Breast-Gao Flashcards
Good prognosis subtypes of breast ca
Colloid/mucinous Papilary Tubular Medullary Cribiform Adenoid cystic
Lesions with similar relative risk of developing invasive carcinoma
Papilloma
Radial scar
Florid hyperplasia
Sclerosing adenosis
PASH is produced by what cell type?
myofibrofblasts
PASH cells lining slit like spaces IHC …
vimentin actin ER CD34 negative for CD31
Independent prognostic factors for breast cancer
grade
lymph node status
LVI
tumor size
Molecular phenotype classification of breast cancer
Luminal A
Luminal B
ERBB2
Basal like
After excision, adjuvant treatment decisions for breast cancer are based on…
tumor size
MBR grade
ERBB2
LVI
pN1 definition
- 1 node positive for macromets, 2 nodes positive for miromets, 1 node positive for ITC
- 2 nodes positive for micromets, 1 node positive for ITC
- 1 node positive for macromets, 1 node positive for micromets, 1 node positive for ITC
- 1 internal mammary sentinel lymph node with a micromet and negative axillary lymph nodes
- 3 nodes positive for macromets, 1 node positive for ITC
myoepithelial markers of breast, list 4
SMMHC
Calponin
p63
actin
most helpful IHC to distinguish between florid ductal hyperplasia of the usual type and atypical ductal hyperplasia (ADH)
CK5/6
excisional biopsy suggested for florid ductal hyperplasia?
NO
excisional biopsy suggested for….
intraductal papilloma
mucocele like lesion
lobular carcinoma in situ
flat epithelial atypia with ADH
which feature does NOT help distinguish between benign from malignant phyllodes
leaflike structures
benign vs malignant phyllodes features
heterologous elements
mitoses
margins
cellularity
breast fibromatosis
proliferation of myofibroblastic cells
positive for beta catenin
a/w trauma
a/w gardner syndrome
does fibromatosis consistently respond to hormonal therapy
NO
IHC for granular cell tumors
neuron specific enolase vimentin S100 CEA negative for ER
paget disease cells positive for…
EMA CEA CK CAM5.2 HER2
FEA is independently most a/w increased incidence of which lesion
ADH
low grade dcis is more positive for ____ than high grade dcis
ER
PR
Cyclin D1
near diploidy
which clinical presentation is most a/w breast carcinoma
palpable mass
which breast lesions have NO increased relative risk of developing breast carcinoma
apocrine cysts
duct ectasis
mild hyperplasia
adenosis
risk factors for breast carcinoma
breast density
ethnicity
hormone replacement therapy
alcohol consumption
are breast implants a/w breast carcinoma
NO
name of postmastectomy angiosarcomas
Stewart-Treves
biomarker profile for BRCA1 associated breast cancers
ER neg, PR neg, Her2 neg, CK5/6 pos
Histologic features of diabetic mastopathy
keloidal like stromal fibrosis
lymphocytic ductitis
lymphocytic lobulitis
lymphocytic vasculitis
what favours dx of ADH over DCIS
Overlapping nuclei= ADH
the most concern in interpreting ER/PR IHC
no staining in an invasive lobular carcinoma
Extensive Intraductal Carcinoma positive (EIC+) is defined as:
DCIS present involving at least 25% of the area of the invasive carcinoma AND extending outside the invasive carcinoma mass
Toker cell IHC
CK7 positive
Her2 positive
CD138 negative
better prognosis for patients with IDC NOS
high percentage of tubule formation (>75%)
Definition of isolated tumor cells
single cluster of tumor cells - 0.2 mm or - 200 cells
clinical response to herceptin has been shown in trials with cutoff ERBB2/CEP17 ratios as low as:
2.0
Classify stromal tumors of the breast
Biphasic tumors:
- fibroadenoma
- phyllodes
- periductal stromal tumor
Pure stromal tumors: according to tissue of origin
Benign stromal tumors of breast
- benign stromal spinde cell tumors (BSCT)
- PASH
- nodular fasciitis
- fibromatosis
- lipoma, spindle cell lipoma
- leiomyoma neural: - granular cell tumor - neurofibroma - schwannoma
vascular:
- angioma, angiomatosis
Benign stromal spindle cell tumors subtypes
BSCT with predominant myofibroblastic differentiation: myofibroblastoma
BSCT with predominant fibroblastic differentiation: solitary fibrous tumor/ hemangiopericytoma
Malignant stromal tumors of breast
- malignant stromal cell tumor with predominant myofibroblastic differentiation
- malignant stromal cell tumor with predominant fibroblastic differentiation
- liposarcoma
- leiomyosarcoma
- angiosarcomas: primary, postrads, post radical mastectomy
5 features of sclerosing adenosis that distinguish it from tubular carcinoma
- lobulated clustered arrangement- retention of the lobular architecture vs. haphazard distribution of tubules
- compressed and distorted tubular lumens- vs. open angulated tubules
- fibrous stroma compressing tubules- vs. desmoplastic stroma
- tubules lined by 2 layers of cells (luminal epithelial and outer myoepithelial)
- tubules invested by basement membrane - PAS highlights
Features of microglandular adenosis
- haphazard proliferation of small round tubules
- tubules have open lumens
- tubules lined by single layer of epithelial cells- absent myoepithelial cell layer
- lumen contains colloid-like secretory material
- dense fibrous stroma
- multilayered basement membrane on EM
- epithelial cells are positive for S100 and cytokeratins
Classify benign prolfierative lesions of the breast
- Proliferative disease without atypia
2. Proliferative disease with atypia
Classify proliferative disease without atypia
- Moderate to florid hyperplasia
- Sclerosing adenosis
- Papilloma
- Complex sclerosing lesion
Relative risk of developing carcinoma in proliferative disease without atypia
1.5- 2 % (5-7% lifetime risk)
Classify proliferative disease with atypia
- atypical ductal hyperplasia
2. atypical lobular hyperplasia
Relative risk of developing carcinoma in proliferative disease with atypia
4 - 5 (13-17% lifetime risk)
What malignant lesions can mimic collagenous/mucinous spherulosis?
- Adenoid cystic carcinoma
2. Signet ring cell carcinoma
2 clinical features of nipple adenoma
- nippe discharge
2. swelling of the nipple +/- erosion
4 histologic features of nipple adenoma
- well circumscribed
- haphazardly arranged, proliferating tubular structures
- 2 cell types lining these tubules
- varying degrees of epithelial hyperplasia
- fibrous stroma
Risk factors of breast cancer
- female
- age- peak 75-80yo
- age at first live birth (nulliparous or >35 at first birth)
- age at menarche/menopause- younger than 11 and later menopause
- breast feeding DECREASES RISK
- carcinoma of the contralateral breast
- estrogen exposure
- FDR with breast cancer
- alcohol
- history of atypical hyperplasia in previous biopsies
- race/ ethnicity: nonhispanic whites > african americans > asian/pacific islanders > hispanics
- radiation exposure
GENETIC risk factors
BRCA1 BRCA2 CHEK2 Li Fraumeni Cowden syndrome- PTEN
QA/QC: a mammotome biopsy for calcifications does not show any calcifications in the sections. What are your next steps…
- check the accompanying specimen radiographs for calcifications
- use polarized light to detect calcium oxalate crystals
- cut deeper levels X3
- if calcifications are still not seen, take XRs of the block
- if the XRs show calcs, cut the block at the level of the calcifications
- the Xrays do not show calcifications, have the specimen radiographs and block XRs reviewed by radiology to confirm the presence or absence of calcifications in the respective images
- if the specimen radiograph has confirmed calcifications, but the slide sections and block Xrs do not, then report as calcifications not seen in slide sections or block XRs. Calcifications may have fallen out during block trimming
a breast lumpectomy specimen suspicious for malignancy is received in the lab. you cannot feel the mass. how do you handle the specimen?
- check if patient identification is correct (at least 2 identifiers should match)
- check if the correct side of the breast was operated on
- look up the pertinent imaging modality for the size and location of the mass
- if you still cannot identify the mass, have a specimen radiograph done to localize any abnormalities for sectioning
- if you still cannot identify the lesion, take random samples of the 4 quadrants and map them. focus sections on the area in the breast where the abnormality was initially suspected
- if any of the samples are positive histologically, go back and take more samples from that specific quadrant
- if none of the samples are positive, submit the entire specimen serially, or after mapping it
gross characteristics of phyllodes
- well circumscribed and firm
- cut surface: gray-white, solid with cystic areas, with fleshy leaflike processes that protrude into the cystic spaces
histo features of phyllodes
- stromal hypercellularity - pronounced in the periductal areas
- benign glandular/epithelial elements, projecting into cystic spaces as leaflike processes
list 5 histo features that help differentiate benign and malignant phyllodes
- increased mitotic activity- seen in an area away from the ductts, 5/10 hpf indicates borderline malignancy (in the absence of any worrisome features listen below, 10/10 hpf is significant)
- marked atypia of the stromal cells
- stromal overgrowth– absence of epithelial elements at least 1 low power (X4) field
- an infiltrating margin- versus a pushing margin
- tumor necrosis (and hemorrhage)
- malignant heterologous elements present even in the absence of other criteria
how to differentiate phyllodes tumor from a fibroadenoma
most helpful feature= cellular hyperplastic spindle cell stroma
leaf like processes– note that these alone in the absence of a hypercellular stroma DO NOT qualify the lesion as a phyllodes tumor
recommended treatment for phyllodes
local excision with a wide margin (at least 1 cm) of normal tissue (presence of tumor at the resection margin is a major determinant of local recurrence)
how would you word your diagnosis in a core needle biopsy/FNA cytology where you cannot differentiate a cellular fibroadenoma from a benign phyllodes tumor
Wording: biphasic tumor, with stromal and epithelial elements.
- as the stromal cellularity can be variable within a tumor and the margins cannot be assessed, the differential between a fibroadenoma and a benign phyllodes tumor would be deffered to the resection specimen (a malignant phyllodes tumor can be diagnosed on a core needle biopsy)
OR
Wording: fibroepithelial lesion with increased stromal cellularity. Recommend excision for further evaluation of the lesion.
how would you differentiate a malignant phyllodes tumor from a sarcomatoid (metaplastic) carcinoma?
IHC: stromal cells are negative for epithelial markers like AE1/AE3 and CAM 5.2, and positive for CD 34 and Bcl2 in a phyllodes
What other mesenchymal elements/metaplasias can be found in a phyllodes?
adipose, osseous, chondroid, smooth muscle, rhabdomyoblastic. Any of these can show a malignant component (presence of stromal elements other than fibromyxoid indicate a worse prognosis)
histologic features of a radial scar
- stellate configuration (flower head)
- central elastosis and fibrosis
- entrapped distorted ductules in the central scar
- dilated ductules at the periphery with various patterns of epithelial hyperplasia
- tubules lined by 2 layers of cells (luminal epithelial and outer myoepithelial)
clinical significance of radical scar
- benign mimic of cancer
- some authors believe most tubular carcinomas arise from radial scars, particularly if the radial scar is > 1 cm
- the RR of subsequent breast carcinoma is twice that of normal
- for most clinicians, the finding of a radical scar on a core biopsy is an indication for excision
Usual ductal hyperplasia features
Architectural:
- peripheral elongated clefts
- intratubular lumina, irregular in size, shape and location
- streaming (cells arranged in parallel bundles)
- tufts and mounds projecting into the lumen
- irregularly shaped/twisted bridges (long axis of nuclei are parallel to the long axis of the bridge)
Cellular:
- 2 cell types (epithelial and myoepithelial)
- nuclei oval, monochromatic, overlapping with indistinct nucleoli
- indistinct cell borders, nuclei seem to lie in a syncytial mass
- apocrine metaplasia, foamy macrophages common
- absence of necrosis
epithelial hyperplasia features
intratubular lumens: irregular, slit like, mainly peripheral
streaming: present
bridges: long axis of nuclei parallel to the bridge
cell types: polymorphous (epithelial and myoepithelial)
cell margin: indistinct
nucleus: overlapping monochromatic nuclei with indistinct nucleoli
apocrine metaplasia: can be focally present
necrosis: absent
low grade DCIS features
intratubular lumens: regular, rounded, rigid
streaming: absent
bridges: roman arches - long axis of nuclei perpendicular to the bridge
cell types: monotonous (only epithelial cells)
cell margin: well defined
nucleus: evenly spaced nuclei with or without obviously malignant features (atypia, hyperchromasia, prominent nucleoli)
apocrine metaplasia: absent
necrosis: present/absent
UDH vs. ADH immunostains
HMWCK: positive in UDH, negative in ADH
ER: patchy in UDH, diffuse in ADH
3 benign breast conditions whose histology is commonly confused with that of invasive breast carcinoma
- complex sclerosing lesion- radial scar
- sclerosing adenosis
- microglandular adenosis
list 6 histologic subtypes of DCIS
solid cribiform papillary micropapillary comedo clinging
what histologic features should be included in a report of DCIS
nuclear grade: I, II, III
necrosis: absent-I, punctate-II, comedo-III
pattern: cribiform, solid, micropapillary, papillary, comedo
size of largest focus (cm)
microinvasion: present/absent
distance to resection margins or involvement of resection margin(s) and extent of involvement
calcification: intraluminal, stromal, in benign breast tissue
low grade DCIS
well defined cell membranes
uniform nuclear and cell size and shape
rare mitosis
punched out appearance of lumen with polarization of cells around
aracdes and bridges uniform in thickness with rigid contours
necrosis unusual but possible
calcifications frequent
intermediate grade DCIS
cells do not fulfill criteria of either low grade or high grade
some intermediate grade lesions grow in patterns mimicking UDH (irregular architecture, streaming)
high grade DCIS
cells with large pleomorphic nuclei
coarse chromatin
prominent nucleoli
frequent mitosis
frequent central comedo necrosis (necrosis can be so extensive that only 1 layer of atypical cells is left at periphery of duct: clinging DCIS)
demosplasia and angiogenesis can be seen in stroma
reporting elements for DCIS in CAP
- procedure
- lymph node sampling
- specimen laterality
- tumor site (optional)
- size (extent) of DCIS
- histologic type
- architectural patterns- optional
- nuclear grade
- necrosis
- margins
- treatment effect– response to presurgical therapy
- lymph nodes– required only if lymph nodes are present in the specimen
- pathologic staging, pTNM
- additional pathologic findings- optional
- ancillary studies- optional
- microcalcifications- optional
- clinical history- optional
- comment- optional
goals of specimen sampling in DCIS
- clinical or radiologic lesion for which the surgery was performed must be examined microscopically
- if DCIS, LCIS or atypical hyperplasia is identified, all fibrous tissue should be examined
- all other gross lesions noted in the specimen must be sampled
how should resection margins be reported in DCIS?
if margins are samples with perpendicular sections, the pathologist should report the distance from the DCIS to the closest margin, when possible
The color of ink of any margin that is positive should be documented
If DCIS present at the margin, the extent of margin involvement should be reported:
- Focal (DCIS at margin in a <1mm area in 1 block)
- minimal/moderate (between focal and extensive)
- extensive (DCIS at the margin in an area >/- 15mm or in 5 or more low power fields and/or in 8 or more blocks)
clinical importance of finding ITC’s in lymph node in patients with DCIS
NO prognostic importance, since almost all tumor cells present in lymph nodes of patients with DCIS are isolated tumor cells or the cells may be artifactually displaced from a previous procedure
Lymph node met found in a patient with DCIS… now what….?
if a larger met is found, additional tissue sampling and review of slides is helpful to determine if an area of invasion is present
how should axillary nodes be examined…
- grossly involved nodes, which may have 1 or more sections submitted for microscopic evaluation
- all other nodes (should be thinly sectioned and entirely submitted for microscopic evaluation)
- a single H&E from each lymph node block is considered sufficient for routine evaluation
how to report axillary nodes
- total number of lymph nodes examined, including sentinel lymph nodes
- the number of nodes with mets– only nodes with micro and macromets are included for the total number of involved nodes for N classification. NOT ITC’s
- greatest dimension of largest metastatic focus
- presence of ENE, because it may be a/w higher frequency of axillary recurrence
list six types of invasive ductal carcinoma
tubular mucinous medullary invasive papillary apocrine metaplastic
prognostic factors that assess outcome at time of diagnosis….
distant mets axillary node mets size of primary tumor skin invasion/inflammatory carcinoma tumor grade LVI histo subtype
prognostic factors that assess likelihood to respond to a given therapy
ER/PR/ERBB2
subtypes of invasive breast carcinoma that indicate a better prognosis than IDC NOS
colloid/mucinous papillary tubular medullary cribiform adenoid cystic
sentinel node negative on FS and positive on permanent section…. what to do….
- document in final report that the sentinel LN is positive on permanent section, and comment on whether it was a sampling issue (not present in frozen) or an interpretive issue (ITCs, or difficult to identify subtype) as the reason for reporting the frozen section as negative.
Make sure the pathologist who has reported the frozen section is aware of the discrepancy
if a sentinel node is reported as positive, what is the expected treatment….
ALND for macromets (>2mm) historically
Currently– axillary radiation = acceptable alternative, with no role for further treatment.
Treatment varies by institution, surgeon and patient factors.
For micromets treatment varies with institution policy, surgeon decision and patient factors.
ITCs in sentinel node= NODE NEGATIVE= no need for ALND
what to report in a positive lymph node…
number of nodes / TOTAL
size of deposit
extracapsular extension
histologic subtype of met and whether it resembles the identified primary tumor
Luminal type
ER positive, HER2 negative
Luminal A
low proliferation
Luminal B
high proliferation
some luminal B
ERBB2 positive
Basal like
ER negative, ERBB2 negative
prognosis of luminal A
good
prognosis of luminal B
not as good
prognosis of ERBB2 positive
poor
prognosis of basal like
poor (except medullary carcinoma)
features of BRCA1 breast carcinomas
poorly differentiated syncytial growth pattern pushing margins prominent stromal lymphocytic response ER/PR negative ERBB2 negative high Ki67 high mitotic count CK 5/6 positive EGFR positive
what % of tumors with BRCA1 are medullary….
13%
ALH
acini: not distended or distorted
lumen: present
pagetoid spread: absent
lobular involvement: partial involvement of the acini within a TDLU
cell composition: variable cell types
LCIS
acini: distended and distorted
lumen: absent
pagetoid spread: along terminal ducts
lobular involvement:
- more than half of the acini within a TDLU
- more than 1 TDLU involved
- enlarged acini may show confluence, with little intervening stroma (macroacini)
cell composition: monotonous cells
histologic types/patterns of LCIS
classic pleomorphic necrotic signet ring cell type macroacinar (forms a mass)
implications of LCIS
some 20-30% patients develop invasive carcinoma (diagnosis on core needle biopsy), after long term follow up of 30 years
- this increased risk applies to both breasts (slightly larger on the side of the biopsy)
- the invasive carcinoma can be either ductal or lobular type
- the RR increases from 4.9 after 1 biopsy to 16.1 after a second biopsy shows LCIS
WHO implications of LCIS
if classical on core:
- close, long term follow up
- excision when pathologic-radiologic discordance
if pleomorphic LCIS of classical LCIS with comedo necrosis or bulky mass forming LCIS
- excision with negative margin or mastectomy
clinical mgmt of LCIS
- LCIS at margins is not reported nor an indication for reexcision (WHO). patient requires lifelong follow up with or without tamoxifen
- reexcision is recommended for LCIS of the following subtypes or with following features: pleomorphic, necrotic, pure signet-ring cell, solid duct involvement, presence of comedo necrosis, and macroacinar variant
- reexcision can be considered in cases of strong family history, patient apprehension and where prolonged follow up cannot be ensured
- reexcision is recommended if LCIS does not account for mammographic abnormality or if something else was found that is usually excised (ADH)
2 architectural features of classic ILC
- single file pattern
- targetoid pattern– neoplastic cells invade the stroma of residual ducts in concentric fashion
3 cytological features of classic ILC
- small uniform cells with bland nuclei
- lack of cohesiveness
- presence of intracellular mucin
what are the histological variants of ILC
- classic
- alveolar
- tubulolobular
- mixed
- solid
what are the cytologic variants of ILC
pleomorphic signet ring histiocytoid apocrine myoepithelial mixed
name 2 associated genetic abnormalities of ILC
LOH on 16q- site of E-cadherin and beta-catenin genes
LOH at 11q13
