery | Fertility-sparing surgery is standard real-world management for many unilateral stage I tumors; unilateral salpingo-oophorectomy is commonly used. | NCIT: Unilateral salpingo-oophorectomy; Fertility-sparing surgery | Registry data show most stage IA cases treated with surgery alone; exact operative distributions require full-text confirmation. (pqac-00000010, pqac-00000019) |
| Systemic therapy | BEP (bleomycin, etoposide, cisplatin) is a commonly used regimen, especially for advanced, recurrent, or poorly differentiated disease. | NCIT: Bleomycin; Etoposide; Cisplatin; BEP regimen | In the registry, BEP/cisplatin-etoposide-bleomycin was the most common chemotherapy regimen. (pqac-00000010) |
| Systemic therapy | Carboplatin plus paclitaxel is an actively studied alternative regimen for advanced/recurrent sex cord-stromal tumors. | NCIT: Carboplatin; Paclitaxel | Phase II randomized GOG-0264 compares paclitaxel/carboplatin versus BEP in advanced or recurrent sex cord-stromal tumors including SLCT. (pqac-00000012, pqac-00000013) |
| Targeted/antiangiogenic therapy | Bevacizumab has been studied in recurrent ovarian sex cord-stromal tumors, including SLCT-relevant populations. | NCIT: Bevacizumab | Completed Phase II NCI study enrolled recurrent ovarian sex cord-stromal tumors; applicability to SLCT is indirect because histologies were pooled. (pqac-00000011) |
| Prevention / surveillance | There is no established primary prevention for SLCT itself. In DICER1 syndrome, cascade testing and surveillance are important; pelvic ultrasound is used in surveillance frameworks. | NCIT: Genetic counseling; Cascade testing; Pelvic ultrasound | Surveillance is relevant mainly for DICER1 carriers and families rather than the general population. (pqac-00000015, pqac-00000017) |
| Inheritance | For DICER1-related predisposition, inheritance is autosomal dominant with reduced/incomplete penetrance. | MONDO/NCIT: DICER1 syndrome; autosomal dominant inheritance [curator validation needed] | Applies to the hereditary predisposition syndrome, not to every SLCT case because some are tumor-limited. (pqac-00000020, pqac-00000021) |
| Other species / models | Mouse evidence suggests biallelic Dicer1 alterations can drive lineage-specific gynecologic tract tumors, but SLCT-specific model details were not available in full in current context. | MGI/NCBI model annotations: curator validation needed | Mention as emerging mechanistic support only; not enough detail in available context for robust annotation. (pqac-00000008) |
| Evidence gaps | Limited disease-specific randomized therapy evidence; incomplete population incidence/prevalence data; uncertain exact ontology mappings for malignant subset and ovarian Sertoli-/Leydig-like neoplastic cells; sparse epigenomic/proteomic/metabolomic evidence in available context. | Curator validation needed across MONDO, CL, some HPO lab terms, and NCIT procedure/drug IDs | Important to annotate uncertainty explicitly to avoid overclaiming in the knowledge base. (pqac-00000000, pqac-00000008, pqac-00000011, pqac-00000012) |


*Table: This table summarizes high-value knowledge-base annotations for malignant ovarian Sertoli-Leydig cell tumor, including ontology suggestions, core genetic and mechanistic findings, and clinically relevant evidence with uncertainty flags for curator review.*