Robbins Essential Pathology PDF

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5 Neoplasia O U T L I N E Definition of Neoplasia, 63 Hallmarks of Cancer, 73 Benign and Malignant Neoplasms, 63 Self-Sufficiency in Growth Signals, 74 Nomenclature, 64 Insensitivity to Growth-Inhibitory Signals, 75 Nomenclature of Benign Tumors, 64 Altered Cellular Metabolism, 77 Nomenclature of Malignant Tumors, 64 Evasion of Cell Death, 79 Characteristics of Benign and Malignant Neoplasms, 66 Limitless Replicative Potential (Immortality), 79 Differentiation of Neoplasms, 66 Sustained Angiogenesis, 80 Local Invasion, 68 Invasion and Metastasis, 80 Metastasis, 68 Evasion of Immune Surveillance, 81 Molecular Basis of Neoplasia, 69 Genomic Instability as an Enabler of Malignancy, 83 Cancer Genes and “Driver” Mutations, 69 Tumor-Promoting Inflammation as an Enabler of Malignancy, 83 Epigenetic Alterations in Cancer, 70 Clinical Aspects of Neoplasia, 83 Carcinogenesis: A Multistep Process Directed by Darwinian Evolution, 70 Clinical Effects of Tumors, 84 Origin of Carcinogenic Mutations, 71 Grading and Staging of Cancer, 84 Role of Infectious Agents in Cancer, 72 Cancer Diagnosis, 85 Significance of Passenger Mutations, 73 Cancer, the most feared form of neoplasia, remains the second srkng propery o neopasms, er aby o produce a ocazed leading cause of death in both children and adults. mass reerred o as a umor (rom e L an tumere, o swe). he Despe consderabe progress n undersandng e boog y o neo- sudy o umors s caed oncoog y (rom e Greek oncos, “umor, ” pasms and n er dagnoss and reamen, cancer ras ony cardo- and ogos, “sudy o ”). he muaons a cause neopasms are usu- vascuar dsease as a cause o morbdy and moray n e Uned ay acqured bu aso may be nered. We w reurn o e ssue o Saes. Approxmaey 1.69 mon new cases o cancer and over muaons and cancer aer. 600,000 cancer deas were recorded n 2017 n e counr y. Incdence In conras o neopasa, yperpasa occurs wen many ces wn daa or e mos common orms o cancer, w e major kers den- afeced ssues begn o proerae smuaneousy n response o ed, are presened n Fg. 5.1 pysoogc or paopysoogc grow sgnas; as a resu, yperpa- Our sudy o neoplasa begns w e denng bologc and mor- sas are poycona. Exampes o yperpasas ncude enargemens o pologc caracerscs o bengn and malgnan neoplasms. hs s ympod ssues caused by nlammaor y medaors and o e uerus oowed by a dscusson o e genec and moecuar bass o cancer n response o gesaona ormones durng pregnancy. Unke neo- and e common eaures a are sared by a magnan neopasms, pasas, yperpasas are reversbe: Lymp node sweng abaes as an e so-caed “amarks o cancer. ” Fnay, we dscuss e cnca necon s ceared, and e uerus revers o s pror sae ater dev- manesaons and aboraor y dagnoss o cancer. er y o e eus. DEFINITION OF NEOPLASIA BENIGN AND MALIGNANT NEOPLASMS Neoplasia (literally, new growth) refers to a clonal proliferation of Benign neoplasms generally are well circumscribed, are easily cells that have “escaped” from normal growth control mechanisms excised, and do not spread from their site of origin, whereas malig- because of the acquisition of genetic aberrations. nant neoplasms often inltrate surrounding tissues and have the In vruay a nsances, ever y ce wn a gven neopasm sares capacity to spread to distant sites (metastasize). a se o paogenc muaons, ndcang a neopasms are com- Neopasms are dened as bengn and magnan based on e gross posed o genecay reaed “dauger” ces derved  rom a snge and mcroscopc appearance o e proeraon (descrbed aer), aberran oundng ce. B ecause o er orgn rom a snge progen- wc s predcve o a gven umor’s probabe cnca beavor. or ce, neopasc ces are sad o be cona n orgn he mua-    Bengn mpes a a umor w reman ocazed and s amenabe ons a cause neopasa aer e uncon o genes a reguae ce o compee surgca remova. Afeced paens generay sur vve, grow and sur vva (descrbed aer), ereby conerrng e mos bu even “bengn” umors may occasonay cause serous morbdy 63 64 CHAPTER 5 Neoplasia A 2019 ESTIMATED CANCER INCIDENCE BY SITE AND SEX* B 2019 ESTIMATED CANCER DEATHS BY SITE AND SEX Men 870,970 Women 891,480 Men 321,670 Women 282,210 Melanoma 7% 5% Melanoma of the skin 3% Brain of the skin Lung and 24% Oral cavity 4% bronchus 4% Thyroid Lung and 23% Esophagus 4% Lung and 13% bronchus 13% Lung and Liver and 7% bronchus bronchus 15% Breast bile duct Kidney 5% 30% Breast Kidney 3% 4% Liver Pancreas 3% Pancreas 7% 3% Kidney 8% Pancreas Colon and 9% 3% Pancreas Colon and 9% 8% Colon and rectum rectum 7% Colon and rectum Urinary 4% rectum Urinary 7% 4% Uterine corpus bladder bladder 7% Uterine corpus 5% Ovary Prostate 10% 3% Ovary Prostate 20% Leukemia 4% 3% Leukemia Leukemia 4% Non-Hodgkin 4% 3% Non-Hodgkin Non-Hodgkin 5% 4% Non-Hodgkin lymphoma lymphoma lymphoma lymphoma All other sites 23% 21% All other sites All other sites 24% 24% All other sites Fig. 5.1 Estimated cancer incidence and death rates by site and sex in the United States. Excludes basal cell and squamous cell skin cancers and in situ carcinomas, except those of urinary bladder. (Adapted from Cancer Facts and Figures 2019. American Cancer Society. www.cancer.org/research/cancer-facts-statistics/ all-cancer-facts-figures/cancer-facts-figures-2019.html ) or even moray, or exampe, by causng a oca mass efec n a 5.2). Aoug s erm commony s used or bengn umors, some crca organ (e.g., e bran). magnan umors begn as poypod grows, parcuary n e gu.    Mag nant s appe d o esons  a c an  nvade and d e s roy adj a - Nomenclature of Malignant Tumors cen  ssues and me  as as z e o d s an s es , u  maey re su   ng n de a . Ma g nan umors are co  e c  vey reer re d o as can- he nomencaure o magnan umors essenay oows a o cers (der ve d  rom  e L a  n word or “c rab”) b e c aus e  e r  n   - bengn umors (see Tabe 5.1), w ceran addons and excepons:  ra ve g row  c aus es  em o “g rab” ono nor ma   ssues and    Carcnomas are magnan neopasms o epea ces, and are ur- ad ere  g  y, sm  ar o a crab’s b eav  or. A  oug  no a c an- er subdvded based on paerns o grow and dferenaon. cers pursue a de ad y cours e and s ome o  e mos ag g re ss ve are    S arcomas are magnan neopasms composed o ces smar o a s o among  e mos c urabe,  e de s g na  on mag nant s a re d ose ound n sod mesencyma ssues. Sarcomas are desgnaed   ag. based on e norma ce ype or ssue ey mos cosey resembe. A umors, bengn and magnan, are composed o wo compo-    Leukemas and ympomas are magnan neopasms derved rom nens: (1) neopasc ces and (2) a nonneopasc sroma, made up o e emaopoec progenor ces a gve rse o bood and connecve ssue, bood vesses, and nlammaor y ces. As w be ds- mmune ces. Leukemas preerenay nvove marrow and bood, cussed n e Hamarks o Cancer secon, e beavor o a neopasm and ympomas nvove ympod ssues (ymp node and speen) depends no ony on e nrnsc properes o e neopasc ces bu (see Caper 9). aso on e naure o e sroma response, wc umor ces “manp- he ransormed ces n a neopasm, weer bengn or magnan, uae” n order o avor er grow and sur vva. usuay resembe e ces o a snge neage. In some umors, owever, e neopasc ces oow more an one ne o dferenaon. hese ncude peomorpc adenoma o e savar y gand, a cassc mxed NOMENCLATURE tumor, wc (aoug cona) s comprsed o neopasc epea The nomenclature of various neoplasms is important because and mesencyma eemens (Fg. 5.3). Uncommony, magnan umors each name carries with it certain associated characteristics that conss o magnan eemens rom dferen neages, suc as carc- are related to the biology of the neoplasm and its likely clinical nosarcomas, wc are composed o bo mesencyma and epea behavior. componens. Teratoma s anoer ype o umor a sows mupe nes o dferenaon (Suppemena eFg. 5.1). Teraomas orgnae Nomenclature of Benign Tumors rom opoena germ ces a ave e capacy o dferenae no Mos bengn umors are desgnaed by aacng e suix “ oma” o e any ce ype and may conan apazardy arranged eemens resem- ce ype rom wc e umor arses (Tabe 5.1). Oers ave names bng many dferen ssues. a relec er grow paerns. A papoma s a bengn epea neo- Some garng nconssences n e namng convenons ad ou pasm growng on a surace a produces mcroscopc or macroscopc above may be noed n Tabe 5.1. For exampe, ympoma, mesoe- nger-ke projecons. A poyp s a mass a projecs above a mucosa oma, meanoma, and semnoma “sound” bengn bu are a magnan surace, as n e gu, o orm a macroscopcay vsbe srucure (Fg. neopasms.  CHAPTER 5 Neoplasia 64.e1 A B Supplemental eFig. 5.1 (A) Gross appearance of an opened cystic teratoma of the ovary. Note the presence of hair, sebaceous material, and tooth. (B) A microscopic view of a similar tumor shows skin, sebaceous glands, fat cells, and a tract of neural tissue (arrow).  CHAPTER 5 Neoplasia 65 Table 5.1 Nomenclature of Tumors Tissue of Origin Benign Malignant Composed of One Parenchymal Cell Type Connective tissue and derivatives Lipoma Liposarcoma Chondroma Chondrosarcoma Osteoma Osteosarcoma Blood vessels Hemangioma Angiosarcoma Mesothelium Mesothelioma Brain coverings Meningioma Invasive meningioma Hematolymphoid cells Leukemias, lymphomas Smooth muscle Leiomyoma Leiomyosarcoma Stratified squamous Squamous cell papilloma Squamous cell carcinoma Basal cells of skin or adnexa Basal cell carcinoma Epithelial lining of glands or ducts Adenoma Adenocarcinoma Papilloma Cystadenoma Liver cells Hepatic adenoma Hepatocellular carcinoma Urinary tract epithelium (transitional) Urothelial papilloma Urothelial carcinoma Placental epithelium Hydatidiform mole Choriocarcinoma Testicular epithelium (germ cells) Seminoma Embryonal carcinoma Tumors of melanocytes Nevus Malignant melanoma Composed of More Than One Neoplastic Cell Type: Mixed Tumors, Usually Derived from One Germ Cell Layer Salivary gland Pleomorphic adenoma (mixed tumor of salivary gland) Malignant mixed tumor of salivary gland Renal anlage Wilms tumor More Than One Neoplastic Cell Type Derived from More Than One Germ Cell Layer: Teratogenous Totipotential cells in gonads or in embryonic rests Mature teratoma, dermoid cyst Immature teratoma, teratocarcinoma Fig. 5.3 Mixed tumor of the parotid gland. Small nests of epithelial cells and myxoid stroma forming cartilage and bone (an unusual feature) are Fig. 5.2 Colonic polyp. This glandular tumor (adenoma) projects into the present in this field. (Courtesy of Dr. Vicky Jo, Department of Pathology, colonic lumen and is attached to the mucosa by a distinct stalk. Brigham and Women’s Hospital, Boston.) 66 CHAPTER 5 Neoplasia Endometrium Fallopian tube Tumor Vein Ovar y BENIGN MALIGNANT (Leiomyoma) (Leiomyosarcoma) Small Noninvasive Large Locally invasive Well demarcated Nonmetastatic Poorly demarcated Metastatic Slow growing Well differentiated Rapidly growing with Poorly differentiated hemorrhage and necrosis Fig. 5.4 Comparison between a benign tumor of the myometrium (leiomyoma) and a malignant tumor of similar origin (leiomyosarcoma). CHARACTERISTICS OF BENIGN AND MALIGNANT NEOPLASMS Most benign and malignant tumors can be distinguished based on the evaluation of three features: degree of differentiation, local invasion, and metastasis. In mos nsances, e deermnaon o bengn versus magnan s made w remarkabe accuracy usng ong-esabsed cnca and anaomc crera. he eaures a usuay perm e dferenaon o bengn and magnan neopasms, usng umors o e myomerum as an exampe, are summarzed n Fg. 5.4 and descrbed n dea nex. Differentiation of Neoplasms Differentiation refers to the extent to which tumor cells resem- ble their parenchymal cells of origin, both morphologically and Fig. 5.5 Pleomorphic malignant tumor (poorly differentiated sarcoma). functionally. Note the marked variation in cell and nuclear sizes, the hyperchromatic In genera, bengn neopasms are composed o we-dferenaed nuclei, and the presence of tumor giant cells. (Courtesy Dr. Trace Wor- ces a cosey resembe er norma counerpars. By conras, mos rell, Department of Pathology, University of Texas Southwestern Med- magnan neopasms exb morpoogc aeraons a beray er ical School, Dallas.) magnan naure. Tumors composed o undferenaed ces are sad o be anapasc, a eaure a s a reabe ndcaor o magnancy.    Nucear abnormates, ncudng ypercromasm (dark-sanng), Anapasa eray means “backward ormaon, ” mpyng dedferen- varaon n nucear sze and sape, or unusuay promnen snge or aon, or oss o e srucura and uncona caracerscs o norma mupe nuceo. Enargemen o nuce may resu n an ncreased dferenaed ces. Anapasc ces oten dspay one or more o e nucear-o-cyopasmc rao, and nuceo may aan asoundng oowng eaures: szes a approac e dameer o norma ympocyes.    Peomor psm (varaon n ce sze and sape; Fg. 5.5). Exreme    Atypca mtoses, wc may be numerous. Abnorma separaon o exampes ncude umor gan ces a are consderaby arger an cromads durng ce dvson may produce rpoar or quadrpo- er negbors, w eac possessng eer one enormous nuceus ar moc gures (Fg. 5.6). or severa nuce.    L oss of poar ty, suc  a g roups o ne op as c c e s  a ck nor ma  p aer ns o or en a  on o one ano e r. In  e mos anap as c  CHAPTER 5 Neoplasia 67 umors, ce s g row n d s organ  ze d se es, w   o a   oss o orga - nze d s r uc ures suc as g  ands or s r a    e d s qu amous arce c - ure. We  - d   e re n  ae d u mor c e s are   key o re  a n  e  u nc -   ona  c ap ab    e s o  e  r nor ma  c ou ne r p ar  s , w e re as ana - p as  c u mor c e s are mu c  e ss   key o do so ( d s c uss e d  ae r, re g ard  ng u mor g r a d  ng ). For e x amp e, b engn ne op as ms and we  - d   e re n  ae d c anc e rs o e nd o c r  ne g  ands  re qu e n y e ab o - r ae  e or mone s car a c e r s  c o  e  r c e  o or  g  n. S m   ary, we  - d   e re n  ae d s qu amous c e  c arc  nomas pro du c e ke r a  n (F  g. 5.7) and we  - d   e re n  ae d e p ao c e u  ar c arc  nomas s e c re e b  e. In o e r  ns anc e s , u nan  c p ae d  u nc   ons e me rge. Mo s no aby, c anc e rs o none nd o c r  ne or  g  n may c aus e s  g ns and s y mpoms by s e c re   ng s o-caed e c op c or mone s , su c as a d re no c or   c o rop c or mone ( AC T H ) , p ar a y ro d or mone - re ae d proe  n ( P Tr P ) ,  nsu   n , g u c agon , and o e rs. More s s a d ab ou  e s e s o-caed Fig. 5.6 High-power detail view of anaplastic tumor cells shows cellular p ar ane op as  c s y nd rome s  ae r. and nuclear variation in size and shape. The prominent cell in the center field has an abnormal tripolar spindle. Dysplasia is disordered growth of epithelial cells that are abnor- mal but not malignant. Dyspasa s mporan o recognze because  s a we-documened precursor o carcnoma n many ssues, suc as e cer vx, endome- rum, and gasronesna rac. Feaures a are used o assess dys- pasa ncude e oowng:    Ceuar and nucear peomor psm, ypcay n e orm o abnor- may arge, ypercromac nuce    Abnorma mtotc actvty, ncudng more numerous moc gures and moses n superca ayers o sraed squamous epeum, were ey are no normay seen    Arctectura dsarray. Exampes ncude e para or compee oss o e usua progressve mauraon o ces n sraed squamous epeum or ransona epeum n e badder, resung n a dsordered odgepodge o dark basa-appearng ces. Wen dys- pasc canges are severe and nvove e enre ckness o e epeum, e eson s reerred o as carcnoma n su, a prenva- sve sage o cancer (Fg. 5.8). he prog resson o dyspas a o c ancer s no ne v  abe, and dys- pasas may reg ress compeey, p ar  c u  ary  nc ng caus es are remove d Ne ver  eess, as a genera  r u e,  e pres ence o dyspasa Fig. 5.7 Well-differentiated squamous cell carcinoma of the skin. The tumor cells are strikingly similar to normal squamous epithelial cells, marks a  ssue as b eng a ncre as e d r sk or de veopng an nvasve with intercellular bridges and nests of keratin (arrow). cancer. A B Fig. 5.8 Carcinoma in situ. (A) Low-power view shows that the entire thickness of the epithelium consists of dysplastic cells lacking orderly differentiation. The basement membrane is intact and there is no tumor in the subepithelial stroma. (B) High-power view of another region shows failure of normal differentiation, marked nuclear and cellular pleomorphism, and numerous mitotic figures extending toward the surface.