Biopsy Principles in MSK Oncology

Biopsy of a suspected musculoskeletal (MSK) tumour is one of the most critical and consequential procedures in orthopaedic oncology. A poorly planned or executed biopsy can contaminate tissue planes, seed the tumour into adjacent compartments, compromise surgical margins, and convert a limb-salvageable tumour into one requiring amputation. The Mankin study (1982) demonstrated that biopsy-related problems occurred in approximately 19% of cases and that unnecessary amputations were performed in up to 4.5% as a direct result of biopsy errors. This landmark paper established the principle that biopsy of a suspected bone or soft tissue sarcoma should ideally be performed — or at minimum planned — at the treating specialist tumour centre, not at the referring hospital.

• The Mankin principle: biopsy of a suspected sarcoma should be performed by the surgeon who will perform the definitive resection, or in direct consultation with that surgeon; the biopsy approach must be planned so that the biopsy tract can be excised en bloc with the tumour at definitive surgery; a biopsy performed by an inexperienced surgeon through an incorrect approach may contaminate the neurovascular bundle, joint, or adjacent compartment, converting a wide resection into amputation
• The general principle of `see one, do one, teach one` does not apply to sarcoma biopsy — the consequences of a poor biopsy are irreversible and potentially catastrophic for the patient

• Complete imaging before biopsy: all staging imaging must be completed BEFORE biopsy; biopsy-induced haemorrhage, oedema, and tissue reaction alter MRI signal and can obscure the true tumour extent, making post-biopsy MRI unreliable for surgical planning; the sequence is: (1) plain X-ray; (2) local MRI (with and without contrast — T1, T2, STIR, gadolinium); (3) CT chest (for pulmonary metastases); (4) bone scan or PET-CT (for polyostotic disease or distant bone metastases); (5) CT of the lesion if required for biopsy planning or bone architecture; then biopsy
• Staging: the Enneking surgical staging system for bone tumours — Stage I (low grade: IA intracortical/intracompartmental; IB extracompartmental); Stage II (high grade: IIA intracompartmental; IIB extracompartmental); Stage III (any grade with regional or distant metastasis); staging guides surgical planning and prognosis
• MDT discussion: all suspected sarcomas must be discussed at an MDT (multidisciplinary team meeting) at a specialist sarcoma centre BEFORE biopsy if at all possible; the MDT reviews imaging, plans the biopsy approach, and ensures the correct tissue is sampled; referral to a specialist sarcoma centre (e.g., NCIN-designated bone sarcoma centres in the UK) is mandatory for suspected bone and soft tissue sarcomas

• Longitudinal incision: the biopsy incision must be longitudinal (parallel to the long axis of the limb) — NOT transverse; a transverse incision cannot be easily excised en bloc with the tumour at definitive surgery; a transverse incision that crosses multiple tissue planes would contaminate them all and require a much wider resection to excise the biopsy tract; all biopsy incisions must be planned in the line of the definitive resection
• Do not cross fascial planes: the biopsy approach must remain within a single compartment; crossing fascial planes contaminates adjacent compartments with tumour cells, potentially requiring resection of the adjacent compartment at definitive surgery; approach through the muscle (not between muscles) directly overlying the tumour
• Avoid neurovascular structures: the biopsy approach must not violate the neurovascular bundle; once the bundle is contaminated by tumour cells, it may need to be resected at definitive surgery (converting a nerve-sparing operation into one with neurological sacrifice)
• Avoid joint contamination: if the joint is contaminated during biopsy (by entering the joint capsule), joint excision or joint sacrifice may be required at definitive surgery; this is particularly critical for distal femoral tumours (knee joint) and proximal femoral tumours (hip joint)
• Drain placement: if a drain is placed after open biopsy, it must exit through the incision or immediately adjacent to it — NOT through a separate remote stab incision; the drain tract is a potential seeding site and must be excised at definitive surgery; a drain exiting through a separate incision creates a second biopsy tract requiring separate excision
• Haemostasis: meticulous haemostasis is essential to prevent haematoma formation; a post-biopsy haematoma spreads tumour cells throughout the contaminated field; if a haematoma forms, it must be treated as contaminated and the entire haematoma field may need to be resected at definitive surgery
• Send fresh, fixed, and frozen tissue: fresh tissue (in saline) is required for flow cytometry, cytogenetics, and molecular testing; fixed tissue (formalin) for standard histopathology and immunohistochemistry; frozen section (for intraoperative confirmation that viable tumour tissue has been sampled); send representative tissue from the most aggressive-appearing area on imaging

• Distal femur: the biopsy incision must be anteromedial or anterolateral — NOT posterior (popliteal contamination) and not crossing into the knee joint; the vastus lateralis or medialis approach keeps the biopsy within the anterior compartment; a posterior approach would contaminate the popliteal fossa (neurovascular bundle, posterior compartment) and make limb salvage impossible
• Proximal tibia: anterolateral or anteromedial approach; avoid the popliteal space posteriorly; keep the biopsy tract within the anterior compartment; the peroneal nerve must be protected laterally
• Proximal femur: direct lateral approach through the vastus lateralis; avoid the femoral vessels and nerve anteromedially; avoid the sciatic nerve posteriorly; stay within the lateral compartment
• Pelvis: CT-guided core needle biopsy preferred for most pelvic lesions; if open biopsy required, the approach is planned to avoid contaminating the neurovascular bundle, hip joint, and abdominal viscera
• Spine: CT-guided transpedicular or posterolateral approach; the biopsy tract must not enter the spinal canal; the approach should allow excision of the biopsy tract at definitive surgery if posterior resection is planned

• The Mankin study revisited: the 1982 Mankin study (Journal of Bone and Joint Surgery) analysed 329 tumour biopsies performed at referring hospitals before transfer to a tumour centre; biopsy-related problems (wrong approach, joint contamination, fracture through biopsy site, inadequate tissue, infection) occurred in 18.2%; unnecessary amputations in 4.5%; a 2000 repeat audit by Mankin showed improvement but persistent problems; these figures illustrate why biopsy of a suspected sarcoma by a non-specialist is dangerous; the message — refer before biopsying
• Liquid biopsy and molecular diagnostics: modern sarcoma diagnosis increasingly relies on molecular characterisation; specific translocations are diagnostic for certain sarcomas — EWSR1 gene fusion (Ewing sarcoma); FUS-DDIT3 (myxoid liposarcoma); SS18-SSX (synovial sarcoma); MDM2 amplification (well-differentiated/dedifferentiated liposarcoma); next-generation sequencing (NGS) panels can detect these and other mutations from core biopsy material; adequate tissue for molecular testing must always be obtained at biopsy; liquid biopsy (circulating tumour DNA from blood) is an emerging tool for monitoring treatment response and disease recurrence but is not yet standard for initial diagnosis
• Frozen section at biopsy: the role of intraoperative frozen section in tumour biopsy is to confirm that viable tumour tissue has been obtained (not necrotic tumour, normal muscle, or fibrous tissue); it does NOT provide a definitive diagnosis (which requires permanent section and full immunohistochemistry); frozen section at biopsy prevents the situation where the surgeon closes the biopsy wound and the pathologist later reports `insufficient or non-diagnostic tissue` — requiring a repeat biopsy; all open biopsies should have intraoperative frozen section confirmation of viable tumour tissue

• Mankin principle: biopsy by the definitive surgeon or at the specialist centre; biopsy errors occurred in 18.2% in the original Mankin study; 4.5% required unnecessary amputation; REFER BEFORE BIOPSY
• Complete imaging BEFORE biopsy: MRI + CT chest + bone scan → then biopsy; post-biopsy imaging is unreliable due to oedema and haematoma
• Longitudinal incision: parallel to long axis of limb; can be excised en bloc at definitive surgery; transverse incision = WRONG; contaminates multiple tissue planes
• Do not cross fascial planes: stay within one compartment; contamination of adjacent compartment → requires wider resection at definitive surgery
• Avoid joint contamination: joint entry = joint may require sacrifice at definitive surgery; critical for distal femur (knee) and proximal femur (hip)
• Drain: exit through incision or immediately adjacent; NOT through separate remote stab; the drain tract must be excised at definitive surgery
• CT-guided core needle biopsy: gold standard first-line technique; minimal contamination; multiple cores (3–5); adequate for histology + IHC + molecular testing
• Excisional biopsy: CONTRAINDICATED for suspected sarcoma; if malignant, field is contaminated → wider resection or amputation required
• FNAC: insufficient for primary bone sarcoma (no tissue architecture); acceptable only for known metastatic carcinoma (breast, prostate) identification
• Frozen section: confirms viable tumour tissue obtained intraoperatively; does NOT give definitive diagnosis; prevents repeat biopsy for non-diagnostic tissue