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


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


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


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











Secretory carcinoma







Mucinous carcinoma

Tubular carcinoma









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?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?n=35&Case=290



MITOSES = 2

HISTOLOGIC

GRADE 2

(NOTTINGHAM

SCORE 6 OF 9)

Comments:

INVASIVE MAMMARY CA











Secretory carcinoma







Mucinous carcinoma

Tubular carcinoma









INVASIVE LOBULAR CARCINOMA

Classical form

Pleomorphic variant

Alveolar variant

Signet ring cell variant

Histiocytoid variant


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



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


ductal

ductal

lobular lobular

INVASIVE MAMMARY CA











Secretory carcinoma







Mucinous carcinoma

Tubular carcinoma









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











Secretory carcinoma







Mucinous carcinoma

Tubular carcinoma









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











Secretory carcinoma







Mucinous carcinoma

Tubular carcinoma









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











Secretory carcinoma







Mucinous carcinoma

Tubular carcinoma









QUESTIONS?

Welcome to GATRA - Breast histology and Pathology Cancer...OBJECTIVES Overview of normal breast...

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