History Admitted to Wrexham Hospital Injuries: 1)fractures of maxilla and mandible, floor of R...

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History History Admitted to Wrexham Hospital Injuries: 1) fractures of maxilla and mandible, floor of R orbit, nasal bones & soft tissues 2) fracture one rib, collapse R lung. Bilateral pneumothoraces. Onset of adult respiratory distress syndrome (ARDS) 3) ventilated for eight weeks. Transplant?

Transcript of History Admitted to Wrexham Hospital Injuries: 1)fractures of maxilla and mandible, floor of R...

Page 1: History Admitted to Wrexham Hospital Injuries: 1)fractures of maxilla and mandible, floor of R orbit, nasal bones & soft tissues 2)fracture one rib, collapse.

HistoryHistory

Admitted to Wrexham Hospital

Injuries:

1) fractures of maxilla and mandible, floor of R orbit, nasal bones & soft tissues

2) fracture one rib, collapse R lung. Bilateral pneumothoraces. Onset of adult respiratory distress syndrome (ARDS)

3) ventilated for eight weeks. Transplant?

Page 2: History Admitted to Wrexham Hospital Injuries: 1)fractures of maxilla and mandible, floor of R orbit, nasal bones & soft tissues 2)fracture one rib, collapse.

Clinical ProgressClinical Progress

• Jan 1997; referred for transplant assessment. QoL good and lung disease static

• August 97; holiday in Spain!

• Sept 98; sad, breathless and no QoL Isolated

• Oct 98; transplant assessment

Page 3: History Admitted to Wrexham Hospital Injuries: 1)fractures of maxilla and mandible, floor of R orbit, nasal bones & soft tissues 2)fracture one rib, collapse.

Pathologists and clinicians each developed their own nomenclature

Differing terminologies in different countriesDiffering terminologies in different countries

IPF (USA and ASIA) = CFA (GB)

Idiopathic BOOP (USA ) = COP (GB)

+ many synonyms for IPF/CFA

such as: Hamman-Rich syndrome

"honeycomb lung'

Osler-Charcot disease

Realisation - a worse prognosis with some patterns, e.g. UIP cf. DIP

HRCT, correlated with pathology, separated the different groups

Page 4: History Admitted to Wrexham Hospital Injuries: 1)fractures of maxilla and mandible, floor of R orbit, nasal bones & soft tissues 2)fracture one rib, collapse.

ATS – ERS classificationATS – ERS classification

Histological pattern Clinico-path-radiologic diagnosis

DAD AIP

UIP Idiopathic pulmonary fibrosis

Cryptogenic fibrosing alveolitis

NSIP Non-specific interstitial pneumonia

Organising pneumonia Cryptogenic organising pneumonia

DIP (RB) DIP (RBILD)

LIP LIP

Page 5: History Admitted to Wrexham Hospital Injuries: 1)fractures of maxilla and mandible, floor of R orbit, nasal bones & soft tissues 2)fracture one rib, collapse.

AIP - histopathologyAIP = ARDS on histology - no identifiable aetiology in AIP

Exudative phase dev. in week 1 post - insult - interstitial &

intra-alveolar oedema, hyaline membranes, type II

pneumocytes, intra-alveolar haem. and interstitial

mononuclear inflamm.

In hrs. after insult, ?only in neutrophils in alv. cap. and

interstitial oedema

Bouros D Eur Respir J 2000; 15: 412 -18

Page 6: History Admitted to Wrexham Hospital Injuries: 1)fractures of maxilla and mandible, floor of R orbit, nasal bones & soft tissues 2)fracture one rib, collapse.

AIP – histopathology (2)

Prolif. stage during week 2 – ↑ fibroblastic proliferation in interstitium & alveoli, ↑ type II cells & nuclear atypia - ?malignant, esp. on cytology

Combinations of patterns often seen

Bouros D Eur Respir J 2000; 15: 412 -18

Page 7: History Admitted to Wrexham Hospital Injuries: 1)fractures of maxilla and mandible, floor of R orbit, nasal bones & soft tissues 2)fracture one rib, collapse.

NSIPNSIP

DefinitionDefinition - “an idiopathic interstitial pneumonia with a histologic patten that does not conform to the characteristic features of UIP, RB-ILD, DAD, or COP.”

Main feature is a temporarily HOMOGENEOUSHOMOGENEOUS pattern of inflammation or fibrosis

Page 8: History Admitted to Wrexham Hospital Injuries: 1)fractures of maxilla and mandible, floor of R orbit, nasal bones & soft tissues 2)fracture one rib, collapse.

Causes of NSIPCauses of NSIP

CT disease (inc. undiff. CT disease) (Kinder BW AJRCCM 2007; 176: 691 – 7)

10% dev. collagen dis. (Park IN Eur Resp J 2009; 33: 68 – 76)

Other diseases:

PBC

Hashimoto's thyroiditis

Acute G/N

Chronic renal failure

Exposures - birds, wood stove, various occupations (e.g. grain dust in brewing, cleaning jacuzzi)

Drugs (gold, penicillamine, hydralazine)

DAD

Smokers (assoc. emphysema) (Marten K Eur Radiol 2009; 19: 1675-85)

Page 9: History Admitted to Wrexham Hospital Injuries: 1)fractures of maxilla and mandible, floor of R orbit, nasal bones & soft tissues 2)fracture one rib, collapse.

UIP (Usual Interstitial Pneumonia)UIP (Usual Interstitial Pneumonia)

DefinitionDefinition - “UIP is a histologic pattern seen in the clinical setting of diffuse, bilateral interstitial lung disease. Changes often distributed along the subpleural and paraseptal regions”

Main feature is a PATCHY, PATCHY, TEMPORALLYTEMPORALLY HETEROGENEOUSHETEROGENEOUS fibrosis with scattered fibroblastic foci at the edge of fibrotic scars, causing lung remodeling and honeycombing

Page 10: History Admitted to Wrexham Hospital Injuries: 1)fractures of maxilla and mandible, floor of R orbit, nasal bones & soft tissues 2)fracture one rib, collapse.

Differential diagnosis ofDifferential diagnosis ofUIP histologyUIP histology

Mixed UIP/NSIP

NSIP – fibrosing pattern

DIP

Fibrotic phases of other interstitial diseases

- LCH

- EAA

- DAD

Page 11: History Admitted to Wrexham Hospital Injuries: 1)fractures of maxilla and mandible, floor of R orbit, nasal bones & soft tissues 2)fracture one rib, collapse.

Aetiological differentialAetiological differentialdiagnosis of UIP patterndiagnosis of UIP pattern

Collagen vascular disease

Drug - induced pneumonitis

Asbestosis

Radiation pneumonitis

Hermansky - Pudlak syndrome

EAA

Idiopathic UIP

Page 12: History Admitted to Wrexham Hospital Injuries: 1)fractures of maxilla and mandible, floor of R orbit, nasal bones & soft tissues 2)fracture one rib, collapse.

Histological patterns are distinctive but Histological patterns are distinctive but not not specificspecific

UIPUIP - collagen diseases, asbestosis

COP or idiopathic BOOPCOP or idiopathic BOOP - can be seen in a variety of conditions (Tx, infection)

NSIPNSIP - EAA, collagen diseases, end result of DAD, drugs etc

Page 13: History Admitted to Wrexham Hospital Injuries: 1)fractures of maxilla and mandible, floor of R orbit, nasal bones & soft tissues 2)fracture one rib, collapse.

Variation in histological patterns of ILD between Variation in histological patterns of ILD between connective issue diseasesconnective issue diseases

PM/DM (13) - OP +/- NSIP (one UIP)

RA (17) - Follicular bronchiolitis +/- NSIP (two UIP)

Sjögrens (5) - Chronic bronchiolitis +/- NSIP

SLE (2) - UIP (1), other follicular bronchiolitis & minor compnt. cellular NSIP

Tansey D et al. Histopathology 2004; 44: 585-96

CTD-UIP has ↓fibroblast foci, emphysema & honeycombing, ↑

germinal centre & total inflamm. scores (Song JW Chest 2009;136: 23)

Page 14: History Admitted to Wrexham Hospital Injuries: 1)fractures of maxilla and mandible, floor of R orbit, nasal bones & soft tissues 2)fracture one rib, collapse.

UIP + NSIP

Cases with mixed patterns (NSIP plus UIP)

64 cases of ‘CFA’ with multiple bx. showed 25 concordant cases of UIP (present in all lobes), 8 discordant (UIP + NSIP) and 31 NSIP (3 cellular and 28 fibrotic)

Patients in concordant NSIP group had significantly better survival than discordant or concordant UIP (p = 0.02 and p = 0.04, respectively)

No significant diff btwn. concordant and discordant UIP grps. (p = 0.48)

75% of concordant NSIP group alive 5 years after biopsy, 17% of concordant and 37% of in the discordant UIP group alive

Monaghan H et al. Chest 2004; 125: 522 – 6

Page 15: History Admitted to Wrexham Hospital Injuries: 1)fractures of maxilla and mandible, floor of R orbit, nasal bones & soft tissues 2)fracture one rib, collapse.

NSIP vs. UIPUIP pattern most important predictor of prognosis

Risk ratio of mortality in UIP (106 pts) >28.5, after controlling for age, symptom duration, radiology, physiology & sex

NSIP pts. (28 fibrotic & 5 cellular) more likely to respond or remain stable Honeycombing on HRCT indicated UIP – sens, 90%, spec of 86%

Flaherty KR et al. Eur Resp J 2002; 19: 275 – 283

Page 16: History Admitted to Wrexham Hospital Injuries: 1)fractures of maxilla and mandible, floor of R orbit, nasal bones & soft tissues 2)fracture one rib, collapse.

UIP- Histological predictorsUIP- Histological predictorsof prognosisof prognosis

Honeycombing

Dense interstitial inflammation involving 60% or of bx

Intrapleural fat

< 50% fibroblastic foci/cm2 in biopsy - median survival of 89m. cf. 49m. in those with > 50 FF/cm.2

No assocn. between FF at ∆ and DAD at autopsy

Travis WD et al. Am J Surg Pathol 2000; 24: 19-33

Titto, L et al. Thorax 2006; 61: 1091 – 5

Page 17: History Admitted to Wrexham Hospital Injuries: 1)fractures of maxilla and mandible, floor of R orbit, nasal bones & soft tissues 2)fracture one rib, collapse.

Acute exacerbations of UIP

Defined as acute, clinically significant deteriorations of unidentifiable cause in pts. with underlying UIP

Proposed diagnostic criteria include; subjective worsening over 30 days or less, new bilateral radiographic opacities & nono infection or Identifiable aetiology. Histology – DAD (75%), OP or ↑ fib. foci

Potential causes include; infection (? CMV) disordered cell biology (loss of epithelial cell integrity, fibrocyte

function, TGFβ), abnormal coagulation (procoagulant environ. as in ARDS), and genetic factors (polymorphism in erythrocyte complement receptor 1 and mutations in surfactant protein genes)

Churg A Am J Surg Pathol 2007; 31: 277 Kim DS et al ERJ 2006; 27: 143Collard HR et al. AJRCCM 2007; 176: 636

Page 18: History Admitted to Wrexham Hospital Injuries: 1)fractures of maxilla and mandible, floor of R orbit, nasal bones & soft tissues 2)fracture one rib, collapse.

CFA - EBVCFA - EBV

IHC EBV DNA

CFA 12/27 14/27

control 3/28 4/28

p=0.005 p=0.007

81% of PCRassays confirmed

IHC results

Stewart, Egan, Hasleton et al. Am J Respir Crit Care Med 1999; 159: 1336

Page 19: History Admitted to Wrexham Hospital Injuries: 1)fractures of maxilla and mandible, floor of R orbit, nasal bones & soft tissues 2)fracture one rib, collapse.

Idiopathicpleuroparenchymal fibroelastosis

Clinical presentation suggestive of chronic idiopathic interstitial pneumonia Marked pleural & parenchymal radiographic involvement with UL predominance

Pathology includes; Marked visceral pleural fibrosis ; Prominent, homogenous, subpleural fibroelastosis; Sparing of parenchyma distant from the pleura; Mild, patchy, lymphoplasmacytic infiltrates; and Small numbers of fibroblastic foci present at the leading edge of the fibrosis.

Frankel SK CHEST 2004; 126:2007–2013Becker CD Mod Pathol 2008;21: 784 – 7

Page 20: History Admitted to Wrexham Hospital Injuries: 1)fractures of maxilla and mandible, floor of R orbit, nasal bones & soft tissues 2)fracture one rib, collapse.

Bronchiolocentric interstitialBronchiolocentric interstitialpneumonia (BrIP)pneumonia (BrIP)

BrIP - marked predilection for women (80%) in middle age (40–50 years)C/O SOB, cough, wheeze, chest pain and recurrent Pneumonia. 8/12 Churg’s pts had history of inhalational exposures (wood smoke, birds, cocaine etc) CT and PFT show restrictive diseaseMean FU of approx. 4 years in nine patients, 33% were DOD and 56% had persistent or progressive disease.? BrIP a unique entityYousem S Mod Pathol 2002; 15: 1148-53. Churg A Am J Surg Pathol 2004; 28: 62-8 Fukuaka J Am J Surg Pathol 2005; 29: 948-954

Page 21: History Admitted to Wrexham Hospital Injuries: 1)fractures of maxilla and mandible, floor of R orbit, nasal bones & soft tissues 2)fracture one rib, collapse.

Bronchiolocentric interstitialBronchiolocentric interstitialpneumoniapneumonia (BrIP)(BrIP)

Centrilobular damage with peribronchiolar scarring (remodelled

fibrotic lung) and very focal interstitial and air - space granulation

tissue

– Scar extends from centrilobular area out into peripheral

lobule

– Bronchiolar metaplasia – may be exuberant

What should not be present

1. Granulomas – implies HP

2. Bronchiectasis – can cause a distal pattern

of centrilobular injury/scar

3. Aspirated food

4. BO/OP – obliterative luminal airway damage