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Heart 79

Tumours

Cardiac Myxoma

Usu. atrial wall

Polypoid (smooth / fronded) ± stalk and attached atrial patch (= excision margin)

Sparsely cellular myxoid matrix (hyaluronic acid) ± outer endothelial lining

Stromal haemorrhage, Ca

± Gamna-Gandy bodies (see Chapter 10: Lymphoreticular)

Myxoma cells:

 elongated / stellate / polygonal; may be single or multinucleated (syncytial giant cells)

 ﬁnely vacuolated eosinophil cytoplasm with variably dense nuclei

 distribution: perivascular, nested, dispersed

 no mitoses

 immuno: vimentin +ve

Other cells: M, siderophages, myoﬁbroblasts, smooth muscle, lymphocytes, plasma cells

± Mucous gland-like structures (+ve for CK, AB, DPAS)

d/dg ﬁbroelastoma (which is more likely if on a valve)

d/dg myxoid MFH and myxoid liposarcoma

Rhabdomyoma

Infant / child, nearly all have tuberose sclerosis

Often multifocal, may be intracavitary

Very swollen myocytes

Glycogenic cytoplasmic clearing

‘Spider cells’ – central nucleus supported by strands of cytoplasm

Cardiac Fibroma

Infant / child

Interweaving bundles of collagen / elastic

Haemopoietic islands

Smooth muscle

Giant Lambl’s Excrescence (Papillary Fibroelastoma)

Adults

Endocardial surfaces esp. aortic valve

Filiform architecture with central dense collagenous cores covered by loose connective tissue

Elastic ++

Malignant Tumours in the Heart

◦

: angiosarcoma, RMS, mesothelioma, liposarcoma, MFH

◦

: lung, breast, lymphoma, thyroid, tongue, stomach, pancreas, kidney, bladder, etc.

Bibliography

Becker, A.E. and Anderson, R.H. (1983) Cardiac Pathology: An integrated text and color atlas,1

edn, Churchill Livingstone, Edinburgh.

Billingham, M.E., Cary, N.R., Hammond, M.E. et al. (1990) A working formulation for the standardization of nomenclature in the diagnosis of heart

and lung rejection: heart rejection study group. Journal of Heart Transplantation, 9 (6), 587–93.

Burke, M.M. (1994) Complications of heart and lung transplantation and of cardiac surgery, in Recent Advances in Histopathology, (eds P.P.

Anthony, R.N.M. MacSween and D.G. Lowe.), Churchill Livingstone, Edinburgh, vol.16, pp. 95–122.

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

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

Crespo-Leiro, M., Veiga-Barreiro, A., Dom´enech, N. et al. (2005) Humoral heart rejection (severe allograft dysfunction with no signs of cel-

lular rejection or ischaemia): Incidence, management, and the value of C4d for diagnosis. American Journal of Transplantation, 5 (10),

2560–2564.

Gallagher, P.J. (1994) The investigation of cardiac death, in Recent Advances in Histopathology, (eds P.P. Anthony, R.N.M. MacSween and D.G.

Lowe), Churchill Livingstone, Edinburgh, vol. 16, pp. 123–146.

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

edn, Churchill Livingstone, Edinburgh.

Pomerance, A. and Davies, M.J. (eds) (1975) The Pathology of the Heart,1

edn, Blackwell Scientific Publications, Oxford.

Silver, M.D. (ed) (1983) Cardiovascular Pathology,1

edn, Churchill Livingstone, NY.

Slootweg, P.J. and de Weger, R.A. (1998) Cardiac transplantation pathology: an update. Current Diagnostic Pathology, 5 (4), 198–203.

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Heart 80

Snell, R.S. (1986) Clinical Anatomy for Medical Students,3

edn, Little, Brown & Co. Inc., Boston.

Stewart, S., Winters, G., Fishbein, M. et al. (2005) Revision of the 1990 Working formulation for the standardization of nomenclature in the diagnosis

of heart rejection. Journal of Heart and Lung Transplantation, 24 (11), 1710–1720.

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

edn, Churchill Livingstone, London.

Willis, R.A. (1952) The Spread of Tumours in the Human Body, Butterworth & Co. Ltd., London.

Web sites

University of Pittsburgh, Transplant Pathology Internet Service. www.tpis.upmc.edu (accessed April 2007).

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Respiratory and Mediastinum 81

8. Respiratory and Mediastinum

Upper Respiratory Tract

Rhinosporidiosis (Rhinosporidium seeberi)

This PAS and mucicarmine +ve protofungus has its 200–300 sporangia in the mucosa and submucosa

d/dg vacuoles of cylindrical cell Schneiderian papilloma (mucosal only)

d/dg myospherulosis: Grocott −ve encysted balls of swollen, pale RBC

following oleic nasal packing. (A d/dg of myospherulosis is protothecosis

which is Grocott +ve)

Rx is excision ± antifungals

The spores in a rhinosporidian

sporangium get smaller towards the

homogeneous wall of the cyst. Effete

spherules may also be present

FIGURE 8.1 Rhinospo-

ridian sporangia

Rhinoscleroma (Klebsiella rhinoscleromatis)

Gram −ve organisms (++ on silver stains) – d/dg non-tuberculoid leprosy

Submucosal granulomas, plasma cells and clear foamy M (Mikulicz cells)

Rx is antibiotics (e.g. tetracyclines)

Inﬂammatory Nasal Polyps

Uncommon before 20 years old, often bilateral ± Hx of asthma, aspirin sensitivity, etc.

Mucoﬁbrous stroma ±radiation-like atypical ﬁbroblasts; (d/dg Microsporidiosis in the maxillary sinus)

Schneiderian (‘Transitional Cell’) Papillomas

Usu. >30 years old, unilateral (± multifocal), tend to recur

Variant: fungiform – often on nasal septum

Variant: inverted – often on lateral wall and assoc

with ↑risk of malignancy

Variant: oncocytic (= cylindrical cell) – inverted, intraepithelial vacuoles contain inspissated mucus;

d/dg Rhinosporidian sporangia (vide supra) or papillary variant of adenocarcinoma

May have focal nuclear atypia or aggregates of atypical nuclei in lower

of the mucosa

PMN inﬁltration → inﬂammatory atypia

Mitoses usu. few and parabasal but may be more extensive – never atypical

d/dg papillary SCC (shows widespread severe atypia and & focal squamous nests), TCC

Nasopharyngeal Carcinoma (NPC)

Keratinising SCC (usual histology)

Non-keratinising SCC: cells have distinct cell borders and a ‘paving stone’ arch

Undifferentiated NPC (lymphoepithelial carcinoma or lymphoepithelioma)

 bimodal (children/teens–‘50s), most radiosensitive of the group, best prognosis

 uniform epithelial cells with vesicular nuclei and indistinct cell borders (syncytial-like) ar-

ranged in solid patches (Regaud) or scattered small groups (Schmincke) in a lymphoid back-

ground

 submucosal origin – may present with cervical LNs in which the LN metastasis may be

misdiagnosed as lymphoma, esp. Hodgkin’s if Schmincke type

 tumour cells EBNA +ve and EBV serology +ve (if EBV −ve = ‘lymphoepithelioma-like

CA’)

 prognosis ∝ stage: I = conﬁned, II = cervical LN +ve, III = into surrounding structures

 pseudoepitheliomatous hyperplasia incited by T-cell lymphomas may cause misdiagnosis of

lymphoepithelial carcinoma or mixed carcinoma / lymphoma

d/dg Sinonasal Undifferentiated Carcinoma: this is organoid with necrosis, vasc. invasion, ↑ NCR and

distinct cell borders but no squamous / glandular / neural diff

(d/dg NB). CK and EMA +ve, NSE

and S100 ±ve, CD99 and HMB45 −ve, NE granules on EM. It is insensitive to chemo/radioRx and

survival is <1 year. d/dg NSE +ve high grade olfactory neuroblastoma, but NB has focal / weak / −ve

CK and EMA staining

. it is important to distinguish this from Sinonasal Undifferentiated Carcinoma (see d/dg)

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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Respiratory and Mediastinum 82

Other Sinonasal Lesions

Vascular: angioﬁbroma (≈ erectile tissue), HPC-like tumour, glomus tumour

Neural/endocrine: paraganglioma, olfactory neuroblastoma (see Chapter 13: Central Nervous System

and Skeletal Muscle), SmCC

Soft tissue: RMS, leiomyoma / leiomyosarcoma, angioma / angiosarcoma, nerve sheath tumours

Lymphoid: lymphomas (esp. angiocentric TCL and lymphomatoid granulomatosis), ﬂorid lymphoid

hyperplasia, plasmacytoma (d/dg plasma cell granuloma)

Inﬂammatory pseudotumour (= plasma cell granuloma)

 unlike d/dg plasmacytoma, this has:

other cell types

—–

a range of plasma cell differentiation

prominent Russell bodies.

Larynx

Lesions in the d/dg of SCC

Squamous papilloma: juvenile ones are prepubertal, multiple, due to HPV, non-keratinising, show koilo-

cytosis but no dysplasia and are benign but may be obstructive / recurrent; adult ones are keratinising,

may show dysplasia and may be the tip of a verrucous carcinoma or assoc

with SCC

PEH (see Chapter 11: Alimentary Tract, under ‘Mouth and Oropharynx’ and Chapter 20: Skin) e.g.

associated with a granular cell tumour

CIS/severe dysplasia: desmoplasia, single cell invasion and stromal reaction to keratin favour early

invasion

Soft tissue lesions (e.g. plasma cell granuloma) vs. spindle cell SCC

FS for margins: ! do not confuse radiation atypia (in spindle stromal cells or epithelium) for SCC

Laryngeal Nodule / Singer’s Node in Reinke’s Space

Vascular type: dilated thin vessels with intra and extravascular ﬁbrinoid ± granulation tissue – d/dg

haemangioma (but these are supraglottic and have thicker-walled vessels)

Myxoid type: myxohyaline stroma, fewer vessels – d/dg amyloid(Congo red +ve), myxoma (has stellate

and mast cells)

Contact Granuloma (Contact Ulcer) of the True Cord

Florid granulation tissue radiating to the surface ±ulceration; d/dg pyogenic granuloma (is lobular not

radiating)

Cystic Lesions

Laryngocoele (of the saccule): usu. acquired (forced blowing), stratiﬁed ciliated lining ± focal lym-

phocytic aggregates

Laryngeal cyst: retention (respiratory-type lining) or congenital (squamous lining) ± lymphocytes

Laryngeal duct cyst with papillary hyperplasia (‘adenoma’ / ‘cystadenoma’): tall cells, often oncocytic,

line tubules, acini and papillae ± goblet cells; usu. occurs in the saccule and is rare

Cystic lesions / neoplasms of minor salivary glands (see pp.133–134)

Malformative/Congenital Anomalies

Congenital Cystic Adenomatoid Malformation (CCAM / CAM / CPAM)

Stocker Classiﬁcation (Stocker, 2002):

Type 0: = acinar dysplasia: widespread and bilateral, small cysts (5mm

), respiratory epithelial lining,

cartilage (i.e. bronchial structures) but no normal alveoli (macro: lungs are small and solid)

Type I: localised mass, large cysts (2–10cm

), resp. epithelium, mucus cell rows, polypoidal infolds,

intervening ﬁbromuscular tissue, presents at all ages, risk of malig. transformation (to BAC / sarcoma)

Type II: usu. conﬁned to 1 lobe (d/dg sequestration), medium cysts (0.5–2.0cm

, back-to-back), simple

columnar cells, interspersed alveolar ducts ± striated muscle ± renal anomalies (= rhabdomyomatous

dysplasia if widespread ± CVS anomalies)

Type III: solid/small cysts with simple cuboidal lining (mimics late fetal lung), may involve upto whole

lung

Type IV: peripheral location, mesenchymal cysts with alveolar lining, no resp. epithelium / cartilage, risk

of blastematous transformation if stromal hypercellularity. d/dg pleuropulmonary blastoma

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Respiratory and Mediastinum 83

Except for type II, CCAM presents in neonates. Types II and IV have a good prog. (others poor)

d/dg CCAM I vs. simple foregut cyst: CCAM has polypoidal infolds and rows of pure mucus cells

d/dg CCAM I vs. bronchogenic cyst: CCAM lacks cartilage and mural mucus glands

d/dg CCAM IV vs. grade I pleuropulmonary blastoma: may be histologically identical – use CPC

d/dg CCAM vs. cystic mesenchymal hamartoma: CCAM lacks a mesenchymal cambium layer

d/dg CCAM vs. sequestration: CCAM has a pulmonary arterial supply, communication with bronchial

tree and presence of normal alveoli (usu. at the periphery of the lesions) except type 0

Sequestration

Lower lobe regions affected in

of cases

Common to all: arterial supply is systemic and ‘airways’ do not communicate with rest of the lungs

Intralobar (i.e. within the visceral pleura): adults, has a pulmonary venous drainage, usu. acquired

Extralobar: infants, systemic venous drainage, developmental, like CCAM II ± lymphangiectasia

Poorly developed lung with columnar / cuboidal epithelium lining dilated spaces ± cartilage

Normal alveoli are not usu. present though there may be collapsed / consolidated alveolar tissue

Cystic Mesenchymal Hamartoma

Multilocular cyst; bland simple cuboidal/columnar lining

(Endometrial stroma-like) mesenchyme with a cambium layer (see CCAM d/dg), mitoses are rare

d/dg endometrial stromal sarcoma (metastatic) or pleuropulmonary blastoma (vide infra)

Chronic Bronchitis, Emphysema and Bronchiectasis

Chronic Bronchitis

Def

: phlegmatic cough on most days for ≥3 months for ≥ 2 consecutive years

Goblet cell hyperplasia

↑Bronchial gland volume – can be estimated by the Reid Index (= thickness of mucosal glandular

layer [superﬁcial surface of glandular layer to superﬁcial perichondrium] divided by the total mucosal

thickness [surface epithelial BM to superﬁcial perichondrium]) using main or lobar bronchi where the

epithelium is parallel to the cartilage. Reid’s original mean values: healthy ≈ 0.25 (upper limit 0.36),

bronchitic ≈ 0.6 (lower limit 0.4) – but other studies showed sig. overlap

Pulmonary Emphysema

Def

: airway dilatation and destruction distal to the terminal bronchioles

Centrilobular:  respiratory bronchioles worst affected

 occurs in smokers / coal workers

 severe effectsdue to shunting ++(‘bluebloater’ hypercapnoeic respiratory failure,

pulm. HT, cor pulmonale)

Panacinar:  alveolar ducts and alveoli worst affected

 focal form is very common in elderly, diffuse form occurs in 

AT deﬁciency

 milder effects, compensatable by ↑ventilation (‘pink puffer’)

Localised forms: paraseptal, paracicatricial, unilateral (McLeod’s syndrome), etc.

Bronchiectasis

Def

: airway dilatation and destruction proximal to the terminal bronchioles

Due to scarring 2

◦

to bronchopneumonia, pertussis, measles, CF, bronchiolitis, narcotics, etc.

Cavities accumulate infected ﬂuid →ulceration, haemoptysis, metastatic abscesses, amyloid, inﬂam-

matory atypical squames on cytology

Interstitial Lung Disease

Non-Speciﬁc / Insigniﬁcant Changes (d/dg Lung Disease)

Non-speciﬁc inﬂam

, ﬁbrosis ± honeycombing may occur in the extreme tips of the lobes (esp. the

lingula and right middle lobe) without implying speciﬁc disease

Sub-pleural ﬁbrosis, non-speciﬁc chronic inﬂam

and larger alveoli may occur in the lung apices

Scarring (any cause) may have adjacent type II pneumocyte hyperplasia: d/dg BAC (p. 92)

Scarring (any cause e.g. smoking/city dwellers) may have adjacent pulm. artery endarteritic changes

(incl. intimal ﬁbrosis and medial hypertrophy) without pulmonary HT

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Respiratory and Mediastinum 84

Lung Transplant Pathology

Rejection and infect

may be asymptomatic and are more common in the lungs cf. heart in combined

Acute rejection: perivenular mononuclear cell inﬁltration (d/dg infection – can be difﬁcult)

Intermediate: diffuse and patchy peribronchial and peribronchiolar mixed mononuclear inﬁltration with

exocytosis (into the respiratory epithelium) ± granulation tissue but no collagen ﬁbrosis

Chronic rejection: patchy obliterative bronchiolitis (q.v.) →vanishing bronchiole syndrome

Cryptogenic Fibrosing Alveolitis (CFA / IPF) Showing Usual Interstitial Pneumonia (UIP)

Chronic, terminal (median survival 3–5 year) condition requiring strong immunosuppression

Dry cough, bibasal creps, restrictive pattern ± characteristic HRCT, non-organ-speciﬁc auto-Abs

Hamman-Rich acute terminal deterioration (ARDS-like) may occur (= AIP)

BAL show lymphocytes and granulocytes

Bronchial Bx can exclude bronchocentric disease (sarcoid, EAA, RBILD) but cannot diagnose CFA

Only diagnose CFA on open lung Bx or PM and then only if speciﬁc features present (else = NSIP)

Periph. (sub-pleural) disease with central sparing. Basal lower lobes worst affected (± honeycomb)

Distal acinar involvement with central sparing (else rethink the diagnosis)

Temporal heterogeneity is the hallmark (ﬁbroblastic foci and mature collagenised areas)

Variegate pathology (normal septa to gross thickening and distortion in the same section)

Lymphoplasmacytic inﬁltrate in septa (and granulocytes in alveoli) ± giant cells with blue bodies

Fibroblastic foci (re-epithelialised Masson bodies) ± marked Type II pneumocyte atypia

Alveolar lining varies from normal to columnar with ciliated / mucus metaplasia

Stromal smooth muscle and arterial thickening with intimal proliferation

DIP is no longer considered part of CFA as it has a distinct, more benign course

d/dg of UIP:

 CTD: pleural thickening/inﬂam

suggests a CTD, look for other signs (vasculitis, nodules,

etc.)

 nitrofurantoin (can look identical to CFA), NSIP, LIP

 EAA, BOOP, chronic eosinophilic pneumonia, sarcoid, radiation, HX

 infection, pneumoconioses, lymphangitis carcinomatosa, Goodpasture’s

 pulmonary alveolar proteinosis

Desquamative Interstitial Pneumonia (DIP)

Diffuse distribution of lightly haemosiderotic M in alveoli

Mild interstitial inﬂam

/ light ﬁbrosis – no temporal heterogeneity

d/dg of DIP:

 smoking (RBILD): patchy (bronchocentric), brown M (‘smokers M’)

 amiodarone / other drugs

 2

◦

to proximal airway obstruction

 EAA, chronic eosinophilic pneumonia, pulmonary alveolar proteinosis, HX

Honeycomb Lung (Causes)

CFA, sarcoidosis, asbestosis, HX, EAA and non-speciﬁc

Non-Speciﬁc Interstitial Pneumonia (NSIP)

Grade 1 = cellular (d/dg LIP – but NSIP does not expand septa like LIP)

Grade 2/3 = ﬁbrotic: spatially and temporally uniform without ﬁbroblastic foci (cf. CFA)

Exclude causes: drugs, hypersensitivity, etc.

Giant Cell Interstitial Pneumonia (GIP)

Peribronchiolar DIP with multinucleated alveolar M ± eos. (! = measles epithelial GC pneumonia)

Multinucleated cells may show emperipolesis / phagocytosis of other inﬂammatory cells

Usu. Hx of hard metal exposure (e.g. tungsten, cobalt, titanium and their alloys)

Diffuse Alveolar Damage (DAD)

Fibroblastic expansion of the interstitium with variable inﬂammation

Hyperplasia of atypical type 2 pneumocytes

Hyaline membranes (∝ disease phase)

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Respiratory and Mediastinum 85

Thrombi in small pulmonary arteries

Megas in capillaries (d/dg viral/malig. cells) – also seen in sepsis without DAD and in normal lungs

See ‘Shock lung’ (ARDS) on p. 383 and d/dg OP (vide infra).

Bronchiolitis Obliterans (Organising Pneumonia [OP], COP and BOOP)

Plugs of cellular myxoid tissue (Masson bodies) in bronchiole lumens and peribronchiolar alveoli

Inﬂam

cells and proteinaceous exudate may be prominent in early lesions

Alveolar reaction to terminal obstructions:

◦

type 2 pneumocyte hyperplasia,

◦

intra-alveolar foamy

(lipoid) M,

◦

cellular debris ± cholesterol clefts

◦

: COP (= idiopathic BOOP) – BAL shows a mixed cell content

◦

: infection, WG, EAA, HX, eosinophilic pneumonia, allergies, some gases

Granulomas, vasculitis, PMN, necrosis, and BAL showing single cell type predominance are all features

which may help identify the underlying aetiology in any given case of OP

d/dg DAD, AIP and NSIP: in OP, the changes are patchy and restricted to peribronchiolar tissue; also

there are no hyaline membranes

Obliterative Bronchiolitis / Bronchitis

Fibrosis within and around bronchial / bronchiolar wall (cf. lumenal in OP), epithelial sloughing

Bronchovascular bundles with missing bronchi are the end result and a good diagnostic clue

Distally the air spaces may accumulate foamy M

Seen 2

◦

to BMTx, lung Tx, RhA and drugs (esp. gold / penicillamine), viruses, mycoplasma, gases

Extrinsic Allergic Alveolitis (EAA)

Peribronchiolar and centriacinar (cf. CFA which is distal acinar)

Spatially heterogeneous (i.e. patchy) but temporally uniform (unlike CFA)

Inﬂam

: lymphocytes (T8) and plasma cells > PMN; eos. are sparse; ± intra and extra-alveolar foam

cells

Lymphocyte-rich BOOP-like areas

Bronchiolar muscle hypertrophy

Most cases have poorly formed granulomas ± giant cells containing cholesterol clefts

± DIP-like pattern

Pneumoconioses

Coal worker’s pneumoconiosis

Upper

of the lung worst affected

Simple: 2–5mm stellate macules of anthracotic M in immobile alveoli (centrilobular) and sub-

pleurally (may follow lymphatics). Nodules (<1cm

) are well-circumscribed and palpable due to

↑collagen (a reaction to coal with higher mineral:carbon ratio)

Complicated (= progressive massive ﬁbrosis): ≥1cm  (Caplan nodules are excluded from PMF),

compensatable, haphazard collagen with pigment, well-circumscribed, ± central breakdown and TB

Caplan’s syndrome (in RhA): upto 5cm , necrobiotic collagen with concentric bands of dust (cf.

randomly intermingled dust) and palisaded M

Grade the amount of dust present from i. to v. thus:

State if dust foci are soft or palpable

i. dust-free

ii. slight diffuse pigmentation

iii. sparse dust foci (≥1cm apart)

iv. moderate dust foci (>1 per cm)

v. numerous dust foci

Silicosis

Whorled laminar collagen with birefringent silicates

and peripheral plasma cells

Asbestosis

This is a clinicopathological diagnosis; histological conﬁrmation, when needed, requires:

◦

diffuse

interstitial ﬁbrosis of the asbestotic type and

◦

evidence of asbestos as the cause (asbestos bodies)

The interstitial ﬁbrosis should be EITHER of at least grade 3 (vide infra) OR, if lowergrades,the distribution

and clinical should be typical (i.e. not elderly smokers with mainly upper lobe disease)

Typical pattern: symmetric, lower lobes worst affected with sub-pleural accentuation but broad areas

of ﬁbrosis (i.e. obliterating architecture), not lace-like (preserved arch.) as in CFA.

silicates are co-inhaled with the silica but it is the silica which causes the ﬁbrosis

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Respiratory and Mediastinum 86

Asbestos bodies:

 only visible when ferruginated →golden [unstained] / Prussian blue [stained] coat

 found in the walls of the RB +/ assoc

with intra-alveolar M

 >1 asbestos body in 1 or several 5 thick Perls-stained tissue section(s) from 1 or several

blocksis usu. considered signiﬁcant. Normal (non-asbestotic) controls may show, on average, 1

asbestos bodyper 100 sections, each section being 2cm

in area.

However, in somepopulations

the norm is higher (e.g. in Finland, ≈

of people unlikely to have been exposed to asbestos

had an average of 1 body per section)

 asbestos body concentrat

can vary 10-fold depending on site (for sampling, see p. 48)

 use of 30 thick unstained sections greatly reduces the time it takes to ﬁnd asbestos bodies

 asbestos bodies may also be quantiﬁed by EM or in BAL ﬂuid (for sample acceptability criteria

and reference ranges see De Vuyst et al., 1998)

 asbestos (and erionite) bodies have a long and (usu.) straight core (0.5 thick) that is clear

(not yellow) and transparent (not black). The Fe-protein coating may be uniform or segmented

and it stiﬂes birefringence (.

. they are usu. not birefringent)

 d/dg other ferruginous bodies: sheet silicates (e.g. talc, kaolinite) are broader/scrolled with

a yellow clear core. Black-cored bodies are usu. carbon (not birefringent, many shapes incl.

long and thin) or titanium oxide rutile (birefringent).

 ! mixed dust inhalation occurs incl. asbestos with other types so:

1. ﬁnding other ﬁbre types does not exclude asbestosis, and

2. ﬁnding a heavily ferruginated body in a patient with a PMHx of asbestos exposure

should not be assumed to be an asbestos body if the core is obscured

Asbestos-related pleural plaques (may have nodular macro and ‘basket weave’ collagen micro) are

common and are not compensatable

Compensation is given for asbestosis, diffuse pleural ﬁbrosis, or asbestos-related neoplasia

Asbestos-related neoplasms are mesothelioma and any histotype of lung carcinoma

d/dg of asbestos-related diffuse pleural ﬁbrosis: sarcomatoid mesothelioma, TB, CTD, adenoCA

Grading the severity of ﬁbrosis (esp. w.r.t. asbestosis)

◦

No ﬁbrosis around respiratory bronchioles (RB)

◦

Mild peribronchiolar ﬁbrosis ± non-linking septa (involving the immediate layer of adjacent alveoli)

◦

As for 1 but septa involve ≥2 adjacent layers of alveoli or alveolar ducts

◦

As for 2 but with at least focal bridging (no non-ﬁbrotic alveolar septa between two bronchioles)

◦

As for 2 but with new spaces forming (> alveolar size – upto 1cm ) – ‘honeycomb lung’

Grading the extent of RB ﬁbrosis (esp. w.r.t. asbestosis)

A. An occasional RB only (affected by any grade of ﬁbrosis) Latterly, the term ‘occasional’ has

B. More than occasional but <50%



been interpreted to mean <25% of

C. 50% of all RB involved the lung tissue.

Immunological / Autoimmune / Connective Tissue Diseases

Relapsing Polychondritis

Death is usu. due to resp. cartilage involvement (esp. tracheal)

Perichondrium is the original site of inﬂam

→invasion of cartilage with ↓basophilia and ↑PA S +vity

Changes over time: PMN → plasma cells → lymphocytes → ﬁbrosis and cartilage atrophy in late

stages

Systemic CTD with vasculitis may develop later or be concurrent

Asthma and Status Asthmaticus

See p. 382, under ‘Anaphylaxis’.

Necrotising Sarcoid Angiitis (NSA) / Necrotising Sarcoid Granulomatosis / Necrotising Sarcoidosis

Peribronchiolar (obliterated), conﬂuent, sarcoidal granulomatous areas

Irregular areas of necrosis (non-caseating) that are not intimately assoc

with the granulomas

Roggli and Pratt, 1983

Asbestos is probably not a cause of laryngeal carcinoma (related to alcohol and tobacco – which were confounding factors in earlier

studies that suggested an asbestos link).

JWBK208-08 December 8, 2007 16:2 Char Count= 0

Respiratory and Mediastinum 87

More typical sarcoid granulomas elsewhere [i.e. tight, non-necrotising, naked, ±Schaumann or asteroid

bodies]

Pulmonary arteritis of the giant cell type or wall inﬁltrated by sarcoidal granulomas

d/dg WG: WG may have a few sarcoid-like granulomas but not as many as NSA

d/dg infective granulomas – must be excluded

d/dg berylliosis (a classical mimic of sarcoid)

Eosinophilic Pneumonia

This is a clinical term for patients with radiological pulm. inﬁltrates and PB eosinophilia

Histologically: eosinophils in alveoli and alveolar septa +/ granulomatous inﬂammation

Later ±→organising pneumonia with diminished eosinophils

Main causes :

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Churg-Strauss syndrome (for more details on the vasculitis see pp. 69–71)

 clinically: fever, asthma, blood eosinophilia

 histologically (esp. skin, kidney, lung):

1. tissue eosinophilia All three need not be

2. vasculitis (PAN-like, WG-like)



present in the same

3. granulomas:  eosinophilic granulomas / abscesses tissue.

 necrobiotic palisaded granulomas

 d/dg eosinophilic variant of WG

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Asthma (esp. if there is mucus plugging or allergic bronchopulmonary aspergillosis)

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Drugs / toxins (e.g. penicillin, smoke, some metals)

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Reaction to infection: e.g. fungi, helminthes (e.g. tropical eosinophilia due to ﬁlariasis)

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Simple pulmonary eosinophilia (Loefﬂer’s syndrome):

 transient eosinophilic pneumonia (changes last 1 month to 1 year)

 retrospective diagnosis

 due to toxocariasis, drugs or intestinal ascaris in some cases

 ‘Loefﬂer’s syndrome’ may also refer to endomyocardial ﬁbrosis with eosinophilia.

Wegener’s Granulomatosis (WG)

Clin: URT/LRT mucosal ulceration (esp. nasal septum) and c-ANCA +vity are good clinical pointers

WG is currently deﬁned by:

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necrotising extravascular granulomas in the URT and LRT

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generalised vasculitis

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GN (necrotising FSGN / crescentic, pauci-immune)

Pulmonary histology

Vasculitis (for the features, see p. 70) – essential for a conﬁdent histodiagnosis

Serpiginous / geographic necrosis with nuclear debris ++ (‘dirty’ necrosis)

Necrosis is surrounded by loose / palisaded granulomatous inﬂam

± giant cells

Multifocal ulceration of airways

The (lung) limited form (± skin) has a better prognosis (but may heal with ﬁbrosis ++)

Limited WG may develop into classic WG with renal / other organs involved years later

Variants: eosinophilic, bronchocentric, BOOP-like

d/dg lymphomatoid granulomatosis (has atypical lymphocytes, vide infra)

d/dg Wegener’s cavitating lung granulomas may resemble TB

d/dg necrotising sarcoid angiitis (has many more sarcoid-like granulomas cf. Wegener’s)

d/dg invasive (necrotising) pulmonary Aspergillosis

Pulmonary Haemorrhagic Syndromes

Wegener’s Granulomatosis (vide supra)

Idiopathic Pulmonary Haemosiderosis

Recent and old intra-alveolar haemorrhage (do Perls – intra-alveolar RBC may be due to Bx artefact)

Minimal / no inﬂammation or ﬁbrosis

Diagnosis of exclusion

Goodpasture’s Syndrome

Recent and old intra-alveolar haemorrhage (do Perls – intra-alveolar RBC may be due to Bx artefact)

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Respiratory and Mediastinum 88

± Leukocytoclastic vasculitis

Necrotising FSGN

Immunoﬂuorescence: linear IgG and C3 on BM of alveolar septa and capillaries

25% are p-ANCA +ve

Pulmonary Hypertension

Normal Histology

Left: Normal pulm. artery with

supernumary arteriole (EVG); Right

plexiform lesion with distal dilatation

lesion & medical hypertrophy (H&E)

FIGURE 8.2 Pulmonary arteries

Pulm. arterial pressure is 25 (at rest) to 30 mmHg (during exercise)

Arteries travel with bronchi, have distinct internal and external elastic

laminae and muscle wall thickness is upto 7% of vessel external



Veins travel in interlobular septa and have indistinct muscle and elastic

Arterioles and venules lack muscle and have a single elastic lamina

Supernumerary arterioles branch directly from larger arteries into the

respiratory parenchyma (these branch points are the typical site of

plexiform and dilatation lesions – see Figure 8.2)

Progression of Lesions in Congenital / 1

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Arterial Pulmonary HT

1. Muscularisation of arterioles (esp. in children and hypoxic adults)

2. Medial hypertrophy (thickness >15% of

 is deﬁnitely abnormal)

3. Concentric cellular intimal thickening (d/dg acellular hyaline venous sclerosis of the aged)

4. Concentric laminar ﬁbroelastosis These four

5. Dilatation lesions (may occur as clusters = angiomatoid lesions)

⎫

⎪

⎬

⎪

⎭

are

6. Necrotising arteritis (ﬁbrinoid necrosis) irreversible

7. Plexiform lesions (usu. <300 and focal .

. may need serials to detect) changes.

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Arterial Pulmonary HT

Associations: youth, female, CTD, liver disease, HIV, miscellaneous (toxic oil, aminorex, eosinophilia

myalgia syndrome, schistosomiasis)

Plexiform lesions: VEGF-1 +ve cellular recanalisation-like plugs but with proximal local cellular

intimal thickening, distal dilatation lesions and occur at supernumerary arterioles; d/dg thrombotic or

embolic recanalisation sites which usu. affect larger vessels and don’t show dilatation lesions.

Thrombotic (small distal arteries .

. normal angiogram or distal pruning)

Medial and intimal thickening (changes 2. and 3. above) may be the only anomalies seen

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Venous Pulmonary HT (Pulmonary Veno-Occlusive Disease)

Associations: BMTx and chemoRx; arterial pulm. HT occurs secondarily but no plexiform lesions

Thrombosed and recanalised septal veins with local congestion and loose-textured intimal ﬁbrosis

Septal ﬁbrosis, capillary haemangiomatosis ± granulomatous reaction to Fe/Ca

deposits in elastic

Larger veins are normal

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Venous Pulmonary HT

Associations: acquired heart disease (LVF, myxoma), mediastinal disease, sarcoid

Venous medial hypertrophy and arteriolisation (i.e. inner and outer elastic laminae become distinct)

Haemosiderosis, ↑ lymphatics, septal oedema and ﬁbrosis, osteoliths, ↑ in arterial adventitia and

media

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Arterial Pulmonary HT

Thromboembolic:  radiol: arterial ﬁlling defects and ventilation-perfusion mismatches

 recanalisation in larger elastic arteries

Thrombotic:  smaller muscular arteries show eccentric ﬁbrosis or multilumenal recanalisation

 2

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to low ﬂow (pulm. stenosis), haematological conditions and emboli (talc / tumour)

Interstitial lung disease and chronic hypoxia: changes 1. 2. and 3., above. Hypoxia may also result in

longitudinal smooth muscle cells / bundles on the intimal side of the IEL