By MRCSA in MRCS Part A — 04 Jul 2026

81 BIOPSY

# 82 BIOPSY

Biopsy is the removal of tissue from a living patient to establish a diagnosis. In MRCS Part A, the examiners do not ask you to define it — they ask you to pick the right biopsy for the right lesion. Every wrong choice on the exam (and in clinical practice) is either too superficial, too aggressive, or carries a specific complication you should have anticipated.

This lesson groups biopsy techniques by what they actually deliver to the pathologist — cytology, histology, or whole specimen — and then applies them to the high-yield clinical scenarios that come up repeatedly in SBAs.

Why we biopsy

➡ Tissue diagnosis — distinguish benign from malignant, grade and subtype the lesion.

➡ Pre-treatment staging — biopsy + imaging together decide whether the next step is surgery, chemotherapy, radiotherapy, or surveillance.

➡ Monitor disease — repeat biopsies in transplant rejection, inflammatory bowel disease, residual breast disease post-chemo.

👩‍⚕️ MRCS examiners love the phrase "triple assessment" for breast disease: clinical examination + imaging (mammography ± USS) + tissue (core biopsy). All three are needed before definitive treatment.

What the pathologist receives

The fundamental distinction is cells vs tissue:

	Cytology (cells)	Histology (tissue)
Sample	Loose individual cells	Intact cylinder/block of tissue
Architecture	Lost	Preserved
Can grade tumour?	No	Yes
Can stage invasion?	No	Yes (depth, margins)
Techniques	FNA, brush, washings, ROSE	Core, punch, incisional, excisional
Speed	Minutes (ROSE on-site)	Days
Complication risk	Lowest	Higher (bleeding, seeding)

If you remember nothing else: cytology screens; histology decides treatment. Whenever an SBA stem hints at grading, margins, lymphovascular invasion, or subtyping (especially lymphoma) — you need histology.

Pre-biopsy work-up

➡ Coagulation screen, platelet count.

➡ Stop anticoagulants where safe (warfarin, DOACs, clopidogrel — timing depends on bleeding risk of the site).

➡ Image first — never biopsy a pulsatile mass, suspected aneurysm, hydatid cyst, or phaeochromocytoma blindly.

➡ Consent: explicitly mention bleeding, infection, pain, needle-tract seeding, and failed sampling.

Fine needle aspiration cytology (FNA / FNAC)

A small-bore needle (typically 22–25G) is passed through the lesion and cells are aspirated for cytology.

➡ Best for: thyroid nodules, palpable lymph nodes, salivary gland lumps, breast (as part of triple assessment in some centres).

➡ Strengths: quick, cheap, near-zero complication rate, can be done in clinic.

➡ Limitations: no architecture → cannot reliably distinguish follicular adenoma from follicular carcinoma (which requires capsular/vascular invasion). Cannot subtype lymphoma.

Reporting categories you must know

Site	System	Categories
Thyroid FNA	Thy	Thy1 non-diagnostic, Thy2 benign, Thy3 atypia/follicular, Thy4 suspicious for malignancy, Thy5 malignant
Breast cytology	C	C1 inadequate, C2 benign, C3 atypia probably benign, C4 suspicious, C5 malignant

👩‍⚕️ Thy3 (follicular lesion) is the classic exam trap. FNA cannot tell follicular adenoma from carcinoma — the answer is diagnostic hemithyroidectomy, not repeat FNA.

Core (Tru-cut) biopsy

A spring-loaded cutting needle (typically 14–18G) takes a cylinder of tissue preserving architecture. Local anaesthetic is required.

➡ Best for: breast lumps (gold standard), prostate (12-core trans-rectal or trans-perineal), liver, kidney, soft-tissue masses, deep retroperitoneal masses (image-guided).

➡ Strengths: preserves architecture → allows grading, receptor status (ER/PR/HER2), molecular profiling.

➡ Limitations: higher bleeding risk than FNA; small risk of needle-tract seeding (particularly HCC and sarcoma — biopsy tract must be planned to lie within the future resection field).

Reporting categories

Site	System	Categories
Breast core	B	B1 normal, B2 benign, B3 uncertain malignant potential, B4 suspicious, B5 malignant (B5a in situ, B5b invasive)
Prostate	P	P1–P5 with Gleason grading

Punch biopsy

A circular blade (typically 3–6 mm) takes a full-thickness disc of skin down to subcutaneous fat.

➡ Best for: rashes, chronic ulcers with suspected malignant transformation (Marjolin's ulcer), Paget's disease of the nipple, inflammatory dermatoses.

➡ Strengths: full-thickness, simple, sutured with a single stitch.

➡ Avoid in suspected melanoma — depth (Breslow thickness) determines staging and prognosis, and a punch may miss the deepest part of the lesion.

Incisional biopsy

Removes part of a lesion through a planned incision.

➡ Used when a lesion is too large to excise primarily but tissue is needed before definitive treatment (large sarcoma, oral cavity tumour, vulval lesion).

➡ The incision must be placed so it can be excised en-bloc with the definitive specimen — a poorly planned incisional biopsy can compromise subsequent oncological resection.

➡ Largely superseded by core biopsy for deep masses.

Excisional biopsy

Removes the entire lesion with a narrow margin — both diagnostic and often curative.

➡ Best for: small skin lesions, breast lumps <3 cm where core biopsy is non-diagnostic, suspected melanoma (2 mm margin), lymph node biopsy for suspected lymphoma.

➡ Strengths: gold standard — provides full architecture, margins, and complete staging.

➡ Avoid for large or deep lesions — risks contamination of tissue planes and inadequate margins without prior diagnosis.

👩‍⚕️ Lymphoma rule: excisional > core > FNA. Architecture is essential for subtyping (Hodgkin vs non-Hodgkin, follicular vs diffuse large B-cell). FNA alone is almost never enough.

Endoscopic biopsy

Pinch biopsies taken via flexible endoscope — OGD, colonoscopy, bronchoscopy, cystoscopy.

➡ Multiple small samples allow mapping (e.g. quadrantic biopsies in Barrett's, random colonic biopsies in UC surveillance).

➡ Endobronchial ultrasound (EBUS)-FNA of mediastinal nodes is now standard for lung cancer staging — often with ROSE (rapid on-site evaluation) where a cytotechnologist confirms adequacy before the scope is withdrawn.

➡ Pneumothorax is the classic complication of transbronchial biopsy.

Image-guided biopsy

USS, CT, or MRI guidance allows accurate sampling of deep lesions with minimal collateral damage.

➡ USS — real-time, no radiation: thyroid, breast, liver, superficial lymph nodes.

➡ CT — best for deep retroperitoneal, lung, bone lesions.

➡ MRI — used selectively for prostate (multiparametric MRI-targeted) and breast lesions only visible on MRI.

Sentinel lymph node biopsy (SLNB)

A diagnostic operation that identifies the first draining lymph node from a tumour — if it is negative, full nodal clearance can be avoided.

➡ Indications: melanoma with Breslow thickness >0.8 mm (or thinner with ulceration/high mitotic rate); early breast cancer for axillary staging.

➡ Technique: dual localisation — patent blue dye + radioactive technetium-99m colloid injected peritumourally; the sentinel node is identified by blue staining and gamma probe.

➡ Why it matters: spares patients the morbidity of full axillary clearance (lymphoedema, nerve injury, shoulder dysfunction) when the sentinel is negative.

Frozen section

Tissue snap-frozen in liquid nitrogen, sectioned on a cryostat, and reported within ~20 minutes intraoperatively.

➡ Used to assess resection margins (e.g. breast WLE, head and neck), sentinel node positivity, and to confirm tissue is diagnostic before completing a procedure (e.g. suspected lymphoma — confirm lymphoid tissue is present).

➡ Less accurate than paraffin sections — fatty tissue freezes poorly, and small foci of malignancy may be missed. Never used as the final diagnostic standard.

Site-specific rules (high-yield)

Testis — NEVER biopsy directly

A scrotal needle biopsy risks seeding tumour cells along the inguinal and scrotal lymphatics, changing the drainage pattern from para-aortic (normal testicular drainage) to inguinal. The correct approach to a suspected testicular tumour is radical inguinal orchidectomy — the cord is clamped before mobilisation to prevent venous spread.

Suspected melanoma

Excisional biopsy with a 2 mm margin, oriented along skin tension lines so wide local excision is straightforward later. Never shave (loses depth → loses Breslow → loses staging). Never punch through a pigmented lesion for the same reason. Definitive wide local excision (1–2 cm margin depending on Breslow) is performed after histological confirmation.

Suspected lymphoma

Excisional lymph node biopsy is preferred — architecture is essential for subtyping. If excision is not feasible (e.g. deep mediastinal node), core biopsy is acceptable. FNA alone is rarely sufficient.

Breast lump

Core (Tru-cut) biopsy as part of triple assessment. Excisional biopsy reserved for B3 lesions or small lumps where core is non-diagnostic.

Thyroid nodule

FNA under USS guidance. Core biopsy is avoided due to vascularity of the thyroid and risk of haemorrhage around the airway.

Soft tissue sarcoma

Core biopsy at a specialist sarcoma centre — the tract must be planned along the line of any future resection. Inappropriate biopsy is one of the commonest reasons for compromised limb-sparing surgery.

Hepatocellular carcinoma

Often diagnosed radiologically (LI-RADS criteria on multiphase CT/MRI) without biopsy. When biopsy is needed, the seeding risk along the needle tract is real (~1–3%) — discussed at MDT.

Complications

➡ Bleeding — commonest; particular care in liver, kidney, prostate.

➡ Infection — skin commensals; sepsis after trans-rectal prostate biopsy (now largely replaced by trans-perineal).

➡ Pain.

➡ Needle-tract seeding — HCC, sarcoma, pleural mesothelioma, testicular tumours.

➡ Pneumothorax — transbronchial, percutaneous lung biopsy.

➡ Failed sampling / non-diagnostic — Thy1, C1, B1 reports; repeat or escalate.

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Test yourself

A lump is detected on physical examination and visualised on mammography. What is the next best step?

((FNAC::Cytology only, no architecture — cannot grade or assess receptor status.))
((Core / Tru-cut biopsy::☑️ Gold standard for breast lumps; preserves architecture, allows ER/PR/HER2 status.))
((Excision biopsy::Too aggressive without prior tissue diagnosis; reserved for B3 or small lumps.))
((Incisional biopsy::Largely superseded by image-guided core biopsy for breast.))

👩‍⚕️ Triple assessment = clinical examination + imaging + core biopsy.

A 1 cm pigmented skin lesion is suspected to be a melanoma. What is the next step?

((Punch biopsy::May miss the deepest part of the lesion and underestimate Breslow thickness.))
((Shave biopsy::Contraindicated — loses depth, destroys staging information.))
((Excision biopsy::☑️ Narrow-margin (2 mm) excision preserves full Breslow depth for staging.))
((FNAC::Useless for pigmented lesions — no architecture, no depth.))
((Incisional biopsy::Reserved for lesions too large to excise primarily.))

A patient has a 1 cm pigmented lesion that is itchy and bleeding on the back. What is the next step?

((Punch biopsy::Incomplete sampling risks underestimating Breslow depth.))
((Excision biopsy with 2 mm margin::☑️ Standard diagnostic step for suspected melanoma — preserves depth.))
((Wide local excision with 1 cm margin::Definitive treatment — performed after histological confirmation.))
((Shave biopsy::Contraindicated in any suspected melanoma.))

A patient has a 15 cm retroperitoneal mass displacing the stomach, spleen and kidney. What is the best investigation to establish the diagnosis?

((CT-guided needle core biopsy::☑️ Safe, accurate, preserves architecture for sarcoma or lymphoma diagnosis.))
((Open surgical biopsy::Invasive; risks contaminating tissue planes before definitive resection.))
((FNAC::Inadequate architecture for sarcoma or lymphoma subtyping.))
((PET-CT::Stages disease but does not provide tissue.))
((MRI::Imaging only — no histology.))

👩‍⚕️ Retroperitoneal sarcoma — biopsy tract must be planned to lie within the future resection field.

A 15 x 9 cm thigh mass deep to the deep fascia is identified. What is the most appropriate method to obtain tissue?

((FNAC::Insufficient for sarcoma diagnosis or grading.))
((Core biopsy::☑️ Provides architecture; tract planned along future resection line.))
((Incisional biopsy::Reserved for when core biopsy is non-diagnostic.))
((Excision biopsy::Inappropriate for large deep masses without prior diagnosis.))

👩‍⚕️ Any deep soft-tissue mass >5 cm = refer to a sarcoma centre before biopsy.

A patient with a chronic venous ulcer is suspected to have malignant transformation. Which biopsy is most appropriate?

((Shave biopsy::Too superficial to capture invasive squamous cell carcinoma.))
((Punch biopsy::☑️ Full-thickness sample of the ulcer edge — ideal for suspected Marjolin's ulcer.))
((Excision biopsy::Too aggressive before histological confirmation.))
((FNAC::Not appropriate for ulcerated skin lesions.))

A 3 cm right upper outer quadrant breast mass is found. What is the best biopsy method?

((FNAC::Cytology only — no architecture, no receptor status.))
((Core (Tru-cut) biopsy::☑️ Gold standard for breast lumps; component of triple assessment.))
((Excision biopsy::Reserved for B3 lesions or non-diagnostic core.))
((Incisional biopsy::Not standard for breast.))

A retro-alveolar mass (palate/jaw region) is suspected. Which biopsy is preferred?

((FNAC::Inadequate tissue for diagnosis of bony or deep oral lesions.))
((Core biopsy::☑️ Preserves architecture for diagnosis of deep head and neck masses.))
((Incisional biopsy::Reserved for large accessible lesions where core fails.))
((Excision biopsy::Inappropriate without prior diagnosis.))

A patient with an eczema-like lesion of the nipple and areola is suspected to have Paget's disease of the breast. Which biopsy is indicated?

((Shave biopsy::Too superficial — misses underlying ductal involvement.))
((Punch biopsy::☑️ Full-thickness skin sample confirms Paget cells; prompts search for underlying DCIS/invasive cancer.))
((Core biopsy::Used for any associated deeper breast mass — not the nipple skin itself.))
((Excision biopsy::Unnecessarily aggressive as first step.))

👩‍⚕️ Paget's = always investigate the breast — most cases have underlying DCIS or invasive cancer.

A 30-year-old man presents with a 6-week history of a thigh lump, 9 x 15 cm, deep to fascia. What is the most appropriate diagnostic procedure?

((FNAC::Insufficient tissue for sarcoma diagnosis.))
((Core biopsy::☑️ Gold standard for soft-tissue sarcoma; tract aligned with future resection.))
((Incisional biopsy::Reserved for non-diagnostic core.))
((Excision biopsy::Inappropriate — risks compromising limb-sparing surgery.))

A man presents with a solitary thyroid nodule. What is the best discriminative investigation?

((Ultrasound::Characterises (TIRADS) but does not diagnose.))
((CT scan::Not first-line; risks contrast-induced thyrotoxicosis.))
((FNAC::☑️ Gold standard for thyroid nodules — Thy1–Thy5 categorisation guides management.))
((Core biopsy::Avoided due to vascularity and proximity to airway.))
((Thyroid function tests::Assess function, not the nature of the nodule.))

👩‍⚕️ Thy3 (follicular lesion) = diagnostic hemithyroidectomy, because FNA cannot distinguish follicular adenoma from carcinoma.

A young man presents with a painless testicular lump. What is the most appropriate next step to establish diagnosis?

((Trans-scrotal needle biopsy::Contraindicated — risks seeding tumour to inguinal nodes, altering drainage.))
((FNAC of the testis::Contraindicated for the same reason.))
((Radical inguinal orchidectomy::☑️ Diagnostic and therapeutic — cord clamped early to prevent venous spread.))
((Punch biopsy of scrotum::Never indicated.))
((Incisional biopsy::Contraindicated; violates oncological principles.))

A patient has a 4 cm cervical lymph node suspicious for lymphoma. Which biopsy is preferred?

((FNAC::Inadequate architecture — cannot reliably subtype lymphoma.))
((Core biopsy::Acceptable if excision not feasible, but second choice.))
((Excisional lymph node biopsy::☑️ Gold standard — full architecture for subtyping (Hodgkin vs NHL, follicular vs DLBCL).))
((Punch biopsy::Not applicable to deep nodal tissue.))

Revision summary

➡ Cytology vs histology — FNA gives cells (cannot grade); core gives architecture (can grade).

➡ Breast lump → core biopsy (triple assessment); reporting B1–B5.

➡ Thyroid nodule → FNA under USS; reporting Thy1–Thy5; Thy3 → diagnostic hemithyroidectomy.

➡ Suspected melanoma → excisional biopsy with 2 mm margin; never shave, never punch.

➡ Lymphoma → excisional > core > FNA (architecture for subtyping).

➡ Soft tissue sarcoma / retroperitoneal mass → image-guided core biopsy at a specialist centre; tract within future resection.

➡ Testis → NEVER biopsy; radical inguinal orchidectomy.

➡ Skin ulcer / Paget's of nipple / Marjolin's → punch biopsy (3–6 mm).

➡ Sentinel node → melanoma (Breslow >0.8 mm), breast cancer; blue dye + Tc-99m.

➡ Frozen section → intraoperative margins, sentinel nodes, tissue adequacy.

➡ Seeding risk → HCC, sarcoma, mesothelioma, testis.

➡ ROSE → on-site cytology for EBUS-FNA, confirms adequacy before scope withdrawn.