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Invasive breast carcinoma - IARC

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Fig. 1.160 CD20 immunoexpression in diffuse large<br />

B-cell lymphoma.<br />

The relationship of the surrounding mammary<br />

tissue to the lymphomatous infiltration<br />

differs from case to case. In some,<br />

the bulk of the lesion is located in the<br />

subcutaneous tissue, and bre a s t<br />

parenchyma is found only peripherally.<br />

In others, numerous ducts and lobules<br />

are embedded in the infiltrate but clearly<br />

separated from it. Sometimes lymphoma<br />

cells infiltrate the ducts to diff e re n t<br />

degrees and, in rare cases, the latter are<br />

overgrown by lymphoma cells and barely<br />

visible, sometimes revealed only by<br />

using keratin immunostaining. The stroma<br />

may be scant or abundant and the<br />

infiltrates may have a “medullary ”<br />

appearance. In some cases, lymphoma<br />

cells form cords and ribbons simulating<br />

an infiltrating lobular carc i n o m a .<br />

Diffuse large B-cell lymphoma<br />

ICD-O code 9680/3<br />

Lymphoma of this type is characterized<br />

by a diffuse pattern of infiltration of bre a s t<br />

tissue by large lymphoma cells varying in<br />

appearance from quite uniform to pleomorphic.<br />

Generally, the lymphoma cells<br />

resemble centroblasts or immunoblasts.<br />

The nuclei are oval, indented or even<br />

lobated, usually with distinct, single or<br />

multiple nucleoli, and the amount of cytoplasm<br />

is variable. Mitoses are usually<br />

n u m e rous, various numbers of cells are<br />

apoptotic and necrotic foci may be found.<br />

Lymphoma cells are often admixed with<br />

smaller reactive lymphocytes of B or T<br />

type; macrophages may be pro m i n e n t ,<br />

i m p a rting a “starry sky” appearance to<br />

the tumour. In some cases, pseudofollicular<br />

structures are seen due to selective<br />

infiltration of ductal-lobular units {18}.<br />

Adjacent mammary tissue may exhibit<br />

lobular atrophy or lymphocytic lobulitis<br />

{18,113}; the latter may be prominent and<br />

w i d e s p read, featuring lymphocytic mastopathy<br />

{113}.<br />

Lymphoma cells are immunoreactive for<br />

CD20, CD79a, and CD45RB and negative<br />

for CD3 and CD45RO. Cases with<br />

immunoblastic features may demonstrate<br />

light chain restriction. Exceptionally, lymphoma<br />

cells express CD30 antigen {18}.<br />

Burkitt lymphoma<br />

ICD-O code 9687/3<br />

The morphological features of Burkitt<br />

lymphoma of the <strong>breast</strong> are identical<br />

with those seen in such a lymphoma in<br />

other organs and tissues: the infiltrate is<br />

composed of sheets of uniform, primitive<br />

looking, cells of medium size, with<br />

round nuclei, multiple nucleoli, coarse<br />

c h romatin and a rather thick nuclear<br />

membrane. The cells are cohesive and<br />

the cytoplasm is moderate in amount<br />

with fine vacuoles containing lipids; it<br />

s q u a res off with the cytoplasm of adjacent<br />

cells. Mitoses are very numero u s .<br />

N u m e rous tingible-body macro p h a g e s<br />

a re evenly dispersed among the neoplastic<br />

cells producing the characteristic,<br />

but by no means pathognomonic,<br />

“ s t a r ry sky” appearance of the lymphoma.<br />

The <strong>breast</strong> tissue is usually<br />

hyperplastic and secre t o ry.<br />

Patients are usually pregnant or lactating<br />

women, particularly from tro p i c a l<br />

Africa where Burkitt lymphoma is<br />

endemic {2643}. Less fre q u e n t l y, nonendemic,<br />

sporadic cases, primarily presenting<br />

in the <strong>breast</strong>s, have been<br />

observed {1378}. Tumours typically<br />

p resent with massive bilateral bre a s t<br />

swelling {2643}.<br />

Fig. 1.161 Burkitt lymphoma. Bilateral <strong>breast</strong><br />

involvement may be the presenting manifestation<br />

during pregnancy and puberty. BL cells have prolactin<br />

receptors.<br />

I m m u n o h i s t o c h e m i c a l l y, pan-B markers<br />

a re positive, surface Ig, usually of IgM<br />

type, is also positive. In addition, CD10<br />

and bcl-6 are commonly positive, while<br />

CD5, bcl-2 and TdT are negative. EBV<br />

is frequently demonstrated in endemic<br />

but not in sporadic cases. IgH and IgL<br />

genes are re a r r a n g e d .<br />

Extranodal marginal-zone B-cell<br />

lymphoma of MALT type<br />

ICD-O code 9699/3<br />

At least some <strong>breast</strong> lymphomas<br />

appear to belong to the category of<br />

M A LT lymphomas although the data<br />

on their frequency vary substantially.<br />

The <strong>breast</strong> was suggested to be one<br />

component of a common mucosal immune<br />

system {268} and may acquire<br />

lymphoid tissue as a part of an autoimmune<br />

process {2585} within which<br />

the lymphoma may develop. A number<br />

of recent series on <strong>breast</strong> lymphoma<br />

include examples of MALT lymphoma<br />

{534,994,1261,1580,1792}; they were<br />

not encountered in other series {117,<br />

296,1346,1665}.<br />

C l a s s i c a l l y, MALT lymphomas are composed<br />

of small lymphocytes, marginal<br />

zone (centrocyte-like) and/or monocytoid<br />

B-cells, often interspersed with<br />

larger blastic cells. Monotypic plasma<br />

cells may be numerous and sometimes<br />

p redominant. The infiltrate is diff u s e<br />

and neoplastic colonization of pre - e x i s-<br />

tent reactive follicles may be seen. A<br />

lymphoepithelial lesion, defined originally<br />

as an infiltration of glandular<br />

epithelium by clusters of neoplastic<br />

c e n t rocyte-like cells {1305}, is rare l y<br />

seen. Neoplastic infiltration and destruction<br />

of mammary ducts by lymphoma<br />

cells, most commonly encount<br />

e red in large B-cell lymphomas or infiltration<br />

of ductal epithelium by non-neoplastic<br />

T cells should not be confused<br />

with a true lymphoepithelial lesion.<br />

H o w e v e r, the presence of such a lesion<br />

is not a pre requisite for a diagnosis of<br />

M A LT lymphoma.<br />

I n f l a m m a t o ry reactive conditions may<br />

mimic MALT lymphomas; perhaps<br />

many cases previously described as<br />

pseudolymphoma were in reality MALT<br />

lymphomas given enough time to follow<br />

their evolution.<br />

I m m u n o h i s t o c h e m i c a l l y, MALT lymphoma<br />

expresses pan-B cell markers<br />

108 Tumours of the <strong>breast</strong>

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