PSA. HMCK, p63, Racemase. HMCK, p63, Racemase

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1 Case 1 67 year old male presented with gross hematuria H/o acute prostatitis & BPH Urethroscopy: small, polypoid growth with a broad base emanating from the left side of the verumontanum Serum PSA :7 ng/ml A biopsy of the lesion was performed

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4 PSA HMCK, p63, Racemase HMCK, p63, Racemase

5 Case 1 - Diagnosis: Verumontanum, biopsy: Atypical papillary intraductal proliferation of the prostatic epithelium, highly suspicious for adenocarcinoma of prostate with ductal features Follow up: 72 months NED; post re-turp and peripheral zone bxs Questions Posed by Case Current status of prostatic ductal carcinoma Does it exist? What are the diagnostic criteria? What is the clinico-pathologic significance? Reporting guidelines Approach to atypical intraductal proliferations (exceeding those of HGPIN) What Is a Prostatic Duct? The ducts and acini are morphologically identical except for their geometry The duct acinar system functions as distensible secretory reservoirs Each is lined by: secretory cells - PSA, PSAP positive basal cells - 34BE12 positive Difficult to distinguish between ducts and acini except sections cut along the ductal long axis

6 Prostatic Ductal Carcinoma Ducts of Prostate Originate at urethra, terminate at the capsule or anterior FM stroma Lining: Urothelium Vicinity of urethra for variable distance Columnar secretory epithelium Rest of the entire duct-acinar system Carcinomas involving prostate ducts Prostatic ductal (endometroid) carcinoma Transitional cell carcinoma involving prostatic ducts and acini

7 PROSTATIC DUCTAL CARCINOMA Architecture: Large glandular: Tubulo-papillary Growth pattern: Cribriform Solid Invasive Back-to-back Interanastomosing glands EPE, perineural invasion 34ßE 12 (-) Intraductal Basal cell layer preserved 34ßE 12 (+) PROSTATIC DUCTAL CARCINOMA Cytology: Cell type: Tall columnar Oval Pseudostratified Round Nuclear grade: Low : Banal High : Irregular nuclear chromatin Comedonecrosis Frequent mitoses Multiple nucleoli PROSTATIC DUCTAL CARCINOMA

8 PROSTATIC DUCTAL CARCINOMA PROSTATIC DUCTAL CARCINOMA PROSTATIC DUCTAL CARCINOMA Gleason grading: Grade 4 (most) Grade 5 (if necrosis) WHO and ISUP Recommendations

9 PROSTATIC DUCTAL CARCINOMA Clinical: Central: exophytic papillary growth in urethra present earlier with obstruction, hematuria frequently seen in TURP specimens Diffuse: wide-spread involvement of prostate gland abnormal DRE or elevated PSA

10 Racemase

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14 DUCTAL CANCER OF PROSTATE HG-PIN Invasive cancer Intraductal cancer HG-PIN Pre-existing ductacinar structure individual glandular unit basal cell layer attenuated maturation lacks true papillary core may be unrelated to cancer DUCTAL CANCER OF PROSTATE INVASIVE CANCER Infiltrative growth back-to-back interanastomosis perineural invasion EPE 34ßE12 (-) INTRADUCTAL CANCER pre-existing duct-acinar structure within or at periphery of invasive carcinoma basal cell layer often intact and well-defined isolated (without invasive cancer) in bx difficult/impossible to separate 34βE12(+) & Racemase (+) DUCTAL CANCER OF PROSTATE HG-PIN Invasive cancer Intraductal cancer

15 Acinar carcinoma Acinar carcinoma with ductal histology Ductal carcinoma Acinar carcinoma Acinar carcinoma with ductal histology Ductal carcinoma Acinar carcinoma (pure or >80%) Acinar carcinoma with ductal histology Ductal carcinoma (pure or >80% in RP) more common occasional most common histology when ductal pattern is present very rare

16 DUCTAL HISTOLOGY IN PROSTATIC SPECIMENS Needle bx Diagnosis: Adenocarcinoma with ductal features Comment: If this pattern is still present as predominant pattern, diagnosis of ductal cancer may be rendered Radical prostatectomy >80% or pure ductal histology Prostatic adenocarcinoma, Gleason score 4+4 = 8, ductal variant INTRADUCTAL GROWTH INTRADUCTAL GROWTH

17 INTRADUCTAL GROWTH INTRADUCTAL GROWTH INTRADUCTAL GROWTH

18 Atypical Large Glandular Proliferation - intraductal growth of ductal carcinoma Criteria: Cytologically malignant epithelial cells filling large acini and prostatic ducts and with preserved basal cell layer Cells spanning the entire gland lumen without maturation Solid or dense cribriform growth Complex glandular architecture with gland branching Comedo necrosis Frequent mitoses Cytologic and architectural atypia exceeding HGPIN?? Intraductal carcinoma of Prostate??

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23 Prostatic Ductal Carcinoma Clinical outcome Dube, Farrow (Mayo) Central (papillary) tumors 5-year survival 42.8% Diffuse (comedo/cribriform) 5-year survival 24.2% Bostwick et al (Stanford) year survival 15%; median survival 37 mos. All cases metastasis or recurrence Prostatic Ductal Carcinoma Clinical outcome Epstein et al (Memorial Sloan Kettering) % metastatic disease Ro et al (MD Anderson) year survival 30%;median survival 46.3 mos Prostatic Ductal Carcinomas Clinical Outcome Advanced pathologic stage and recurrence (compared to similar clinical stage acinar carcinoma) 93% Capsular penetration 47% Surgical margin 40% Invade seminal vesicle 27% Positive pelvic lymph nodes Larger tumor volume: 8.4cc vs. 4.2cc % of gland involved: 23% vs. 10% Christensen et al, Johns Hopkins, 1991

24 Approach for Atypical Intraductal Lesions of the Prostate Exceeding HGPIN In needle biopsy In TURP Intraductal growth in R. Prostatectomy McNeal,Yemoto (1996) Frequent EPE, LN involvement, PSA recurrence Rubin et al (1998) Higher tumor volume, independent predictor of prognosis Wilcox et al (1998) Higher Gleason score, tumor volume, SV involvement and disease progression Dawkins et al (2000) Greater allelic instability compared to accompanying PIN and cancer Samaratunga et al (2010) Any proportion predicts EPE Atypical intraductal proliferation without invasive adenocarcinoma Intraductal carcinoma of prostate- IDC-P Guo, Epstein, 2006: 21 cases with FU: 6 treated with RP, 7 with radiation, 5 with hormones, 1 with hormone and radiation and 2 with waitful watching 6 cases with RP: Gleason score 8 or 9, EPE in 5/6 cases, vascular-lymphatic invasion in 2/6 cases 3/16 cases without RP: developed bone metastasis Recommendation by authors: patients with IDCP on biopsy should be considered for aggressive treatment even in the absence of documented invasive cancer

25 Terminology: IDC-P Caution: Distinction between HGPIN and IDC-P is not always clear cut Designation as HGPIN may lead to under-management Overcall of multifocal HGPIN as IDC-P may prompt more aggressive management than required Recommended Terminology Atypical Large Glandular Proliferation- cannot rule out IDC-P Presence of basal cell layer by light microscopy & / or IHC (HMCK +/-, p63 +/-, racemase +) Atypical large glandular lesions (exceeding HGPIN) that have an exclusive intraductal growth or Architecture not sufficiently complex to designate as ductal carcinoma Ductal or IDC-P Presenting as Urethral Polyps Small lesions presenting as urethral polyps Distinct from obvious carcinomas presenting in TURP due to obstruction Samaratunga and Letizia, (2007) 8 cases, all with some component of intraductal growth- 3 cases had ductal carcinoma and 5 had acinar carcinoma in other specimens Bland cytology in 5 cases- misdiagnosis as benign lesion

26 Intraductal Lesions Presenting as Urethral Polyps: Personal experience 9 cases Lesion size: 0.2 to 0.7 cm Intraductal growth: 100% Invasive growth: 0% Approach: Repeat TURP Multiple peripheral zone biopsies Follow up: 2 cases NED (12 & 72 mos) FU on more cases being obtained Differential Diagnosis Acinar carcinoma secondarily involving prostate Urothelial carcinoma involving prostatic ducts and acini Villous adenoma of prostatic urethra and/or surface of metastatic colonic carcinoma Nephrogenic adenoma/ metaplasia

27 U. Ca involving prostatic ducts and acini

28 PROSTATE NEEDLE BX-pT CIS,PD HMCK HMCK

29 ENTERIC TYPE GLANDULAR LESIONS Villous adenoma Primary adenocarcinoma of urethra Colorectal carcinoma, metastatic or direct extension PSA, PSAP, PSMA (-) CDX2, CK20 (+)

30 METASTASIS OR LOCAL EXTENTION FROM COLORECTAL CARCINOMA

31 B catenin CDX-2

32 Nephrogenic adenoma of prostatic urethra Nephrogenic adenoma of prostatic urethra Thank you!!!