Invasive breast carcinoma - IARC

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Fig. 1.39 Apocrine carcinoma. Note abundant eosinophilic cytoplasm and vesicular nuclei. Fig. 1.40 Apocrine carcinoma, surperficially resembling a granular cell tumour. Fig. 1.41 Apocrine carcinoma. Immunostaining shows intense positivity for GCDFP-15. to as myoblastomatoid {806}. Type B cell shows abundant cytoplasm in which fine empty vacuoles are seen. These latter result in foamy appearance so that the cells may resemble histiocytes and sebaceous cells. Nuclei are similar to those in type A cells. These same cells have been designated as sebocrine {2876}. (See also Sebaceous carc i n o- ma, page 46). C a rcinomas composed p u rely of foamy apocrine cells may s u r p e rfically resemble a histiocytic proliferation or even an inflammatory re a c- tion {806}. In difficult cases, both granular cell tumours and histiocytic pro l i f e r a- tions can be easily distinguished by staining the tumours with keratin antibodies that are positive only in apocrine c a rc i n o m a s . Immunoprofile Apocrine carcinomas are typically GCDFP-15 positive and BCL2 pro t e i n negative. Expression of GCDFP-15 is a f e a t u re common to many variants of b reast carcinoma, however, and has been used to support breast origin in metastatic carcinomas of unknown prim a ry site. Estrogen and pro g e s t e ro n e receptors are usually negative in apocrine carcinoma by immonuhistochemical assessment. Interestingly, many ER-, PR- apocrine carcinomas do have the ERmRNA, but fail to produce the pro t e i n {336}. The expression of other biological markers is in general similar to that of other carcinomas {177,1605,2425}. A n d rogen receptors have been re p o rted as positive in 97% of ADCIS in one series {1605} and 81% in another {2624}. Sixty-two percent of invasive duct carcinomas were positive in the latter series {2624} and in 22% of cases in another study {1874}. The significance of AR in apocrine carcinomas is u n c e rt a i n . G e n e t i c s Molecular studies in benign, hyperplastic and neoplastic apocrine lesions parallel those seen in non apocrine tumours {1357,1673}. Prognosis and predictive factors Survival analysis of 72 cases of invasive apocrine duct carcinoma compared with non apocrine duct carcinoma re v e a l e d no statistical diff e rence {17,809}. Metaplastic carcinomas D e f i n i t i o n Metaplastic carcinoma is a general t e rm referring to a hetero g e n e o u s g roup of neoplasms generally characterized by an intimate admixture of aden o c a rcinoma with dominant areas of spindle cell, squamous, and/or mesenchymal diff e rentiation; the metaplastic spindle cell and squamous cell carcinomas may present in a pure form without any admixture with a re c o g n i z a- ble adenocarcinoma. Metaplastic carc i- nomas can be classified into bro a d subtypes according to the phenotypic appearance of the tumour. ICD-O code 8 5 7 5 / 3 S y n o n y m s Matrix producing carcinoma, carc i n o- s a rcoma, spindle cell carc i n o m a . E p i d e m i o l o g y Metaplastic carcinomas account for less than 1% of all invasive mammary c a rcinomas {1273}. The average age at p resentation is 55. Clinical features Clinical presentation is not diff e rent fro m that of infiltrating duct NOS carc i n o m a . Most patients present with a well circ u m- scribed palpable mass, with a median size of 3-4 cm, in some re p o rts more than half of these tumours measure over 5 cm, with some massive lesions (>20 cm) which may displace the nipple and ulcerate through the skin. On mammography, most metaplastic c a rcinomas appear as well delineated mass densities. Microcalcifications are not a common feature, but may be pre s- ent in the adenocarcinomatous are a s ; ossification, when present, is, of course, a p p a rent on mammography. Macroscopy The tumours are firm, well delineated and often solid on cut surface. Squamous or chondroid diff e rentiation is reflected as pearly white to firm glistening areas on the cut surface. One large and/or multiple small cysts may be a p p a rent on the cut surface of larger squamous tumours. Table 1.08 Classification of metaplastic carcinomas. Purely epithelial Squamous Large cell keratinizing Spindle cell Acantholytic Adenocarcinoma with spindle cell differentiation Adenosquamous, including mucoepidermoid Mixed epithelial and Mesenchymal (specify components) Carcinoma with chondroid metaplasia Carcinoma with osseous metaplasia Carcinosarcoma (specify components) Invasive breast cancer 37
Fig. 1.42 Squamous cell carcinoma. A well circumscribed mass shows numerous irregularly shaped depressions on cut surface. Fig. 1.43 Squamous cell carcinoma, acantholytic variant, which is often mistaken for a n g i o s a r c o m a . A Squamous cell carcinoma A breast carcinoma entirely composed of metaplastic squamous cells that may be keratinizing, non-keratinizing or spindled; they are neither derived from the overlying skin nor re p resent metastases f rom other sites. ICD-O codes Squamous cell carcinoma 8070/3 Large cell keratinizing variant 8071/3 Spindle cell variant 8074/3 Acantholytic variant 8075/3 Histopathology Squamous cell carcinomas assume several phenotypes including large cell keratinizing, non-keratinizing, and less frequently spindle cell and acantholytic types; some show a combination of these patterns {752,987,1022, 1928,2520,2932,3061}. The most bland appearing and well diff e rentiated cells often line cystic spaces; as the tumour cells emanate out to infiltrate the surrounding stroma, they become spindle shaped and lose their squamous feat u res. A pronounced stromal reaction is often admixed with the spindled squamous carcinoma. The squamous d i ff e rentiation is retained in metastatic foci. Squamous cell carcinoma can be B graded based mainly on nuclear feat u res and, to a lesser degree, cytoplasmic diff e re n t i a t i o n . Immunoprofile The spindle cell and acantholytic variants re q u i re immunohistochemical conf i rmation of their epithelial nature. The epithelial tumour cell components are positive for broad spectrum and high molecular weight cytokeratins (CK5 and CK34betaE12), but negative for vascular endothelial markers. Nearly all squamous cell carcinomas are negative for both estrogen (ER) and pro g e s- t e rone receptors (PR) {3059,3061}. Adenocarcinoma with spindle cell metaplasia Definition An invasive adenocarcinoma with abundant spindle cell transformation. The spindle cells are neither squamous, nor mesenchymal, but rather glandular in n a t u re . ICD-O code 8572/3 Clinical features This tumour occurs mainly in postmenopausal women and presents as a d i s c rete mass. Pathologic features M a c ro s c o p i c a l l y, a well circ u m s c r i b e d , solid mass, the tumour is composed of tubules of adenocarcinoma admixed with neoplastic spindle cells. The spindle cells immunoreact with epithelial markers including CK7, but not with CK5,6 or other markers of squamous/myoepithelial diff e re n t i a t i o n . At the ultrastructural level, the spindle C Fig. 1.44 Squamous cell carcinoma of the breast. A Macroscopically, there are often central cystic areas. B Variously shaped spaces lined by squamous epithelium are characteristic of the more common mammary squamous cell carcinoma. C Higher magnification showing a range of squamous cell differentiation with the most differentiated at the right. D Immunostain for cytokeratins 5, 6 is positive as expected for squamous epithelium. D Fig. 1.45 Adenocarcinoma with spindle cell metaplasia. The spindle cells are neither squamous nor mesenchymal, but rather glandular, intermixed with glands. 38 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 40 and 41: cells contain intracytoplasmic lume
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/
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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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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
Page 386 and 387:
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
Page 430:
Small cell / oat cell carcinoma, 32
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