INTERPRETING BREAST CORES:

DIAGNOSTIC CHALLENGES AND

CLINICAL IMPLICATIONS

Sunati Sahoo, MD
Associate Professor
Department of Pathology
UT Southwestern Medical Center, Dallas, TX
ORIGINAL ARTICLE
Effect of three decades of screening mammography on
breast-cancer incidence
Archie Bleyer, M.D., And H. Gilbert Welch, M.D., M.P.H.
N ENGL J MED 2012; 367:1998-2005 NOV 2012

• Estimated that breast cancer was over diagnosed (i.e.,

tumors were detected on screening that would never
have led to clinical symptoms) in 1.3 million U.S.
women in the past 30 years
• Estimated that in 2008, breast cancer was over-
diagnosed in more than 70,000 women; this accounted
for 31% of all breast cancers diagnosed
The New York Times, Feb 11, 2014
“ Vast study casts doubts on value of mammograms”

25 year follow-up for breast cancer incidence and mortality of

the Canadian National Breast Screening Study: randomized
screening trial
Miller AB, Wall C, Baines CJ, Sun P, To T, Narod SA.
BMJ (Published 11 February 2014)
• Overall, 22% of screen detected invasive breast
cancers were over-diagnosed, representing 1 in
every 424 women who received mammography
screening in the trial
AMERICAN CANCER SOCIETY: NEW GUIDELINES
• While mammography is beneficial, the balance of its
potential to reduce death from breast cancer to the harms
associated with false positive imaging tests, additional
procedures (biopsies), and potential over-diagnosis
becomes more favorable at age 50

• All women should understand the benefits, limitations, and

potential harms of false positive findings and over-diagnosis
associated with screening mammography
American Cancer Society
recommendations for early detection:

Women age 50 and older should have a screening

mammogram annually and should continue to do so for
as long as they are in good health

 The goal of screening exams is to find cancers

before they cause symptoms

 Most feel that early detection saves thousands

of lives each year
Which mammal is represented in this picture?
Pathology Misdiagnoses
Overdiagnosis or Underdiagnosis
Reasons:
• In the past, FNA to diagnose breast lesions
• Patterns that are shared by benign and
malignant lesions
• Sampling error
• Inter-observer variation (ADH vs. DCIS)
• Unfamiliarity with the spectrum of changes
Patterns that are shared by benign and
malignant lesions

• Solid intraductal pattern

• Cribriform pattern
• Papillary pattern
• Small gland pattern
• Spindle cell pattern
• Others (inflammatory, metastases)
Case 1: A 60 year old was found to have a 1.2
cm density in the left breast on screening
mammogram. This finding was new since her
previous mammogram 3 years ago.
Ultrasound revealed this to be a 1 cm hypo-
echoic complex cystic lesion.

She underwent US-guided core biopsy

Case 1: US-guided core biopsy
Case 1: US-guided core biopsy
Case 1: US-guided core biopsy
Case 1: US-guided core biopsy
Case 1.
Core biopsy diagnosis: DCIS
ER and PR: Focally Positive
ER
Case 1: Partial Mastectomy
Case 1: Partial Mastectomy
Case 1: Partial Mastectomy
Case 1: Partial Mastectomy
Partial Mastectomy: IHC for ADH-5
- Mosaic pattern in UDH (CK5, 14, 7, 18, p63)
Final Diagnosis:
Left Breast, Partial mastectomy:
- Nodular area of proliferative breast
disease including fibrocystic change with
florid UDH
- No DCIS identified (Note)
Case 2: 49 year old FM with microcalcs
CASE 2: 49 YEAR OLD FM WITH MICROCALCS
Case 2: 49 year old FM with microcalcs

Diagnosis: Low grade DCIS

with streaming/spindling
Case 1: Nodular area of fibrocystic change with
florid UDH

• Were there clues in the core?

• Clinical/radiologic presentation?
• Showing it around?
• IHC Stains?
Clues: Complex cystic mass lesion, association with apocrine
metaplasia, intranuclear helioid inclusion, ER staining pattern
Florid usual ductal hyperplasia Low grade DCIS with streaming

ER ER
Clinical Implications:
The word “CARCINOMA” including DCIS or LCIS
on a core biopsy can lead to:

Bilateral Mastectomy!
Solid Intraductal Pattern: Continued
Case 4: 47-year old had a core biopsy for 7 mm cluster
of microcalcifications, had surgery and based on the
findings of the surgical specimen, core bx was reviewed
Case 3: 47-year old had a core biopsy for 7 mm cluster
of microcalcifications, had surgery and based on the
findings of the surgical specimen, core bx was reviewed
Case 5: Stereotactic-guided core biopsy
Case 5. Core biopsy diagnosis:
DCIS, high grade, solid type with cancerization of
lobules
Case 5: Stereotactic-guided core biopsy
Final Dx: Pleomorphic Lobular Carcinoma In-situ

E-cadherin
Pleomorphic lobular carcinoma in-situ
(PLCIS)
• Surgical management same as DCIS diagnosed
on a core biopsy (i.e., partial or total
mastectomy)
• Currently most report PLCIS at margins and
positive margin for PLCIS is re-excised
• Adjuvant RT is debatable
• Endocrine therapy is based on ER/PR status
Case 5: 49-year old with h/o right breast CA.
High risk MRI screening revealed suspicious
enhancement in the left breast
MRI guided core BX
Case 5: 49-year old with MRI-guided core biopsy
Case 5: 49-year old with MRI-guided core biopsy
Diagnosis: DCIS, solid type

E-cadherin
It’s not what it looks like
Case 6: 42 year old with a breast mass,
Radiologic D/D: FA vs. IDC
US-guided core BX
Case 6: US-guided core biopsy
CASE 6: US-GUIDED CORE BIOPSY
 Case 6:
core biopsy: SMM
Case 6. DX: invasive ductal carcinoma, TNBC

p63 IHC
Case 7: US-guided core biopsy for mass lesion
Case 7: US-guided
core biopsy
Case 7: US-guided core biopsy
p63 D2-40
 Invasion vs. In situ carcinoma: Clues

• Mass lesions
• Intervening desmoplastic stroma
• Generous in using IHC, preferably two different
myoepithelial markers (p63, myosin heavy chain)
Cribriform pattern growth
Case 1: 53 year old female with a small cluster
of microcalcs, stereotactic core biopsy
Case 1: Stereotactic core biopsy for Microcalcs
Case 1. Core biopsy diagnosis: Low grade DCIS
Case 1: Excisional Biopsy
Case 1: Excisional Biopsy
Case 1: Excisional Biopsy
Dx. LCIS, classic type involving collagenous spherulosis
 LCIS involving
Collagenous Spherulosis

E-cadherin
LCIS involving collagenous spherulosis

SMM
Cribriform Pattern Growth
Case 2: Cribriform DCIS
Invasive cribriform carcinoma vs. Cribriform DCIS
Case 3. Mass lesion with invasive cribriform
growth pattern
Case 3. Adenoid cystic carcinoma
Luminal cells positive for CK7 and C-kit
Papillary pattern growth
PAPILLARY PATTERN GROWTH

• Intraductal papilloma
• Papilloma with atypia (ADH) or DCIS
• Papillary carcinoma in situ (papillary DCIS,
small duct)
• Intracystic (encapsulated) papillary carcinoma
• Other papillary lesions (metastatic serous
carcinoma)
Case 1: US-guided biopsy was done for complex
cystic mass
Core Bx Diagnosis:
Intraductal papilloma
Excision:
Intraductal papilloma with cystic areas
Intraductal papilloma with cribriform areas
Papilloma with atypia (ADH) or DCIS
 Papilloma with atypia (atypical papilloma) vs.
Papilloma with DCIS

• Epithelial proliferation that would qualify for

ADH or DCIS outside of a papilloma
• Some use size/extent criteria
 Papilloma with DCIS when atypical
proliferation is ≥ 3 mm or occupies >30% of
the papilloma
• Absence of myoepithelial cells within these areas
(also HMW cytokeratins, e.g. CK5/6)
• DCIS is usually low to intermediate grade
Intraductal Papilloma
SMM
Papilloma with ADH vs. DCIS

SMM
Papillary DCIS
SMM
Case 2: Cystic mass in a 70 year old
Encapsulated
Papillary
Carcinoma

SMM
Intracystic (encapsulated) papillary carcinoma

• Older age, often presents as a mass lesion and has an

indolent clinical course
• Single or multiple nodules of papillary carcinoma
surrounded by fibrous capsule, lack myoepithelial cells
• Most consider this to be a form of low-grade invasive
cancer with expansile growth pattern
• Foci of frankly invasive carcinoma may be seen in the
adjacent breast tissue
• As per WHO 2012, the T staging is pTis, unless frank
invasion is identified in the adjacent tissue
Intracystic papillary carcinoma
with frank invasion
Small gland pattern
 Small gland pattern
Case 1. A 73 year old underwent partial
mastectomy and SLNB for a core biopsy
diagnosis of invasive carcinoma. The partial
mastectomy had positive margins for
carcinoma. Was referred for re-excision of
the positive margin
Case 1. Core biopsy
Case 1. Sclerotic lesion with epithelial proliferation
Partial Mastectomy: Radial scar with DCIS
Radial scar with DCIS
CASE 2: MASS LESION
RADIAL SCAR
Radial Scar Tubular carcinoma
Case 3: 45 year old with breast mass found on
screening mammogram
Case 3
Case 3
Case 3
 Sclerosing Adenosis: Pathology

• Proliferation of the glandular structures resulting

in increased number of acini in TDLUs

• Often with the spectrum of fibrocystic changes

• Presentations varies from calcifications

detectable only by mammo to a palpable mass
 Sclerosing Adenosis

SMM P63
Microglandular adenosis
Spindle cell pattern
Spindle cell lesion with bland cytology
Case 1. 42 year old FM, history of breast
reduction 18 months ago, now has mass
Case 1. US-guided core biopsy
Case 1. US-guided core biopsy
Differential Diagnoses: “Pure Spindle Cell” lesions

Bland cytomorphology
Presence of Atypia
• Spindle cell metaplastic • Spindle cell metaplastic
carcinoma carcinoma
• Mammary fibromatosis • Malignant phyllodes tumor
• Myofibroblastoma • Biopsy site changes
• Benign phyllodes tumor
• Other primary mammary
• Biopsy site scar sarcoma
• Others • HG angiosarcoma
- PASH • Metastases
- Schwannoma
- melanoma
- LG angiosarcoma
Case 1. IHC for Beta-catenin
Note: Nuclear and cytoplasmic staining
Case 1. Partial Mastectomy
Mammary Fibromatosis
Case 1. Partial Mastectomy
Mammary Fibromatosis
Spindle cell lesion with bland cytology……
Case 2. 64 year old with 1 cm mass, r/o carcinoma
Spindle cell lesion with bland cytology….
Case 2. 1 cm mass lesion
Spindle cell lesion with bland cytology….
Case 2. 1 cm mass
Diagnosis: Metaplastic carcinoma,
Spindle cell type
IHC for CK AE1/AE3
Metaplastic carcinoma, spindle cell type
p63

CK
Scar Metaplastic carcinoma
Failure to diagnose “CARCINOMA” may lead to
delay in treatment and when carcinoma is
detected in the future at the same site -
Spindle cell lesion: continued
Case 3. 46 year old with 1 cm mass
Spindle cell lesion: continued
Spindle cell lesion: continued
SMA CD34
Myofibroblastoma: Positive staining for ER
Be aware of epitheloid variant of myofibroblastoma
(can mimic invasive lobular carcinoma)

ER
Cellular variant of Myofibroblastoma
Cellular variant of Myofibroblastoma
Myofibroblastoma: Estrogen receptor
Myofibroblastoma: CD 34
Spindle cell lesion with atypical features………

Case 1. 44 year old with right breast surgery

many year s ago, skin scar with underlying
nodular masses. Radiology impression fat
necrosis, rule out IDC
Case 1. Cellular spindle cell lesion
Case 1. Cellular spindle cell lesion
 Case 1. Spindle cell lesion with atypical features
CK β-Catenin
Diagnosis: Dermatofibrosarcoma protruberance

CD 34
Case 2. 56 year old FM 7 cm mass
Differential Diagnoses: “Pure Spindle Cell” lesion

Bland cytomorphology
Presence of atypia
• Spindle cell metaplastic • Spindle cell metaplastic
carcinoma carcinoma
• Mammary fibromatosis • Malignant phyllodes tumor
• Myofibroblastoma • Biopsy site changes
• Benign phyllodes tumor
• Other primary mammary
• Biopsy site scar sarcoma
• Others • HG angiosarcoma
- PASH • Metastases
- Schwannoma
- melanoma
- LG angiosarcoma
 Work up for mammary spindle cell lesions:
IHC stains to consider:
• Keratins, multiple types, p63 (metaplastic CA)
• CD 34, SMA, Desmin, ER (myofibroblastoma)
• Beta-catenin, nuclear staining (fibromatosis)
• CD-31, CD-34, factor VIII, FLI-1 (vascular lesions)
• CD-68, beta-catenin (reactive changes/bx site)
• S-100, HMB45, Melan A (neural, melanoma)

Varma S, Shin SJ. An algorithmic approach to spindle cell lesions of the breast
Adv Anat Pathol. 2013 Mar;20(2):95-109
 Pathologists will play an important role in
the diagnosis of breast lesions

Diagnostic errors in core biopsy can be minimized:

 continuous dialogue with breast radiologists
 frequently sharing cases among pathologists
 educating clinical colleagues the difficulty areas
in pathology
 discussing difficult cases in multidisciplinary
conferences
Thank You