Seeding evidence

All PMIDs verified via NCBI E-utilities. Quotes verbatim from abstract/full text. UNVERIFIED items listed at end.

1. Chordoma seeding

• Fernandes Cabral DT, Zenonos GA, Fernandez-Miranda JC, Wang EW, Gardner PA. Iatrogenic seeding of skull base chordoma following endoscopic endonasal surgery. J Neurosurg 2018;129:947. PMID 29271711. "Among 173 EESs performed for clival chordomas … 2 cases complicated by iatrogenic seeding (incidence 1.15%)". Denominator = 173 resections. Neither case followed biopsy alone. Both tumours aggressive (1p36 deletion, Ki-67 10–20%+). Mechanism: "decreased visualization during tumor removal combined with mucosal trauma and exposure of subepithelial elements".
• Gersey ZC … Gardner PA. Techniques to Reduce Iatrogenic Nasal Seeding in EES for Skull Base Chordoma. J Neurol Surg B 2026;87(4):e115. PMID 42404185, PMC13331662. 271 surgeries/194 patients 2001–2020; 3 seeding = 1.1%; mean 32.7 months to diagnosis. "lower incidence of surgical pathway seeding with EEA for chordomas (1.1%) when compared with studies done on open approaches (2.8–7.3%)". No biopsy-only seeding reported.
• Iloreta AM … Evans JJ. Surgical pathway seeding of clivo-cervical chordomas. J Neurol Surg Rep 2014;75:e246. PMID 25485223, PMC4242824. Pooled open literature: "14 of 497 (2.8%)". Table 1: every documented case followed a resection; zero followed diagnostic biopsy alone. Biopsy listed only as theoretical mechanism.
• Arnautović KI, Al-Mefty O. Surgical seeding of chordomas. J Neurosurg 2001;95:798. PMID 11702870. 82 patients, 6 (7.3%) surgical seeding, all after open resections; sites along operative route and at abdominal fat-graft harvest site; diagnosed 5–15 months post-op.
• Fischbein NJ et al. AJNR 2000;21:578. PMID 10730655. 3 patients; "noted only rarely".
• Fagundes MA et al. IJROBP 1995;33:579. PMID 7558946. 204 pts; 3/63 relapses (5%) in surgical pathway = 1.5% of cohort. Metastases lungs and bones.
• Austin JP et al. IJROBP 1993;25:439. PMID 8436522. ~10% of 26 recurrences in surgical pathway (~2/141).
• Vogin G et al. Head Neck 2016;38 Suppl 1:E1238. PMID 26339866. 371 pts; seeding along surgical pathway n=5 (1.3%).
• Nguyen B … Folbe AJ. Recurrence of Ventral Skull Base Lesions Attributed to Tumor Seeding: Systematic Review. World Neurosurg 2019;124:e395. PMID 30605757. 69 pts all pathologies; chordoma 33%; craniotomy 62%, endoscopic 7%.
• Krengli M et al. Tumour seeding in the surgical pathway after resection of skull base chordoma. Rep Pract Oncol Radiother 2016;21:407. PMID 27330428, PMC4899426. 34 patients described; in 5 largest series 1.3%–7.3% (mean 3.9%); median time 7–78 months. Framed as after resection.
• Bergh P et al. Prognostic factors in chordoma of sacrum and mobile spine, 39 pts. Cancer 2000;88:2122. PMID 10813725. Adverse factor: "performance of an invasive morphologic diagnostic procedure outside of the tumor center" (not biopsy per se). "FNA is the preferred method".
• Stacchiotti S, Sommer J. Lancet Oncol 2015;16:e71. PMID 25638683 (paywalled). Chordoma Foundation booklet (authorised restatement): "biopsies are not recommended if the tumor cannot be reached safely or when there is a high risk of spreading tumor cells… trocar CT-guided biopsy… needle is enclosed in a tube to keep tumor cells from spreading… surgeon take out the tissue around the area of the biopsy during surgery".
• Radaelli S et al. The sacral chordoma margin. EJSO 2020;46:1415. PMID 32402509. Specimen removed en bloc "including the biopsy track"; "Biopsy tract or surgical scars should be included in the low-dose CTV".
• Kaiser TE et al. Cancer 1984;53:2574. PMID 6713355. Sacrococcygeal: recurrence 28% without wound contamination vs 64% when tumour entered at surgery.
• Freeman JL et al. Acta Neurochir 2018;160:731. PMID 29270681. VERBATIM CONFIRMED: "Biopsy followed by attempted radical resection at a dedicated center does not affect PFS and, therefore, represents a reasonable first step in management for patients presenting outside of multidisciplinary setting." Initial surgery outside MDT centre: HR 2.83 for progression (multivariate); PFS 64 vs 25 months.
• Gokaslan ZL et al. J Neurosurg Spine 2016;24:644. PMID 26682601. Enneking-inappropriate margins HR 7.02 local recurrence.
• Boriani S et al. Spine 2006;31:493. PMID 16481964. Only margin-free en bloc gives CDF >5 yr.
• NOT FOUND: any numeric biopsy-tract recurrence rate after percutaneous CT-guided chordoma biopsy.

2. Cross-cancer needle-tract seeding and survival

• HCC: Silva MA et al. Gut 2008;57:1592. PMID 18669577. Pooled 2.7% overall, 0.9%/yr. No survival analysis in abstract.
• HCC survival: Fuks D et al. J Hepatol 2014;61:589. PMID 24818985. 309 transplant-listed, 80 biopsied; recurrence 9.3% vs 8.9% p=0.904; 5-yr OS 60% vs 61% p=0.601; "no argument to restrict biopsy".
• Breast: Diaz LK et al. AJR 1999;173:1303. PMID 10541110. 352 cases; displacement 32%; 42% <15 days, 31% 15–28 d, 15% >28 d (p<.005): "tumor cells do not survive displacement".
• Liebens F et al. Maturitas 2009;62:113. PMID 19167175. Displacement 22%; "No increase in local recurrence was reported after CNB".
• Maseki H et al. Asian J Surg 2023;46:3700. PMID 36732183. 4405 pts; seeding 3.0%; IBTR no different.
• Liikanen J et al. EJSO 2016;42:64. PMID 26427542. 1525 pT1, 9.5 yr median: CNB no adverse effect on survival.
• COUNTER: Sennerstam RB et al. Cancer Cytopathol 2017;125:748. PMID 28837268. CNB vs FNAB higher late distant mets; but eras differ (1971–76 vs 1991–95).
• Lung: Ayar D et al. J Thorac Imaging 1998;13:2. PMID 9440831. 68,346 TNB, 8 NTM = 0.012%. Ibukuro K AJR 2009 PMID 19843723: 4/713 (0.56%). Sano Y Cancer 2009 PMID 19685526: no chest-wall implantation; no pleural dissemination. COUNTER: Inoue M Ann Thorac Surg 2011 PMID 21440124 (pleural implantation risk in stage IB subpleural, DFS unaffected); Matsuguma H Ann Thorac Surg 2005 PMID 16305838 (8.6% vs 0.9% pleural recurrence/implantation).
• Sarcoma: Barrientos-Ruiz I et al. CORR 2017;475:511. PMID 27655183, PMC5213942. 180 pts; tract contamination 12% overall; open 20/62 (32%) vs percutaneous 1/118 (0.8%), OR 56; LRFS 107 vs 11 months if contaminated.
• Mankin HJ, Mankin CJ, Simon MA. JBJS Am 1996;78:656. PMID 8642021 (original 1982 PMID 7130225). 597 pts; diagnostic error 17.8%; outcome change 10.1%; "Errors, complications, and changes in the course and outcome were two to twelve times greater (p < 0.001) when the biopsy was done in a referring institution instead of in a treatment center."
• Brain: no denominatored rate for primary tumours. Cooper ME BJR Case Rep 2020 PMID 33029363 (complications 0.4–4%; seeding "rare"). Pinggera D Acta Neurochir 2017 PMID 28154933. Carnevale JA J Neurosurg 2022 PMID 34507279: brain METASTASES, 6/12 with follow-up tract recurrence (of 499 biopsies overall).
• Reviews: Robertson EG, Baxter G. Clin Radiol 2011;66:1007. PMID 21784421. "tumour seeding is a rare occurrence, yet… often regarded as a major contraindication". Shyamala K et al. J Int Soc Prev Community Dent 2014;4:5. PMID 24818087: 5/5000 FNA (0.1%).

3. Analogies

• Hydatid: Brunetti E et al. WHO-IWGE consensus. Acta Trop 2010;114:1. PMID 19931502. Bhutani N, Kajal P. Ann Med Surg 2018;36:99. PMID 30450204, PMC6226561: germinal membrane, brood capsules, protoscolices, "hydatid sand"; rupture → IgE anaphylaxis; "Ruptured cysts can release viable cystic contents and protoscolices… secondary hydatidosis". Akhan O, Ciftci T. Visc Med 2025. PMID 41064524: PAIR anaphylactic shock <0.5%, reversible reactions <2%; PAIR is WHO-endorsed treatment.
• Chordoma structure: Sun X et al. Curr Rev Musculoskelet Med 2015;8:344. PMID 26493697: lobules, physaliferous cells, myxoid stroma, "slow aggressive and locally invasive"; notochordal remnant origin. Akiyama T et al. Ann Surg Oncol 2018;25:912. PMID 29181683: "micro-skip metastasis" in 42.5%, infiltrative; vascular invasion and size predict OS. Radaelli 2020: microsatellite nodules below imaging resolution. Walcott BP Lancet Oncol 2012 PMID 22300861: "aggressive, locally invasive".
• Genetics: Vujovic S J Pathol 2006 PMID 16538613 (brachyury in all 53 chordomas, none of 300 other neoplasms). Yang XR Nat Genet 2009 PMID 19801981 (T duplication familial). Pillay N Nat Genet 2012 PMID 23064415 (rs2305089 OR 6.1). Tarpey PS Nat Commun 2017 PMID 29026114 (104 WGS: T duplication 27%, PI3K 16%, LYST 10%). No infectious agent ever identified; PubMed search chordoma + microbiome/parasite → only therapeutic (oncolytic virus, C. novyi-NT, CAR-T).
• Tumour microbiome caveat: Nejman D Science 2020 PMID 32467386 (1526 tumours incl. "bone"; chordoma not identified). Gihawi A mBio 2023 PMID 37811944 (major errors). Poore GD Nature 2020 PMID 32214244 RETRACTED 2024 (PMID 38926587).

4. Mechanism

• FOR the fear (animal): Juratli MA Head Neck 2014 PMID 23913663 (mouse; pressure/biopsy CTC up to 60-fold). Mathenge EG Neoplasia 2014 PMID 25425969 (mouse 4T1; CNB more lung mets).
• AGAINST (human): Atilla MK Turk J Med Sci 2019 PMID 31655516 (prostate; no CTCs after biopsy). Ngamruengphong S Gut 2015 PMID 25575893 (SEER, 2034 pancreatic; EUS-FNA HR 0.84 OS, cancer-specific 0.87 NS). Fuks 2014; Liebens 2009; Liikanen 2016; Maseki 2023; Freeman 2018.

UNVERIFIED

1. Exact biopsy wording in Stacchiotti 2015 (paywalled; CF restatement used). 2. Biopsy wording in 2026 JAMA Oncol consensus (paywalled). 3. Robertson & Baxter per-site tables. 4. Survival analysis in Silva 2008. 5. Numeric rate for percutaneous chordoma biopsy tract seeding (none found). 6. Rate for primary brain tumour stereotactic biopsy seeding (none). 7. WHO-IWGE exact anaphylaxis wording.