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Invasive breast carcinoma - IARC

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A<br />

B<br />

Fig. 1.88 Large excision biopsy of a high grade ductal<br />

<strong>carcinoma</strong> in situ. A Note the sharp demarcation<br />

between DCIS, comedo type (left), and adjacent<br />

fibrous stroma. B Mammography showing a large<br />

area with highly polymorphic microcalcifications.<br />

mammogram, the specimen X-ray and<br />

the histologic slides. Since the majority of<br />

DCIS is non palpable, the mammographic<br />

estimate is the sole guide for re s e c t i o n .<br />

T h e re f o re, data on the mammographic<br />

pathological correlation of the tumour size<br />

a re essential for guiding the extent of surg<br />

e ry. The mammographic extent of a<br />

DCIS is defined as the greatest distance<br />

between the most peripherally located<br />

clusters of suspicious micro c a l c i f i c a t i o n s ,<br />

and the histologic extent as the gre a t e s t<br />

distance between the most peripherally<br />

located, histologically verified, DCIS foci.<br />

Histologic evaluation supported by correlation<br />

with the X-ray of the sliced specimen<br />

allows a precise and re p ro d u c i b l e<br />

assessment of the extent of any DCIS<br />

p resent. Whole organ studies have shown<br />

that mammography, on the basis of significant<br />

microcalcifications, generally<br />

u n d e restimates the histologic or "re a l "<br />

size of DCIS by an average of 1-2 cm. In<br />

a series of DCIS cases with mammographic<br />

sizes up to 3 cm, the size diff e r-<br />

ence was less than 2 cm in more than<br />

80% of the cases {1231}.<br />

DCIS may appear as a multifocal pro c e s s<br />

due to the presence of multiple tumour<br />

foci on two-dimensional plane sections.<br />

H o w e v e r, these tumour spots may not<br />

necessarily re p resent separate foci.<br />

Intraductal tumour growth on thre e -<br />

dimensional studies appears to be continuous<br />

rather than discontinuous {831}.<br />

M o re specifically, whereas poorly diff e r-<br />

entiated DCIS shows a pre d o m i n a n t l y<br />

continuous growth, the well diff e re n t i a t e d<br />

DCIS, in contrast, may present a more<br />

discontinuous (multifocal) distribution.<br />

These results have a direct implication on<br />

the reliability of the margin assessment of<br />

surgical specimens. In cases of poorly<br />

d i ff e rentiated DCIS, margin assessment<br />

should, theore t i c a l l y, be more re l i a b l e<br />

than well diff e rentiated DCIS. In a multifocal<br />

process with discontinuous gro w t h ,<br />

the surgical margin may lie between the<br />

tumour foci, giving the false impression of<br />

a free margin.<br />

The distribution of DCIS in the <strong>breast</strong> is<br />

typically not multicentric, defined as<br />

tumour involvement in two or more re m o t e<br />

a reas separated by uninvolved glandular<br />

tissue of 5 cm. On the contrary, DCIS is<br />

typically ‘segmental’ in distribution<br />

{1230}. In practical terms, this implies that<br />

two apparently separate areas of "malignant"<br />

mammographic micro c a l c i f i c a t i o n s<br />

usually do not re p resent separate fields of<br />

DCIS but rather a larger tumour in which<br />

the two mammographically identified<br />

fields are connected by DCIS, which is<br />

mammographically invisible due to the<br />

lack of detectable size of micro c a l c i f i c a-<br />

tions. One should be aware that single<br />

m i c roscopic calcium particles smaller<br />

than about 80µ cannot be seen on conventional<br />

mammograms.<br />

Grading<br />

Although there is currently no universal<br />

a g reement on classification of DCIS, there<br />

has been a move away from traditional<br />

a rchitectural classification. Most modern<br />

systems use cytonuclear grade alone or<br />

in combination with necrosis and or cell<br />

polarization. Recent international consensus<br />

conferences held on this subject<br />

endorsed this change and re c o m m e n d e d<br />

that, until more data emerges on clinical<br />

outcome related to pathology variables,<br />

grading of DCIS should form the basis of<br />

classification and that grading should be<br />

based primarily on cytonuclear feature s<br />

{6,7,1565,2346}.<br />

Pathologists are encouraged to include<br />

additional information on necrosis, arc h i t e c-<br />

t u re, polarization, margin status, size and<br />

calcification in their re p o rt s .<br />

Depending primarily on the degree of<br />

nuclear atypia, intraluminal necrosis and,<br />

to a lesser extent, on mitotic activity and<br />

Table 1.13<br />

Features of DCIS to be documented for the surgical<br />

pathology report.<br />

Major lesion characteristics<br />

1. Nuclear grade<br />

2. Necrosis<br />

3. Architectural patterns<br />

Associated features<br />

1. Margins<br />

If positive, note focal or diffuse involvement.<br />

Distance from any margin to the nearest<br />

focus of DCIS.<br />

2. Size (either extent or distribution)<br />

3. Microcalcifications (specify within DCIS or<br />

elsewhere)<br />

4. Correlate morphological findings with specimen<br />

imaging and mammographic findings<br />

calcification, DCIS is generally divided<br />

into three grades; the first two features<br />

constitute the major criteria in the majority<br />

of grading systems. It is not uncommon<br />

to find admixture of various grades<br />

of DCIS as well as various cytological<br />

variants of DCIS within the same biopsy<br />

or even within the same ductal space.<br />

When more than one grade of DCIS is<br />

present, the proportion (percentage) of<br />

various grades should be noted in the<br />

diagnosis {2876}. It is important to note<br />

that a three tiered grading system does<br />

not necessarily imply progression from<br />

grade 1 or well differentiated to grade 3<br />

or poorly differentiated DCIS.<br />

Histopathology<br />

Low grade DCIS<br />

Low grade DCIS is composed of small,<br />

monomorphic cells, growing in arcades,<br />

m i c ropapillae, cribriform or solid patterns.<br />

The nuclei are of uniform size and<br />

have a regular chromatin pattern with<br />

inconspicuous nucleoli; mitotic figures<br />

Table 1.14<br />

Minimal criteria for low grade DCIS.<br />

Cytological features<br />

1. Monotonous, uniform rounded cell<br />

population<br />

2. Subtle increase in nuclear-cytoplasmic ratio<br />

3. Equidistant or highly organized nuclear<br />

distribution<br />

4. Round nuclei<br />

5. Hyperchromasia may or may not be present<br />

Architectural features<br />

Arcades, cribriform, solid and/or<br />

micropapillary pattern<br />

Intraductal proliferative lesions<br />

69

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