Most carcinomas of the head of the pancreas obstruct the distal common bile duct asitcoursesthroughtheheadofthepancreas.In50%ofsuchcases,thereismarkeddistentionofthebiliarytree,andpatientstypicallyexhibitjaundice.Incontrast,carcinomasofthebodyandtailofthepancreasdonotimpingeonthebiliarytract.Pancreaticcancersoftenextendthroughtheretroperitonealspace,entrappingadjacentnerves(thus,accountingforthepain),andoccasionallyinvadethespleen,adrenalglands,vertebralcolumn,transversecolon,andstomach.Peripancreatic,gastric,mesenteric,omental,andportahepaticlymphnodesfrequentlyareinvolved,andtheliveroftenisenlargedwithmetastaticdeposits.Distantmetastasesmayoccur,principallytothelungsandbones.
Onmicroscopicexamination,pancreaticcarcinomausuallyisamoderately to poorly differentiated adenocarcinoma formingabortiveglandswithmucinsecretionorcellclustersandexhibitinganaggressive,deeplyinfiltrativegrowthpattern(see
Fig.17.9B ).Densestromalfibrosisaccompaniestumorinvasion,andthereisaproclivityforperineuralinvasionwithinandbeyondtheorgan.Lymphaticinvasionalsoiscommonlyseen.
Fig. 17.9 Carcinomaofthepancreas.(A)Cross-sectionthroughtheheadofthepancreasandadjacentcommonbileductshowingbothanill-definedmassinthepancreaticsubstance(arrowheads) andthegreendiscolorationoftheductresultingfromtotalobstructionofbileflow.(B)Poorlyformedglandsarepresentinadenselyfibrotic(desmoplastic)stromawithinthepancreaticsubstance.
Lesscommonvariantsofpancreaticcancerincludeadenosquamous carcinomas withfocalsquamousdifferentiationinadditiontoglandulardifferentiation;andundifferentiatedcarcinomaswithosteoclast-likegiantcellsofmonocyticlineageintermixedwithintheneoplasm.
Carcinomas of the pancreas typically remain silent until their extension impinges on some other structure. Pain usually is the first symptom, but by that point these cancers are often beyond cure. Obstructive jaundice can be associated with carcinoma in the head of the pancreas, but it rarely draws attention to the cancer soon enough for timely intervention. Weight loss, anorexia, and generalized malaise and weakness are manifestations of advanced disease. Migratory thrombophlebitis (Trousseau syndrome) occurs in about 10% of patients and is attributable to the elaboration of platelet-aggregating factors and pro-coagulants from the tumor or its necrotic products (Chapter 6). As previously stated, new-onset diabetes is the first manifestation of pancreatic cancer in some patients.
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The clinical course of pancreatic carcinoma is rapidly progressive and often distressingly brief. Less than 20% of pancreatic cancers are resectable at the time of diagnosis. It has long been recognized that there is a profound need for biomarkers capable of detecting early, potentially curable, pancreatic cancers. Although serum levels of many enzymes and antigens (e.g., carcinoembryonic and CA19-9 antigens) are elevated, these markers are neither specific nor sensitive enough to be useful for screening. Several imaging techniques, such as endoscopic ultrasonography and high-resolution CT scans, are helpful for investigation in cases of suspected cancer but are not practical screening tests.