pred 8-patologija respiratornog sistema
TRANSCRIPT
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PATOLOGIJA RESPIRATORNOG
SISTEMA
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Glava i vrat
Glava i vrat
USNA DUPLJA
GORNJI DIŠNI PUTEVI
UHO
VRAT
PLJUVAČNE ŽLJEZDE
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Head and Neck
Gornji dišni putevi
NOS
Nasopharynx
TumorINosa, Sinusa, Nasopharynx
Larynx
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OBOLJENJA NOSA I PARANAZALNIH ŠUPLJINA
Pločasti, respiratorni pseudostratificirani cilindrični epitel, prijelazni epitel Podsluznica-krvne žileLimfne žile u limfne čvorove ždrijela
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Rhinitis
INFEKTIVNI RINITIS:bakterijski akutni i kronični;
NEALERGIJSKI(VASOMOTORNI) RINITIS: hormonalni, Ljekovima izazvan, Atrofični, imedikamentozom rinitis,
ALERGIJSKI RINITIS:
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Alergijski rinitis
Blijeda edematozna sluznica debeli sekret
sluzav sekret, neutrofili i obilje eozinofila
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Rhinitis Chronica
Nastavak akutnog rinitisa(simptomi traju 6 tjedana ili manje), uz razvoj sekundarne bakterijske infekcije
nosna polipoza, devijacija, ulceracija i infekcija se proteže u sinuse
Endoskopski slike: blijeda i suha sluznica, sekret u pušača
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Churg-Strauss sindrom (poznat i kao alergijska
granulomatoza) Autoimuni vaskulitis, dovodi do nekroze. krvne žile i pluća (što počinje kao teške vrsta astme), probavni sistem i periferne živce, srce, koža i bubreg
rijetka bolest ne-nasljedna, ne-prenosiva. Churg-Strauss sindrom je nekad smatran vrstom Polyarteritis nodosa (PAN), zbog slične morphologijeMIKRO: diskretni necrotizirajući granulomi sa brojnim eozinofilima, često formiraju microabscese
DD: Wegener's granulomatosis
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Eosinophilic angiocentric fibrosis
• Vrlo rijedak; nepoznat uzrok
bilo koji dio gornjih dišnih puteva, često nosni septum i sluznica sinusa
Obično žene, srednje dobi 44 godina
Liječenje: kortikosteroidi, resekcija
Mikro: debeli snopovi kolagena, perivascularna lukovici slična fibroza, eosinofilni upalni infiltrat , bez granuloma, bez nekroze, bez vaskulitisa
DD: granuloma faciale (upalne vaskularne reakcije lica, neutrophilni i eozinofilni infiltrat, vaskulitis
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Nasal polyps
Kod djece isključiti cističnu fibrozu
Edematozna lamina propria s promjenjivim upalni infiltrat uključujući eozinofile;
Podtipovi:angiectatic (angiomatous), cistični,edematozni,vlaknasti,
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Rhinoscleroma(scleroma)
Rijetka granulomatozna hronična bolest uzrokovana Klebsiella rhinoscleromatis
1.nosna šupljina (95-100%),2.nasopharynx (18-43%), 3.grkljan (15-40%), 4.traheja (12%) ili 5.bronhije (2-7%)
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Obično Južna Amerika, Afrika, Bliski Istok, Filipini, Indija; rijetko u SAD (uglavnom imigranti)
češća u mladih odraslih
U početku nespecifična rinitis, Gnojan granulomatozna intranasalni ožiljci nalik na gumuMIKRO: granulacijsko tkiva; kasnije hiperplastična sluznice s pseudoepitheliomatoznom skvamoznom hiperplazijom, granulomatozna upala, pjenasti makrofazi (Mikulicz ćelije koje sadrže bakterije) i plazma stanica s Russellom tijela, vaskulitis i ulkus, kasno-fibroza, limfociti i plazma stanice, ali ne Mikulicz staniceDD: Rosai-Dorfman disease, guba
PAS, Giemsa, Steiner ili Hotchkiss-McManus premazi za gram negativne bakterije
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Rhinosporidiosis
Uzrokovane Rhinosporidium seeberi, tradicionalno se smatralo da su uzročnici gljivice, ali su zapravo paraziti
MAKROSKOP: hiperplastična, polipoidna, crvena, nosna šupljina;
MIKROSKOP: velike (100 - 450 mikrona), debele sporangije uz više od 1000 endospora uz mješoviti upalni infiltrat,
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Zapaljenje sinusa- sinusitis
• Sinusitis je upala paranazalnih sinusa čiji uzrok mogu biti bakterije, virusi, gljivice, alergije ili autoimune bolesti.
• Upala može zahvatiti bilo koji od nazalnih sinusa.
• Prema trajanju razlikujemo akutne upale (tijek kraći od 4 tjedna), subakutne upale (tijek od 4 do 12 tjedana) i kronične upale (tijek duži od 12 tjedana).
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Akutni gljivični sinusitis
• u imunokompromitiranih ili dijabetičara, • Uključuje infekciju oka, intrakranijalno širenja, • udružen uz progresivne bolesti i smrti
Liječenje: sistemska antifungalna terapija
Mikroskop: vaskularna invazija gljivice, može izazvati trombozu, upalni infiltrat neutrofila, eozinofila, nekroza tkiva i krvarenja
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Hronični sinusitis • Mješana bakterijska flora, • nakon akutnog sinusitis-a• može dovesti do osteomijelitis-a orbite ili thrombophlebitis-a
venskih sinusa• najčešće maksilarni sinus, • prethodno periapikalna infekcija• Često-Aspergillus• Može dovesti do empijema
• MIKRO: žljezdana hiperplazija, pločasta metaplazija, zadebljanje bazalne membrane, upalne stanice uključujući eozinofile, edem;
• Kosti zadebljanje, fibroza koštane srži; prisustvo mucina sugerira gljivičnih
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Chronic noninvasive fungal sinusitis
• bezbolni gljivični sinusitis• povezan s dijabetesom, imunokompetentnim• u endemskim područjima (Sudan, Saudijska Arabija)
MIKROSKOP: gljive okružene, upalom stranog tijela, granulomi, po definiciji ne vaskularna invazija
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Granulomatozni sinusitis
• Sarcoidosis• Wegener-ova granulomatosa• Tuberculosis• Steroidna injekcija
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Wegener’s granulomatosis
• Klasična forma – gornji i donji respiratorni putevi i bubrezi
• Ograničena forma – gornji respiratorni
• putevi ili pluća (1/4 slučajeva, 80% zahvata i bubrege)
• MIKRO: leukocytoclastični vaskulitis obuhvata arteriole, male arterije i vene sa geografskom nekrozom, palisadama histiocita, gigantskim stanicama
•
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Tumori nosa i paranazalnih šupljina
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Nasal pseudopolyps
Eosinophilsedematous
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Tumori
• 1. Nasopharyngeal Angiofibroma– Vrlo vaskularan inkapsuliran tumora, adolescenata muškaraci,
epistaxis, kontraindikacija biopsija
• 2. Papilloma– HPV asocirani– Proliferacija epitelnog tkiva u nosu, grlu, ustima
• 3. Inverted Papilloma– Ekstenzija u mukozu invertirani egzofitični
rast– Benigni tumor Lokalno agresivan (visok stepen
recidiva)– Rijetka progresija do karcinoma
• 4. Izolirani Plasmacytoma– Maligni plasma cell tumor
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5. Olfactory Neuroblastoma– proizlazi iz stanica neuralnog grebena – Vrlo maligan, metastase udaljene– pozitivan na NSE i S-100, t (11:22) odsutna, ima Pseudo-
rozete
6. Nasopharyngeal Carcinoma – prepoznatljiva geografska distribucija
rak djece u Africi, odrasli u Kini, Eskimi, vrlo rijedak u SAD– povezan s Epstein Barr Virus (EBV) infekcijom
7. Squamous cell carcinoma– Tri paterna rasta: – Keratinizirajući-WHO-1),nekeratinizirajući-
WHO-2), Undifferentiated carcinoma -WHO-3)– Undifferentiated- bolji odgovor na
radioterapiju od ostalih
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Nasopharyngeal carcinoma
• Rijedak u SAD-u, češći u Aziji• Nazofaringealni tumori
– SCCA (nazofaringealni karcinom)– Lymphoma– tumori žlijezda slinovnica– Sarkomi
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Tumori nosa, sinusa i ždrijela Nasopharinx-a
Angiofibroma Papilloma:
Inverted PapillomaIsolated Plasmacytoma
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ETIOLOGIJA
• povezan s EBV infekcijom (nediferencirani i nekeratinizirajući subtip)
• Ostali faktori rizika: – Potrošnja ribe (sadrže kancerogene
nitrosamine), obiteljska povijest, specifičnih HLA I genotip, pušenje, i niska potrošnja svježeg voća i povrća
• Dijagnoza: biopsija• Terapija: imunoterapija, radijacija,
hemoterapija
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• Dobar prognostički faktori:– mlađe životne dobi, – Niži stadij, – ipsilateral metastaze, – metastaze ograničeea na gornjih vrata, bez
uključivanja kranijalnih živaca, orbite ili kranija; nekeratinizirajući subtipovi
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Keratinizirajući tip-WHO 1
• Često EBV negativan, • starije dobne skupine• 5 godišnje preživljavanje ~0%• Liječenje: ne reagiraju na radioterapiju, • Mikro: skvamozna diferencijacija, keratinizacija, rijetko
adenoidni ili akantolitični oponaša adenokarcinom
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• Rijetko u djece,• 5 godina preživljenje 35-50%• Liječenje: radiosensitivan, metastazeregionalni l.č.
MIKRO: nedostatak diferenciranja, različit stepen diferencijacije
• IMUNO +: CK5/CK6, CK8, CK13, CK14, CK19• IMUNO - : CK4, CK7
nekeratinizirajući tip -WHO 2
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Tumors of the Nose, Sinuses & Naso-pharynx
Olfactory Neuroblastoma
Nasopharyngeal Carcinoma = squamous cell
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Papilarni adenokarcinom nasopharynx-a
• iz sluznica • 60% muškaraca; srednja dob 33 godina (raspon
11-64 godina), nije povezan izloženošću prašine ili drugih poznatih faktora
• dobra prognoza; bezbolan i sporo raste, rijetko recidivira, nema metastaza
• Pozitivan: keratin (difuzno), Ema (difuzno), CEA (žarišno), PAS (intracytoplasmic granule), mucin (intracelularan ili luminalan)
• Negativan: GFAP, S100, tireoglobulin
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Leon Barnes Schneiderian Papillomas and Nonsalivary Glandular Neoplasms of the Head and Neck Mod Path 2002;15(3):279–297
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Sinonasal carcinoma
• Obično HPV i EBV negativan• nos - obično vestibulum i lateralni zid; rijetko septum;• sinus – etmoid obično, rijetko u frontalni sinus• Obično kasna dijagnoza i s opsežnom destrukcijom kosti• Lokalno agresivan, metastaze na plućima, ponekad i
kosti• 5 godina preživljenje 60%• adenocarcinoma, low grade adenocarcinoma, intestinal
adenocarcinoma, cylindrical (transitional), small cell, squamous cell, undifferentiated (anaplastic)
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Intestinal-type adenocarcinoma. Papillary tubular cylinder cell-I variant (papillary type).
Sinonasal undifferentiated carcinoma consists of sheets of moderately sized cells with prominent eosinophilic nucleoli and numerous, often atypical mitotic figures
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Hematološke neoplazme
• sinonazaln ili nazofaringealni• Gotovo uvijek ne-Hodgkin limfom• Većina pacijenata je starije dobi• Često pozamašane lezije sinusa i nosne šupljine, uz proširenje
na nasopharynx• 5 godina preživljavanje je 55% u fazi I / II• Najčešći: NK / T stanice, difuzno velikih stanica B, peripheral T
cell; mantle cell limfoma
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• angiotropic lymphoma, • diffuse large B cell lymphoma, • follicular lymphoma, • lymphoid hyperplasia, • lymphomatoid granulomatosis, • mantle cell lymphoma, • NK/T cell lymphoma, • peripheral T cell lymphoma, • plasmacytoma
Hematološke neoplazme
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Larynx
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Endoscopic images
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Larynx • Laryngitis
– Vrlo česta infekcija gornjeg respiratornog trakta (izloženost duhanskom dimu)
– U djece, laringitis dovodi do suženja grkljana, uzrokuje stridor = teško disanjeU mlade dojenčadi, uzrokuje edem larinksa opstrukciju (smrt)
• Gušobolja – Laryngotracheobronchitis u djece– Upalno sužavanje dišnih putova proizvodi stridor
• Hronični laryngitis– Uzrokovan pušenjem cigareta uzrokuje metaplasia
& dysplasia (precancerosa)
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• Laryngealni čvorovi– Mali reaktivni polipi glasnica – Obično u pjevače ( "pjevači 'nodul") i nastavnika promuklost
Oni nikada ne dovode do raka
• Papillomi– neoplazme, fragmentacija i krvarenja
više u djece (juvenilna papilomatozu grkljana), vezan uz HPV infekciju, ponavlja se nakon ekscizije, kancerogena promjena je vrlo rijetkaHistologija - Koilocytes-pločastih stanica, imaju perinuklearna halozovu se condyloma acuminatum (bradavice) sa HPV (serotipova 6 i 11) - (16, 18, 33, 35 - uzrok raka)
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Larynx
Papillomi
Koilocytic change(Perinuclear halo) Also seen in the cervix Infected by HPV(DNA)
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LarynxCarcinomaCarcinoma in Situ
Or severe carcinoma
CarcinomaCarcinoma
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Larynx
Laryngeal Carcinoma
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Respiratorne bolesti
• Plućne bolesti (osobito infektivne) zajedno sa gastrointestinalnim infekcijama su najčešći uzrok smrti zemalja u razvoju
• Plućne bolesti- odgovor na okoliš, a ne genetski faktor
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Anatomija
Dva bronha, segmentalni bronhi, lobarni bronhBronchiole nemaju hrskavicu i submukozne žlijezdeDesno plućno krilo ima 3 lobusa, lijevo plućno krilo ima 2 lobusa i linguluDesni bronh više vertikalanDupla cirkulacija: bronchalna i plućnaRegionalni limfni čvorovi: paratracheal, pre-i retrotracheal, aortal, subcarinal, periesophageal, inferiorni plućna ligament, hilar, peribronchial, intrapulmonary
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Respiratorni acinus
Hrskavica je prisutna do terminalnog bronha
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• Parenhim pluća:
– bronhije
– bronchiole i
– alveole
• Acinus / terminalna respiratorna jedinica sadrži 3-5 terminalnih bronchiola, alveolarne vodove i alveole
•
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Alveole su obložene (pseudostratificiranim cilindričnim epitelom sa cilijama)
Alveole sadrže pneumocite tipa I i II
pneumociti tip I: 95%, spljošteni
pneumociti tip II: 5%, proizvode sufraktant , koji je uključen u popravak, ako je tip I uništen
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• Bronhalni epitel:• goblet stanice,
• neuroendokrine (Kultschitsky's) stanice,
• serozne stanice,
• bazalne stanice,
• Clara stanice • Cilindrične stanice
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• Neuroendokrine stanice: • brojne u neonatalnim bronhima i bronhiolama;
• rijetke u odraslih,
Clara ćelije: • terminalne bronchiole;
• sekretorna funkcija;
• imaju apikalne PAS +, diastase rezistentne sekretorne granule
Submucosalne žlijezde: • serozne i sluz producirajuće stanice mogu imati oncocitne promjene
limfne žile: ne postoje u alveolarnim zidovima
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Funkcija pluća
• Osnovna ali ne i jedina funkcija pluća jest proces respiracije ili staničnog disanja
• Izmjena gasova (O2, CO2)
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Patern ne-neoplastičnih promjena
• Intersticijalna inflamacija/ fibroza: DIP, UIP, alveolarno difuzno oštećenje, Langerhansova histiocitoza, azbestoza, amiloidoza, Sarkoidoza, vanjski alergijski alveolitis
• Intraalveolarna reakcija: DIP, plućna alveolarna proteinosa, infekcije, vanjski alergijski alveolitis, eozinofilne kronične upale pluća
• Bolesti malih zračnih puteva: bronhiolitis obliterans, respiratorni bronhiolitis, mycoplasma infekcije, virusne infekcije, vanjski alergijski alveolitis, eozinofilna pneumonija
• Bolesti malih zračnih puteva: alergijska bronhopulmonalna aspergiloza bronchocentric granulomatosis, TB, gljive, Wegener's
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• Granulomatous vaskulitis: Wegener's, Sarkoidoza, Churg-Strauss, bronchocentric granulomatosis, gljive, TB
Bolesti krvotoka: primarna plućna hipertenzija, tromboembolija, polyarteritis nodosa, veno-occlusivne bolesti, Churg-Strauss sindrom
Krvarenje: Goodpasture's, SLE, imuni kompleks glomerulonefritis, idiopatska plućna hemosiderosis, Wegener's
Limfoidni infiltrati: lymphocytic interstitial pneumonia, limfoma, lymphoidni agregat, alergijski alveolitis
Eozinofili: eozinofilni kronična upala pluća, Churg-Strauss sindrom, bronchocentric granulomatosis, Langerhansova histiocitoza
Patern ne-neoplastičnih promjena
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Kongenitalne i stečene anomalije
Kongenitalne: ciste, cistične adenomatoidne malformacije, lobarna hiperinflacija, sekvestracija
Stečene: emfizem, liječeni apsces, saćasta pluća
Miješane: cistična fibroza
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Atrezija pluća
• Dio bronhalnog stabla s normalnim grananjem, ali bez dokazane veze sa centralnim bronhalnim stablom
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Bronhopulmonarna displazija (BPD)
Komplikacija prijevremenosti
Pacijenti imaju ograničenu plućnu rezervu, ponovljene infekcije, česta plućna hipertenzija i razvijaju cor pulmonale
Mikroskopski:bronhalna i intersticijalna fibroza, Kompenzacijski emfizem manje oštećeni acinusi, neadekvatni alveolarni razvoj
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Cistična adenomatoidna malformacija
• Rijedak hamartomatozni poremećaj, 1 na 25.000 rođenih• Promjenljive veličine ciste • Povezane s mrtvorođenom djecom, bronhalna atresia; tip I
u starije djece i odraslih• Mogu se razviti i biti povezane s drugim urođenim
anomalijama pluća (Archiv 2002; 126:934)• Može regredirati spontano• 4 tipa
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• Klasifikacija:
Tip 0: 1-3%, nekad se zvao acinarna displazija; povezana s drugim malformacijama, nespojiva sa životom
Tip I: 60-70%: cista velika do 10 cm, prekriven cilijama i sa sluzavim stanicama; mogu se javiti kasnije; dobra prognozua jer se mogu operativno odstraniti
Tip II: 10-15%: male ciste do 2 cm, nalikuju dilatiranim bronhiolama; povezane s drugim malformacijama; loša prognoza
Tip III: 5%, solidan izgled pluća, bronhalne strukture odvojene malim prostorima koji su obloženi kubičnim epitelom koji je sličan fetalnim plućima; slaba prognoza
Tip IV: 15%, velike ciste do 10 cm, epitel je spljošten, dobra prognoza, sličan pleuropulmonarnom blastomu gradus 1 iako je manje celularan;
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Cistična fibroza
• smanjenje sekrecije hlora , • gust respiratorni sekret, • infekcija gornjih dišnih
puteva, • insuficijencija gušterače• Meconialni ileus u 5-10%
bolesnika,
MAKROSKOP: emfizem, bronchiectasis, apsces, fibroza
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• Ciste Obično su bronchogene, ne povezane sa dišnim putevima, ispunjene zrakom / mucinom, mogu se inficirati
• Emfizem zbog nedostatka alfa-1-antitripsinaAlfa-1-antitripsin (AAT) inhibira proteaze, osobito elastase (koji probavlja pluća tkivo), koji luče neutrofili tokom upale
•
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• Hipoplazija pluća manje težine od očekivanog za gestacijsku dob Bilateralna bolest je fatalna Uzroci: Oligohidramnion (agenezija bubrega, ruptura fetalne membrane), smanjen intratorakalni prostor (cistične bolesti bubrega, dijafragmalna hernija), smanjene disanja (anencefalija, musculoskeletalni poremećaji)
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• Lobarna hiperinflacija-lobarni emfizemDojenčad i mala djeca
Možda zbog hipoplazije bronhalne hrskavice,
povezane s drugim anomalijama ilijevi ili desni gornji režanj desno ili srednji lobus
Mikro: masivna distenzija alveola, bez tkivne destrukcije
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• Mesenchymal cystic hamartoma
Multifokalne, bilateralne ciste <1 cm,Obložene nižim epitelom od normalnog ili metaplastičnim respiratornim epitelom
• Sequestracija (intralobarna i extrapulmonarni lobus)
Lobus ili segment pluća bez normalne veze s dišnim sistemom, bilo gdje u grudnom košu ili medijastinumu, uglavnom djeca, abnormalne težine, 90% na lijevoj strani, 20% povezan sa drugim kongenitalnim anomalijamaNema plućnih arterija
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Chronic obstructive pulmonary disease (COPD)
• Glavni simptom: dispneja (otežano disanje)• Uzrok: pušenje• Opstruktivne bolesti dišnih puteva: opstrukcija na
bilo kojoj razini, emfizem, kronični bronhitis, bronchiectase, astma, tumor, strana tijela, smanjene maksimalne stope protoka zraka (FEV1)
• Restriktivne bolesti: smanjene širenja plućnog parenhima uz smanjenje ukupnog kapaciteta pluća, normalan FEV1, bolesti pleure, intersticijske / infiltrativne bolesti (ARDS, prašina , interstitial fibrosis)
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Normal versus Diseased Bronchi
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Asthma
• Alergija• Upala• Bronhospazam• Hiperinflacija• Respiratorne infekcije
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Asthma
• Kronična recidivirajuća upala poremećaj karakteriziran hiperaktivnošću dišnih puteva, uzrokujući reverzibilne bronhokonstrikcije
Obično je povezana s atopijom, IgE posredovana
Extrizična: Tip I preosjetljivost; ili atopijski (zbog alergije), profesiona ili zbog bronhopulmonalne aspergiloze
Intrinzična: neimunološka; zbog aspirina, upale pluća, prehlada, stres, vježbe
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• Status asthmaticus: – može biti koban– zbog izloženosti na
antigen na koji je osoba prethodno senzibilizirana
makroskop: prekomjerno distendirana pluća, mala područja atelektaze, gusta sluz u bronhijama, poput čepa
Asthma
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Mikroskopski– Curschmann spirale, eozinofili,
Charcot-Leyden crystali (eosinophilni membranski protein);
– povećan broj peharastih stanica i submucosalnih žlijezda, zadebljana bazalna membrana, hipertrofija glatkih mišića bronhija, edem zračnih puteva
Asthma
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Atopijski astma
• Počinje u djetinjstvu, izazvana alergenima okoliša (perut, prašina, pelud, hrana), često pozitivna obiteljska anamneza
• tip I IgE posredovana reakcija preosjetljivosti
• Inicijalna preosjetljivost zahvaća T helper 2 stanice, koje oslobađaju IL-4 / 5, koji promovira oslobađanje IgE od B stanica, mastocita i eozinofila
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• Ponovni dolazak u kontakt sa alergenom dovodi do otpuštanja mastocita iz sluznice
akutni odgovor je bronhokonstrikcija, edem, izlučivanje sluzi, hipotenzija
Kasna faza reakcije, s obzirom na priljev drugih upalnih stanica, se otpuštaju glavni bazični proteini iz eozinofila, koji uzrokuje oštećenja epitela i suženje dišnih puteva
medijatori: leukotrieni C4, D4, E4 i acetilholin, histamin, prostaglandin D2
Atopijski astma
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• Okupaciona asthma: dim, prašina, plinovi, kemikalije, često i male količine
• Lijekovima izazvana asthma: aspirin
• Neonatalna astma-često familijarna, virusima izazvana
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• Respiratorna infekcija• Hiperinflacija• Bronchospazam• Upala • Alergija
Bronchiectasis
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Bronchiectasiae• Hronična nekrotizirajuća infekcija bronhija i bronhiola
povezana s trajnom dilatacijom dišnih putova
Dijagnoza se temelji na prisutnosti infekcije (staza u dilatiranom bronhu) i opstrukcije
Simptomi: kašalj, temperatura, obilne količine smrdljivog, gnojnog sputuma
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• Uzroci: bronhalna opstrukcija (lokalizirane bronhiektazije), kongenitalne bronhiektazije, cistična fibroza, intralobarna sekvestracija, imunodeficijentna stanja, slaba pokretljiost cilindričnog epitela / Kartegeners sindrom, Young's syndrome, nekrotizirajuća pneumonija (Staphylococcus, tuberkuloza)
Opstrukcija (zbog tumora, stranih tijela) distalno od opstrukcije, atelectaza, intraluminal sekreti
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• neobstruktivne bronhiektazije zbog upale pluća i atelektaze, (lijeva strana, niži lobusi)
Cistična fibroza: opstrukcija zbog čepova sluzi, infekcija zbog smanjenja pokretljivosti cilindričnih stanica
Kartegenerov sindrom: autosomno recesivno stanje koje uzrokuje defekt u akciji cilijarne sluznice dišnih puteva (donje i gornje, sinusima , Eustahijeva cijev, srednjem uhu) i jajovodu
Young's syndrome: neplodnost uzrokovana azoospermijom, ali bez ultrastrukturalnih abnormalnosti cilindričnog epitela
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1950, Reid opisuje tri tipa bronhiektazija:
saccularne cistične, fusiform (cilindrične).
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Bronchiectasis with chronic suppuration
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Bronchiectasie
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Bronchiectasiae distalno od obstrukcije izazvane tumorom
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• Mikroskopski: hronične upale, ulkus, okoštavanje bronhalne hrskavice; varijabilne upale i fibroze alveola; zadebljana pleura
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Bronchitis-zapaljenje bronchija
• je upala sluznice bronhija,• akutni i kronični
• Virusi uzrokuju oko 90% slučajeva akutnog bronhitisa, • bakterije manje od 10%
• Kronični bronhitis- produktivni kašalj koji traje 3 ili više mjeseci godišnje najmanje 2 godine.
• Pušenje , zagađenje zraka i profesionalne izloženosti iritansima i hladnom zraku.
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Bronchitis chronica• gnojan sputum, • hypercapnia, • hipoksija češće nego emfizem,
može dovesti do: plućne vaskularne hipertenzije, cor pulmonale, kongestivnog zatajenja srca, smrt zbog respiratorne acidoze i kome, pneumotoraks
• rani-hipersekrecija sluzi u dišnim putovima, hipertrofija submukoznih žlijezda
kasnije povećanje peharastih stanica u malim dišnim putevima dovodi do povećane produkcije sluzi i obstrukcije;
• povećan Reid index (omjer debljine sloja sluznice žlijezda u odnosu distancu između epitela i hrskavica ); varijabla displazija, metaplazija, bronhiolitis obliterans
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Emphysema
• trajno proširenje zračnih prostora distalno od terminalne bronchiole sa destrukcijom zida, ali bez fibroze
klasifikacija:1. Centriacinarni ( centrilobularni) 2. Panacinar 3. Paraseptal 4. Senilni emphysema
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Centroacinar emfizem:
– Učestalost 95%,– Uzrokuje opstrukciju,– štedi distalne alveole; – Gornji lobus, osobito apeks;– Stjenka sa antrakozom i parabronhalnom
upalom,– Kod teških pušača, – Radnika u rudnicima uglja,pneumoconiosis; – klinički značajna iznad 40 god.
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• Panacinar (panlobular) emfizem: učestalost 5% uzrokuje značajne opstrukcije protoka zraka; acinusi jednako proširena od terminalnih bronchiola do alveola, obično niži lobusi; povezan s deficitom alfa-1-antitripsin; pluća obično voluminozan
• Paraseptal (distalni acinar) emfizem: pogođeni samo distalni acini, emfizem u blizini pleure, u blizini fibroze, ožiljaka ili atelektaze; kod mladih izaziva spontani pneumotoraks
• Kompenzacijski emfizem• Senilni emfizem• Opstrukcioni emfizem• Bulozni emfizem• Intersticijalni emfizem
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Infekcije
• Pneumonija (grč.),upala pluća je akutna upala plućnog parenhıma ,koja može biti uzrokovana bakterijama, virusima, gljivicama ili parazitima
• Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influence, Pseudomonas aeruginosa, koliformi
• Komplikacije: apsces, empyema, organizacija, sepsa, meningitis
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Klasifikacija Pneumonia
• Po okruženju• po organizmu (Mycoplasma, pneumokok i sl.)• po morfologiji (lobar pneumonija,
bronchopneumonia)
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• Virusi – influenza, parainfluenza, measles, varicella-zoster, respiratory syncytial virus (RSV)
• Bakterija• Chlamydia, mycoplasma• Gljivice
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Bronchopneumonia
• Bronchopneumonia (lobular pneumonia) karakterizirana multiplim fokusima izolirane akutne konsolidacije, obuhvata jedan ili više lobusa
• Strep. Pneumoniae, Haemophilus influenza, Staphylococcus, anaerobes, coliform.
• Staph/anaerobi/coliform. u aspiraciji
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• Makroskopski: – Višestruki žarištima konsolidacije u bazalnim
lobusima, često bilateralno. 2-4 cm u promjeru, sivo-žuta, suha, često usmjeren na bronchiole, slabo su ograničena i imaju tendenciju da se slivaju, posebno u djece.
• Mikroskopski: – upalni kondenzat usmjeren na bronchiole s
akutnim bronhiolitisom (suppurativni eksudat- gnoj - u lumenu). Alveole su ispunjene neutrofilima ( "leukocytic alveolitis").
Bronchopneumonia
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Bronchopneumonia
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• Komlipakcija virusne infekcije (influenza) • Aspiracija sadržaja želudca• Srčane greške• COPD
Bronchopneumonia
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Bronchopneumonia – Abscess
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Bronchopneumonia_CT
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Virusna pneumonia
• Izgled akutne ozljede pluća kao u odraslih respiratorni distres sindrom (ARDS)
• Akutna upalna infiltracija manje očite
• Virusne inkluzije se ponekad vide u epitelnim stanicama
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Imunokompromitirani domaćin
• Virulentan infekcija sa (npr. TBC) • Infekcija s oportunističkim infekcijama
– virus (citomegalovirus – CMV)– bakterije (Mycobacterium avium intracellulare)– gljivice (Aspergillus, Candida, pneumocystis)– protozoa (cryptosporidia, Toxoplasma)
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Lobarna Pneumonia
• Konfluentna konsolidacija obuhvata cjelo pluće – Streptococcus pneumoniae (pneumococcus)– (Klebsiella, Legionella)
• Obično kod zdrae mlađe populacije
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• Klasični akutni upalni odgovorEksudacija fibrinom-bogate tekućineInfiltracija neutrofilimaInfiltracija MakrofazimaRezolucijaImunološki sistem-protutijela dovesti do opsonizacije, fagocitirati bakterije
KOMPLIKACIJE• Organizacija• Abscess• Bronchiectasis• Empyema
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Lobar Pneumonia
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Macroscopic pathology
• Heavy lung– Congestion – Red hepatisation– Grey hepatisation– Resolution
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Pneumonia – fibrinopurulentni eksudat u alveolama (“red hepatisation”)
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Lobar pneumonia (gornji lobus-siva hepatizacija)
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Pneumonia – neutrophili i makrofazi ( “siva hepatizacija”)
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Komplikacije
• Organizacija( fibrozni ožiljak)• Abscess• Bronchiectasiae• Empyema
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Pneumonia – Organizacija( fibrozni ožiljak)
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Plućni apces (Abscessus pulmonis)
Lokalizirana kolekcija gnojaCentralna destrukcija
parenhimaOkružen granulacionim
tkivomTumoru sličnaSlabost i temperatura
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Plućni apces (Abscessus pulmonis)
• Infekcije:– Staphylococcus– Anaerobes– Gram negativni
• Klinički:– Aspiracija– Prateća pneumonia– Infekcija gljivama– Bronchiectasiae– Embolia
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Plućni apces (Abscessus pulmonis)
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Lung Fungal Abscess: Candida
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Dijagnoza
• Timski rad (ljekar, mikrobiolog, patolog)Bronhoalveolarni lavatBiopsija (s mnogo posebnih bojenja!)
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Aspergillus
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Aspergillus
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HIV-pozitivan pacijent sa CMV (cytomegalovirus)
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Pneumocystis
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Echinococcal cyst
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Histoplasma capsulatum
nalikuje tuberkulozi
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Legionella pneumonia
• Uzrokovan gram-negativnim bacilima
na obdukciji:• hilarni limfnih čvorovi obuhvaćeni u 50% slučajeva , • u 25% slučajeva se proširio na druge organe
• Mikroskopski: – opsežna bronchopneumonia – intra-alveolar ni neutrofili, makrofagi, fibrin, – vasculitis i nekroza
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Granulomatozne plućne bolesti
• Infekcije• Sarcoidosis• Hypersensitivity
pneumonitis (EAA)
• Wegener’s granulomatosis (WG)
• Reakcija na tumor• Granulom stranog tijela
• Pneumoconiosis (Berrylium, Aluminium, Cobalt)
• Reakcija na ljekove• Nekrotizirajuća sarkoidoza (NSG)• Eosinophilic pneumonia• Bronchocentric granulomatosis
(BCG)• Churg Strauss syndrome• Lymphoid interstitial pneumonia
(LIP)• Sjogren’s disease• Amyloidosis• incidentalno
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Šta je granulom?
“kompaktana (organizirana) kolekcija zrelih mononuklearnih fagocita (makrofaga i / ili
epithelioidnih stanica) koje može ali I nemora pratiti nekroza ili infiltracija leukocita
" Adams, 1983
Ključne riječi. Granulom je:Diskretan
Avascularanobuhvata epithelioidne histiocyte
EJ Mark, 2004
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Granulomas and granulomatous inflammation: synonymous or
different?
• Granuloma is well defined (sarcoidal or tuberculoid type)
• Granulomatous inflammation– Diffuse process, ill-defined– Palisading histiocytes in zones
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Granulomatous Lung Disease : Making a diagnosis
• The clinical context• The granulomas • Location and distribution• Accompanying features and
pathology
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The granulomas
• Necrotising or non-necrotising?• Is the necrosis
– Caseous– Abscess-like– Degeneration / fibrinoid necrosis
• ‘Distinct and compact’ or ‘Soft and diffuse’?
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Location / distribution of the process
•Diffuse process or Mass lesion?•Value of radiology•Microanatomical relationships (if any)
– centriacinar– bronchocentric– septal / lymphatic– vascular / perivascular– random
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Prateća obilježja i patologija
• Jesu li granulomi glavna značajka ili su dio 'veće' kliničke slike?
• Reakcija na strano tijelo, mikroorganizam ili tumor?
• Ima li vaskulitisa ili nekroze tkiva?• Ima li intersticijalne inflamacije?
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Nekrotizirajući granulomi
Izgled favorizira infekciju
• Mikrorganizmi - ZN, GMS, PAS
• Abscesu-slične formacije ili kazeozna nekroza
• Masivna lezija• Klinička istorija
• M. tuberculosis
Atypical mycobacteria
• Histoplasma, coccidioides
cryptococcus, blastomyces
pneumocystis, candida,
aspergillus
• Actinomyces, nocardia• Virusi
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Nekrotizirajući granulomi
Kazeozna nekroza
TB
Histoplasmosis
Coccidioidomycosis
Pneumocystis
Gljive CandidaAspergillusPhycomycosisBlastomycosisCrypococcosis
Bakterije Nocardia, Actinomyces
Virusi
Abscesu-slična nekroza
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Necrotising Sarcoidal Granulomatosis (NSG) vs
Nodular Sarcoidosis: different entities or the same disease?
NSG shows• Conglomerate granulomatous masses• ‘Geographic’ necrosis, probably of
ischaemic origin• Granulomatous vasculitis• Lower zone distribution• Less tendency to extra-pulmonary
disease
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Necrotising Sarcoidal Granulomatosis (NSG) vs Nodular Sarcoidosis: različiti entiteti ili slična bolest?
NSG:Konglomerate, granulomatozne mase'Geografsku' nekrozu, vjerojatno ishemijskog porijeklaGranulomatozni vasculitisdistribucija u donjem lobusuManja tendencija za ekstra-plućne bolesti
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Non-necrotising granuloma (u kontekstu difuznih bolesti)
• Da li je povezan sa intersticijskim pneumonitisom?Priroda granulomi?Raspodjela bolesti?
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Non-necrotising granulomas: Intersticijalna upalna ODSUTNA
Ako postojedobro formiran granulomiDokaz o multisistemskoj bolestilimfatična distribucija
RazmotritiSarkoidozu
BeriliozuAluminium
Ako ne• Slučajna distribucija? • Primarna plućna? Krvne
žile?• Pod polarizacijskom
svjetlošćuHrana, prašina, haemosiderin, amiloid, IVDAPomoć!
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Non-necrotising granulomas: Intersticijalna upalna PRISUTNA
Ako postojeUpala i granulomi su centriacinarniGranulomi često 'meki'Pjenasti makrofazi, kolesterolske pukotine,
COP-sličan izgled
U obzir uzeti
Hypersensitivity Pneumonitis (EAA)
Ako ne postoje• Bez reda razbacani?• Istorija bolesti• Druge patološke slike
Reakcija na ljekoveAspiraciona pneumonia
Strani materijal?Eosinophilic pneumonia
LIP, LYG(ipak uzeti u obzir HP/EAA)
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• Sistemska bolest karakterizirana granulomatoznim vaskulitisom – OBUHVATA
• gornje dišne putova (upala uha, sinusa, nosa)
• Pluća
• bubreg Ostali organskih sistema: koža, zglobovi, nervni sistem(periferni ili središnji)
Wegener’s granulomatosis
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• Sve uzraste, ali najčešće u dobi 45 +
Lab: c-ANCA pozitivan u 90% (aktivna generalizirana bolest ) i 60% (ograničena)
• Mikro: • likvefakcijska ili koagulacijska nekroza uz
eozinofile, gigantske stanice (loše formirani granulomi okruženi histiocitima sa centralnom nekrozom);
• destruktivni leukocitni angiitis; bronh je rijetko uključen;
• fulminantan podtip ima dominantno eksudativne promjene;
• (nalikuje SLE)
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Wegener’s granulomatosis
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Intersticijske plućne poremećaje Poznata Etiologija
OPĆIPneumoconioses (udisanje anorganske prašine)Hypersensitivity pneumonitis (inhalacija organske prašine)LijekoviRadijacijaUpala pluća povezana sa infekcijom
NEUOBIČAJENIUdisanje plinova, dima, pare, aerosoliotrov faza oporavka od ARDS
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Interstitial Lung Disorders of Unknown Etiology
Common Sarcoidosis Idiopathic pulmonary fibrosis Collagen-vascular disorders
Uncommon Histiocytosis X Chronic eosinophilic
pneumonia Idiopathic pulmonary
hemosiderosis Good pasture’s syndrome Hypereosinophilic syndrome
Uncommon (cont.) Immunoblastic
lymphadenopathy Lymphocytic infiltrative
disorders Lymphangioleiomyomatosis Amyloidosis Alveolar proteinosi’s Bronchocentric
granulomatosis Inherited disorders Secondary to disorders of
other organs
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Current Definition of IPF“... Posebni oblik kronične intersticijske
fibrozirajuće pneumonije ograničene na pluća, povezane s histološkom slikom uobičajene intersticijske pneumonije (UIP)...”
ATS/ERS. Am J Respir Crit Care Med. 2000;161:646-664.
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High Resolution Chest CT Findings in IPF
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Patološka Evaluacija IPF
• Transbronhijalna biopsija nije korisna za dijagnozu– Može se koristiti za isključivanje drugih
bolesti
• Kirurška biopsija pluća *– UIP uzorak
• Fibroblastna žarišta• Vremenska heterogenost• saćasta pluća• Minimalno upale
Adapted from ATS/ERS. Am J Respir Crit Care Med. 2000;161:646-664.
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Pathology of IPF: Temporal Heterogeneity and Peripheral Accentuation of Disease
Pathology of IPF: Temporal Heterogeneity and Peripheral Accentuation of Disease
Slide courtesy of William Travis, MD
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Fibroblastic Foci in UIP
Slide courtesy of William Travis, MD
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Nonspecific Interstitial Pneumonia (NSIP) Key Features
• Cellular pattern– Mild to moderate interstitial chronic inflammation– Type II pneumocyte hyperplasia
• Fibrosing and cellular/fibrosing patterns– Dense or loose interstitial fibrosis lacking the
temporal heterogeneity pattern and/or patchy features of UIP
– Interstitial chronic inflammation – mild or moderate
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Bronchiolitis obliterans-organizing pneumonia (BOOP)
Bronhiolitis obliterans (BO), ili Obliterirajući bronhiolitis (OB) i constrictivni bronhiolitis (CB), je rijedak i životno opasan oblik ne-reverzibilne opstruktivne bolesti pluća
djelomična obliteracija dišnih puteva.
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Ground Glass Opacities
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NSIP: Cellular Pattern
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NSIP: Fibrosing Pattern
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Roger Parra, E. et al. Thorax 2007;62:428-437
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Diagnostic Process in Idiopathic Diffuse Diagnostic Process in Idiopathic Diffuse Parenchymal Lung DiseaseParenchymal Lung Disease
Diagnostic Process in Idiopathic Diffuse Diagnostic Process in Idiopathic Diffuse Parenchymal Lung DiseaseParenchymal Lung Disease
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Epithelial cells
Collagen
Myofibroblast
Cell death
Growth factors and other products of epithelial cell Injury
(TGF- IGF-1, KGF, CTGF, PDGF)
Tissue Model of Lung Fibrosis
Slide courtesy of Paul Noble, MD
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Bronchiolocentric interstitial pneumonitis
• 80% žena, dobi 40-50 godina
Xray: intersticijska i restriktivne bolesti pluća
Loša prognoza - 33% smrtnost u toku 4 godine
Sličan uzorak: reumatoidni artritis, Sjogren sindrom, scleroderma, metotreksat, Amiodaron (5-10% bolesnika)
Mikro: centrilobular na upala s peribronchalnom fibrozom i intersticijalnom upalom u distalnim acinusima;
• Centrilobularna fibroza i metaplazija, saćasto pluće
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Lung – Pathology
Diffuse Interstitial (Restrictive) Diseases
Fibrosing
Pneumoconioses
Coal worker’s Pneumoconiosis(CWP) Silicosis
Asbestos-Related Diseases
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Patogeneza i Teorije nastanka
• PATOGENEZA:
• infektološka (TBC)
• infektološka • Nervna• imunobiološka
• TEORIJE:• 1. mehanička• 2. toksična
H2SiO3
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Glavne Pneumokonioze• Udisanje prašine dovodi do fibroze, što
rezultira poremećajem plućne arhitekture ili testova plućne funkcije.
– Silica silicosis– Asbestos asbestosis – Talc talcosis– Coal coal workers pneumoconiosis
(anthracosis)
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• vrsta prašine • veličina čestice • dužina ekspozicije • dubina respiratornih pokreta • kvaliteti odbrambenih mehanizama čovjeka• individualna dispozicija
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• Silicosis• MC chronic occupational disease in the world• caused by inhalation of crystalline silicon dioxide (silica).• Acute silicosis -accumulation of a lipoproteinaceous material within alveoli • Chronic silicosis - slowly progressing, nodular, Fibrosing pneumoconiosis• Pathogenesis• crystalline forms -more fibrogenic (quartz –worst)• silica particles lung macrophages ingest them activation and release of
mediators IL-1, TNF, oxygen-derived free radicals• Anti-TNF monoclonal antibodies can block lung collagen accumulation in
mice • Morphology.
– Early stages –tiny nodules in the upper zones – disease progresses –nodules coalesce into hard, collagenous scars
central softening and cavitation (due to superimposed tuberculosis or to ischemia)
– X-ray – egg shell calcification in the lymph nodes– Advanced stage - PMF
• Histology• Nodular lesions -concentric layers of hyalinized collagen surrounded by a
dense capsule• Birefringent silica particles in polarized microscopy
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Silicosis
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• Asbestos-Related Diseases• Localized fibrous plaques or diffuse pleural fibrosis • Pleural effusions • Parenchymal interstitial fibrosis (asbestosis)• Lung carcinoma• Mesotheliomas • Laryngeal and extra pulmonary neoplasms, (colon carcinomas)
• Pathogenesis.• Two forms of asbestos• serpentine (curly and flexible fibers) • most of the asbestos used in industry• amphibole (straight, stiff, and brittle fibers). • induction of malignant pleural tumors (mesotheliomas)
• Morphology. • Asbestosis – diffuse pulmonary interstitial fibrosis, • Asbestos bodies or Ferruginous bodies• golden brown, fusiform or beaded rods • macrophages engulf of asbestos fibers coated with an iron-containing
proteinaceous material
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• Asbestos-Related Diseases• Localized fibrous plaques or diffuse pleural fibrosis • Pleural effusions • Parenchymal interstitial fibrosis (asbestosis)• Lung carcinoma• Mesotheliomas • Laryngeal and extra pulmonary neoplasms, (colon carcinomas)
• Pathogenesis.• Two forms of asbestos• serpentine (curly and flexible fibers) • most of the asbestos used in industry• amphibole (straight, stiff, and brittle fibers). • induction of malignant pleural tumors (mesotheliomas)
• Morphology. • Asbestosis – diffuse pulmonary interstitial fibrosis, • Asbestos bodies or Ferruginous bodies• golden brown, fusiform or beaded rods • macrophages engulf of asbestos fibers coated with an iron-containing
proteinaceous material
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Asbestosis
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• Asbestos & Neoplasms• act as a tumor initiator & tumor promoter. • Oncogenic effects mediated by • 1. reactive free radicals generated by asbestos fibers (localize in the distal lung &
close to the mesothelial layers)• 2. chemicals adsorbed onto the asbestos fibers
– Example- tobacco smoke • Lung involvement• Begins as fibrosis around respiratory bronchioles and alveolar ducts • Extends to adjacent alveolar sacs and alveoli. • Eventually - honeycombed. • In contrast to CWP and silicosis, • Begins in the lower lobes and subpleurally. • middle and upper lobes affected later• Pleural plaques• MC manifestation of asbestos exposure• MC site- anterior and posterolateral aspects of parietal pleura
& domes of the diaphragm. • not contain asbestos bodies • always history of evidence of asbestos exposure.
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Lung & Pleural involvement
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Tumori pluća
• Benigni • Maligni
1- epidermiod [squamous] -35% 2- adeno carinema -30%3- large cell carcinoma -15%
4- small cell lung cancer -20%Metastatski
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Differential Diagnosis for Solitary Pulmonary Nodules (not exhaustive)
Type of Cause Disease Entity
Neoplastic
Malignant Primary pulmonary carcinoma
Primary pulmonary lymphoma
Primary pulmonary carcinoid
Solitary metastasis
Benign Hamartoma
Chondroma
Inflammatory
Infectious Granuloma (tuberculous, fungal)
Nocardia
Abscess
Non-infectious Rheumatoid arthritis
Wegener’s granulomatosis
Vascular A-V malformation
Hematoma
Infarction
Congenital Bronchial atresia
Sequestration
Other External object (nipple, mole)
Pseudotumor (fluid in fissure)
Pleural plaque or mass
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Definitive diagnosis of solitary pulmonary nodules can only be made by tissue diagnosis.
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Classification of Lung Tumours
• Very heterogeneous• 4 common smoking-associated types
– adenocarcinoma (35%)– squamous carcinoma (30%)– small cell carcinoma (25%)– large cell carcinoma (10%)
• Neuroendocrine tumours• Bronchial gland tumours
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• Smoking• Second hand smoke• Sex - men• Race - African American• Environmental gases - Asbestos,
radon, tar soot, arsenic, silica etc.• Excessive alcohol use• Radiation therapy to chest• Family history of lung cancer
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PathogenesisMutational Process• Oncogenes• Gene Deletions• Tumor Suppressor Genes
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OncogenesOncogene Mechanism Tumorc-myc gene amplification small cell
k-ras point mutation Non small cell
c-erbB-2 alt. transcription Non small cell
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Oncogenes
• c-myc family– encode nuclear DNA binding proteins
– important in transcriptional regulation
– associated with small cell lung cancer (up to 25% of specimens)
– associated with poor response to therapy
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c-myc expression and survival in small cell lung cancer
00,10,20,30,40,50,60,70,80,9
1
12 24 36 48 60 72 84 96 108
c-myc
non-c-myc
Pro
po
rtio
n s
urv
ivin
g
Survival in weeks
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Oncogenes
• ras family (k-ras, H-ras, N-ras)– 90% are K-ras– Proto-oncogene codes for
cytoplasmic/membrane protein– involved in signal transduction– transformed by point mutations, ususally at
codons 12, 13 or 61
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Oncogenes
• k-ras– found in 25 - 40% of NSCLC specimens– associated with poorer survival despite
otherwise favorable treatment features– K-ras mutations appear to be more
common in smokers than nonsmokers with adenocarcinoma
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K-ras oncogene and survival in NSCLC
0
0,2
0,4
0,6
0,8
1
1,2
0 10 20 30 40 50
Su
rviv
al P
rob
abili
ty (
%)
Months after Surgery
k-ras mutation
No mutation
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Oncogenes• c-erb family of protooncogenes• c-erbB-2 ( HER2, neu)
– encodes a tyrosine kinase – important regulator of cell growth
– found in squamous cell and adenocarcinoma lines– associated with poorer survival in
adenocarcinomas
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0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
0 50 100 150 200 250 300
Weeks after Diagnosis
Pro
bab
ilit
y o
f S
urv
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c-erbB-2 Expression and Survival in Adenocarcinoma
No expression Expression
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Retinoblastoma Gene
• Rb codes for a nuclear phosphoprotein
• Regulates transcription• Deletions, mutations very
common in SCLC, rare in NSCLC
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p53 gene and 3p deletion• p53 mutation found in both SCLC (70%) and NSCLC
(20%)• predictive importance not known• 3p chromosome deletion found in almost all Small
Cell and 25%NSCLC• specific tumor suppressor gene lost in deletion not
identified
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DiagnosisDiagnosis
sputumsputumcytologycytology
bronch-bronch-oscopyoscopy
transthoracicneedle biopsy
openbiospy
leastleastinvasiveinvasive
mostmostinvasiveinvasive
lesslessdefinitivedefinitive
moremoredefinitivedefinitive
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Squamous Cell
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Squamous Cell
• Centrally located 60 – 80%
• Peripheral “Scar” carcinomas
• Propensity to cavitate
Well-differentiated with keratin “pearl”
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Peripheral Adenocarcinomas
• Atypical adenomatous hyperplasia• Spread of neoplastic cells along alveolar walls
(bronchioloalveolar carcinoma)• True invasive adenocarcinoma• THIS PATTERN IS BECOMING COMMONER
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Adenocarcinoma • najčešći rak među ženama• obično u blizini vanjskih rubova
pluća• Invazija pleura i medijastinuma i
limfnih čvorova• mogu se vidjeti kod ne pušača
– Bronchial surface cell type with little/no mucin
– Goblet cell type– Bronchial gland cell type– Clara cell type– Type II alveolar epithelial cell type– Hepatoid
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Bronchoalveolar Cell Carcinoma
• Subtype of Adeno• May mimic
pneumonia (infiltrate on CXR)
• Bronchorrhea• Propensity for
aerogenous and lymphatic spread
• Lepidic growth pattern
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Adenocarcinoma (gland forming)
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Adenocarcinoma with mucin (blue stained)
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Adenocarcinoma
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• manje dobro – diferencirani• Može se pojaviti u bilo kom dijelu pluća• Tumori su veliki po vremena su dijagnosticira• ima veću mogućnost širenja na mozak i
medijastinum
Large cell carcinoma – 15% :
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Large-Cell Undifferentiated
Low power: sheets oftumor cells
High power:disorganized tumorcells with lack ofdifferntiation(keratin, mucin, etc)
Large Cell Undifferentiated
Low power: sheets of tumor cells
High power: disorganized, lack of glands, mucin or keratin
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Large cell carcinoma
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Small Cell Cancer
• Extensive mediastinal adenopathy
• Very rare in nonsmokers
• Early metastases
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Small Cell Carcinoma
Pleomorphic small cells with dense chromatinand neuropeptide secretory bodies (yellow arrow)
EMMed. power
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Small cell carcinoma
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A bronchial biopsy
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Cancer….which type?
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Malignant cells in cytological specimen
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Pathogenesis
• Pulmonary epithelium– Bronchial (ciliated, mucous,
neuroendocrine, reserve)– Bronchioles/alveoli (Clara cells, types 1
and 2 alveolar lining cells)
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Bronchial (large airway) Tumours
• Squamous metaplasia• Dysplasia• Carcinoma in situ• Invasive malignancy
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Normal bronchial mucosa
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Basal cell hyperplasia
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Squamous metaplasia
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Dysplasia/carcinoma in situ
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Atypical adenomatous hyperplasia
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Prognostic Indicators in Lung Cancer
• Tumour stage• Tumour histological subtype
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TNM staging
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Other Lung Neoplasms
• Carcinoid: Neuroendocrine neoplasms of low grade malignancy
• Bronchial gland neoplasms (tumours more often seen in salivary glands)– Adenoid cystic carcinoma– Mucoepidermoid carcinoma
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Large obstructing carcinoid tumour
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Carcinoid histology
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Molecular Genetic Abnormalities (potential therapeutic targets)
•
p53, 1q, 3p,9p,11p, Rb
p53, Rb, 3pTumour suppressor genes
myc, K-ras, her2(neu)
mycOncogenes
NSCLCSCLC
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The Pleura
• A mesothelial surface lining the lungs and mediastinum
• Mesothelial cells designed for fluid absorption
• Hallmark of disease is the effusion
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Pleural Effusion
• Transudate (low protein)– cardiac failure– hypoproteinaemia
• Exudate (high protein)– pneumonia– TB– connective tissue
disease– malignancy (primary or
metastatic)
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Purulent Effusion
Full of acute inflammatory cells• Empyema• Can become chronic
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Pneumothorax
Air in pleural space• Trauma• Rupture of bulla
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Large bullae
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Pleural Neoplasia
• Benign tumours rare• Primary malignant neoplasm – mesothelioma
(see lecture on pleural disease)• Also a very common site of invasion by lung
carcinomas and metastatic cancers
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Mesothelioma
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Pleural biopsy - mesothelioma
• Mixed spindle cell (mesenchymal) and epithelial differentiation
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Metastases in Pleura
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Differential diagnosis of malignant effusions…..
• Cytology, biopsy• Difficult• Immunohistochemistry for lineage specific
antigens may help• Medicolegal importance