Invasive breast carcinoma - IARC

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Mesenchymal tumours and related lesions M.R. Hendrickson F.A. Tavassoli R.L. Kempson W.G. McCluggage U. Haller R.A. Kubik-Huch Definition Uterine mesenchymal tumours are derived from the mesenchyme of the corpus consisting of endometrial stroma, smooth muscle and blood vessels or a d m i x t u res of these. Rare l y, these tumours may show mesenchymal differentiation that is foreign to the uterus. Epidemiology The most common malignant mesenchymal tumours of the uterine corpus are leiomyosarcoma and endometrial stromal tumours, and both are more frequent in Black than in White women {1139, 1729}. Clinical features Signs and symptoms The most common presentation for mesenchymal tumours is uterine enlargement, abnormal uterine bleeding or pelvic pain. Imaging Non-invasive imaging, usually by ultrasound, but occasionally by magnetic resonance imaging (MRI), can be utilized in selected cases to distinguish between a solid ovarian tumour and a pedunculated leiomyoma or to distinguish leiomyomas from adenomyosis. On MRI leiomyomas present as well delineated lesions of low signal intensity on T1 and T2-weighted images. They may, however, undergo degenerative changes resulting in various, non-specific MRI appearances {1947,2971}. On MRI the presence of a large, heterogeneous mass with irregular contours should raise concern for sarcoma. Endometrial stromal and related tumours Definition and historical annotation Endometrial mesenchymal tumours in their better-differentiated forms are composed of cells resembling those of proliferative phase endometrial stro m a . N u m e rous thin-walled small art e r i o l a r type (plexiform) vessels are characteristically present. Endometrial stromal sarcomas (ESS) have been traditionally divided into low and high grade types based on mitotic count. However, since high grade endometrial sarcomas lack specific diff e rentiation and bear no histological resemblance to endometrial stroma, it has been proposed that they be designated undiff e rentiated endometrial or uterine sarcoma {811}. In this classification the distinction between low grade ESS and undiff e rentiated endometrial sarcoma is not made on the basis of mitotic count but on features such as nuclear pleomorphism and necrosis. ICD-O codes Endometrial stromal sarcoma, low grade 8931/3 Endometrial stromal nodule 8930/0 Undifferentiated endometrial sarcoma 8930/3 Histopathology Endometrial stromal tumours are composed of cells resembling those of proliferative endometrial stroma and are far less frequent than smooth muscle tumours. Endometrial stromal tumours are subdivided into benign and malignant groups based on the type of tumour margin {1432,2054,2097,2883}. Those with pushing margins are benign stromal nodules, whereas those with infiltrating margins qualify as stromal sarcomas. There is general agreement on the morphologic definition of typical cases of both low grade ESS and undifferentiated endometrial sarcoma. Characteristically, low grade ESS, a clinically indolent neoplasm, features a plexiform vasculature, minimal cytological atypia and infrequent mitotic figures. The usual undifferentiated sarcoma, a highly aggressive neoplasm, lacks a plexiform vasculature, features substantial cytological atypia and has frequent and often atypical mitotic figures. However, there is no valid evidence that the isolated finding of a mitotic index of 10 or more per 10 high power fields is an adverse prognostic finding in a neoplasm that is otherwise a typical low grade ESS. A small minority of cases share features of low grade ESS and undifferentiated sarcoma, and their classification is controversial. Immunoprofile The neoplastic cells of both the stromal nodule and low grade ESS are i m m u n o reactive for vimentin, CD10 A B Fig. 4.25 Low grade endometrial stromal sarcoma (ESS). A Worm-like, soft, yellow masses focally replace the myometrium. B The myometrium is extensively infil - trated by basophilic islands of low grade ESS. C A tongue of low grade ESS protrudes into a vascular space. C Mesenchymal tumours and related lesions 233
A Fig. 4.26 Low grade endometrial stromal sarcoma (ESS). A There is a proliferation of endometrial stromal cells lacking atypia around spiral arteriole-like blood vessels. B Note a sex cord-like pattern in a low grade ESS. B {486,1821} and at least focally for actin {914}. They are usually, but not always {914}, negative for desmin and h-caldesmon {2065,2101,2488}. Low grade ESS is almost always positive for both estrogen and progesterone receptors. {1411,2350,2502}. Rarely, low grade endometrial stromal tumours, particularly those with areas displaying a sex cord pattern, may be positive for alpha-inhibin {1521}, CD99 {167} and cytokeratin {29}. The sex cord areas may also be immunoreactive for desmin, whereas the s u r rounding endometrial stromal cells are not {678,1661}. Somatic genetics Fusion of two zinc finger genes (JAZF1 and JJAZ1) by translocation t(7;17) is present in most low grade endometrial s t romal tumours {1189,1252,1503}. Endometrial stromal nodules and low grade ESSs are typically diploid with a low S-phase fraction {292,1220}. Prognosis and predictive factors The histological distinction between u n d i ff e rentiated endometrial sarc o m a and low grade ESS has import a n t implications re g a rding pro g n o s i s {2601} Low grade ESSs are indolent tumours with a propensity for local re c u r rence, usually many years after h y s t e re c t o m y. Distant metastases are less common. In contrast, undiff e re n t i- ated endometrial sarcomas are highly a g g ressive tumours with the majority of patients presenting with extrauterine disease at the time of diagnosis and dying within two years of diagnosis { 2 3 2 , 8 1 1 } . Endometrial stromal sarcoma, low grade Definition This tumour fits the definition of endometrial stromal tumour presented above and is distinguished from the stromal nodule on the basis of myometrial infiltration and/or vascular space invasion. Epidemiology Low grade ESS is a rare tumour of the uterus accounting for only 0.2% of all genital tract malignant neoplasms {645, 1509,1745}. In general low grade ESSs affect younger women than other uterine malignancies; studies have demonstrated that the mean age ranges from 42-58 years, and 10-25% of patients are premenopausal {437,645}. Clinical features The clinical features have been discussed above. Macroscopy Low grade ESS may present as a solitary, well delineated and predominantly intramural mass, but extensive permeation of the myometrium is more common, with extension to the serosa in approximately half of the cases. The sectioned surface appears yellow to tan, and the tumour has a softer consistency than the usual leiomyoma. Cystic and myxoid degeneration as well as necrosis and haemorrhage are seen occasionally. Localization Metastases are rarely detected prior to the diagnosis of the primary lesion {29,684,3222}. Extrauterine extension is present in up to a third of the women with low grade ESS at the time of hysterectomy. The extension may appear as wormlike plugs of tumour within the vessels of the broad ligament and adnexa. Histopathology Low grade ESS is usually a densely cellular tumour composed of uniform, oval to spindle-shaped cells of endometrial s t romal-type; by definition significant atypia and pleomorphism are absent. Although most tumours are paucimitotic, mitotic rates of 10 or more per 10 high power fields can be encountered, and a high mitotic index does not in itself alter the diagnosis. A rich network of delicate small arterioles resembling the spiral arterioles of the late secretory endometrium supports the proliferating cells. Cells with foamy cytoplasm (tumour cells, foamy histiocytes, or both) are prominent in some cases. Endometrial type glands occur in 11-40% of endometrial stromal tumours {516,1343,2054}. Sex cord-like s t r u c t u res may also be found {511}. Myxoid and fibrous change may occur focally or diffusely {2054,2102}. Perivascular hyalinization and a stellate pattern of hyalinization occur in some cases. Reticulin stains usually reveal a dense network of fibrils surrounding individual cells or small groups of cells. Necrosis is typically absent or inconspicuous. Focal smooth muscle diff e re n t i a t i o n (spindle or epithelioid) or cells with differentiation that is ambiguous between stromal and smooth muscle cells may develop in endometrial stromal tumours; these 234 Tumours of the uterine corpus
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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
Page 184 and 185: Fig. 2.117 Small cell carcinoma, hy
Page 186 and 187: Clinical features Adenoid cystic-li
Page 188 and 189: Histopathology This epithelial tumo
Page 190 and 191: sis. Corpus luteum of pregnancy has
Page 192 and 193: Lymphomas and leukaemias L.M. Roth
Page 194 and 195: Secondary tumours of the ovary J. P
Page 196 and 197: Occasionally, the colonic adenocarc
Page 198 and 199: Peritoneal tumours S.C. Mok J.O. Sc
Page 200 and 201: A B Fig. 2.140 Cystic adenomatoid m
Page 202 and 203: whelmingly poor {1038,1547,2310}. H
Page 204 and 205: CHAPTER 3 Tumours of the Fallopian
Page 206 and 207: TNM and FIGO classification of carc
Page 208 and 209: Endometrioid adenocarcinoma Endomet
Page 210 and 211: Two examples of adenofibroma of bor
Page 212 and 213: A Fig. 3.11 Adenomatoid tumour. A T
Page 214 and 215: Clinical features Patients range in
Page 216 and 217: Fig. 3.16 Uterus-like mass. The cys
Page 218 and 219: CHAPTER 4 Tumours of the Uterine Co
Page 220 and 221: TNM and FIGO classification of non-
Page 222 and 223: Epithelial tumours and related lesi
Page 224 and 225: endometrioid adenocarcinoma fro m a
Page 226 and 227: fers from the prototypical type I e
Page 228 and 229: the ovary and bladder. Unlike prima
Page 230 and 231: schema {1535,2602}. Although this c
Page 232 and 233: Table 4.03 Altered gene function in
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Page 238 and 239: A B C Fig. 4.30 Leiomyosarcoma. A T
Page 240 and 241: e used sparingly and is reserved fo
Page 242 and 243: A B Fig. 4.38 Leiomyoma with perino
Page 244 and 245: cytological atypia, tumour cell nec
Page 246 and 247: Mixed epithelial and mesenchymal tu
Page 248 and 249: Prognosis and predictive factors Th
Page 250 and 251: tumours may superficially invade th
Page 252 and 253: A Fig. 4.46 A Gestational choriocar
Page 254 and 255: A Fig. 4.49 A Classic complete hyda
Page 256 and 257: Sex cord-like, neuroectodermal and
Page 258 and 259: Secondary tumours of the uterine co
Page 260 and 261: WHO histological classification of
Page 262 and 263: Epithelial tumours M. Wells J.M. Ne
Page 264 and 265: Fig. 5.04 Mechanisms of human papil
Page 266 and 267: Fig. 5.08 Keratinizing squamous cel
Page 268 and 269: in their Asian population {2957}. I
Page 270 and 271: have a strong association with high
Page 272 and 273: e red by squamous epithelium {380}.
Page 274 and 275: endometrioid adenocarcinoma of the
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
Page 282 and 283: {781}, liposarcoma {2840,3016}, ost
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Mixed epithelial and mesenchymal tu
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Fig. 5.44 Wilms tumour. The tumour
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A Fig. 5.47 Implant of endometrial
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CHAPTER 6 Tumours of the Vagina Alt
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Epithelial tumours E.S. Andersen A.
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Aetiology The fact that both VAIN a
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Fig. 6.10 Fibroepithelial polyp.A m
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er of mitoses varies but is usually
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ICD-O codes Adenosquamous carcinoma
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A C Fig. 6.17 Sarcoma botryoides. A
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1-11 cm. They may arise anywhere in
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elsewhere in the female genital tra
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A Fig. 6.24 Yolk sac tumour. A The
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g rowing in sheets. Some may have s
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WHO histological classification of
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Epithelial tumours E.J. Wilkinson M
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even with additional sectioning, it
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type) is a highly diff e rentiated
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Clinical features Bartholin gland c
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glandular elements surrounded by fi
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Mesenchymal tumours R.L. Kempson M.
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Table 7.03 Differential diagnosis o
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Prognosis and predictive factors A
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Table 7.04 Clark levels of cutaneou
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A Fig. 7.23 Vulvar peripheral primi
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Familial aggregation of cancers of
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BRCA1 syndrome Definition Inherited
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dispose individuals to the developm
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Fig. 8.05 To assess whether wild-ty
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Fig. 8.07 Factors that modify risk
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BRCA2 syndrome R. Eeles S. Piver S.
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tubal or ovarian carcinomas. Howeve
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in typical nuclear foci that may re
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Breast tumours Frequency Breast can
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Fig. 8.14 Codon distribution of som
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Breast tumours Age distribution and
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Hereditary non-polyposis colon canc
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essary in the evaluation of the pat
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Age distribution and penetrance Mos
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Contributors Dr Vera M. ABELER** De
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Dr Carlo LA VECCHIA Laboratory of E
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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,
Page 378 and 379:
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
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MPNST, see Malignant peripheral ner
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Small cell / oat cell carcinoma, 32
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