INTRADUCTAL LESIONS OF THE PROSTATE. Jonathan I. Epstein

Transcription

1 INTRADUCTAL LESIONS OF THE PROSTATE Jonathan I. Epstein

2 Topics Prostatic intraepithelial neoplasia (PIN) Intraductal adenocarcinoma (IDC-P) Intraductal urothelial carcinoma Ductal adenocarcinoma

3 High Prostatic Intraepithelial Neoplasia (HGPIN) Considered to be a precursor to many prostatic adenocarcinomas, especially ones arising in the peripheral zone.

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11 Low Grade PIN (LGPIN)

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14 Low Grade PIN Do not comment on in diagnosis Lack of reproducibility in diagnosis Lack of prognostic significance Patients subjected to unnecessary procedures and concern

15 Incidence of High Grade PIN (HGPIN) on Biopsy Mean 7.6% Median 5.2%

16 Variations in Incidence of HGPIN on Biopsy Fixative Sampling Patient population? Interobserver threshold

17 HGPIN on Biopsy: Subsequent Risk of Cancer (35 Studies) Mean 31.5 Mean >50 patients 25.3 Median 24.1 Following Needle of a Benign Diagnosis (21 studies) Risk for Cancer (Mean & Median): 19%

18 Pathological Factors Most studies have shown if 1 core of HGPIN is present, it does not help predict which men are at higher risk of having cancer following a needle biopsy diagnosis of HGPIN. Risk of cancer following >2 cores with HGPIN is 30%-40%. Reasonable to recommend repeat biopsy.

19 Clinical Factors to Predict Cancer Of 16 studies, 13 found that serum PSA levels were not predictive of cancer on re-biopsy. Digital rectal exam or transrectal ultrasound not influential in predicting which men with HGPIN on needle biopsy will have carcinoma on re-biopsy.

20 Repeat Biopsy Recommendation Men do not need a routine repeat needle biopsy within the first year following the diagnosis of HGPIN on 1 core If multifocal HGPIN on biopsy, repeat biopsy 3-6 months. Reasonable to repeat biopsy at 2 or 3 years after limited HGPIN since we don t know the long-term risk of cancer and medicolegal issues if patient not followed-up.

21 Human Pathology 32: , 2001

22 PINATYP High grade PIN with small focus of atypical glands. See note: Note: Adjacent to glands of high grade PIN are a few small atypical glands. While these small glands may represent a small focus of infiltrating cancer, we can not exclude that they represent outpouching or tangential sections off of the adjacent high grade PIN.

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28 PINATYP Follow-up Risk of cancer on repeat biopsy 46% Repeat biopsy recommended

29 Intraductal Adenocarcinoma of the Prostate (IDC-P)

30 Cancer 1985; 56: Am J Surg Pathol 1996; 20: 802-4

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32 Of 901 RPs, 141 had IDC with adjacent invasive carcinoma (regular IDC) and 14 (1.5%) showed IDC with cancer distant from IDC (precursor IDC) Regular IDC with cancer had significantly higher Gleason score, more frequent EPE and SVI, more advanced pathological T stage, and lower 5-year BCR than IDC w/o adjacent carcinoma. Prostate cancer with Gleason score >8 in the RP was observed in 73 (52%) cases with regular type IDC-P and in 3 (21%) cases with precursor-like IDC-P.

33 Multivariate analysis revealed nodal metastasis and the presence of regular type IDC as independent predictors for biochemical recurrence The 5-year biochemical recurrence-free rates were 61% in patients with regular type IDC-P vs. 93% for precursorlike IDC-P.

34 Precursor-like IDC-P is very uncommonly identified in RPs IDC does not always represent intraductal spread of pre-existing high-grade invasive carcinoma, and at least a subset of IDC could account for a precursor lesion of invasive carcinoma

35 Intraductal Carcinoma Solid or dense cribriform pattern Loose cribriform or micropapillary pattern with either Marked nuclear atypia: Nuclei 6x normal Comedonecrosis Basal cell layer preserved

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45 PIN vs. IDC-P Atypical glands surrounded by basal cells where the differential diagnosis is between high grade PIN and intraductal carcinoma of the prostate. Repeat biopsy is recommended.

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49 Loss of PTEN (IHC) IDC + infiltrating cancer 38/50 (76%) IDC alone 20/33 (61%) HGPIN 0/19 (0%) Borderline PIN/IDC 11/21 (52%) 7/11 (64%) with loss PTEN subsequent carcinoma on biopsy 5/10 (50%) with intact PTEN subsequent carcinoma on biopsy

50 IDC-P vs. Infiltrating Carcinoma

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62 When to do IHC for Basal Cells on?idc-p Do basal cell stains when it could make a difference if infiltrating cancer vs. IDC-P only Do basal cell stains if it could possibly make a difference in the grade

63 Intraductal Carcinoma of the Prostate vs. Intraductal Spread of Urothelial Carcinoma

64 IDC-P

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69 Intraductal Urothelial Carcinoma

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74 HMWCK

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76 GATA3

77 Significance of IDC-P only or IDC-P with Low Grade Prostate Cancer on Biopsy

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79 All 6 six RPs with high-grade infiltrating carcinoma with Gleason score 8 or 9 Non-focal EPE in 5/6 RPs 3/16 who did not undergo RP developed bone metastases

80 Support prior studies that IDC-P represents an advanced stage of tumor progression with intraductal spread of tumor. Consideration should be given to treat patients with IDC-P on biopsy aggressively even in the absence of documented infiltrating cancer.

81 J Urol 2010; 184:

82 Follow-up available in 66 cases with only IDC on biopsy Of the 21 RPs available for review findings revealed pathological stage pt3a in 8 (38%), pt3b in 3 (13%), pt2 in 8 (38%). IDC only without identifiable invasive cancer in 2 (10%). Average Gleason score 7.9.

83 At RP, men in whom prior biopsies showed only IDC typically have high grade (Gleason score >7) invasive adenocarcinoma and most have advanced stage disease (pt3). Definitive therapy is recommended in men with IDC on needle biopsy even in the absence of pathologically documented invasive prostate cancer.

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88 3+3=6 with IDC on Biopsy 51 Total Patients Treated After Diagnosis 4 Chemotherapy (Metastatic at Diagnosis) 14 Radical Prostatectomy 31 Radiation Therapy (+/- ADT) 1 ADT Alone 1 Cryotherapy 13 (+) ADT 18 (-) ADT

89 Grade and Stage on Reviewed Radical Prostatectomy Specimens (N=14) Gleason Grade Number of Cases 3+3=6 3 (21%) 3+4=7 5 (36%) 4+3=7 4 (29%) 4+4=8 2 (14%) Pathologic Stage Number of Cases pt2 5 (36%) pt3a 5 (36%) pt3b 4 (28%)

90 Report Intraductal carcinoma is more frequently seen with Gleason patterns 4-5 carcinoma although these are not present on the current tissue samples.

91 Intraductal Carcinoma Distinctive morphology vs. HGPIN Associated with high grade cancer and poor pathology at RP & relatively poor prognosis with other therapies In most cases it is an advanced stage of tumor progression with intraductal spread of tumor; rarely an in-situ high grade cancer Justified to treat patients with intraductal carcinoma on biopsy even in the absence of documented infiltrating cancer

92 Grading Intraductal Cancer: Pro Hard to tell if IDC or infiltrating high grade cribriform cancer in many cases w/o doing stains Recommend to treat as if high grade infiltrating cancer so why not just call high grade cancer

93 Grading Intraductal Cancer: Con In other organ systems (ie. breast) don t grade IDC. Uncommonly, only IDC may be present in the RP so grading biopsy as high grade cancer gives wrong prognostic information. Current recommendation is to do basal cell stains if no obvious infiltrating cancer present and?idc

94 VOTE IDC should not be graded as Gleason pattern 4 but should be noted typically correlated with aggressive behavior. 82% 1. Yes 2. No 18% 1 2

95 Prostatic Duct Adenocarcinoma May arise in large periurethral ducts and project into the urethra around verumontanum clinically mimicking UC. Presents with LUTS and hematuria. Rectal often normal. Diagnosis made on TURP

96 May arise in secondary (peripheral) ducts May present as ordinary (acinar) adenocarcinoma with abnormal DRE or elevated serum PSA levels and diagnosed on needle biopsy.

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100 Relation to Acinar Adenocarcinoma Separate peripheral acinar and central duct Comingling of duct and acinar

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104 Findings at Radical Prostatectomy Large tumor volume Advanced stage Frequent positive margins Higher risk of post-operative failure

105 Am J Surg Pathol 1999; 23: Ductal Adenocarcinoma of the Prostate Diagnosed on Needle Biopsy Brinker DA, Potter SR, Epstein JI

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111 PIN-Like Ductal Adenocarcinoma

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118 Grading Ductal Adenocarcinoma Usual (cribriform; papillary) Ductal: Gleason pattern 4 With central necrosis: Gleason pattern 5 PIN-like Ductal: Gleason pattern 3

119 Ductal Adenocarcinoma Growing within Ducts Convention has been to grade and diagnose the same as infiltrating ductal adenocarcinoma as these tumors typically are aggressive and cases of pure intraductal growth of ductal adenocarcinoma have not been reported.

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121 Ductal Terminology Confusing Intraductal carcinoma (ductal refers to location) Acinar morphology (cuboidal cells) growing within ducts and acini Ductal adenocarcinoma (ductal refers to cytology) Ductal morphology (tall pseudostratified columnar cells) typically invasive but also can be growing within ducts and acini

122 Summary Wide spectrum of intraductal/intraacianr lesions in the prostate Some are precursor lesions and others reflect spread of invasive cancer into ducts/acini. Range from lesions that have very low risk of association with prostate cancer to those associated with increased risk of aggressive prostate cancer Need to differentiate from non-prostatic mimickers