Invasive breast carcinoma - IARC

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type) is a highly diff e rentiated lesion resembling well differentiated squamous cell carcinoma in which the atypia is most prominent in or confined to the basal and parabasal layers of the epithelium, where the cells have abundant cytoplasm and form pearls and the nuclei are relatively uniform in size and contain coarse chromatin and prominent nucleoli {3175}. Somatic genetics The only cytogenetically analysed case of VIN 3 (squamous cell carcinoma in situ) of the vulva had a rearrangement of 11p as the sole anomaly {2818}. Genomic deletions have been demonstrated in the simplex (diff e re n t i a t e d ) form of VIN and its subsequent squamous carcinoma unrelated to HPV infection {1663}. These also express TP53 {1824,3175}. Prognosis and predictive factors VIN is usually treated by local excision. Laser or other ablative procedure may also have a role {1197,1369,3124}. Spontaneous regression of VIN 2 and 3 in younger women with papular pigmented lesions is recognized, and such lesions are re f e r red to clinically as Fig. 7.07 Condyloma acuminatum. Papillary fronds with fibrovascular cores are lined by squamous epithelium with hyperkeratosis, acanthosis and koilocytosis. bowenoid papulosis by some investigators {1369}. The recurrence of VIN is well recognized, especially in women who are heavy cigarette smokers or positive for HIV. Condyloma acuminatum Definition A benign neoplasm characterized by papillary fronds containing fibrovascular cores and lined by stratified squamous epithelium with evidence of HPV infection, usually in the form of koilocytosis. Tumour spread and staging Co-infection of the vulva and cervix is well recognized {1528}. Vulvar carcinoma in young women has been associated with genital condyloma {2945}. Fig. 7.08 Vestibular papilloma. Smooth surfaced squamous epithelium without acanthosis or koilocytotic atypia lines a delicate fibrovascular s t a l k . Histopathology The lesions are typically multiple and papillomatous or papular. The epithelium is acanthotic with parabasal hyperplasia and koilocytosis in the upper portion. Hyperkeratosis and parakeratosis are usual, and binucleated and multinucleated keratinocytes are often present. The rete ridges are elongated and thickened. A chronic inflammatory infiltrate is usually present within the underlying connective tissue. HPV infection in the vulvar epithelium is expressed in three broad categories: (1) Fully expressed, with morphological features of HPV infection, as seen in condyloma acuminatum (2) Minimally expressed, with only mild morphological changes, e.g. koilocytosis (3) Latent, in which no characteristic morphological changes are seen, although HPV can be detected with the use of molecular techniques {1013}. Vestibular papilloma Definition A benign papillary tumour with a squamous epithelial mucosal surface that overlies a delicate fibrovascular stalk. Synonyms M i c ropapillomatosis labialis, vestibular micropapillomatosis. These terms are applicable when numerous lesions are present. Clinical features The lesions may be solitary but frequently are multiple, often occurring in clusters near the hymenal ring, resulting in a condition referred to as vestibular papillomatosis or micropapillomatosis or m i c ropapillomatosis labialis {238,644, 980,1930,2277}. They are less than 6 mm in height. Unlike condylomas, they do not typically respond to podophyllin and/or interferon {2277}. Histopathology These lesions have papillary architecture and a smooth surface without acanthosis or koilocytotic atypia. They lack the complex arborizing architecture of condyloma. Aetiology The great majority of studies of vestibular m i c ropapillomatosis as defined above have demonstrated no relationship of these lesions to HPV {238,644,1856, 2118,2277}. Fibroepithelial polyp Definition A polypoid lesion covered by squamous epithelium and containing a central core of fibrous tissue in which stellate cells with tapering cytoplasmic processes and 320 Tumours of the vulva
A B Fig. 7.09 Fibroepithelial polyp of the vulva. A The central core of fibrous tissue contains thin-walled vessels. The epithelium is not acanthotic. B Stratified squamous epithelium covers dense fibrous stroma. C Note the scattered bizarre multinucleated giant cells in the stroma. C i r regularly shaped thin-walled vessels are prominent features. Histopathology These polypoid lesions are characterized by a prominent fibrovascular stroma covered by squamous epithelium without evidence of koilocytosis. In contrast to vulvar condylomas, fibroepithelial polyps do not show epithelial acanthosis or papillary architecture. Bizarre stromal cells have been described in these polyps that do not influence behaviour {416}. Aetiology In contrast to condylomas, fibroepithelial polyps appear unrelated to HPV infection and rarely contain HPV nucleic acids {1837}. Prognosis and predictive factors Although benign, the lesion may recur if incompletely excised {2141}. Seborrheic keratosis and inverted follicular keratosis Definition A benign tumour characterized by pro l i f- eration of the basal cells of the squamous epithelium with acanthosis, hyperkeratosis and the formation of keratin-filled p s e u d o h o rn cysts. Some cases may have an incidental HPV infection {3263}. Inverted follicular keratosis is a seborrheic keratosis of follicular origin and contains prominent squamous eddies. An inverted follicular keratosis of the vulva has been reported that may have been related to close shaving {2467}. Keratoacanthoma This rare squamoproliferative lesion commonly occurs on sun-exposed skin. It is thought to arise from follicular epithelium and was originally considered to be benign. It has a central keratin-filled crater and focal infiltration at its dermal interface. In some instances the lesion re g resses spontaneously {2361}. Tw o cases have been described in the vulva {997}. At present the lesion originally described as keratoacanthoma is generally accepted as a well differentiated squamous cell carcinoma, keratoacanthoma type {1227}, and the latter diagnosis is recommended (see section on squamous cell carcinoma). Glandular tumours ICD-O codes Paget disease 8542/3 Bartholin gland tumours Adenocarcinoma 8140/3 Squamous cell carcinoma 8070/3 Adenoid cystic carcinoma 8200/3 Adenosquamous carcinoma 8560/3 Small cell carcinoma 8041/3 Transitional cell carcinoma 8120/3 Adenoma 8140/0 Adenomyoma 8932/0 Papillary hidradenoma 8405/0 Adenocarcinoma of Skene gland origin 8140/3 Adenoma of minor vestibular glands 8140/0 Mixed tumour of the vulva 8940/0 Vulvar Paget disease Definition An intraepithelial neoplasm of cutaneous origin expressing apocrine or eccrine glandular-like features and characterized by distinctive large cells with prominent cytoplasm referred to as Paget cells. It may also be derived from an underlying skin appendage adenocarcinoma or anorectal or urothelial carcinoma {3121}. Epidemiology Primary cutaneous Paget disease is an uncommon neoplasm, usually of postmenopausal White women. In approximately 10-20% of women with vulvar Paget disease, there is an invasive component or an underlying skin appendage adenocarcinoma {825,3121}. Clinical features Paget disease typically presents as a symptomatic red, eczematoid lesion that may clinically resemble a derm a t o s i s {1028,3121,3267}. Paget disease that is related to anorectal adenocarc i n o m a Epithelial tumours 321
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Previous volumes in this series Kle
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World Health Organization Classific
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Published by IARC Press, Internatio
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CHAPTER 1 Tumours of the Breast Can
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TNM classification of carcinomas of
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Invasive breast carcinoma I.O. Elli
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Rapid growth and greater adult heig
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tives, administrative and clerical
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Grade 1 - well differentiated: 3-5
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ent and this is occasionally extens
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Most melanotic tumours of the breas
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A Fig. 1.22 A Classic invasive lobu
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yet others at 90% {97,2147}. For pr
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Fig. 1.27 Medullary carcinoma. The
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myoepithelial cells in fibro a d e
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A Fig. 1.33 Neuroendocrine carcinom
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Macroscopy Fisher et al. reported t
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Fig. 1.39 Apocrine carcinoma. Note
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cells contain intracytoplasmic lume
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A Fig. 1.50 Carcinosarcoma. A Two a
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A B C Fig. 1.75 Lobular neoplasia.
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Intraductal proliferative lesions F
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A B absence of either microcalcific
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Fig. 1.83 Atypical ductal hyperplas
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A B Fig. 1.88 Large excision biopsy
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unusual variants as well. Using thi
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esemble those identified in invasiv
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A B Fig. 1.97 Microinvasive carcino
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A Papilloma may be subject to morph
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A B C Fig. 1.103 Papillary intraduc
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colour measuring from 0.5 to 12 cm.
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Immunoprofile The cases studied by
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Glycogen-rich, clear cell carcinoma
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Differential diagnosis There may be
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quality metaphase spreads from an i
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Fig. 1.67 Lobular carcinoma of brea
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detectable distant metastasis displ
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detected at a late stage as small t
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Extent of ductal carcinoma in situ
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Benign epithelial proliferations G.
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Fig. 1.112 Microglandular adenosis.
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A Apocrine adenoma ICD-O code 8401/
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A B Fig. 1.128 Adenomyoepithelioma,
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Mesenchymal tumours M. Drijkoningen
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1113,1275}. There is a complex patt
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A B Fig. 1.137 A Lipoma. Intraparen
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Fig. 1.141 Angiosarcoma after breas
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A Fig. 1.144 Mammary osteosarcoma.
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Fibroepithelial tumours J.P. Belloc
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aged women (average age of presenta
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lished data suggests a 21% rate of
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A Fig. 1.157 Syringomatous adenoma
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Malignant lymphoma and metastatic t
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used. Inflammatory conditions in th
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male population both in the USA and
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CHAPTER 2 Tumours of the Ovary and
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Polyembryoma 9072/3 Non-gestational
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Surface epithelial-stromal tumours
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A Fig. 2.04 A Serous borderline tum
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A Fig. 2.06 Serous borderline tumou
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A Fig. 2.10 Invasive peritoneal imp
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Fig. 2.15 Mucinous carcinoma with i
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Fig. 2.20 Mucinous endocervical-lik
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A Fig. 2.28 Mucinous cystic tumour
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early secretory endometrium {2605}.
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IV, 6% {2233}. Patients with grade
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A Fig. 2.37 A This polypoid intracy
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Fig. 2.40 Endometrioid cyst with at
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1 tumours are extremely rare. Almos
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Fig. 2.50 Borderline Brenner tumour
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express thrombomodulin and have bee
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serous and transitional cell carcin
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is yellow to tan with a variable ad
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Genetic susceptibility JGCTs may pr
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Clinical features F i b romas may b
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distinguishes this tumour from the
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A Fig. 2.77 A Retiform Sertoli-Leyd
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Mean ages of 21 and 38 years and me
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Tumours unassociated with PJS form
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mal origin without crystals of Rein
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Germ cell tumours F. Nogales A. Tal
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cases, anisokaryosis has no prognos
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ation may coexist in the same neopl
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Table 2.06 Grading of ovarian immat
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A B Fig. 2.102 A Mature cystic tera
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Diagnostic procedures Elevated urin
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associated with mature teratomas sh
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atives intimately admixed. The germ
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Fig. 2.113 Mixed germ cell-sex cord
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A Fig. 2.116 A Adenomatous hyperpla
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Fig. 2.117 Small cell carcinoma, hy
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Clinical features Adenoid cystic-li
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Histopathology This epithelial tumo
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sis. Corpus luteum of pregnancy has
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Lymphomas and leukaemias L.M. Roth
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Secondary tumours of the ovary J. P
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Occasionally, the colonic adenocarc
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Peritoneal tumours S.C. Mok J.O. Sc
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A B Fig. 2.140 Cystic adenomatoid m
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whelmingly poor {1038,1547,2310}. H
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CHAPTER 3 Tumours of the Fallopian
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TNM and FIGO classification of carc
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Endometrioid adenocarcinoma Endomet
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Two examples of adenofibroma of bor
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A Fig. 3.11 Adenomatoid tumour. A T
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Clinical features Patients range in
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Fig. 3.16 Uterus-like mass. The cys
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CHAPTER 4 Tumours of the Uterine Co
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TNM and FIGO classification of non-
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Epithelial tumours and related lesi
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endometrioid adenocarcinoma fro m a
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fers from the prototypical type I e
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the ovary and bladder. Unlike prima
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schema {1535,2602}. Although this c
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Table 4.03 Altered gene function in
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Mesenchymal tumours and related les
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areas are limited to less than 30%
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A B C Fig. 4.30 Leiomyosarcoma. A T
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e used sparingly and is reserved fo
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A B Fig. 4.38 Leiomyoma with perino
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cytological atypia, tumour cell nec
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Mixed epithelial and mesenchymal tu
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Prognosis and predictive factors Th
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tumours may superficially invade th
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A Fig. 4.46 A Gestational choriocar
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A Fig. 4.49 A Classic complete hyda
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Sex cord-like, neuroectodermal and
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Secondary tumours of the uterine co
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WHO histological classification of
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Epithelial tumours M. Wells J.M. Ne
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Fig. 5.04 Mechanisms of human papil
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Fig. 5.08 Keratinizing squamous cel
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Page 272 and 273: e red by squamous epithelium {380}.
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Page 276 and 277: metrial epithelium. In some cases t
Page 278 and 279: with distinct cell borders and a gr
Page 280 and 281: Mesenchymal tumours M.L. Carcangiu
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Page 284 and 285: Mixed epithelial and mesenchymal tu
Page 286 and 287: Fig. 5.44 Wilms tumour. The tumour
Page 288 and 289: A Fig. 5.47 Implant of endometrial
Page 290 and 291: CHAPTER 6 Tumours of the Vagina Alt
Page 292 and 293: Epithelial tumours E.S. Andersen A.
Page 294 and 295: Aetiology The fact that both VAIN a
Page 296 and 297: Fig. 6.10 Fibroepithelial polyp.A m
Page 298 and 299: er of mitoses varies but is usually
Page 300 and 301: ICD-O codes Adenosquamous carcinoma
Page 302 and 303: A C Fig. 6.17 Sarcoma botryoides. A
Page 304 and 305: 1-11 cm. They may arise anywhere in
Page 306 and 307: elsewhere in the female genital tra
Page 308 and 309: A Fig. 6.24 Yolk sac tumour. A The
Page 310 and 311: g rowing in sheets. Some may have s
Page 312 and 313: WHO histological classification of
Page 314 and 315: Epithelial tumours E.J. Wilkinson M
Page 316 and 317: even with additional sectioning, it
Page 320 and 321: Clinical features Bartholin gland c
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Page 324 and 325: Mesenchymal tumours R.L. Kempson M.
Page 326 and 327: Table 7.03 Differential diagnosis o
Page 328 and 329: Prognosis and predictive factors A
Page 330 and 331: Table 7.04 Clark levels of cutaneou
Page 332 and 333: A Fig. 7.23 Vulvar peripheral primi
Page 334 and 335: Familial aggregation of cancers of
Page 336 and 337: BRCA1 syndrome Definition Inherited
Page 338 and 339: dispose individuals to the developm
Page 340 and 341: Fig. 8.05 To assess whether wild-ty
Page 342 and 343: Fig. 8.07 Factors that modify risk
Page 344 and 345: BRCA2 syndrome R. Eeles S. Piver S.
Page 346 and 347: tubal or ovarian carcinomas. Howeve
Page 348 and 349: in typical nuclear foci that may re
Page 350 and 351: Breast tumours Frequency Breast can
Page 352 and 353: Fig. 8.14 Codon distribution of som
Page 354 and 355: Breast tumours Age distribution and
Page 356 and 357: Hereditary non-polyposis colon canc
Page 358 and 359: essary in the evaluation of the pat
Page 360 and 361: Age distribution and penetrance Mos
Page 362 and 363: Contributors Dr Vera M. ABELER** De
Page 364 and 365: Dr Carlo LA VECCHIA Laboratory of E
Page 366 and 367: Dr Manuel TEIXEIRA Department of Ge
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02.100 Dr. A. Ostor 02.101 Dr. F.A.
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52. Akhtar M, Robinson C, Ashraf Al
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180. Bapat K, Brustein S (1989). Ut
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307. Bolis GB, Maccio T (2000). Cle
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436. Chang J, Sharpe JC, A'Hern RP,
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562. Costa MJ, Ames PF, Walls J, Ro
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689. Di Domenico A, Stangl F, Benni
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820. Falck J, Petrini JH, Williams
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943. Gad A, Azzopardi JG (1975). Lo
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1067. Grimes MM (1992). Cystosarcom
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1197. Herod JJ, Shafi MI, Rollason
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1323. Jacques SM, Qureshi F, Ramire
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1449. Khalifa MA, Mannel RS, Harawa
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1564. Lagios MD (1977). Multicentri
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1687. Loman N, Johannsson O, Kristo
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1807. McCluggage G, McBride H, Maxw
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1937. Mukai M, Torikata C, Iri H (1
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2056. Norris HJ, Taylor HB (1967).
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2180. Park JS, Jones RW, McLean MR,
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2304. Puls LE, Hamous J, Morrow MS,
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2 4 3 4 . Rosen PP, Groshen S, Saig
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2559. Schlesinger C, Silverberg SG
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2686. Silverberg SG (1999). Protoco
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2806. Stutz JA, Evans AJ, Pinder S,
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2942. Tornos C, Silva EG, Ordonez N
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3061. Wargotz ES, Norris HJ (1990).
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3189. Yoshioka T, Tanaka T (2000).
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References 425
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Biphasic teratomas, 168 BLM, 341, 3
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G GADD45, 343, 353 GCDFP-15, 25, 33
Page 428 and 429:
MPNST, see Malignant peripheral ner
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Small cell / oat cell carcinoma, 32
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