Open questions — uterine adenosarcoma¶
Last curated: 2026-08-31. Replaces the seed set. In this condition, “open” usually means no adequately powered study exists, not that two well-powered studies disagree. A question that can only be answered by a rare-tumour consortium or pathology-linked registry says so. Stable IDs (OQ-n). Supporting PMIDs/NCTs were retrieved live in the 2026-08-31 build session.
How to read priority¶
Tier 1 = answering it would change practice or reorder counselling, and a study is designable today (usually as a multi-institutional registry or basket, not a classical RCT). Tier 2 = important, but blocked on tools, numbers, or a Tier-1 answer. Tiers are curator judgment.
Dots not yet connected¶
Cross-domain junctions where two bodies of evidence both exist in this knowledge base but no study has joined them.
| # | Dot A | Dot B | The missing junction | Powers |
|---|---|---|---|---|
| D1 | Morcellation-safety literature is written about uterine sarcoma as a class (occult sarcoma 1/278 leiomyoma hysterectomies; PMID 26646120, 30447212) | Adenosarcoma-specific presentation as a polyp, not a fibroid, and SO-stratified outcome (PMID 2156771, 25449308) | No study reports how often adenosarcoma is morcellated, or whether morcellation changes adenosarcoma-specific survival | OQ-3 |
| D2 | SO is a morphological ≥25% volume call (PMID 2535774) with independent survival effect (PMID 25449308) | SO tracks copy-number complexity, not mutation count (mean CNVs 24.6 vs 5; PMID 25231023); high-grade disease is TP53-enriched (PMID 28834809) | No study has asked whether a genomic complexity score outperforms or refines the 25% volume rule | OQ-1, OQ-4 |
| D3 | PI3K/AKT/PTEN pathway alteration in 13/18 (72%) in a selected sequencing series (PMID 25231023) | No PI3K-pathway-selected adenosarcoma trial identified (ClinicalTrials.gov search rerun 2026-09-01) | The most frequent pathway finding in that small series has not yet been tested prospectively in this histology | OQ-6 |
| D4 | Carroll’s non-significant adjuvant signal in stage I SO (PFS 46.7 vs 29.4 months, p=0.28; PMID 25449308) | ESGO “option” vs French “not established” for adjuvant chemo (PMID 39322612, 37202293) | Guidelines disagree in wording over a comparison that has never been run multi-institutionally | OQ-2 |
| D5 | Nodal metastasis ~3% but aHR 2.34 for CSS when present (PMID 28109626) | SO, large tumour and deep invasion associated with nodal risk in a 230-case literature review (PMID 28109626) | No prospective selection rule for lymphadenectomy has been tested | OQ-5 |
| D6 | Late local recurrence (⅓ of Clement recurrences ≥5 years; PMID 2156771) and lung as 75% of Tate’s distant recurrences (PMID 29441675) | No prospective surveillance schedule | Timing and site of imaging are extrapolated, not measured against outcome | OQ-7 |
| D7 | den Hollander HRQoL in mixed uterine sarcoma (n=13): sexual/urological/menopausal, shock, missing sarcoma knowledge (PMID 35443673) | Standard operation is TAH-BSO (PMID 27718181) with ovarian preservation unproven in this histology (PMID 28541635) | No adenosarcoma-specific HRQoL module or ovarian-preservation decision aid exists | OQ-8 |
| D8 | ATRX mutation in 2 high-grade recurrences after low-grade primaries (PMID 36138078) | Pathology-at-recurrence influences OS (PMID 29445312) | Low-grade → high-grade transformation is observed, not mapped as a surveillance or treatment trigger | OQ-4, OQ-7 |
| D9 | Atypical polyps share 12q13–15 and 6q25.1 gains with early adenosarcoma but had zero progression over 150 months (PMID 34675347) | Diagnostic criteria versus adenofibroma remain mitotic-count conventions from 1981/1990 (PMID 6263458, 2156771) | Morphology, copy number and outcome have not been jointly modelled as a diagnostic rule | OQ-9 |
When a junction study appears, connect the dot here and sharpen or close the powered question.
Tier 1 — highest-value directions¶
OQ-1. Is anything other than sarcomatous overgrowth independently prognostic once analyses are restricted to multivariable models with sarcoma-pathologist review?¶
SO is the consistent independent factor (Carroll 2014, PMID 25449308; Howitt 2015, PMID 25231023). LVSI is the leading additional candidate (median OS 1.0 vs 8.9 years; Nathenson 2018, PMID 30044322) but the two large multivariable series are from the same institution with overlapping years. Yuan’s LVSI HR 11.95 is n=49 (PMID 31139558). A pooled multi-institutional dataset with path review, SO, LVSI, invasion, age and stage in one model is designable from existing records. → staging-and-prognostic-factors, sarcomatous-overgrowth
OQ-2. Does adjuvant chemotherapy change outcome in stage I sarcomatous overgrowth?¶
Carroll’s numerical PFS/OS benefit is not significant (p=0.28 / 0.18) and is the entire comparative signal (PMID 25449308). ESGO allows considering chemo after morcellated high-grade/SO and in resected stage II–IV; French GSF says the role is not established (PMID 39322612, 37202293). A GCIG/EURACAN registry-randomised or carefully matched comparison is the feasible design; a classical phase 3 is not. → adjuvant-and-systemic-therapy, guidelines
OQ-3. Can preoperative diagnosis be made reliably enough to change the morcellation decision for this histology?¶
Occult uterine sarcoma 1/278 is a class estimate (PMID 26646120); adenosarcoma often presents as a polyp (PMID 2156771). MRI features have been catalogued (Morikawa 2025, PMID 39729099) and compared with polyps (Harada 2025, PMID 40210681) without a locked diagnostic threshold or a hysterectomy-gold-standard accuracy study. An adenosarcoma-specific morcellation outcome does not exist (one case-report PubMed hit, PMID 27769260). → clinical-presentation-and-imaging, red-flags-and-safety-concerns
OQ-4. Do any molecular findings support a diagnostic or prognostic test yet?¶
Howitt: no diagnostic tool (PMID 25231023). BAP1 loss ~25% and relatively specific among 196 gyn mesenchymal tumours (PMID 36138078) is the closest marker and is untested in the atypical-polyp differential. TP53/p53 identifies high-grade disease (PMID 28834809). DICER1 is useful only when negative, to make ERMS unlikely (PMID 31900434). ATRX as a transformation marker is n=3 (PMID 36138078). → molecular-and-genomic-features
OQ-5. Who, if anyone, should have a lymphadenectomy?¶
Nodal metastasis 2.9–3.1% (PMID 28109626, 27771166). When present, CSS aHR 2.34, comparable to ESS/LMS (PMID 28109626). SO, size and deep invasion associate with nodal risk in a 230-case literature review. Whether dissection changes outcome is untested. A preoperative/intraoperative rule could be specified and validated. → surgical-management
OQ-6. What would an adequately powered interventional study even look like?¶
258 PubMed records; largest institutional series 165; largest dataset 2,205 NCDB without path review. FUCHSia enrolled 17 across several histologies (NCT03926936). Elacestrant NCT07467772 estimates 30 across four uterine-sarcoma subtypes. The design that matches the disease is a rare-tumour consortium basket with pre-specified adenosarcoma reporting, or a registry-randomised adjuvant question in stage I SO — not a stand-alone phase 3. → clinical-trials-landscape
Tier 2 — by theme¶
Pathology and diagnosis¶
- OQ-7. Surveillance: does lung imaging at defined intervals in SO-positive disease change outcome, or only the time metastasis is labelled? Tate: 75% of distant recurrences included lung, in a literature-assembled series (PMID 29441675). Clement: late local recurrence (PMID 2156771). No schedule has been tested. → recurrence-and-surveillance
- OQ-8. Does BSO change outcome in premenopausal stage I disease without SO? Nasioudis could not conclude for this histology (PMID 28541635); Li n=6 with no recurrences (PMID 35005157). Hormone-receptor biology makes this different from LMS. → surgical-management, patient-experience-and-advocacy
- OQ-9. Can a mitotic/cellularity/copy-number rule separate adenosarcoma from adenofibroma and from atypical polyps with a known error rate? Gallardo’s two fatal “adenofibromas” (PMID 18941402) versus Chapel’s 150-month benign follow-up of atypical polyps that share copy-number events (PMID 34675347). → pathology-and-diagnosis
- OQ-10. Is 25% the right SO cut? Historical (PMID 2535774). SO as a continuous volume fraction against survival has not been modelled. High-grade stroma without SO is a 9-case argument (PMID 28834809). → sarcomatous-overgrowth
Registries and measurement¶
- OQ-11. How much do registry 5-year survival figures (Arend stage I 79%) mislead once SO is restored? Opposite biases: registries miss SO; literature-assembled series (Tate 34% death) enrich for published catastrophe (PMID 20688363, 29441675, 33680946). A pathology-linked registry is the design. → epidemiology-and-burden
- OQ-12. Did FUCHSia (NCT03926936) enrol any adenosarcomas, and did they respond? Completed 2022, n=17,
hasResultsfalse, not PubMed-indexed this session. → clinical-trials-landscape, adjuvant-and-systemic-therapy
Experience¶
- OQ-13. Do adenosarcoma HRQoL priorities differ from LMS enough to need a histology-specific module? den Hollander cannot answer (n=13 mixed; PMID 35443673). Items on sarcoma knowledge, diagnostic shock and menopause are already missing from EORTC tools. → patient-experience-and-advocacy
Closed¶
None. This is the first build; the seed questions SQ-1 through SQ-6 are rewritten above as OQ-1, OQ-2, OQ-3, OQ-4, OQ-11, OQ-6.