Invasive breast carcinoma - IARC

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Fibroepithelial tumours J.P. Bellocq G. Magro Definition A heterogeneous group of genuine biphasic lesions combining an epithelial component and a quantitatively predominant mesenchymal component (also called stromal component) which is responsible for the gross appearance. Depending on the benign or malignant nature of each component, various combinations may occur. They are classified into two major categories: fibroadenomas and phyllodes tumours. H a m a rtomas are not fibro e p i t h e l i a l tumours, but represent pseudotumoral changes. As they contain glandular and s t romal tissue, and sometimes may resemble fibroadenomas, they have been included in this chapter. Fibroadenoma Definition A benign biphasic tumour, fibro a d e n o- ma (FA) occurs most frequently in women of childbearing age, especially those under 30. ICD-O code 9010/0 Aetiology Usually considered a neoplasm, some believe FA results from hyperplasia of normal lobular components rather than being a true neoplasm. Clinical features FA presents as a painless, solitary, firm, slowly growing (up to 3 cm), mobile, well defined nodule. Less frequently it may occur as multiple nodules arising sync h ronously or asynchronously in the same or in both breasts and may grow very large (up to 20 cm) mainly when it occurs in adolescents. Such lesions, may be called “giant” fibroadenomas. With the increasing use of screening mammography, small, non-palpable FAs are being discovered. Macroscopy The cut surface is solid, firm, bulging, greyish in colour, with a slightly lobulated A Fig. 1.146 A Fibroadenoma showing lobulated, bulging cut surface. B Fibroadenoma with intracanalicular growth pattern. pattern and slit like spaces. Variations depend on the amount of hyalinization and myxoid change in the stromal component. Calcification of sclerotic lesions is common. Histopathology The admixture of stromal and epithelial proliferation gives rise to two distinct g rowth patterns of no clinical significance. The pericanalicular pattern is the result of proliferation of stromal cells around ducts in a circumferential fashion; this pattern is observed most frequently during the second and third decades of life. The intracanalicular pattern is due to compression of the ducts into clefts by the proliferating stromal cells. The stromal component may sometimes exhibit focal or diffuse hypercellularity (especially in women less than 20 years of age), atypical bizarre multinucleated giant cells {233,2278}, extensive myxoid changes or hyalinization with dystrophic calcification and, rare l y, ossification A B (especially in postmenopausal women). Foci of lipomatous, smooth muscle {1040}, and osteochondroid {1852,2762} metaplasia may rarely occur. Mitotic figures are uncommon. Total infarction has been reported, but rarely. The epithelial component can show a wide spectrum of typical hyperplasia, mainly in adolescents {411,1525,1861, 2250}, and metaplastic changes such as apocrine or squamous metaplasia may be seen. Foci of fibrocystic change, sclerosing adenosis and even extensive myoepithelial proliferation can also occur in FA. In situ lobular, and ductal carcinoma occasionally develop within FA s {693,1525}. Juvenile (or cellular) fibroadenomas are characterized by increased stromal cellularity and epithelial hyperplasia {1861, 2250}. The term giant FA has been used as a synonym for juvenile fibroadenoma by some, but is restricted to massive fibroadenomas with usual histology by others. Fig. 1.147 Juvenile fibroadenoma. A Lobulated sectioned surface in a 8 cm tumour. Patient was 16 years old. B Periductal growth pattern with moderate stromal hypercellularity. B Fibroepithelial tumours 99
Fig. 1.148 Phyllodes tumour. A well circumscribed 6.5 cm mass with a few clefts was histologically benign. Fig. 1.149 Phyllodes tumour. A circumscribed 9 cm tumour contained a large yellow nodule of liposarcoma (yellow) adjacent to a nodule of malignant phyllodes tumour (pink). Differential diagnosis Most FAs, especially those of large size, cellular stroma and epithelial clefts need to be distinguished from phyllodes tumours (see below). Another bre a s t lesion, which can simulate FA, is hamartoma. Prognosis and predictive features Most FAs do not recur after complete surgical excision. In adolescents, there is a tendency for one or more new lesions to develop at another site or even close to the site of the previous surgical t re a t m e n t . The risk of developing cancer within a FA or in breasts of patients pre v i o u s l y t reated for FA is low, although a slightly i n c reased risk has been re p o rted {734, 1 6 4 0 } . Phyllodes tumours Definition A group of circumscribed biphasic tumours, basically analogous to fibroadenomas, characterized by a double l a y e red epithelial component arranged in clefts surrounded by an overgro w i n g h y p e rcellular mesenchymal component typically organized in leaf-like struct u res. Phyllodes tumours (PTs) are usually benign, but recurrences are not uncommon and a relatively small number of patients will develop haematogenous metastases. Depending on the bland or o v e rtly sarcomatous characteristics of their mesenchymal component (also called stromal component), PTs display a morphological spectrum lying between fibroadenomas (FAs) and pure stromal sarcomas. Still widespread in the literature, the generic term “cystosarcoma phyllodes”, is currently considered inappro p r i a t e and potentially dangerous since the majority of these tumours follow a benign course. It is highly preferable to use the neutral term “phyllodes tumour”, according to the view already expressed in the WHO classification of 1981 {3154}, with the adjunction of an adjective determining the putative behaviour based on histological characteristics. ICD-O codes Phyllodes tumour, NOS 9020/1 Phyllodes tumour, benign 9020/0 Phyllodes tumour, borderline 9020/1 Phyllodes tumour, malignant 9020/3 Periductal stromal sarcoma, low grade 9020/3 A Fig. 1.150 Benign phyllodes tumour. A Leaf-like pattern and well defined interface with the surrounding normal tissue. B Higher magnification shows stromal cellularity. B Epidemiology In western countries, PTs account for 0,3- 1% of all primary tumours and for 2,5% of all fibroepithelial tumours of the breast. They occur predominantly in middle- A Fig. 1.151 Malignant phyllodes tumour. A Periductal stromal growth with malignant features. B Note severe stromal atypia and multiple mitoses. B 100 Tumours of the breast
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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
Page 50 and 51: Fig. 1.83 Atypical ductal hyperplas
Page 52 and 53: A B Fig. 1.88 Large excision biopsy
Page 54 and 55: unusual variants as well. Using thi
Page 56 and 57: esemble those identified in invasiv
Page 58 and 59: A B Fig. 1.97 Microinvasive carcino
Page 60 and 61: A Papilloma may be subject to morph
Page 62 and 63: A B C Fig. 1.103 Papillary intraduc
Page 64 and 65: colour measuring from 0.5 to 12 cm.
Page 66 and 67: Immunoprofile The cases studied by
Page 68 and 69: Glycogen-rich, clear cell carcinoma
Page 70 and 71: Differential diagnosis There may be
Page 72 and 73: quality metaphase spreads from an i
Page 74 and 75: Fig. 1.67 Lobular carcinoma of brea
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Page 78 and 79: detected at a late stage as small t
Page 80 and 81: Extent of ductal carcinoma in situ
Page 82 and 83: Benign epithelial proliferations G.
Page 84 and 85: Fig. 1.112 Microglandular adenosis.
Page 86 and 87: A Apocrine adenoma ICD-O code 8401/
Page 88 and 89: A B Fig. 1.128 Adenomyoepithelioma,
Page 90 and 91: Mesenchymal tumours M. Drijkoningen
Page 92 and 93: 1113,1275}. There is a complex patt
Page 94 and 95: A B Fig. 1.137 A Lipoma. Intraparen
Page 96 and 97: Fig. 1.141 Angiosarcoma after breas
Page 98 and 99: A Fig. 1.144 Mammary osteosarcoma.
Page 102 and 103: aged women (average age of presenta
Page 104 and 105: lished data suggests a 21% rate of
Page 106 and 107: A Fig. 1.157 Syringomatous adenoma
Page 108 and 109: Malignant lymphoma and metastatic t
Page 110 and 111: used. Inflammatory conditions in th
Page 112 and 113: male population both in the USA and
Page 114 and 115: CHAPTER 2 Tumours of the Ovary and
Page 116 and 117: Polyembryoma 9072/3 Non-gestational
Page 118 and 119: Surface epithelial-stromal tumours
Page 120 and 121: A Fig. 2.04 A Serous borderline tum
Page 122 and 123: A Fig. 2.06 Serous borderline tumou
Page 124 and 125: A Fig. 2.10 Invasive peritoneal imp
Page 126 and 127: Fig. 2.15 Mucinous carcinoma with i
Page 128 and 129: Fig. 2.20 Mucinous endocervical-lik
Page 130 and 131: A Fig. 2.28 Mucinous cystic tumour
Page 132 and 133: early secretory endometrium {2605}.
Page 134 and 135: IV, 6% {2233}. Patients with grade
Page 136 and 137: A Fig. 2.37 A This polypoid intracy
Page 138 and 139: Fig. 2.40 Endometrioid cyst with at
Page 140 and 141: 1 tumours are extremely rare. Almos
Page 142 and 143: Fig. 2.50 Borderline Brenner tumour
Page 144 and 145: express thrombomodulin and have bee
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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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in their Asian population {2957}. I
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have a strong association with high
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e red by squamous epithelium {380}.
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endometrioid adenocarcinoma of the
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metrial epithelium. In some cases t
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with distinct cell borders and a gr
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Mesenchymal tumours M.L. Carcangiu
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{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,
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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
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MPNST, see Malignant peripheral ner
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Small cell / oat cell carcinoma, 32
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