Andrew Churg, Mu ueparLmenLs of aLhology unlverslLy of 8rlush Columbla and vancouver Ceneral PosplLal vancouver, 8C achurg[mall.ubc.ca
D|sc|osure l have no conlcLs of lnLeresL Lo dlsclose Cb[ecnves 1o revlew normal lung anaLomy 1o revlew Lhe paLhology of lung cancer 1o revlew Lhe paLhology of CCu and AsLhma 1o revlew oLher forms of alrways dlsease 1op|cs normal lung anaLomy Lung cancer CCu Alrway dlseases AsLhma lnfecuous bronchlollus 8ronchopneumonla 8ronchlollus obllLerans (consLrlcuve bronchlollus) Bronchovascular bundle Normal lung (formalin vapor fixed) Bronchovascular bundle: bronchi and pulmonary artery branches run together 01-3517 Bronchovascular bundle Normal bronchus Bronchus defined by presence of cartilage Bronchial glands normal Lung Bronchioles Interlobular septum Pleura M8 09-12948 Normal membranous bronchiole: Bronchioles are defined by lack of cartilage Pulmonary artery branch Membranous bronchiole Alveoli MB RB RB AD 1H-75 AD Membranous bronchiole (MB): continuous wall Respiratory bronchiole (RB): partially alveolated wall Alveolar duct (AD): completely alveolated wall
Alveoli Type 2 Cell Capillary Alveolus Alveolus Parenchyma LUNG CANCLk
Common 1ypes of Lung Cancer usually smoklng relaLed Squamous cell carclnoma Adenocarclnoma 8ronchoalveolar carclnoma (adenocarclnoma ln slLu) Small cell carclnoma Large cell carclnoma noL smoklng relaLed Carclnold A 6S year o|d man w|th a 40 pack-yr smok|ng h|story presents w|th hemoptys|s and |s found to have a mass |nvo|v|ng the r|ght upper |obe bronchus. Cn the r|ght |s a p|cture of the b|opsy. 1he correct d|agnos|s |s:
1. Squamous cell carclnoma 2. Small cell carclnoma 3. Adenocarclnoma 4. noL a carclnoma of any klnd Squamous Ce|| Carc|noma Not Lhe mosL common Lype of lung cancer SLrongly smoklng relaLed usually falrly bulky cenLral leslons usually accesslble by bronchoscopy Cood yleld on washlng/brushlng/spuLum cyLology May cause obsLrucuve (golden) pneumonla behlnd Lumor May cause bronchlecLasls behlnd Lumor May cause lobar collapse Squamous cell ca with lower lobe collapse and distal bronchiectasis C82-79 Collapsed lower lobe Bronchiectasis Tumor Squamous Ce|| Carc|noma aLhologlc denluon of squamous cell carclnoma Cells make keraun and/or Cells are connecLed by lnLercellular brldges 18308-1 Squamous cell ca Keratinized cells 18308-3 Squamous cell ca Intercellular bridges Adenocarc|noma 1he mosL common Lype of lung cancer MosL adenocarclnomas are smoklng-relaLed Powever, adenocarclnoma ls Lhe common Lype of lung cancer ln non-smokers Many adenocarclnomas are perlpheral leslons Cen noL accesslble by bronchoscopy Core needle blopsy or lnA oen needed for lnlual dlagnosls Adenocarcinoma Peripheral, subpleural lesion Adenocarc|noma aLhologlc denluon of adenocarclnoma Makes glands and/or SecreLes mucln Mucln can be demonsLraLed by AS or muclcarmlne sLaln (or someumes on P&L) 163327-1 Adenocarcinoma Glands Mucin 8ronchoa|veo|ar Carc|noma (8AC) = Adenocarc|noma |n S|tu (AIS) usually perlpheral leslons ure 8AC appears as ground glass nodules on C1 8elleved Lo be Lhe ln slLu phase of adenocarclnoma new A1S/L8S classlcauon (! 1hor Cncol 2011) suggesLs uslng Adenocarclnoma ln slLu" lnsLead of 8AC 8y denluon Lumor cells grow along alveolar walls (leplJlc qtowtb) 8y denluon Lumor cells do noL lnvade 06-3659-2 BAC: Appears as a ground glass opacity The greater the amount of solid opacity, the greater the likelihood of invasive carcinoma 06-3659 BAC/AIS 06-3659-2 BAC/AIS: Lepidic growth and mild fibrosis of underlying alveolar walls 06-3659-4 BAC/AIS: Lepidic growth/cytologic atypia vs07-111-1 Needle core bx of peripheral lung nodule in a cigarette smoker vs07-111-2 Tumor cells show lepidic growth 1he correct d|agnos|s for the |mages |n the |ast 2 s||des |s: 1. ALyplcal adenomaLous hyperplasla (AAP) 2. 8ronchoalveolar carclnoma/adenocarclnoma ln slLu (8AC/AlS) 3. Adenocarclnoma, nCS 4. MallgnanL buL wheLher Lhls ls a 8AC/AlS or lnvaslve adenocarclnoma cannoL be deLermlned on Lhls Lype of blopsy (compleLe exclslon requlred) 8AC]AIS and Adenocarc|noma 8AC belleved Lo be Lhe precursor leslon of many (? all) perlpheral adenocarclnomas Adenocarclnomas are lnvaslve by denluon Cver ume 8AC develops cenLral scar and Lhen cenLral lnvaslve adenocarclnoma lncreaslng evldence LhaL perlpheral adenocarclnomas LhaL are largely 8AC wlLh less Lhan 3mm of cenLral lnvaslon can probably be LreaLed by wedge resecuon raLher Lhan lobecLomy (however, Lhls ldea ls somewhaL conLroverslal) Survival Using Sub-lobar Resection for Pure BAC (AIS) D Arenberg Chest 2007 roposed new lASLC/A1S/L8S Classlcauon of Adenocarclnomas
(1ravls eL al: ! 1horaclc Cncol 2011) roposed New IASLC]A1S]LkS C|ass|hcanon of Adenocarc|nomas (1rav|s et a|: I 1horac|c Cnco| 2011) lor leslons < 3cm ln dlameLer nonmuclnous 8AC now classled as adenocarclnoma ln slLu" Can be LreaLed by wedge exclslon SollLary Lumors wlLh predomlnanLly lepldlc growLh and less Lhan 3mm of lnvaslon classled as mlnlmally lnvaslve adenocarclnoma" SollLary Lumors wlLh predomlnanLly lepldlc growLh and more Lhan 3mm of lnvaslon classled as lepldlc predomlnanL adenocarclnoma Muclnous 8AC vlewed as lnvaslve muclnous adenocarclnomas Pure lepidic growth = BAC/AIS Lepidic growth, <5mm invasion = Minimally invasive adenoca
Lepidic growth, >5mm invasion = Lepidic predominant adenoca <5mm >5mm vS11-20176 Adenocarcinoma with peripheral lepidic growth and < 5mm of invasion: Under new proposed classification: Minimally Invasive Adenocarcinoma 1mm lnvaslve focus 1mm focus of lnvaslon: CorrecL ux: Mlnlmally lnvaslve adenocarclnoma (or 8AC wlLh 1mm of lnvaslve carclnoma) 1mm focus of lnvaslon: CorrecL ux: Mlnlmally lnvaslve adenocarclnoma (or 8AC wlLh 1mm of lnvaslve carclnoma) As yeL unclear wheLher Lhese Lumors can be LreaLed by wedge exclslon alone Solld aplllary Mlcropaplllary Aclnar From Yoshizawa et al: Mod Path 2011 Plgh grade Plgh grade lnLermedlaLe grade lnLermedlaLe grade SLage 1 Adenocarclnoma: ulsease lree Survlval by PlsLologlc auern From Yoshizawa et al: Mod Path 2011 Low grade (lncl AlS) lnLermedlaLe grade Plgh grade Sma|| Ce|| Carc|noma SLrongly smoklng relaLed usually cenLral leslons (perlpheral leslons uncommon) usually accesslble by bronchoscopy Cood yleld on washlng/brushlng/spuLum cyLology usually wldespread aL presenLauon rlmary leslon may be very small Surgery usually conLralndlcaLed Sma|| Ce|| Carc|noma aLhologlc denluon: Cells usually 2-3 umes slze of a lymphocyLe Cells have very hlgh nuclear: cyLoplasmlc rauo nuclel oen mold Lo each oLher usually very hlgh mlLouc raLe usually exLenslve necrosls of Lumor Clder name of oaL cell carclnoma" no longer used 77-9368-2 Small cell carcinoma 77-9368 Small cell carcinoma Small cells Scanty cytoplasm High N:C ratio Fine stippled chromatin Small cell carcinoma Squamous cell carcinoma Large Ce|| Carc|noma SLrongly smoklng relaLed 1umors usually cenLral usually accesslble by bronchoscopy Cood yleld on washlng/brushlng/spuLum cyLology buL dlsuncuon from adenocarclnoma on cyLology alone ls dlmculL 8y denluon relauvely large cells LhaL do noL have Lhe feaLures of squamous or adenocarclnoma 8y elecLron mlcroscopy [usL very poorly dlerenuaLed squamous or adenocarclnomas
169670-1 Large cell carcinoma 169670-2 Does not have features of squamous or adenocarcinoma Why the C|d atho|og|c D|agnos|s "Sma|| Ce|| vs Non-Sma|| Ce|| Carc|noma" Isn't Good Lnough Any More - 8AC/AlS can be LreaLed by wedge resecuon Small cell carclnoma LreaLed by chemoLherapy/ radlauon raLher Lhan surgery MosL adenocarclnomas and squamous cell carclnomas have meLasLaslzed aL ume of presenLauon and chemoLherapy ls Lhe only LreaLmenL opuon Why the C|d atho|og|c D|agnos|s "Sma|| Ce|| vs Non-Sma|| Ce|| Carc|noma" Isn't Good Lnough Any More lncreaslngly LargeLed Lherapy depends on cell Lype Adenocarclnomas may respond Lo: LCl8 lnhlblLors (lressa, 1arceva) emeLrexed (AllmLa) Anu-vLCl Lherapy (8evaclzumab) Crlzounlb for Lumors wlLh ALk-LML4 Lranslocauon Why the C|d atho|og|c D|agnos|s "Sma|| Ce|| vs Non-Sma|| Ce|| Carc|noma" Isn't Good Lnough Any More - lncreaslngly LargeLed Lherapy depends on cell Lype Squamous cell carclnomas Lyplcally do noL show LCl8 or k8AS muLauons Squamous cell carclnomas may bleed masslvely wlLh anu- vLCl Lherapy (8evaclzumab) Squamous cell carclnomas oen harbor lCl81 muLauons: LargeLed Lherapy belng developed ko|e of Immunoh|stochem|stry |n Subc|ass|fy|ng r|maryLung Cancers Squamous Adeno Small Cell p63+ 11l-1+ 11l-1+ Ck3/6+ p63- Chromogranln+ 11l-1- Ck3/6- SynapLophysln+ Ck7- Ck7+ Cu36+ napsln- napsln + napsln-
Ck = cyLokeraun ko|e of Immunoh|stochem|stry |n Subc|ass|fy|ng Lung Cancers Sorung ouL small cell from non-small cell carclnoma Separaung squamous cell from adenocarclnoma lmmooocbemlstty most osefol wbeo tbe blopsy ls vety smoll ot tomot pootly Jl[eteouoteJ Also useful for sorung ouL prlmarles from meLs lf Lumor noL classlable by lmmunochemlsLry, Lhen Lhe Lerm non-small cell carclnoma" ls sull approprlaLe Poorly differentiated carcinoma on bx ?Features suggestive of squamous cell Tumor is p63 and CK5/6 + Confirms diagnosis of squamous cell ca p63 CK5/6 Malignant appearing cells in pleural fluid cytology specimen Tumor cells are TTF-1 + Indicates that this is metastatic from a lung adenocarcinoma 11l-1 Carc|no|d MosL common lung Lumor aer bronchogenlc carclnoma noL smoklng relaLed Cells are neuroendocrlne cells and conLaln neurosecLory granules SeroLonln (carclnold syndrome -- rare) AC1P (Cushlng's syndrome - rare) All carclnolds are mallgnanL 1yplcal" carclnold = low grade, 90 10 yr survlval ALyplcal" carclnold = hlgh grade, 33-60 10 yr survlval Carc|no|d - atho|ogy usually cenLral endobronchlal Lumors usually slow growlng: produce bronchlecLasls behlnd Lumor Always lnvade bronchlal wall CannoL cure by curremng 8y mlcroscopy a varleLy of neuroendocrlne" growLh pauerns 8land appearlng cells, round or splndled very vascular Lumors -Lend Lo bleed when blopsled 8y lmmunochemlsLry posluve for synapLophysln, chromogranln, 11l-1, Cu36 Carcinoid Bronchial wall Tumor in distended bronchus 87-3332 Distal bronchiectasis Carcinoid
Carcinoid Note marked vascularity
Carcinoid Synaptophysin CD56 CCD Lno|og|es Clgareue smoke (mosL cases ln norLh Amerlca) Cccupauonal dusL exposure (for ex, coal mlners) Cccupauonal fume exposure ? Plgh levels of amblenL alr polluuon Cooklng wlLh blomass fuels Anatom|c]C||n|ca| Lnnnes |n CCD Lmphysema Small alrway remodellng (small alrway dlsease) 8ronchlal mucus gland hyperplasla wlLh excess mucus producuon (chronlc bronchlus) vascular remodellng wlLh pulmonary hyperLenslon AcuLe exacerbauon urely cllnlcal enuLy-no clear anaLomlc correlaLe Ac|n| and Lobu|es Aclnus conslsLs of all alrways and parenchyma dlsLal Lo Lhe lasL generauon (Lermlnal) membranous bronchlole Lobule conslsLs of all ussue bounded by lnLerlobular sepLa up Lo 6 aclnl are found ln Lhe cenLer of Lhe lobule, hence cenLrllobular" and cenLrlaclnar" are roughly equlvalenL Aclnl are noL dlagnosucally useful buL lobules are Plgh resoluuon C1 scans can see lobules Many dlseases have dlsuncL dlsLrlbuuons wlLhln Lhe lobule 01-3517 Lobule (case of lymphangitic ca) Pulmonary Lobule: Gough section Interlobular septum Bronchovascular bundle 152314 Interlobular septa Lobule Pleura Lmphysema: Dehn|non A condluon of Lhe lung characLerlzed by abnormal permanenL enlargemenL of alrspaces dlsLal Lo Lhe Lermlnal bronchlole, accompanled by desLrucuon of Lhelr walls and wlLhouL obvlous gross brosls Centr||obu|ar (Centr|ac|nar) Lmphysema Poles are ln cenLers of lobules (aclnl) wlLh surroundlng normal lung upper zone predomlnanL Classlc clgareue smoke-assoclaLed form of emphysema CenLrllobular Lmphysema u807-181 Lmphysema: Centr||obu|ar (centr|ac|nar) CenLrllobular (cenLrlaclnar) Lmphysema
CenLrllobular Lmphysema Emphysematous area = destroyed RB M8 88 Surrounding normal parenchyma MB=membranous bronchiole RB=respiratory bronchiole an|obu|ar (anac|nar) Lmphysema Poles LhroughouL lobule (aclnus) usually lower zone predomlnanL AssoclaLed wlLh -1-anuLrypsln declency AssoclaLed wlLh clgareue smoklng
Panlobular Emphysema anlobular Lmphysema A37-3 arasepta| Lmphysema (D|sta| ac|nar emphysema) Poles wlLh walls perpendlcular Lo Lhe pleura Can have some degree of brosls ln walls Luologles uncerLaln buL seen ln smokers Also assoclaLed wlLh sponLaneous pneumoLhorax ln young (nonsmoklng) adulLs Lmphysema: arasepta| Pleura Pleura 1he best way to d|agnose emphysema |s by: 1. vA1S blopsy 2. 1ransbronchlal blopsy 3. Core needle blopsy 4. C1 scan Comments re Lmphysema C1 scan ls a very accuraLe meLhod of dlagnoslng emphysema aLhologlcally emphysema ls besL dlagnosed on gross speclmens of resecLed lobes or lungs or auLopsy speclmens 8lopsy speclmeos ote oot soltoble fot evoloouoq empbysemo no one does a surglcal lung blopsy Lo dlagnose emphysema! C|gareue Smoke-Induced A|rway D|sease Smoker's resplraLory bronchlollus (88): resplraLory bronchloles Small alrway remodellng (small alrway dlsease): predomlnanLly membranous bronchloles, and Lo some exLenL resplraLory bronchloles Chronlc bronchlus: large alrways (bronchl) C84-64 Smoker's 8esplraLory 8ronchlollus (88") 8esplraLory 8ronchlole Smokers macrophages 09-12948 Normal membranous bronchiole Small Alrway 8emodellng - Clgareue Smoker 03-2738 03-2738 Small Alrway ulsease--Clgareue Smoker 03-2738 Small Alrway 8emodellng ln Clgareue Smokers 1. Narrowed or obliterated lumen 2. Increased fibrous tissue in airway wall leading to thick airway wall 3. Inflammation in airway wall 4. Mucus plugs in lumen
Result: Decreased flow/turbulent flow Mucus plug S|gn|hcance of C|gareue Smoke- Induced A|rway D|sease Small alrway remodellng ls an lmporLanL cause of alrow obsLrucuon cbtoolc btoocblus ptobobly Joes oot ptoJoce oltfow obsttocuoo (coottovetslol)! uened enurely by spuLum producuon AssoclaLed wlLh cllnlcal exacerbauons (lnfecuous eplsodes wlLh funcuonal deLerlorauon) I|nd|ngs |n Asthma 1hlckened alrway basemenL membrane MosL conslsLenL ndlng (ln large alrways) lncreased alrway smooLh muscle MosL conslsLenL ndlng ln large and small alrways Loslnophlls ln alrway wall or lumen uenuded alrway eplLhellum lncreased gobleL cells ln alrway eplLhellum Mucus plugs ln alrways wblcb feototes ote pteseot lo oo loJlvlJool cose ls vety votloble auenL dylng ln sLaLus asLhmaucus Mucus plug ln lumen 1hlck 8M AC06-0239 Increased smooth muscle Increased airway smooth muscle Thick basement membrane Airway epithelium denuded Asthma: eosinophils in airway wall Infecnous 8ronch|o||ns ln lmmunocompeLenL pauenLs: Wlde range of agenLs buL especlally seen wlLh: Mycoplasma vlral lnfecuons of all Lypes very varlable morphology AcuLe lnammauon Chronlc lnammauon AcuLe lnammauon ln lumen, chronlc lnammauon ln wall Alrway eplLhellal damage Morphology usually does noL lndlcaLe agenL unless vlral lncluslons found CulLure or serology cruclal lmmunohlsLochemlsLry someumes helpful (vlruses) vlral lncluslons more commonly seen ln lmmunocompromlsed pauenLs Influenza - bronchiolitis 6C-77 Mns ln lumen uamaged alrway eplLhellum Chronlc lnammaLory cells ln alrway wall vA06-90 Perpes slmplex - necrouzlng alrway cenLered leslon M8 lmmunocompromlsed pauenL Herpes simplex Immunohistochemistry Long 1erm Seque|ae of Infecnous 8ronch|o||ns 8eporLed long Lerm uncommon (morphologlc) sequelae 8ronchlollus obllLerans (lncl Swyer-!ames syndrome) 8ronchlecLasls Lung abcess lnLersuual brosls 8eporLed long Lerm cllnlcal sequelae Alrway hyper-reacuvlLy/asLhma 8ronchopneumon|a 1he ulumaLe lnfecuous bronchlollus lnammaLory process sLarLs ln/around bronchloles, spreads Lo parenchyma aLhology lllllng of bronchlolar lumens and parenchyma by neuLrophlls (early), macrophages (laLe) c82-363 8ronchopneumonla Yellow = bronchioles containing pus Red = inflammation & congestion in parenchyma v82-92 8ronchopneumonla M8 PMNs M8 Constr|cnve 8ronch|o||ns (8ronch|o||ns Cb||terans) Luologles lume lnhalauon (example, farmer's lung) Collagen vascular dlsease, esp 8A osL-lnfecuous (example, Swyer-!ames syndrome) lnammaLory bowel dlsease urug-lnduced AssoclaLed wlLh bronchlecLasls (especlally cysuc brosls) Lung LransplanLauon (8C syndrome) ldlopaLhlc rogresslve, xed alrow obsLrucuon Alr-Lrapplng on C1 buL brouc bronchloles are Loo small Lo be seen on lmaglng ConsLrlcuve bronchlollus ln 8A CourLesy ur. nesLor Muller Constr|cnve 8ronch|o||ns - atho|ogy narrowed or obllLeraLed alrway lumen a conslsLenL ndlng alrow obsLrucuon Larly: lnammaLory cells or granulauon ussue ln lumen LaLe: Collagen deposluon beLween eplLhellum and smooLh muscle n8: CompleLely obllLeraLed bronchloles appear as scars on P&L oslly mlsseJ/JlsmlsseJ os ooospeclfc scots losuc stolos ctoclol to mokloq tbe Jloqoosls 09-12948 Normal membranous bronchiole: Pulmonary artery branch Membranous bronchiole Larly ConsLrlcuve 8ronchlollus ln 8A Narrowed lumen Granulation tissue Cld ConsLrlcuve 8ronchlollus ? Secondary Lo MeLhoLrexaLe ? Caused by 8A Dense collagen between epithelium and muscle Markedly narrowed lumen What to 1h|nk About When an Cpen] 1horacoscop|c 8|opsy Appears to be Comp|ete|y "Norma|" at I|rst G|ance 8lopsy mlssed Lhe leslon aLhologlsL mlssed Lhe leslon ConsLrlcuve bronchlollus (bronchlollus obllLerans) 8esplraLory bronchlollus wlLh lnLersuual lung dlsease (88lLu) ulmonary hyperLenslon Changes of asLhma no one does a blopsy Lo dlagnose emphysema! 1op|cs normal lung anaLomy Lung cancer CCu Alrway dlseases AsLhma lnfecuous bronchlollus 8ronchopneumonla 8ronchlollus obllLerans (consLrlcuve bronchlollus)