Prostate Flashcards
Prostatitis
Clinical Classification:
* Acute bacterial prostatitis
* Chronic bacterial prostatitis
* Chronic abacterial prostatitis
* Infectious granulomatous prostatitis
* Non-specific (idiopathic) granulomatous prostatitis
Abacterial:
* Heterogeneous condition with many possible causes; however, aberrant cytokine function seems to be a final common pathway
* Newly recognized cause is IgG4 related prostatitis, which presents with obstruction and resolves with steroids and rituximab
Bacterial:
* Escherichia coli (accounts for > 70% of cases), Klebsiella, Pseudomonas, Proteus, Enterobacter, Enterococcus species, Staphylococcus aureus
Infectious granulomatous prostatitis:
* Hx of infection by…
* Bacteria –> TB, syphilis, brucella
* Fungi –> Cryptococcus, blastomycosis, coccidioidomycosis)
* Viruses –> Herpes
* Parasites –> Schistosomiasis, echinococcosis
Non-specific (idiopathic) granulomatous prostatitis:
* After bacillus Calmette-Guerin (BCG) therapy
Benign prostatic hyperplasia
- Benign nodular lesion
- Proliferation of stromal and glandular components
- Predominantly located in the transition zone of the prostate
- Increased bladder outlet resistance
Lower urinary tract symptoms (LUTS), including: - Obstructive symptoms (hesitancy, intermittent stream and straining)
- Urinary bladder irritation symptoms (frequency, urgency and urge incontinence)
- Urinary retention (whether acute or chronic)
- Central role of sex steroids (5 α-dihydrotestosterone, estrogens) and growth factors (fibroblast growth factor, transforming growth factor beta)
- PSA may be elevated
- Not a precursor or risk factor for prostate cancer
Micro:
* Epithelial hyperplasia is characterized by nodular lesions composed of variably sized glandular structures lined by basal and secretory cells
* Glandular dilatation with papillary infoldings and cysts, often containing corpora amylacea, sometimes calcifications
* Epithelial lining ranging from flat to columnar, with pink pale cytoplasm, regular, centrally located nuclei and inconspicuous nucleoli
* Stromal nodules are composed of bland spindle cells with round to ovoid nuclei with open chromatin
* Thick walled small capillary vessels can be seen on cross sections
* Ischemic changes / infarcts can be seen within the nodules
Morphologic variants include:
* Clear cell cribriform hyperplasia
* Basal cell hyperplasia
* Adenosis / atypical adenomatous hyperplasia
* Leiomyomatous nodules
* Fibroadenomatous
* Phyllodes type hyperplasia
IHC:
Basal cells:
* High molecular weight cytokeratin
* p63
Secretory (luminal) cells:
* PSA
* PSAP
* NKX3.1
Stromal cells:
* CD34
* smooth muscle actin (SMA)
* Desmin variable
Prostatic Intraepithelial Neoplasia
- High-grade prostatic intraepithelial neoplasia (PIN) is considered to be a premalignant condition
- HGPIN –> associated with adenocarcinoma on rebiopsy in 25% of patients
- Presence of PIN madates rebiopsy
- Clinical significance of LGPIN is unclear
Micro:
LGPIN:
* Morphologic features not rigourously defined –> should not be diagnosed
* At scanning magnification, darker and more complex than normal glands
* Cellular crowding, pseudostratification with irregular spacing
Intact basal layer
HGPIN:
* Diagnostic feature: prominent nucleoli visible at 200x or lower magnification
* Medium to large ducts and acini with enlarged hyperchromatic nuclei and amphophilic cytoplasm
Common architectural patterns:
* Flat: 1 - 2 layers of simple epithelium
* Tufted: stratified epithelium with small luminal protrusions
* Micropapillary: filliform structures lacking true fibrovascular core
* Cribriform: epithelial proliferation with punched out spaces
Molecular:
* Deletions of 8p most common allelic loss
* gains of chromosomes 7, 8, 10 and 12
* TMPRSS - ERG fusion
IHC:
Basal cells: high molecular weight cytokeratin
p63; may be discontinuous
Acinar cells: P504S / AMACR
PTEN: normal retained pattern
Serum PSA
- Exist in blood bound mainly to alpha-chymotrypsin
- Small portion as free PSA
- Free/Total PSA is useful for distinguishing carcinoma from benign causes of increased PSA
- Strong correlation between the volume of prostate and PSA
- Elevated in CAP, BPH, Prostatitis, Protatic infarct and Prostatic injury
- Organ specific, not disease specific
- PSA may be normal –> anaplastic cancer, NETs, sarcomas, TCCs, Lymphoma
Values:
0 to 4ng/ml
Velocity <0.75ng/ml/year
Density <0.15ng/ml
Gleason score
Patterns
1 –> small, uniform glands
2 –> More stroma between glands
3 –> Distinctly infiltrative margins
4 –> Irregular masses of neoplastic glands
5 –> Only occasional gland formation
Grade Groups
* 2014, the ISUP and World Health Organization adopted a simplified patient centric grading system composed of 5 prognostic grade groups
Grade groups are as follows:
1. Gleason score 3+3=6
2. Gleason score 3+4=7
3. Gleason score 4+3=7
4. Gleason score 8 (4+4=8, 3+5=8, 5+3=8)
5. Gleason score ≥ 9 (4+5=9, 5+4=9, 5+5=10)
- Note that Gleason grades 1 and 2 are no longer recommended for use, since those patterns of cancer have an outcome no different from grade 3; moreover, pure grade 3 cancer almost never metastasizes
In radical prostatectomy:
* Gleason score should be based on the primary and secondary patterns; if a minor pattern constitutes < 5%, the pattern should be mentioned as a minor (tertiary) pattern
- In needle biopsy:
Most prevalent pattern is graded as primary and any amount of a worst pattern is graded as secondary
Prostate Adenocarcinoma
- Most common malignancy of the prostate gland
- Originates from prostatic secretory epithelium
- Often diagnosed by nontargeted needle biopsies investigating raised serum prostate specific antigen (PSA)
- Absence of basal cell layer is a pathognomonic histological feature
- TURP <12g —> submitted in its entirety
- TURP >12g –> initial 12g submitted (6 to 8 cassettes), 1 cassette for every additional 5g
Molecular:
* Most common somatic genomic rearrangement is fusion of the androgen regulated gene TMPRSS2 with a member of the ETS transcription family
* Somatic mutations in genes such as ERG, ETV1/4, FLI1, SPOP, FOXA1, IDH1, PTEN, TP53, MYC, CDH1
* BRCA2 –> significantly increases the risk of prostate cancer
IHC:
PIN4 cocktail –> AMACR, p63, CK5/14
PSA
PSAP
NKX3.1 –> highly specific and sensitive
Prostein
Basal cells are absent
Stains for basal cells –> ck5/6, p63, p40
