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Vascular 69

Malignant HT:

Hypertrophic arteriolosclerosis: concentric smooth muscle cell onion skin thickening of the intima

Fibrinoid necrosis (necrotising arteriolitis) esp. kidney (‘ﬂea bite’ haemorrhages and haematuria) –

assoc

with more severe HT

Microangiopathy → haemolytic anaemia, retinal haemorrhages, exudates and papilloedema

The above changes are also seen in severe forms of TMA (see p. 207).

d/dg athero/lipid emboli and the renal vascular changes of Alagille’s syndrome (look for lipid)

d/dg: PSS arteritis (vide infra)

Pulmonary HT

See Chapter 8: Respiratory and Mediastinum.

Vasculitides

Diagnostic Table

In Table 6.1

√

means typically present and × typically absent – although exceptions occur. GN refers

to the presence of glomerulonephritis (usu. necrotising FSGN or crescentic), not intra-renal arterial

branch involvement. An important d/dg is TMA (see p. 207)

d/dg of necrotising vasculitides includes radiation vasculopathy, severe HT changes and TMA (q.v.)

Giant Cell (Temporal) Arteritis

Patients are usu. > 50 years old (a strong feature)

Changes are focal and GC present in only 55% cases .

. take multiple levels of long Bx (e.g. 4 cm)

Early: medial necrosis and many PMN, smaller branch involvement.

Later: granulomatous lesions in relation to fragments of the IEL (↑refractility but ↓staining)

Non-speciﬁc transmural mononuclear cell inﬁltrate and scattered eos. ± PMN ± lumenal thrombus

Healed phase:  extensive ﬁbrotic replacement of the IEL (e.g.

circumference)

 patchy lymphohistiocytic aggregates in media

 patchy ﬁbrosis of media ± neovascularisation

 irregular intimal ﬁbrosis.

Steroids cause resolution of histology after 14 days continuous use

d/dg normal age change (= elastic splitting, concentric intimal ﬁbrosis, medial hyalinisation ± Ca

)

d/dg: Buerger’s, Takayasu’s, Bazin’s/nodular vasculitis, Wegener’s, Churg-Strauss

Takayasu’s Disease (Takayashu’s Disease, Pulseless Disease)

< 50 years (strong feature), HT, arm claudication, BP difference >10mmHg between arms, visual Sx

Early: granulomatous inﬂam

(± greater adventitial and intimal involvement cf. giant cell arteritis)

Mixed chronic inﬂam

inﬁltrate (esp. adventitial) with elastic destruction

± Medial necrosis (proper)

Intimal ﬁbrosis ± proliferative endarteritis ± thrombosis

d/dg giant cell arteritis, Syphilis, clinically other causes of ‘pulseless disease’ e.g. dissection

Polyarteritis Nodosa (PAN)

Asthma and eosinophilia are strongly associated with the Churg-Strauss variant

Main visceral arteries (no GN), cutaneous leukocytoclastic vasculitis may accompany PAN

Patchy, transmural, ﬁbrinoid necrosis with healing by ﬁbrosis

Leukocytes (PMN early, later mixed incl. variable eosinophils) are biased to the adventitia

Acute, healing and healed stages usu. co-exist

Segmental erosion → aneurysm/rupture/local inﬂam

→ palpable nodule

Consequences: ischaemic injury/infarcts/ulcers/thrombosis

d/dg 2

◦

arteritis (due to infarction, inﬂammation or infection)

Microscopic Polyarteritis

Segmental ﬁbrinoid necrosis ± leukocytoclasia (incl. venules)

Necrotising GN and pulmonary capillaritis, also skin, muscle, GIT and mucosae

All lesions tend to be of the same stage

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TABLE 6.1 Diagnosing vasculitides

Vessel Type Lung GN Skin Diagnostic Antibodies/Comments

Large Elastic Arteries

Giant cell arteritis ±×±older patients & more restricted to media cf. Takayasu

Takayasu’s disease ±×±exclude Syphilis

Syphilitic aortitis conﬁrm with serology

CTD aortitis ±±±usu. ascending only, sparing of major branches (cf.

Takayasu) e.g. ankylosing spondylitis, RhA, SLE

Medium-sized Muscular

Arteries

Giant cell arteritis ±×±±↑ESR, 50% have polymyalgia rheumatica (PMR)

Takayasu’s disease ±×±vide supra for d/dg with giant cell arteritis

PA N

√

HBV (40%), p-ANCA/c-ANCA (≤10%)

Buerger’s disease ××±

Wegener’s

√√√

c-ANCA (70%), p-ANCA (20%), neither (10%)

Churg-Strauss

√√√

p-ANCA (75%)

Kawasaki’s disease

Fungal

√

CTD arteritis ±±±Lupus can have dermo-renal involvement with

non-proteinase-3 p-ANCA in 25%. RhA are

seropositive for IgG rheumatoid factor

Arterioles +/ Capillaries

Microscopic polyarteritis

√√√

c-ANCA (45%), p-ANCA (45%), neither (10%)

PA N

√

vide supra. Larger vessels also involved

Wegener’s

√√√

c-ANCA (70%), p-ANCA (20%), neither (10%)

Churg-Strauss

√√√

Rickettsial

lymphocytic vasculitis ××

√

see Chapter 20: Skin

◦

pauci-immune GN ×

√

× p-ANCA (60%), c-ANCA (30%), neither (10%)

Goodpasture’s

√√

× linear IgG + C3 in BMs. p-ANCA (25%).

leukocytoclastic vasculitis ±±

√

HSP (± IgA ANCA), cryoglobulins (± HCV Ags) and

serum-sickness can have dermo-renal involvement ±

elastase p-ANCA. Drug reactions may have

MPO/lactoferrin p-ANCA

Veins/Venules

Buerger’s disease ××±

Wegener’s

√√√

c-ANCA (70%), p-ANCA (20%), neither (10%)

◦

cutaneous

granulomatous phlebitis

××

√

very rare

Trousseau’s syndrome ××

√

migratory thrombophlebitis assoc

with metastatic

adenocarcinoma. PMNs early, granulomas later

leukocytoclastic ±±

√

Lymphatics

Crohn’s/Sarcoid ±±

√

Granulomatous vasculitis may be 2

◦

to perivascular

lymphatic involvement.

Wegener’s Granulomatosis (WG)

For def

and lung and kidney features, see p. 87.

Necrotising vasculitis away from necrotic areas (extensive ﬁbrinoid change is unusual)

Affects arteries, arterioles and veins

Lymphocytes and plasma cells > giant cells and PMN, eos. are usu. sparse (except in the eosinophilic

variant)

Granulomatous inﬂammation may involve whole vessel wall and extend into lumen

Arterioles, capillaries and veins may be involved (e.g. in alveolar septa) ± leukocytoclasia

d/dg other granulomatous/PAN-like vasculitides (giant cell, Takayasu’s, Churg-Strauss, etc.)

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Churg-Strauss Vasculitis

Eosinophilic PAN

Eosinophilic microscopic polyarteritis

Eosinophilic WG-like granulomatous vasculitis

Eosinophilic phlebitis

Eosinophilic leukocytoclastic vasculitis

Necrotising FSGN (rarely)

For extravascular details and deﬁnition, see p. 87.

Buerger’s Disease (Thromboangiitis Obliterans)

Strong (≈ dose-response) association with tobacco smoking

Muscular arteries of the forelimbs, skip lesions early on, and involves adjacent veins

Acute inﬂam

(early) → chronic inﬂam

→ﬁbrosis affects whole vessel wall incl. adventitia and

surrounding veins and nerves

Inﬂamed, cellular thrombus

± Giant cells in/adjacent to thrombus (cf. in the media in other arteritides) These are said to be

± Microabscesses in vessel wall



pathognomonic

Separation of layers of the vessel wall by inﬂam

/ﬁbrosis

Good preservation of the IEL (cf. giant cell/other arteritis or atheroma)

d/dg atheroma: preserved IEL, early onset, upper limb involvement, vein involvement, inﬂam

nature,

small vessel involvement.

d/dg giant cell arteritis: distribution, giant cell location, preservation of IEL, adventitial involvement,

vein involvement.

Leukocytoclastic Vasculitis (LCV)

For morphology and further information, see p. 301. Example causes are given below.

Most drug reaction vasculitides

Henoch-Sch¨onlein purpura (HSP)

Cryoglobulinaemia (also results in membranoproliferative GN)

Serum sickness (see p. 350)

Beh¸cet’s disease (see p. 194 and p. 341)

Some forms of paraneoplastic vasculitis

Neisseria infections (e.g. N. meningitidis)

Urticarial Vasculitis and Lymphocytic Vasculitis

See Chapter 20: Skin.

Rheumatoid Vasculitis

Nerves, skin and main visceral small arteries and capillaries, esp. hands and nail folds

Transmural ﬁbrinoid necrotising vasculitis

Cutaneous lymphocytic vasculitis These are said to be

Cutaneous urticarial vasculitis



pathognomonic

d/dg drug reaction

SLE Vasculitis

Nerves, skin and main visceral small arteries and capillaries

Transmural necrotising vasculitis (PAN-like with ↓overall inﬂam

±↑PMN)

Cutaneous urticarial vasculitis

LN and spleen arteries may show ‘onion skin’ perivascular ﬁbrosis

For GN spectrum, see pp. 204–205; for further detail see pp. 297–298.

d/dg lupus ‘anticoagulant’ thrombotic vasculopathy (ﬁbrin thrombi in small vessels → et seq.) [also

called antiphospholipid Ab syndrome: see p. 351 and pp. 61–62]

Progressive Systemic Sclerosis (PSS) Vasculitis

Fibrinoid necrotising vasculitis of small arteries

↑ Mucopolysaccharide in intima

Onion skinning of intima

d/dg severe HT changes

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Kawasaki’s Disease

Seen in children with the mucocutaneous LN syndrome (MCLNS)

Transmural necrotising vasculitis with PMN predominating early on (PAN-like)

Later → mixed mononuclear cell inﬁltrate (incl. intramural T-cells) and PMN

Arterioles and venules may be involved in addition to muscular arteries

d/dg: see p. 119, under ‘Kikuchi-Fujimoto disease’

Miscellaneous

Radiation Angiopathy

Muscular arteries, arterioles and capillaries. For veno-occlusive disease, see p. 169

Early:  endothelial atypia (nuclear hyperchromasia, swelling)

 ﬁbrinoid necrosis

 RBC extravasation

 thrombosis

Later:  proliferative endarteritis and intimal ﬁbroplasia

 foam cell accumulation and accelerated atherosclerosis

 small vessel telangiectasia

 adventitial ﬁbrosis and distortion, fragmentation of the IEL ± inﬂam

(d/dg vasculitis)

 hyaline arteriolosclerosis-like changes (q.v. – d/dg HT)

Congophilic (Amyloid) Angiopathy (CAA)

Clin.: multifocal superﬁcial cerebral haemorrhage/SAH (± Alzheimer’s)

Hyaline eosinophilic material in meningeal +/ cerebral vessels These H&E features may

± Evidence of previous haemorrhage



be subtle

Immuno for A4 () amyloid is more sensitive cf. Congo red

Aneurysms

Deﬁnition

An abnormal localised dilatation of a vessel

True – surrounded by a complete vessel wall (e.g. atheromatous, congenital, luetic, mycotic)

False – extravascular haematoma communicating with the intravascular space (e.g. anastomotic leak,

mycotic aneurysm)

Atherosclerotic:

Usu. abdominal and below the renal arteries. Grow by deposition of thrombus (→ laminar structure)

Atheromatous erosion (and .

. weakening) of media

Complications:  rupture

 occlusion of vessels/ostia by pressure or thrombus (e.g. renal/vertebral)

 compress/erode adjacent structures (e.g. ureter/vertebrae)

 embolism

 infection (‘mycotic aneurysm’)

 retroperitoneal ﬁbrosis ± ureteric involvement

Luetic (syphilitic)

Thoracic aorta (usu. the arch)

Proliferative endarteritis of vasa vasorum → patchy necrosis (loss) of medial ﬁbroelastic tissue

Lymphoplasmacytic periarteritis of vasa vasorum

Dense collagenous ﬁbrous patches of intima with grooves (‘tree bark’ macro)

Complications:  rupture

 occlude coronary ostia

 compress/erode adjacent structures (→ respiratory difﬁculties/cough/pain)

 annuloaortic ectasia et seq. → cor bovinum

d/dg: aortitis of psoriasis, Reiter’s or ankylosing spondylitis

Cirsoid aneurysms (Racemose aneurysms)

These are dilated AVMs (congenital +/ traumatic)

Occur in the scalp, leptomeninges and elsewhere

Venous aneurysms

Rare and usu. 2

◦

to trauma or abnormal inﬁltrates of the wall (vide infra)

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Other conditions weakening the vessel wall

Congenital (e.g. berry aneurysm)

Inﬂammatory (e.g. PAN)

Infective (‘mycotic aneurysm’)

Inﬁltration by diffuse NF tissue in NF-1

Trauma (as a result of stretching of the scar) e.g. cardiac, arteriovenous-ﬁstula and caroticocavernous

sinus aneurysms

DM (capillary aneurysms e.g. retina)

Arterial Dissection (Dissecting ‘Aneurysm’)

Tracking of blood between (usu.) the middle and outer thirds of the media. Commonest in the aorta

Potentiating factors: HT and conditions with ↑ MPS deposition e.g. pregnancy/Marfan’s

Atheromatous plaques act as barriers to dissection

Aortic dissection:

± Intimal tear on ascending aorta (a distal tear → double barrel aorta →↓risk of complications)

± ‘Cystic medial necrosis’ (disorganisat

of the media, elastic fragmentat

and pools of acid MPS

forming pseudocystic [i.e. no lining] spaces – see also p. 78)

Complications:  rupture into a coelomic cavity → exanguination/cardiac tamponade

 occlusion of ostia (e.g. carotid, coronary, renal, mesenteric)

 impaired aortic valve function

Fibromuscular Dysplasia (Fibromuscular Arterial Hyperplasia)

Muscular arteries; renal > carotid/other sites

One or more of the following may be seen:

 segmental medial hypertrophy alternates with medial thinning and attenuation of IEL

 ﬁbrous replacement of outer half of media

 cellular concentric intimal ﬁbroplasia

 adventitial ﬁbrous encasement

Complications: stenosis, thrombosis, aneurysm (in thinned segments), dissection

d/dg NF-1 assoc

arterial dysplasia/vasculopathy (vide infra)

NF-1 Associated Vasculopathy (Vascular Neuroﬁbromatosis)

Veins and muscular arteries: → renovascular HT, aneurysm, ﬁstulae, haemorrhage (! a per-operative

risk)

Veins (± arteries) may have their walls weakened by inﬁltration with diffuse NF spindle tissue

Arteries show concentric cellular myointimal proliferation (MSA +ve cells) with MPS ++

Nodules of smooth muscle spindle-cells may be seen in the arterial media and intima (S100 −ve)

d/dg ﬁbromuscular dysplasia (vide supra)

Thrombus and Thromboembolus (Features and Dating Criteria)

d/dg embolus (e.g. PE)/thrombus vs. PM clot:

 embolus is ﬁrmer (cf. ‘chicken-fat’ clot) and is not a cast of the vessel

 clot does not have a laminar cross-section (lines of Zahn)

 thrombus/embolus stands proud of the vessel wall when cut

Dating thrombus:

 sampling: take a block from the junction of thrombus and vessel wall

 two days: endothelial bud proliferation begins

 eight days to one year: haemosiderin deposits

 age of ﬁbrin (by the MSB method): early = yellow, medium = red, very old = blue

Ehlers Danlos Syndrome

Excessive elastic tissue in small arteries

Thrombotic Microangiopathy (TMA) and DIC

See p. 207.

Transplant Rejection Angiopathy

See organ-speciﬁc chapters.

Tumours and Malformations

See Chapter 5: Paediatric and Placental, and Chapter 21: Soft Tissues.

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Vascular 74

Bibliography

Bellamy, C.O.C. (2004) Microangiopathies and malignant vascular injury in the kidney. Current Diagnostic Pathology, 10 (1), 36–51.

Cavallo, T. (1998) Pathologic approach to the diagnosis of vasculitis. Current Diagnostic Pathology, 5 (2), 70–81.

Cotran, R.S, Kumar, V. and Collins, T. (eds) (1999) Robbins Pathologic Basis of Disease,6

edn, W.B. Saunders Co., Philadelphia.

Knight, B. (1983) The Coroner’s Autopsy,1

edn, Churchill Livingstone, Edinburgh.

Mooney, E.E. and Shea, C.R. (1997) Cutaneous vasculitis. Current Diagnostic Pathology, 4 (1), 1–9.

Ng, W-K. (2003) Radiation-associated changes in tissues and tumours. Current Diagnostic Pathology, 9 (2), 124–136.

Nopajaroonsri, C. and Lurie, A.A. (1996) Venous aneurysm, arterial dysplasia, and near-fatal hemorrhages in neurofibromatosis type 1. Human

Pathology, 27 (9), 982–985.

Sheaff, M. and Baithun, S.I. (1997) Pathological effects of ionising radiation. Current Diagnostic Pathology, 4 (2), 106–115.

Sternberg, S.S. (ed) (1997) Histology for Pathologists,2

edn, Lippincott Williams & Wilkins, Philadelphia.

Symmers, W. St. C. (ed) (1976) Systemic Pathology, Vol. 1, 2

edn, Churchill Livingstone, London.

Wheater, P.R., Burkitt, H.G. and Daniels, V.G. (1987) Functional Histology: A text and colour atlas,2

edn, Churchill Livingstone, Edinburgh.

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Heart 75

7. Heart

Normal and Age-Related Changes

Valves

Avascular except for microvessels at the root

Three-layer sandwich of (from ventricular surface outwards):

◦

lamina ventricularis lined by endothelium and containing most elastic ﬁbres

◦

lamina spongiosa (MPS-rich, containing muscle in the AV valves near the valve root)

◦

lamina ﬁbrosa lined by endothelium, focally thickened at contact points (lines of closure)

Blood Supply

LAD supplies: apex, anterior LV, anterior

of the septum

RMC supplies: RV free wall, posterior LV (→ Posterior Descending if right dominant)

LCirc supplies: lateral LV (→ Posterior Descending if left dominant)

Posterior descending supplies the posterior

of the septum

Age-Related Changes

Brown atrophy (lipofuscin) and basophil degeneration (glucan)

Right shift and tortuosity of ascending aorta → HOCMoid sigmoid septum

Aortic valve: calcinosis (± stenosis)

Mitral valve: bulging, atheromatoid changes, Ca

, Lambl’s excrescences

Ischaemic Heart Disease

Angina

May show myocardial scarring / infarction

Sig. coronary disease may be absent in LVH or hyperthyroidism

MI (Regional)

Usu. transmural and involving: LAD (50%), RMC (30%), LCirc (15%), LMC/combined (5%)

Macro:  8–10 hours none, but NBT test may show focal lack of enzyme activity

 1–2 days swelling, lack-lustre

 2–3 days pale, soft, ± beginning of ‘tigroid’ haemorrhages

 3–7 days yellow-grey, haemorrhages, softening (‘myomalacia cordis’)

 7–10days sharp deﬁnition with vascular granulation tissue

 1–2 weeks ‘gelatinous transformation’ at the centre of the infarct

 3–12 weeks scar tissue

Micro:  2–12 hours blurring of striations, ‘cloudy swelling’ (=eosinophilia and granularity)

 1day ↑eosinophilia, myocytes become angulated, wavey and ‘pinched’

 2–7 days PTAH shows striations undergoing granular disintegrat

with clumping

into ‘contraction bands’ (likened to Chinese writing), ↓nuclear staining,

variable PMN inﬁltrate, beginning of granulation tissue by 1 week

 1st week PMN are prominent

 2nd week granulation tissue is prominent

 3rd week collagenisation (scarring) begins

 6–12 weeks ﬁbrosis, ↓vascularity, myohypertrophy, chamber dilatation

 months–years fossilised infarct (an old MI containing a central area that looks like a

recent MI)

Complications:

 immediate: arrhythmias and SCD

 acute  rupture of ventricle, septum, pap. muscle

 pericarditis

 intracardiac thrombus (due to ↑thromboplastin and eddying)

 LVF / CCF / cardiogenic shock

Diagnostic Criteria Handbook in Histopathology: A Surgical Pathology Vade Mecum. Paul J. Tadrous



2007 by John Wiley & Sons, Ltd. ISBN: 978-0-470-51903-5

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Heart 76

 chronic  aneurysm (15%) → LVF / emboli

 angina (relief or production)

 re-infarction (esp. smokers)

 antimyocardial autoimmunity (→ Dressler’s: fever, tachycardia, pleuroperi-

carditis)

MI (Subendocardial)

Severe coronary atheroma (except in aortic valve disease)

Usu. whole LV circumference ± regional transmural infarct

Sudden Cardiac Death (SCD)

May see an old infarct or angina changes

Most do not have a fresh infarct

Inﬂammatory Heart Disease

Viral Myocarditis

Coxsackie B (common in the UK) – diagnose by serology, pericardial ﬂuid, throat swab / faeces

Mixed mononuclear cell inﬁltrate

± Necrosis, ± granulomatous myocarditis

Systemic Diseases

RhA: nodules

SLE: ﬁbrinoid, histiocytes, apoptoses, Libman-Sacks ﬁbrin vegetations (not related to closure lines,

present on the surface of the inﬂux of blood, valve shows ﬁbrinoid necrosis at site of attachment)

Vasculitides: Wegener’s, PAN, Kawasaki

Sarcoid

Whipple’s disease: focal ﬁbroses, valve deformities (d/dg rheumatic fever), DPAS +ve foamy M

Chagas’ disease (of Trypanosoma cruzi): acute → fever, LNp, unilateral orbital oedema, rash, etc.;

Chronic → megaoesophagus/colon/heart (cardiomegaly); see Chapter 23: Infection and Immunity

Granulomatous Myocarditis

Idiopathic (not to be confused with idiopathic giant cell myocarditis)

Sarcoid

Infective: usu. TB or viral

Rheumatic fever (Aschoff bodies)

d/dg M cytomyolysis which accompanies cerebral infarct, head injuries, etc.

Idiopathic Giant Cell Myocarditis

Rapid clinical deterioration → death

Serpiginous necrosis

Giant cells at periphery

Floppy Mitral Valve

◦

focal destruction of the lamina ﬁbrosa with replacement by . . .

◦

. . . accumulations of MPS

Acute Rheumatic Fever

Pancarditis: pericarditis, myocarditis, endocarditis

Aschoff bodies:

 Aschoff cells:  eosinophilic ragged cytoplasm

 nucleus has a clear zone around elongated nucleolus to give an ‘owl’s

eye’ or ‘caterpillar’ appearance

 early:  swelling, fragmentation and eosinophilic change of connective tissue

 interstitial basophilic material

 later: granulomatous foci and ﬁbrinoid change

 located around small vessels

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Heart 77

Myocardial damage:  lymphocyte predominant inﬁltrate

 muscle necrosis, vacuolation and multinucleation

 ± Aschoff bodies (esp. in septum)

Vasculitis:  affects vessels of any size

 may be PAN-like in larger vessels

 perivascular ﬁbrin

 adventitial scarring

 medial oedema

 intimal and medial elastiﬁcation with loss of distinction between intima and media

 thromboses and recanalisation

Valve disease:  seen along lines of closure

 intimal ulceration

 ‘verrucae’ of platelets and ﬁbrin

 ± Aschoff bodies

Chronic Rheumatic Fever Valve Disease

Fibrosclerotic thickening

Vascularisation of the valve

± Non-speciﬁc chronic inﬂammation

Cardiac Allograft (Transplant) Rejection

Predominantly T-cell inﬁltrate

± Granulocytes (usu. eosinophils > PMN)

± Myocyte necrosis

A mixed inﬁltrate (lymphocytes, plasma cells, histiocytes ±granulocytes) is said to be evidence against

rejection

Changes due to healing of a previous biopsy site:

 granulation tissue ± organising ﬁbrin with local distortion of myocytes

 ± early lipofuscin (‘ceroid’) M

 usu. seen on only one of the submitted fragments

Ischaemia and reperfusion injury: foci of myocyte necrosis / vacuolisation / dropout ± a mild PMN

inﬁltrate. No evidence of a rejection inﬁltrate (mononuclear cells ± eosinophils)

Subendocardial thickening / ﬁbrosis

Subendocardial dense lymphocyte collections (‘Quilty lesions’) without (Type A) or with (Type B)

inﬁltration of adjacent myocardium are of uncertain signiﬁcance (? localised rejection)

Mild Acute Rejection = sparse T-cells, no eosinophils or necrosis

Moderate / Severe Acute Rejection = moderate multifocal inﬁltrate with eosinophils ± necrosis

Chronic rejection:

 graft vasculopathy: concentric proliferative endarteritis with atheromatoid features

 myocardial cellular rejection

 myocyte vacuolisation / coagulative necrosis

 parenchymal ﬁbrosis and atrophy

Humoural rejection:

 = donor Ab-mediated vascular endothelial damage occurring during the acute and chronic

rejection time periods (manifest as graft dysfunction not attributable to cellular rejection or

ischaemia on endomyocardial biopsy)

 PMN/M in capillaries, endothelial swelling, congest

/haemorrhage, interstitial oedema

 immuno: C4d +vity in capillary endothelia (becomes negative as humoural rejection resolves)

The presence of contraction band necrosis is said to be evidence against rejection if this is the only

feature but within the context of a picture of acute rejection it is considered to be one form of ‘myocyte

damage’ for grading purposes

Opportunistic infection (if present, rejection cannot be reliably assessed):

 uncommon but important to exclude due to implications for immunosuppression Rx

 CMV: serology is best as inclusions tend to be cytoplasmic only and fragmented

 Toxoplasma: ! do not confuse intracellular granular Ca

for Toxoplasma (do von Kossa)

 a prominent PMN component should raise suspicion for infection

Grading acute cellular rejection (Billingham et al., 1990; Stewart et al., 2005):

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Heart 78

TABLE 7.1 Grading acute cellular rejection

2004 Revised ISHLT Myocyte Other

Grade Grade Damage

Large Lymphocytes Granulocytes Features

mild

⎧

⎨

⎩

1A absent multifocal (perivasc./interstitial) absent

1B absent diffuse but sparse absent

2 1 focus only present absent

mod. 2R 3A multifocal multifocal absent

severe



3B multifocal more diffuse present

4 present diffuse diffuse oedema, vasculitis,

haemorrhage

myocytedamageincludesmyocyteswithirregularborderduetoencroachmentbyinﬂam

cells,architecturaldsturbance,

partial replacement of myocytes or myocyte necrosis (incl. contraction band necrosis)

For updates and illustrations see: University of Pittsburgh Transplant Internet Service

(www.tpis.upmc.edu) and Slootweg & de Weger (1998).

Non-Inﬂammatory Heart Disease

Inﬁltrates / Deposits

Amyloid

Iron: haemochromatosis

Calcium: calcinosis

Oxalate: oxalosis

Storage diseases (e.g. in rhabdomyomas or in glycogenosis Type 2 = Pompe’s disease)

Hypertrophic Obstructive Cardiomyopathy (HOCM)

All ages (even elderly, esp. if assoc

with myosin binding protein mutation). Macro may look normal

Thickened endocardial patch with sharp lower border on the LV side of the septum is said to be

pathognomonic (if present)

‘Disarray’ is the hallmark feature:

 present in ≥2 blocks (away from the insertion of the LV into the septum)

 ﬁbre bundle disarray: loss of parallel arrangement and presence of ﬁbroid-like whorls

 myocyte disarray: bizarre shapes and nuclear pleomorphism

 myoﬁbrillar disarray: do a PTAH stain

Interstitial ﬁbrosis

The RV is involved in ≈

of cases

Arrythmogenic Right Ventricular Dysplasia (ARVD)

See Chapter 25: Autopsy.

Syndromic Conditions

The Marfan Syndrome / Cystic Medial Necrosis / Floppy Mitral Valve

Aorta:  disorganisation of the media

 disruption of medial elastic ﬁbres

 pools of AB +ve MPS

Valves:  disruption of lamina ﬁbrosa and elastica

 pools of acid MPS

 thickened and opaque cusp may develop 2

◦

infective endocarditis

Pseudoxanthoma Elasticum

Irregularly thickened and fragmented elastic ﬁbres (in arteries and subendocardially)

Fibrosis

Sudden Cardiac Death, Congential Heart Disease, Examination of the Heart

See Chapter 25: Autopsy.