You are doing a rotation in an oncology clinic and meet three women who presented with masses in their breasts. They are both here to discuss their results.
The first patient is a 65 year old female with no family history of breast cancer.
Describe what you see histologically:
- increased cellularity
- cells look uniform
- dysplasia: note this is low grade so minor atypia - cells still look pretty uniform
- no/few mitotic figures
- no atypia
- does not breach BM
- glandular formation without interveneing stroma = low grade cribiform DCIS
Is this DCIS or invasive? High grade or low grade?
- DCIS: does not cross basement membrane
- low grade - differentiated, few/no mitotic figures, minimal atypia
The second patient is a 72 year old female with no family history of breast cancer.
Describe what you see histologically:
- increased cellularity
- atypical pleomorphic nuclei
- prominent nucleoli
- dysplasia: high grade
- prominent nucleoli
- mitotic figures (tripolar @ arrow)
- necrosis/ calcifications
- does not breach BM
- central necrosis = comedo
Is this DCIS or invasive? High grade or low grade?
- DCIS: does not cross basement membrane
- high grade with central necrosis/calcifications
The third patient is a 32 year old female whose mother was diagnosed with breast cancer at age 40.
What do you want to test her for?
- BRCA1/2
What other TSGs are associated with cancer?
Tumor Suppressor Genes:
**both alleles must be altered for cell transformation = 2-hit hypothesis**
Activation: mutation/deletion/gene loss
P53
|
Chromosome 17
|
Most common mutation +/or loss in cancer
Li-Fraumeni syndrome
|
RB
|
Chromosome 13
|
Retinoblastoma, osteosarcoma
|
WT-1
|
Chromosome 11
|
Wilm’s tumor
|
NF-1
|
Chromosome 17
Negative regulator of Ras signal transduction pathway
|
Neurofibromatosis (1)
Café-au-lait spots,
Neural tumors, Lisch nodules
|
NF-2
|
Chromosome 22
|
Neurofibromatosis type 2
Bilateral acoustic schwannomas &
Juvenile cataracts
|
P16
|
Chromosome 9
|
Melanoma
|
APC
|
Chromosome 5
|
Colorectal cancer (assoc. w/ FAP)
|
VHL
|
Chromosome 3p = gene deletion
|
Renal cell carcinoma (multiple bilateral tumors)
Hemangioblastoma retina, medulla, cerebellum
|
BRCA1 + 2
|
DNA repair protein
BRCA1: 17q
BRCA2: 13q
|
Breast cancer + ovarian (1>2)
|
DPC
|
Chromosome 18
deleted
|
Pancreatic cancer
|
DCC
|
chromosome 18
deleted
|
Colon cancer
|
Describe what you see histologically:
- advanced dysplasia/anaplasia
- pleomorphism
- desmoplasia
- hyperchromasia
- loss of normal architecture
What is the difference between DCIS & infiltrating ductal carcinoma?
DCIS:
|
Infiltrating Ductal carcinoma:
|
·
Dysplasia:
entire thickness of epithelium but does not go through BM
o
Maybe precancerous
·
No evidence of invasion into surrounding
stroma
·
Comedo: prominent necrosis in the center –
high risk of invasion, necrotic material fq calcifies
·
Cribiform: back to back glands without stroma
between them, uniform hyperchromatic nuclei, infrequent necrosis or mitosis
·
Micropapillary: lack fibrovascular cores
·
Papillary: intraluminal projections with
fibrovascular cores
·
Solid: lack significant necrosis,
papillations, fenestrations
|
·
Dysplastic
cells breach basement membrane
·
>70% infiltrating breast cancer
·
Hard, grey white gritty masses
·
Cords/nests of tumor cells +/- gland formation
·
Malignant cells induce fibrous rresponse –
desmoplasia
o
Well differentiated
(grade 1): low mitotic activity, nuclei relatively uniform
o
Moderately
differentiated (grade 2): cells infiltrate as sheets/ nests (some glandular
differentiation), some pleomorphism, increased mitotic rate (moderate)
o
Poorly differentiated
(grade 3): solid nests neoplastic cells
- no glandular formation, nuclear atypia (pleomorphism) + lots of
mitotic activity
|
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