Dealing with atypia and papillary lesions of breast

1. DEALING WITH ATYPIAAND
PAPILLARY LESIONS OF
BREAST
CHAIRPERSON : DR SACHIN KOLTE
MODEARATOR : DR AKANSHA
PRESENTOR : DR SADIYA SHAIKH

2. CONTENTS
• Introduction
• Atypia in pathology
• Lesions with Atypia in breast
• Papillary lesions in breast
• Summary
• Conclusion
• references

3. INTRODUCTION
• Atypia in breast pathology may be cytonuclear and/or architectural with different
applications and implications.
• Cytonuclear atypia is used to assist the distinction of various intraductal epithelial
proliferative lesions
• Stromal cell cytonuclear atypia is one of the key features used to distinguish Fibroadenoma
from Phyllodes tumour (PT) and to classify PT as benign, borderline or malignant.
• Architectural atypia is used to differentiate flat epithelial atypia (FEA) from ADH or
DCIS.

4. WHO Classification of Breast tumors

5. NORMALANATOMY
Gross arrangement: 15-20 secretory lobes
separated by suspensory ligaments.
Secretory lobes: consist of lobules and tubule
alveolar glands, which produce milk in response
to prolactin.
Lactiferous ducts: these secretory ducts of the
lobes are formed by converging lobules and
intralobular ducts.

6. HISTOLOGY
Ductal - lobular system
Acini are grouped together in clusters to form
lobules
Cellular lining of the ductal - lobular system is
bilayered and consists of:
• Inner (luminal) epithelial cells: cuboidal to
columnar epithelium with pale
eosinophilic cytoplasm
• Outer (basal) myoepithelium: variably
distinctive, varies in appearance from
flattened cells with compressed nuclei to
prominent epithelioid cells with abundant
clear cytoplasm, can sometimes have
myoid appearance
Stroma:
Consists of varying amounts of fibrous tissue and
adipose tissue
Nipple - areolar complex: skin variably
pigmented, contains numerous sebaceous glands

7. Normal breast tissue, small terminal
ductule: small epithelial tissue fragment
showing larger ductal nuclei with bland
chromatin and smaller oval darker
myoepithelial nuclei; bare bipolar oval
nuclei in the background (Giemsa, ×400).
CYTOLOGY

8. ATYPIA
• Refers to deviation from normal or typical morphology
• Presence of one or more cellular or architectural features
that deviate from an otherwise normal appearing cells or
group of cells
• Dysplasia –used to describe morphological change
resulting from genetic mutations that facilitate malignant
transformation
• Atypia also includes reactive atypia secondary to
inflammation ,trauma,radiation or other external insults

9. • In contrast to organs like cervix, no evidence that atypia in breast is
reversible, regardless of grade or that there is progression from low to
high grade atypia.
• All the changes from low to high grade DCIS appear to develop
secondary to different genetic pathways of carcinogenesis.

10. EPITHELIAL ATYPIA IN BREAST PATHOLOGY
• NUCLEAR FEATURES
NUCLEAR SIZE Increase in size as compared to normal epithelial cells of TDLU, RBC or
lymphocytes
NUCLEAR OUTLINES Nuclear membrane folding /angulation
May show regular outlines also
PLEOMORPHISM Variability in size shapes and staining of nuclei.
Usually a feature invasive and high grade carcinomas
CHROMATIN PATTERN Hyperchromasia, polychromasia, vesicular
NUCLEOLI Enlarged ,multiple and prominent
NUCLEAR SHAPE Spindle ,bi-lobed, multilobed and multinucleated

11. Cytoplasmic features:
N:C ratio
• Reaches 1:1 or even reversed
Cytoplasmic staining
• Eosinophilia with well defined cell membranes
seen

12. Additional features
Architectural atypia
(cell polarization and abnormal patterns: cribriform, micropapillae, reverse polarity)
Myoepithelial cells
absence= invasive malignancy
Bland looking cells can be atypical/neoplastic
Cellular cannibalism Cell dyscohesion
Mitosis
Atypical forms and increase in
number
Cellular clonality
(monoclonality is a feature of
malignancy)

13. Use of epithelial atypia in breast lesions
• Nottingham Grading System (grading of IBC)

14. Grading of DCIS
• Ductal carcinoma in situ (DCIS) is a
neoplastic proliferation of mammary
ductal epithelial cells confined to the
ductal-lobular system.
• No evidence of invasion through the
basement membrane into the
surrounding stroma
• Non-obligate precursor lesion of
invasive breast cancer

15. • DCIS traditionally classified based on
architectural growth pattern (no
clinical relevance other than comedo
pattern):
• Cribriform:
• Micropapillary:
• Papillary:
• Solid:
• Flat or clinging:
• Comedo:
Duct space involved by an intraductal
epithelial proliferation with low grade
nuclear atypia and cribriform growth
pattern.
Intraductal epithelial proliferation with
intermediate grade nuclear atypia,
cribriform growth pattern and
microcalcifications.
Intraductal epithelial proliferation
with high grade nuclear atypia, solid
growth pattern, lobular extension and
focal necrosis.

16. A-Sheets of mildly atypical ductal cells, necrotic
debris and calcium granules
B- large sheet of ductal epithelium with many holes
suggestive of cribriform pattern, no myoep cells.

17. Reporting pattern of DCIS
CORE NEEDLE BIOPSY
• Procedure
• Laterality
• Tumor site (specify clockwise)
• Histological type
• Architectural pattern
• Nuclear grade
• Necrosis
• Microcalcifications
• Special studies
RESECTION SPECIMENS
Additional things apart from biopsy:
• Margins
• Regional lymph nodes
• Metastasis
• pTNM

18. Limitations of core needle biopsies
• Tissue fragmentation/distortion
• Difficulty in distinguishing ADH and low grade DCIS
• Loss of foci of microinvasions
• Difficulty in evaluation of papillary lesions
• Loss of microcalcifications
• Entire architecture of the lesion cannot be assessed.

19. ASSESSING ATYPICAL DUCTAL HYPERPLASIA
• Intraductal clonal epithelial cell
proliferation with cytologic and
morphologic features similar to low
grade ductal carcinoma in situ
• Similar histologic patterns as DCIS
• Distinguished on basis of size
ADH with cribriform architecture. Note the polarization around
the lumina.

20. Large sheets of mildly atypical cells , holes
indicating cribriform pattern, no myoep cells seen.
Aggregates of moderately atypical ductal epithelial
cells, some loss of cohesion, no myoep cells

22. Epithelial atypia post therapy
• Following RT and systemic CT , epithelial
cells may show atypia which may be
difficult to distinguish from neoplastic
atypia or recurrent/residual DCIS
• Cellular enlargement , multi-nucleation,
vacuolisation and chromatin clearing can be
seen
Tumor cells showing pyknosis and karyorrhexis

23. Key features in recognizing therapeutic effect
Retention of normal lobular configuration and
atrophy with surrounding inflammation and fibrosis
Preservation of myoepithelial cells and absence of
mitosis
Similar alterations in surrounding tissues suggest a
therapeutic process rather than neoplastic
• Challenging cases –
use Ki67 along with
IHC findings

24. Epithelial atypia and metaplastic changes
• Benign metaplastic epithelial cells may
show features that overlap with atypia.
• Apocrine metaplasia: cytoplasmic and
nuclear changes with nuclear
pleomorphism and prominent nucleoli
• Not regarded as atypical if variation in
nuclear size is less than 3 fold slight variation in nuclear size can be present in
apocrine metaplasia; this is not considered to be an
atypical feature.

25. •Nuclei of benign apocrine cells are
eccentrically located with slight variation in size;
the nuclear membrane is smooth with fine
granular dispersed chromatin and a single
prominent nucleolus
•Cytoplasm is abundant and dense with distinct
cell borders with diffuse finely granular
cytoplasm that stains pink / blue in PAP stains
and purple / gray in Romanowsky stains

26. • Atypical apocrine adenosis- three fold
variation in nucleus size
• Apocrine DCIS-
• High grade atypia
• Easy to diagnose
High
grade
• Architectural atypia,
extent
• Demonstration of
clonality
Low
grade
Large atypical epithelial cells with abundant eosinophilic and
granular cytoplasm, enlarged nuclei and prominent nucleoli.

27. Epithelia atypia and nuclear size
• Comparison of tumor cell nuclear size to epithelial nucleus size is an
objective criterion
• Limitations of this approach:
Epithelial cells may show variation in size and
shape owing to age, hormonal effects and
metaplastic change
Size of RBC is considered equal to normal
epithelial cells which is not accurate
Size of RBC or epithelial cell may vary
according to cytological preparations

28. ATYPIA IN BREAST MYOEPITHELIAL CELLS (MECs)
• Usually frame the glandular structures resulting in double cell layer
• Spindle, stellate or polygonal in shape
• Cytoplasm is variously eosinophilic or clear
• Nucleus – central or eccentric (plasmacytoid)
• Size range – 3.52-7.91 micro meter.
• Comparison with normal MECs not used as a standard by pathologists
• Lesions of myoepithelial cells are rare

30. Atypia in breast stromal cells
• Reference cells are fibroblasts in
stroma
• Fibroepithelial lesions are common in
breast therefore assessment of atypia
helps in distinction of Fibroadenoma
and Phyllodes tumor
• Can alse be used for grading of
Phyllodes tumor

32. PHYLLODES TUMOR:
• Fibroepithelial neoplasm with leaf-like epithelial (phyllodal) pattern and
stromal proliferation
• Leaf-like (phyllodal) epithelial pattern formed by an exaggerated
intracanalicular pattern
• Graded into benign, borderline and malignant histologic grades
Cystic degeneration, hemorrhage, stromal hyalinization and myxoid change
reported
• On IHC:
• Epithelial cells
• Cytokeratins, ER, PR, GCDFP-15
• Stromal cells
• Vimentin, CD34, BCL2, ER beta

33. Hyperchromatic and irregular stromal
cells in borderline phyllodes tumor
Fine-needle aspiration cytology benign phyllodes tumor (H and E,
×400) showing stromal hyperplasia embedded in a loose myxoid
tissue. Cell block benign phyllodes tumor (H and E, ×100) showing
stromal cellularity having a characteristic leaf-like pattern

34. Grading of phyllodes tumor

35. • NOTE:
• Stromal cells in FA can show morphological changes in the form of large cells with
bizarre nuclei and clumped chromatin, similar to the changes seen following
chemotherapy or radiotherapy.
• These changes may also occur in benign PT, other benign soft tissue lesions of the breast
and in the normal background breast stroma.
• Cells showing these features are described as atypical stromal cells or stromal
multinucleated giant cells. The nature and clinical significance of these cells are still not
clear, but they typically lack proliferative activity and p53 alterations.
• Awareness of this morphological alteration helps to avoid misdiagnosis as borderline or
malignant, particularly in FELs.

36. Atypia in endothelial cells of breast
• Atypical endothelial cells show nuclear enlargement, which may become plump (hobnail),
hyperchromatic and may show discernible nucleoli.
• In atypical vascular lesions seen following radiotherapy, the vascular spaces are lined by
mildly atypical endothelial cells
• Assessment of endothelial cell atypia is important in needle core biopsy of the breast, as
exclusion of angiosarcoma is crucial.

37. • In angiosarcoma, endothelial cell atypia ranges
from minimal to significant atypia resembling
that seen in high-grade IBC nuclei, particularly
in the solid areas.
• Therefore, high nuclear grade endothelial cell
atypia is a feature of angiosarcoma.
• Cytological changes are subtle and diagnosis is
supported by destructive invasion but some
degree of atypia can be seen
Complex
anastomosing vessels
with hyperchromatic
endothelial cells.
Large
hemorrhagic mass
involving breast
skin and
parenchyma.

38. The term Atypical in breast refers to presence of cytological features seen predominantly in
benign lesions but with addition of few features that are uncommon in benign lesions and may
be seen in malignant lesions

39. Cytological features of Atypical category in Yokohama system
• High cellularity
• Increased dispersal of single intact cells
• Enlargement and pleomorphism of nuclei
• Presence of necrosis or mucin
• Complex micropapillary or cribriform
architecture of epithelial tissue fragments
LESIONS ASSOCIATED
• Usual epithelial hyperplasia
• Fibroadenomas with atypia
• Radial scars
• Intraductal papillomas
• Adenomyoepithelioma
• Spindle cell lesions

42. MANAGEMENT OF THE LESIONS
• Atypical diagnosis due to technical problem- repeat FNAC
• Clinical and imaging findings are suspicious-repeat FNAC mandatory
• If neither clinical or imaging findings are of concern-review patient
after 3-6 mnths.

43. Clinical impact of diagnostic discordance of atypia
• Inter/intra observer diagnostic discordance can lead to repeat or open diagnostic
procedure, changes in follow up protocols and adjuvant treatment regimes.
• Failure to recognize atypia may lead to:
1. Under treatment
2. Progression of disease
3. Negative impact on prognosis

44. Measures to minimize discordance
Application of standardized histological criteria
wherever applicable
Double reporting of borderline cases
Considering expert opinion in
challenging cases

45. PAPILLARY LESIONS OF BREAST

46. Papillary neoplasm of Breast
• Composed predominantly papillae with fibrovascular core covered by
epithelium with or without a myoepithelial depending on type of neoplasm.
• Nature of epithelium determines neoplasm as benign, atypical or malignant
• Most of them confined are within ducts and tend to distended or cystic with
thick fibrous wall
• Myoepithlial cells has to be assesed within the FV core as well as in the
periphery of the duct

47.  Difficult to diagnose due to overlapping radiological, morphological and immunohistochemical
profiles.
Radiological
IHC
Histopathological
Molecular
Diagnosis of papillary breast
neoplasm is mainly based on
histomorphology and IHC.
Role of molecular studies is
still limited.

48.  Papillae: Finger like projections
composed of fibrovascular core
covered by epithelium
 Micropapillae: Small papillary
tufts without a fibrovascular
core

49. Fragment of micro-architecture
showing papillae with a fibrovascular
core compatible with breast papillary
carcinoma (Papanicolaou x10).

50. Classification Of Papillary Neoplasm Of Breast
• Solitary(central) Intraductal papilloma
• Multiple(peripheral) Intraductal papilloma
Benign
• Intraductal papilloma with atypical hyperplasia
• Intraductal papilloma with DCIS
Atypical
• Papillary DCIS
• Encapsulated papillary carcinoma
• Solid papillary carcinoma
• Invasive papillary carcinoma
Malignant

51. Concept of Myoepithelial Cells
Intraductal papilloma
Intraductal papilloma
with ADH/DCIS
Papillary DCIS

52. Encapsulated
papillary carcinoma
Solid papillary
carcinoma

53. IHC Markers for Myoepithelial Cells
P63- Nuclear p40- Nuclear Calponin-Cytoplasmic
SMA- Cytoplasmic SMMHC-Cytoplasmic CK5/6, CK14- Cytoplasmic

54. Aberrant p63 staining
p63- Stain nuclei of carcinoma cells in papillary
carcinoma
SMA, Calponin staining MEC as well as
pericytes of vessels

55. CK5/6, CK14: positive in hyperplastic
proliferations
CK5/6, CK14: negative in
clonal/neoplastic proliferations

56. INTRADUCTAL PAPILLOMA
• Benign breast lesion arising within a duct
• Composed of papillary projections and fibrovascular
cores covered by epitheial and myoep layer
• 5% of all benign breast lesions
• Aspirates of IDP yields small amount of fluid and
maybe the most cellular smears seen in FNA of breast
• Complex folded sheets with collagenous stromal cores
–most characteristic feature
• Hemosiderin pigment and debris are common finding

58. Pathogenesis:
 Monoclonal proliferations.
 Activating point mutations in PIK3CA/AKT1
pathway
 Loss of heterozygosity on 16p13
Grossly:
 Appears as tan-pink well circumscribed round tumor
protruding into dilated duct or cystically dilated
space.
 Papillary fronds attached by one or more pedicles to
the wall of dilated ducts
 Focal areas of necrosis and hemorrhage Cohesive arborising papillary fronds
within duct space lined by layer of
myoepithelial cells

59. Broad and blunt fibrovascular core in
a hyalinized stroma  Fibrovascular cores covered by myoepithelial cells and overlying
epithelial cells.
 Epithelial cells are single layer of cuboidal to columnar cells with
minimal pleomorphism, normochromatic, absent mitotic activity.
 Myoepithelial cells are in continuous layer in fibrovascular core and
at periphery.

60. P63 staining: MEC along the fibrovascular
core as well at the periphery of duct
Cytoplasmic SMMHC: continuous layer of
myoepithelium.

61. Morphological Variations in Intraductal Papilloma
• 2) Usual ductal hyperplasia
1) Apocrine Metaplasia Infarction, Necrosis, Hemorrhage:
Epithelial cells: heterogenous
with crowded overlapping nuclei.
Epithelial cells: Large with abundant
cytoplasm, opened up chromatin, lack
of cytological atypia.
• Occurs due to torsion of stalk or
after a needling procedure (FNA or
biopsy)
• Associated with bloody nipple
discharge

62.  ESSENTIAL CRITERIA:
o A breast lesion occurring
within a duct, composed of
papillary projections with
fibrovascular cores, covered by
an epithelial and myoepithelial
layer.
 DESIRABLE CRITERIA:
o Demonstration of
myoepithelial cells within and
at the periphery of lesion by
IHC.
 PROGNOSIS:
o Proliferative disease without atypia,
o 1.5-2 fold relative risk or 5-7% absolute lifetime risk of
breast carcinoma,
o Increases with peripheral papilloma.
 TREATMENT:
 Follow up: Asymptomatic IDP without
atypia
 Excision is recommended:
1. Symptomatic papilloma(nipple
discharge, palpable mass)
2. Large papilloma(≥3cm)
3. Discordant pathological and
radiological findings
4. Papilloma with atypia

63. Intraductal Papilloma with ADH
Focal areas of of ADH (<3mm)
Proliferation of monotonous epithelial
cells with low grade nuclear features.
Punched out luminal spaces.
Cells are uniform with round
hyperchromatic nucleus
MEC: absent from these foci
Present at periphery

64. INTRADUCTAL PAPILLOMA with ADH/DCIS
WHO recommends relying on size as criterion for
distinguishing ADH and DCIS arising in underlying
papilloma :
 Atypical epithelial proliferation measuring < 3mm in
papilloma is diagnosed as ADH
 Atypical epithelial proliferation measuring ≥ 3mm in
papilloma is diagnosed as DCIS
When epithelial proliferation
with intermediate or high nuclear
grade are seen, diagnosis of
DCIS within a papilloma should
me made regardless of extent.

65. PAPILLARY DCIS
 Morphological subtype of DCIS
 It is characterized by an intraductal papillary
proliferation, with arborizing fibrovascular cores,
covered by neoplastic epithelial cells and are devoid
of intervening myoepithelial cells.
 Myoepithelial cells are retained at periphery of duct.
 Constitutes around 3% of all DCIS cases.

66. Delicate, branching fibrovascular core, lined by
neoplastic ductal epithelial cells
Epithelial cells are monotonous with low-grade
nuclei forming cribriform and glandular spaces.

67. Luminal cytokeratins
(CK7, CK18) positive
CK5: Absent in neoplastic epithelial
cells. But, stains the MEC at periphery
but not in fibrovascular core.
Strong and diffuse ER staining.

68. Papillary ductal carcinoma in situ
(DCIS) showing a cellular
fibrovascular core covered in a
multi- layered, crowded epithelial
proliferation with dispersed single
often columnar cells in the
background (Pap ×10);
(b) Papillary DCIS showing a thin
fibrovascular core cov- ered in a
multilayered crowded columnar cell
prolifera- tion, with small crowded
tissue fragments and some single
cells in the bloody background
(Giemsa ×10);
(c) Papillary DCIS showing a
fibrovascular core, small
dyscohesive tissue fragments of
crowded cells and some single cells
in the background (Giemsa ×10);

69. Diagnostic Criteria (WHO 5th
Edition)
 ESSENTIAL CRITERIA:
o A neoplastic proliferation of epithelial cells
covering delicate arborizing fibrovascular
cores devoid of myoepithelium but
contained within a duct with a surrounding
myoepithelial layer.
 DESIRABLE CRITERIA:
o Demonstration of absence of
myoepithelium along the fibrovascular
cores but presence of myoepithelium along
the duct wall by IHC.
 Molecular description: LOH at loci 16q13, 16q21,
and 16q23
 Staging: “pTis (DCIS)”
 Prognosis: Good, associated with recurrence
 Treatment:
1. Breast conservation surgery +/- adjuvant
radiation therapy
2. Hormonal therapy (ER/PR positive)

70. Underlying benign papilloma
that has been partially effaced
by conventional type DCIS
process
Intraductal malignant
proliferation where the papillae
themselves are a part of
neoplastic process.

71. Encapsulated Papillary Carcinoma
 Previously termed as Intracystic or Encysted
papillary carcinoma.
 It is an expansile papillary neoplasm that is well
circumscribed, present within a cystic space, and
surrounded by a fibrous wall/capsule.
 Characterized by fine fibrovascular stalks covered
by neoplastic epithelial cells of low or intermediate
nuclear grade.
 There is absence of myoepithelial cells along the
papillae as well as at the periphery of the lesion.
 Represents 0.5–1% of all breast carcinomas.

73.  Round, pushing borders
 Surrounded by a fibrous capsule
 Papillary mass within a cystic
space
 Multiple delicate fibrovascular
stalks.
Fibrovascular core is covered by single or multiple layer of
monomorphic neoplastic epithelial cells with low to intermediate
grade nuclei.
 Pseudostratification and polarisation around cores.
 MEC absent along the papillae as well as at periphery

74. p63 : negative staining of
MEC both along papillae and
at periphery
CK14: absence of staining
of neoplastic epithelial cells
Strong and diffuse staining
of ER in neoplastic cells

75. Encapsulated Papillary Carcinoma with Invasion
 Frank invasion -neoplastic elements that permeate beyond
the fibrous capsule with an irregular infiltrative
appearance.
 Myoepithelial cells are absent in invasive component.
 IHC: Show strong and diffuse ER positivity, HER2
negative
 Grading: Invasive component graded according to the
Nottingham grading system
 Staging: pT (according to size of invasive component)

76. C-Magnification x 100, MGG.
Monolayer (two-dimensional)
sheets as well as a complex
partly three-dimensional and
partly monolayer aggregate. In
additon we can see numerous
single cells and some “strips”
D- Magnification x 100, MGG.
Numerous micropapillary cell
groups
E. Magnification x 200, MGG.
The cells groups are loosely
cohesive with numerous single
cells. There is a mild to
moderate pleomorphism.
Microcalcification (arrow).
F. Magnification x 400, MGG. A
loosely cohesive sheet with
nuclei in the size range of 2-3 X
RBC

77. Solid Papillary Carcinoma
 It is a subtype of papillary DCIS.
 Characterized by a solid growth pattern with
interspersed delicate fibrovascular cores resulting in a
solid-papillary architecture.
 MEC are absent along the cores and at periphery, but
may have scattered and focal residual myoepithelial
cells.
 Often display neuroendocrine differentiation and are
biologically indolent.
 Constitute 1–2% of all primary breast cancers.

78.  Localization: central/subareolar , unifocal
 Age: Post menopausal women (7th decade)
 C/F: palpable breast mass +/- nipple discharge
 Imaging:
o USG: Solid, well-defined heterogeneous
mass, coexisting stromal distortion implies
an associated invasive component.
o Mammography: round, circumscribed mass
Well circumscribed, firm to soft
tumor with tan-white to tan-pink cut
surfaces

79. C. Magnification x 100, MGG.
Abundant cell material with large,
pseudopapillary and three-
dimensional epithelial aggregates,
smaller groups and a large single
cell population
D-. Magnification x 100, MGG.
Loosely cohesive cells with
abundant single cells
E- Magnification x 100, PAP.
Large, three-dimensional
aggregates, loosely cohesive cells
F-Magnification x 400, MGG.
Loosely to non- cohesive, low-
grade carcinoma cells with
plasmacytoid appearance.
Microcalcification (arr

80.  Well defined expansile nodules
 Solid growth pattern
 Inconspicuous, delicate fibrovascular
cores
 Monotonous population of round epithelial
cells with low-to intermediate grade
nuclear atypia.
 Polarization: cellular palisading around
cores

83. Invasive Papillary Carcinoma
 Rare subtype of invasive breast carcinomas
with infiltrative papillary growth.
 It is an invasive carcinoma with fibrovascular
cores covered by neoplastic epithelium.
 Characterized by papillary architecture in
>90% of invasive tumor.
 Myoepithelial cells are absent.

84.  Localization: Central or perpheral
 Age: Post menopausal women (7th decade)
 C/F: palpable breast mass +/- nipple
discharge
 Imaging:
o USG: hypoechoic mass with indistinct
margins .
o Mammography:
Microcalcifications
Hypodense mass

85. Microscopy:
Shows a frankly invasive growth pattern.
Predominantly papillary morphology (> 90%)
Lacks fibrous capsule
Desmoplastic reaction at invasive tumor front
Invasive Papillary Carcinoma

86. • IHC: Myoepithelial markers → negative
: HMCK(CK5/6, CK14) → negative
: ER/PR → positive
• Grading: according to the Nottingham
grading system
• Staging: pT according to the size of the
lesion
MEC absent at the periphery and along
papillary stalks

89. Diagnostic approach to papillary lesions of breast

90. REFERENCES
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