Robbins Essential Pathology PDF - Lung and Upper Respiratory Tract
Document Details
Uploaded by CleanlyBoston
Mansoura
Tags
Summary
This document is a chapter from Robbins Essential Pathology focusing on lung and upper respiratory tract diseases. It describes various morphologies, clinical features, and fungal infections. It's likely for undergraduate medical or biology studies.
Full Transcript
CHAPTER 10 Lung and Upper Respiratory Tract 179...
CHAPTER 10 Lung and Upper Respiratory Tract 179 In e Uned Saes, dmorpc ung ave caracersc geo- Morphology. In uncompcaed cases, e neced ung sows grapc dsrbuons: canges smar o oer vra pneumonas, w mononucear H. capsulaum s endemc n e Oo and cenra Msssspp Rver nammaor y niraes and edema o e aveoar wa. Severe vaeys and aong e Appaacan Mounans n e Soueas. necons can ead o dfuse aveoar damage and acue respraor y Warm, mos so conanng droppngs rom bas and brds provdes dsress syndrome, or may be compcaed by supermposed a medum or e grow o e mycea orm, wc produces nec- bacera pneumona by organsms suc as S. aureus. ous spores. C. mms s endemc n e souwesern and wesern regons o more wdespread an epdemcs, occur wen bo e emaggu- e Uned Saes, parcuary n Caorna’s San Joaqun Vaey, nn and neuramndase are repaced roug recombnaon o RNA were coccda necon s known as “vaey ever. ” segmens w ose o anma vruses (suc as brd or pg vruses), B. dermads as a dsrbuon n e Uned Saes a overaps makng a members o a speces suscepbe o e new nluenza vrus w a o sopasmoss. (antgenc st). he irs u pandemc o s cenur y, n 2009, resued rom an angenc st nvovng a vrus o swne orgn (as dd e nuenza vrus rom e 1918 epdemc). Morphology. e yeas orms are dsncve, wc eps n er denicaon n ssue secons: Cln cal Feature s. C omorbd es suc as d ab ees, e ar ds e as e, H. capsulaum: round o ova, sma yeas orms measurng 2 o ung ds e as e, and mmunosuppresson are ass o c ae d w a g er 5 μm n dameer (Fg. 10.14A) r sk or s e vere ne c on. Tre a men nvoves supp or ve c are and ( C. mms: ck-waed, nonbuddng sperues, 20 o 60 μm n d ag nos e d e ary) neuramnd as e n bors, w c are ac ve agans dameer, oten ied w sma endospores (see Fg. 10.14B) b o n uenza A and B and c an sor en e dura on o sy mp- B. dermads: round o ova, arge yeas orms (5 o 25 μm n oma c ds e as e. In uenza vaccnes prov de re as onabe proe c on dameer) a reproduce by caracersc broad-based buddng agans e ds e as e, esp e c a y n vu nerabe nans and oder adu s. (see Fg. 10.14C and D). Fungal Infections Prmary pumonary dsease mmcs ubercuoss and consss o aggregaes o macropages ied w organsms, wc evove no Histoplasmosis, Coccidioidomycosis, and Blastomycosis sma granuomas compee w gan ces and cenra necross, Inecons caused by e dmorpc ung Hsoplasma capsulaum, oowed by ibross and cacicaon. Smar esons may be seen Coccdodes mms, and Blasomyces dermads range rom soaed n dranng ymp nodes. Dferenaon rom ubercuoss requres pumonar y nvovemen n mmunocompeen ndvduas o dssem- denicaon o e yeas orms (bes seen w sver sans). I T-ce naed dsease n mmunocompromsed paens. A B C D Fig. 10.14 (A) Histoplasma capsulatum yeast forms fill phagocytes in a lymph node of a patient with disseminated histoplasmosis (silver stain). (B) Coccidioidomycosis with intact spherules within multinucleated giant cells. (C) Blas- tomycosis, with rounded budding yeasts, larger than neutrophils. Note the characteristic thick wall and nuclei (not seen in other fungi). (D) Silver stain highlights the broad-based budding seen in Blastomyces immitis organisms. 180 CHAPTER 10 Lung and Upper Respiratory Tract uncon s suppressed, we-ormed granuomas are absen and e necon oten dssemnaes. In suc cases, oca coecons o mac- ropages conanng yeas orms are seen n mupe organs. Clncal Features. Cnca manesaons may ake e orm o acue (pr- mary) pumonary necon, cronc (granuomaous) pumonary dsease, or dssemnaed mary dsease. Sympoms and sgns n mos prmary necons resembe ose o a “lu-ke” syndrome and are usuay se-m- ed. In e vunerabe os, cronc cavary pumonary dsease deveops, w a predecon or e upper obe, resembng e secondary orm o ubercuoss. Inecons aso may o gve rse o perar mass esons a resembe broncogenc carcnoma radoogcay. Sympoms may ncude coug, emopyss, dyspnea, and ces pan. In nans or mmunocom- promsed adus, parcuary ose w HIV necon, dssemnaed dsease may deveop, caracerzed by a ebre ness marked by epao- spenomegay, anema, eukopena, and rombocyopena. Dssemnaed dsease s dcu o rea and may prove aa. Fig. 10.15 Cytomegalovirus infection of the lung. A distinct nuclear inclu- sion and multiple cytoplasmic inclusions are seen in an enlarged cell. Opportunistic Infections caracersc nraaveoar, oamy exudae a appears pnk w a Opportunistic microbes do not cause disease in healthy individu- emaoxyn-eosn (H&E) san (coon candy exudae) (Fg. 10.16A). als but may cause serious infections in individuals whose immune Sver sanng o ssue secons reveas round or cup-saped cyss (4 o systems are suppressed by disease or therapy. 10 μm n dameer) wn e aveoar exudaes (Fg. 10.16B). Opporunsc pumonar y paogens ncude cyomegaovrus and Te d ag noss sou d be c ons d ere d n any m muno c ompro- ceran ung, wc are dscussed urer n e oowng. ms e d p a en w resp raor y s y mpoms and abnor ma nd ngs on Cytomegalovirus Infection ces radog rap. Fe ver, dr y c ou g , and dy spne a o c c ur n 90 % o 95% o p a ens. Te mos s e ns ve and e e c ve me o d o d ag no- Infection by cytomegalovirus (CMV), a member of the herpesvirus ss s o d en y e organ s m n spuum or bronco a ve o ar avage family, manifests in various forms depending on the age and the ud usng mmuno uores c enc e. I re a me n s n ae d b eore immune status of the host. w despre ad nvovemen, e ou o ok or re c over y s go o d ; ow - Mos peope are exposed o CMV a some pon durng e. Inec- e ver, b e c aus e resdu a org an s ms are key o p ers s , p ar c u ary on o e eus ranspacenay can ead o serous congena abnor- n p a ens w AID S , re aps e s are c ommon u n ess e und ery ng maes. Transmsson occurs more commony n cdren or adus mmuno d e cenc y s cor re c e d or propy ac c erapy s g ven. exposed o neced sava, secreons, or semen. Transmsson may aso occur roug organ ranspanaon and bood ransuson. In eay Candidiasis cdren and adus, CMV necon s usuay asympomac, bu ere Candda abcans s e mos common cause o unga dsease. I s a may be a se-med necous mononuceoss–ke ness. Foowng norma naban o e ora cavy, gasronesna rac, and vagna. necon, e vrus remans aen wn eukocyes, e major reser- Canddass can nvove e mucous membranes, skn, and deep organs vors o e vrus rougou e. suc as e ungs (nvasve canddass). O ese vared presenaons, Wen T-ce mmuny s suppressed, as n recpens o organ or severa mer a bre menon: emaopoec sem ce ranspans and n paens w AIDS, aen Super ica necton on mucosa sur aces o the ora cavty (thrush) CMV necon may be reacvaed or, ess commony, prmary CMV s e mos common presenaon. rus s seen n newborns and necon can occur. e dsease many afecs e ungs (pneumon- debaed paens, n ndvduas recevng ora corcoserods or s), gasronesna rac (cos), and rena (rens). Ineced ces broad-specrum anbocs (wc desroy compeng norma bac- are markedy enarged, and conan promnen nranucear basopc era ora), and n HIV-posve paens. Proeraon o e ung ncusons se of rom e nucear membrane by a cear ao (Fg. 10.15). creaes gray-we pseudomembranes composed o maed organ- Wn e cyopasm o ese ces, smaer basopc ncusons aso sms, nammaor y ces, and ssue debrs. may be seen. Vagnts s exremey common n women, especay ose wo are Dagnoss o CMV necon s made by demonsraon o caracer- dabec or pregnan or are akng ora conracepve ps. sc vra ncusons n ssue secons, vra cuure, rsng anvra an- Esophagts s common n paens w AIDS and n ose w body er, and PCR assay–based deecon o CMV DNA. e aer as emaoympod magnances. ese paens presen w dys- revouonzed e approac o monorng paens ater ranspanaon. paga (panu swaowng) and reroserna pan; endoscopy Pneumocystis Infection demonsraes we paques and pseudomembranes. Skn necton can manes n many dferen orms, ncudng Pneumocysts jrovec s an opporunsc ungus a causes cnca ds- necon o e na, na ods, ar oces, pene skn, and mos, ease amos excusvey n mmunocompromsed ndvduas. Paens nerrgnous skn suc as armps or webs o e ingers and oes w AIDS are exremey suscepbe o necon w P. jrovec (aoug Daper ras s a cuaneous candda necon seen n e perneum s seen muc ess oten snce e adven o efecve anvra erapy), o nans, n e regon o conac w we dapers. and aso may cause dsease n severey manoursed nans and nd- Invasve canddass mpes bood-borne dssemnaon o organ- vduas wo are mmunosuppressed oowng organ ranspanaon or sms o varous ssues or organs. Paens w acue eukemas wo reamen w cyooxc cemoerapy or corcoserods. are prooundy neuropenc ater cemoerapy are parcuary Pneumocysts necon s argey conined o e ung, were prone o e deveopmen o nvasve dsease. produces an nersa pneumons. Invoved areas conan a CHAPTER 10 Lung and Upper Respiratory Tract 181 A B Fig. 10.16 Pneumocystis pneumonia. (A) The alveoli are filled with a characteristic foamy acellular exudate. (B) Silver stain demonstrates cup-shaped and round cysts within the exudate. In ssue secons, C. abcans demonsraes yeas-ke orms (baso- LUNG, PLEURAL, AND UPPER AIRWAY TUMORS conda), pseudoypae, and rue ypae (Fg. 10.17A). Pseudoy- Lung Carcinoma pae are an mporan dagnosc cue and represen buddng yeas Lung carcinoma is most frequently caused by exposure to carcin- ces joned end o end a consrcons, us smuang rue unga ogens in tobacco smoke. ypae. he organsms are vsbe w roune H&E sans bu are e Amercan Cancer S ocey esmaed a ere woud be beer gged w a varey o speca “unga” sans (Gomor approxmaey 228,820 new cases o ung cancer n 2019 and 135,720 meenamne–sver, perodc acd–Scf ). deas. e ncdence s graduay decreasng, argey arbuabe o Cryptococcosis canges n smokng abs n e popuaon. e peak ncdence s n adus pas 50 years o age. A dagnoss, more an 50% o paens Two speces o Cryptococcus cause dsease. Cryptococcus neoformans ave dsan measases, and an addona one our ave dsease n amos excusvey necs mmunocompromsed oss, parcuary e regona ymp nodes. e prognoss remans dsma: e 5-year paens w AIDS or emaoympod magnances. Cryptococcus gatt sur vva rae or a sages o ung cancer combned s abou 24%. s an emergng paogen a causes dsease n mmunocompeen nd- Carcnomas o e ung are cassied based on soogc eaures vduas. Bo ung appear as 5- o 10-μm yeass, ave ck, geanous no our major ypes: adenocarcnoma, squamous ce carcnoma, capsues, and reproduce by buddng (Fg. 10.17D). Perodc acd–Scf arge ce carcnoma, and sma ce carcnoma (a subype o neuroen- sanng efecvey ggs e yeas orms. he capsuar poysacca- docrne carcnoma). Adenocarcnoma, squamous ce carcnoma, and rde angen s e subsrae or e crypococca aex aggunaon assay, arge ce carcnoma are oten grouped ogeer or cnca purposes wc s posve n more an 95% o paens neced w eer speces. under e erm “non–sma ce carcnoma” n recognon o e d- Bo crypococca speces are acqured by naaon o aerosozed erences n beavor and reamen o ese umors as compared o conamnaed so or brd droppngs. he ungus nay ocazes n e sma ce carcnoma. Squamous ce and sma ce carcnomas ave ungs and en dssemnaes o oer ses, parcuary e mennges. he e sronges assocaon w smokng, bu an assocaon w adeno- mmune response may be mnma (n mmunodeicen oss) or gran- carcnoma aso exss. Adenocarcnoma s e mos common ype and uomaous (n a more reacve os). In e cenra nervous sysem, ese occurs a a ger requency an oer ypes n women, never-smok- ung grow n geanous masses wn e mennges or expand e per- ers, and ndvduas under 45 years o age. vascuar Vrcow-Robn spaces, producng so-caed soap-bubbe esons. Opportunistic Molds Pathogeness. Mos carcnomas o e ung arse by a sepwse accumu- aon o drver muaons nduced by carcnogens n obacco smoke. Mucormycoss and nvasve aspergoss are uncommon necons a Ceran genec canges assocaed w ung cancer are ound n e occur many n mmunocompromsed oss, parcuary ose w bengn-appearng bronca epeum o smokers (ied efec). e proound neuropena. Poory conroed dabecs aso are a g rsk. muaons ound n smokng-reaed cancers sow a “sgnaure” a Mucormycoss s caused by ung o e Zygomycetes cass. Bo zygomy- s specic or e muagenc efecs o carcnogens n obacco smoke. cees and Aspergus ave a predecon or nvadng bood vesse was, Abou 90% o ung cancers occur n acve smokers or ose wo causng emorrage, vascuar necross, and narcon (Fg. 10.17B). sopped receny, and ere s a neary near correaon beween e In rnocerebra and pumonar y mucormycoss, zygomycees coo- requency o ung cancer and pack-years o cgaree smokng. Ces- nze e nasa cavy or snuses and en spread drecy no e bran, saon o smokng decreases e rsk or deveopng ung cancer over orb, and oer oca srucures. Paens w dabec keoacdoss me, bu never o basene eves. Passve smokng (proxmy o cg- are mos key o deveop a umnan nvasve orm o rnocerebra aree smokers) aso ncreases e rsk or deveopng ung cancer, as mucormycoss. Invasve aspergoss preerenay ocazes o e does smokng o ppes and cgars, abe ony modesy. ungs, and necon mos oten maness as a necrozng pneumona Oer carcnogenc nuences ac n concer w smokng or (Fg. 10.17C). Sysemc dssemnaon, especay o e bran, s a com- may ndependeny cause ung cancer. Exampes o occupaona pcaon a s oten aa. 182 CHAPTER 10 Lung and Upper Respiratory Tract A B C D Fig. 10.17 The morphology of fungal infections. (A) Candida organism has pseudohyphae and budding yeasts (silver stain). (B) Invasive aspergillosis (gross appearance) of the lung in a hematopoietic stem cell transplant recipient. (C) Gomori methenamine–silver (GMS) stain shows septate hyphae with acute-angle branching, consistent with Aspergillus. (D) Cryptococcosis of the lung in a patient with AIDS. The organisms are some- what variable in size. (B, Courtesy of Dr. Dominick Cavuoti, Department of Pathology, University of Texas Southwestern Medical School, Dallas.) carcnogens ncude exposure o radaon (n uranum mners), expo- n nonsmokng women, and afec severa dferen knases, suc as sure o asbesos, and naaon o duss conanng arsenc, cromum, e epderma grow acor recepor (EGFR), ALK, ROS1, HER2, and ncke, or vny corde. he rsk assocaed w exposure o asbes- c-MET. Eac o ese knases s opmay argeed by a dferen drug, os and obacco smokng s mupcave: Nonsmokers exposed o wc as spurred a new era o “personazed” ung cancer reamen, asbesos ave a 5-od rsk o deveopng ung cancer, wereas n eavy n wc e genecs o e umor gude erapy. smokers exposed o asbesos, e rsk s eevaed approxmaey 55-od. No a ndvduas exposed o obacco smoke deveop cancer Morphology. Adenocarcnomas are usuay perperay ocaed and (⁓11% o eavy smokers do), and s key a e muagenc efec may dspay a varey o grow paerns, ncudng acnar (gand- o carcnogens s modied by eredar y (genec) acors. Indvd- ormng) (Fg. 10.18A and B), papar y, mucnous, and sod ypes. uas w ceran poymorpsms nvovng e P-450 genes ave an ese umors oten ave spread by e me o dagnoss, possby ncreased capacy o acvae procarcnogens ound n cgaree smoke, because ey produce ew sympoms eary n er course due o and are us exposed o arger doses o carcnogens and ncur a greaer perpera ocaon. rsk o deveopng ung cancer. Smary, ndvduas wose perpera Squamous ce carcnomas end o arse cenray n major bood ympocyes undergo cromosoma breakage ater exposure bronc and evenuay spread o ar nodes. Large esons may o carcnogens n obacco smoke (muagen-sensve genoype) ave undergo cenra necross, gvng rse o cavaon. ese umors a greaer an 10-od ncreased rsk or deveopng ung cancer over oten become sympomac wen e umor obsrucs a broncus, conro subjecs. eadng o dsa coapse o aveo (aeecass) and supermposed Some o e muaons a drve ung cancer grow acvae yro- necon (Fg. 10.19A). On soogc examnaon, ese umors sne knases, wc are exceen drug arges. Tyrosne knase mua- sow a wde range o dferenaon (Fg. 10.19B). ons are mos common n adenocarcnomas, parcuary ose arsng CHAPTER 10 Lung and Upper Respiratory Tract 183 A B Fig. 10.18 (A) Early in situ lung adenocarcinoma growing along alveolar septae. (B) Invasive gland-forming lung adenocarcinoma; inset shows thyroid transcription factor 1 (TTF-1) positivity, which is seen in a majority of cases. A B Fig. 10.19 Squamous cell carcinoma. (A) Squamous cell carcinoma appearing as a central (hilar) mass that is invading contiguous parenchyma. (B) Well-differentiated squamous cell carcinoma, showing keratinization and pearls. Large ce carcnomas are undferenaed magnan epea supracavcuar node (Vrcow node) s caracersc and some- umors a ack e cyoogc eaures o neuroendocrne carcnoma mes cas aenon o an occu prmar y umor. Wen advanced, and sow no evdence o ganduar or squamous dferenaon. ese cancers oten exend no e peura or percarda space, ead- Sma ce ung carcnomas generay appear as pae gray, cen- ng o nammaon and magnan efusons. ey may compress ray ocaed masses a exend no e ung parencyma. ese or nirae e superor vena cava o cause vena cava syndrome. cancers are composed o reavey sma umor ces w a round Apca neopasms may nvade e braca or cer vca sympaec o usorm sape, scan cyopasm, and iney granuar croman. pexus, causng severe pan n e dsrbuon o e unar ner ve Numerous moc igures are presen (Fg. 10.20). ese umors or Horner syndrome (psaera enopamos, poss, moss, and may secree a os o poypepde ormones a resu n para- andross). neopasc syndromes. By e me o dagnoss, mos umors w ave measaszed o e ar and medasna ymp nodes. In e Clncal Features. Carcnomas o e ung are nsdous and oten 2015 Word Hea Organzaon cassicaon, sma ce ung car- ave spread beyond e ung beore sympoms appear. Uncommony, cnoma s grouped ogeer w arge ce neuroendocrne carc- squamous ce carcnomas or adenocarcnomas are deeced beore noma, anoer ver y aggressve umor a exbs neuroendocrne measass or oca spread, makng a surgca cure possbe. Unresecabe morpoog y and expresses neuroendocrne markers. adenocarcnomas assocaed w argeabe muaons n yrosne Eac o ese ung cancer subypes ends o spread o ymp knases suc as EGFR oten respond o specic nbors. A ew paens nodes and, sooner or aer, o dsan ses. Invovemen o e et w ese ypes o esons ave ong-erm remssons on e order 184 CHAPTER 10 Lung and Upper Respiratory Tract w squamous ce neopasms, e emaoogc syndromes w adeno- carcnomas, and e neuroogc syndromes w sma ce neopasms. Carcinoid Tumors Carcinoid tumors are malignant neuroendocrine tumors that con- tain dense-core neurosecretory granules in their cytoplasm and sometimes secrete biologically active polypeptide hormones. Carcnod umors many arse n e ung and n e gasrones- na rac. Bronca carcnods occur n young adus (mean 40 years) and represen abou 5% o a pumonar y neopasms. Morphology. Mos carcnods orgnae n e man bronc, eer as an obsrucng poypod, sperca, nraumna mass (Fg. 10.21A) or a mucosa paque a peneraes e bronca wa and ans ou n e perbronca ssue (coar-buon eson). e Fig. 10.20 Small cell carcinoma with small deeply basophilic cells and esons are we demarcaed. Aoug 5% o 15% o carcnods ave areas of necrosis (top left). Note basophilic staining of vascular walls measaszed o e ar nodes a presenaon, dsan measases due to encrustation by DNA from necrotic tumor cells (Azzopardi effect). are rare. e umor consss o ness o unorm ces a ave reguar round nuce w “sa-and-pepper” croman, absen or rare moses, and e peomorpsm (see Fg. 10.21B). o years, bu reapse wn severa mons o a year s more ypca. Inevaby, ressan umors ave new muaons a eer aer e drug Clncal Features. Mos pumonar y carcnod umors manes w arge (e.g., an addona muaon n EGFR a prevens drug bndng) sgns and sympoms reaed o er nraumna grow, ncudng or a crcumven e umor’s dependence on e drug arge. Immune coug, emopyss, and bronca and pumonar y necons. Perp- ceckpon nbors produce responses n some umors, parcuary era umors are oten asympomac and are dscovered ncdenay. ose a are smokng reaed (key because e g burden o Ony rarey do pumonar y carcnods cause e carcnod syndrome, carcnogen-nduced muaons creaes more umor neoangens). caracerzed by nermen aacks o darrea, usng, and cyano- By conras, e pcure or sma ce ung cancers as canged ss; ese sympoms are muc more commony produced by carcnods e. ese umors nvaraby spread beore dagnoss, and surgca arsng n e gasronesna rac. e repored 5- and 10-year sur- resecon s no an opon. Sma ce ung cancers are ver y sensve o vva raes or carcnod umors are above 85%. cemoerapy bu rapdy recur, and argeed erapes ave ye o be deveoped. e medan sur vva w reamen s 1 year, and ony 5% Malignant Mesothelioma o paens are ave a 10 years. Malignant mesothelioma is strongly associated with exposure to Up o 10% o paens w ung cancer deveop paraneopastc syn- airborne asbestos. dromes reaed o ormones secreed by e umor ces. ese syn- s rare cancer o mesoea ces usuay arses n e parea or vs- dromes ncude (1) ypercacema (rom secreon o a parayrod cera peura or, muc ess commony, n e peroneum and percardum. ormone–reaed pepde [PTHrP]); (2) Cusng syndrome (rom Approxmaey 80% o 90% o ndvduas w mesoeoma ave a s- ncreased producon o adrenocorcoropc ormone [ACTH]); ory o exposure o asbesos. ose wo work drecy w asbesos (sp- (3) e syndrome o napproprae secreon o andurec ormone yard workers, mners, nsuaors) are a greaes rsk, bu mesoeoma as (ADH); (4) neuromuscuar syndromes, ncudng a myasenc dsor- occurred n ndvduas wose ony exposure was vng n proxmy o der, perpera neuropay, and poymyoss; (5) cubbng o e ingers an asbesos acory or beng a reave o an asbesos worker. e aen and yperropc pumonar y oseoarropay ; and (6) coaguaon perod ater e na exposure s ong, oten 25 o 40 years. Smokng does abnormaes, ncudng mgraor y rombopebs and dssemnaed no ncrease e ncdence o mesoeoma, n conras o ung carcnoma nravascuar coaguaon. Hypercacema s mos oten encounered A B Fig. 10.21 Bronchial carcinoid. (A) Carcinoid growing as a spherical, pale mass (arrow) protruding into the lumen of the bronchus. (B) Histologic appearance demonstrating small, rounded, uniform nuclei and moder- ate cytoplasm (Courtesy Dr. Thomas Krausz, Department of Pathology, University of Chicago Pritzker School of Medicine, Chicago.)
