Welcome to GATRA - Breast histology and Pathology Cancer...OBJECTIVES Overview of normal breast...
Transcript of Welcome to GATRA - Breast histology and Pathology Cancer...OBJECTIVES Overview of normal breast...
BREAST HISTOLOGY AND
PATHOLOGY
Dr. Deborah Marks-Jones, MD
Anatomic & Clinical Pathology
Cytopathology
Phoebe Putney Memorial Hospital
OBJECTIVES
Overview of normal breast histology
Understand the histopathology of in-situ breast
lesions (DCIS and LCIS)
Understand the histopathology of invasive
mammary carcinoma with important subtypes
Unless otherwise noted, images and
information obtained from:
Biopsy Interpretation of the Breast, 3rd
Edition
Stuart J. Schnitt and Laura C. Collins
Series editor Jonathan I. Epstein
L = lobules
TD = terminal
ducts
ELD =
extralobular
ducts
STROMA – predominant
component of non-
lactating breast
Collagen
Adipose tissue
FIBROTIC STROMA
FATTY STROMA
P63 IMMUNOHISTOCHEMICAL
STAIN Myoepithelial cells
IN-SITU CARCINOMAS
LOBULAR CARCINOMA IN-SITU (LCIS)
Classical LCIS
Pleomorphic LCIS
DUCTAL CARCINOMA IN-SITU (DCIS)
Comedo
Cribiform
Micropapillary
Papillary (encapsulated papillary CA, solid papillary CA)
Solid
CLASSICAL LOBULAR
CARCINOMA IN-SITU (LCIS)
-Small cells
-Small, uniform round nuclei
-Nucleoli are absent
-Cells distend at least half of
the acini in a lobule
CLASSICAL LOBULAR
CARCINOMA IN-SITU (LCIS)
-Low proliferative rate
-Typically strongly
diffusely Estrogen
Receptor (ER) positive
-Rarely HER2 positive
E-CADHERIN IHC
Lobular carcinoma
E-cadherin negative
Normal ducts/
ductal phenotype E-
cadherin positive
Wide age range, but more common in premenopausal
women
Usually an incidental finding in breast biopsies performed
for another abnormality; rare cases with comedo necrosis
may present with mammographic microcalcifications
Multicentricity in 60%–80% of cases; bilaterality in 25%–
30%
Associated with 7- to 10-fold increase in breast cancer
risk (absolute risk ~1%–2% per year)
CLINICAL FEATURES OF CLASSICAL LCIS
PLEOMORPHIC
LOBULAR
CARCINOMA IN-SITU
PLEOMORPHIC LCIS
Larger cells
Nuclear pleomorphism
Nuclear size variation
Nuclear membrane irregularity
Variably prominent nucleoli
May show comedonecrosis (rule out DCIS)
PLEOMORPHIC LCIS
Controversy regarding management
? Treat like DCIS due to “aggressive”
features
? Need to excise with negative margins
E-cad negative
HER2-NEU positive
Pleomorphic LCIS
- Usually estrogen receptor (ER)
positive (but weaker than
classical LCIS)
- Moderate to high proliferative
rate
- May show HER2
overexpression
DUCTAL CARCINOMA IN-SITU (DCIS)
presence of neoplastic epithelial cells
confined to the mammary ductal–lobular
system, without extension beyond the
basement membrane.
DCIS may involve ducts and/or
identifiable lobules.
NUCLEAR GRADE
Low
Intermediate
High
DUCTAL CARCINOMA IN-SITU (DCIS)
ARCHITECHTURAL
PATTERNS
Comedo
Cribiform
Micropapillary
Papillary
Solid
NUCLEAR GRADING
low
intermediate high
comedo
cribiform
micropapillary
papillary
solid
KEY FEATURES OF LOW-GRADE
DCIS
Cytologic features
Monotonous, uniform, rounded cell population
Subtle increase in nuclear–cytoplasmic ratio
Equidistant or highly organized nuclear distribution
Rounded nuclei with inconspicuous nucleoli
Hyperchromasia may or may not be present
Architectural features
Cribriform, micropapillary, or solid patterns most frequent
Bridges and arcades, when present, of uniform thickness
Cells polarize around extracellular lumens
Comedo necrosis rare
Atypical ductal
hyperplasia (ADH)
VS
Low grade DCIS
DUCTAL CARCINOMA IN-SITU (DCIS)
Low grade
Small cells
Uniform size and
shape
Small nucleoli
Homogenous cells
Mitotic figures are rare
Intermediate grade
Mild to moderate
variability in nuclear
size and shape
Variably conspicuous
nucleoli
+/- necrosis
High grade
Large, pleomorphic
nuclei
Prominent nucleoli
+/- necrosis
Mitotic figures are
frequent
NUCLEAR GRADING
ENCAPSULATED PAPILLARY
CARCINOMA
Variant of DCIS
Previously called intracystic or
encysted papillary CA
Elderly women
Nipple discharge or subareolar
mass
p63 IHC
Circumscribed nodule
of papillary CA w/
fibrous capsule
Often contains
surrounding foci of
grade 1-2 DCIS
No myoepithelial cells
within AND
surrounding the nodule
May have
surrounding
invasive
carcinoma
Invasive ductal CA
Encapsulated
papillary CA
SOLID PAPILLARY CARCINOMA
Elderly women
circumscribed, solid nodules of
neoplastic epithelial cells
may have a streaming or
swirling appearance similar to
usual ductal hyperplasia
(UDH)
SOLID PAPILLARY CARCINOMA
Absence of myoepithelial
cells within and
surrounding the lesion
If there is uncertainty
about invasion, treat like
in-situ Smooth muscle IHC
INVASIVE MAMMARY CA
Fibromatosis-like metaplastic carcinoma
Metaplastic carcinoma, spindle cell type
Metaplastic carcinoma, mixed epithelial and mesenchymal type
Invasive carcinoma with metaplastic features
Squamous cell carcinoma
Adenoid cystic carcinoma
Invasive carcinoma with apocrine features
Invasive carcinoma with clear cell (glycogen rich) features
Invasive carcinoma with neuroendocrine features
Invasive carcinoma, with signet-ring cell features
Secretory carcinoma
Invasive carcinoma, type cannot be determined
Invasive carcinoma of no special type (invasive ductal carcinoma, not otherwise specified)
Micro-invasive carcinoma
Invasive lobular carcinoma
Invasive carcinoma with lobular features
Invasive carcinoma with ductal and lobular features (“mixed type carcinoma”)
Mucinous carcinoma
Tubular carcinoma
Invasive carcinoma, tubulo-lobular variant
Invasive cribriform carcinoma
Invasive micropapillary carcinoma
Invasive papillary carcinoma
Invasive carcinoma with medullary features
Metaplastic carcinoma
Low-grade adenosquamous carcinoma
From CAP Sept 2019 protocol
INVASIVE MAMMARY CARCINOMA
https://breast-cancer.ca/wp-content/uploads/2014/11/Fig-5-1-Annotated-Breast-Cancer-Types-copy.jpg
INVASIVE DUCTAL CA
(NOS)
INVASIVE LOBULAR CA
MIXED DUCTAL-LOBULAR
CA
TUBULAR CA
MUCINOUS CA
MEDULLARY CA
MICROINVASIVE CARCINOMA
Cancer cells beyond the
basement membrane with no
focus more than 1mm in
greatest dimension
Most often seen in association
with extensive high-grade DCIS
P63 can be helpful to prove
invasion (lack of myoepithelial
cells)
Microinvasive lobular carcinoma Microinvasive ductal carcinoma
INVASIVE MAMMARY CA
Fibromatosis-like metaplastic carcinoma
Metaplastic carcinoma, spindle cell type
Metaplastic carcinoma, mixed epithelial and mesenchymal type
Invasive carcinoma with metaplastic features
Squamous cell carcinoma
Adenoid cystic carcinoma
Invasive carcinoma with apocrine features
Invasive carcinoma with clear cell (glycogen rich) features
Invasive carcinoma with neuroendocrine features
Invasive carcinoma, with signet-ring cell features
Secretory carcinoma
Invasive carcinoma, type cannot be determined
Invasive carcinoma of no special type (invasive ductal carcinoma, not otherwise specified)
Micro-invasive carcinoma
Invasive lobular carcinoma
Invasive carcinoma with lobular features
Invasive carcinoma with ductal and lobular features (“mixed type carcinoma”)
Mucinous carcinoma
Tubular carcinoma
Invasive carcinoma, tubulo-lobular variant
Invasive cribriform carcinoma
Invasive micropapillary carcinoma
Invasive papillary carcinoma
Invasive carcinoma with medullary features
Metaplastic carcinoma
Low-grade adenosquamous carcinoma
From CAP Sept 2019 protocol
INVASIVE DUCTAL CARCINOMA, NOS
Accounts for 70-76% of invasive carcinoma
Highly heterogenous with regard to
- pattern
- cytologic features
- mitotic activity
- stromal desmoplasia
- extent of associated DCIS
Combined histologic grade
Degree of gland formation
Nuclear atypia
Mitotic activity
(Microinvasive carcinoma is not given a histologic grade)
HISTOLOGIC GRADE (NOTTINGHAM
HISTOLOGIC SCORE)
Glandular (Acinar)/Tubular Differentiation
Score 1 (>75% of tumor area forming glandular/tubular structures)
Score 2 (10% to 75% of tumor area forming glandular/tubular structures)
Score 3 (<10% of tumor area forming glandular/tubular structures)
Score 1
Score 3
NUCLEAR
PLEOMORPHISM
Low =1
Intermediate =2 High= 3
MITOSES
-number of mitotic figures
found in 10 consecutive
HPFs in the most
mitotically active part of
the tumor
Score 1, 2 or 3
https://www.webpathology.com/image.asp?case=290&n=49
OVERALL NOTTINGHAM
GRADE
GRADE 1 (SCORES OF 3, 4 OR 5)
GRADE 2 (SCORES OF 6 OR 7)
GRADE 3 (SCORES OF 8 OR 9)
https://www.webpathology.com/image.asp?case=290&n=29
https://www.webpathology.com/image.asp?n=35&Case=290, https://www.webpathology.com/image.asp?case=290&n=38
TUBULES = 2
NUCLEAR ATYPIA = 2
https://www.webpathology.com/image.asp?case=290&n=49
MITOSES = 2
HISTOLOGIC
GRADE 2
(NOTTINGHAM
SCORE 6 OF 9)
Comments:
INVASIVE MAMMARY CA
Fibromatosis-like metaplastic carcinoma
Metaplastic carcinoma, spindle cell type
Metaplastic carcinoma, mixed epithelial and mesenchymal type
Invasive carcinoma with metaplastic features
Squamous cell carcinoma
Adenoid cystic carcinoma
Invasive carcinoma with apocrine features
Invasive carcinoma with clear cell (glycogen rich) features
Invasive carcinoma with neuroendocrine features
Invasive carcinoma, with signet-ring cell features
Secretory carcinoma
Invasive carcinoma, type cannot be determined
Invasive carcinoma of no special type (invasive ductal carcinoma, not otherwise specified)
Micro-invasive carcinoma
Invasive lobular carcinoma
Invasive carcinoma with lobular features
Invasive carcinoma with ductal and lobular features (“mixed type carcinoma”)
Mucinous carcinoma
Tubular carcinoma
Invasive carcinoma, tubulo-lobular variant
Invasive cribriform carcinoma
Invasive micropapillary carcinoma
Invasive papillary carcinoma
Invasive carcinoma with medullary features
Metaplastic carcinoma
Low-grade adenosquamous carcinoma
From CAP Sept 2019 protocol
INVASIVE LOBULAR CARCINOMA
Classical form
Pleomorphic variant
Alveolar variant
Signet ring cell variant
Histiocytoid variant
INVASIVE LOBULAR CARCINOMA
CLASSICAL FORM
- small, uniform neoplastic cells
-invade in single file pattern
-little or no desmoplastic response
-eccentric nuclei (plasmacytoid)
-infrequent mitoses
E-cad negative
CLASSICAL FORM
https://www.google.com/imgres?imgurl=http%3A%2F%2Fimagebank.hematology.org
Plasma cell
PLEOMOPRHIC VARIANT
- invade in single file pattern
- larger cells with nuclear variation
-little or no desmoplastic response
-may show apocrine features
-infrequent mitoses
INVASIVE LOBULAR CARCINOMA
INVASIVE LOBULAR CARCINOMA
Classical type may have more favorable
outcome
Pleomorphic and signet ring cell variant poor
clinical outcome
More common metastasis to leptomeninges
(carcinomatous meningitis), peritoneum, GI
tract
MIXED INVASIVE DUCTAL AND
INVASIVE LOBULAR CARCINOMA
ductal
ductal
lobular lobular
INVASIVE MAMMARY CA
Fibromatosis-like metaplastic carcinoma
Metaplastic carcinoma, spindle cell type
Metaplastic carcinoma, mixed epithelial and mesenchymal type
Invasive carcinoma with metaplastic features
Squamous cell carcinoma
Adenoid cystic carcinoma
Invasive carcinoma with apocrine features
Invasive carcinoma with clear cell (glycogen rich) features
Invasive carcinoma with neuroendocrine features
Invasive carcinoma, with signet-ring cell features
Secretory carcinoma
Invasive carcinoma, type cannot be determined
Invasive carcinoma of no special type (invasive ductal carcinoma, not otherwise specified)
Micro-invasive carcinoma
Invasive lobular carcinoma
Invasive carcinoma with lobular features
Invasive carcinoma with ductal and lobular features (“mixed type carcinoma”)
Mucinous carcinoma
Tubular carcinoma
Invasive carcinoma, tubulo-lobular variant
Invasive cribriform carcinoma
Invasive micropapillary carcinoma
Invasive papillary carcinoma
Invasive carcinoma with medullary features
Metaplastic carcinoma
Low-grade adenosquamous carcinoma
From CAP Sept 2019 protocol
MUCINOUS CARCINOMA
Previously called colloid
carcinoma
Extracellular mucin production
Nuclei generally low to
intermediate grade
90% of lesion with mucinous
histology to make the
diagnosis
If <90% classify as “mixed”
mucinous tumor
• Variable cellularity
• Typically ER positive
• Approximately 70% PR positive
• Typically HER2 negative
• Often accompanied by DCIS
• Pure mucinous favorable prognosis
• Nodal involvement most important adverse prognostic factor
MUCINOUS CARCINOMA
INVASIVE MAMMARY CA
Fibromatosis-like metaplastic carcinoma
Metaplastic carcinoma, spindle cell type
Metaplastic carcinoma, mixed epithelial and mesenchymal type
Invasive carcinoma with metaplastic features
Squamous cell carcinoma
Adenoid cystic carcinoma
Invasive carcinoma with apocrine features
Invasive carcinoma with clear cell (glycogen rich) features
Invasive carcinoma with neuroendocrine features
Invasive carcinoma, with signet-ring cell features
Secretory carcinoma
Invasive carcinoma, type cannot be determined
Invasive carcinoma of no special type (invasive ductal carcinoma, not otherwise specified)
Micro-invasive carcinoma
Invasive lobular carcinoma
Invasive carcinoma with lobular features
Invasive carcinoma with ductal and lobular features (“mixed type carcinoma”)
Mucinous carcinoma
Tubular carcinoma
Invasive carcinoma, tubulo-lobular variant
Invasive cribriform carcinoma
Invasive micropapillary carcinoma
Invasive papillary carcinoma
Invasive carcinoma with medullary features
Metaplastic carcinoma
Low-grade adenosquamous carcinoma
From CAP Sept 2019 protocol
TUBULAR CARCINOMA
Haphazard proliferation of well-formed
glands or tubules
Glands tend to be ovoid in shape
have sharply angular contours with
tapering ends and open lumens
Apical cytoplasmic snouts
Low nuclear grade
Need 90%+ of tumor with this morphology
to call it tubular (otherwise with tubular
features)
TUBULAR CARCINOMA
Majority are associated with low-
grade DCIS
Virtually always ER positive
Most are PR positive
Rarely HER2 positive
EXCELLENT PROGNOSIS
INVASIVE MAMMARY CA
Fibromatosis-like metaplastic carcinoma
Metaplastic carcinoma, spindle cell type
Metaplastic carcinoma, mixed epithelial and mesenchymal type
Invasive carcinoma with metaplastic features
Squamous cell carcinoma
Adenoid cystic carcinoma
Invasive carcinoma with apocrine features
Invasive carcinoma with clear cell (glycogen rich) features
Invasive carcinoma with neuroendocrine features
Invasive carcinoma, with signet-ring cell features
Secretory carcinoma
Invasive carcinoma, type cannot be determined
Invasive carcinoma of no special type (invasive ductal carcinoma, not otherwise specified)
Micro-invasive carcinoma
Invasive lobular carcinoma
Invasive carcinoma with lobular features
Invasive carcinoma with ductal and lobular features (“mixed type carcinoma”)
Mucinous carcinoma
Tubular carcinoma
Invasive carcinoma, tubulo-lobular variant
Invasive cribriform carcinoma
Invasive micropapillary carcinoma
Invasive papillary carcinoma
Invasive carcinoma with medullary features
Metaplastic carcinoma
Low-grade adenosquamous carcinoma
From CAP Sept 2019 protocol
MEDULLARY CARCINOMA
Syncytial growth pattern in >75% of tumor
cells
Admixed lymphoplasmacytic infiltrate
Microscopic circumscription
Intermediate or high nuclear grade
Absence of glandular differentiation
MEDULLARY CARCINOMA/
Usually ER/PR/HER2 negative
(triple negative)
Association with germline BRCA1
mutations
Present in younger patients
CARCINOMA WITH
MEDULLARY FEATURES
https://www.webpathology.com/image.asp?n=21&Case=298
INVASIVE MAMMARY CA
Fibromatosis-like metaplastic carcinoma
Metaplastic carcinoma, spindle cell type
Metaplastic carcinoma, mixed epithelial and mesenchymal type
Invasive carcinoma with metaplastic features
Squamous cell carcinoma
Adenoid cystic carcinoma
Invasive carcinoma with apocrine features
Invasive carcinoma with clear cell (glycogen rich) features
Invasive carcinoma with neuroendocrine features
Invasive carcinoma, with signet-ring cell features
Secretory carcinoma
Invasive carcinoma, type cannot be determined
Invasive carcinoma of no special type (invasive ductal carcinoma, not otherwise specified)
Micro-invasive carcinoma
Invasive lobular carcinoma
Invasive carcinoma with lobular features
Invasive carcinoma with ductal and lobular features (“mixed type carcinoma”)
Mucinous carcinoma
Tubular carcinoma
Invasive carcinoma, tubulo-lobular variant
Invasive cribriform carcinoma
Invasive micropapillary carcinoma
Invasive papillary carcinoma
Invasive carcinoma with medullary features
Metaplastic carcinoma
Low-grade adenosquamous carcinoma
From CAP Sept 2019 protocol
QUESTIONS?