Breast Flashcards
AJCC
T4a group for breast carcinomas includes carcinomas with __. This does not include ___.
Invasive carcinomas greater than __ mm and less than or equal to __ mm are staged as T2; those greater than __ mm are T3.
The AJCC T4a group for breast carcinomas includes carcinomas with extension to the chest wall. This does not include invasive carcinomas adhering to or invading the pectoralis muscle. The carcinoma must penetrate beyond the pectoralis muscle into the chest wall to be classified as T4a. Invasive carcinomas greater than 20 mm and less than or equal to 50 mm are staged as T2; those greater than 50 mm are T3.
Is it positive for CK 5/6?
What is the risk of a radiologically occult invasive carcinoma?
Is sentinel lymph node procedure is not recommended?
It exhibits ___ nuclear grade.
Is comedo necrosis is common?.
High grade DCIS is non-reactive with CK 5/6 as opposed to ductal hyperplasia which shows significant positivity.
The risk of occult invasive carcinoma in high grade DCIS is about 50%, and, therefore, sentinel lymph node procedure is recommended in those cases.
Which immunohistochemical markers are most useful in distinguishing between benign and atypical epithelial foci within papillary proliferations of the breast?
ER and CK5 staining, when used together, are valuable adjunct stains to differentiate usual duct hyperplasia from atypical proliferations within papillary lesions on breast core biopsy.
- Diffuse ER expression with lack of CK5 staining is seen in atypical epithelial proliferations.
- Mosaic expression of both ER and CK5 is generally encountered in usual hyperplasia.
Hormone receptor assay and reporting
- The CAP recommends that the cold ischemia time of ___ or less.
- Samples should be fixed for at least __ to a maximum of __ hours for receptor stability.
- Positivity for ER or PR is based on finding of __% immunoreactive tumor cell nuclei.
- A specimen may have to be rejected if __
- The CAP recommends that the cold ischemia time be kept to one hour or less.
- Samples should be fixed for at least 6 hours to a maximum of 72 hours for receptor stability.
- Positivity for ER or PR is based on finding of ≥1% immunoreactive tumor cell nuclei.
- A specimen may have to be rejected if the slide lacks staining of included normal epithelial elements and/or normal positive control on same slide.
According to the 2007 ASCO/CAP guidelines for Her2/neu testing, a Her2/neu positive result includes at least one of the following:
- Immunohistochemical staining of __+ (uniform, intense membrane staining of >__% of invasive tumor cells
- FISH result of more than __ HER2 gene copies per nucleus
- FISH ratio (HER2 gene signals to chromosome 17 signals) of more than __
According to the 2007 ASCO/CAP guidelines for Her2/neu testing, a Her2/neu positive result includes at least one of the following:
- Immunohistochemical staining of 3+ (uniform, intense membrane staining of >30% of invasive tumor cells
- FISH result of more than 6.0 HER2 gene copies per nucleus
- FISH ratio (HER2 gene signals to chromosome 17 signals) of more than 2.2.
Adenoid cystic carcinoma (ACC) of the breast
- Incidence?
- Age?
- Hormone receptor profile?
- Clinical course?
- More aggressive behavior can be seen in the __ variant
- Morphologically, ACCs of the breast are similar to those seen in salivary glands, composed of two cell types
- one which stains with luminal epithelial markers ____ (4)
- the other staining with ___ (4) and ___(4)
- ACCs of the salivary gland and breast consistently harbor the hallmark __ fusion gene resulting from a __ translocation.
Adenoid cystic carcinoma (ACC) of the breast
- rare tumor accounting for less than 0.1% of all breast carcinomas
- occurs predominantly in postmenopausal women (mean age of 60)
- triple negative (ER/PR/HER2) receptor profile
- indolent clinical course, presenting with localized disease
- more aggressive behavior can be seen in the solid variant
- Morphologically, ACCs of the breast are similar to those seen in salivary glands, composed of two cell types
- one which stains with luminal epithelial markers CK7, EMA, CEA, and CD117
- the other staining with high molecular weight/basal cytokeratins CK5, CK5/6, CK14, CK17 and myoepithelial markers p63, S100, actin, calponin
- ACCs of the salivary gland and breast consistently harbor the hallmark MYB–NFIB fusion gene resulting from a t(6;9)(q22–23;p23–24) translocation.
Small cell carcinoma breast primary v. met
Similar?
Distinguising?
Small cell carcinoma breast primary v. met
Similar
- expression of pan-cytokeratin in a dot-like paranuclear staining pattern
- immunoreactive for CAM5.2, CK7, synaptophysin and TTF-1
- negative for CK20
- +/- ER/PR positivity
Distinguising?
- presence of DCIS with similar cytologic features
Dx?
E-cadherin staining?
Tubulolobular carcinoma.
- shows abortive tubule formation in addition to the characteristic single file pattern
- demonstrates intense membranous staining for E-cadherin in both the tubular and lobular components, similar to that seen in infiltrating ductal carcinoma.
- DDx
- Histology
- Staining
- Genetics
Microglandular adenosis
- DDx: invasive tubular carcinoma
- proliferation of small round glands composed of a single layer of epithelial cells surrounded by a basement membrane
- glands lack both myoepithelial cells and a lobular architecture
- not associated with a desmoplastic stroma
- strong S100 expression and a triple negative (ER/PR/HER2) receptor profile
- Chromosomal aberrations suggest the lesion to be a neoplastic clonal lesion and a possible precursor of a subset of breast cancers
DDx?
Histology?
Tubular adenoma
- circumscribed proliferation of closely packed tubules lined by two cell layers, epithelial and myoepithelial
- benign neoplasm related to fibroadenoma
DDx
Tubular carcinoma
- haphazard infiltration of bland tubules with angular contours
- Individual cells often show apical snouts
Microglandular adenosis
- comprised of infiltrating, uniform, round tubules which contain central eosinophilic secretion and which do not exhibit a myoepithelial layer.
Adenomyoepithelioma
- circumscribed proliferation of both myoepithelial and epithelial cells, the proportions of which vary
- myoepithelial cells may be either closely associated with epithelial tubules, or they may be present as aggregates of spindle, polygonal, or clear cells
DDx?
Age?
Genetics?
Primary (de novo) angiosarcoma of the breast
- rare, occurring almost exclusively in women with a median age of 40
- occur in the breast parenchyma, often presenting as a painless mass
- no myc amplification
- histologic grading does not correlate with clinical behavior and outcome
Secondary (radiation-associated) angiosarcoma
- occurs predominantly in the skin following surgery and radiotherapy
- median latent stage is 5-6 years
- myc amplification
- must be differentiated from atypical post-radiation vascular proliferation (APRVP)
APRVP
- generally follows a benign clinical course
- no myc amplification
Stains?
Pseudoangiomatous hyperplasia (PASH)
- benign mesenchymal proliferation
- frequently an incidental histologic finding
- rarely, it can present as a mass
- slit-like spaces
- positive for CD34, SMA, BCL-2
- negative for CD31
- not associated with microcalcifications
DDx?
Best IHC panel?
Best single stain?
Paget’s disease of the nipple
- the presence of carcinoma cells in the keratinizing epithelium of the nipple, often with ductal carcinoma in situ involving the adjacent lactiferous ducts
- Invasive or in situ carcinoma is present elsewhere in the breast in >90% of cases
DDx
Paget’s
- Positive: HER2, CK7, CAM5.2, CEA, +/-S100
- Negative: ER, HMB45, Melan-A, CK5/6, CK20
Toker cells
- Positive: ER, CK7, CAM5.2, CEA, +/-S100
- Negative: HER2
Squamous cell carcinoma in situ/Bowen’s disease
- Positive: CK5/6, CK20
- Negative: HER2
Melanoma
- Positive: HMB-45, Melan-A
- Negative: HER2
Best 4 stains (all negative in Paget’s)
- HMB-45, Melan-A, CK5/6, CK20
HER2 is the most useful single immunostain
- positive in up to 80-90% of Paget’s disease
- negative in the other entities in the differential
What is the typical immunoprofile of in situ and invasive lobular carcinoma? (E-cadherin, catenin P120)
Lobular neoplasia, including both in situ and invasive lesions
- typically lacks membranous staining for both E-cadherin and catenin P120
- typically display positive cytoplasmic staining for P120
Dx?
Incidence?
Prognosis?
Pure or mixed?
ER, PR and Her-2?
Age?
Invasive micropapillary carcinoma
- relatively uncommon
- highly aggressive
- mostly occurs in mixed form with other types of invasive ductal carcinoma
- >50% of cases are ER, PR and Her-2 positive
- no specific age range
Dx?
Stains?
DDx?
Spindle cell carcinoma
- type of metaplastic carcinoma of the breast
- positive: high molecular weight keratins (CK5/6) and the myoepithelial cell marker p63
- may be positive for only one of these markers and also show only focal positivity
DDx
- Malignant spindle cell neoplasm
- Sarcoma
- Malignant phyllodes tumor
- Nodular fasciitis
Despite that it is rare to be associated with an atypical proliferative lesion, when it occurs, the most common atypical lesion encountered is __
Although atypical or neoplastic proliferations are not often encountered in fibroadenomas, when they occur, lobular carcinoma in situ (LCIS) is most common.
Dx?
How is it detected?
Prognosis?
Treatment?
Mucocele-like lesion
- mucinous lesion of the breast with highly variable upgrade rates to atypia and malignancy on excision
- clinically occult and presents with microcalcifications on imaging
- not considered a premalignant lesion
- often associated with ADH and, therefore, follow-up excision is commonly recommended
Special Subtypes of Invasive Breast Cancer
Prognosis?
Special Subtypes of Invasive Breast Cancer:
a/w good prognosis
- luminal A, mucinous, tubular, cribriform, and medullary
- Better prognosis than NST
a/w bad prognosis
- inflammatory carcinoma, which currently is defined primarily on clinical grounds
- having an erythematous or peau d’orange skin appearance and carcinoma anywhere in the breast
Invasive micropapillary carcinoma
- aggressive tumor, a/w high lymphatic and lymph node metastasis rate (75%) regardless of tumor size, even for T1a lesions
central fibrotic focus a/w poor prognosis
Worse prognosis than invasive ductal NST
- luminal B
- HER2 amplified
- most basal-type
Basal-type a/w good prognosis
- Pure medullary carcinoma
- secretory carcinoma
- adenoid cystic carcinoma
Special Subtypes of Invasive Breast Cancer: Inflammatory Breast Carcinoma
Associated with a bad prognosis
defined primarily on clinical grounds—having an erythematous or peau d’orange skin appearance and carcinoma anywhere in the breast.
Sclerosing adenosis
Paget disease
- nipple and subareolar region
- DCIS arising in lactiferous ducts and extending into the epidermis
Florid papillomatosis of the nipple
- potentially mass-forming lesion
- aka nipple adenoma
- characterized by ductular proliferation arising from lactiferous ducts and florid intraductal epithelial hyperplasia, varying degrees of atypia
- may be a/w cancer
Subareolar sclerosing duct hyperplasia
- characterized by a geographic area of duct sclerosis and stromal elastosis with florid epithelial proliferation
- looks like nipple adenoma but nipple isn’t involved
- this lesion is in the family of radial sclerosing lesions but tends to show less cyst formation
- may be a/w carcinoma
- myoepithelial cells surround the intraductal epithelial proliferation
- highlighted with a smooth muscle actin, smooth muscle myosin heavy chain, or p63 immunostain
Syringomatous adenoma of the nipple
- benign, locally infiltrating neoplasm histologically similar to the tumor of the skin
- does not appear to arise from skin, and it is not typically associated with intraductal epithelial proliferation
- should be distinguished from florid papillomatosis of the nipple (nipple adenoma).
- small tubular and ductular structures with elongated architecture in a teardrop shape
- infiltrative pattern that should not be confused with an invasive carcinoma
- ducts are lined by one or more layers of small uniform cells
Gynecomastia
- intraductal epithelial hyperplasia and periductal increased cellularity and edema
- 3 stages
- early florid, intermediate, and late inactive or fibrotic
- may be seen in the female breast
- most common lesion of the male breast
- bimodal distribution but may be seen at any age
- affects 30% to 60% of boys and 30% of adults
- most are ER positive
- occasionally, breast lobules may be seen
- a/w hyperthyroidism; cirrhosis; chronic renal failure; use of hormones; and use of numerous common drugs (digitalis, cimetidine, and spironolactone)
- NO increased incidence of breast carcinoma
- Pseudogynecomastia may be seen in obese males because of lipomastia (i.e., fat in the breast, lacking glandular proliferation).
