Pathology: Pathology in practice - histopathology, cytology, autopsy and the coroner

🩻 Pathology in practice - histopathology, cytology, autopsy and the coroner. Every foundation doctor sends specimens, receives pathology reports, completes death certification and speaks to bereaved families about post-mortems. Doing these well depends on knowing how specimens are processed, what pathology reports mean, the legal framework for death certification (including the medical examiner system introduced in England and Wales in September 2024), when to refer a death to the coroner, and the Human Tissue Act. These topics appear frequently in the UKMLA professional knowledge content.
Your four questions: Have I sent the right specimen in the right container with full clinical details? Do I understand the report and its implications (margins, grade, stage, biomarkers)? Can I certify this death, or must it be referred to the coroner? Have I obtained valid consent for any retention or post-mortem examination?

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Sending Specimens Correctly

• Label correctly - at least three identifiers (full name, date of birth, NHS or hospital number) on both the specimen and the request form; label at the bedside; unlabelled or mislabelled specimens are rejected (zero tolerance for blood transfusion samples).
• Clinical information - relevant history, clinical question, site, laterality, previous pathology, urgency; poor clinical details are a common cause of diagnostic error.
• Fixative: most tissue in 10% neutral buffered formalin (about 10 times the specimen volume). Send fresh (unfixed) - frozen sections, suspected lymphoma (flow cytometry and molecular studies), muscle and nerve biopsies, renal biopsies (immunofluorescence and electron microscopy), cytogenetics, microbiology culture, and some placental and fetal tissue; tell the laboratory in advance.
• Orientation - mark margins with sutures or clips and a diagram (wide local excisions, skin, breast).
• High-risk specimens - label as infection risk (TB, hepatitis, HIV, prions - CJD tissue needs special handling).
• Never send tissue in saline long-term or freeze tissue meant for histology.

How Tissue Is Processed and Stained

• Steps: fixation (formalin cross-links proteins) → grossing (macroscopic description and sampling) → dehydration → paraffin wax embedding → cutting sections (about 3–5 µm) → staining → microscopy → report. Routine histology takes about 2–7 days; decalcification of bone adds time.
• Haematoxylin and eosin (H&E) - routine stain: haematoxylin stains nuclei blue/purple (basophilic - DNA, RNA, ribosomes); eosin stains cytoplasm and collagen pink (eosinophilic).
• Frozen section - rapid intraoperative diagnosis (about 20 minutes) - margins, unexpected lesions, sentinel nodes; less detail than paraffin sections.
• Electron microscopy - renal biopsies (podocyte effacement in minimal change disease; deposits), some tumours, cilia (primary ciliary dyskinesia).
• Turnaround targets and urgent requests - discuss with the pathologist; for suspected cancer, pathology is on the 28-day Faster Diagnosis Standard pathway.

Special Stains and Techniques

Stain	Identifies	Use
Periodic acid–Schiff (PAS)	Glycogen, mucin, basement membranes, fungi	Whipple's disease (PAS-positive macrophages), fungal infections, glycogen storage disease
Ziehl–Neelsen	Acid-fast bacilli	TB, leprosy (Nocardia weakly)
Congo red	Amyloid - apple-green birefringence	Amyloidosis
Perls' Prussian blue	Iron (haemosiderin)	Haemochromatosis, bone marrow iron stores, ring sideroblasts
Reticulin, Masson trichrome, Sirius red	Collagen and fibrosis	Liver fibrosis staging, marrow fibrosis
Grocott (silver)	Fungi	Pneumocystis, Aspergillus, Candida
Gram stain	Bacteria	Infections in tissue
Giemsa	H. pylori, blood parasites, leucocytes	Gastric biopsies, malaria films
Oil red O / Sudan black	Lipid (frozen tissue)	Fat emboli, fatty change
Alcian blue, mucicarmine	Mucin	Signet ring cells, Barrett's goblet cells, Cryptococcus capsule
Von Kossa, alizarin red	Calcium	Calcification
Orcein / Shikata	Hepatitis B surface antigen, copper-associated protein	Liver biopsies
Elastic van Gieson (EVG)	Elastic fibres	Vasculitis, temporal artery biopsy (disrupted internal elastic lamina in GCA)

• Immunohistochemistry (IHC) - antibodies against specific proteins visualised with a coloured chromogen: tumour typing, ER/PR/HER2, Ki-67 (proliferation index), MMR proteins, PD-L1, infectious agents (CMV, HPV p16 surrogate), C4d (antibody-mediated rejection).
• Immunofluorescence - renal biopsies (linear IgG - anti-GBM; granular - immune complex), skin biopsies (pemphigus - intercellular IgG "fishnet"; pemphigoid - linear IgG/C3 at the basement membrane; dermatitis herpetiformis - granular IgA in dermal papillae).
• In situ hybridisation - EBV (EBER), HPV, light chain restriction, HER2 (FISH or SISH).

Cytology and Screening

• Exfoliative cytology - cells shed naturally or scraped: cervical samples (liquid-based cytology), urine (urothelial carcinoma), sputum, pleural and ascitic fluid, CSF.
• Fine needle aspiration (FNA) - thyroid nodules (Thy1–Thy5 categories), lymph nodes, salivary glands, breast (as part of triple assessment, though core biopsy is preferred), pancreatic lesions via EUS, lung lesions via EBUS.
• Advantages - quick, cheap, minimally invasive, can be done in clinic (rapid on-site evaluation); limitations - cannot assess architecture or invasion, sampling error, non-diagnostic samples.
• NHS Cervical Screening Programme (England) - primary HPV testing; if high-risk HPV positive, cytology triage; ages 25–64; since July 2025 people in England with an HPV-negative result are recalled every 5 years at all ages (previously every 3 years for ages 25–49); cytology results: negative, borderline/low-grade dyskaryosis, high-grade dyskaryosis (moderate or severe), possible invasive cancer, glandular neoplasia → colposcopy as indicated.
• Thyroid cytology (Thy) - Thy1 non-diagnostic, Thy2 benign, Thy3a/3f atypia or follicular lesion (follicular carcinoma cannot be diagnosed on cytology - needs capsular or vascular invasion on histology), Thy4 suspicious, Thy5 malignant.

Reading a Histopathology Report

• Structure: clinical details, macroscopic description (size, weight, appearance, margins), microscopic description, conclusion/diagnosis (often with a SNOMED code), comments (differential diagnosis, recommendations, further tests to follow), and supplementary reports (molecular results).
• Cancer resection reports follow Royal College of Pathologists datasets - tumour type and grade, size, depth, margins (and distances), lymphovascular and perineural invasion, lymph nodes, pTNM stage, biomarkers.
• Key terms: "suspicious of" / "in keeping with" / "consistent with" (graded certainty); "non-diagnostic" or "insufficient" (repeat the biopsy); "atypia" (abnormal but not definitely neoplastic); "reactive" (benign response); "dysplasia" (pre-malignant); "margins involved" (incomplete excision - discuss further treatment at MDT).
• Always act on the report - read it, document it, inform the patient, discuss at MDT if relevant; discrepancy between clinical picture and pathology - talk to the pathologist (wrong site sampled, missed lesion, specimen mix-up).
• Second opinion and review - complex cases go to specialist pathologists; double reporting for some diagnoses (Barrett's dysplasia, melanoma).

Death Certification and the Medical Examiner

• Statutory medical examiner system (England and Wales, from 9 September 2024) - every death not investigated by a coroner is independently scrutinised by a medical examiner (a senior doctor not involved in the patient's care) before registration. The ME reviews records, discusses the cause of death with the certifying doctor, and speaks to the bereaved to answer questions and identify concerns.
• Medical Certificate of Cause of Death (MCCD) - any registered medical practitioner who attended the deceased during their lifetime (at any time - the previous 28-day rule was removed) can complete it, if they can state the cause of death to the best of their knowledge and belief and the death does not require coroner referral.
• Completing the MCCD:
  • Part I - the sequence leading directly to death: 1a the disease or condition directly leading to death, 1b the condition that led to 1a, 1c the condition that led to 1b (the underlying cause should be the lowest completed line).
  • Part II - other significant conditions contributing to death but not part of the sequence.
  • Avoid modes of dying alone (cardiac arrest, respiratory failure, multi-organ failure, "old age" - although "old age" is acceptable in Part I as a sole cause in people aged 80 or over with gradual decline and no identifiable disease, with ME agreement), and avoid abbreviations.
  • Example: 1a Bronchopneumonia; 1b Cerebral infarction; 1c Atrial fibrillation; II Type 2 diabetes mellitus.
• Industrial diseases (mesothelioma, asbestosis, pneumoconiosis) - always referred to the coroner.
• Cremation - the second confirmatory cremation certificate (Cremation 5) was abolished in September 2024 because the medical examiner now scrutinises every death; the attending doctor still records whether there are pacemakers or other implants that must be removed before cremation (battery explosion risk).

Referral to the Coroner

• Notification of Deaths Regulations 2019 - a registered medical practitioner must notify the coroner when there is reasonable cause to suspect that death was due to:
  • Poisoning, including by an otherwise benign substance; use of a controlled drug, medicinal product, or toxic chemical.
  • Violence, trauma or injury; self-harm; neglect (including self-neglect).
  • A person undergoing any treatment or procedure of a medical or similar nature (e.g. death after surgery or anaesthesia, or a complication of treatment).
  • An injury or disease attributable to any employment (industrial disease - asbestos, pneumoconiosis, occupational cancer).
  • Unnatural causes not covered above.
  • The cause of death is unknown.
  • The death occurred while in custody or otherwise in state detention (prison, police custody, detained under the Mental Health Act; Deprivation of Liberty Safeguards no longer require coroner referral since 2017 unless another reason applies).
  • The deceased cannot be identified, or no attending practitioner is available to certify.
• The coroner may: accept the cause of death and allow certification by the doctor (no further action), order a post-mortem examination (consent from family not required, but their views are considered), and/or open an inquest (a public, fact-finding hearing into who died, when, where and how - not to apportion blame). Conclusions include natural causes, accident or misadventure, suicide, unlawful killing, industrial disease, narrative and open conclusions.
• Prevention of Future Deaths reports (Regulation 28) - sent to organisations when risks are identified.
• Doctors may be asked for a statement and to give evidence; seek advice from your defence organisation and trust legal team; be factual and honest (duty of candour).

The Post-mortem Examination

• Coroner's (medicolegal) post-mortem - ordered by the coroner; consent not required.
• Hospital (consented) post-mortem - requested by clinicians with the written consent of the next of kin (or the person's own prior consent) under the Human Tissue Act; can be full, limited (specific organs or areas), or minimally invasive (post-mortem CT/MRI with or without targeted biopsies - increasingly available and acceptable to some faith groups).
• Value - confirms or refutes clinical diagnoses (major discrepancies in about 10–20%), audit and education, genetic diagnoses for families (sudden cardiac death - cardiac genetic testing), public health, research.
• Faith and cultural needs - many Muslim and Jewish families wish burial within 24 hours and may object to invasive post-mortem; coroners' services offer out-of-hours certification and post-mortem imaging where possible - discuss sensitively.
• Organ and tissue retention - families must be informed and consent to retention beyond what is needed for the cause of death (after the Alder Hey and Bristol inquiries, which led to the Human Tissue Act 2004).

The Human Tissue Act and Consent

• Human Tissue Act 2004 (England, Wales, Northern Ireland; Human Tissue (Scotland) Act 2006) - regulated by the Human Tissue Authority; appropriate consent is the fundamental principle for the removal, storage and use of human tissue from the deceased, and storage and use of tissue from the living for scheduled purposes (e.g. research, transplantation, education, public display).
• Exceptions not needing HTA consent - diagnostic tissue from the living for the patient's own care, and coroner's post-mortems (governed by coroner law).
• Hierarchy of qualifying relationships for consent after death (if the person did not decide): spouse or partner, parent or child, sibling, grandparent or grandchild, child of a sibling, stepfather or stepmother, half-sibling, friend of long standing.
• Organ donation - deemed consent (opt-out): England (Max and Keira's Law, May 2020), Wales (2015), Scotland (2021), Northern Ireland (2023). Adults are considered to have agreed unless they opted out or are in an excluded group (under 18, lacking capacity for a significant time before death, not ordinarily resident for 12 months); the family is still consulted. Specialist nurses for organ donation approach families - refer potential donors early (e.g. when withdrawing treatment or after brainstem death testing).
• Offence - storing or using tissue without appropriate consent; analysing DNA without consent ("DNA theft").

At a Glance

Item	Remember
Lymphoma biopsy	Send fresh, not in formalin
H&E	Nuclei blue, cytoplasm pink
Congo red	Amyloid
Perls'	Iron
Ziehl–Neelsen	Acid-fast bacilli
PAS	Glycogen, fungi, Whipple's
Follicular thyroid carcinoma	Cannot be diagnosed on FNA
Medical examiner	Scrutinises every non-coroner death (from Sept 2024)
MCCD Part I	Sequence to death - underlying cause on lowest line
Coroner referral	Unknown cause, unnatural, procedure, industrial, custody/MHA, drugs, self-harm, neglect
Human Tissue Act	Consent for storage and use of tissue; deemed consent for organ donation

Spot the Answer

• A surgeon removes a neck node for suspected lymphoma and asks whether to put it in formalin. → No - send it fresh, urgently, to the laboratory.
• A man dies of mesothelioma at home under palliative care. → Refer to the coroner (industrial disease) even though the death was expected.
• A patient dies on day 2 after a hip hemiarthroplasty with pneumonia. → Discuss with the medical examiner and refer to the coroner if the death may be related to the procedure.
• A patient detained under section 3 dies of a myocardial infarction on the ward. → Coroner referral (state detention) - an inquest will be held.
• A temporal artery biopsy shows disrupted internal elastic lamina with giant cells on EVG staining. → Giant cell arteritis.

Exam-style Scenarios

• Scenario. A 90-year-old woman with dementia, frailty and gradual decline dies in a care home with no acute illness. You saw her last month. Can you complete the MCCD?
  Answer: Yes - you attended her in life and can state a cause of death; there is no reason for coroner referral. "Old age" or "frailty of old age" may be acceptable as a sole Part I cause in someone over 80 with gradual decline, or a specific cause (e.g. 1a Dementia, Alzheimer's type) may be given. The medical examiner will review and speak to the family before registration.
• Scenario. A family asks why a hospital post-mortem is being requested after their father died of an uncertain cause of heart failure in a 45-year-old.
  Answer: Explain sensitively: it may identify an inherited cardiomyopathy that could affect other family members (cascade screening), clarify the diagnosis and improve care. It requires their written consent; they can choose a limited examination, decide about tissue retention, and the timing of the funeral can usually be preserved. If the cause cannot be certified, the coroner may need to be informed instead.
• Scenario. A breast core biopsy report states: "Invasive ductal carcinoma (no special type), grade 2, ER 8/8, PR 6/8, HER2 2+ - FISH to follow." What does this mean?
  Answer: An invasive breast carcinoma of no special type, moderately differentiated, strongly hormone receptor-positive (likely to respond to endocrine therapy). HER2 IHC 2+ is equivocal - FISH (or ISH) will determine whether HER2 is amplified (eligibility for anti-HER2 therapy). Discuss at the breast MDT once complete.

Key Points

• Correct labelling, clinical details and the right container (formalin versus fresh) prevent errors.
• Know the main special stains and what they show.
• Cytology cannot assess invasion; follicular thyroid carcinoma needs histology.
• The medical examiner scrutinises every death not referred to the coroner (England and Wales, from September 2024).
• Learn the Notification of Deaths Regulations 2019 categories.
• Hospital post-mortems need consent; coroner's post-mortems do not.
• Deemed consent for organ donation now applies across the UK.

Guidelines and Further Reading

• Department of Health and Social Care: Death certification reforms and the statutory medical examiner system (September 2024)
• Ministry of Justice: Guidance for registered medical practitioners on the Notification of Deaths Regulations 2019
• Chief Coroner: Guidance No. 16 (Deprivation of Liberty Safeguards)
• Human Tissue Authority: Codes of Practice
• Royal College of Pathologists: Datasets and tissue pathways; Guidelines on autopsy practice
• NHS Cervical Screening Programme: Screening interval changes (2025)