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Invasive breast carcinoma - IARC

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cases, anisokaryosis has no prognostic<br />

implication The behaviour of dysgerminoma<br />

with trophoblastic differentiation is<br />

identical to the usual type, but with the<br />

advantage of having β-hCG as a serum<br />

marker.<br />

Yolk sac tumour<br />

Definition<br />

Yolk sac tumours are morphologically<br />

h e t e rogeneous, primitive teratoid neoplasms<br />

differentiating into multiple endodermal<br />

structures, ranging from the primitive<br />

gut to its derivatives of extraembryonal<br />

(secondary yolk sac vesicle) and<br />

embryonal somatic type, e.g. intestine,<br />

liver {2035}. These neoplasms have<br />

many epithelial patterns and are typically<br />

immunoreactive for alpha-fetoprotein.<br />

Synonym and historical annotation<br />

Since the secondary yolk sac component<br />

represents only one of its many lines of<br />

differentiation, the current nomenclature<br />

is clearly restrictive. Perhaps the term<br />

“endodermal primitive tumours” would<br />

be more accurate in defining all the possible<br />

lines of differentiation, both epithelial<br />

and mesenchymal, that occur in<br />

these neoplasms.<br />

The term “endodermal sinus tumour”,<br />

although still in use, is misleading, since<br />

the endodermal sinus is neither a structure<br />

present in human embryogenesis<br />

{1463} nor is it a constant feature of these<br />

neoplasms, as it only occurs in a minority<br />

of cases {1537}.<br />

Macroscopy<br />

These tumours are usually well encapsulated<br />

with an average diameter of 15 cm<br />

{1537}. The sectioned tumour surface is<br />

soft and grey-yellow with frequent areas<br />

Fig. 2.89 Yolk sac tumour. Sectioned surface is predominately<br />

solid and fleshy with areas of haemorrhage,<br />

necrosis and cyst formation.<br />

Table 2.05<br />

Morphological patterns of yolk sac tumours with their equivalent types of tissue differentiation.<br />

Site differentiated Tissue differentiated Histological pattern<br />

Extraembryonal endoderm<br />

Somatic endoderm<br />

Primitive endoderm and<br />

secondary yolk sac<br />

Allantois<br />

Murine-type (?) parietal<br />

yolk sac<br />

of necrosis, haemorrhage and liquefaction.<br />

Cysts can be found in the periphery<br />

f o rming a honeycomb appearance<br />

{2043}; rare l y, they can be unicystic<br />

{522}. A relatively frequent finding is the<br />

presence of a benign cystic teratoma in<br />

the contralateral ovary {3033}.<br />

Histopathology<br />

Although a marked histological heterogeneity<br />

due to numerous patterns of differentiation<br />

coexisting in the same neoplasm<br />

may occur, almost invariably characteristic<br />

areas are present that allow for<br />

the correct diagnosis.<br />

The characteristic reticular pattern<br />

formed by a loose, basophilic, myxoid<br />

stroma harbouring a meshwork of microcystic,<br />

labyrinthine spaces lined by clear<br />

or flattened epithelial cells with various<br />

degrees of atypia and cytoplasmic PASpositive,<br />

diastase-resistant hyaline globules<br />

permits tumour identification.<br />

Irregular but constant amounts of hyaline,<br />

amorphous basement membrane<br />

material are found in relation to the<br />

epithelial cells. Both hyaline globules<br />

and the coarse aggregates of basement<br />

membrane material {2032,2979} are<br />

good histological indicators for tumour<br />

identity. Less frequently, in 13-20% of<br />

cases, papillary fibrovascular projections<br />

lined by epithelium (Schiller-Duval bodies)<br />

are found that bear a resemblance to<br />

the structures of the choriovitelline placenta<br />

of the rat, a fact that permitted the<br />

establishment of the teratoid, endodermal<br />

identity of these tumours {2896}.<br />

Histological variants<br />

Less common histological variants<br />

include the polyvesicular vitelline tumour,<br />

solid yolk sac tumour, parietal yolk sac<br />

Primitive intestine and lung (?)<br />

Early liver<br />

Reticular<br />

Solid<br />

Endodermal sinus<br />

Polyvesicular<br />

Parietal<br />

Glandular<br />

Hepatic<br />

t u m o u r, glandular types of yolk sac<br />

tumour and hepatoid yolk sac tumour.<br />

In the polyvesicular vitelline tumour cystic,<br />

organoid change of the epithelial<br />

spaces occurs that consists of multiple<br />

dilatations lined by mesothelial-like cells<br />

that coexist with a columnar, PAS-positive<br />

epithelium {2043}.<br />

The solid yolk sac tumour shows areas of<br />

solid epithelial sheets of cells with a characteristic<br />

abundant clear cytoplasm and<br />

numerous hyaline globules. These areas<br />

may resemble anaplastic changes of<br />

d y s g e rminoma or even clear cell<br />

tumours {1537} but have the distinctive<br />

immunophenotype of a yolk sac tumour.<br />

Although exceptionally rare, parietal-type<br />

yolk sac tumours that are AFP-negative<br />

have been described {598,620}. They<br />

a re analogous to the experimental<br />

murine tumour of the same name and<br />

can be identified by the massive deposition<br />

of amorphous extracellular basement<br />

membrane, a material similar to the<br />

Reichert membrane of the murine parietal<br />

yolk sac.<br />

D i ff e rentiation into organized somatic<br />

endodermal derivatives such as endodermal<br />

type gland-like structures resembling<br />

early lung and intestine as well as<br />

liver tissue can occur in a focal fashion in<br />

as many as a third of tumours {1968,<br />

2515,2979}. In rare instances these differentiated<br />

tissues may become the predominant<br />

elements in the tumour.<br />

Extensive differentiation of endodermal<br />

type glands characterizes the glandular<br />

variants of yolk sac tumours, which may<br />

adopt different morphological subtypes.<br />

F rom an embryological viewpoint the<br />

more immature type is represented by<br />

n u m e rous dilated angular glands or<br />

papillae lined by an eosinophilic colum-<br />

Germ cell tumours 165

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