DECEPTIVELY BENIGN- I have nothing to disclose APPEARING PROSTATE - PowerPoint PPT Presentation

5/22/2015 DISCLOSURE DECEPTIVELY BENIGN- � I have nothing to disclose APPEARING PROSTATE CANCER Peter A. Humphrey, MD, PhD Yale University School of Medicine New Haven, Connecticut FALSE NEGATIVE DIAGNOSES OF FALSE NEGATIVE DIAGNOSIS OF MALIGNANCY IN SURGICAL PATHOLOGY : PROSTATIC ADENOCARCINOMA TOP 5 MALPRACTICE CLAIMS � Overall false negative rate in needle core biopsy Specimen type % False negatives in claims tissue = 1.1% to 1.7% Melanoma 95% � Reasons : Breast biopsy 48% - Low # of glands (<10) Gyn path 74% - Intermingled with benign glands Sarcomas 80% - Lack of architectural disorder Lymphoma 57% - Foamy gland or pseudohyperplastic variants Prostate (#8) 67% � AJSP 34:35-43, 2010; Histopathology 58:759, 2011 Troxel DB. Arch Pathol Lab Med 2006; 130:617-619 1

5/22/2015 FALSE NEGATIVE DIAGNOSIS OF PSEUDOBENIGN PROSTATIC PROSTATIC ADENOCARCINOMA ADENOCARCINOMAS � Pale Minimal Adenocarcinomas � 793 needle biopsies diagnosed as benign by H and E stained for AMACR � Atrophic Pattern Adenocarcinoma � 9/793 (1.1%) diagnosed as carcinoma – all less � Foamy Gland Adenocarcinoma than 1 mm (minimal or limited carcinoma) � Pseudohyperplastic adenocarcinoma � Atrophic, foamy, and pseudohyperplastic � Ductal Adenocarcinoma pattern adenocarcinomas accounted for most false-negative prostate needle biopsy � Crushed Small Cell Carcinoma interpretations � Single cell and linear array Gleason grade 5 � Carswell BM, et al. Histopathology 48:666, 2006 � Hormonal and radiation treatment effect MINIMAL SMALL PALE ACINAR CROWDED BENIGN GLANDS IN ADENOCARCINOMA : CROWDED NEEDLE BIOPSY GROWTH 2

5/22/2015 SMALL PALE ACINAR MINIMAL MINIMAL SMALL PALE ACINAR ADENOCARCINOMA MAY BE MISTAKEN ADENOCARCINOMA FOR BENIGN GLAND OUTPOUCHINGS AT SCANNING MAGNIFICATION A B C D C,D : p63/AMACR immunostain ATROPHIC PATTERN HORMONAL THERAPY EFFECT ADENOCARCINOMA ON PROSTATIC CARCINOMA : � CAN BE SEEN WITH ATROPHY OR WITHOUT PRIOR HORMONAL THERAPY � ATROPHY IN BENIGN OR MALIGNANT GLANDS = CYTOPLASMIC VOLUME LOSS PERINEURAL INVASION 3

5/22/2015 ATROPHIC PATTERN ATROPHIC PATTERN ADENOCARCINOMA ADENOCARCINOMA IN NEEDLE BIOPSY CYSTIC ATROPHIC ADENOCARCINOMA CYSTIC ATROPHIC ADENOCARCINOMA : MICROCYSTIC ADENOCARCINOMA : MICROCYSTIC ADENOCARCINOMA Am J Surg Pathol 34: 556-561, 2010 4

5/22/2015 CYSTIC ATROPHIC ATROPHY = CYTOPLASMIC ADENOCARCINOMA IN NEEDLE VOLUME LOSS BIOPSY NUCLEAR ATYPIA IN BENIGN SCLEROTIC ATROPHY ATROPHY Misdiagnosed as adenocarcinoma 5

5/22/2015 POSTATROPHIC HYPERPLASIA PARTIAL ATROPHY IN NEEDLE BIOPSY POSTATROPHIC HYPERPLASIA : CASE MISDIAGNOSED AS ADENOCARCINOMA DIAGNOSIS : ATROPHIC ADENOCARCINOMA � Infiltrative process with individual small atrophic glands situated between larger benign glands � Presence of co-existing non-atrophic adenocarcinoma � Greater cytological atypia than benign atrophy � AFIP Fascicle, 4 th edition, 2011 6

5/22/2015 ALPHA-METHYLACYL-CoA RACEMASE ATROPHIC PATTERN (AMACR; P504S) AS A MARKER FOR ADENOCARCINOMA ATROPHIC PROSTATIC � VS. BENIGN ADENOCARCINOMA ATROPHY : NUCLEAR ATYPIA AND DIFFUSE LOSS OF BASAL CELLS, BEST DEMONSTRATED BY HIGH MOLECULAR WEIGHT CYTOKERATIN AND/OR p63 IMMUNOSTAINS “ TRIPLE STAIN ” “ “ “ ” ” TRAP : ” GENE EXPRESSION PROFILES OF ATROPHY VS. NORMAL VS. PIN VS. PARTIAL ATROPHY CARCINOMA Mogal AP, et al. The Prostate 72: 931, 2012 7

5/22/2015 ATROPHIC PATTERN ATROPHIC VS. NONATROPHIC ADENOCARCINOMA : A ADENOCARCINOMA PROLIFERATIVE, NON- � WITH ATROPHIC � WITHOUT QUIESCENT GROWTH CHANGE : ATROPHIC CHANGE: � MEDIAN GLEASON � MEDIAN GLEASON � Proliferation index (by KI-67 labeling) : 4% SCORE = 6 SCORE = 6 � MEDIAN TUMOR � MEDIAN TUMOR for atrophic pattern vs. 5.3% for usual VOLUME = 1.4 CC VOLUME = 1.1 CC pattern � pT3 : 26% � pT3: 31% � Apoptotic index (by TUNEL labeling) : � MARGIN+ : 26% � MARGIN+ : 32% 0.4% for atrophic pattern vs. 0.4% for All non-significant differences usual pattern FOAMY GLAND INITIAL DEFINITION : FOAMY GLAND ADENOCARCINOMA ADENOCARCINOMA � Infiltrative small acini � First formally with characteristic described in 1996 xanthomatous cytoplasm without nuclear � Incidence in needle enlargement or nucleolar biopsy : 17% (2% prominence in most pure) cases � Incidence in radical � Intraluminal pink prostatectomy : 15% secretions in about one- to 23% half of cases � AJSP 20:419, 1996 8

5/22/2015 VALUE OF p63/AMACR COCKTAIL IN NUCLEAR ATYPIA IN USUSAL DIAGNOSIS OF MINIMAL FOAMY ACINAR VERSUS FOAMY GLAND GLAND CARCINOMA ADENOCARCINOMA AMACR positive in 68% of cases (AJSP 27:772, 2003) GLEASON GRADE OF FOAMY FOAMY GLAND ADENOCARCINOMA IN NEEDLE BIOPSY GLAND ADENOCARCINOMA � Needle biopsy : 80% 6s � Radical prostatectomy : median Gleason score = 7 Hudson J, et al. Hum Pathol � 43:974, 2012 Warrick JI and Humphrey PA. � AJSP 37:1709, 2013 9

5/22/2015 DIFFERENTIAL DIAGNOSIS : SPREAD OF FOAMY GLAND ADENOCARCINOMA XANTHOMA OF PROSTATE Extraprostatic extension Lymph node metastasis Xanthoma Foamy gland carcinoma OUTCOME AFTER RADICAL FOAMY GLAND CARCINOMA VS. BENIGN ATROPHY WITH FOAMY PROSTATECTOMY : FOAMY VS. FEATURES NON-FOAMY ADENOCARCINOMA Hudson J, et al. Hum Pathol 43:974, 2012 10

5/22/2015 PSEUDOHYPERPLASTIC PSEUDOHYPERPLASTIC ADENOCARCINOMA : ADENOCARCINOMA - WILLIS, 1948 : “ Other tumors show tubular, cystic, HISTORICAL PERSPECTIVE � First rigorously or papillary structure… ” characterized and named - ACKERMAN, 1964 : “ Epithelium formed in early in 1998 (Am J Surg Pathol 22:1239-1246, increased columnar cells… ” 1998) - EPSTEIN, 1992 : “ Prostate adenocarcinomas carcinoma often shows small acini, numerous papillae, � Needle biopsy features : resembling benign glands ” Am J Surg Pathol 8:1039-1046, 2000 � A variant included in - RO et al, 1997: Transition zone carcinomas may 2004 WHO Blue Book closely mimic BPH Index case PSEUDOHYPERPLASTIC PSEUDOHYPERPLASTIC ADENOCARCINOMA : PAPILARY ADENOCARCINOMA PATTERN 11

5/22/2015 PSEUDOHYPERPLASTIC PSEUDOHYPERPLASTIC ADENOCARCINOMA : BRANCHING ADENOCARCINOMA : MICROCYSTIC PATTERN ADENOCARCINOMA MIXED BRANCHING AND MIXED PATTERN – LARGE AND SMALL GLANDS PAPILLARY PATTERNS MICROCYSTIC MICROCYSTIC ADENOCARCINOMA ADENOCARCINOMA 34betaE12 immunostain p63/AMACR cocktail 12

5/22/2015 PSEUDOHYPERPLASTIC NODULOCYSTIC ADENOCARCINOMA : NODULOCYSTIC PSEUDOHYPERPLASTIC PATTERN ADENOCARCINOMA CYSTIC CHANGE IN PROSTATIC NODULOCYTIC PATTERN GLANDS : USUALLY A BENIGN PSEUDOHYPERPLASTIC INDICATOR ADENOCARCINOMA IN METASTATIC DEPOSIT (IN TESTIS) CYSTIC ATROPHY IN CYSTIC BPH PERIPHERAL ZONE 13

5/22/2015 PSEUDOHYPERPLASTIC PSEUDOHYPERPLASTIC ADENOCARCINOMA IN TURP ADENOCARCINOMA : CHIPS APPEARANCE IN NEEDLE BIOPSY TISSUE IMMUNOSTAINS FOR BASAL CELLS PSEUDOHYPERPLASTIC AND AMACR : PSEUDOHYPERPLASTIC ADENOCARCINOMA VS. BPH NODULE CARCINOMA IN NEEDLE BIOPSY 34βE12 IMMUNOSTAIN AMACR IMMUNOSTAIN NEOPLASTIC MIMICS IN GENITOURINARY PATHOLOGY, 2013 Note : 77% of cases positive 14

5/22/2015 PATHOLOGIC ATTRIBUTES OF DUCTAL ADENOCARCINOMA VS. PSEUDOHYPERPLASTIC PROSTATIC TYPE EPITHELIAL POLYP CARCINOMA � ANATOMIC LOCALIZATION : TRANSITION OR PERIPHERAL ZONE � TUMOR SIZE : 14.2 % OF WHOLE GLAND INVOLVED VS. 9.9% FOR USUAL CARCINOMA (P=0.038) � pT3 STAGE : 36% VS. 30% FOR CARCINOMA WITHOUT PSEUDOHYPERPLASTIC FEATURES (P=0.7) � GLEASON GRADE = 3 NEOPLASTIC MIMICS IN GENITOURINARY PATHOLOGY, 2013 DECEPTIVELY BENIGN SMALL CELL CARCINOMA VS. CRUSHED DUCTAL CARCINOMA IN LYMPHOCYTES NEEDLE BIOPSY TISSUE NEOPLASTIC MIMICS IN GENITOURINARY PATHOLOGY, 2013 15

5/22/2015 GLEASON PATTERN 5 : GLEASON GRADE PATTERN 5 : SINGLE CELLS LINEAR ARRAY NEOPLASTIC MIMICS IN GENITOURINARY PATHOLOGY, 2013 Am J Surg Pathol 35:1706, 2011; Am J Surg Pathol 36:900, 2012 RADIATION TREATMENT HORMONAL TREATMENT EFFECT ON PROSTATIC ADENOCARCINOMA EFFECT ON CARCINOMA “ Triple stain ” 16

5/22/2015 DIAGNOSIS OF DECEPTIVELY PSEUDOBENIGN CARCINOMAS : BENIGN-APPEARING ADDENDA TO STOUT CRITERIA (PSEUDOBENIGN) CARCINOMAS � Diagnose with great � Stout criteria hold true for usual and caution in needle biopsy pseudobenign prostatic carcinomas tissue � GLANDULAR PATTERN – disordered � Search for continuity with usual infiltrative growth adenocarcinoma � LACK OF BASAL CELLS � Apply markers : basal cell � CELLULAR DETAILS – large deeply-staining stains (high molecular weight cytokeratin, p63) nucleoli and AMACR � Arch Pathol 55:131, 1953 17