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Flashcards in Breast Path: Gupta Deck (14)
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Identify the most frequently diagnosed breast lesions by age of the patient, based on the most common clinical presentations.

::If you can feel it on exam, it is probably benign fibrocystic change.
::10% of masses in 50 yo are cancer.
::If it's cancer and you can feel it (2-3cm), it has probably already metastasized.
:: cancer's most common presentation is abnormal mammogram.


Discuss the clinical significance of proliferative and non-proliferative fibrocystic change and affects the subsequent risk of developing breast cancer.

::Non-proliferative changes (cysts, fibrosis, apocrine metaplasia) carry less risk of transformation.
::Sclerosing adenosis (radial sclerosis on gross/rad exam), ductal papilloma, hyperplasia w/o atypia carries 1.5-2x risk of transformation.
::Atypical ductal and lobular hyperplasia carry 5x risk of transformation.


Compare and contrast fibroadenoma and phyllodes tumor in terms of clinical features, morphologic findings, and prognosis.

Fibroadenoma- most common benign neoplasm of breast. *Biphasic, glands and stroma (only stroma is neoplastic)*.
Movable, well circumscribed.

Phyllodes tumor- distinguished by *higher cellularity*, higher mitotic rate, *nuclear pleomorphism*, stromal overgrowth, and infiltrative borders. Micro looks like a leaf or giant *elephant foot*
Most benign, can be malignant.


Compare and contrast ductal carcinoma in situ (DCIS) and lobular carcinoma in situ (LCIS) in terms of incidence, clinical presentation, morphology, biomarker expression, pattern of spread, natural history, treatment, and prognosis.

Ductal carcinoma in situ (DCIS):
Clinical presentation-
Morphology- solid, comedo (central necr.), cribiform, papillary, micropapillary, calcifications freq.
Biomarker exp- ER+ (germline BRCA2 mut.) or ER- (germline BRCA1 and/or P53 mut., HER2 amplification *BAD-more aggr.*)
Spread- lymph
Natural hx-
Tx- lumpectomy, rad, anti-estrogens (tamoxifen, raloxifene, aromatase inhib.)
Prog.- good prog.

Lobular carcinoma in situ (LCIS):
Clinical presentation-
Morphology- very uniform, low grade. Intracellular "target" mucin. *Loss of e-cadherin* *Nuclear crescents*
Biomarker exp- Loss of CDH1 that encodes E-cadherin
Natural hx- greater risk of gastric singet ring carcinoma.
Tx- chemo or close follow up.


For the most common breast cancer susceptibility genes, describe the normal function of the gene product, incidence of gene mutation, reasons for its association with cancer, percent of hereditary breast cancer, and risk of breast cancer by age 70.

BRCA1/2: tumor suppressor genes. 12% incidence among those w/ BC referred for genetic testing. Most carriers develop cancer by 70. High grade features. High incidence of ductal carcinoma in-situ (DCIS).
BRCA1- Triple negative status. AD inheritance, but can be spontaneous. Tx- close follow up or proph. mastectomy. Tamoxifen may prevent bilateral BC in ER neg. tumors. No worse prog. compared to non-BRCA. My be more resistant to some chemo. Micro: High-grade, basal-like phenotype. **Lots of lymphocytes**.
BRCA2- Usually get BC by age 50. *Pts. also have higher risk of cancers of ovary, bone, pharynx, prostate, pancreas, others.* Micro: Usually invasive ductal carcinoma, high grade features.


Explain the major molecular classes of invasive ductal carcinoma of the breast identified by gene expression profiling, and describe how each correlates with prognosis and response to therapy.

Luminal A:- ER (+), HER2 (-) GREAT PROG
Luminal B:- ER (+), HER2 (overexpressed) NOT SO GREAT PROG
HER2:- positive- ER (-), HER2 (overexpressed) WOST PROG
Basal Type:- all negative (BAD PROG)


How do you know it is an INVASIVE carcinoma (as opposed to ductal/lubular carcinoma in-situ)?!

No myoepithelial cells in invasive!


etiology, pathogenesis, clinical presentation, gross and microscopic morphology, grade, molecular classification, patterns of spread of:
Invasive lobular carcinoma

Etiology: no CDH1 expression (E-cadherin)
Pathogenesis: cells are discohesive and invade surrounding tissue.
Clinical presentation: hard mass
Gross and microscopic morphology: discohesive infiltrating tumor cells. *Signet-ring cells containing mucin droplets* *(like orphan annie eyes)* *Indian files* *Crescent nuclei*
Grade: High grade
Molecular classification: Biallelic loss of expr. of CDH1 (E-cadherin)
Patterns of spread: peritoneum, retroperitoneum, leptomeninges, GI tract, ovaries, uterus.


Incidence, etiology, microscopic morphology of:
Invasive ductal carcinoma

Incidence: 70-80% of tumors fall into this category
Etiology: Associated with DCIS
Microscopic morphology: *NO myoepithelial cells*


Incidence, gross and microscopic morphology, presentation, molecular classification, clinical course, prognostic indicators of:
Medullary carcinoma

Incidence: RARE
Gross and microscopic morphology: indistinct cell borders. Prominent lymphaplasmacytic infiltrates at periphery of tumor. Pushing rather than infiltrative border, histologically.
Presentation: Soft, fleshy mass
Molecular classification: *BRCA1 mut.*
Clinical course: Does not recur 5 yrs after detection
Prognostic indicators: If nodes are NEG. prog. is GOOD


age predilection, pathogenesis, gross and microscopic morphology, and survival rates of:
Colloid (mucinous) carcinoma

Age predilection: older women around 70
Pathogenesis: slow growing
Gross and microscopic morphology: looks like cells swimming in colloid.
Survival rates: 10 yr survival for pure form is 90%


gross and microscopic morphology and survival rates of:
tubular carcinoma

Gross and microscopic morphology: distinct, well-differentiated angular tubular structures w/ open lumina, lined by a single layer of epithelial cells.
Survival rates: good prog.


What is metaplastic breast cancer?

::Metaplastic breast cancer describes a cancer that begins in one type of cell, such as those from the glands of the breast, and changes into another type of cell.
::Most often, metaplastic breast cancer starts in the epithelial cells, and then changes into squamous or nonglandular cells.
::Metaplastic breast cancer does not have estrogen receptors (ERs), progesterone receptors (PRs), or the HER2 receptor, which is a protein found in ductal and lobular breast cancers.
::Triple negative BC


Your pt has the micropapillary variant of breast carcinoma.
How did you recognize it? What's the prognosis?

Cells adhere to each other, but not to the stroma. So you'll see a ring of cells with a clear ring around them.
Prognosis is BAD. 95% have mets to lymph @ presentation. 70% recur, 50% die.