Unusua| and Uncommon

u|monary D|sorders

!ay P. 8yu

Iacu|ty D|sc|osures
no relauonshlps exlsL wlLh lndusLry.
Learn|ng Cb[ecnves
Aer Lhls sesslon, learners wlll be able Lo:
8ecognlze characLerlsucs of several unusual and
uncommon pulmonary dlsorders.
ldenufy dlagnosuc feaLures of Lhese dlsorders.
uescrlbe managemenL opuons for Lhese dlsorders.
kare (Crphan) D|seases
uenluon: a dlsease or condluon aecung <200,000
persons ln Lhe uS.
LsumaLed 23 mllllon people (8) ln Lhe uS have one
of Lhe >6,000 rare dlseases.
lallure Lo dlagnose a rare dlsease - generally due Lo a
fallure Lo conslder Lhe dlagnosls ln Lhe rsL place.
ulagnosls of rare pulmonary dlsorders
Conslder a broad dlerenual dlagnosls aL Lhe ouLseL
8e able Lo recognlze characLerlsuc cllnlcal conLexL and
lmaglng feaLures
Unusua| and Uncommon u|monary
D|sorders
ulmonary Alveolar roLelnosls
ulmonary Amyloldosls
8lrL-Pogg-uube Syndrome
lgC4-relaLed ulsease
ConsLrlcuve 8ronchlollus
SponLaneous neumomedlasunum
Aud|ence kesponse uesnon #1
Whlch one of Lhe followlng sLaLemenLs perLalnlng Lo
pulmonary alveolar proLelnosls (A) ls Lrue?
A. Crazy pavlng" pauern seen on P8C1 ls nearly
paLhognomonlc.
8. Cf Lhose undergolng whole lung lavage LreaLmenL, Lhe
ma[orlLy wlll need repeaL LreaLmenL.
C. CurrenLly, subcuLaneous admlnlsLrauon of CM-CSl ls
consldered sLandard LreaLmenL.
u. Secondary forms of A ouLnumber Lhe prlmary
(ldlopaLhlc) cases.
u|monary A|veo|ar rote|nos|s
Also known as pulmonary alveolar
phosphollpoproLelnosls.
Accumulauon of llpoproLelnaceous maLerlal ln Lhe
alveoll
MosL (90) ldlopaLhlc, remalnder - congenlLal and
secondary forms.
lmpalred surfacLanL meLabollsm by macrophages
due Lo alLerauons ln CM-CSl slgnallng.
Id|opath|c A
MosL are 20-60 yr of age (medlan aL dlagnosls = 39
yr).
nonspeclc presenLauon: lnsldlous onseL of
exeruonal dyspnea and cough. Also fever, faugue,
welghL loss, chesL paln, and hemopLysls.
Someumes asympLomauc.
lnsplraLory crackles ln 20- 30, dlglLal clubblng
uncommon.
Id|opath|c A
^ serum levels of LuP, surfacLanL A and u (S-A and
S-u), and mucln-llke glycoproLeln (kL-6) common,
buL nonspeclc.
Anu-CM-CSl anubodles deLecLable ln serum and 8AL
uld ln mosL cases of ldlopaLhlc A.
Id|opath|c A
Ckk: bllaLeral, paLchy alr-space lnlLraLes, less commonly
lnLersuual pauern, oen more promlnenL ln Lhe perlhllar
reglons (baL-wlng").
nkC1: ground-glass and/or consolldauve lnlLraLes ln
paLchy or dluse dlsLrlbuuon wlLh sharp demarcauon
from normal lung. 8eucular opaclues or lnLerlobular
sepLal Lhlckenlng presenL wlLhln Lhe alr-space lnlLraLes
(crazy-pavlng" pauern) - nonspeclc.
I1s: a resLrlcuve defecL, reduced uLCC.
Pulmonary Alveolar Proteinosis
39M Ex-smoker, DOE x 1 yr
Pulmonary Alveolar Proteinosis
39M Ex-smoker, DOE x 1 yr
Crazy paving
Id|opath|c A
ulagnosls
Mllky eMuenL 8AL ln an approprlaLe cllnlcal
semng.
PlsLologlc conrmauon by bronchoscoplc blopsy,
occaslonally surglcal.
(NEJM 2007)
Id|opath|c A
1reaLmenL: whole lung lavage for Lhose wlLh
moderaLe Lo severe dyspnea and hypoxemla.
Medlan durauon of beneL = 13 mo
60-70 requlre repeaL lavage.
CM-CSl subcuLaneous (3-20 mcg/kg/day) or
aerosollzed (230-300 mcg Lwlce dally every oLher
week)
8lLuxlmab
Id|opath|c A
Whole lung lavage
8esponse raLe 1
sL
lavage: 70-84.
CM-CSl
Cverall response raLe: 39 (range, 43-92)
SC: 48 (43-73)
lnhaled: 77 (62-92)
Cverall relapse raLe: 30 (range, 0-83)
SC: 44 (0-44)
lnhaled: 13 (4-36)
(Kahn. Chest 2012)
Id|opath|c A
Cllnlcal course ls varlable, sponLaneous resoluuon
and progresslon Lo resplraLory fallure
3- and 10-year survlval: 73 and 68, respecuvely
ueaLhs usually relaLed Lo resplraLory fallure or
unconLrolled lnfecuon (especlally wlLh opporLunlsuc
paLhogens such as NocotJlo)
Lung LransplanLauon - A can recur
Aud|ence kesponse uesnon #2
Whlch of Lhe followlng sLaLemenLs perLalnlng Lo amyloldosls and
Lhe resplraLory LracL ls Lrue?
A. LxLernal beam Lherapy can be eecuve ln Lreaung
Lracheobronchlal amyloldosls.
8. Amylold lung nodules do noL cavlLaLe.
C. ulmonary lnvolvemenL ls mosL commonly seen wlLh AA
(secondary) Lype of amyloldosls.
u. Amyloldosls does noL cause dluse lnLersuual lnlLraLes ln
Lhe lung.
u|monary Amy|o|dos|s
Amyloldosls ls a heLerogeneous group of acqulred or
lnherlLed dlseases characLerlzed by deposluon of
amylold ln Lhe exLracellular ussue space.
MosL frequenL Lypes of amyloldosls - AL (prlmary)
and AA (secondary).
ulmonary lnvolvemenL by AL (prlmary) sysLemlc
amyloldosls ls relauvely common, lnfrequenL wlLh AA
(secondary) and famlllal amyloldosls.
u|monary Amy|o|dos|s
Amylold can deposlL ln Lhe Lracheobronchlal Lree or
pulmonary parenchyma, locallzed or dluse pauern.
May presenL wlLh sympLoms or radlologlc
abnormallues.
Alrway: focal nodules/plaques or dluse submucosal
lnlLrauon of larynx and Lracheobronchlal Lree.
arenchyma: slngle or muluple nodules, or dluse
parenchymal lnlLraLes.
u|monary Amy|o|dos|s
arenchymal nodules may grow slowly, cavlLaLe
(30), or calclfy (20).
uluse lnLersuual pauern - bllaLeral nodular and/or
reucular pauern wlLh sepLal Lhlckenlng on P8C1,
usually sysLemlc AL amyloldosls. Can calclfy.
leural euslon
Medlasunal and/or hllar adenopaLhy
CbsLrucuve sleep apnea
Diffuse Interstitial Pulmonary Amyloidosis
56M Primary Systemic (AL) Amyloidosis
Diffuse Interstitial Pulmonary Amyloidosis
68F
55M
Tracheobronchial
Amyloidosis
Nodular
Amyloidosis
26M
Pulmonary Cystic Amyloidosis
u|monary Amy|o|dos|s
ulagnosls: blopsy maLerlal reveallng characLerlsuc
apple-green blrefrlngence wlLh polarlzed mlcroscopy
on Congo red sLaln.
1reaLmenL: varles wlLh Lype of pulmonary
lnvolvemenL and underlylng cause.
1racheobronchlal - bronchoscoplc laser, exLernal
beam Lherapy.
uluse parenchymal - LreaL underlylng plasma
cell dyscrasla ln AL amyloldosls.
Aud|ence kesponse uesnon #3
Whlch of Lhe followlng sLaLemenLs regardlng 8lrL-Pogg-
uube (8Pu) syndrome ls Lrue?
A. 8Pu ls an auLosomal recesslve dlsorder.
8. Cysuc lung dlsease can be seen ln adulLs wlLh 8Pu buL
ls uncommon.
C. ApproxlmaLely 23 of 8Pu pauenLs wlll experlence
pneumoLhorax.
u. Cysuc lung dlsease ln 8Pu ls radlologlcally
lndlsungulshable from pulmonary Langerhans' cell
hlsuocyLosls.
8|rt-nogg-Dub syndrome
8are, lnherlLable dlsorder (auLosomal domlnanL)
Cermllne muLauons ln Lhe 8Pu (llcN) gene
(chromosome 17), encodes for Lumor-suppressor
proLeln, folllculln.
CuLaneous Lrlad of brofolllculomas, Lrlchodlscomas,
and skln Lags, along wlLh a propenslLy for renal
Lumors.
AssoclaLed wlLh cysuc lung dlsease and
pneumoLhoraces.
8|rt-nogg-Dub syndrome
CharacLerlsuc skln leslons - rm, dome-shaped
papules appear durlng Lhe 3rd or 4Lh decade,
predomlnanLly face, scalp, neck, and upper chesL.
auenLs who presenL wlLh cysuc lung dlsease or
pneumoLhorax Lend Lo be mlddle-aged wlLhouL a
prevlous dlagnosls 8Pu.
90 of adulL pauenLs have lung cysLs on C1, 23
experlence pneumoLhorax.
Birt-Hogg-Dub syndrome
57F Ex-smoker Pneumothoraces x 12
Birt-Hogg-Dub syndrome
58M with pneumothoraces x 2
Birt-Hogg-Dub syndrome
50M fibrofolliculomas
8|rt-nogg-Dub syndrome
Some germllne muLauons can cause pulmonary
manlfesLauons ln Lhe absence of skln or kldney leslons
need Lo be dlsungulshed from oLher dlfuse cysuc lung
dlseases
LAM
ulmonary Langerhans cell hlsuocyLosls
Lymphocyuc lnLersuual pneumonlus
loeomocysus pneumonla
LlghL chaln deposluon dlsease & amylold
D|use Cysnc Lung D|seases
LAM LCn 8nD Amy|o|d LI
C||n|ca| nearly all
women, some
have, renal
AML, 1SC
MosL are
smoklng-
relaLed
osluve lP,
skln & renal
Lumors
underlylng
sysLemlc
amyloldosls,
C1u, eLc
underlylng
lmmune
declency,
C1u, eLc
Lab LlevaLed
serum vLCl-u
level, PM8-43
sLaln, geneuc
LesL (1SC)
Cu1a
sLaln
Ceneuc LesL uysproLeln-
emla
(monoclonal),
Congo red
sLaln
uysproLeln-
emla
(polyclonal)
nkC1 uluse, round
cysLs
lrregular
cysLs,
cavlLaung
nodules,
basllar
sparlng
CysLs
varylng slzes
& shapes,
more ln
lower lung
CysLs varylng
slzes &
shapes, oen
wlLh nodules
CysLs of
varylng slzes
& shapes,
CCCs,
nodules,
sepLal
IgG4-re|ated D|sease
lnlually descrlbed ln 2001 as auLolmmune
pancreauus" assoclaLed wlLh lgC4+ plasma cells.
Slmllar lgC4-relaLed leslons ldenued ln oLher organs
lncludlng lung.
Can be locallzed Lo one or more slLes.
Lymphoplasmacyuc lnlLraLe (lgC4+ plasma cells, 1
cells) and brosls.
usually adulLs, more commonly men.
Spectrum of IgG4-kD: Lxamp|es
ancreas - auLolmmune pancreauus
Lye - dacryoadenlus, orblLal pseudoLumor
Sallvary glands - slaladenlus
1hyrold - 8ledel's Lhyroldlus
AorLa - aoruus/perlaoruus
Lymph node - lymphadenopaLhy
erlcardlum - perlcardlus
8eLroperlLoneum - brosls
kldney - nephrlus, eLc
Current D|agnos|s of IgG4-kD
2 of 3 ma[or hlsLopaLhologlcal feaLures:
uense lymphoplasmacyuc lnlLraLe
llbrosls, aL leasL focally sLorlform
CbllLerauve phleblus
lmmunohlsLochemlcal - ^ number of lgC4
+
plasma cells
and ^ lgC4
+
/lgC
+
cell rauo (cuLos vary dependlng on
organ).
ANu
Cllnlcal conLexL - presenLauon, serum lgC4 level,
response Lo sLerolds.
IgG4-re|ated D|sease
lnLraLhoraclc manlfesLauons (ln 14 Lo >30)
local parenchymal opaclues (pseudoLumor)
lnLersuual lung dlsease (C, nSl)
MedlasL / hllar adenopaLhy, medlasL brosls
Alrway (sLenosls), pleural (nodules, euslon)
L1-posluve
LlevaLed serum lgC4 level - common
8esponds Lo corucosLerold Lherapy: prednlsone
30-60 mg/d Lhen Laper wks-mos.
44M cough, lymphadenopathy,
systemic symptoms x 2 yr.
TBLBx: chronic inflamm, fibrosis
- many IgG4+ cells.
IgG4: 2020 mg/dL (NL 8-140)
IgG4-re|ated D|sease
Treated with pred 40/d -
symptom, CT findings
resolved at 1 mo.
IgG4
Bronchial bx
59F
multiple nodules
59M ILD
IgG4-re|ated D|sease
(Inoue. Radiol 2009)
Aud|ence kesponse uesnon #4
Whlch of Lhe followlng sLaLemenLs regardlng
consLrlcuve bronchlollus (obllLerauve bronchlollus)
ls correcL?
A. MosL commonly assoclaLed wlLh clgareue smoklng.
8. Can be seen ln pauenLs wlLh rheumaLold arLhrlus.
C. lnsplraLory crackles are usually heard.
u. 8esponds well Lo corucosLerolds.
Constr|cnve 8ronch|o||ns
Also called obllLerauve bronchlollus" or bronchlollus
obllLerans"
Can be classled by euology:
Allogra reclplenLs
osL-lnfecuous
Connecuve ussue dlseases
lnhalauonal ln[ury
lngesLed Loxlns
urugs
CrypLogenlc
Constr|cnve 8ronch|o||ns
1yplcally presenL wlLh slowly worsenlng exeruonal
dyspnea, chronlc cough
Lungs usually sound clear, wheezlng ln some
l1: alrow obsLrucuon, usually wlLhouL
bronchodllaLor response
Cx8: shows hyperlnauon
P8C1: mosalc pauern wlLh paLchy areas of alr
Lrapplng, scauered bronchlecLasls
Constrictive Bronchiolitis
21F RA x 9 yr , severe obstructive lung disease (FEV1 19%)
Constrictive Bronchiolitis
21F RA x 9 yr , severe obstructive lung disease (FEV1 19%)
Expiration
Inspiration
Expiration
Normal
Constrictive bronchiolitis
Inspiration
Constr|cnve 8ronch|o||ns |n So|d|ers keturn|ng
from Iraq and Afghan|stan (nL!M 2011)
80 soldlers from lorL Campbell, kenLucky, wlLh
lnhalauonal exposures, eq, 2003 sulfur-mlne re,
durlng servlce ln lraq and AfghanlsLan were
evaluaLed for dyspnea on exeruon.
38/49 undergolng vA1S lung blopsy had consLrlcuve
bronchlollus.
Some had C1 and/or l1 abnormallues.
Constr|cnve 8ronch|o||ns
8elongs ln Lhe dlerenual dlagnosls of obsLrucuve
lung dlsease.
1reaLmenL: varles wlLh Lhe underlylng cause.
CorucosLerolds, sysLemlc or lnhaled, generally
lneecuve.
ln allogra reclplenLs, macrolldes, eq, azlLhromycln
230 mg 3x per week.
Lung LransplanLauon
Cbstrucnve Lung D|seases
Common causes
CCu
AsLhma
8ronchlecLasls
uncommon Lo rare causes
upper alrway leslons
Some lnLersuual lung dlseases - eq, LAM, LCP
8ronchlolar dlsorders - eq, consLrlcuve bronchlollus
Mlscellaneous - eq, kyphoscollsosls
Case resentanon
28M, nonsmoker, unemployed, comes Lo Lu for evaluauon
of chesL paln slnce earller ln Lhe day.
no dyspnea, cough or wheezlng. no fever, chllls, sweaLs.
no h/o Lrauma.
MP: mlxed personallLy dlsorder, acuve marl[uana use.
Meds: none.
Lxam: normal, lungs sound clear.
Lab: normal C8C, chemlsLry, LCC. urug screen - 1PC.
Cx8, C1 chesL - Lo be shown.
Spontaneous Pneumomediastinum
Spontaneous Pneumomediastinum
Aud|ence kesponse uesnon #S
WhaL ls Lhe mosL approprlaLe nexL sLep ln Lhe
managemenL of Lhls pauenL ?
A. 8ronchoscopy and CasLrogran swallow sLudy
8. 1horaclc surgery consulLauon
C. AdmlL Lo MlCu
u. none of Lhe above
Spontaneous neumomed|asnnum
neumomedlasunum = free alr ln Lhe medlasunum
Source of alr: alrways, lung, esophagus (rarely, gas-
produclng paLhogens)
SponLaneous, Lraumauc, laLrogenlc
SponLaneous pneumomedlasunum (S)
rlmary (no lung dlsease)
Secondary (eq, asLhma, CCu, lLus)
Spontaneous neumomed|asnnum
1yplcally young adulLs, buL wlde age range.
ChesL paln and/or dyspnea, someumes, dysphagla,
neck paln/swelllng or no sympLoms. SC emphysema,
Pamman slgn ln some.
May be preceded by coughlng, sneezlng, vomlung,
exerclse, lnhalauonal drug use, dlvlng, eLc.
Spontaneous neumomed|asnnum
Cenerally noL assoclaLed wlLh a paLhologlc cause -
exLenslve dlagnosuc Lesung noL necessary.
neumoLhorax (occurs ln 10-30) usually does noL
requlre dralnage.
8esolves ln 1- 2 weeks.
Unusua| and Uncommon u|monary
D|sorders
ulmonary Alveolar roLelnosls
ulmonary Amyloldosls
8lrL-Pogg-uube syndrome
lgC4-relaLed ulsease
ConsLrlcuve 8ronchlollus
SponLaneous neumomedlasunum
Summary of key o|nts
A ls commonly assoclaLed wlLh anu-CM-CSl anubodles.
Amyloldosls ln Lhe lung can occur as alrway, parenchymal,
pleural, or medlasunal leslon.
8Pu syndrome causes cysuc lung dlsease and pneumoLhorax.
lgC4-relaLed dlsease can be assoclaLed wlLh a wlde array of
lnLraLhoraclc leslons.
ConsLrlcuve bronchlollus presenLs wlLh obsLrucuve lung
dlsease ln dlverse cllnlcal conLexLs.
SponLaneous pneumomedlasunum ls usually benlgn.
kecommended kead|ng and Add|nona|
kesources
khan A, eL al. Lecuveness of CM-CSl herapy ln auLolmmune
pulmonary alveolar proLelnosls. ChesL 2012,141:1273-83.
lnney !P, eL al. Amyloldosls and Lhe lung. Lur 8esplr Mon
2011,34:132-70.
1oro !8, eL al. Lung cysLs, sponLaneous pneumoLhorax, and
geneuc assoclauons ln 89 famllles wlLh 8lrL-Pogg-uube
syndrome. Am ! 8esplr CrlL Care Med 2007,173:1044-33.
8yu !P, eL al. ulmonary ManlfesLauons of lgC4-relaLed
Scleroslng ulsease . Lur 8esplr ! 2012,39:180-86.
8yu !P. Classlcauon and approach Lo bronchlolar dlseases.
Curr Cpln ulm Med 2006,12:143-31.
8CNUS CIN1 DISLASLS
(lf ume allows)
Another Rare Lung Disease
31M with abnormal CXR
u|monary A|veo|ar M|cro||th|as|s
LxLenslve lnLraalveolar deposluon of concenLrlcally lamellaLed
calclum phosphaLe spheres - dlsuncuve calclc mlcronodular
lnlLraLe on Cx8/C1.
Ceneuc dlsease (auLosomal recesslve), muLauons of Lhe
5lcJ4A2 gene - encodes a Lype llb sodlum phosphaLe
coLransporLer .
Abnormal phosphorus meLabollsm by Lype ll cells.
MosL asympLomauc aL dlagnosls.
no known Lherapy.
Can progress Lo resplraLory fallure.
80F nonsmoker, s/p L mastectomy 1991 (14 yrs before)
with cough & mediastinal lymphadenopathy
Silicone Lymphadenopathy
S|||cone Lymphadenopathy
lrequency of asympLomauc rupLure of slllcone
envelopes ~ 0.2-4, lncreases wlLh aglng of Lhe
lmplanL.
CharacLerlsuc hlsLologlc ndlngs: foamy
macrophages and forelgn body glanL cell reacuon
wlLh promlnenL vacuoles, lymphocyuc lnlLraLe.
Slllcone lymphadenopaLhy can mlmlc recurrenL
cancer, eq, breasL cancer or lymphoma.


Silicone Embolism
Feb. 12, 2011 (Reuters) - Philadelphia police
suspect a London woman who died after a botched
buttocks enhancement may have been killed when
a fumbled injection filled her lung with silicone and
caused a fatal embolism.
The End

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