MPNST mit widrigen molekularen / klinischen Eigenschaften: biallelic CDKN2A/B Verlust (> 80%...

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ID	`RF-MPNST-HIGH-RISK-BIOLOGY`
Art	Warnhinweis
Status	reviewed 2026-04-27 \| pending_clinical_signoff
Erkrankungen	`DIS-MPNST`
Quellen	`SRC-NCCN-SARCOMA`

Ursprung der Roten Flagge

Begriffsbestimmung	MPNST with adverse molecular / clinical features: biallelic CDKN2A/B loss (>80% high-grade MPNST; defines transition from atypical neurofibroma to malignancy), TP53 mutation (~50% high-grade, prognostically poor), NF1 germline loss-of-function (~50% MPNST cases — NF1-associated, worse prognosis than sporadic), tumor size >10 cm, or post-radiation MPNST (10% — biologically aggressive) — each shifts toward intensified neoadjuvant doxorubicin + ifosfamide and aggressive surgical margins.
Klinische Richtung	Intensivierung
Kategorie	high-risk-biology

Logik auslösen

{
  "any_of": [
    {
      "finding": "BIO-CDKN2A",
      "value": "biallelic_loss"
    },
    {
      "finding": "BIO-TP53-MUTATION",
      "value": "positive"
    },
    {
      "finding": "nf1_germline_loss_of_function",
      "value": true
    },
    {
      "comparator": ">",
      "finding": "primary_tumor_size_cm",
      "threshold": 10
    },
    {
      "finding": "post_radiation_mpnst",
      "value": true
    }
  ],
  "type": "biomarker"
}

Anmerkungen

CDKN2A/B biallelic loss is the defining genomic event differentiating high-grade MPNST from atypical neurofibromatous neoplasm of uncertain biologic potential (ANNUBP) per recent consensus criteria. TP53 mutations co-occur in high-grade — confer chemoresistance signal. NF1-associated MPNST has worse 5-yr OS (~30%) vs sporadic (~50%). Post-radiation MPNST (latency 10-20 yr) — biologically aggressive, often unresectable due to RT field constraints. Size >10 cm is Joensuu prognostic threshold. Intensification: neoadjuvant AI (doxorubicin + ifosfamide) followed by R0 resection + adjuvant RT — improves limb salvage rate. Selumetinib has activity in NF1- related plexiform NF (SPRINT) but data in frank MPNST limited.

Verwendet von

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