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Red flags and safety concerns in uterine adenosarcoma

TL;DR — The safety problem is preoperative misidentification as a polyp or fibroid, which leads to incomplete excision, delayed diagnosis, and occasionally morcellation. Occult uterine sarcoma among hysterectomies for presumed leiomyomas was 1 in 278 (3.60 per 1,000, 95% CI 2.97–4.23) in a 34,728-procedure Kaiser cohort; occult leiomyosarcoma 1 in 429 (Raine-Bennett 2016, PMID 26646120). Unexpected sarcoma among benign-indication hysterectomies was 0.13% (1 in 752) in Olmsted County, 0.39% (1 in 256) among fibroid surgeries, and all unexpected fibroid-associated sarcomas in that series were leiomyosarcoma — not adenosarcoma (Multinu 2019, PMID 30447212). Adenosarcoma-specific morcellation data are essentially absent (one adenosarcoma+morcellation PubMed hit this session, a case report: Krentel 2016, PMID 27769260). The adenosarcoma-specific trap is the “recurrent polyp”: five of Clement’s 100 patients had presented that way (Clement 1990, PMID 2156771). Under-recognition of sarcomatous overgrowth converts a high-risk tumour into a “low-grade” label (Carroll 2014, PMID 25449308).

Preoperative misdiagnosis as polyp or fibroid

Clement: five patients presented on multiple occasions with “recurrent polyps” interpreted retrospectively as adenosarcoma (Clement 1990, PMID 2156771). Tate: preoperative radiology and pathology “occasionally failed to help reach the correct diagnosis” (Tate 2018, PMID 29441675). Howitt’s overlapping polyps and Chapel’s atypical polyps show that even expert pathologists draw a line that follow-up then tests; those lesions were benign in follow-up, which does not make the line easy on the first sample (Howitt 2015, PMID 25118811; Chapel 2022, PMID 34675347).

Small biopsies or partial polypectomies may not represent the architecture of the whole mass. That sampling explanation is an inference from Clement’s recurrent-polyp cases and Tate’s documented preoperative diagnostic failures, not a measured biopsy sensitivity or a quantified mechanism (Clement 1990, PMID 2156771; Tate 2018, PMID 29441675).

Qualitative work in uterine sarcoma as a class documents the lived version: “I thought I had fibroids, and now I don’t” (den Hollander 2022, PMID 35443673). That study interviewed 13 patients with mixed uterine-sarcoma histologies; it is not adenosarcoma-specific and is cited here as the patient-facing form of the same misidentification.

Morcellation and upstaging

The morcellation literature is about occult leiomyosarcoma and uterine sarcoma as a class.

Study Population Occult sarcoma estimate Morcellation outcome
Raine-Bennett 2016, PMID 26646120 34,728 hysterectomies for leiomyomas, Kaiser 2006–2013 Occult uterine sarcoma 1/278 or 3.60/1,000 (2.97–4.23); occult LMS 1/429 or 2.33/1,000 (1.83–2.84) Stage I LMS: 8 (7.2%) power-morcellated, 27 (24.3%) non-power. Unadjusted 3-year DFS 0.54 / 0.19 / 0.51 for none / power / non-power (p=0.15); OS 0.64 / 0.75 / 0.68 (p=0.97). Combined morcellation vs none: death at 1 year RR 5.12 (1.33–19.76, p=0.02). Underpowered for 3-year OS and for power morcellation
Multinu 2019, PMID 30447212 4,232 hysterectomies, Olmsted; 3,759 benign-indication Unexpected sarcoma 0.13% (5/3,759, 95% CI 0.04–0.31%); among fibroids 0.39% (1 in 256). All 4 unexpected sarcomas in fibroid surgeries were LMS Incidence rose with uterine weight: 0.03% <250 g vs 15.4% (2/13) ≥2000 g. Peri/postmenopausal, large uteri, age ≥45 were risk factors

Neither study reports an adenosarcoma-specific morcellation outcome. A PubMed search for uterine adenosarcoma AND morcellation returned one record: Krentel 2016, a case of submucous adenosarcoma treated with minimally invasive technique (PMID 27769260). Do not generalise LMS morcellation survival splits to adenosarcoma.

ESGO 2024: avoid morcellation; if a high-grade component/SO tumour is morcellated, post-operative chemotherapy could be considered (Ray-Coquard 2024, PMID 39322612). That last clause is an option, not a standard, and is not supported by an adenosarcoma morcellation cohort.

Hur 2015 modelled laparoscopic hysterectomy with morcellation versus abdominal hysterectomy for large fibroids as a shared decision tool after the FDA communication: abdominal hysterectomy produced more adhesions, hernias, SSI, bowel obstruction and VTE, longer stay and slower return to work; 0.28% of fibroid-hysterectomy patients would have unsuspected sarcoma, with worse 5-year OS if morcellated (Hur 2015, PMID 26520875). Decision-tool modelling, not adenosarcoma data.

Under-recognition of sarcomatous overgrowth

Carroll’s stage I split — 77% recurrence with SO versus 22% without — makes an omitted SO assessment consequential (Carroll 2014, PMID 25449308). SO is a volume fraction (≥25%), so incomplete sampling can in principle miss a focal overgrown component; the rate of that error has not been measured. High-grade stroma without meeting 25% is a related concern: Hodgson argued any high-grade component should be reported even without SO, based on 9 cases (Hodgson 2017, PMID 28834809). No study measuring the rate of SO missed at initial diagnosis was identified in the PubMed search rerun 2026-09-01.

Delayed referral and rare-tumour expertise

French GSF and ESGO both locate care in specialist networks (Karabajakian 2023, PMID 37202293; Ray-Coquard 2024, PMID 39322612). The qualitative uterine-sarcoma study identified “dealing with lacking knowledge regarding sarcoma” as an HRQoL theme among patients and clinicians (den Hollander 2022, PMID 35443673). Trial ineligibility is structural: no dedicated adenosarcoma trial exists (see clinical-trials landscape).

Tamoxifen

NCI PDQ lists tamoxifen as a uterine-sarcoma risk factor and advises yearly pelvic exam and prompt report of non-menstrual bleeding (NCI PDQ — "Uterine Sarcoma Treatment", accessed 2026-09-01). Adenosarcoma-on-tamoxifen is a case-report association (Ceylan 2015, PMID 28913077; Soh 2008, PMID 19143068). ESGO: do not give tamoxifen as treatment for ER-positive adenosarcoma (agonist risk) (Ray-Coquard 2024, PMID 39322612). These are different claims — tamoxifen as a possible causal association versus tamoxifen as treatment — and both rest on weak histology-specific data.

Practical red flags (research knowledge, not advice)

Findings in this literature that precede a missed adenosarcoma:

  • Recurrent “benign” endometrial polyps, especially after more than one polypectomy (Clement 1990, PMID 2156771).
  • A polypoid mass with leaf-like architecture, periglandular cuffing, or unexpected stromal mitoses on a polyp report — the Howitt/Chapel atypical-polyp zone, which is usually benign and is the reason to get the diagnosis right rather than to assume sarcoma (Howitt 2015, PMID 25118811; Chapel 2022, PMID 34675347).
  • Planned morcellation of a uterus or fibroid without a strategy for unsuspected sarcoma (Raine-Bennett 2016, PMID 26646120; Multinu 2019, PMID 30447212) — a uterine-sarcoma-class problem that includes adenosarcoma by adjacency.
  • A “low-grade adenosarcoma” report that does not comment on sarcomatous overgrowth, myometrial invasion, or LVSI (Carroll 2014, PMID 25449308; Nathenson 2018, PMID 30044322).

Open questions

  • What fraction of adenosarcomas are first labelled polyp or fibroid, and how often does that labelling involve morcellation? Not measured histology-specifically.
  • A PubMed search rerun 2026-09-01 found no study measuring how often expert gynaecologic-pathology review changes an SO call or whether routine second review changes outcomes.

References

  1. Clement PB, Scully RE. Mullerian adenosarcoma of the uterus: a clinicopathologic analysis of 100 cases. Hum Pathol. 1990;21:363-81. PMID 2156771
  2. Tate K, et al. Uterine adenosarcoma in Japan. Asia Pac J Clin Oncol. 2018;14:318-325. PMID 29441675
  3. Howitt BE, et al. Uterine polyps with features overlapping with those of Müllerian adenosarcoma. Am J Surg Pathol. 2015;39:116-26. PMID 25118811
  4. Chapel DB, et al. Atypical uterine polyps show morphologic and molecular overlap with mullerian adenosarcoma but follow a benign clinical course. Mod Pathol. 2022;35:106-116. PMID 34675347
  5. Raine-Bennett T, et al. Occult Uterine Sarcoma and Leiomyosarcoma: Incidence of and Survival Associated With Morcellation. Obstet Gynecol. 2016;127:29-39. PMID 26646120
  6. Multinu F, et al. Incidence of sarcoma in patients undergoing hysterectomy for benign indications: a population-based study. Am J Obstet Gynecol. 2019;220:179.e1-179.e10. PMID 30447212
  7. Krentel H, et al. Submucous uterine adenosarcoma-minimally invasive treatment. World J Surg Oncol. 2016;14:271. PMID 27769260
  8. Hur HC, et al. Fibroid morcellation: a shared clinical decision tool for mode of hysterectomy. Eur J Obstet Gynecol Reprod Biol. 2015;195:122-127. PMID 26520875
  9. Carroll A, et al. Uterine adenosarcoma: an analysis on management, outcomes, and risk factors for recurrence. Gynecol Oncol. 2014;135:455-61. PMID 25449308
  10. Hodgson A, et al. High-grade Müllerian Adenosarcoma. Am J Surg Pathol. 2017;41:1513-1522. PMID 28834809
  11. Nathenson MJ, et al. The Importance of Lymphovascular Invasion in Uterine Adenosarcomas. Int J Gynecol Cancer. 2018;28:1297-1310. PMID 30044322
  12. den Hollander D, et al. 'I thought I had fibroids, and now I don't': a mixed method study on health-related quality of life in uterine sarcoma patients. Health Qual Life Outcomes. 2022;20:65. PMID 35443673
  13. Karabajakian A, et al. Uterin adenosarcoma: French Guidelines. Bull Cancer. 2023;110:836-843. PMID 37202293
  14. Ray-Coquard I, et al. ESGO/EURACAN/GCIG guidelines for the management of patients with uterine sarcomas. Int J Gynecol Cancer. 2024;34:1499-1521. PMID 39322612
  15. Ceylan Y, et al. Mullerian adenosarcoma of the uterus associated with tamoxifen treatment for breast cancer. Turk J Obstet Gynecol. 2015. PMID 28913077
  16. Soh E, et al. MRI findings of tamoxifen-associated uterine Müllerian adenosarcoma: a case report. Acta Radiol. 2008. PMID 19143068