Issue 4 - August 2010 - Pacini Editore

130
New and old entities in breast pathology
V. Eusebi
Sezione di Anatomia Istologia e Citologia Patologica “M. Malpighi”
Università di Bologna
To use Goethe’s words “we see what we know”. As we know
very little new entities usually emerge as the result of better
technology as well as more accurate methods of analysis. In
addition some lesions tend to become obsolete and periodically
are rediscovered and rejuvenated.
In recent years very powerful molecular techniques have appeared
which has lead to the statement by some molecular
pathologists that by the year 2020, histopathology is going
to be history and all diagnostic work up is going to be in the
hands of scientists or machines.
This might be the case although, to use the words of Lorenzo
il Magnifico, “del diman non c’è certezza”. For the time being
it appears that in spite of great expectations in molecular
techniques, no very consistent achievements have been obtained.
One example for all. Perou et al. 1 , at the beginning of
this century, using a DNA array technique, reclassified breast
cancer among groups different from those classically used.
After nearly 10 years since the publication of Perou’s article,
it appears that the new classification is not very useful in
routine practice. One for example is the basal like carcinoma.
In spite of myriads of papers published on it, there is still no
a consensus on the definition of this type of tumor. Basal like
molecular profile appears to be in common with a heterogeneous
group of tumors which include very aggressive lesions
that are G. 3 and triple negative carcinomas together with
lesions that are quasi benign as well differentiated adenoid
cystic carcinomas.
Therefore we discuss here cases whose definition is mainly
based on morphology.
Breast carcinomas are simulated by a number of inflammatory
conditions.
Nodules either single, multiple or even bilateral are shown
by IgG4-related sclerosing mastitis 2 which is a new entry of
the syndrome of the IgG4-related sclerosing disease. This is a
recently recognized syndrome characterized clinically by tumour-like
enlargement of one or more exocrine glands as well
as extra-glandular tissue. There is raised serum IgG4 level and
histologically there is lymphoplasmacytic infiltration together
with sclerosis. There are an increased number of IgG4-secreting
plasma cells. The syndrome is believed to be autoimmune
in origin, it was originally observed in autoimmune sclerosing-pancreatitis
but a number of different sites have been
reported such as hepatobiliary tree, lachrymal glands, salivary
glands, lymph node, prostate, lung, kidney, retro-peritoneum
and mesentery, mediastinum, meninges and breast 2-5 . In this
latter site, of the 5 cases reported 2 were unicentric, 3 multifocal
and 1 bilateral. Breast lesions are characterized by dense
masses of lymphocytic infiltrate associated to intense sclerosis
and loss of lobules. Reactive lymphoid follicles can be seen
but granulomas as well as lympho- epithelial lesions are lacking.
IgG4+ ought to be no less than 50% of IgG+ elements.
This “inflammatory” lesion has to be distinguished from
low grade B cell lymphoma and Castleman’s disease. In addition
an inflammatory quasi neoplastic condition is Rosai
Dorfman’s disease that can affect the breast. Of the 7 cases
reported by Green et al. 6 , 3 patients had disease confined to
the breast, one had involvement of the breast and ipsilateral
auxiliary lymph nodes and two had bilateral breast involvement.
A xantomatous infiltrate with scattered Touton’s giant
cells and patchy lymphocytic infiltrate are the features of
5 th triennial congress of the italian society of anatomic Pathology and diagnostic cytoPathology
Erdheim-Chester (E-C) disease that may involve the breast
presenting as bilateral clinically malignant breast masses.
E-C disease is a rare non Langerhans cell histiocytosis of
unknown aetiology. The commonest sites of involvement are
long bones, skin, orbit pituitary and retro peritoneum. A number
of granulomatous mastitis can clinically simulate a breast
carcinoma among which idiopathic granulomatous mastititis 7 ,
sarcoid 8 and cat scratch disease.
Among the lesions that are rejuvenated, the most obsolete
entity that only recently has been brought up again is infiltrating
epitheliosis 9 .
Infiltrating epitheliosis (IE) was described by Azzopardi in
1979 in Chapter 9 “Overdiagnosis of malignancy” of his book
“Problems in breast pathology” 10 as “a lesion which is not
uncommon but which has not received adequate recognition
in the literature”, a statement very pertinent 30 years later.
Infiltrating epitheliosis (IE) is usually a microscopic lesion,
observed incidentally in cystic disease but which may infrequently
present as a palpable lump. The lesion is generally located
far from the nipple as epitheliosis (also known as usual
duct hyperplasia-UDH), which is the main component, affects
the acinar, terminal duct lobular unit (TDLU) and small duct
portions of the mammary lobes 10 .
The lesion is a complex epithelial-stromal interaction composed
of epitheliosis (UDH) which constitutes the bulk of the
lesion, and sclero-elastotic stromal changes.
At low power IE appears as an asymmetrical lesion, with
sclero- elastotic areas located randomly either in the centre
or at the periphery. The borders vary from irregular to circumscribed.
In palpable lesions the scleroelastotic areas can
be multiple.
Morphologically the lesion is composed of Epitheliosis (synonym
usual duct hyperplasia), and Scleroelastotic areas the
latter characterized by a stromal reaction which is not only
desmoplastic, but may also contain dense sclerotic and hyaline
collagenous bands…” not unlike the appearances seen in
a keloid” 10 . Finally abundant elastic tissue (elastosis) is seen
intermingled with the desmoplastic reaction or around small
ducts forming nodular foci. Infiltrating epitheliosis has to be
distinguished from Radial Scar (benign scleroelastotic lesion
simulating invasive duct carcinoma) which Hamperl in 1975
described as a microscopic lesion that he named in German
“strahligen narben”. In the summary this was translated as
“radial scar” 11 . A few months later, Eusebi et al. 12 independently
reported on the mammographic, macroscopic and
microscopic features 4 cases showing a lesion they named in
Italian “lesioni focali scleroelastotiche mammarie simulanti il
carcinoma infiltrante”. In the summary this was translated as
“mammary focal scleroelastotic lesions simulating an infiltrating
carcinoma”.
Both papers dealt with the same identical lesion 10 , the only
difference being the size. The lesions described by Hamperl 11
were selected on microscopic grounds and therefore were
minute. Those reported by Eusebi et al. 12 were selected at
mammography and all were palpable nodules, the largest
measuring 2.5 cm in greatest axis.
Both reports were in languages (German and Italian) that,
especially 30 years ago, were not readily available to the
scientific community. As a result the histological features of
radial scar (scleroelastotic lesion) were not fully appreciated
and the terms radial scar and infiltrating epitheliosis (and its
synonyms) that describe two different lesions (see later) are
used interchangeably by many authors.
RS has a central zone of sclero-hyaline fibrous tissue mixed
with abundant elastic tissue (elastosis). The sclero-elastotic