Intraductal Proliferative Lesions Flashcards
What entities are included in this category ?
- Usual ductal hyperplasia (UDH)
- Atypical ductal hyperplasia (ADH)
- Ductal carcinoma in situ (DCIS)
Clinically important because they increase the risk of breast cancer, although to different degrees.
What are the key findings for
UDH ?
- benign epithelial proliferation
- can show mild epithelial proliferation of 2-4 layers
- various architecture types
- Micropapillary: tuft like, elongated, and tapering with broad bases & narrow tips
- Cytology
- heterogeneous cell population
- variation in cell size, shape and orientation
- poorly defined cell borders
- nuclear grooves, intracytoplasmic inclusions
- Architecture
- solid, fenestrated, micropapillary
- lumens irregular, variable size and shape, often slit like and peripheral
- No cell polarization
- bridges stretched or twisted with central attenuation
What are occasional findings
seen in UDH ?
- multiple cell types:
- metaplastic cells: apocrine or squamous
- foamy histiocytes
- calcifications
- rarely necrosis (often in florid UDH)
What are uncommon findings
in UDH ?
- alterations such as fibroblastic proliferations, elastosis
- or mononuclear cell infiltrates in the stroma
What is the immunophenotype of UDH ?
- variable ER expression with heterogeneity
- low proliferation rate
- HMWK (CK 5/6) mosaic pattern – characteristic feature
note:
- LMWK - stains luminal cells
- HMWK- stains basal cells
What are the genetics of UDH ?
- subset of UDH show chromosomal losses and gains
- no consistent genetic alterations in these lesions
- share some alterations with ADH and DCIS
IMP: not a direct precursor but show generalized increased breast cancer risk
What is the clinical course
and prognosis of UDH ?
- associated with a 1.5 to 2 fold increased risk of breast cancer and the subsequent cancer can occur in either breast
- risk is slightly higher in women who have a family history
What is the definition of
atypical ductal hyperplasia ?
- epithelial proliferation confined to the mammary duct-lobular unit
- neoplastic population similar to LG- DCIS
- the area of involvement can also have non-neoplastic proliferations such as UDH or normal epithelium
What is the cytology and the architecture
of ADH ?
- Cytology
- monomorphic cells with well-defined borders
- rounded nuclei that are evenly spaced
- Architecture
- arcades, rigid bridges or bars of uniform thickness
- micropapillae (broader at the tips than at the base)
- solid or fenestrated (cribriform) patterns
- cell polarization around extracellular lumens
What differentiates the diagnosis
of ADH from DCIS ?
- ADH is a diagnosis when the size or extent of the proliferation does not meet criteria for DCIS
- only a portion of the involved space or spaces is occupied by the atypical cell population
What size criteria have been
proposed for diganosis
of ADH?
- lesions with architectural and cytologic features of low grade DCIS
- < 2 mm in size with < 2 duct involvement
- but some authors will even accept 3-4 mm in size
- Goal
- conservative diagnosis particularly in biopsies
- could call “atypical intraductal proliferative lesion”
- then give the differential and would prompt an excision
IMP: these criteria only apply to low-grade lesions and not high grade
What is the immunophenotype
of ADH ?
- strong, uniform expression of ER
- low proliferation rate
- CK5/6 (HMWK)- negative
- can stain the myoepithelial cell layer
What is the association of ADH with
breast cancer ?
- confers a 3-5 fold increased risk
- both breast have increased risk
- 2x as frequent in the ipsilateral breast
IMP: the finding of ADH on a biopsy is an indication for surgical excision
- 10-15% of women on excision have a worse lesion
What is the pattern of involvement
of the breast by DCIS ?
- usually unicentric, segmental distribution
- multicentric disease is uncommon
IMP: generally presents as mammographic microcalcifications; infrequently it presents with a palpable mass
What are the macroscopic findings of DCIS ?
- generally do not have any
- but if present you see cords of pasty, material exuding from the cut surface
What are the main architectural
features of DCIS ?
- comedo
- cribriform
- micropapillary
- papillary
- solid
What are the key features
of low-grade DCIS ?
- monotonous, uniform, rounded cell population
- subtle increase in N:C ratio
- highly organized nuclear distribution
- round nuclei with inconspicuous nucleoli
- hyperchromasia may or may not be present
Architecture:
- bridges and arcades will be of uniform thickness
- cells polarize around extracellular lumens
- comedo necrosis is rare
What other findings in the breast
can be seen in association with high grade DCIS ?
- fibroblastic proliferation with collagen deposition (desmoplasia)
- chronic inflammation and vascular proliferation (angiogenesis)
- Paget disease of the nipple
What are some of the unusual types
of DCIS ?
- apocrine DCIS
- cystic hypersecretory
- Squamous
- clear cell
- signet ring cell
- mucinous
- spindle cell features
review morphology and biomarkers p. 97-101
What is unique about spindle cell DCIS ?
- the spindle cells demonstrate neuroendocrine differentiation with positivity for chromogranin and synaptophysin
What immunostain pattern favors a diganosis of LCIS ?
- E-cadherin and Beta-catenin negative
- p120 catenin- positive in the cytoplasm
What immunostain pattern favors a diagnosis of DCIS ?
- strong membrane staining for E-cadherin, p120 catenin, and Beta-catenin
