Intraductal Proliferative Lesions Flashcards

1
Q

What entities are included in this category ?

A
  • 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.

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2
Q

What are the key findings for

UDH ?

A
  • 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
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3
Q

What are occasional findings

seen in UDH ?

A
  • multiple cell types:
    • metaplastic cells: apocrine or squamous
  • foamy histiocytes
  • calcifications
  • rarely necrosis (often in florid UDH)
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4
Q

What are uncommon findings

in UDH ?

A
  • alterations such as fibroblastic proliferations, elastosis
  • or mononuclear cell infiltrates in the stroma
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5
Q

What is the immunophenotype of UDH ?

A
  • 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
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6
Q

What are the genetics of UDH ?

A
  • 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

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7
Q

What is the clinical course

and prognosis of UDH ?

A
  • 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
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8
Q

What is the definition of

atypical ductal hyperplasia ?

A
  • 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
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9
Q

What is the cytology and the architecture

of ADH ?

A
  • 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
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10
Q

What differentiates the diagnosis

of ADH from DCIS ?

A
  • 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
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11
Q

What size criteria have been

proposed for diganosis

of ADH?

A
  • 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

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12
Q

What is the immunophenotype

of ADH ?

A
  • strong, uniform expression of ER
  • low proliferation rate
  • CK5/6 (HMWK)- negative
    • can stain the myoepithelial cell layer
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13
Q

What is the association of ADH with

breast cancer ?

A
  • 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
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14
Q

What is the pattern of involvement

of the breast by DCIS ?

A
  • usually unicentric, segmental distribution
  • multicentric disease is uncommon

IMP: generally presents as mammographic microcalcifications; infrequently it presents with a palpable mass

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15
Q

What are the macroscopic findings of DCIS ?

A
  • generally do not have any
  • but if present you see cords of pasty, material exuding from the cut surface
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16
Q

What are the main architectural

features of DCIS ?

A
  • comedo
  • cribriform
  • micropapillary
  • papillary
  • solid
17
Q

What are the key features

of low-grade DCIS ?

A
  • 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
18
Q

What other findings in the breast

can be seen in association with high grade DCIS ?

A
  • fibroblastic proliferation with collagen deposition (desmoplasia)
  • chronic inflammation and vascular proliferation (angiogenesis)
  • Paget disease of the nipple
19
Q

What are some of the unusual types

of DCIS ?

A
  • apocrine DCIS
  • cystic hypersecretory
  • Squamous
  • clear cell
  • signet ring cell
  • mucinous
  • spindle cell features

review morphology and biomarkers p. 97-101

20
Q

What is unique about spindle cell DCIS ?

A
  • the spindle cells demonstrate neuroendocrine differentiation with positivity for chromogranin and synaptophysin
21
Q

What immunostain pattern favors a diganosis of LCIS ?

A
  • E-cadherin and Beta-catenin negative
  • p120 catenin- positive in the cytoplasm
22
Q

What immunostain pattern favors a diagnosis of DCIS ?

A
  • strong membrane staining for E-cadherin, p120 catenin, and Beta-catenin