In addition to the direct effects of the tumor cells, it is estimated that 3% to 10% of patients with lung cancer develop paraneoplastic syndromes (Chapter 6). These include hypercalcemia caused by secretion of a parathyroid hormone–related peptide; (2) Cushing syndrome (from increased production of adrenocorticotropic hormone); syndrome of inappropriate secretion of anti-diuretic hormone; (4) neuromuscular syndromes, including a myasthenic syndrome, peripheral neuropathy, and polymyositis; clubbing of the fingers and hypertrophic pulmonary osteoarthropathy; and (6) coagulation abnormalities, including migratory thrombophlebitis, nonbacterial endocarditis, and disseminated intravascular coagulation. Hypercalcemia most often is encountered with squamous cell neoplasms, the hematologic syndromes with adenocarcinomas, and the neurologic syndromes with small cell neoplasms, but exceptions abound.
•Thethreemajorhistologicsubtypesareadenocarcinoma(mostcommon),squamouscellcarcinoma,andsmallcellcarcinoma,eachofwhichisclinicallyandgeneticallydistinct.Adenocarcinomasarethemostcommoncancersoverallandareespeciallycommoninwomenandinnonsmokers.
Smokingisthemostimportantriskfactorforlungcancer.
Precursorlesionsincludeatypicaladenomatoushyperplasiaandadenocarcinomainsituforadenocarcinomasandsquamousdysplasiaforsquamouscancer.
Tumors3cmorlessindiametercharacterizedbypuregrowthalongpreexistingstructureswithoutstromalinvasionarecalledadenocarcinomainsitu.
SCLCsarebesttreatedwithchemotherapy,becausealmostallaremetastaticatpresentation.Theothercarcinomasmaybecurablebysurgeryiflimitedtothelung.Targetedtherapies,suchasEGFRinhibitortherapyforadenocarcinomaswithEGFRmutations,canbeeffective,anexcellentexampleofpersonalizedcancertherapy.Immunotherapiesareunderdevelopmentandshowpromise.
Lungcancerscommonlycauseavarietyofparaneoplasticsyndromes.
Carcinoid tumors are malignant tumors composed of cells that contain dense-core neurosecretory granules in their cytoplasm and, rarely, may secrete hormonally active polypeptides. They are best thought of a low-grade neuroendocrine carcinomas and are subclassified as typical or atypical; both are often resectable and curable. They occasionally occur as part of the multiple endocrine neoplasia syndrome (Chapter 20). Bronchial carcinoids occur in young adults (mean 40 years) and represent about 5% of all pulmonary neoplasms.
MORPHOLOGYMostcarcinoidsoriginateinmainbronchiandgrowinoneoftwopatterns:(1)anobstructingpolypoid,spherical,intraluminalmass(
Fig.13.47A );or(2)amucosalplaquepenetratingthebronchialwalltofanoutintheperibronchialtissue—theso-calledcollar-button lesion. Evenpenetratinglesionspushintothelungsubstancealongabroadfrontandarewelldemarcated.Peripheralcarcinoidsarelesscommon.Although5%to15%ofcarcinoidshavemetastasizedtothehilarnodesatpresentation,distantmetastasesarerare.Histologically,typical carcinoids, liketheircounterpartsintheintestinaltract,arecomposedofnestsofuniformcellsthathaveregularroundnucleiwith“salt-and-pepper”chromatin,absentorraremitosesandlittlepleomorphism(see