Eble JN, Sauter G., Epstein JI, Sesterhenn IA - iarc

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Infiltrating urothelial carcinoma A. Lopez-Beltran G. Sauter T. Gasser A. Hartmann B.J. Schmitz-Dräger B. Helpap A.G. Ayala P. Tamboli M.A. Knowles D. Sidransky C. Cordon-Cardo P.A. Jones P. Cairns R. Simon M.B. Amin J.E. Tyczynski Definition Infiltrating urothelial carcinoma is defined as a urothelial tumour that invades beyond the basement membrane. ICD-O code 8120/3 Synonym Transitional cell carcinoma. Epidemiology of urothelial bladder cancer Bladder cancer is the 7th most common cancer worldwide, with an estimated 260,000 new cases occurring each year in men and 76,000 in women {749}. Cancer of the urinary bladder accounts for about 3.2% of all cancers worldwide and is considerably more common in males than in females (ratio worldwide is about 3.5:1) {2014}. In both sexes, the highest incidence rates of bladder cancer are observed in Western Europe, North America and Australia {2016}. The highest incidence rates of bladder cancer in males in 1990s were observed in the following registries: Limburg (Belgium) – 42.5/105, Genoa Province (Italy) – 41.1/105, and Mallorca (Spain) – 39.5/105 {2016}. The highest rates in females were noted in Harare (Zimbabwe) – 8.3/105, Scotland (UK) – 8.1/105, North Western England (UK) – 8.0/105, and white population of Connecticut (USA) – 8.0/105. The highest prevalence of bladder cancers in both males and females is observed in North America and in countries of the European Union {2084}. In general, the prevalence of bladder tumours in developed countries in approximately 6-times higher compared with that in developing countires. The most common type of bladder cancer in developed countries is urothelial carcinoma, derived from the uroepithelium, which constitutes more than 90% of bladder cancer cases in USA, France or Italy. However, in other regions (e.g. Eastern and Northern Europe, Africa, Asia) the relative frequency of urothelial carcinoma of the bladder is lower. In general, among all registries included into the 8th volume of "Cancer Incidence in Five Continents" {2016} urothelial carcinoma constitutes 84% of bladder cancer in males and 79% in females. Other types of bladder cancer, i.e. squamous cell carcinoma and adenocarcinoma have much lower relative frequency. In all "Cancer Incidence in Five Continents" {2016} registries squamous cell carcinoma accounts for 1.1% and 2.8% of all bladder cancers in men and women respectively. Adenocarcinoma of the bladder constitutes respectively 1.5% and 1.9% of all bladder tumours worldwide {2016}. It is estimated that approximately 70-80% of patients with newly diagnosed bladder cancer present with non-invasive or early invasive (i.e. stage Ta, Tis, or T1). Etiology of urothelial bladder cancer Risk factors There are several known and potential risk factors of bladder cancer. Cigarette smoking and occupational exposure to aromatic amines are the most important among them {1877}. Tobacco smoking Tobacco smoking is the major established risk factor of bladder cancer. It is estimated that the risk of bladder cancer attributed to tobacco smoking is 66% for men and 30% for women {1158}. The risk of bladder cancer in smokers is 2-6 fold that of non-smokers {313,391, 1877}. The risk increases with increasing duration of smoking, and for those with the longest history of smoking (60 years or more) reaches approximately 6 in men and 5 in women {313}. The excess of risk is observed also with increasing intensity of smoking (number of cigarettes per day), reaching maximum of about 3 for those smoking 40 or more cigarettes per day {313}. The increase of risk with the increasing duration and intensity of smoking is similar in both sexes {1158} but, some studies indicate higher risk in women than in men at the equivalent level of exposure {391}. Fig. 2.01 Estimates of the age-standardized incidence rates of bladder cancer in males, adjusted to the world standard age distribution (ASR). From Globocan 2000 {749}. Infiltrating urothelial carcinoma 93
The risk of bladder cancer goes down after stopping smoking, and 15 years cessation tends to be approximately that of non-smokers {1158}. The decrease of risk after cessation is similar in both sexes {391}. Glutathione S-transferase M1 (GSTM1) null status is associated with a modest increase in the risk of bladder cancer {700}. Occupational exposure Bladder cancer is associated with a number of occupations or occupational exposures. The first such association was observed in 1895 by Rehn, who reported high rates of bladder cancer among men employed in the aniline dye industry {617}. Subsequent research among dyestuffs workers identified the aromatic amines benzidine and 2-naphthylamine, and possibly 1-naphthylamine, as bladder carcinogens {1150}. It has been estimated that contact with occupational carcinogens causes up to 25% of all bladder tumours {2025}. Fig. 2.02 Relative frequency of major histological types of bladder tumours in females. From D.M. Parkin et al. {2016}. The underlying mechanism may lead to chronic irritation of the bladder epithelium, which may increase bladder cancer risk. causes urinary bladder cancer. Key evidence came from ecological studies in Chile and Taiwan (China) where large populations were exposed {1157}. Phenacetin Several epidemiological studies indicate that chronic abuse of analgesics containing phenacetin greatly enhance the risk of developing urothelial cancer of the renal pelvis, ureter and bladder. The relative risk has been estimated in the range of 2.4 to more than 6 {1150}. Early cases have been reported from Scandanavia {253,460}, Switzerland {1729} and Australia {1668}. Medicinal drugs The cytostatic agent, cyclophosphamide, has long been associated with the development of leukemia and lymphoma. In addition, treatment with cyclophosphamide has been reported to be associated with an increased risk of squamous cell carcinomas and sarcomas, especially leiomyosarcomas {1150, 2577}. Similarly, chlornaphazine is associated with the development of bladder cancer {2606}. Chronic infections Chronic cystitis caused by Schistosoma haematobium is an established cause of bladder cancer. The resultant bladder tumours are usually squamous cells carcinomas. Some authors suggested association between bladder cancer and urinary tract infections and urinary tract stones. Arsenic Several studies showed that use of drinking water containing chlorination byproducts or contaminated by arsenic may increase risk of bladder cancer {367,1117,1150,2444}. An IARC Monographs Working Group reviewed in 2004 the relevant epidemiological studies and concluded that arsenic in drinking-water is carcinogenic to humans (Group 1) and that there is sufficient evidence that it Table 2.01 Alphabetical list of agents, mixtures or exposure circumstances associated with bladder cancer. Aluminium production 4-Aminobiphenyl Analgesic mixtures containing phenacetin Arsenic in drinking water Auramine manufacture Benzidine Chlornaphazine Coal gasification Coal-tar pitch Cyclophosphamide Magenta manufacture 2-Naphthylamine Rubber industry Schistosoma haematobium (infection) Tobacco smoke ________ Compiled from the IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. The above exposures have been classified into IARC Group-1 (carcinogenic to humans). Coffee There is no clear evidence of carcinogenic effect of coffee or caffeine in experimental animals {1151}, but some epidemiological studies in humans showed elevated risk in coffee drinkers as compared with non-coffee drinkers. {1027}. A recent study showed increased risk of bladder cancer caused by coffee drinking only in never smokers, while no increase of risk was observed in ever smokers {2840}. Artificial sweeteners There is no convincing evidence that artificial sweeteners (such as saccharin) play a role in the etiology of bladder cancer {1877}. The IARC currently classifies saccharin in group 3, i.e. not classifiable as to its carcinogenicity to humans {1155}. Clinical features Signs and symptoms The type and severity of clinical signs and symptoms of infiltrating urothelial carcinoma depends on the extent and location of the tumour. Most patients with urothelial tumours present with at least microscopic hematuria {1718}. The most common presenting symptom of bladder cancer is painless gross hematuria which occurs in 85% of patients {2713}. Subsequent clotting and 94 Tumours of the urinary system
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World Health Organization Classific
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This volume was produced in collabo
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Contents 1 Tumours of the kidney 9
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CHAPTER 1 Tumours of the Kidney Can
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TNM classification of renal cell ca
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one quarter of kidney cancers in bo
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Familial renal cell carcinoma M.J.
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Table 1.02 Genotype - phenotype cor
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A B Fig. 1.11 A Multiple cutaneous
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A B Fig. 1.14 Birt-Hogg-Dubé syndr
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Clear cell renal cell carcinoma D.J
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Fig. 1.20 Clear cell renal cell car
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Papillary renal cell carcinoma B. D
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A B Fig. 1.29 Papillary renal cell
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Fig. 1.33 Chromophobe RCC with sarc
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Carcinoma of the collecting ducts o
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Renal medullary carcinoma C.J. Davi
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Renal carcinomas associated with Xp
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Renal cell carcinoma associated wit
Page 39 and 40: Papillary adenoma of the kidney J.N
Page 41 and 42: of this tumour. Microscopic extensi
Page 43 and 44: A B Fig. 1.59 Metanephric adenoma.
Page 45 and 46: esults in intratumoral aneurysms. O
Page 47 and 48: peritumoural fibrous pseudocapsule.
Page 49 and 50: increases in prevalence to approxim
Page 51 and 52: Nephrogenic rests and nephroblastom
Page 53 and 54: Cystic partially differentiated nep
Page 55 and 56: A B Fig. 1.80 Clear cell sarcoma of
Page 57 and 58: A B Fig. 1.85 Rhabdoid tumour of th
Page 59 and 60: transcription factor is fused to th
Page 61 and 62: Leiomyosarcoma S.M. Bonsib Definiti
Page 63 and 64: Angiomyolipoma G. Martignoni M.B. A
Page 65 and 66: melanocytic and smooth muscle marke
Page 67 and 68: Multinucleated and enlarged ganglio
Page 69 and 70: Haemangioma P. Tamboli Definition H
Page 71 and 72: Fig. 1.107 Juxtaglomerular cell tum
Page 73 and 74: Intrarenal schwannoma I. Alvarado-C
Page 75 and 76: Mixed epithelial and stromal tumour
Page 77 and 78: Synovial sarcoma of the kidney J.Y.
Page 79 and 80: Renal carcinoid tumour L.R. Bégin
Page 81 and 82: Primitive neuroectodermal tumour (E
Page 83 and 84: Paraganglioma / Phaeochromocytoma P
Page 85 and 86: Leukaemia A. Orazi Interstitial inf
Page 87 and 88: WHO histological classification of
Page 89: TNM classification of carcinomas of
Page 93 and 94: Tumour spread and staging Urinary b
Page 95 and 96: feature in such patients undergoing
Page 97 and 98: A Fig. 2.12 Infiltrative urothelial
Page 99 and 100: A Fig. 2.15 A Infiltrating urotheli
Page 101 and 102: A B Fig. 2.19 A Infiltrative urothe
Page 103 and 104: Fig. 2.23 Infiltrative urothelial c
Page 105 and 106: ing systems have been proposed on t
Page 107 and 108: Non-invasive urothelial tumours G.
Page 109 and 110: chronically inflamed urothelium and
Page 111 and 112: Inverted papilloma G. Sauter Defini
Page 113 and 114: muscle invasive disease, but there
Page 115 and 116: Fig. 2.42 Non-invasive urothelial n
Page 117 and 118: A Fig. 2.45 Non-invasive urothelial
Page 119 and 120: for DBCCR1 silencing {984,2476}. Th
Page 121 and 122: Squamous cell carcinoma D.J. Grigno
Page 123 and 124: Fig. 2.51 Squamous cell carcinoma.
Page 125 and 126: Adenocarcinoma A.G. Ayala P. Tambol
Page 127 and 128: A B Fig. 2.61 A Adenocarcinoma in s
Page 129 and 130: A B Fig. 2.65 Intramural urachal ca
Page 131 and 132: Müllerian origin is postulated for
Page 133 and 134: A Fig. 2.69 Small cell carcinoma. A
Page 135 and 136: Carcinoid L. Cheng Definition Carci
Page 137 and 138: Leiomyosarcoma J. Cheville Definiti
Page 139 and 140: Osteosarcoma L. Guillou Definition
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Leiomyoma J. Cheville Definition A
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Haemangioma L. Cheng Definition Hae
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Metastatic tumours and secondary ex
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Tumours of the renal pelvis and ure
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nodular, ulcerative or infiltrative
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Tumours of the urethra F. Hofstädt
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usually show enteric, colloid or si
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CHAPTER 3X Tumours of of the the Pr
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TNM classification of carcinomas of
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contrast, mortality among migrants
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Fig. 3.06 Transrectal ultrasound of
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PSA-related diagnostic strategies.
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A B C Fig. 3.10 A,B Section of pros
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pale-clear, similar to benign gland
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A B Fig. 3.20 A, B Adenocarcinoma w
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prostate adenocarcinomas exhibit AR
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A Fig. 3.27 A, B Foamy gland adenoc
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A B Fig. 3.32 A Sarcomatoid carcino
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A B Fig. 3.37 A Gleason score 1+1=2
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A B Fig. 3.43 A Prostate cancer Gle
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Fig. 3.48 Heat map-nature. From S.M
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Fig. 3.51 Prostate cancer. Major su
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many stage T1b cancers. Stage T2 Mo
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Fig. 3.58 Patterns of seminal vesic
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Prostatic intraepithelial neoplasia
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A B Fig. 3.63 A Micropapillary high
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A B Fig. 3.68 A Ductal carcinoma in
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Ductal adenocarcinoma X.J. Yang L.
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Papillary pattern can be seen in bo
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A B Fig. 3.74 A Inflammation withou
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Squamous neoplasms T.H. Van der Kwa
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Neuroendocrine tumours P.A. di Sant
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Mesenchymal tumours J. Cheville F.
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Fig. 3.89 Sarcoma of the prostate.
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Miscellaneous tumours P.H. Tan L. C
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A Fig. 3.96 A Adenocarcinoma of the
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WHO histological classification of
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Introduction F.K. Mostofi I.A. Sest
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wartime birth cohorts illustrate th
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Similar tumours as those of group 1
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crucial for the development of this
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A B Fig. 4.09 Spermatocytic seminom
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A B Fig. 4.14 Intratubular germ cel
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A B Fig. 4.19 Seminoma. A Typical s
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Fig. 4.24 Seminoma. Vascular invasi
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Fig. 4.28 Spermatocytic seminoma wi
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A B Fig. 4.33 Embryonal carcinoma.
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A B Fig. 4.38 Yolk sac tumour. A En
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have cytoplasmic lacunae that conta
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A Fig. 4.46 Teratoma. A Longitudina
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A B Fig. 4.51 A Cut surface of derm
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Fig. 4.54 Mixed germ cell tumour. L
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Sex cord / gonadal stromal tumours
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A B C Fig. 4.67 Malignant Leydig ce
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A Fig. 4.73 A Sertoli cell tumour.
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ICD-O codes Granulosa cell tumour 8
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ICD-O code 8592/1 Clinical features
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A B Fig. 4.83 Germ cell-sex cord/go
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A Fig. 4.85 A, B Brenner tumour of
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typical grade III follicular morpho
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testicular parenchyma and tumour te
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A B the surgical scar and adjacent
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Immunoprofile Ordóñez and associa
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often have a grey-white cut surface
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Fig. 4.111 Angiomyofibroblastoma-li
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A B Fig. 4.119 Embryonal rhabdomyos
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Table 4.05 Secondary tumours of the
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WHO histological classification of
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A Fig. 5.04 A, B Squamous cell carc
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deformed by an exophytic mass. In s
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A B C Fig. 5.12 A Warty (condylomat
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A Fig. 5.20 Bowenoid papulosis. A,
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three had been circumcized by 9 yea
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Mesenchymal tumours J.F. Fetsch M.
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Fig. 5.31 Neurofibroma of the penis
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oectodermal tumour/Ewing sarcoma [p
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Secondary tumours of the penis C.J.
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Dr John N. EBLE* Dept. of Pathology
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Dr Ricardo PANIAGUA Department of C
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Source of charts and photographs 1.
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References 1. Anon. (1955). Case re
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115. Ariel I, Sughayer M, Fellig Y,
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246. Birt AR, Hogg GR, Dube WJ (197
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374. Cardone G, Malventi M, Roffi M
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502. Corti B, Carella R, Gabusi E,
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633. Donhuijsen K, Schmidt U, Richt
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768. Fischer J, Palmedo G, von Knob
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900. Goedert JJ, Cote TR, Virgo P,
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1028. Hartmann A, Dietmaier W, Hofs
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1162. Iezzoni JC, Fechner RE, Wong
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1293. Keetch DW, Catalona WJ (1995)
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1424. Ladanyi M, Lui MY, Antonescu
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1548. Lopez-Beltran A, Croghan GA,
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1681. McLaughlin JK, Silverman DT,
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CCNB, 226 CCND1, 105, 108 CCND2, 22
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J Juvenile type granulosa cell tumo
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Promoter methylation, 21 Prostate s
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