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?
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
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
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
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
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
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
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)
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
Differential diagnosis ofDifferential diagnosis ofUIP histologyUIP histology
Mixed UIP/NSIP
NSIP – fibrosing pattern
DIP
Fibrotic phases of other interstitial diseases
- LCH
- EAA
- DAD
Aetiological differentialAetiological differentialdiagnosis of UIP patterndiagnosis of UIP pattern
Collagen vascular disease
Drug - induced pneumonitis
Asbestosis
Radiation pneumonitis
Hermansky - Pudlak syndrome
EAA
Idiopathic UIP
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
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)
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
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
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
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
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
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
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
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