Updates on who

1. UPDATES ON 5TH EDITION
WHO 2022 CLASSIFICATION
OF PROSTATE CANCER
22/09/2022
Presenter: - Dr. Jagriti Singh Fartiyal
Moderator: - Dr. Aasma Nalwa

2. CONTENTS
• Anatomy and normal histology of prostate
• Patterns of Gleason grades
• Difference between Gleason grade, Gleason score and Gleason grade
group
• Definition of commonly used terms like PIN, IDC-P, acinar and ductal
adenocarcinoma
• Old WHO classification of prostate cancer
• New updates 2022, 5th edition on prostate cancer
• Summary

4. ZONES OF PROSTATE

6. GLEASON GRADE/ PATTERN
• Based solely on the architectural pattern
• Three grades: - 3, 4 and 5
• Gleason pattern 3: - Variably sized individual glands that are well
formed and discrete units
• Gleason pattern 4: - Cribriform pattern, glomeruloid glands (a variant
of cribriform), poorly formed/fused glands
• Gleason pattern 5: - Sheets of tumor, individual cells, cords, linear
arrays, solid nests, comedonecrosis (irrespective of architecture)

7. GLEASON GRADE PATTERN
ISUP 2005 and 2014 modifications
Gleason pattern Key morphological features Comments
1 and 2 Discrete regular glands; circumscribed, rounded
nodules
Not used now
3 Discrete glands with marked variation in size and
shape; infiltrating b/w non- neoplastic acini
No longer includes cribriform or
glomeruloid glands
4 Fused microacinar glands, poorly formed glands
without well defined lumina, cribriform glands or
glomeruloid glands
5 Minimal glandular differentiation, C/O solid sheets,
cords or single cells OR
Solid, cribriform or papillary structures with central
necrosis (comedonecrosis)
Most (but not all) comedocarcinomas
are now recognized as IDC-P

10. Glomeruloid glands (type of Gleason pattern 4)

12. GLEASON SCORE
• Recommended for use in all prostatic specimens containing
adenocarcinoma (except those showing treatment effect)
• Specimens: - Core biopsies, TURPT chips, enucleation and resection
specimen
• Primary pattern: - Most predominant Gleason grade in terms of
surface area involvement
• Secondary pattern: - Second most predominant Gleason grade in
terms of surface area involvement

13. • “Gleason score is the sum of the primary Gleason grade and the
secondary Gleason grade”
• Scoring depends on the type of prostate specimen it is applied to

14. Gleason scoring in TURP chips/ core biopsies
• A minor secondary component (<5% of tumor), if is of higher grade,
the latter should be reported
• If a minor secondary pattern is of lower grade, it not to be reported
• If more than 2 patterns are present, and the worst grade is neither
predominant nor secondary, the predominant and the highest grade
should be chosen

15. • Case with 95% pattern 3 and < 5% pattern 4
 3+4 = 7
• Case with 95% pattern 4 and < 5% pattern 3
 4+4 = 8
• Case with 75% pattern 3, 20-25% pattern 4 and <5% pattern 5
 3+5 = 8

16. Gleason scoring in resection specimen
• A Gleason pattern 5 present as a minor tertiary (<5%) pattern should
be recognized in the report
• If Gleason pattern 5 is 5% or more and constitutes the 3rd most
common pattern, it should be included as secondary pattern

17. • Primary Gleason pattern 4 is 80%, 17% Gleason pattern 3 and 3%
Gleason pattern 5
 3+4 = 7 with minor tertiary Gleason pattern 5
• Primary Gleason pattern 4 is 70%, 20% Gleason pattern 3 and 10%
Gleason pattern 5
 4+5 = 9

18. GLEASON GRADE GROUP

19. TERMINOLOGIES
• Acinar adenocarcinoma
Consisting of neoplastic prostatic epithelial cells with secretory
differentiation
• Ductal adenocarcinoma
 Consisting of large glands lined by tall pseudostratified columnar
cell
M/C has cribriforming or papillary architecture
Graded as grade 4, unless comedonecrosis is present

20. • High- grade prostatic intraepithelial neoplasia (HGPIN)
 Neoplastic proliferation of secretory cells within pre-existing ducts
and acini
 With cytological changes resembling those seen in cancer
 Nuclear enlargement and prominent nucleoli
 Significance: - It’s recognition is associated with subsequent
detection of prostatic carcinoma (precancerous lesion)
 Follow up biopsy is recommended in multifocal HGPIN (>1 core)
within 1 year
 HGPIN alone should not lead to definitive therapy

23. • Intraductal carcinoma (IDC- P)
 Intraductal/ intra- acinar neoplastic epithelial proliferation
 Some features of HGPIN, but much more greater architectural and/or
cytological atypia
 Typically associated with high grade- high stage prostate cancer
 Represents an advanced stage of tumour progression with intraductal
spread

27. WHO CLASSIFICATION OF THE TUMORS OF
THE PROSTATE, 5TH EDITION
• Epithelial tumors of the prostate
Glandular neoplasms of the prostate
Prostatic cystadenoma
High- grade prostatic intraepithelial neoplasia
Intraductal carcinoma of the prostate
Prostatic acinar adenocarcinoma
Prostatic ductal adenocarcinoma
Treatment- related neuroendocrine prostatic carcinoma

28. Squamous neoplasms of the prostate
Adenosquamous carcinoma of the prostate
Squamous cell carcinoma of the prostate
Adenoid cystic (basal cell) carcinoma of the prostate
• Mesenchymal tumours unique to the prostate
Stromal tumours of the prostate
Prostatic stromal tumour of uncertain malignant potential
Prostatic stromal sarcoma

29. 5 TH EDITION CHANGES

30. INTRODUCTION
• Earlier in 3rd edition: Acceptance of Gleason grading
• 4th edition (2016): Concepts of grade grouping and acceptance of IDC-
P as a new entity
• Replacement of term “variants” with “subtypes” for distinct
clinicopathological entities
• Still confusion, whether or not to include IDC-P when assessing the
Gleason score

31. • A subtype is defined as “variant of a type with one or two parameters
(e.g. clinical, location, histopathological, and/or molecular) makes it a
distinct entity from other subtypes but still related to parent type”
• Term “variants” is reserved for genomic rather than morphological
alterations
• Tumor with unusual morphologies like- atrophic or pseudo-
hyperplastic acinar carcinoma, been included as alternative histological
patterns

32. Difference between ISUP and GUPS 2019 guidelines regarding IDC-P
ISUP 2019 GUPS 2019 SUPPORTING EVIDENCE
Yes, incorporate into Gleason
score
No, do not incorporate into
Gleason score
Overall evidence for or against
inclusion is inconclusive
Often cannot reliably identify
IDC-P without using IHC for basal
cells
Cases with IDC-P would alter
Gleason score represent a small
subset of cohorts, effect on
inclusion on outcome is not
apparent
Avoids need of IHC whenever
cribriform glands or
comedocarcinoma are present
IHC to be performed only, if
results would change the
Gleason score
Limited data available on how it
might affect percentage of
Gleason pattern 4 in scoring
Precursor like IDC-P a/w with
invasive carcinoma is rare,
incorporation into Gleason score
is not a major issue
Lead to incorporation of
precursor like IDC-P into score, ?
Including an in-situ component
in the grade
Yes, if higher grade component
represents </= 5% of tumor
volume is not included in
scoring, but reported as minor
component
No, by GUPS definition, minor
tertiary pattern does not exist in
these grading scenarios
Mixed evidence, data not
conclusive, compared relatively
small case numbers

33. • Whether to include IDC-P in grading system???
5th edition has not endorsed either position. Instead , recommended
that pathologist should specify which variant of Gleason grading
recommendations is being used in their routine case reporting

35. CLASSIFICATION
• DUCTAL ADENOCARCINOMA AND PROSTATIC INTRAEPITHELIAL
NEOPLASIA (PIN)- LIKE CARCINOMA
Ductal adenocarcinoma has been retained as a separate type of
prostatic adenocarcinoma
oTerm “ductal adenocarcinoma” reserved for radical prostatectomy
specimen with > 50% ductal morphology
oIn needle biopsy, term “adenocarcinoma with ductal features” for
pure ductal and mixed ductal and acinar features

36. Why to mention ductal and acinar adenocarcinoma separately??
Ductal carcinoma has poorer prognosis as compared to acinar
adenocarcinoma

37. PIN- like carcinoma
• Looks like high- grade PIN, but completely lacks basal cell layer
• PIN- like carcinoma reclassified as a subtype of acinar rather than
ductal adenocarcinoma
• PIN- like carcinoma lacks the papillary or cribriform architecture
typical of ductal adenocarcinoma, but is instead characterized by
large discrete glands lined by flat or tufted epithelium
• PIN- like carcinoma also has a more favorable prognosis, similar to
low- grade acinar adenocarcinoma and is assigned GS of 6

38. • TREATMENT- RELATED NEUROENDOCRINE PROSTATIC CARCINOMA
Defined as “tumors demonstrating complete or partial neuroendocrine
differentiation with adenocarcinoma following ADT”
oApplied to both primary and metastatic tumours
oUse of IHC for synaptophysin and chromogranin not recommended
since, almost all prostatic adenocarcinomas show neuroendocrine
differentiation
o Poorer prognosis

40. • ADENOID CYSTIC (BASAL CELL) CARCINOMA OF THE PROSTATE
o Defined from prostatic basal cells
oName is revised to reflect the close morphological and molecular
similarities between these tumors and their salivary gland counterpart
oHistologically typically exhibits
 An adenoid cystic pattern with hyaline globules (inspissated secretions)
A basal pattern comprising small solid nests of basal cells
Or a mixture of both

41. o Harbors MYB::NFIB gene fusions
Seen in majority of adenoid cystic carcinoma of salivary gland
Exclusion of metastasis from salivary gland or other organs is an
essential diagnostic criterion

42. CRIBRIFORMING GROWTH PATTERNS
• Sheet of contiguous malignant epithelial cells with multiple glandular
lumina that are easily visible at low power (10x).
• No intervening stroma or mucin separating individual/ fused
glandular structure
• In radical prostatectomy specimen it is significantly correlated with
poor prognosis

43. • Large cribriform pattern: having >12 luminal spaces or twice the
diameter of adjacent benign glands as the cut point or > 0.25mm
cribriform gland size
• Associated with worse prognosis

44. IDC-P, GRADING AND RELATED ISSUES
• 5th edition has retained and expanded the separate section on IDC-P
• “IDC-P is a neoplastic epithelial proliferation involving pre-existing,
generally expanded, duct -acinar structures and characterized by
architectural and cytological atypia beyond what is accepted for
HGPIN”
• Old criterion: nuclear size should be >6 x normal or larger when the
architectural pattern was loose cribriform or micropapillary, have
been removed in the 5th edition

46. • Some intraductal neoplastic proliferation fall short of
architectural/cytological atypia for IDC-P, but have more atypia than
usual HGPIN
• Designated “atypical intraductal proliferation (AIP)” in the 5th edition
• Especially, loose cribriforming proliferation lacking severe nuclear atypia
or necrosis fit into this category
• AIP is a potential marker of unsampled high- grade prostate carcinoma

48. SUMMARY
• PIN- like carcinoma is not synonymous with a pattern of ductal
carcinoma, but better classified as a subtype of acinar
adenocarcinoma
• Treatment related neuroendocrine prostate carcinoma (tight
correlation with ADT)
• Terminology change: - Basal cell carcinoma to “adenoid cystic (basal
cell) cell carcinoma”; underlying MYB::NFIB gene fusion
• Prognostic significance of cribriform growth pattern

49. • AIP (atypical intraductal proliferation) for lesion falling short of IDC-P
but with more atypia than seen in HGPIN
“lesions previously regarded as cribriform pattern of HGPIN are now
included in AIP category”
• Metastatic, haematolymphoid, mesenchymal, neuroendocrine, and
genetic syndrome- related tumors are each consolidated across all
genitourinary sites.

50. THANK YOU