ILD Flashcards
Path buzzword: UIP
Lymphoplasmacytic inflammation with fibroblastic foci and honeycomb change
–Temporal heterogeneity (juxtaposition of fibrosis and normal lung)
Path buzzword: LIP
Dense accumulation or “sheets” of lymphocytes and plasma cells within interstitium and alveolar spaces
Path buzzword: RBILD
accumulation of pigmented macrophages within respiratory bronchioles and alveolar ducts with bronchiolcentric distribution
-No significant fibrosis, interstitial inflammation, germinal centers
Path buzzword: DIP
Similar to RBILD but with alveolar spaces uniformly filled of pigmented macrophages. Homogeneous filling with preserved alveolar architecture and minimal fibrosis.
Features consistent with UIP
- Basal and subpleural predominant
- Reticular opac (with traction supportive of fibrosis)
- Honeycombing
- Absences of Inconsistent Features
Inconsistent with UIP
- GGO (outside areas of fibrosis)
- Mosaicism/air trapping
- Nodules- centrilobular, perilymphatic
- Parahilar, peribronchovascular
- Upper lobe distribution
- Peripheral fibrosis with minimal honeycombing, subpleural sparing
- lower lobe distribution, not subpleural
Mutation leading to PAM
SLC34A2; autosomal recessive
Type IIb sodium-phosphate cotransporter
PAP associated with Ab against
GM-CSF
Genetic pulmonary fibrosis:
hTERT and hTR are AD
Pathologic hallmark of NSIP
cellular infiltrate with temporal uniformity
BAL lymphocytosis >20%
RB-ILD pathology
Pigmented alveolar macrophages in and around respiratory bronchioles and surrounding alveoli
DIP pathology
alveolar spaces uniformly filled with pigment-laden macrophages. Homogenous with preserved alveolar architecture and minimal fibrosis or honeycombing.
LIP Pathology
interstitial and bronchovascular infiltrate of lymphocytes and plasma cells. Can have poorly formed granulomas and multinuc giant cells
PLCH: diagnosis
-IHC
BAL with >5% CD1a positive cells
-IHC with CD1a and S-100
PLCH: pathology
bronchiolocentric stellate lesions with central scar; intracellular inclusions (Birbeck granules) on EM, extensive Eos in early phase
LAM: pathology
hamartomatous proliferation of atypical smooth muscles along lymphatics in lung, thorax, abdomen/pelvis
LAM: Cell expression
HMB-45; CD-63 on
1. myofibroblast-like spindle-shaped cells 2. epithelioid-like polygonal cells
-just spindle-shaped cells: muscle alpha-actin, vimentin, desmin (on )
BAL Findings in IIP:
1. NSIP
BAL with >20% lymphs (overlap with HP and drug-induced)
BAL Findings in IIP:
COP
Charac mixed pattern: lymphocytes (20-40%), neutrophil (10%), and Eos (5%) with some plasma/mast cells
-CD4/CD8 is decreased
BAL Findings in IIP:
PLCH
> 5% CD1a-positive cells
BAL Findings in IIP:
AEP
> 25% Eos, normal periph Eos
-Tbbx with marked eosinophilic infiltration of alveoli and interstitium
BAL Findings in IIP:
CEP
> 25% Eos
-Tbbx whos eosinophilic microabscesses, low grade vasculitis, and interstitial fibrosis
Nintedanib
- Mech
- Side effects
TK receptor blockers- mediate fibrogenic growth factors (PDGF, VEGF, FGF)
Diarrhea and LFT derangements, CytP3A4
Pirfenidone
- Mech
- Side effects
- Antifibrotic agent, inhibits TGF-b stimulated collagen synthesis, block fibro last proliferation
- nausea, rash
Mutations leading to IPF
hTERT, hTR, Muc 5B
HRCT RB-ILD vs DIP
- RBILD: fine centrilobular nodules, bilat patch GGOs upper and lower lung zones.
- DIP peripheral GGO, in lower lung zones, possible cyst/emphysema, no honeycombing
Classic CTc findings for LIP
- Bilat GGO
- Centrilobular nodules
- Bronchovascular bundle thickening and interlobular septal thickening
- thin-walled cysts
Gene assoc with LAM
TSC1 and TSC2
Diagnostic test to differentiate berylliosis from sarcoid:
Lymph transfer test on BAL or beryllium lymphocyte proliferation test
CD4/CD8:
- Normal= 1.5-2
- Sarcoidosis: >3.5 has sens of 50% and spec of 94%
- Organizing pneumonia: CD4/CD8 is decreased
- HP: decreased CD4/CD8
Tumors associated with Birt Hogg Dube:
Renal cell carcinoma, oncocytic hybrid tumor, clear cell carcinoma
Birt Hogg Dube mutation
AD, chr 17
BHD gene, encodes folliculin (tumor suppressor)
Classic Histopath finding with amiodarone lung toxicity
Foamy macrophages with fibrosis and lamellated inclusions
Lung toxicity with 5-ASA and sulfasalazine
Eosinophilia, OP, BO
Caplan Syndrome
Nodular reaction in patient with RA (or will develop RA in 5-10yr) exposed to coal dust. Focal lesion with necrotic center surrounded by lymphocytes and plasma cells and coal dust
Histology of silicotic nodule
Central dense hyalinzed collaged contained silica particle surrounded by concentric collagen fibers, peripheral thick capsule of dust-lade macrophages, lymphocytes, and collagen
Talc Pathology
Granulom with multinucleated giant cells in interstitium and pulmonary arteries (in IVDU). WITH birefringent talc crystals
Factors that determine degree of injury to upper and lower respiratory tract
- particle size
>10um filtered by upper pharyngeal anatomy, <5um bypass resp tract and desposit in lower resp tract - concentration
- water solubility
-water soluble react with mucosal surfaces of upper airway
-less water soluble- lower resp tract and delayed parenchymal abnml - location- ventilation or not
- physical properties
Water soluble inhalation injuries
immediate irritation and reactivity of conjunctival surfaces
- Ammonia
- SO2
- chlorine
Less water soluble agents
No acute, irritating symptoms, react with lower resp tract and cause delayed, severe parenchymal abnml
- NO2 (silo fillers)
- phosgene (welding, meth)
- SO2
Classic BAL Findings PAP
Milky effluent
- alveolar macrophages filled with PAS- + material
- Lamellar bodies
Distinguish berrylium form sarcoid
Beryllium proliferative test (lymphocytes stimulated with soluble beryllium salts)
Pathology: HP
airway-centered, variably cellular chronic interstitial pneumonia, a lymphocyte-rich chronic bronchiolitis, and poorly formed nonnecrotizing granulomas distributed mainly within peribronchiolar interstitium
Skin manifestations of BHD
- Fibrofolliculoma
- trichodiscoma
- Skin tag
Renal tumors seen with BHD
- Oncotic hybrid tumor
- RCC
- Clear cell carcinoma
- papillary renal cell carcinoma
Most common Ab in DM/PM and ILD
Anti-Jo (90% with this Ab have ILD)
Other DM/PM ILD Ab
SRP, Mi-2, amino-acyl transfer RNA synthetase
Amyositis DM/PM ILD
anti-MDA5 (rapidly progressive)
PL-12 (anti-synthetase)
Associated with myositis/scleroderma overlap
Anti-Ku
Assoc with severe necrotizing myopathy (DM/PM)
anti-SRP
CREST syndrome assoc with Ab:
anti-centromere
Homogeneous/diffuse ANA assoc with
SLE or MCTD
Nucleolar ANA assoc with:
Systemic sclerosis, PM
Centromere ANA assoc with:
Systemic sclerosis
Mixed Connective Tissue disease assoc with Ab:
anti-RNP, anti-U1
Sjogren Syndrome Ab
SSA (Ro), SSB (La)
Systemic scerlosis/scleroderma assoc with Ab:
Scl-70 (anti-DNA topoisomerase 1)
Characteristic features of IgG4 related disease
- Dense lymphoplasmacytic infiltrate
- Storiform fibrosis
- obliterative phlebitis
- IHC with IgG4+ cells
5 drugs cause drug-induced lupus
hydralazine, isoniazid, procainamide, quinidine, penicillamine
Major Drugs causing drug-induced HP
MTX, Taxanes
Abx, TNF alpha inhibitors
BCNU toxicity:
dose
timing: days to 17 years
Dose: >1500mg/m2 (25-50% will develop pulmonary toxicity)
Mech: oxidant-induced (decreased glutathione)
~90% mortality
Bleomycin- 6wk- 6mos
-with high O2 can awaken fibrosis/inflammation (binds histones)
> 500 units
Increased risk with age >70, O2, radiation, abnormal renal function
Most common type of pulmonary toxicity with methotrexate
HSP
Amiodarone: dose for lung toxicity
Much more common at >400mg/d
-increased in >60yo
Anti-TNF alpha inhibitors: forms of toxicity
- granulomatous (sarcoid) ILD
- lymphohistiocytic reaction
Rituximab pulmonary toxicity
Can cause acute/subacute cellular ILD, profound lymphocytosis on BAL
-also BOOP or pulmonary fibrosis
