Mucinous Adenocarcinoma

Patients’ entire prostatectomy slide sets were rereviewed. The slides containing cancer (average ± SD per case, 8.0 ± 4.3) were digitally scanned as virtual slides using a ScanScope XT (Aperio Technologies, Vista, CA). By using ImageScope software (Aperio), we manually annotated all foci of 9 histologic patterns in a nonoverlapping manner, using a different color for each pattern, denoted as follows: (1) S, single, separate small acini, like 3B pattern^{3 (link)} without blue mucin Image 1A; (2) B, single, separate small acini with blue mucin Image 1B; (3) U, undulated, stellate, or branching medium acini, like 3A pattern^{3 (link)} lined by a single cell layer Image 1C; (4) F, fused, ragged small acini, including those with mucin Image 1D; (5) P, (micro)papillary consisting of medium to large spaces with stromal cores or strands of cells with 1 or more cell layers bridging across the acinus, with intervening slit-like spaces Image 1E; (6) SC, small cribriform, mediumsized acinar spaces with rounded contour, no solid foci, and 12 or fewer lumen spaces (inclusive of the glomeruloid pattern^{18 (link)}) Image 1F; (7) LC, large cribriform, with expansive cribriform to focally solid large acini with more than 12 lumen spaces Image 1G; (8) I, individual infiltrating or sheet-like cells lacking lumen formation Image 1H; and (9) M, mucinous (colloid) carcinoma in which nonfused acini (excluding single cells) floated in mucin pools Image 1I. Note that although the lumen contours of the U and P patterns were somewhat similar, strict criteria (as stated) were adhered to for P, (micro)papillary. Based on the assertion that small, rounded cribriform cancer might be graded as Gleason grade 3,^{10 (link),13 (link),15 (link)} specimens with any cribriform pattern were further subdivided by annotating the SC and LC areas. Image 2 shows an example of an annotated slide.
The rare cancer subtypes of ductal^{19 (link),20 (link)} (excluding some papillary patterns that were encompassed in a broader definition of ductal^{21 (link)}), and adenoid cystic/basal cell carcinoma^{22 (link)} were denoted, if present, according to established criteria. To verify all annotations considered to be LC or SC or to have ductal cancer, consensus conferences were held by 4 of us (K.A.I., G.R.K., F.G.L., and M.S.L.), at which annotated slide images were projected on a screen. For each specimen, taking together all pertaining slides, the area sum of each cancer pattern was determined by summation of all digitally annotated foci belonging to that pattern. In this manner, each distinct pattern could be considered individually from a statistical viewpoint. The amount of each pattern per specimen was also expressed as percentage of the total cancer area. However, area sums rather than pattern percentages were used as the main method of analysis to approximate the cancer contribution of each pattern.
To determine the relative tendency of each pattern toward extraprostatic extension or seminal vesicle invasion, the cancer patterns responsible for these findings were tabulated. As a separate analysis, to explore the effect of having a sizable amount of large acinar (LA, or P plus cribriform [C] patterns) cancer, a cut point of P + C patterns forming more than one third of the total cancer area per patient was chosen. The one-third cut point was chosen for its ease of perception at diagnosis and because it produced a category that included 17 cases, allowing meaningful statistical comparison with the other 136.