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PATHOLOGY of the PROSTATE - Coggle Diagram
PATHOLOGY of the PROSTATE
normal histology
glandular component
eepithelial cells,
organized in two layers
luminal cells
basal cells
cigarette-like nuclei
absence of basal layer: malignancy!
neuroendocrine cells
interspersed between basal and luminal cells
autocrine and paracrine functions (through peptidic hormones production, e.g. Bombesin)
NEN markers +++; androgen receptors ---
fibromuscular stroma
smooth muscle and fibroblasts
SM actin +++
both components express hormone receptors
functional zones
peripheral
central
transitional
(periurethral)
different diseases occur in different portions of the prostate
benign conditions are more frequent in the transitional zone
urethral obstruction
malignant consitions arise primarily in the peripheral zone
either asymptomatic or with pain due to bone metastases
BENIGN PROSTATIC HYPERPLASIA
macroscopy
bladder
damage of the bladder wall
predisposition to diverticuli
the detrusor is not homogeneous: in areas with lower density, diverticuli may occur
prostate
nodular arrangement,
very heterogeneous
it depends if the changes are predominant in the glandular or stromal component
NOT CLINICALLY RELEVANT
more commonly the condition is mixed
in the stroma, it looks like something of soft tissue origin
firm whitish without cribriform appearance
if glandular, more cribriform due to increased size of glandular structure
microscopy
the pathologist may receive two types of materials:
biopsy, coming from TURP
surgical samples, coming from adenomectomy
in BPH, the tissue appears with a heterogeneous arrangement, with increased glandular and stromal components
very frequent (paraaphysiological)
localization: transitional zone
both stromal and glandular components are involved
either small or large
symptoms do not depend on the size of the hyperplasia, but rather on the closeness to the urethra
URETHRAL STENOSIS
complications:
urinary retention
cystitis
stones
bilateral hydronephrosis
PROSTATE CANCER
clinical detection: peak at 65-75y
50% of pts >80y have prostate cancer
overall detection (including incidental findings and autopsies): 50% at >80 y
typical of peripheral zone (no obstruction)
first symptom: pain due to bone metastases
the tumor starts in the oeriphery, but it may grow either towards the central zone or outside of the prostate
diagnosis
needle core biopsy
transrectal mapping
usually at least 12 sites
(sometimes up to 20)
1 mm in thickness,
1-2 cm in length
histology
ARCHITECTURAL HOMOGENEITY
in benign conditions in which it appears heterogeneous and disorganized
it is enough to get low magnification for this first evaluation
in the presence of glands looking all the same, suspicion of malignancy is raised
BACK-TO-BACK or
FUSION of GLANDS
in benign conditions, there is glands overcrowding, but basal membrane is still present to separate each gland
in malignant forms, glands overcrowding is accompanied by loss of basal membrane and thus fusion
CYTOLOGICAL ATYPIA
with marginally-located nucleoli
in malignancies, nucleoli are present, they are large and marginated (close to where the basal membtane should be)
LOSS of BASAL EPITHELIAL LAYER
cancer is made up only
of luminal type cells
these cells may be organized in layers
similar to what happens in the breast with the concept of myoepithelial cells
PERINEURAL INVASION
with biopsy, it is difficult to get info on this
it is frequent to observe nerve fibers in core biopsies: it is possible to detect dense perineural invasion by neoplastic cells
malignant in 100% of the cases
IHC
markers for basal epithelial layer must be negative in the presence of a carcinoma
HMW-cytokeratins and/or p63 or p40
p63 is sensitive, but
not sufficiently specific
most important positive marker
AMACR
enzyme, unknown function
very sensitive and very specific
almost never needed
grading
(GLEASON'S)
ARCHITECTURAL ONLY
(no cytological features)
there is not a clear cutoff, thus
reproducibility is not so good
evaluate
tumor shape
peripheral borders
stromal invation
tumor cell arrangement
size of glands
score = sum of different patterns
grades
gleason 2
no epithelial basal component
some kinds of nucleoli may be present
no back-to-back or fusion of glands
associated with the best prognasis
gelason 3
most common form
well-organized architecture
some fusion and nuelci are more evident
no basal membrane and no basal epithelial component
gleason 4
cribriform appearance or large areas with gland fusions (solid areas with lumina in it)
clear cell appearance or more solid growth
no indivisual glands distinguishable
strange findings: glomerular appearance, papillary arrangement, Paneth-like appearance
gleason 5
complete loss of glandular differentiation
either presenting as a solid growth without glandular structure or even single cell invasion of the stroma
associated with the worst prognosis
gleason 1
almost never seen
prototypical situation of best differentiation possible
then, pathologists have to estimate the 2 most relevant patterns in order to obtain Gleason score
surgical specimen
GS is obtained by the sum of the 2 most predominant patterns
if there is the presence of a tertiary pattern with higher grade, it has still to be mentioned in the report, but it is not used for scoring
biopsy
GS is obtained by the sum of the most prevalent pattern and the worst pattern found
Gleason score will range from 2 (1+1) to 10 (5+5)
it is the best prognostic evaluation method
risk groups
it will help to decide if the patient will undergo an intra or extra fascial prostatectomy or even to decide for sampling of the lymph nodes
these groups come from patterns defined at biopsy, then, based on the group, patients will either undergo follow-ups or radical prostatectomy, and in the latter case the lesion will be graded again, but the surgical sample will be used this time
groups
group 1
GS ≤ 6
clinically not aggressive
only individual, discrete, well-formed glands
group 2
GS 7 (3+4)
predominantly well-formed glands with a lesser component of poorly formed/fused/cribriform glands
group 3
GS 7 (4+3)
predominantly poorly formed/fused/cribriform glands
lesser component of well-formed glands
group 4
GS 8 (3+5, 4+4, 5+3)
poorly formed/fused/cribriform glands or predominantly well-formed glands
lesser component lacking glands or predominantly lacking glands
lesser component of well-formed glands
grade 5
GS 9-10 (4+5, 5+4, 5+5)
no gland formation/necrosis
with or without poorly formed/fused/cribriform glands
N staging
the prognostic value of LN metastases is low
most cases do not undergo lymphadenectomy
prognostic value of lymph nodes metastases is low
there is either N0 (no metastasis) or N1 (presence of metastasis)
prognostic stratification
low risk
all of the following:
PSA < 10 ng/ml; Gleason score biopsy <= 6;
cT1/T2a; <2 biopsies positive at mapping
follow-up can be performed
"ACTIVE SURVEILLANCE"
periodic checking of PSA, imaging and repeated biopsies
if the subsequent biopsy results with a higher risk stratification, surgery will be performed
MRI is used to detect the presence of prostate cancer
classification in case of targeted biopsies of areas identified with MRI is the PI-RADS score
1 more item...
intermediate risk
any of the following:
PSA 10 - 20 ng/ml; Gleason score biopsy = 7;
cT2b T3a; >=3 biopsies positive at mapping
surgery is performed
high risk
any of the following:
PSA > 20 ng/ml; Gleason score biopsy 8-10; cT3b
T staging
low power prognostic indicator
clinical and pathological staging rules are not the same
pathological staging
it starts directly from T2 (organ-confined, irrelevant of size, multifocality, bilaterality), T3 if it grows outside the prostate (further divided in “a” if it invades soft tissue or “b” if it invades the seminal vesicles), while T4 is usually not seen as it is not resectable
clinical staging
there are additional stages in terms of T1 (clinically inapparent tumor) based on what is detected by biopsy
T1a if the cancer is < 5%
T1b if it is > 5%
T1c if it is identified by needle biopsy
not something relevant for the prognosis
BENIGN LESIONS
MIMICKING CARCINOMA
they generally fall under the term of ATROPHY
simple atrophy
post-atrophic hyperplasia
partial atrophy
simple atrophy with cyst formation
basal cells are dominant in atrophy
(important for the differential diagnosis)
glands are smaller and architecture is all the same
usually related to inflammation
clue for the differentiation is IHC
the basal component will be predominant,
the luminal component will be reduced
other entities: adenomatous hyperplasia and sclerosing adenosis
PRE-NEOPLASTIC LESIONS or
LESIONS INDICATING A RISK FOR CANCER
PIN
grades
high grade
clinically relevant as cells are the same as cancer but are not invasive
basal component is still there!
IHC: HMWCK and AMACR +++
histological variants
micropapillary (pattern 4)
cribriform (pattern 4)
tufting (smaller glands --> pattern 3)
flat
low grade
relevance for the pathologist
high positive predictive value of HGPIN for adenocarcinoma
DD with adenocarcinoma
problems for Gleason grading
relevance for the clinician
in HG PIN risk for cancer (synchronous or metachronous) of about 30% within 1y
ASAP
abnormal/atypical glands with cytological and architectural features suggestive, but inconclusive, for cancer
few nucleoli or fusion, but both unsure
the follow up is another biopsy
molecular background of prostate cancer
easily defined as something that is ETS-positive (family of TF activated via different mechanisms) or ETS-negative (alternative pathway) prostate cancer
in ETS+ cancers, the dominant alteration is the fusion TMPRSS2-Erg (50% of the cases)
in 20% of cases, BRCA mutations
screening for BRCA syndrome (hereditary cancer syndrome)
possibility to use PARP inhibitor drugs for treatment in the presence of progressive disease
prostate cancer patients usually have a long clinical history
most have even metastatic cancer managed with hormonal treatment or chemotherapy
a shift may happen due to the hormonal treatment (androgen deprivation) and they will start to progress very rapidly
most frequent phenomenon:
TRANSFORMATION INTO NEUROENDOCRINE PROSTATE CANCER
these cells do not express androgen receptors anymore, so they are resistant to hormonal therapy
shift from castration-sensitive to castration-resistant cancer
only PARP inhibitors can be used
NEN differentiation pathologic classification
pure cases --> from normal NE cells of the prostate, very rare
carcinoids --> very well-differentiated
high-grade aggressive cases --> small cell carcinoma and large cell NE carcinoma
adenocarcinomas with NE differentiation --> the most frequent and most relevant for pathologists