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BREAST PATHOLOGY 2 (OPACITIES) - Coggle Diagram
BREAST PATHOLOGY 2
(OPACITIES)
FIBROADENOMA
very common also in young women, completely benign (B2 or C2) and diagnosed preoperatively
they do not need surgery
(unless it is growing too much)
clinically, it presents as a mobile lump,
slipping between fingers, hard and painless
cysts are lumps and elastic,
but they are not slippery or hard
at US, they show circumscribed margins, a roundish or oval appearance and they are hypoechoic
calcifications may be present or not
if they are present, they usually refer to an old fibroadenoma, typical of older women
coarse popcorn calcification appearance
due to regression of fibroadenoma
cause: HYPERESTROGENISM
the fibroadenoma acts into the stroma on the cells that are present between the acini in the TDLU (mantle stroma), which have estrogen receptors
estrogen receptors can be alpha or beta
generally, tumors are rich in ERalpha; however, the cells of the mantle stroma of the lobules are rich in ERbeta
the growing part is the mantle/intralobular stroma
usually associated with some collagen deposition
--> hard consistency
PHYLLOIDES TUMOR
rarer than fibroadenoma, typical of older
women, more frequent after menopause
the main difference from fibroadenoma is that at radiology PT does not appear completely hypoechoic, it has something inside of it; moreover, at mammography, PT borders are not so roundish
most important clinical sign:
RAPID GROWTH
based on the diagnosis coming from core
biopsy, surgery will be more or less aggressive
(but it is needed mandatorily)
margins of resection must be clear
(even benign cells can transform into
malignant ones)
criteria for PT classification
proliferation of the stroma, which becomes very rich in cells
it is important to evaluate pleomorphism of the nuclei, then mitotic and necrotic indices
subtypes
benign (B3)
malignant (B5)
borderline (B3, B4)
BENIGN: the stroma proliferates crushing the epithelium cavities, which are elongated and contain histiocytes; no mitosis and atypia
BORDERLINE: aome atypia and
mitosis are observed in the stroma
MALIGNANT: rapid growing lump,
necrosis, numerous mitoses, atypia
since it is a sarcoma, metastases can move through blood
analysis of the sentinel lymph node and its dissection are not recommended
remember that analysis of the lymph node would instead be recommended in carcinomas, which generally metastasize through the lymphatic system
it is important to perdoem a PET scan before surgery
RADIAL SCAR
usually classsified R3, R4
not malignant, but at risk of transformation
if these lesions are found, a core biopsy has to be performed to be sure of the nature of the lesion
radiological distortion
the lesion is not roundish and there is something that is stretching the profile of the gland
stellate lesion
histologically, it appears like a branching pattern with a central core
the central core is elastic and it has some
collagen deposition (fibroelastic core);
small tubules are also observed (made of epithelial and myoepithelial cells)
around the core, hyperplasia can be found together within situ carcinoma (ductal or lobular)
they are not invasive cancers, but around them there might be some lesions that may evolve into an invasive carcinoma (RISK OF PROGRESSION)
classified as either B3 or C3
(indicative for surgery)
DD
tubular carcinoma, an invasive cancer that presents a similar aspect to radial scars (radiologically and histologically)
myoepithelial cells present in radial scars are absent in the tubular carcinoma
INVASIVE CARCINOMA
cancer that grows by invading the stroma and likely to metastasize by invasion of blood and lymphatic vessels
not confined within the cortex of the gland: it goes through the cortex, the basal membrane and the stroma
typical macroscopic feature: peau d'orange sign
CT is started before surgery, even without biopsy
it generally arises from an in situ carcinoma that, by growing, induces the breakage of the basal membrane and the neoplastic cells may move from inside the gland into the stroma
if vessels are present, cells may enter in them
and five rise to metastases around the body
standard parameters
morphological
tumor extent
tumor size
lymph node status
histotype
grade
vascular invasion
TILs
TUMOR EXTENT: determining the involvement of the breast by the tumor
it can be unifocal (one single nodule), multiple (more nodules) or diffuse (breast is completely involved by the tumor)
TNM: "T" refers to tumor size ("M" is added if there are more lesions and you measure the largest one)
also consider the presence of microinvasion: if the lesion is microinvasive, the prognosis is very good
immunophenotypic
steroid receptor status
HER2
Ki67
steroid receptor status
in the nucleus of cancer cells there are many steroid receptors (ER, PR, AR), but the most important one from a therapeutic point of view is the estrogen receptor (heterogeneous, found on luminal cells and determining cellular proliferation); also progesterone receptors must be evaluated, as they are important to regulate cellular proliferation as well
prognostic marker: ER/PR presence
is indicative for a better prognosis
prefictive factor: high ER/PR expression is associated with a better response to hormonal therapy
tamoxifen
antagonist of ER, blocking proliferation in breast (but stimulating proliferation in endometrium)
aromatase inhibitors
involved in estrogen synthesis blockage by inhibiting the aromatase enzyme
ER and PR expression also plays a role in recurrence rate determination
if a tumor is ER+/PR- the recurrence is higher than in a ER+/PR+ tumor
the cutoff for PR expression is 20%
HER2
member of the epidermal growth factor receptors, present in all cells
we use FISH to detect its presence on ch17
in the case of true amplification, the number of centromeres does not increase, while the number of genes does; if the ratio between the number of chromosomes and genes is >2, the gene is amplified and the cancer may be considered for specific treatment with HER2 drugs
scores:
3+: very brown staining, found in >10% of cancer cells
2+: staining is around 10%, but cells are not completely stained or the staining is heterogeneous
--> in this case, FISH is recommended
1+: negative, just a few stainings are observed
tts activation induces cell proliferation, migration, differentiation and apoptosis
activation of HER2 happens upon dimerization
even tumors with very low HER2 expression may respond to double treatment including anti-HER2, e.g. trastuzumab + CT
Ki67 proliferation index
Ki67 is a moAb staining all the cells that are in the mitotic phase and it is both prognostic and predictive
stained nuclei have to be counted to calculate the percentage of positivity: the cutoff is 20%
if there is high proliferation, the tumor is more aggressive, but it also responds better to treatment
lymph node metastasis
tumor emboli may enter into the lymphatic system and arrive at the first lymph node of the axillary lesion (SENTINEL LN)
this LN is removed by surgeons in order to examine it to look for the presence of metastases
the pathologist has to measure the volume of metastases inside the sentinel LN, on the basis of which categories can be defined
completely free LN
some new isolated cells
micrometastases
large metastases
if the metastatic content is greater than 2 mm then all the lymph nodes have to be taken away
molecular classification
ER+
expression of ERs
subtypes
Luminal A
good prognosis
expression of some specific genes
HER2-
low proliferation index
treated with endocrine therapy
Luminal B
more aggressive
Luminal B HER2+ (ER+, PR+, HER2+): treated with endocrine therapy, CT, anti-HER2
Luminal B HER2- (ER+, PR+, HER2-): high proliferation index, treated with endocrine therapy, CT
ER-
no ERs expression
subtypes
ERBB2+
only HER2+ (ER-, PR-)
treated with CT and anti-HER2
triple negative (basal-like)
ER-, PR-, HER2-
treated with CT
metastases mainly tend to spread via blood to lungs, CNS, liver and bones
the tumor size does not impact on prognosis and, if the patient is alive after 5 years, she can be considered cured
after such a diagnosis, the pt must be evaluated to check for the eventual presence of PIK3CA gene mutation
association with ovarian cancer (women), prostate and pancreatic cancer (men)
if the pt is positive for this mutation, Alpelisib can be used for the treatment (good response); this mutation is not responsive to endocrine therapy
also evaluate PD-L1 expression
in particular in women who had breast cancer, were treated with CT and, at the end of the treatment, still showed metastases development
in the case of positivity, Atezolizumab is a treatment option
histotype
it correlates with the aspect of the mammogram
not special types (NTS): 83%
lobular
tubular: appearing like a distortion (stellate lesion)
medullary: roundish, low frequency (2%)
mucinous: roundish, low frequency (2%)
mixed
NTS
it correlates with spiculated lesions, with histological variation from a lot of ducts to a solid growth with no lumen
the pathologist must look for the presence of tubular structures with a lumen, all devoid of myoepithelial cells
tubular carcinoma
characterized by a distorted stellate lesion (DD: radial scar), which in this case does not have myoepithelial cells around the tubules
also look for markers for myoepithelial cells, e.g. p53 which stains the nuclei of the basal cells (to be found in the case of radial scars)
it has a very good prognosis
lobular carcinoma
it may arise from a lobular in situ carcinoma, which is generally not seen on mammogram; it may be bilateral, multifocal and it needs surgery (not mastectomy)
only part of the gland where the biopsy is done is removed, then the patient might receive hormonal therapy, blocking the growth of other lobular carcinoma foci
the diagnosis is very complex
it grows as single cells not producing collagen deposits, but rather growing in the stroma of the breast, following a natural way of progression
cells may frequently have vacuoles inside the cytoplasm and they have a low pleomorphism
they may invade the whole breast
(SPIDER-WEB INVASION PATTERN)
look for CDH1 mutation (+++) and e-cadherin mutation (---)
e-cadherin absence is an indication for the likelihood of cellular invasion of the stroma
moreover, e-cadherin mutation is indicative for the risk of both breast and gastric cancers
medullary-like carcinoma
chronic inflammation in the stroma, where a lot of lymphocytes are found; association with BRCA1
roundish shape at microscope, cluster of atypical cells, with a lot of mitosis within a stroma rich in lymphocytes
the presence of lymphocytes ameliorates the prognosis
immunotherapy can be used as a treatment if patients show metastases
no estrogen-progesterone receptor expression, HER2 negativity
TRIPLE NEGATIVE CANCER
not all triple neg cancers have a good prognosis, but th presence of a surrounding inflammation indicates a better condition
grading
(Elston and Ellis)
important in any histotype, but most of all in NST
parameters
presence of tubules with a lumen
if a lot of structures with a lumen are present, it will be more similar to a normal mammary gland
the greater the presence of tubules, the lower the score assigned to the tumor
a lot of tubules (>70%)
some tubules (10-70%
just a few tubules (<10%)
pleomorphism (look at nuclei)
low pleomorphism
in between
high pleomorphism
number of mitoses
few mitoses
in between
numerous mitoses
the sum of these data gives a final score
G1: 3-5
G2: 6-7
G3: 8-9
vascular invasion
remember that both blood and lymphatic vessels invasion must be assessed, but in this case lymphatic vessels are more likely to be involved
tumor infiltrating lymphocytes (TILs)
they are conditions in which there is the presence of lymphocytes into the stroma
TILs presence predicts the response to noadjuvant therapy in all molecular subtypes: it is considered a marker of CT response
TIL correlates with the prognosis of the patient: the higher the TIL the better the overall survival