Prof. Bethy S. Hernowo, dr.

, SpPA(K), PhD

Department of Anatomical Pathology, Faculty of Medicine, Universitas

Padjadjaran, Bandung, Indonesia
Globocan, 2018
Your Picture Here
Diagnosis

Clinical Examination

- Both its sensitivity and

discriminatory power are
limited

- Only 10% of the tumors

being detected solely by
palpation

Ackerman, 2018
Your Picture Here
Diagnosis

Clinical Examination Radiology Examination

- Both its sensitivity and - Majority breast cancers are

discriminatory power are detected through imaging
limited studies

- Only 10% of the tumors - Calcification in breast

being detected solely by carcinoma is approximately
palpation 50-60% and 20% in benign
breast disease

Ackerman, 2018
Breast Revision Article, 2011
Breast Revision Article, 2011
 Breast Carcinoma Diagnosis

Clinician Findings Radiologist Findings

Pathologist Findings
 ne
Ben

li
er
ign

rd
Malignant

Bo
Benign Breast Lesions That
Mimic Malignancy
MUCOCELE LIKE LESIONS
Vs Mucinous Carcinoma
Mucocele like lesions
• Mucocele-like lesions are characterised by ducts and
cysts distended by mucin, typically associated with
extravasation of mucin into the surrounding stroma,
creating stromal mucin pools of varying size.

• The stromal mucin pools are characteristically

acellular, but may occasionally contain detached
fragments and strips of epithelium from the duct orcyst
lining.
Microscopic
• Cystically dilated ducts contain luminal mucin:
• Space lined by cuboidal to attenuated
epithelium
• Histocytes and inflammatory cells may be
present
• Epithelium may show spectrum of proliferative
change including hyperplasia, ADH or DCIS
• Ruptured ducts with extravasated mucin in
surrounding stroma are common
 Microscopic

Cystically dilated ducts contain luminal mucin: Space lined by cuboidal to attenuated epithelium
Mucocele-like lesion (MLL)
consists of multiple mucin-
filled cysts.

Ruptured ducts with

extravasated mucin in
surrounding stroma are
common .
(A) Low power of a mucocele like lesion in which some of the epitelial lining has become detached
feom the duct wall
(B) Highe power view illustrating the detached strips of benign epithelium.
Epithelium may show spectrum of proliferative change including hyperplasia,
ADH or DCIS
Epithelium may show
spectrum of proliferative
change including hyperplasia,
ADH or DCIS
QUIZ

BENIGN or MALIGNANT
QUIZ #1
MUCINOUS CARCINOMA
QUIZ #2
MUCOCELE LIKE LESION
QUIZ #3
MUCOCELE LIKE LESION WITH DCIS
 Mucocele Like Lesion Mucinous Carcinoma

Often incidental, may be Usually presents as a mass

identified as microcalcifications Clinical lesion, either image detection
in mammogram or palpable

Usually acellular, without

Cellular, with
vessels, but may contain
detached strips or fragmen of
Histology Mucin neovascularization composed of
thin walled vessel
epithelium

Most often low cuboidal to

Tumour cells in small clusters
columnar cells lining cysts, typically
dispersed within mucin pools,
with no atypia or stratification, but Epithelial Element generally with low to intermediate
may show proliferative changes
grade nuclear atypia
including UDH, ADH and DCIS

Myoepithelial markers highlight

myoepithelial cells associated with
detached epithelial fragments, but Immunophenotype No associated myoepithelial cells
may be negative if only epithelial using myoepithelial markers
cells are detached
MUCOCELE LIKE LESIONS
Vs Mucinous Carcinoma

TUBULAR ADENOSIS
Vs Tubular Carcinoma
TUBULAR ADENOSIS

The term adenosis refers to a group of

benign, non-neoplastic breast lesions that
share in common an increase in the number
of mammary acini.
Microscopic
• Tubular adenosis is characterised by a haphazard
proliferation of elongated tubules that lacks the
circumscription seen with other forms of adenosis.

• The tubules branch and intersect at varied angles, and

appear rounded when cut in cross section. The tubules
may be well-defined, collapsed, slit-like, or mildly
cystically dilated, and may have either blunted or
occasionally pointed ends.
Tubular adenosis. Low power view demonstrating the haphazard
arrangement of the tubules.
Tubular adenosis. Higher power view showing the angled tubules and the
presence of myoepithelial cell layer surrounding the tubules.
Tubular adenosis. Myoepithelial cell layer highlighted with a smooth muscle
myosin heavy chain immunostain.
QUIZ

BENIGN or MALIGNANT
QUIZ #1
p63
Tubular Adenosis
 Tubular Adenosis
Often incidental, may be
identified as microcalcifications
or mass on imaging studies
Haphazard proliferation lacking
circumscription. Tubules branch
and intersect at different
angles, blunted ends, typically
with luminal secretions that
often calcify
Tubules composed of epithelial
cells with surrounding
myoepithelial cell layer
Myoepithelial markers highlight
surrounding myoepithelial layer
Immunophenotype
Tubular Carcinoma
Usually presents as a mass
lesion, either image detected
Clinical or palpable; rarely may be an
incidental finding
Tubules with sharply angular contours
and tapering ends (in tubular
carcinoma), and an infiltrative growth
Histology
pattern; may have secretions and/or
calcifications; prominent apical
luminal snouts
Tubules/glands composed of
Cell Layer epithelial cells without a
surrounding myoepithelial cell
layer
Negative for myoepithelial
markers
QUIZ #2
Myoepithelial Marker (SMA)
Benign or Malignant
Let’s do S100
S100
Microglandular Adenosis
MUCOCELE LIKE LESIONS
Vs Mucinous Carcinoma

TUBULAR ADENOSIS
Vs Tubular Carcinoma

MICROGLANDULAR ADENOSIS
Vs Tubular Carcinoma
MICROGLANDULAR
ADENOSIS
• A rare form of adenosis in which small,
uniform glands with open lumina
containing eosinophilic secretions are
distributed in a haphazard fashion within
the fibrous tissue or fat
Microscopic

• The glands are composed of a single layer of

small, uniform cuboidal cells with vacuolated or
granular cytoplasm, lacking apocrine-type
“snouts.”

• In contrast to other forms of adenosis, the

myoepithelial layer is absent.
Microglandular adenosis (MGA) consists of small, round tubules lined by epithelial
cells that appear to be randomly scattered in normal fibroadipose tissue
The tubules of MGA consist of a single cell layer of uniformappearing epithelial
cells with small, bland nuclei. The lumina are typically filled with dense
eosinophilic secretory material. No myoepithelial cells are present.
 MGA is not associated with myoepithelial cells. There is weak
cytoplasmic immunoreactivity for p63. In contrast, normal lobules show
p63(+) myoepithelial cells .
MGA is negative for myoepithelial markers, such as smooth muscle myosin
heavy chain . Surrounding normal lobules show positivity in
myoepithelial cells .
MGA is strongly positive for nuclear and cytoplasmic S100. Carcinomas
arising in association with MGA also show strong S100 positivity.
 Microglandular Adenosis Tubular Carcinoma

Often incidental, may be Usually presents as a mass

identified as lesion, either image
Clinical
microcalcifications or mass detected
on imaging studies or palpable; rarely may be
an incidental finding

Round shape tubules,

Pointed shape tubules, variable in
uniform in size, absent of Histology
size, apical snouts often present.
apical snouts.

Myoepithelial Cell
Absent Absent
Layer

Negative for hormone Positive for hormone

receptor. Immunophenotype receptor.
Positive (strong) for S100 Negative (or weak) for S100
QUIZ

BENIGN or MALIGNANT
QUIZ #1
TUBULAR CARICNOMA
 Microglandular Adenosis Tubular Carcinoma

Often incidental, may be Usually presents as a mass

identified as lesion, either image
Clinical
microcalcifications or mass detected
on imaging studies or palpable; rarely may be
an incidental finding

Round shape tubules,

Pointed shape tubules, variable in
uniform in size, absent of Histology
size, apical snouts often present.
apical snouts.

Myoepithelial Cell
Absent Absent
Layer

Negative for hormone Positive for hormone

receptor. Immunophenotype receptor.
Positive (strong) for S100 Negative (or weak) for S100
Microglandular Adenosis
TUBULAR CARICNOMA
MUCOCELE LIKE LESIONS
Vs Mucinous Carcinoma

TUBULAR ADENOSIS
Vs Tubular Carcinoma

MICROGLANDULAR ADENOSIS
Vs Tubular Carcinoma

COLLAGENOUS SPHERULOSIS
Vs Adenoid Cystic Carcinoma or DCIS
COLLAGENOUS SPHERULOSIS

Benign epithelial proliferation of luminal cells and

matrix producing myoepithelial cells

Collagenous spherulosis is a benign histological

alteration of the breast epithelium that is most
often found in association with other breast
lesions.
Microscopic
• The hallmark feature of collagenous spherulosis is the presence of acellular,
hyaline, eosinophilic spherules or fibrillary, eosinophilic to
basophilic/mucoid amorphous material within lumina conferring a
fenestrated or cribriform configuration

• Myoepithelial cells of CS produce extracellular basement membrane-like

material (matrix)
- Made up of polysaccharides, laminin, and type IV collagen
- Positive for PAS and Alcian blue
- This cribriform or fenestrated pattern mimics punched out spaces
formed by luminal cells in cribriform DCIS

• Immunohistochemical studies (calponin, p63, myosin heavy chain) to

highlight myoepithelial cells may be helpful
Collagen spherulosis is characterised by the presenceof myoepithelial cells
surrounding the “punch out” space. The epithelial cells present are benign
 The basement membrane-like material in this lesion has a very mucinous appearance . There is a
thicker densely pink cuticle at the periphery ﬉. A true empty lumen formed by luminal cells is also
present.
 The basement membrane-like material ﬉, includingpolysaccharides, laminin, and type IV collagen,
shows similar staining features on Alcian blue/PAS to those of the basement membrane seen at the
periphery of this duct .
 The spherules in CS are lined by p63(+) myoepithelial cells . Myoepithelial cells are
also present at the periphery . Luminal cells show red cytokeratin positivity ﬈. Apical
blebs project into the true lumina.
In cribriform DCIS, normal p63(+) myoepithelial cells are present at the periphery on the
basement membrane ﬈. The lumina are formed by p63(-) tumor cells .
 Immunoperoxidase studies are useful to demonstrate the 2 distinct tumor cell
populations in ACC. The luminal-type cells are positive (in some cases) for CD117 as
well as low molecular weight keratins. The myoepithelial cells are negative .
 Collagen Spherulosis
Usually incidental microscopic
finding; may present as
mammographic microcalcifications
CS lesion usually < 0,5 cm
Not infiltrative, confined to
preexisting ducts, lobules, or
epithelial proliferative lesions
Spherules containing acellular,
hyaline, eosinophilic or basophilic
fibrillary basement membrane
material, within an epithelial
proliferation; myoepithelial cells
surround material
Positive for SMA, S100, p63
Positive for calponin, smooth
muscle myosin heavy chain
Negative for c-kit
Adenoid Cystic Carcinoma
Usually presents as a mass lesion,
either image detected or palpable
Clinical
ACC lesion more than 1 cm, usually >
2 cm
Invasive growth pattern, with variable
Histology architectural patterns, including solid,
cribriform, tubular, and trabecular
Nests or glands composed of
epithelial cells, myoepithelial
Morphology /basaloid cells, and acellular,
eosinophilic basement membrane
material
Positive for SMA, S100, p63
Variable expression of calponin,
Immunophenotype
smooth muscle myosin heavy chain
Positive for c-kit
MUCOCELE LIKE LESIONS
Vs Mucinous Carcinoma

TUBULAR ADENOSIS
Vs Tubular Carcinoma

MICROGLANDULAR ADENOSIS
Vs Tubular Carcinoma

COLLAGENOUS SPHERULOSIS
Vs Adenoid Cystic Carcinoma or DCIS

RADIAL SCAR
Vs Invasive Carcinoma
RADIAL SCAR / RADIAL
SCLEROSING LESION
Complex sclerosing lesion (CSL) includes lesions
consisting of confluent sclerosing adenosis,
sclerosing papillomas, &/or multiple RSLs

RSL is subcategory of CSL, which has central

hyalinized nidus and radiating arms forming
irregular mass or area of architectural distortion
on imaging
Microscopic

• Essential features of RSL are central fibrotic nidus surrounded by

radiating arms (corona), creating overall mass with irregular margins

• Central nidus
○ Entrapped and distorted small glands in cellular or collagenized
stroma

• Corona
○ Radiating epithelial components appear to expand or enlarge,
moving away from central nidus
○ Varying degrees of proliferative epithelial changes present
 RSL is characterized by a central fibrotic nidus surrounded by radiating arms with
proliferative changes (the corona ) forming an irregular mass. "Early" RSL is described
as having numerous compressed glands in the central fibrotic nidus.
 This RSL forms an irregular mass with a central area of stromal sclerosis that
contains entrapped and distorted glands and epithelial cell nests. The periphery of
RSL is frequently associated with adenosis and epithelial hyperplasia.
 The central fibroelastotic zone of a typical RSL demonstrates a dense sclerotic
stroma , which is paucicellular and at times can have a blue-gray color due to
elastosis.
An RSL is composed of cells positive for luminal keratins (red) and basal keratins (brown)
and myoepithelial cells positive for nuclear p63 . However, myoepithelial cells may be
difficult to detect in some of the small glands.
 The malignant tubules of tubular carcinoma are positive for cytokeratin (red cytoplasm)
and lack a surrounding myoepithelial cell layer. In contrast, adjacent normal ducts have a
layer of peripheral myoepithelial cells , positive for p63.
 Radial Scar Invasive Carcinoma

Stellate irregular mass (may

show radiolucent central area);
Clinical Stellate irregular mass; spicules
spicules are longer than size of
are shorter than size of mass
mass

Stellate centrifugal pattern;

Haphazard distribution of neoplastic
radiating proliferation increases Histology
ducts, central and peripheral
in size away from central region

Hyalinized, fibroelastotic
Desmoplastic stroma, more
stroma, less cellular, confined to Stroma cellular, present throughout
center of lesion

Present, surrounding entrapped

ducts (may be focal or
patchy); multiple myoepithelial Immunophenotype Absent around malignant
markers may be tubules
needed to demonstrate
 Take Home Message

To confirm our diagnosis,

immunohistochemistry is a reliable tool
Thank You