Breast pathology Flashcards
Features of juvenile fibroadenoma
Increased stromal cellularity
Increased epithelial hyperplasia with gynecomastoid-like micropapillary projections
Fascicular stromal arrangement
Pericanalicular growth pattern
May show rapid growth and large size
Describe features of this breast lesion in 8 year old girl.
Dx:
Juvenile fibroadenoma:
- Increased stromal cellularity
- Increased epithelial hyperplasia with gynecomastoid-like micropapillary projections
- Fascicular stromal arrangement
- Pericanalicular growth pattern
- May show rapid growth and large size
Usual ductal hyperplasia
There is heterogeneity of epithelial cell size and shape, as well as variability of nuclear size, shape, and location. The lumina are irregular in shape.
Bridges are stretched and thin appearing and nuclei are flattened and parallel to bridges.
54F bx right breast for microcalcifications. No palpable mass.
Dx
Key features
Usual ductal hyperplasia
Heterogeneity of epithelial and nuclear size and shape. Lumina are located peripherally. Thin and stretched bridges are present.
What ICH staining do you expect for UDH.
mixed phenotype staining for both low-molecular-weight cytokeratins (luminal type: CK7, CK8, and CK18) and high-molecular-weight cytokeratins (basal type: CK5/6, CK14, and 34βE12 [CK903]), the latter in a heterogeneous or mosaic pattern
ER staining is also heterogeneous in UDH, in contrast to the strong, diffuse staining seen in ADH and low-grade ductal carcinoma in situ
Bx 54F because of screen-detected microcalifications
Dx?
Columnar cell lesion with focal columnar cell hyperplasia.
FEA
shows cuboidal epithelial cells with apical snouts, displaying mild nuclear atypia with rounded, slightly enlarged vesicular nuclei and discernible nucleoli.
Bx left breast. 54F
Dx?
Rationale?
Dx: ADH
?: reveals the low-grade cytological monotony of the cells making up the arches and small micropapillary structures. These findings are consistent with the diagnosis of atypical ductal hyperplasia.
core needle bx left breast.
Dx/DDx?
Description:
ADH (DDx: Low-grade DCIS)
Description: Intr
Intraductal proliferation with cytological monotony and cribriform, polarized spaces of low-grade ductal carcinoma in situ but due to its limited extent (≤ 2.0 mm) is best classified on core needle biopsy as atypical ductal hyperplasia.
65F, excision of palpable nodule.
dx?
Features?
Dx: Adenomyoepithelioma with tubular growth.
Note: biphasic appearance, with glandular structures lined by an inner layer of epithelial cells and an outer layer of prominent clear myoepithelial cells with
70F, excision of palpable nodule
Dx.
Features.
Adenomyoepithelioma.
Biphasic appearance. Clear myyoepithelial cells can sometimes be prominent, obscuring the epithelial component.
Describe the types of haemartomas that occur in the breast (3)
Adenolipoma: normal ducts/lobules admixed with adipose tissue
Myoid haemartoma: smooth muscle component is prominent
chondrolipomas: chondroid islands exist within adipose tissue
LCIS
What are the three subtypes?
Define each:
Classic, pleomorphic and florid.
Classic LCIS is characterized by dyscohesive proliferations of type A and/or type B epithelial cells. Type A cells are small cells with uniform hyperchromatic nuclei, whereas type B cells have slightly larger vesicular nuclei, with mild variability in size and shape and with small nucleoli.
Pleomorphic LCIS is composed of larger cells with marked nuclear pleomorphism, which are > 4 times the size of a lymphocyte / equivalent to the cells of high-grade DCIS, with or without apocrine features.
In florid LCIS, the LCIS cells show the cytological features of classic LCIS, but there is marked distention of TDLUs or ducts, creating a confluent mass-like architecture. Florid LCIS should have at least one of two architectural features: little to no intervening stroma between markedly distended acini of involved TDLUs and a size cut-off point at which an expanded acinus or duct fills an area equivalent to ~40–50 cells in diameter.
Pleormorphic and florid usu a/w microcalcifications
LCIS
Which subtypes are associated with invasive carcinoma?
Florid and pleomorphic. (prevalence as high as 87%)
LCIS
Discuss staining and limitations of E-cadherin, p120-catenin, b-catenin, ER and HER2 status.
Loss of membranous E-cadherin expression is the characteristic for all forms of LCIS. Approx 15% of invasive lobular lesions, the neoplastic cells have conserved but aberrant E-cadherin expression, and this is recapitulated in LCIS. Therefore, fragmented membranous and/or cytoplasmic aberrant staining should not be used to make a diagnosis of DCIS. LCIS cells exhibit strong, diffuse cytoplasmic staining for p120-catenin and loss of expression of membrane β-catenin. The classic and florid subtypes of LCIS are typically diffusely and strongly positive for ER, have a low Ki-67 proliferation index, and rarely show ERBB2 (HER2) overexpression or gene amplification, or TP53 mutation. The pleomorphic subtype is more likely to be ER-negative (especially apocrine pleomorphic LCIS), may be AR-positive, may demonstrate HER2 overexpression and gene amplification or TP53 mutation, and has a moderate to high Ki-67 proliferation index. Approx 10% cases of pleo are triple (-).
Breast bx
Dx?
Classic LCIS.
More than 50% of the acini in a terminal duct lobular unit are filled and expanded by loosely cohesive monomorphic cells with scant cytoplasm and small uniform nuclei.
Breast excision
Dx?
Dx criteria?
Pleomorphic LCIS.
Essential: large dyscohesive cells with marked nuclear pleomorphism, > 4 times the size of a lymphocyte / equivalent to the cells of high-grade DCIS, with or without apocrine features.
Desirable: loss of E-cadherin membrane staining.
Bx right breast 65F
Dx?
Key features?
Apocrine pleormorphic LCIS.
A subset of pleomorphic lobular carcinoma in situ is further categorized as apocrine type, based on large cells with abundant eosinophilic granular cytoplasm and round to oval nuclei containing prominent nucleoli.
breast lesion.
Dx?
Defining features?
Florid lobular carcinoma in situ has cytological features similar to those of classic lobular carcinoma in situ (type A and/or type B cells) but is distinguished by marked expansion of terminal duct lobular units with little to no intervening stroma between markedly distended acini of involved TDLUs, and/or a size cut-off point at which an expanded acinus or duct fills an area equivalent to ~40–50 cells in diameter.
39F, R) breast mass at 10 OC 2cm from nipple
Dx?
Tubular adenoma. Largely occur in premenopausal women in UOQ.
Essential: a well-circumscribed tumour composed of a dense proliferation of closely approximated round and oval tubular structures with little background stroma; tubules composed of bilayered ductal and myoepithelial cells.
Desirable: immunohistochemical evaluation for confirmation of the dual cell population by myoepithelial markers (p63, p40, SMA, calponin) and luminal markers (EMA, CK19, CK8/18) if needed.
Tubular adenomas are benign, stable neoplasms with no increased risk of
Breast cancer, ductal
Grading?
Nottingham modification of Bloom-Richardson system, based on (a) tumor tubule formation, (b) nuclear pleomorphism and (c) number of mitotic figures in most active areas,
Scoring is done as follows
3 - 5 points: well differentiated (grade I)
6 - 7 points: moderately differentiated (grade II)
8 - 9 points: poorly differentiated (grade III)
Tumor tubule/gland formation:
1 point: > 75% of tumor
2 points: 10 - 75% of tumor
3 points: < 10% of tumor
Nuclear pleomorphism:
1 point: minimal nuclear variation in size and shape (< 1.5 times the size of benign epithelial cell nuclei), even chromatin, inapparent to inconspicuous nucleoli
2 points: moderate nuclear variation in size and shape (1.5 - 2 times the size of benign epithelial cell nuclei), typically visible but small nucleoli
3 points: marked nuclear variation in size and shape (> 2 times the size of benign epithelial cell nuclei), often prominent nucleoli
What is HER2? What is the gene and what does it encode?
How is amplification of this gene detected?
HER2/neu is the human epidermal growth factor receptor 2, also called ERBB2 (Erb-B2 receptor tyrosine kinase 2)
HER2 gene encodes transmembrane growth factor receptor (p185).
Cytoplasmic tyrosine kinase is constitutively active when overexpressed due to homo / heterodimerization.
Immunohistochemistry (IHC) detects evidence of protein overexpression via evaluation of the membranous staining in the tumor cells
To detect, the most commonly used in situ hybridization (ISH) is a dual probe fluorescent ISH (FISH) using fluorochrome labeled probes for (a) the HER2 locus on the long arm of chromosome 17 and (b) a site near the centromere of chromosome 17 (CEN17 or CEP17)
In situ hybridization detects HER2 gene amplification as evaluated by counting at least 20 tumor cells and estimating the HER2 copy number and the HER2/CEP17 ratio
breast ca AJCC staging
breast lesion
dx:
IHC:
Papillary DCIS
Essential: a neoplastic proliferation of epithelial cells covering delicate arborizing fibrovascular cores devoid of myoepithelium but contained within a duct with a surrounding myoepithelial layer.
Desirable: demonstration of the absence of myoepithelium along the fibrovascular cores but presence of myoepithelium along the duct wall by immunohistochemical detection of myoepithelial antigens.
Image: Monotonous cells with low-grade nuclei forming cribriform and glandular spaces line inconspicuous fibrovascular cores.
breast lx
Dx
Key histo features demonstrated in this image:
Papillary DCIS with a dimorphic population of cells.
H&E staining reveals two cell populations. One is luminal with apical snouts. The other, with more-abundant pale cytoplasm, mimics hyperplastic myoepithelium (also called globoid cells);
Although most papillary DCIS lesions consist of a single, uniform cell population, papillary DCIS with a dimorphic pattern has also been described. In addition to neoplastic ductal cells, it features a population of cells (globoid cells) with abundant clear cytoplasm; these morphologically resemble myoepithelial cells but have nuclear features and atypia similar to those of the frankly epithelial cell component
breast lesion
Dx:
Key features exemplified:
IHC:
What defines invasion in this context?
encapsulated papillary ca
Image: A papillary mass within a cystic space with numerous delicate fibrovascular stalks (lined by by a monomorphic population of neoplastic epithelial cells with low- or intermediate-grade nuclei. )
IHC: MEC (-) within and at periphery (can be focally present at periphery), ER/PR/HER2 +/+/-.
Frank invasion in this setting is defined as the presence of neoplastic elements that permeate beyond the fibrous capsule with an irregular infiltrative appearance.
breast lesion
dx?
Key features demonstrated?
IHC?
solid papillary ca
Expansile nodules with a solid growth pattern have inconspicuous, delicate fibrovascular cores, with no convincing evidence of invasion.
IHC: myoep markers (-/+) papillary fronds/periphery of lesion; HMWCK (-) in neoplastic population; ER/PR diffuse strong (+); freq chromo/synapta
breast lesion dx
Dx:
Key features demonstrated
solid papillary carcinoma
High-power view of solid nodules with inconspicuous delicate fibrovascular stalks and a monotonous population of round epithelial cells with low-grade nuclear atypia.
In situ: nodules have rounded, well-circumscribed contours and a distribution pattern consistent with an in situ process (regardless of myoepithelial layer around periphery)
With invasion: SPC is a/w a convention/mucinous/lobular ca etc
Invasive SPC is diagnosed when the nodules have ragged contours
breast lesion
Dx?
Key feature
solid papillary carcinoma
Image: Intracellular mucin (goblet cells) may be prominent in the neoplastic population.
breast lesion
dx
Invasive solid papillary carcinoma
Nodules devoid of a myoepithelial cell layer with ragged contours create a geographical jigsaw pattern within a desmoplastic stroma or infiltrate the fat.
breast lesion
dx
Solid papillary carcinoma with invasive carcinoma
Irregular neoplastic glands and trabeculae infiltrate the breast parenchyma adjacent to solid papillary carcinoma.
breast lesion, dx?
IHC
DDx:
Type A mucinous carcinoma
IHC: ER/PR (+); 80% AR(+); MC and mixed MC WT1 (+); Her2 (-) except in MC where it is amplified > 10%
DDx: mucocoele-like lesions (MLLs) with stromal mucin
27F breast lesion bx
dx?
diagnostic criteria
demographic
lactating adenoma
Essential: a well-circumscribed proliferation of closely packed hyperplastic secretory lobules separated by sparse delicate connective tissue; bland-looking lining epithelial cells containing vacuolated or granular cytoplasm and small nuclei with pinpoint uniform nucleoli.
demographic: most commonly occurs in 3rd trimester
Below: the tubules are lined by single-layered cuboidal epithelial cells with vacuolated cytoplasm and occasional hobnail nuclei, with myoepithelial attenuation. Some dilated tubules contain luminal pink flocculent secretions.
breast lesion
dx
dx criteria
Key features displayed in image
Malignant adenomyoepithelioma
Essential: a malignant tumour arising in association with classic AME, with the luminal or myoepithelial component (or both) being malignant.
Image: cytological atypia is clearly evident in both epithelial and myoepithelial cells. The myoepithelial cells outnumber the epithelial cells in this case.
Nipple lesion
Dx?
Key features
Syringomatous tumour of the nipple
3 types of cells present
Myoepithelial-like cells: p63(+) and high molecular weight keratin (+)
Luminal-like cells: p63(-) and low molecular weight keratin (+)
Squamoid cells: p63(+) and high molecular weight keratin (+)
Cells have small uniform nuclei
Mitotic figures absent or rare
Infiltrates into smooth muscle of areola
Overlying epidermis may be acanthotic
breast ca
How do you calculator residual cancer burden following neoadjuvant chemotherapy
clear cell carcinoma of uterine corpus vs ovarian clear cell
Histo features and IHC
below: clear cell ca uterine corpus (papillary features)
Clear cell carcinoma of uterine corpus:
Tubulocystic/papillary/solid; clear to eosinophilic cuboidal, polygonal, hobnail, or flat cells; stratificaiton, intraglandular tufting and detaching budding F+ or absent; squamous differentiation is absent. Nuclear pleomorphism focally moderate to severe.
IHC: HNF1beta + (67-100%); napsin A (56-93%); AMACR + (75-88%)
Ovarian clear cell:
Same architecture as above. Cells are cuboidal and/or hobnail (but not columnar), arranged in a single layer with only minimal stratification. Stromal hyalinization/myxoid stroma are frequent. Solid pattern exhibits sheets of polyhedral cells separated by delicate septa. Cytoplasm- clear to (less commonly) eosinophilic. The glycogen-rich clear cytoplasm is PAS-positive and diastase-sensitive. Nuclei are large and monomorphic, with rounded to angulated contours, hyperchromasia, prominent nucleoli, and (rarely) nuclear pseudoinclusions. Nuclear pleomorphism may be present focally or in scattered cells, but it is typically not diffusely distributed. Mitotic activity is variable but usually low. Hyaline and psammoma bodies are infrequent. A peritumoural and/or diffuse lymphoplasmacytic infiltrate may be present.
Essential: a combination of architectural patterns (tubulocystic, papillary, and solid architecture) with flat or cuboidal cells (clear, eosinophilic, hobnail) having uniform nuclear features overall and low mitotic counts.
Desirable: associated clear cell adenofibroma; HNF1β and napsin A positivity; WT1 and PR negativity.
IHC: PAX8(+); HNV1beta (+);
Negative: WT1, ER, PR
Dx ?
ddx and how you differentiate them
How do you grade them/what is their grade
Immunoprofile
sclerosing adenosis - has MEC
Mixed tumour composed of < 90% tubules (tumours with 10-90% tubules)
Radial star (as TC can have a stellate profile at low power, but radial scar has MEC)
Graded with the Nottingham criteria and are by definition grade 1 (>90% tubules, uniform small-med nuclei)
Immunoprofle: ER+/PR+/HER2-. If HER2 positive, reconsider dx. Usu has luminal profile (LMWCK: CK8/18 (+) CK5/14 (-)
Expression of high-molecular-weight cytokeratins and/or ER negativity (especially in small diagnostic biopsies) should raise the possibility of a basal-phenotype carcinoma with tubule formation, such as adenoid cystic carcinoma or low-grade adenosquamous carcinoma.
breast mass 60F
Dx
invasive pleomorphic lobular carcinoma
papillary lesions
Define the categories of papillary lesions of the breast
palpable mass
dx?
Key features
Solid papillary carcinoma
characterized by a solid growth pattern with delicate fibrovascular cores. They frequently show neuroendocrine differentiation and are biologically indolent.
Entire lesion occupied by a cell population with cytological features of low or intermediate nuclear grade, growing predominantly in a solid manner; spindle cell component; neuroendocrine and mucinous differentiation is frequent
palpable mass 63F breast
Solid papillary carcinoma with prominent intracellular mucin
Atypical vascular lesion diagnostic features
AVL vs angiosarcoma
IHC and special stains for Pagets
and ddx for pagets w/ IHC
Intracellular mucin
CK7 and cam 5.2 (+)
HER2 (+) in 80-90%
ER 40% and PR 30%
HER IHC interpretation ?
Incidental microscopic finding.
Dx?
Perilobular hemangioma
conglomerate of small, thin walled capillary vessels in and around a lobule
Usu < 2mm and incidental finding. Not to be mistaken for angiosarcoma
