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BREAST LESIONS, Screen Shot 2021-11-01 at 8.41.08 pm, Screen Shot 2021-11…
BREAST LESIONS
FIBROEPITHELIAL
FIBROADENOMA
- Definition: Benign hyperplastic fibroepithelial lesion of the breast
- Composed of both stromal and epithelial components
- Macroscopic:
1)Well-defined round or ovoid gray mass
2) No true capsule
3) Rubbery cut surface
- Microscopic:
1) Stromal component: loosely cellular, lacks cytologic atypia
2) Epithelial component: compressed duct structures or tubules with epithelial and myoepithelial layers; may show epithelial hyperplasia; rarely atypical hyperplasia, lobular neoplasia or DCIS
3) Complex fibroadenoma: sclerosing adenosis, papillary apocrine change, epithelial calcifications or cysts >3 mm
- Cytology:
1) Cellular specimen
2) Abundant sheets and clumps of epithelial cells in a background of scanty stromal fragments and bare/stripped nuclei
3) Epithelial cells may show some variation in size and some discohesion
- DDx:
1) Phyllodes tumor
2) Tubular adenoma
3) Hamartoma
PHYLLODES
- Definition: True fibroepithelial neoplasm, composed of epithelial and stromal components
- Epidemiology:
1) Rare - 0.3 to 1% all breast tumors
2) Any age but usually females in 50s
- Macroscopic:
1) 4-5 cm typically, ranges up to 20 cm in size
2) Well-defined, often lobulated; ill-defined in malignant lesions
3) Cross-sectioning shows elongated clefts within a tan/gray-brown whorled stroma
- Microscopic:
1) Cellular stroma lined by an epithelial and myoepithelial bilayer, forming a leaf-like structure
2) Benign lesions: are composed of cellular stroma showing mild-to-moderate cytologic atypia (<5 per 10 HPF); margins are well-defined; no stromal overgrowth
3) Malignant lesions: composed of an overgrowth of markedly atypical stromal cells with abundant mitoses (>10 per 10 HPF); may show a focally irregular margin; lack stromal overgrowth
STROMAL
PSEUDOANGIOMATOUS STROMAL HYPERPLASIA
- Definition: proliferation of myofibroblasts associated with stromal clefts that resemble anatomosing, slit-like vascular spaces
- Epidemiology:
1) Incidental finding in >25% of biopsies
2) Majority of affected women are of childbearing age or postmenopausal women taking HRT
3) Can increase in size during pregnancy
- Radiologic:
NB: findings are not specific for a mass when a core Bx is performed as the same type of stromal changes can be an incidental finding; therefore, radiologic correlation is necessary to ensure the targeted lesion was biopsied before concluding that PASH is the underlying lesion
- Macroscopic:
1) Mass-forming PASH can appear as a firm, rubbery, circumscribed, white nodule (size range 1-10 cm)
- Microscopic:
1) Prominent, slit-like stromal clefts
2) Clefts are lined by myofibroblasts and mitoses are not seen
3) Clefts can involve both inter- and intralobular stroma and can appear to dissect into lobules
4) Spaces are empty or contain only rare RBCs
5) Stroma is paucicellular in most cases
6) Cellular variant, 'fascicular PASH', is characterized by short, poorly-formed fascicles of spindle cells; clefting may be absent or only present focally
- DDx:
1) Angiosarcoma
2) Myofibroblastoma
3) Fibrous tumors
4) Fibroadenoma and phyllodes tumor
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DUCTAL
ATYPICAL DUCTAL HYPERPLASIA
- Definition: specific histologic patterns of epithelial hyperplasia that imply elevated risk of breast cancer
- Epidemiology: in ~10% of screen-directed Bx
- Macroscopic: N/A
- Microscopic:
1) Most often a solitary lesion
2) Confined to a single lobular unit
3) At least focally a uniform cell population and architectural features suggesting low-grade DCIS
4) Evenly spaced cells with hyperchromatic nuclei
5) Rigid cellular bars and secondary spaces
- Cytology:
1) Variable cellularity
2) Epithelial cells may have a monotonous appearance
3) Nuclei have fine chromatin and inconspicuous nucleoli
4) Loss of cohesion
- Immunohistochemistry:
1) Cell are usually negative with HMW cytokeratins
2) Uniformly positive with ER
- DDx:
1) Low-grade DCIS
2) Usual epithelial hyperplasia
DUCTAL CARCINOMA IN SITU (DCIS)
- Definition: malignant proliferation of epithelial cells within the duct system without evidence of stromal invasion
- Epidemiology: in ~25% of screen-detected breast carcinoma; may arise anywhere in the breast
- Macroscopic:
1) Can be seen as a speckled, ill-defined area
2) Often is not visible, however,
- Microscopic:
1) Epithelial cells proliferate within the ducts, although may extend into the lobular structures as cancerization of lobules
2) The neoplastic cells may be large, pleomorphic and often solid in growth pattern in high-grade DCIS or small and regular, showing polarization around architectural structures, such as micropapillae and cribriform spaces in low-grade disease
INVASIVE DUCTAL CARCINOMA
- Definition: Malignant invasive epithelial lesion of the breast derived from the terminal duct-lobular unit
- Epidemiology:
1) Common - incidence for women 1:9
2) Most common in upper outer quadrant but can arise anywhere in breast
3) Rare in pts 20-30 years without a FHx
- Macroscopic:
1) Firm, well to poorly defined, sometimes stellate mass
2) Wide range of sizes at presentation
- *Microscopic:)
1) Malignant cells, often forming trabeculae or growing in sheets
2) >50% of tumor shows NST pattern
- Immunohistochemistry:
1) 70-80% ER positive
2) 15-25% HER2 positive
- DDx:
1) Other nonepithelial subtypes of breast carcinoma
2) Rare nonepithelial breast lesions (lymphoma, metastases)
LOBULAR
ATYPICAL LOBULAR HYPERPLASIA (ALH) AND LOBULAR CARCINOMA IN SITU (LCIS)
- Definition:
1) A group of breast lesions characterized by cytologically dyshesive uniform cells with eccentric nuclei, frequently with intracytoplasmic mucin vacuoles
2) ALH and LCIS are distinguished by the degree of distension of involved spaces
3) Pleomorphic lobular carcinoma in situ (PCLIS) is characterized by larger, more pleomorphic cells
- Microscopic:
1) Distension of involved lobules by a dyshesive, uniform proliferation of round cells with eccentric cytoplasm
2) Cells frequently contain an intracytoplasmic mucin vacuole, often with a 'targetoid' appearance
3) Classic, type 'A' cells are 1 to 1.5 times the size of lymphocytes; type 'B' cells are larger, 2 times the size of lymphocytes, often with nucleoli; cells are uniform with no pleomorphism
4) Individual cells of ALH and LCIS are identical; distinguished by degree of distension of involved spaces: at least 50% of spaces in a TLDU filled and distended in LCIS
5) PLCIS exhibits a dyshesive growth pattern of LCIS, but cells are larger (4 times the size of lymphocytes) and pleomorphic; mitoses may be found; necrosis is often present
- Immunohistochemistry:
1) ALH, LCIS and PLCIS are negative for E-cadherin in the majority of cases
2) Most LN and PLCIS are positive for estrogen and progesterone receptor and negative for HER2
3) PLCIS has a higher proliferation rate (Ki-67 index) and is more likely to be p53 positive versus classic LN
- DDx:
1) Myoepithelial cells
2) Fixation artefact with 'pseudodyshesion'
3) DCIS
4) Invasive carcinoma (particularly if LN secondarily involves a sclerosing lesion such as a radial scar or sclerosing adenosis)
INVASIVE LOBULAR CARCINOMA
- Definition: Malignant invasive epithelial lesion with more than 90% of the tumor showing lobular morphology
- Macroscopic:
1) Varies from firm, gray, well-circumscribed mass to poorly-defined thickening
2) Average size 24 mm
- Microscopic:
1) Subtypes include classical, tubulo-lobular, solid, alveolar and mixed
2) Cells show a dyshesive pattern of infiltration with oval nuclei, minimal cytoplasm and intracytoplasmic lumina
3) ~75% grade 2; 15% grade 1 (including tubulo-lobular); 10% grade 3 (i.e., pleomorphic ILC)
4) LCIS present in 2/3 cases
- Immunohistochemistry:
1) Negative of reduced staining for E-cadherin
2) Usually positive for ER and PR
3) Usually negative for HER2 (except high-grade ILC)
- DDx:
1) Lymphoid population, either benign or lymphomatous infiltrates
PAPILLARY
INVASIVE PAPILLARY CARCINOMA
- Epidemiology:
1) Up to 2% of all invasive carcinomas
2) Postmenopausal women
- Macroscopic:
1) Well circumscribed
- Microscopic:
1) Fibrovascular cores
2) Background of islands of invasive carcinoma
3) Evidence of tumor circumscription
4) Cells may show apocrine metaplasia
5) Often intermediate nuclear grade
6) Intraductal component usually present
7) Lymphovascular invasion seen in 1/3 cases as well as nodal metastases
INTRADUCTAL PAPILLOMA
- Definition: Benign lesions of true ducts with myoepithelium and epithelium covered by fibrovascular cores; includes central (solitary) and peripheral (multiple) papillomas; usual epithelial hyperplasia is common' atypical hyperplasia may less commonly be seen
- Epidemiology:
1) Solitary occur in 5th and 6th decades
2) Multiple occur in younger age group
- Macroscopic:
1) Well-circumscribed mass with variable solid and cystic components
2) Soft or firm tumors with dense sclerosis
3) Focal hemorrhage and necrosis is common
- Microscopic:
1) Multiple branching papillae lined by myoepithelium and epithelium with varying degrees of epithelial proliferation
2) May have usual or atypical ductal hyperplasia, apocrine or squamous metaplasia
3) Surrounding stroma may be sclerotic with pseudoinvasive foci
- Cytology:
1) Three-dimensional clusters with fibrovascular cores
2) Increased cellularity
- DDx:
1) Nipple adenoma
2) Papillary DCIS
3) Encapsulated papillary carcinoma
4) Invasive carcinoma
ENCAPSULATED (ENCYSTED/INTRACYSTIC) PAPILLARY CARCINOMA
- Definition: Distinctive carcinoma characterized by epithelial-lined fibrovascular cores and pushing borders. Myoepithelial cells are typically absent from both the fibrovascular core and the periphery of the tumor
- Epidemiology:
1) 0.5-2% of all breast cancers
2) 50 arise centrally
3) In older women; disproportionately high representation in males
- Macroscopic:
1) Usually 1-3 cm
2) Distinct from surrounding tissue
3) Cystic and solid areas; often friable and hemorrhagic
4) Thick fibrous wall
- Microscopic:
1) Expansile mass with a smooth, pushing border and surrounding fibrotic rim
2) Fibrovascular cores lined by a malignant epithelium, without intervening myoepithelial layer
3) Epithelium may proliferate between the cores with the formation of cribriform structures or solid sheets
- Cytology:
1) Often bloody
2) Three-dimensional fibrovascular cores with increased cellulariy
3) Monotony of epithelial cells
4) Unreliable in distinguishing from papilloma
- DDx:
1) Benign intraductal papilloma
2) Papilloma involved by DCIS
3) Papillary DCIS
4) Metastatic papillary carcinoma
5) Carcinoma with cystic degeneration
6) Invasive papillary carcinoma
PAPILLARY DUCTAL CARCINOMA IN SITU
- Typically diffuse involvement of small and medium-sized ducts
- Microscopic:
1) Intraductal fibrovascular cores lined by neoplastic epithelium
2) No intervening myoepithelial layer; however, myoeptihelial cells are present at the periphery of the duct spaces
3) Neoplastic cells are usually of low or intermediate nuclear grade
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SPECIAL TYPES
INVASIVE TUBULAR CARCINOMA
- Definition: Malignant epithelial lesion comprised of >90% discrete tubules
- Epidemiology:
1) 0.8-2.3% of invasive breast cancers
2) Mean age range is 58-64 years
- Macroscopic:
1) Moderately well-defined, with stellate/gray cut surface
2) Average size 12-16 mm
- Microscopic:
1) Angulated tubules lined by a single layer of epithelial cells
2) Apical snouts often visible
3) Desmoplastic stroma often present
4) 20% multifocal
- Immunohistochemistry:
1) Usually ER and PR positive
2) Usually HER2 negative
3) Markers for myoepithelial cells (e.g. p63) are negative
INVASIVE CRIBRIFORM CARCINOMA
- Macroscopic:
1) Moderately well-defined with stellate/grey cut surface
2) Average size 26-31 mm
- Microscopic:
1) Islands of mild to moderately pleomorphic cells forming cribriform structures
2) Tumor cells show a mild to moderate degree of pleomorphism
3) Often a desmoplastic stromal reaction, occasionally with giant cells
- Immunohistochemistry:
1) Usually ER and PR positive
2) Usually HER2 negative
- DDx:
1) Adenoid cystic carcinoma
2) In situ cribriform DCIS
3) Neuroendocrine carcinoma
INVASIVE MUCINOUS CARCINOMA
- Macroscopic:
1) Well-defined mass with a gelatinous cut surface
2) Average size approximately 20 mm
- Microscopic:
1) Nests/trabeculae/glandular structures of neoplastic cells within lakes of mucin
2) Tumor cells show mild or moderate nuclear pleomorphism (score 1 or 2)
- Immunohistochemistry:
1) Usually ER or PR positive
2) Usually HER2 negative
3) Neuroendocrine features may be seen
- DDx:
1) Mucocele-like lesions
MEDULLARY CARCINOMA
- Macroscopic:
1) Usually well-defined and circumscribed with grey/tan cut surface
2) Average size 25 to 29 mm
- Microscopic findings:
1) Syncytial growth pattern in >75%
2) Absence of glandular structures
3) Moderate/marked lymphoplasmacytic infiltrate
4) Histologic circumscription
5) Marked (score 3) nuclear pleomorphism
- Immunohistochemistry:
1) ER negative
2) HER2 negative
3) p53 positive
- DDx:
1) Invasive ductal/NST carcinoma
2) Chronic inflammation, lymphoma or lymph node
INVASIVE MICROPAPILLARY CARCINOMA
- Macroscopic:
1) Grey/white, stellate cut surface
2) Average size 24 mm
- Microscopic:
1) Solid/tubular nests within a clear space
2) Usually a component of mixed tumor
3) Lymphovascular invasion common and there is a high rate of axillary nodal metastases
- Immunohistochemistry:
1) EMA: 'inside out pattern'
2) ER and PR positivity in >60%
3) HER2 positive in 8-45%
- DDx:
1) Retraction artefact
2) Ductal/NST carcinoma
3) Invasive papillary carcinoma
4) Metastatic carcinoma from other primary site
5) Mucinous carcinoma
METAPLASTIC CARCINOMA
- Macroscopic:
1) Grey/white, ill-defined cut surface
2) May have cystic areas of foci of necrosis macroscopically
2) Wide range of sizes reported, often larger than other special types
- Microscopic:
1) 70% of tumors have a spindle cell component
2) Spindle cell component may range from low to high grade
3) Spindle or squamous cell differentiation may be present in pure form or admixed with another metaplastic component or with ductal/NST
4) May have heterologous elements (e.g., osteocartilaginous differentiation)
- Immunohistochemisttry:
1) Express cytokeratins, at least focally
2) Often ER, PR and HER2 negative
3) Often p63 positive
- DDx:
1) Metastatic carcinoma (squamous) or sarcoma (either metastatic or primary)
2) Fibromatosis (low-grade variants)
3) Phyllodes tumor
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APOCRINE CARCINOMA
- Macroscopic:
1) As for tumors of ductal/NST
- Microscopic:
1) Must show >90% apocrine morphology
2) Cells have abundant eosinophilic granular cytoplasm
3) Large nuclei with prominent nucleoli
4) May be admixed with other special types
- Immunohistochemistry:
1) GCDFP15 positive
2) ER and PR negative
3) Androgen receptor positive
- DDx:
1) Apocrine atypia in sclerosing lesion
NEUROENDOCRINE CARCINOMA
- Definition: Expressing neuroendocrine markers in >50% of the cell population
- 3 subtypes:
1) Solid neuroendocrine
2) Small cell/oat cell
3) Large cell neuroendocrine
- Macroscopic:
1) No specific macroscopic features
- Microscopic:
1) Solid: formed from cells arranged in nests, sheets or trabeculae typically separated by scant connective tissue. Acinar formation and peripheral palisading of cell groups may be seen and there is a characteristic collagen core. The cells are relatively uniform with eosinophilic granular cytoplasm but may have a polygonal, plasmacytoid or spindle appearance
2) Small cell: composed of relatively small cells with scant cytoplasm, finely granular chromatin and a high mitotic rate. The growth pattern is infiltrative and can be solid, trabecular or single file
3) Large cell: cells arranged in clusters with vesicular nuclei and relatively abundant cytoplasm. Mitoses are abundant (18-65 per HPF) and focal necrosis can be seen. Most tumors are grade 3
- Immunohistochemistry:
1) Grimelius stain positive
2) Small cell: CK7, CAM5.2 and CK19 positive, CK20 negative
3) In general: most synaptophysin, chromogranin, ER, PR positive. Usually HER2 negative. All positive for enolase
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