High grade prostatic intraepithelial neoplasia (HGPIN)
Architecturally benign prostatic acini or ducts, lined by cytologically atypical cells.
Incidence of 4 – 5 % on biopsies (subjective finding based on nucleolar prominence).
Risk of cancer (pre MRI studies):
- 20 – 30 % risk of cancer on subsequent biopsy within 1 year – not different to negative/normal biopsy
- 80 % of cancers detected on repeat biopsy are Gleason 6
- > 2 cores with HGPIN may be higher risk
Considered pre-malignant.
HGPIN can occasionally mimic intraductal carcinoma; consider specialist pathology review if concerns.
Atypical small acinar proliferation (ASAP)
Focus of atypical glands on a biopsy specimen which is quantitatively or qualitatively insufficient for definitive diagnosis of prostate cancer.
Risk of cancer (pre MRI data)
- 40 – 60 % of men with ASAP on biopsy will have cancer on repeat biopsy
- 80 – 90 % of subsequent cancers are Gleason 6, and they are usually in the same area as the ASAP
The emergence of MRI and active surveillance for low risk prostate cancer has meant the significance of these findings is much less.
EAU guideline – “In a contemporary series of biopsies the likelihood of finding a csPCa after follow-up biopsy after a diagnosis of atypical small acinar proliferation and high-grade prostatic intraepithelial neoplasia (PIN) was only 6-8%, not significantly different from follow-up biopsies after a negative biopsy”
Non adenocarcinoma cancer
Rare, < 5 %
- Urothelial carcinoma
- Small cell carcinoma
- Sarcoma
Adenocarcinoma of the prostate
Location:
- 70 % in the peripheral zone
- 20 % transition zone
- Approximately 15 % can be considered “anterior tumours” either in the TZ or anterior horns of peripheral zone.
- May be multifocal in up to 85 % of cases
Spread:
- Extraprostatic extension preferentially occurs posteriorly and posterolaterally
- Seminal vesicle invasion is often penetration out of the gland at the base, into and through peri-vesicular soft tissue and into the SVs
- Direct spread via ejaculatory ducts is rare. Separate deposits in SV is very rare.
- Local extension to rectum is rare
- Extension into the trigone in advanced disease and can cause ureteric obstruction
- Most common sites of metastases are lymph nodes then bones
Volume:
- Size of tumour generally correlates with stage
- EPE uncommon in tumours < 0.5 cm3
- Nodal or SV invasion uncommon in tumours < 4.0 cm3
Diagnostic criteria for cancer
- Prostate adenocarcinoma does not have a basal cell layer (normal prostate glands do)
- Increased cellularity with crowded cells, often enlarged nuclei and cytoplasm
- Cancer stains positive for PSA/PAP. Basal cells stain positive for HMWK.
Gleason Grade
Based on the glandular pattern of the tumour at relatively low magnification. Cytologic features play no role in Gleason grading.
Graded from 1 – 5; with 5 being the most poorly or undifferentiated.
Gleason score is obtained from adding two numbers:
- On biopsy – the most common pattern + second most common pattern (or higher grade pattern if present even in small amount – i.e. only 5% pattern 4, should still be 3+4)
- On radical – the most common pattern + second most common pattern
Gleason score on biopsy has validated significance for:
- Pathological stage
- EPE
- Recurrence or progression after surgery or radiation
- Candidacy for surveillance or brachytherapy
- Prognosis after focal therapy
ISUP Grade Group
Has been validated in terms of prognostication and is in common use since 2014.
What is clinically significant prostate cancer?
EAU – ISUP grade 1 disease bears the hallmarks of cancer histologically, but does not behave in a clearly malignant fashion (0.28 % EPE, no SVI/LNI reported).
ISUP grade 1 disease can be described as clinically insignificant, but should be observed not ignored, as it may progress or be undersampled at biopsy, subsequently becoming significant.
ISUP grade 2 disease is commonly used as threshold for clinically significant, but there is no clear consensus.
Radical prostatectomy prognostic features
- Gleason score / ISUP grade group correlates well with biochemical recurrence risk
- Tertiary high grade increases risk of BCR
- LN + (7 % BCR-free at 15 years if lymph node positive)
- EPE – focal (few glands outside prostate) or nonfocal (more extensive)
- SVI – 65 % progression rate at 5 years
- Positive margins (although 50 % positive margins don’t progress)
- Intraprostatic incision
- Extent/length of positive margin
- Grade of tumour at margin
- Tumour volume has not been shown to provide prognostic information independently
Treatment effect – Gleason score should not be assigned for cancer with histologic treatment effect (i.e. post hormones or radiation).
If there is cancer present without treatment effect, this can be graded.
Other subtypes:
Intraductal carcinoma:
- Architecturally and cytologically atypical proliferation of epithelial cells within pre-existing ducts and acini
- EAU – “an extension of cancer cells into pre-existing prostatic ducts and acini, distending them, with preservation of basal cells”
- Often associated with higher grade disease and poorer prognosis
- May occasionally look like HGPIN on biopsies (similar cellular atypia, but HGPIN has architecturally benign glands)
- Occasionally seen on biopsies in the absence of usual type acinar adenocarcinoma – 90 % repeat biopsies will show adenocarcinoma, usually higher grade. Treatment justified.
Ductal carcinoma
- 4 – 0.8 % adenocarcinoma arises from the prostatic ducts
- Represents a distinct morphologically different subtype (cf. acinar) – previously called endometrioid
- May grow from primary prostatic ducts exophytically into urethra and cause haematuria or retention
- Poorer prognosis, higher rates of recurrence and poorer survival
- Should be graded as Gleason 4
- Often non PSA producing
- May be more avid on FDG PET cf. PSMA
Small cell
- Aggressive with average survival < 1 year
- Do not assign Gleason grade
- Treated with chemotherapy
Other
- Urothelial carcinoma
- Reportedly 1 – 4 % of non adenocarcinomas of the prostate
- Propensity to invade bladder neck and soft tissue – often T3/T4 at diagnosis
- 20 % of patients present with distant metastases
- More often it is CIS of the bladder spreading into prostatic ducts rather than primarily arising in prostatic urethra
- Sarcoma
- 1 – 0.2 %
- Rhabdomyosarcoma – almost exclusively in childhood
- Leiomyosarcoma – in adults
- STUMP
- Stromal tumour of uncertain malignant potential – usually non aggressive but cases exist of rapid re-growth after resection, or co-existence or transformation to sarcoma
- SCC
- Lymphoma / leukaemia (usually secondary cf. primary)