Diagnosis of prostate cancer on needle biopsy: Current practices

1
Diagnosis of prostate cancer on needle biopsy
Current practices

• Medical College of Georgia
• 12/07/2006

Jeremy S. Miller, MD
2
Current practice of diagnosis and reporting of
prostate cancer on needle biopsy among
genitourinary pathologists
Lars Egevad MD, William C. Allsbrook Jr. MD, and
Jonathan I. Epstein MD Karolinska Hospital,
Stockholm, Sweden Medical College of Georgia,
Augusta, Georgia Johns Hopkins Hospital,
Baltimore, Maryland
Human Pathology (November 2006) Volume 37, 292-297
3
Why is this important?

• Authors cited a lack of hard data in the
  literature about many of the issues regarding
  diagnosing and reporting prostate cancer
• They sought to survey current practices in order
  to provide a consistent guideline for the general
  pathologist
• Questionnaire was sent to 93 genitourinary
  pathologists with a response rate of 69

4
Introduction

• Core needle biopsies of the prostate are now
  among the most common specimens received at
  pathology laboratories
• Laboratory techniques for the diagnosis of
  prostate cancer have developed rapidly it is
  unknown to what extent new developments have been
  adopted by pathologists
• Criteria for diagnosis (including new morphologic
  variants) have not been consistently developed
• Reporting parameters (e.g. extent of cancer,
  perineural invasion) have not been consistently
  adopted into all pathology reports

5
Materials and methods

• Questionnaire distributed to 93 GU pathologists
  in 20 countries worldwide
• Demographic, age, nationality, type of practice
• Normal lab routines pertaining to handling and
  processing prostate needle biopsies
• How prostate cancer is diagnosed and reported
• Most questions were fixed response

6
Results - demographics

• Overall response rate 64/93 (69)
• Location
• USA 37
• Canada 3
• Europe 15
• Asia 4
• South America 2
• Australia/ New Zealand 3
• Work environment
• Academic Institution 43
• Private health care (or mixed academic/
  private) 17
• Military or non-academic community health care 4
• Age
• 31-40 6
• 41-50 20
• 51-60 24
• 61-70 13
• 70 1

7
Results - processing

• Routine fixative
• Formalin 94
• Bouins solution 3
• Zn-formalin 2
• Alcohol or Hollandes solution 0
• Number of HE levels
• Mean 3.1
• Median 3
• Range 1-12
• Unstained sections on intervening levels between
  HE slides
• Routine 47
• Immunohistochemical stains used to diagnose
  cancer in uncertain cases
• HMWK (34ßE12) 91
• P63 58
• CK 5/6 9
• Other cytokeratin 2
• AMACR (p504s) 50
• None 2
• Histochemical stains used to diagnose cancer in
  uncertain cases

8
(No Transcript)
9
Circumferential perineural invasion
10
Glomeruloid bodies (glomerulations)
11
Collagenous micronodules (mucinous fibroplasia)
12
Results diagnostic criteria

• Pathognomonic for prostate cancer
• Circumferential perineural invasion 84
• Collagenous micronodules (mucinous
  fibroplasia) 64
• Glomeruloid bodies (glomerulations) 58
• Glands in adipose tissue 36
• If none of the above, require a minimum number of
  glands
• Pathologist older than 50 years 47
• Pathologist younger than 50 years 27
• Number of glands required for diagnosis
• Mean 2.1
• Median 1
• Range 1-10
• Patient age influences diagnosis
• Yes 17
• Liberal approach if patient 70 y/o 6
• Conservative approach if patient

13
Focal prostatic adenocarcinoma, 336
14
Results Gleason grading

• When diagnosing cancer on a small group of
  atypical, non-cribriform glands (
• Gleason score 4 5
• Gleason score 5 3
• Gleason score 6 77
• Gleason pattern but no score 5
• No Gleason score or pattern 9
• Include note stating that grade may not be
  accurate due to sampling error
• Yes 14
• No 86
• Include note stating that cancer may be
  clinically insignificant
• Yes 23
• No 77

15
Results - other

• Report perineural invasion routinely 86
• Extent of cancer quantified 100
• Number of involved cores 80
• Percentage of cancer per core 53
• Overall percentage of cancer per case 41
• Millimeters of cancer per core 39
• Overall millimeters of cancer per case 8
• Subjective measure 8
• i.e. minute, focal, moderate, extensive
• Measure cancer end-to-end 34
• Regardless of intervening benign tissue
• Subtract intervening benign tissue 39

16
End-to-end 34
80 of core
Subtract intervening benign tissue 39
20 of core
17
Discussion

• Bouins and Hollandes solutions have been
  proposed as alternatives to formalin for superior
  nuclear preservation
• The survey shows that formalin remains the
  predominant fixative
• Possible reasons
• Both Bouins and Hollandes solutions contain
  picric acid, which is toxic and potentially
  explosive
• Diagnostic criteria and literature illustrations
  are based on formalin-fixed specimens

18
Discussion

• HMWK stains basal cell cytoplasm p63 stains
  basal cell nuclei AMACR stains prostate cancer
  cells
• HMWK retains leading role as predominant IHC
  marker (91), while p63 is used by 58
• Despite initial enthusiasm for AMACR, only 50 of
  respondents are routinely using it
• A possible reason is lack of specificity for
  prostate cancer

19
Discussion

• Routinely cutting unstained sections between HE
  levels is twice as common in North America than
  elsewhere
• While most pathologists stated a preference for
  this, some cited economic resources as a reason
  for not doing so routinely
• These sections were critical for diagnosis in
  2.8

Green, R, Epstein JI. Use of intervening
unstained slides for immunohistochemical stains
for high molecular weight cytokeratin on prostate
needle biopsies. Am J Surg Pathol 199923567-70
20
Discussion

• Glomeruloid bodies and mucinous fibroplasia
• Relatively uncommon in needle biopsies
• Have been claimed to be pathognomonic for cancer
• Only 58 and 64 use these as cancer-specific
• Circumferential perineural invasion
• Diagnostic utility is limited Extremely low
  incidence in limited cancer
• Used by 84 as cancer specific
• Benign glands in perineural spaces have been
  described
• Glands involving adipose tissue
• Usually means extraprostatic extension
• Rarely, fat is seen in prostate in the absence of
  cancer
• Possibly due to this, only 36 considered this
  pathognomonic for cancer

Baisden BL, Kahane H, Epstein JI. Perineural
invasion, mucinous fibroplasia, and
glomerulations diagnostic features of limited
cancer on prostate needle biopsy. Am J Surg
Pathol 199923918-24
Cohen, RJ, Stables S. Intraprostatic fat. Hum
Pathol 199829424-5
21
Discussion

• Number of malignant glands required for diagnosis
• 61 would occasionally diagnose cancer on a
  single atypical gland
• Mean number required to diagnose was 2.1
• At consensus conference in 1999, 3 glands were an
  agreed requirement
• The number is coming down, most likely due to the
  increasing usefulness of immunohistochemistry and
  pathologists comfort with the morphology of
  limited cancer
• A caveat low figures given in the survey
  responses may reflect unusual cases with a very
  pronounced architectural distortion or severe
  nuclear atypia.

22
Discussion

• Prognostic factors from core needle biopsies,
  according to CAP
• 1. Gleason score
• 2. Amount of cancer
• 3. Perineural invasion
• Only 86 currently assign a Gleason score to a
  small focus of cancer
• It has been demonstrated that biopsy Gleason
  score in such a case correlates almost as well
  with prostatectomy grade as when there is more
  extensive core involvement
• Current recommendations are to use Gleason score
  6 for a small focus of non-cribriform cancer
• 77 currently do so
• 8 preferred to use a lower score
• Several consensus documents recommend reporting
  of perineural invasion
• 86 follow this recommendation

Rubin MA, Dunn R, Kambham N, Misick CP, OToole
KM. Should a Gleason score be assigned to a
minute focus of carcinoma on prostate biopsy? Am
J Surg Pathol 2000241634-40
23
Discussion

• 2004 WHO-sponsored International Consultation on
  Prognostic Factors in Prostate Cancer recommended
  that the pathology report should contain
• Number of involved cores
• At least one measure of linear extent
  (millimeters or percent individual or global)
• 100 of respondents do so
• 80 use percentage
• 41 use millimeters
• 22 use both
• No consensus among survey respondents on the
  technique for measuring linear extent
• End-to-end (34) vs. subtracting intervening
  benign tissue (39)
• This discrepancy warrants further study

24
Summary

• Good agreement
• Formalin for fixative
• Three levels generated for HE stains
• Use of basal cell markers
• Circumferential perineural invasion as a
  pathognomonic feature of cancer
• Lack of relevance of patients age when
  diagnosing cancer
• Routine reporting of perineural invasion and
  Gleason score even in small cancer foci
• Further standardization needed
• Which immunohistochemical stains to diagnose
  cancer
• Minimum number of atypical glands required for
  cancer diagnosis
• Optimal methods for assessment of linear extent
  of prostate cancer in core biopsies