Prostate Pathology: Prostate Carcinoma, variants and Gleason Grading (Part 1) Jae Y. Ro, MD, PhD June 7, 2012
Ten Leading Cancer Types for the Estimated New Cancer Cases and Deaths By Sex, United States, 2012. CA Cancer J Clin 2012; 62(1):10-29
Cancers in Men, 2012 Incidence (41%) Prostate 241,740 29% 1 st Urinary Bladder 55,600 7% 4 th Kidney & renal pelvis 40,250 5% 6 th Estimated deaths (15%) Prostate 28,170 9% 2 nd Urinary Bladder 10,510 3% 8 th Kidney & renal pelvis 8,650 3% 10 th CA Cancer J Clin 2012;62 (1):10-29
Prostate Cancers Most frequently diagnosed cancer in men (total = 241,740; 29%) 2 nd cause of cancer mortality in men (total = 28,170; 9%) Reference: Siegel R et al: Cancer Statistics, 2012 CA Cancer J Clin 2012;62:10 29 American Cancer Society
Do your BeST! B represents Basic. e (effort) S represents Study. T represents Think. E represents Enjoy.
Do your BeST!
1. Basic Prostate anatomy Prostate histology
Disease of Prostate P. Zone (70%) T. Zone (5-10%) C. Zone (20%) CA (70%) CA (25%) CA (<5%) PIN BPH AAH BCH CCCH SA
2. Study Prostate cancers Microacinar carcinoma Gleason grading Variants Precancerous conditions Prostatic intraepithelial neoplasia Atypical adenomatous hyperplasia ASAP Stromal lesions
You have to look for 3 things! In biopsies, TURP and radical prostatectomies Small glands Medium/Large glands with atypia Stromal abnormalities
Prostate Carcinoma Well-diff. and poorly diff. adenocarcinoma well-diff. adenocarcinoma - For screening: three Too (too small, too crowded, and too clear) - For confirmation: nuclear enlargement, prominent nucleoli and lack of basal cells poorly diff. adenocarcinoma - Uniformity, p. nucleolus, no or low mitoses
Adenocarcinoma Other helpful features: Acid mucin Crystalloids Rigid luminal border Collagenous micronodules (mucinous fibroplasia) Glomerulation Perineural circumferential invasion Glands in fat
High grade prostatic carcinoma vs. Non-prostatic carcinoma Prostate Non-prostate N. monotony + - Nucleolus prominent variable Mitoses rare frequent
Gleason Grading, 1974
Pattern 1
Pattern 2
Pattern 3
Pattern 4
Pattern 5
Original, 1977 Revision, 2005
Gleason Grade, Revisited 2005 ISUP consensus (AJSP 29:1228, 2005) Gleason pattern 1, 2 (score 2-4 cancer) Cribriform form Isolated cells Variants of prostate cancers and special features seen in prostate cancers: Grading for variants of adenocarcinoma of prostate Vacuoles, collagenous micronodules, glomerulation
Gleason Grading, Revisited Original Gleason grade 1+1, most likely AAH (adenosis): Gleason score 1+1 should not be diagnosed in any specimens Gleason score 3-4: rarely seen in TURP, radical prostatectomy, and possibly biopsy from transition zone or at apex Gleason score 3-4 in needle biopsy should not make without consultation: 1) poor reproducibility, 2) poor correlation with prostatectomy, 3) misguide clinicians and patients into believing that the patient has an indolent cancer Possible very low-grade on needle biopsy: score 5 (2+3 or 3+2)
Gleason Grading, Revisited Cribriform Gleason pattern 2/3, most likely high grade PIN No cribriform pattern 2 cancers Cribriform 3, rounded, wellcircumscribed glands of similar size of normal glands (no basal cells) Individual cells are Gleason pattern 5, not allowed for Gleason pattern 3 Cribriform, new revision, 4 or 5
Cribriform pattern, 2011 2005 revision No pattern 2 May be pattern 3 2010-2011 revision No pattern 3 All pattern 4/5
No pattern 3, cribriform
Special features and variants of Ca (I) Vacuoles: can be seen in any patterns and should be distinguished from signet ring cell carcinoma Tumors should be graded, as if vacuoles were not present (by evaluating underlying architectural pattern) Adenoca with focal mucin extravasation: ignore mucin extravasation, grade based on the underlying architecture: distinguished from colloid (mucinous) carcinoma, Gleason score 4+4
Gleason Grading, Revisited Mucinous fibroplasia (collagenous micronodules) - Resembling cribriform structures - Subtract away mucinous fibroplasia, grade based on the underlying glandular architecture - Gleason score 3+3 Glomeruloid structures - Cribriform proliferation that is not transmural - Prognostic significance unknown - Lack of consensus, pattern 3 vs. 4 - Either approach is acceptable until future data
Variants of Prostate Ca Mucinous adenocarcinoma: Gleason pattern 4 may be 3 Ductal-endometrioid ca: 4 to 5 Sarcomatoid ca: 5 Signet ring cell ca: 5 LELC: 5 and oncocytic ca: 5 Foamy gland carcinoma: 3, may be higher Ca with atrophic & hyperplastic features: 3 Transition zone ca: 2 Small cell, TCC, squamous and adenosq ca: not be assigned GG
Original, 1974, 1977 Revision, 2005 New Revision, 2010, cribriform, 4 or 5
Gleason 3 vs. 4 Grade 3 Discrete units Can draw a circle around individual glands Presence of a few poorly formed glands under a high power is still O.K. for pattern 3 Grade 4 Fused glands Ill-defined papillary/cribriform glands solid nests with clear cells NOTE: any difficulty in small sample, conservative grading 3 is recommended
Mucinous Adenoca of Prostate Boyd first described a case of mucinous adenocarcinoma of the prostate in 1881 A rare variant of adenocarcinoma (Gleason pattern 4) Accounts for <0.5% of prostatic adenocarcinoma
Mucinous Adenoca of Prostate Criteria: At least 25% of total tumor volume Extracellular mucin pool with single or clusters of tumor cells floating in mucin lakes (nondilated glands containing mucin do not quality) Extraprostatic origin should be excluded: PSA and PAP positive in tumor cells
Mucinous Adenoca of Prostate In the past, most pathologists and clinicians believed 1) less aggressive 2) not likely to metastasize to bone 3) serum PSA and PAP not elevated 4) arose from female portion of gland Recent studies demonstrate as a variant of prostatic ca; prognosis not differ stage by stage
Mucinous Adenoca of Prostate Should exclude metastasis from other sites or direct extension Helpful features for 1st prostate mucinous ca. 1) Association with other histologic types of prostatic ca 2) Cuboidal or oval round tumor cells (not columnar) 3) Signet ring cells, goblet cells not present 4) Tumor cells floating in mucin lakes 5) PSA and PAP positivity in tumor cells.
Mucinous Adenoca of Prostate Age & symptoms not different from acinar carcinoma Elevated serum PSA & PAP LN and bone metastases with osteoblastic nature
Mucinous Adenoca of Prostate Mucin confined within glandular lumina should not be classified as mucinous carcinoma Mucinous areas occupy small portion of tumor designate as prostatic carcinoma with focal mucinous component (particularly in needle biopsies)
Intraluminal Acid Mucin Normal and benign glands usually contain neutral mucin Prostatic ca. contains neutral and acid mucins Intraluminal acid mucin in 70% of prostatic ca However, intracellular mucin not common in prostatic carcinoma Associated with intraluminal crystalloids Seen in benign conditions, such as SA Useful aids in diagnosing prostatic ca
Mucinous Adenoca of Prostate Management and Prognosis: Same as microacinar carcinoma (depends on clinical presentation and stage) Prognosis not different from other prostate carcinoma, stage by stage Neither grade of nonmucinous component nor proportion of mucinous component is associated with prognosis
Mucinous Adenoca of Prostate Differential Diagnosis Prostate Non-prostate Cells Cuboidal Columnar Goblet cells - + Signet ring cells - + Intracytoplasmic mucin Usually absent Present Immuno PSA, PAP + CEA + CK 20 - CK 20 +
Mucinous Adenoca of Prostate Summaries: A variant of prostatic carcinoma Accounts for < 0.5% of prostatic ca Symptoms, signs, Rx and prognosis not different from other prostatic ca Diagnostic criteria
Prostate Pathology: Prostate Carcinoma, variants and Gleason Grading (Part 2) Jae Y. Ro, MD, PhD June 7, 2012