Invasive breast carcinoma - IARC

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Fig. 2.15 Mucinous carcinoma with infiltrative invasive pattern. Irregular glands lined by cells with malignant features infiltrate the stroma. A Fig. 2.16 Mucinous adenocarcinoma with expansile invasive pattern. A Note the complex glandular proliferation. B The glands are lined by cells that have highly atypical nuclei and some intracytoplasmic m u c i n . B pling of all macroscopically suspicious areas has been recommended. Histopathology In the absence of obvious infiltration of the s t roma, invasion is assumed if there are complex papillary areas or back-to-back glands lined by malignant-appearing cells with little or no discernible intervening s t roma. To qualify as frankly invasive, such areas should be at least 10 mm 2 a n d at least 3 mm in each of 2 linear dimensions {1613}. Altern a t i v e l y, invasion may be in the form of infiltrative glands, tubules, cords or cell nests. The stroma may resemble ovarian stroma or be desmoplastic. In most cases there are also are a s that are benign or borderline in a p p e a- rance {1147,1150,1228,2047,2401}. R a rel y, mucinous tumours contain areas of mucinous adenofibroma with malignant epithelial cells and foci of stromal invasion. Differential diagnosis The most important differential diagnosis of mucinous ovarian carcinoma is with metastatic mucinous carcinoma that may present clinically as a primary ovarian tumour. Most of these originate in the large intestine, appendix, pancreas, biliary tract, stomach or cervix {237,639, 1587,1703,2377,2406,3200,3221}. Since this problem has been emphasized relatively recently, it is likely that early reports of the histological appearance and behaviour of ovarian mucinous carcinomas have been contaminated by metastatic carcinomas masquerading as prim a ry ovarian neoplasms (see Ta b l e 2.03). Common features that favour a primary mucinous carcinoma are an expansile pattern of invasion and a complex papillary pattern {1614}. Common features favouring a metastatic mucinous carcinoma are bilaterality, a multinodular growth pattern microscopically, histological surface involvement by epithelial cells (surface implants) and vascular space invasion {1614}. Somatic genetics Tumour heterogeneity is common and p robably is a reflection of the pro g re s s i o n f rom benign to malignant neoplasia that occurs in the development of mucinous c a rc i n o m a s. Recent studies strongly suggest that in the sequence of malignant t r a n s f o rmation from benign and bord e r- line mucinous tumours to infiltrative carc i- noma intraepithelial (non-invasive) carc i- nomas and carcinomas with purely expansile (not obvious) invasion re p re s e n t transitional stages of mucinous carc i n o- genesis {1613}. This hypothesis is a l s o s u p p o rted by recent molecular studies of genetic alterations in mucinous t u m o u r s {591,964,1755,1891}. An increasing frequency of codon 12/13 K R A S m u t a t i o n s in benign, borderline and carc i n o m a t o u s mucinous ovarian tumours has been re p o rted supporting the viewpoint that K R A S mutational activation is an early event in mucinous ovarian tumorigenesis. Mucinous borderline tumours have a higher frequency of K R A S mutations than that of mucinous cystadenomas but a lower rate than that of mucinous carc i n o- mas {591,1755,1891}. Using micro d i s- section, the same K R A S mutation has been detected in separate areas exhibiting diff e rent histological grades within the same neoplasm {591}. Prognosis and predictive factors Clinical criteria Stage I mucinous carcinomas have an excellent prognosis. However, the prognosis in cases with extraovarian spread is very poor {1076,1228,1458,1613,2377, 2401,3069}. Histopathological criteria With the exception of one recent series {3769}, grading of mucinous carc i n o m a s has not been shown to be predictive of behaviour or response to therapy independent of the surgical stage {1076, 1228,1458,1613,2377,3069}. Infiltrative s t romal invasion proved to be biologically m o re aggressive than expansile invasion. If individual invasive foci are all less than 10 mm 2 , they have been termed "micro i n- vasive," and cases with this finding have had a favourable outcome {1453,1613, 1 9 8 7 , 2 0 4 7 , 2 4 0 1 , 2 7 1 3 } . Mucinous borderline tumour, intestinal type Definition Ovarian tumours of low malignant potential exhibiting an epithelial proliferation of mucinous type cells greater than that seen in their benign counterparts but without evidence of stromal invasion. The epithelial component resembles intestinal epithelium, almost always contains goblet cells, usually contains neuroendocrine cells and rarely contains Paneth cells. Synonyms Mucinous tumour of low malignant potential, intestinal type; mucinous tumour of borderline malignancy, intestinal type. Epidemiology These account for 85-90% of mucinous borderline tumours. Macroscopy Mucinous borderline tumours of intestinal type are bilateral in approximately 5% of cases and usually are large, multilocular or unilocular cystic masses containing w a t e ry or viscous mucoid material. Surface epithelial-stromal tumours 125
Table 2.03 Primary vs. metastatic mucinous ovarian carcinomas. Features favouring primary carcinoma Unilaterality Large size, smooth surface Expansile pattern of growth Features favouring metastatic carcinoma Bilaterality Known primary mucinous carcinoma at another site Macroscopically friable and necrotic Variable or nodular pattern of growth Ovarian surface involvement Ovarian vascular invasion Cytokeratin 7-negative Non-contributory Benign or borderline-appearing areas Infiltrative pattern of growth Luminal necrotic debris Tumour grade Velvety excrescences may line the cysts. Haemorrhagic, necrotic, solid or papill a ry areas are occasionally pre s e n t {1613,2605}. Histopathology Areas resembling mucinous cystadenoma are common. In the borderline areas the cells lining the cysts are stratified (usually to no more than 3 layers) and may form filiform intracystic papillae with at least minimal stromal support. Nuclei are slightly larger with more mitotic figures than in cystadenomas. Goblet cells and sometimes Paneth cells are present. The overall appearance resembles a hyperplastic or adenomatous colonic polyp { 3 2 2 , 6 5 3 , 1 0 7 6 , 1 1 4 7 , 1 1 5 0 , 1 6 1 3 , 2 3 7 7 , 2491,2605,2713}. Some or most of the epithelial cells lining the cysts of intestinal type borderline tumours may appear Fig. 2.17 Mucinous borderline tumour, intestinal type. The sectioned surface shows a multiloculated tumour with large cysts. cytologically malignant and may be stratified to four or more layers in a solid, papillary or cribriform pattern. Whether tumours with such foci should be classified as non-invasive carcinomas or as borderline tumours has been a subject of controversy for many years. To provide for uniformity in reporting, it has been recommended that they be classified as borderline with intraepithelial carcinoma {2605}. Prognosis and predictive factors When the tumour is confined to the ovaries at initial staging, the prognosis is excellent with only rarely reported recurrences {1150}. It is likely that most tumours diagnosed as intestinal-type mucinous borderline tumour that are associated with pseudomyxoma peritonei are actually metastatic from a similar-appearing tumour in the appendix (see section on pseudomyxoma peritonei). In the remaining cases with advanced disease, the metastases are usually in the form of invasive pelvic or abdominal implants rather than pseudomyxoma peritonei. In these cases the prognosis is similar to that of ovarian mucinous carcinomas with metastases, and it is likely that areas of invasion within the ovarian tumour were not sampled {1076,1147,1150,1613,2401}. Table 2.04 summarizes the differences in appearance and outcome among neoplasms having the appearance of mucinous borderline tumours. Mucinous borderline tumour, endocervical-like Definition Ovarian tumours of low malignant potential exhibiting an epithelial proliferation of mucinous type cells greater than seen in their benign counterparts but without destructive stromal invasion. The mucinous epithelial cells resemble endocervical epithelium. Synonyms Mucinous tumour of low malignant potential, endocervical-like; mucinous tumour of borderline malignancy, endocervicallike; müllerian mucinous bord e r l i n e tumour. Epidemiology These tumours make up 10-15% of mucinous borderline tumours {1613,2497,2713}. Fig. 2.18 Mucinous borderline tumour, intestinal type. Goblet cells and nuclear stratification are e v i d e n t . Macroscopy Mucinous endocervical-like bord e r l i n e tumours usually are multilocular or unilocular cystic masses containing watery or viscous mucoid material. Haemorrhagic, n e c rotic, solid or papillary areas may be present {1613,2605}. They are smaller than the intestinal type and have fewer cysts. They are bilateral in appro x i m a t e l y 40% of cases and sometimes arise within an endometriotic cyst {2497}. Tumour spread and staging Endocervical-like borderline tumours may be associated with abdominal or pelvic implants, some of which may appear invasive {2497,2713}. Fig. 2.19 Mucinous borderline tumour, intestinal type, with intraepithelial carcinoma. Malignant mucinous epithelium with a cribriform pattern and mitotic figures lines a cyst. 126 Tumours of the ovary and peritoneum
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Previous volumes in this series Kle
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World Health Organization Classific
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Published by IARC Press, Internatio
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CHAPTER 1 Tumours of the Breast Can
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TNM classification of carcinomas of
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Invasive breast carcinoma I.O. Elli
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Rapid growth and greater adult heig
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tives, administrative and clerical
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Grade 1 - well differentiated: 3-5
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ent and this is occasionally extens
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Most melanotic tumours of the breas
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A Fig. 1.22 A Classic invasive lobu
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yet others at 90% {97,2147}. For pr
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Fig. 1.27 Medullary carcinoma. The
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myoepithelial cells in fibro a d e
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A Fig. 1.33 Neuroendocrine carcinom
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Macroscopy Fisher et al. reported t
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Fig. 1.39 Apocrine carcinoma. Note
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cells contain intracytoplasmic lume
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A Fig. 1.50 Carcinosarcoma. A Two a
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A B C Fig. 1.75 Lobular neoplasia.
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Intraductal proliferative lesions F
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A B absence of either microcalcific
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Fig. 1.83 Atypical ductal hyperplas
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A B Fig. 1.88 Large excision biopsy
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unusual variants as well. Using thi
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esemble those identified in invasiv
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A B Fig. 1.97 Microinvasive carcino
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A Papilloma may be subject to morph
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A B C Fig. 1.103 Papillary intraduc
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colour measuring from 0.5 to 12 cm.
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Immunoprofile The cases studied by
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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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Page 80 and 81: Extent of ductal carcinoma in situ
Page 82 and 83: Benign epithelial proliferations G.
Page 84 and 85: Fig. 1.112 Microglandular adenosis.
Page 86 and 87: A Apocrine adenoma ICD-O code 8401/
Page 88 and 89: A B Fig. 1.128 Adenomyoepithelioma,
Page 90 and 91: Mesenchymal tumours M. Drijkoningen
Page 92 and 93: 1113,1275}. There is a complex patt
Page 94 and 95: A B Fig. 1.137 A Lipoma. Intraparen
Page 96 and 97: Fig. 1.141 Angiosarcoma after breas
Page 98 and 99: A Fig. 1.144 Mammary osteosarcoma.
Page 100 and 101: Fibroepithelial tumours J.P. Belloc
Page 102 and 103: aged women (average age of presenta
Page 104 and 105: lished data suggests a 21% rate of
Page 106 and 107: A Fig. 1.157 Syringomatous adenoma
Page 108 and 109: Malignant lymphoma and metastatic t
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Page 112 and 113: male population both in the USA and
Page 114 and 115: CHAPTER 2 Tumours of the Ovary and
Page 116 and 117: Polyembryoma 9072/3 Non-gestational
Page 118 and 119: Surface epithelial-stromal tumours
Page 120 and 121: A Fig. 2.04 A Serous borderline tum
Page 122 and 123: A Fig. 2.06 Serous borderline tumou
Page 124 and 125: A Fig. 2.10 Invasive peritoneal imp
Page 128 and 129: Fig. 2.20 Mucinous endocervical-lik
Page 130 and 131: A Fig. 2.28 Mucinous cystic tumour
Page 132 and 133: early secretory endometrium {2605}.
Page 134 and 135: IV, 6% {2233}. Patients with grade
Page 136 and 137: A Fig. 2.37 A This polypoid intracy
Page 138 and 139: Fig. 2.40 Endometrioid cyst with at
Page 140 and 141: 1 tumours are extremely rare. Almos
Page 142 and 143: Fig. 2.50 Borderline Brenner tumour
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Page 148 and 149: is yellow to tan with a variable ad
Page 150 and 151: Genetic susceptibility JGCTs may pr
Page 152 and 153: Clinical features F i b romas may b
Page 154 and 155: distinguishes this tumour from the
Page 156 and 157: A Fig. 2.77 A Retiform Sertoli-Leyd
Page 158 and 159: Mean ages of 21 and 38 years and me
Page 160 and 161: Tumours unassociated with PJS form
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Page 164 and 165: Germ cell tumours F. Nogales A. Tal
Page 166 and 167: cases, anisokaryosis has no prognos
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Page 170 and 171: Table 2.06 Grading of ovarian immat
Page 172 and 173: A B Fig. 2.102 A Mature cystic tera
Page 174 and 175: Diagnostic procedures Elevated urin
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associated with mature teratomas sh
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atives intimately admixed. The germ
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Fig. 2.113 Mixed germ cell-sex cord
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A Fig. 2.116 A Adenomatous hyperpla
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Fig. 2.117 Small cell carcinoma, hy
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Clinical features Adenoid cystic-li
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Histopathology This epithelial tumo
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sis. Corpus luteum of pregnancy has
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Lymphomas and leukaemias L.M. Roth
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Secondary tumours of the ovary J. P
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Occasionally, the colonic adenocarc
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Peritoneal tumours S.C. Mok J.O. Sc
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A B Fig. 2.140 Cystic adenomatoid m
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whelmingly poor {1038,1547,2310}. H
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CHAPTER 3 Tumours of the Fallopian
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TNM and FIGO classification of carc
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Endometrioid adenocarcinoma Endomet
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Two examples of adenofibroma of bor
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A Fig. 3.11 Adenomatoid tumour. A T
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Clinical features Patients range in
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Fig. 3.16 Uterus-like mass. The cys
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CHAPTER 4 Tumours of the Uterine Co
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TNM and FIGO classification of non-
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Epithelial tumours and related lesi
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endometrioid adenocarcinoma fro m a
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fers from the prototypical type I e
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the ovary and bladder. Unlike prima
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schema {1535,2602}. Although this c
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Table 4.03 Altered gene function in
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Mesenchymal tumours and related les
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areas are limited to less than 30%
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A B C Fig. 4.30 Leiomyosarcoma. A T
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e used sparingly and is reserved fo
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A B Fig. 4.38 Leiomyoma with perino
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cytological atypia, tumour cell nec
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Mixed epithelial and mesenchymal tu
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Prognosis and predictive factors Th
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tumours may superficially invade th
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A Fig. 4.46 A Gestational choriocar
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A Fig. 4.49 A Classic complete hyda
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Sex cord-like, neuroectodermal and
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Secondary tumours of the uterine co
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WHO histological classification of
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Epithelial tumours M. Wells J.M. Ne
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Fig. 5.04 Mechanisms of human papil
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Fig. 5.08 Keratinizing squamous cel
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in their Asian population {2957}. I
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have a strong association with high
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e red by squamous epithelium {380}.
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endometrioid adenocarcinoma of the
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metrial epithelium. In some cases t
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with distinct cell borders and a gr
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Mesenchymal tumours M.L. Carcangiu
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{781}, liposarcoma {2840,3016}, ost
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Mixed epithelial and mesenchymal tu
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Fig. 5.44 Wilms tumour. The tumour
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A Fig. 5.47 Implant of endometrial
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CHAPTER 6 Tumours of the Vagina Alt
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Epithelial tumours E.S. Andersen A.
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Aetiology The fact that both VAIN a
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Fig. 6.10 Fibroepithelial polyp.A m
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er of mitoses varies but is usually
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ICD-O codes Adenosquamous carcinoma
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A C Fig. 6.17 Sarcoma botryoides. A
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1-11 cm. They may arise anywhere in
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elsewhere in the female genital tra
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A Fig. 6.24 Yolk sac tumour. A The
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g rowing in sheets. Some may have s
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WHO histological classification of
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Epithelial tumours E.J. Wilkinson M
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even with additional sectioning, it
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type) is a highly diff e rentiated
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Clinical features Bartholin gland c
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glandular elements surrounded by fi
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Mesenchymal tumours R.L. Kempson M.
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Table 7.03 Differential diagnosis o
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Prognosis and predictive factors A
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Table 7.04 Clark levels of cutaneou
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A Fig. 7.23 Vulvar peripheral primi
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Familial aggregation of cancers of
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BRCA1 syndrome Definition Inherited
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dispose individuals to the developm
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Fig. 8.05 To assess whether wild-ty
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Fig. 8.07 Factors that modify risk
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BRCA2 syndrome R. Eeles S. Piver S.
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tubal or ovarian carcinomas. Howeve
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in typical nuclear foci that may re
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Breast tumours Frequency Breast can
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Fig. 8.14 Codon distribution of som
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Breast tumours Age distribution and
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Hereditary non-polyposis colon canc
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essary in the evaluation of the pat
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Age distribution and penetrance Mos
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Contributors Dr Vera M. ABELER** De
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Dr Carlo LA VECCHIA Laboratory of E
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Dr Manuel TEIXEIRA Department of Ge
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02.100 Dr. A. Ostor 02.101 Dr. F.A.
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52. Akhtar M, Robinson C, Ashraf Al
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180. Bapat K, Brustein S (1989). Ut
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307. Bolis GB, Maccio T (2000). Cle
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436. Chang J, Sharpe JC, A'Hern RP,
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
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Small cell / oat cell carcinoma, 32
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