Invasive breast carcinoma - IARC

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cells contain intracytoplasmic lumens c o n f i rming a glandular cell population. Adenosquamous carcinoma Definition An invasive carcinoma with areas of well developed tubule/gland formation intimately admixed with often widely dispersed solid nests of squamous diff e- re n t i a t i o n . ICD-O code 8560/3 Histopathology While focal squamous diff e re n t i a t i o n has been observed in 3.7% of infiltrating duct carcinomas {878}, a pro m i- nent admixture of invasive ductal and squamous cell carcinoma is rarely observed. The squamous component is often keratinizing, but ranges from very well diff e rentiated keratinizing areas to poorly diff e rentiated non-keratinizing foci. Eight tumours described as examples of low grade m u c o e p i d e rmoid carc i n o m a, comparable to those occuring in the s a l i v a ry glands, have been re p o rted in the breast; these behave as low grade carcinomas {1130,1156,1515, 1 6 2 9 , 1 7 0 9 , 2 1 9 1 , 2 2 3 4 } . Fig. 1.46 Adenosquamous carcinoma. Both glandular and squamous differentiation coexist in this carcinoma. Immunoprofile The squamous component is negative for both ER and PR, while the positivity of the ductal carcinoma component for ER and PR depends on its degree of d i ff e re n t i a t i o n . Low grade adenosquamous carcinoma Low grade adenosquamous carc i n o m a {2431} is a variant of metaplastic carc i- noma which is morphologically similar to adenosquamous carcinoma of the skin and has been classified by some as syringomatous squamous tumour {2816}. The same lesion has been interpreted as an infiltrating syringomatous adenoma by others who prefer to avoid designation of carcinoma for a group of lesions which mainly recur after local excision. ICD-O code 8560/1 Synonym Infiltrating syringomatous adenoma. This entity is also discussed in Tumours of the Nipple. Fig. 1.47 Low grade adenosquamous carcinoma / infiltrating syringomatous adenoma. A highly infiltrative growth pattern is responsible for the high frequency of local recurrence associated with many lesions. Clinical features The age range at presentation is wide. These lesions usually present as a small palpable mass between 5 and 80 mm in size. Histology These tumours are composed of small glandular structure and solid cords of epithelial cells haphazardly arranged in an infiltrative spindle celled stromal component {2421,2995}. The proportions of these three components is variable between cases. The solid nests of cells may contain squamous cells, squamous pearls or squamous cyst formation. The s t roma is typically "fibro m a t o s i s - l i k e " being cellular and composed of bland spindle cells. The stromal component can, however, be collagenous, hyalinized or variably cellular, and osteocartilagenous foci can occur rarely. It has been recognized that some low grade adenosquamous carcinomas may be found in association with a central sclerosing proliferation such as a radial scar, sclerosing papillary lesion or sclerosing adenosis {672,2421,2995}. The frequen- Invasive breast cancer 39
Fig. 1.48 Mucoepidermoid carcinoma.This low grade invasive carcinoma is morphologically similar to its counterpart in the salivary glands. cy of ductal carcinoma in situ in association with adenosquamous carcinomas is variable. These tumours lack estrogen receptor expression {672,3142}. Prognosis and predictive factors The majority of case have an excellent p rognosis, but a pro p o rtion of cases can behave in a locally aggressive manner {2995}, re c u r rence appears to be re l a t e d to adequacy of local excision. Ly m p h node metastatic spread is extremely rare and noted in a single case that was 3.5 cm {2995}. Mixed epithelial / mesenchymal metaplastic carcinomas ICD-O code 8575/3 Synonyms C a rcinoma with osseous metaplasia (8571/3), carcinoma with chondro i d metaplasia (8571/3), matrix producing carcinoma, carcinosarcoma (8980/3). Histopathology This wide variety of tumours, some of which are also re g a rded as "matrix producing carcinomas" {1414,2953}, show infiltrating carcinoma mixed with often h e t e rologous mesenchymal elements ranging from areas of bland chondro i d and osseous diff e rentiation to frank s a rcoma (chondro s a rcoma, osteosarcoma, rhabdomyosarcoma, liposarc o- ma, fibro s a rcoma). When the mesenchymal component is malignant, the designation of carc i n o s a rcoma is used. U n d i ff e rentiated spindle cell elements may form part of the tumour. Grading is based mainly on nuclear features and, to a lesser degree, cytoplasmic diff e r- e n t i a t i o n . Immunoprofile The spindle cell elements may show positive reactivity for cytokeratins, albeit focally. Chondroid elements are frequently S-100 positive and may coexpress cytokeratins, but are negative for actin. Many of these tumours are negative for ER and PR both in the adenocarcinoma and the mesenchymal areas, but the adenocarcinoma component may be ER and PR positive if well to moderately diff e rentiated. In carc i n o s a rcomas, the mesenchymal component fails to immunoreact with any epithelial marker. Differential diagnosis The differential diagnosis varies for the different subtypes of metaplastic carcinoma. Angiosarcoma may be confused with the acantholytic variant of squamous cell carcinoma, but focal areas of squamous differentiation can be found when sampled thoroughly. A negative immunoreaction with vascular endothelial markers and a positive reaction with cytokeratins will support the diagnosis of an epithelial neoplasm. Fibromatosis and a variety of spindled mesenchymal tumours may be confused with spindle cell squamous carcinoma; these are all generally negative for epithelial markers. Myoepithelial carcinoma is the most difficult lesion to distinguish from spindle cell squamous carcinoma. The former often has ducts with prominent to hyperplastic myoepithelial cells at its periphery, while the latter may have clear cut focal squamous differentiation. Reactions to a variety of immunostains may be similar, with the possible exception of those myoepithelial carcinomas that are diffusely S-100 positive. Electron microscopy may be needed to distinguish some of these lesions. Squamous carcinoma cells have abundant tonofilaments and well developed desmosomes whether spindled or polygonal. Intercellular bridges are abundant in the well differentiated areas In contrast, the spindle cell myoepithelial carcinomas often have pinocytotic vesicles, myofibrils and basal lamina in addition to tonofilaments and desmosomes. A B Fig. 1.49 A Metaplastic carcinoma with chondroid differentiation, 77 year old patient, mastectomy. B Carcinoma with mesenchymal (benign osseous and chondroid) differentiation. Typically, these carcinomas have a well delineated pushing margin. Areas of osseous and/or chondroid differentiation are variably scattered in an otherwise typical infiltrating ductal carcinoma. C Carcinoma with mesenchymal (benign osseous and chondroid) differentiation. The adenocarcinoma is admixed, in part, with chondroid matrix containing lacunar spaces and rare chondrocytes. C 40 Tumours of the breast
Page 2: Previous volumes in this series Kle
Page 6 and 7: World Health Organization Classific
Page 8 and 9: Published by IARC Press, Internatio
Page 10 and 11: CHAPTER 1 Tumours of the Breast Can
Page 12 and 13: TNM classification of carcinomas of
Page 14 and 15: Invasive breast carcinoma I.O. Elli
Page 16 and 17: Rapid growth and greater adult heig
Page 18 and 19: tives, administrative and clerical
Page 20 and 21: Grade 1 - well differentiated: 3-5
Page 22 and 23: ent and this is occasionally extens
Page 24 and 25: Most melanotic tumours of the breas
Page 26 and 27: A Fig. 1.22 A Classic invasive lobu
Page 28 and 29: yet others at 90% {97,2147}. For pr
Page 30 and 31: Fig. 1.27 Medullary carcinoma. The
Page 32 and 33: myoepithelial cells in fibro a d e
Page 34 and 35: A Fig. 1.33 Neuroendocrine carcinom
Page 36 and 37: Macroscopy Fisher et al. reported t
Page 38 and 39: Fig. 1.39 Apocrine carcinoma. Note
Page 42 and 43: A Fig. 1.50 Carcinosarcoma. A Two a
Page 44 and 45: A B C Fig. 1.75 Lobular neoplasia.
Page 46 and 47: Intraductal proliferative lesions F
Page 48 and 49: 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
Page 76 and 77: detectable distant metastasis displ
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,
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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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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
Page 366 and 367:
Dr Manuel TEIXEIRA Department of Ge
Page 368 and 369:
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
Page 430:
Small cell / oat cell carcinoma, 32
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