Invasive breast carcinoma - IARC

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Grade 1 - well differentiated: 3-5 points Grade 2 - moderately differentiated: 6-7 points Grade 3 - poorly differentiated: 8-9 points Invasive ductal carcinoma, not otherwise specified (NOS) Definition Invasive ductal carcinoma, not otherwise specified (ductal NOS) comprises the largest group of invasive breast cancers. It is a heterogeneous group of tumours that fail to exhibit sufficient characteristics to achieve classification as a specific histological type, such as lobular or tubular carcinoma. ICD-O code 8500/3 Table 1.05 Semi-quantitative method for assessing histological grade in breast. From Elston and Ellis{777}. Feature Synonyms and historical annotation Invasive ductal carcinoma, no specific type (ductal NST); infiltrating ductal carcinoma. Many names have been used for this f o rm of breast carcinoma including scirrhous carcinoma, carcinoma simplex and spheroidal cell carc i n o m a. Infiltrating ductal carcinoma is used by the Armed Forces Institute of Pathology {1832,2442} and was the nomenclature adopted in the previous WHO classification {2548,3154}. This perpetuates the traditional concept that these tumours are derived exclusively from mammary ductal epithelium in distinction from lobular carcinomas, which were deemed to have arisen from within lobules for which there is no evidence. In addition it has been shown that the terminal duct-lobular unit (TDLU) should be regarded as a Score Tubule and gland formation Majority of tumour (>75%) 1 Moderate degree (10-75%) 2 Little or none (11 >20 >23 single entity from the point of view of the site of origin of most breast carcinomas {147,3091}. Some groups {874,2325} have retained the term ductal but added the phrase 'not otherwise specified (NOS)', whilst others {2147} prefer to use 'no specific type (NST)' to emphasize their distinction from specific type tumours. This latter view is increasingly A B C Fig. 1.10 Well differentiated infiltrating ductal carcinoma, Grade 1. A First screen. Intramammary lymph node and small (
Fig. 1.11 Invasive ductal carcinoma, not otherwise specified. 84 year old patient, mastectomy specimen. accepted internationally, but since 'ductal' is still widely used the terms invasive ductal carcinoma, ductal NOS or NST are preferred terminology options. Epidemiology Ductal NOS carcinoma forms a large proportion of mammary carcinomas and its epidemiological characteristics are similar to those of the group as a whole (see epidemiology). It is the most common 'type' of invasive carcinoma of the b reast comprising between 40% and 75% in published series {774}. This wide range is possibly due to the lack of application of strict criteria for inclusion in the special types and also the fact that some groups do not recognize tumours with a combination of ductal NOS and special type patterns as a separate mixed category, preferring to include them in the no special type (ductal NOS) group. Ductal NOS tumours, like all forms of breast cancer, are rare below the age of 40 but the proportion of tumours classified as such in young breast cancer cases is in general similar to older cases {1493}. There are no well recognized differences in the frequency of breast cancer type and proportion of ductal NOS cancers related to many of the known risk factors including geographical, cultural/lifestyle, reproductive variables (see aetiology). However, carcinomas developing following diagnosis of conditions such as atypical ductal hyperplasia and lobular neoplasia, recognized to be associated with increased risk include a higher proportion of tumours of specific type specifically tubular and classical lobular carcinoma {2150}. Familial breast cancer cases associated with BRCA1 mutations are commonly of ductal NOS type but have medullary carcinoma like features, exhibiting higher mitotic counts, a greater proportion of the tumour with a continuous pushing margin, and more lymphocytic infiltration than sporadic cancers {1572}. Cancers associated with BRCA2 mutations are also often of ductal NOS type but exhibit a high score for tubule formation (fewer tubules), a higher proportion of the tumour perimeter with a continuous pushing margin and a lower mitotic count than sporadic cancers {1572}. Macroscopy These tumours have no specific macroscopical features. There is a marked variation in size from under 10 mm to over 100 mm. They can have an irregular, stellate outline or nodular configuration. The tumour edge is usually moderately or ill defined and lacks sharp circumscription. Classically, ductal NOS carcinomas are firm or even hard on palpation, and may have a curious 'gritty' feel when cut with a knife. The cut surface is usually greywhite with yellow streaks. Histopathology The morphological features vary considerably from case to case and there is frequently a lack of the regularity of structure associated with the tumours of specific type. Architecturally the tumour cells may be arranged in cords, clusters and trabeculae whilst some tumours are characterized by a predominantly solid or syncytial infiltrative pattern with little associated stroma. In a proportion of cases glandular differentiation may be apparent as tubular structures with central lumina in tumour cell gro u p s . Occasionally, areas with single file infiltration or targetoid features are seen but these lack the cytomorphological characteristics of invasive lobular carcinoma. The carcinoma cells also have a variable appearance. The cytoplasm is often abundant and eosinophilic. Nuclei may be regular, uniform or highly pleomorphic with prominent, often multiple, nucleoli, mitotic activity may be virtually absent or extensive. In up to 80% of cases foci of associated ductal carcinoma in situ (DCIS) will be present {147,2874}. Associated DCIS is often of high grade comedo type, but all other patterns may be seen. Some recognize a subtype of ductal NOS carcinoma, infiltrating ductal carcinoma with extensive in situ component. The stromal component is extremely variable. There may be a highly cellular fibroblastic proliferation, a scanty connective tissue element or marked hyalinisation. Foci of elastosis may also be present, in a periductal or perivenous distribution. Focal necrosis may be pres- A B Fig. 1.12 A Infiltrating ductal carcinoma, grade I. B Infiltrating ductal carcinoma, grade II. C Invasive ductal NOS carcinoma, grade III with no evidence of glandular differentiation.Note the presence of numerous cells in mitosis, with some abnormal mitotic figures present. C 20 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 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 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
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Differential diagnosis There may be
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quality metaphase spreads from an i
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Fig. 1.67 Lobular carcinoma of brea
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detectable distant metastasis displ
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detected at a late stage as small t
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Extent of ductal carcinoma in situ
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Benign epithelial proliferations G.
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Fig. 1.112 Microglandular adenosis.
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A Apocrine adenoma ICD-O code 8401/
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A B Fig. 1.128 Adenomyoepithelioma,
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Mesenchymal tumours M. Drijkoningen
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1113,1275}. There is a complex patt
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A B Fig. 1.137 A Lipoma. Intraparen
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Fig. 1.141 Angiosarcoma after breas
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A Fig. 1.144 Mammary osteosarcoma.
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Fibroepithelial tumours J.P. Belloc
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aged women (average age of presenta
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lished data suggests a 21% rate of
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A Fig. 1.157 Syringomatous adenoma
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Malignant lymphoma and metastatic t
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used. Inflammatory conditions in th
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male population both in the USA and
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CHAPTER 2 Tumours of the Ovary and
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Polyembryoma 9072/3 Non-gestational
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Surface epithelial-stromal tumours
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A Fig. 2.04 A Serous borderline tum
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A Fig. 2.06 Serous borderline tumou
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A Fig. 2.10 Invasive peritoneal imp
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Fig. 2.15 Mucinous carcinoma with i
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Fig. 2.20 Mucinous endocervical-lik
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A Fig. 2.28 Mucinous cystic tumour
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early secretory endometrium {2605}.
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IV, 6% {2233}. Patients with grade
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A Fig. 2.37 A This polypoid intracy
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Fig. 2.40 Endometrioid cyst with at
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1 tumours are extremely rare. Almos
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Fig. 2.50 Borderline Brenner tumour
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express thrombomodulin and have bee
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serous and transitional cell carcin
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is yellow to tan with a variable ad
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Genetic susceptibility JGCTs may pr
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Clinical features F i b romas may b
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distinguishes this tumour from the
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A Fig. 2.77 A Retiform Sertoli-Leyd
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Mean ages of 21 and 38 years and me
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Tumours unassociated with PJS form
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mal origin without crystals of Rein
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Germ cell tumours F. Nogales A. Tal
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cases, anisokaryosis has no prognos
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ation may coexist in the same neopl
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Table 2.06 Grading of ovarian immat
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A B Fig. 2.102 A Mature cystic tera
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Diagnostic procedures Elevated urin
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associated with mature teratomas sh
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atives intimately admixed. The germ
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Fig. 2.113 Mixed germ cell-sex cord
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A Fig. 2.116 A Adenomatous hyperpla
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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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