Invasive breast carcinoma - IARC

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A Fig. 1.33 Neuroendocrine carcinoma. A Tumour cells are polarized around lumina; some cells show eosinophilic granules – carcinoid-like pattern. B IHC staining is positive for chromogranin. B be present. Areas of tumour necro s i s containing pyknotic hyperc h ro m a t i c nuclei are rarely detectable. Crush art e- fact and nuclear streaming occur, but a re more typical of aspiration cytology samples. Lymphatic tumour emboli are f requently encountered. Large cell neuroendocrine carcinoma ICD-O code 8013/3 These poorly differentiated tumours are composed of crowded large clusters of cells, with moderate to abundant cytoplasm, nuclei with vesicular to finely granular chromatin and a high number of mitotic figures ranging from 18 to 65 per 10 hpf. Focal areas of necrosis are present {2535}. These tumours exhibit neuroendocrine diff e rentiation similar to those encountered in the lung (see also below). apocrine marker GCDFP-15, which is f requently expressed by well and moderately diff e rentiated endocrine bre a s t c a rcinomas {2535}, are supportive of a p r i m a ry breast carc i n o m a . M a m m a ry small cell carcinoma can be confused histologically with lobular carcinoma. The negative immunore a c t i o n for E-cadherin in lobular carcinomas, in contrast to a positive reaction in 100% of small cell carcinomas, is useful in the d i ff e rential diagnosis {2661}. It is also important to diff e rentiate neuroendocrine breast carcinomas fro m c a rcinomas with neuroendocrine diff e r- entiation. The latter have immunoexp ression for neuroendocrine markers in s c a t t e red cells; this feature is noted in 10-18% of breast carcinomas of the usual type. Such focal neuro e n d o c r i n e d i ff e rentiation does not seem to carry a special prognostic or therapeutic significance {1876}. Immunoprofile A r g y rophilia demonstrated by Grimelius silver precipitation is a feature of neuroendocrine breast carcinomas. Only darkly granulated cells should be cons i d e red as argyrophilic {2536}. E x p ression of chromogranin pro t e i n s and/or synaptophysin also confirm e d Differential diagnosis A nodule of NE carcinoma in the bre a s t may reflect metastatic carcinoid or small cell carcinoma from another site {2022}. Immunohistochemistry may help to distinguish between metastatic and primary small cell carc i n o m a s . M a m m a ry small cell carcinomas are cytokeratin 7-positive and cytokeratin 20-negative, whereas, for example, pulm o n a ry small cell carcinomas are negative for both {2662}. The presence of DCIS with similar cytological features is s u p p o rtive of breast origin. In addition, the expression of estrogen (ER) and p ro g e s t e rone receptors (PR) and of the Fig. 1.34 Neuroendocrine carcinoma of the breast.Alveolar pattern with rounded solid nests of spindle cells invading a dense collagenous stroma. Invasive breast cancer 33
evidence of neuroendocrine diff e re n t i a- tion {2533}. These proteins are identifiable by immunohistochemical and immunoblot analysis. Poorly and moderately diff e rentiated endocrine bre a s t c a rcinomas of the alveolar subtype, in general, express chromogranin A. The mRNA specific for chromogranin A is detectable by in situ hybridization technique {2535}. About 50% of well or moderately diff e rentiated tumours e x p ress chromogranin B and A and only 16% express synaptophysin {2535}. A monoclonal antibody against n e u rone-specific enolase (NSE) has also been used and is expressed in 100% of small cell carcinomas of the b reast {2662}, whereas chromogranin A and synaptophysin are expressed in about 50% of such cases. In addition, 20% of small cell mammary carc i n o m a s e x p ress thyroid transcription factor- 1 (TTF-1) {2661}. Immunodetection of pan-endocrine markers may fail to recognize endocrine tumours, which produce but do not retain the specific antigen in the cells. Estrogen (ER) and pro g e s t e ro n e receptors (PR) are expressed in the majority of tumour cells in well diff e re n- tiated tumours {2535}, and in more than 50% of small cell carcinomas {2662}. E x p ression of somatostatin re c e p t o r s (SSR), a known feature of tumours showing neuroendocrine diff e re n t i a t i o n , has been demonstrated in endocrine b reast carcinomas as well {2169}. U l t r a s t r u c t u r e D i ff e rent types of dense core granules, whose neuro s e c re t o ry nature is conf i rmed by ultrastructural immunolocalization of chromogranin A have been identified by electron microscopy in endocrine breast carcinomas {397}. The presence of clear vesicles of presynaptic type is correlated with the e x p ression of synaptophysin. Both dense core granules and mucin vacuoles are present in neuro e n d o c r i n e mucinous carcinomas {1265}. G e n e t i c s N e u roendocrine breast carc i n o m a s have not been correlated to specific gene mutations. Postulated normal counterpart A r g y rophilic and chromogranin A-re a c- tive cells, located between the basal myoepithelial and the luminal epithelial cells, have been demonstrated in histologically normal breast tissue surro u n d- ing infiltrating and in situ neuro e n- docrine breast carcinomas {382,1995, 2 5 4 2 , 2 9 5 6 } . Prognosis and predictive factors Histological grading is one of the most i m p o rtant prognostic parameters. NE breast carcinomas may be graded using classical criteria described elsew h e re . Excluding the rare small cell variety, 45% of NE breast carcinomas are well d i ff e rentiated, 40% are moderately diff e rentiated, and only 15% are poorly diff e rentiated. Small cell NE carc i n o m a s should be considered as undiff e re n t i a t- ed carcinomas {2535}. Mucinous diff e rentiation is a favourable p rognostic factor {2535}. The prognosis of primary small cell carcinomas of the breast depends on the stage of disease at the time of diagnosis. It has been demonstrated that low stage small cell carcinomas respond to conventional treatment without pro g re s- sion of the disease at a follow up of 33 to 48 months {2662}. Invasive papillary carcinoma Definition When papillary intraductal carc i n o m a s invade, they generally assume the patt e rn of infiltrating duct carcinoma and lack a papillary arc h i t e c t u re. Most of the published literature concerning papillary c a rcinomas of the breast probably include both invasive and in situ papillary lesions as they do not generally specify f e a t u res of an invasive process {413, 603,969,1269,1604,1618,1834}. In this section, however, only data concern i n g invasive papillary carcinomas will be reviewed. Invasive papillary carc i n o m a s comprise less than 1-2% of invasive b reast cancers, and are characterized by a relatively good prognosis {879,2567}. ICD-O code 8503/3 Clinical features Invasive papillary carcinomas are diagnosed predominantly in postmenopausal patients. Fisher et al. {879} noted a disproportionate number of cases in non- Caucasian women. Similar to medullary carcinomas, Fisher et al. noted that a significant pro p o rtion of patients with invasive papillary carcinoma exhibit axill a ry lymphadenopathy suggestive of metastatic disease, but which on pathological examination is due to benign reactive changes {879}. M a m m o g r a p h i c a l l y, invasive papillary c a rcinoma is usually characterized by nodular densities which may be multiple, and are frequently lobulated {1880, 2567}. These lesions are often hypoechoic on ultrasound {1827}. One study noted the d i fficulty in distinguishing between intracystic papillary carcinoma, intracystic p a p i l l a ry carcinoma with invasion, and invasive papillary carcinoma {1827}. A B Fig. 1.35 Invasive papillary carcinoma. A Microfocus magnification image of a papillary carcinoma shows a low density rounded tumour. B Large section histology. C Ultrasonography shows a lobulated, well delineated lesion. C 34 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 36 and 37: Macroscopy Fisher et al. reported t
Page 38 and 39: Fig. 1.39 Apocrine carcinoma. Note
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.
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Fig. 1.112 Microglandular adenosis.
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A Apocrine adenoma ICD-O code 8401/
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A B Fig. 1.128 Adenomyoepithelioma,
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Mesenchymal tumours M. Drijkoningen
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1113,1275}. There is a complex patt
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A B Fig. 1.137 A Lipoma. Intraparen
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Fig. 1.141 Angiosarcoma after breas
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A Fig. 1.144 Mammary osteosarcoma.
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Fibroepithelial tumours J.P. Belloc
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aged women (average age of presenta
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lished data suggests a 21% rate of
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A Fig. 1.157 Syringomatous adenoma
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Malignant lymphoma and metastatic t
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used. Inflammatory conditions in th
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male population both in the USA and
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CHAPTER 2 Tumours of the Ovary and
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Polyembryoma 9072/3 Non-gestational
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Surface epithelial-stromal tumours
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A Fig. 2.04 A Serous borderline tum
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A Fig. 2.06 Serous borderline tumou
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A Fig. 2.10 Invasive peritoneal imp
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Fig. 2.15 Mucinous carcinoma with i
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Fig. 2.20 Mucinous endocervical-lik
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A Fig. 2.28 Mucinous cystic tumour
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early secretory endometrium {2605}.
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IV, 6% {2233}. Patients with grade
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A Fig. 2.37 A This polypoid intracy
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Fig. 2.40 Endometrioid cyst with at
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1 tumours are extremely rare. Almos
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Fig. 2.50 Borderline Brenner tumour
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express thrombomodulin and have bee
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serous and transitional cell carcin
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is yellow to tan with a variable ad
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Genetic susceptibility JGCTs may pr
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Clinical features F i b romas may b
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distinguishes this tumour from the
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A Fig. 2.77 A Retiform Sertoli-Leyd
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Mean ages of 21 and 38 years and me
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Tumours unassociated with PJS form
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mal origin without crystals of Rein
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Germ cell tumours F. Nogales A. Tal
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cases, anisokaryosis has no prognos
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ation may coexist in the same neopl
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Table 2.06 Grading of ovarian immat
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A B Fig. 2.102 A Mature cystic tera
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Diagnostic procedures Elevated urin
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associated with mature teratomas sh
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atives intimately admixed. The germ
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Fig. 2.113 Mixed germ cell-sex cord
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A Fig. 2.116 A Adenomatous hyperpla
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Fig. 2.117 Small cell carcinoma, hy
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Clinical features Adenoid cystic-li
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Histopathology This epithelial tumo
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sis. Corpus luteum of pregnancy has
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Lymphomas and leukaemias L.M. Roth
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Secondary tumours of the ovary J. P
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Occasionally, the colonic adenocarc
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Peritoneal tumours S.C. Mok J.O. Sc
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A B Fig. 2.140 Cystic adenomatoid m
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whelmingly poor {1038,1547,2310}. H
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CHAPTER 3 Tumours of the Fallopian
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TNM and FIGO classification of carc
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Endometrioid adenocarcinoma Endomet
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Two examples of adenofibroma of bor
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A Fig. 3.11 Adenomatoid tumour. A T
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Clinical features Patients range in
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Fig. 3.16 Uterus-like mass. The cys
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CHAPTER 4 Tumours of the Uterine Co
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TNM and FIGO classification of non-
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Epithelial tumours and related lesi
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endometrioid adenocarcinoma fro m a
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fers from the prototypical type I e
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the ovary and bladder. Unlike prima
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schema {1535,2602}. Although this c
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Table 4.03 Altered gene function in
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Mesenchymal tumours and related les
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areas are limited to less than 30%
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A B C Fig. 4.30 Leiomyosarcoma. A T
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e used sparingly and is reserved fo
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A B Fig. 4.38 Leiomyoma with perino
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cytological atypia, tumour cell nec
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Mixed epithelial and mesenchymal tu
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Prognosis and predictive factors Th
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tumours may superficially invade th
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A Fig. 4.46 A Gestational choriocar
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A Fig. 4.49 A Classic complete hyda
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Sex cord-like, neuroectodermal and
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Secondary tumours of the uterine co
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WHO histological classification of
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Epithelial tumours M. Wells J.M. Ne
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Fig. 5.04 Mechanisms of human papil
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Fig. 5.08 Keratinizing squamous cel
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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
Page 376 and 377:
436. Chang J, Sharpe JC, A'Hern RP,
Page 378 and 379:
562. Costa MJ, Ames PF, Walls J, Ro
Page 380 and 381:
689. Di Domenico A, Stangl F, Benni
Page 382 and 383:
820. Falck J, Petrini JH, Williams
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943. Gad A, Azzopardi JG (1975). Lo
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1067. Grimes MM (1992). Cystosarcom
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1197. Herod JJ, Shafi MI, Rollason
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1323. Jacques SM, Qureshi F, Ramire
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1449. Khalifa MA, Mannel RS, Harawa
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1564. Lagios MD (1977). Multicentri
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1687. Loman N, Johannsson O, Kristo
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1807. McCluggage G, McBride H, Maxw
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1937. Mukai M, Torikata C, Iri H (1
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2056. Norris HJ, Taylor HB (1967).
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2180. Park JS, Jones RW, McLean MR,
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2304. Puls LE, Hamous J, Morrow MS,
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2 4 3 4 . Rosen PP, Groshen S, Saig
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2559. Schlesinger C, Silverberg SG
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2686. Silverberg SG (1999). Protoco
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2806. Stutz JA, Evans AJ, Pinder S,
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2942. Tornos C, Silva EG, Ordonez N
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3061. Wargotz ES, Norris HJ (1990).
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3189. Yoshioka T, Tanaka T (2000).
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References 425
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Biphasic teratomas, 168 BLM, 341, 3
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G GADD45, 343, 353 GCDFP-15, 25, 33
Page 428 and 429:
MPNST, see Malignant peripheral ner
Page 430:
Small cell / oat cell carcinoma, 32
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