Invasive breast carcinoma - IARC

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cases, anisokaryosis has no prognostic implication The behaviour of dysgerminoma with trophoblastic differentiation is identical to the usual type, but with the advantage of having β-hCG as a serum marker. Yolk sac tumour Definition Yolk sac tumours are morphologically h e t e rogeneous, primitive teratoid neoplasms differentiating into multiple endodermal structures, ranging from the primitive gut to its derivatives of extraembryonal (secondary yolk sac vesicle) and embryonal somatic type, e.g. intestine, liver {2035}. These neoplasms have many epithelial patterns and are typically immunoreactive for alpha-fetoprotein. Synonym and historical annotation Since the secondary yolk sac component represents only one of its many lines of differentiation, the current nomenclature is clearly restrictive. Perhaps the term “endodermal primitive tumours” would be more accurate in defining all the possible lines of differentiation, both epithelial and mesenchymal, that occur in these neoplasms. The term “endodermal sinus tumour”, although still in use, is misleading, since the endodermal sinus is neither a structure present in human embryogenesis {1463} nor is it a constant feature of these neoplasms, as it only occurs in a minority of cases {1537}. Macroscopy These tumours are usually well encapsulated with an average diameter of 15 cm {1537}. The sectioned tumour surface is soft and grey-yellow with frequent areas Fig. 2.89 Yolk sac tumour. Sectioned surface is predominately solid and fleshy with areas of haemorrhage, necrosis and cyst formation. Table 2.05 Morphological patterns of yolk sac tumours with their equivalent types of tissue differentiation. Site differentiated Tissue differentiated Histological pattern Extraembryonal endoderm Somatic endoderm Primitive endoderm and secondary yolk sac Allantois Murine-type (?) parietal yolk sac of necrosis, haemorrhage and liquefaction. Cysts can be found in the periphery f o rming a honeycomb appearance {2043}; rare l y, they can be unicystic {522}. A relatively frequent finding is the presence of a benign cystic teratoma in the contralateral ovary {3033}. Histopathology Although a marked histological heterogeneity due to numerous patterns of differentiation coexisting in the same neoplasm may occur, almost invariably characteristic areas are present that allow for the correct diagnosis. The characteristic reticular pattern formed by a loose, basophilic, myxoid stroma harbouring a meshwork of microcystic, labyrinthine spaces lined by clear or flattened epithelial cells with various degrees of atypia and cytoplasmic PASpositive, diastase-resistant hyaline globules permits tumour identification. Irregular but constant amounts of hyaline, amorphous basement membrane material are found in relation to the epithelial cells. Both hyaline globules and the coarse aggregates of basement membrane material {2032,2979} are good histological indicators for tumour identity. Less frequently, in 13-20% of cases, papillary fibrovascular projections lined by epithelium (Schiller-Duval bodies) are found that bear a resemblance to the structures of the choriovitelline placenta of the rat, a fact that permitted the establishment of the teratoid, endodermal identity of these tumours {2896}. Histological variants Less common histological variants include the polyvesicular vitelline tumour, solid yolk sac tumour, parietal yolk sac Primitive intestine and lung (?) Early liver Reticular Solid Endodermal sinus Polyvesicular Parietal Glandular Hepatic t u m o u r, glandular types of yolk sac tumour and hepatoid yolk sac tumour. In the polyvesicular vitelline tumour cystic, organoid change of the epithelial spaces occurs that consists of multiple dilatations lined by mesothelial-like cells that coexist with a columnar, PAS-positive epithelium {2043}. The solid yolk sac tumour shows areas of solid epithelial sheets of cells with a characteristic abundant clear cytoplasm and numerous hyaline globules. These areas may resemble anaplastic changes of d y s g e rminoma or even clear cell tumours {1537} but have the distinctive immunophenotype of a yolk sac tumour. Although exceptionally rare, parietal-type yolk sac tumours that are AFP-negative have been described {598,620}. They a re analogous to the experimental murine tumour of the same name and can be identified by the massive deposition of amorphous extracellular basement membrane, a material similar to the Reichert membrane of the murine parietal yolk sac. D i ff e rentiation into organized somatic endodermal derivatives such as endodermal type gland-like structures resembling early lung and intestine as well as liver tissue can occur in a focal fashion in as many as a third of tumours {1968, 2515,2979}. In rare instances these differentiated tissues may become the predominant elements in the tumour. Extensive differentiation of endodermal type glands characterizes the glandular variants of yolk sac tumours, which may adopt different morphological subtypes. F rom an embryological viewpoint the more immature type is represented by n u m e rous dilated angular glands or papillae lined by an eosinophilic colum- Germ cell tumours 165
A B Fig. 2.90 Yolk sac tumour. A The reticular pattern is characterized by a loose meshwork of communicating spaces. B Hyaline globules and amorphous basement membrane material are present. C An endodermal or Schiller-Duval sinus is characteristic. C A nar epithelium and surrounded by an oedematous, mesoblastic-type stro m a that exhibits the characteristic appearance of early endoderm in both early differentiated intestine and the pseudoglandular phase of the embryonal lung {2038}. Indeed, similar tumours are reported in the lung itself {1968}. This gland-like aspect coupled with the presence of subnuclear vacuolization in the columnar lining mimics early secretory endometrium and endometrioid carcinoma of the ovary and, thus, was named the "endometrioid" variant {522}. Some endometroid yolk sac tumours are highly differentiated and difficult to distinguish from grade 1 endometrioid carcinoma. Another type of glandular yolk sac tumour is composed of typical small cribriform glands resembling early intestinal d i ff e rentiation. This type has been termed the intestinal-type of yolk sac tumour {533}. Extensive differentiation into hepatic tissue is another form of somatic differentiation {2515}. In some yolk sac tumours extensive solid nodular areas of liver tissue can be found {2284} and can be so well formed that they reproduce their laminar structure complete with sinusoids and even haematopoiesis. Finally, since any immature teratoid tissue is considered to be capable of undergoing fully accomplished differentiation, it is possible that pure endodermal immature teratoma composed solely of AFPsecreting endodermal glands and mesenchyme may be closely related to yolk Fig. 2.91 Yolk sac tumour, glandular pattern. A Its glands show subnuclear vacuolization characteristic of early differentiated endoderm. B Marked cytoplasmic positivity for alpha-fetoprotein is seen in glandular areas. A Fig. 2.92 A Yolk sac tumour, intestinal type. Note the cribriform pattern. B Yolk sac tumour with hepatic differentiation. The tumour is characterized by liver cell trabeculae and sinusoids. B B sac tumours {2042}. Predominance of mesenchymal, rather than epithelial, elements with differentiation into other components such as cartilage, bone or muscle may occur as a postchemotherapeutic conversion and be responsible for the occurrence of associated sarcomas in some cases {1854}. The haematopoietic capacity of the normal secondary yolk sac may have its neoplastic counterpart in yolk sac tumours, where isolated cases of haematological disorders have been reported associated with ovarian yolk sac tumours {1782} in a similar way to those occurring in extragonadal germ cell tumours. Immunoprofile AFP is the characteristic marker of the epithelial component of yolk sac tumours, although it is not exclusive to them, as it can also be found in some ovarian tumours that are not of germ cell type. AFP is found as a dense granular cytoplasmic deposit and is absent in hyaline globules, which are rare l y immunoreactive. A host of other substances can be found in yolk sac tumours recapitulating the complex functions of early endoderm, including those involved in haematopoiesis {1158,2011}. The usual positivity for cytokeratins may differentiate solid yolk sac tumour from dysgerminoma. CD30 is usually positive in embryonal carcinoma {736} but is only focally positive in yolk sac tumour. Leu M1, which is positive in clear cell carcinoma, is negative in yolk sac tumour. The absence of estrogen and progesterone receptors in yolk sac tumour differentiates areas of yolk sac epithelium from associated areas of true endometrioid tumour {533}. Prognosis and predictive factors Because numerous patterns of differenti- 166 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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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
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 126 and 127: Fig. 2.15 Mucinous carcinoma with i
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 146 and 147: serous and transitional cell carcin
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
Page 162 and 163: mal origin without crystals of Rein
Page 164 and 165: Germ cell tumours F. Nogales A. Tal
Page 168 and 169: ation may coexist in the same neopl
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
Page 176 and 177: associated with mature teratomas sh
Page 178 and 179: atives intimately admixed. The germ
Page 180 and 181: Fig. 2.113 Mixed germ cell-sex cord
Page 182 and 183: A Fig. 2.116 A Adenomatous hyperpla
Page 184 and 185: Fig. 2.117 Small cell carcinoma, hy
Page 186 and 187: Clinical features Adenoid cystic-li
Page 188 and 189: Histopathology This epithelial tumo
Page 190 and 191: sis. Corpus luteum of pregnancy has
Page 192 and 193: Lymphomas and leukaemias L.M. Roth
Page 194 and 195: Secondary tumours of the ovary J. P
Page 196 and 197: Occasionally, the colonic adenocarc
Page 198 and 199: Peritoneal tumours S.C. Mok J.O. Sc
Page 200 and 201: A B Fig. 2.140 Cystic adenomatoid m
Page 202 and 203: whelmingly poor {1038,1547,2310}. H
Page 204 and 205: CHAPTER 3 Tumours of the Fallopian
Page 206 and 207: TNM and FIGO classification of carc
Page 208 and 209: Endometrioid adenocarcinoma Endomet
Page 210 and 211: Two examples of adenofibroma of bor
Page 212 and 213: A Fig. 3.11 Adenomatoid tumour. A T
Page 214 and 215: 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
Page 428 and 429:
MPNST, see Malignant peripheral ner
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Small cell / oat cell carcinoma, 32
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