General Breast Pathology

Question 1

Answer 1

Toker cells

Toker cells are epithelial cells with clear cytoplasm, minimal nuclear atypia, and CK7 positivity which are sometimes present within the nipple epidermis.

They are believed to be derived from underlying sebaceous glands, which also express CK7.

They are a major differential diagnosis for Paget’s disease, as they are often present in a Pagetoid morphology, and many cells of Paget’s disease are also strongly CK7 positive.

Question 2

Differentiating Toker cells from true Paget’s disease of the nipple

Answer 2

Toker cells: CK7+, ER/PR +, HER2 neg, CD138 neg, p53 neg, GCDFP neg

Paget’s disease: CK7+, ER/PR variable, HER2 variable, CD138 variable, p53 variable, GCDFP variable

Caveat: Atypical appearing true Toker cells may weakly express HER2

Combined use of CD138/p53 has been recommended for this purpose.

Question 3

Luminal A genetic pattern

Answer 3

Most common (>40% of all breast cancer)

Strong expression of ER, low expression of HER2 and proliferation-associated genes

Better prognosis, respond well to hormone therapy, but do NOT respond well to chemotherapy (only 0-5% pCR).

Most common mutations:
PIK3CA (45%), MAP3K1, GATA3, TP53, CDH1, MAP2K4

Question 4

Luminal B genetic pattern

Answer 4

Second most common (~20% of all breast cancer)

Lower expression of ER, more variable expression of HER2 cluster genes, higher expression of proliferation-related genes overall.

Tend to be of higher Nottingham grade and have a worse overall prognosis. They respond better than Luminal A to chemotherapy (10-20% pCR).

Most common mutations:
TP53, PIK3CA

Despite often being ER positive, may benefit from more aggressive therapy anyway (less likely to respond to just hormone therapy)

Question 5

HER2-enriched genetic pattern

Answer 5

Accounts for ~10-15% of all breast cancers

Generally high-grade, have apocrine features, and show overexpression of HER2-related genes. Lower expression of ER-related genes.

High frequency of TP53 mutations (~70%), less so PIK3CA (~40%). Higher levels of HER2 staining by IHC, more frequent HER2 amplification by FISH.

Generally these are the best targets for trastuzumab or pertuzumab.

Question 6

Basaloid genetic pattern

Answer 6

Comprises ~15-20% of all breast cancers

Generally these are triple negative breast cancers.

Vast majority are associated with BRCA1 mutations, which are often germline but may also be somatic. Patients tend to be younger and are more frequently of African descent.

Represent 80% of BRCA1 germline-associated breast carcinomas. Poor overall prognosis, but better response to chemotherapy than most breast subtypes (40% pCR).

Many express the EGF receptor rather than classic breast drivers.

Morphologically, these tumors are high grade with brisk mitotic activity, pushing borders, dense lymphocytic infiltration, necrosis, and areas of fibrosis (central scarring). In-situ components are usually not seen in association with these tumors.

Question 7

Apocrine-type genetic pattern

Answer 7

Represents a smaller component of breast carcinomas (minor category)

Have histologic apocrine features and are GCDFP-15 positive. Are ER and androgen receptor positive and of high proliferative index and grade.

Those which are ER negative and AR positive by IHC have a worse prognosis.

Question 8

Three types of mammary stroma

Answer 8

1. Interlobular stroma - denser, more collagenous, surrounds ducts and TDLUs
2. Intralobular stroma - looser, present within lobules between acini
3. Adipose tissue

Question 9

Hormone receptor proxy for genetic category of breast carcinoma

Answer 9

Luminal - ER+, AR+
Basal-like - ER neg, AR neg
Apocrine - ER neg, AR +

Not a perfect 1:1, but gets it right around 80-90% of the time.

Question 10

Claudin-low genetic pattern

Answer 10

Represents a smaller component of breast carcinomas (minor category)

Poorly differentiated tumors with high metastatic potential. Have a stem cell-like molecular profile that is less differentiated than basal-like carcinomas.

Basal marker positive, low ER expression.

Prognosis is slightly better than basal-like tumors, but response to chemotherapy is slightly worse (25-40% pCR).

Question 11

Elston-Ellis modifications to the Bloom criteria

Answer 11

1. Defines field diameter for “10 high power fields”
2. More clearly outlines what patterns count as tubular