Case 2 -

Prostatic Adenocarcinoma with Wide Intraductal Growth (Intraductal carcinoma of the prostate--IDC-P) Ferran Algaba Pathology Section. Fundació Puigvert Universitat Autónoma de Barcelona- UAB Barcelona, Spain

Click on each slide thumbnail image for an enlarged view

Clinical History 57 years old man with perineal pain and painful digital rectal examination. Total serum PSA 3.67µg/L , free PSA 0.33 µg/L, ratio 0.08. A prostate needle biopsy was do. Case 2 - Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Case 2 - Figure 1 Core biopsy with two solid epithelial areas Case 2 - Figure 2 Cribriform well out-line epithelial areas Case 2 - Figure 3 High magnification with secretory atypical cells in a cribriform fused gland pattern Case 2 - Figure 4 34βE12 cytokeratin in both solid epithelial areas Case 2 - Figure 5 34βE12 cytokeratin in both solid epithelial areas Pathological findings Ten core biopsies (five for every site) were received. All cores show many well-outlined nodular areas of a epithelial proliferation of secretory cells with mild nuclear atypia and occasional nucleoli, with a cribriform aspect. Some of them has central comedonecrosis. All of this areas have preserved basal cells with 34βE12 positive expression. Additionally to this predominant aspect isolated monolayer microglands without basal cells and with nuclear atypia are present, some of them with a circumferential intraprostatic nerve invasion. Diagnosis Prostatic Adenocarcinoma with Wide Intraductal Growth (Intraductal carcinoma of the prostate--IDC-P). Bullet points: Are the this intraductal growth a ductal carcinoma or a High Grade Prostatic Intraepithelial Neoplasia or a Intraductal expansion of a standard carcinoma? Is it acceptable the presence of basal cells in a prostatic adenocarcinoma? If the previous question is yes. Are we able to recognize them and what must be our report to the urologist? If it is and adenocarcinoma, What Gleason pattern is it? Commentary Cribriform prostate proliferations can be present without and with basal cells (34βE12 and/or p63 positive). In the first situation it is considered as an invasive prostate carcinoma Gleason pattern 3 or 4, but in the second suppose, what is it?. For some authors it is always a pattern of High Grade Prostatic Intraepithelial Neoplasia (HGPIN) [1], but others believe that some of them may represent a real intraductal carcinoma of the prostate (IDC-P). Four architectural patterns of HGPIN (flat 28%, tufting 87%, micropapillary 85% and cribriform 32%) have been described [1]. Even though the patterns often merge with each other, the possibility of a progressive transformation of the flat pattern into a micropapillary one and a cribriform one is a tempting thought. This hypothesis was partially supported by the observation that patients with isolated papillary-cribriform HGPIN in needle biopsy has a higher incidence of ulterior carcinoma that the other HGPIN patterns (58.3% versus 16.7%) [2]. In other ways this supposition is reinforced by some authors' observation that the most central cells of the papillary and cribriform patterns are more undifferentiated and lose more heterozygosity than those that are closer to the basement membrane, and also that carcinomas associated with cribriform pattern of HGPIN are clinically more aggressive [3, 4, 5], which seems to be confirmed by the description of unusual cells types as signet ring cells PIN and small cell or neuroendocrine cell PIN types in cribriform types [6] similar to invasive carcinomas. All of these observations have been the reason why some authors consider the possibility that some of these changes are IDC-P [7]. This can explain that when the evolution of the isolated HGPIN is considered avoiding the cases with a huge cribriform-solid pattern the ulterior carcinoma incidence is similar among all the HGPIN patterns (31.9% versus 22%) [8]. For all of these considerations it seems that the IDC-P is a real possibility different that the papillary-cribriform HGPIN, with clinical implications, and recently a genetic-molecular correlation is demonstrated with the TMPRSS2-ERG gene fusion [9] For all of these we need a very strict diagnosis criteria to distinguish both lesions. The criteria to recognise the IDC-P, besides the total/partial basal cell preservation, are the enlargement of the large-caliber glands, the spanning of the gland lumen by malignant cells, and the frequent double cell population [10]. A intraductal cellular growth with basal cell preservation with comedonecrosis never must be considered as a HGPIN [10]. Intraductal prostate carcinoma may arise by two non excluding mechanisms, by spread of invasive adenocarcinoma into adjacent normal ducts or by HGPIN evolution. This last is supported in some cases for the distance between both lesions, the right branching with smooth out-line of the glands and the continuum with the non-neoplastic cells. In practice invasive carcinoma is almost always concomitant with the IDC-P as in this case presentation. The infiltrating adenocarcinoma is in general Gleason pattern 4 or 5, and this correlate with the ability of prostatic cells to grow without stromal attachment, similar to the intraductal growth [9], an for this reason the IDC-P can be considered as a Gleason 4 or 5, position that is supported for the high aggressivity of the cases with infiltrating adenocarcinoma associated with IDC-P [11, 12, 13] In the occasional cases with an isolated IDC-P in needle biopsy it is not recommended the biopsy repetition if a comedonecrosis pattern is present [11], in the other patterns it is prudent an immediate repetition of the biopsy, not delayed as in HGPIN. In conclusion: The IDC-P exist. It evolves late in cancer progression. It must be considered Gleason pattern 4 or 5. In case of isolated IDC-P with comedonecrosis no more biopsies are necessary In case of isolated IDC-P without comedonecrosis an immediate repetition of the biopsy is wise. References Bostwick DG, Amin MB, Dundore P et al.: Architectural patterns of high grade Prostatic intraepithelial Neoplasia. Hum. Pathol. 1993; 24: 298-310. Kronz JD, Allan CH, Shaikh AA, Epstein JI.: Predicting cancer following a diagnosis of high-grade prostatic intraepithelial neoplasia on needle biopsy: data on men with more than one follow-up biopsy. Am J Surg Pathol. 2001 ;25:1079-1085. Wilcox G, Soh S, Chakraborty S, Scardino PT, et al.: Patterns of high-grade prostatic intraepithelial neoplasia associated with clinically aggressive prostate cancer. Hum Pathol. 1998; 29::1119-1123. Cohen RJ, McNeal JE, Baillie T. : Patterns of differentiation and proliferation in intraductal carcinoma of the prostate: significance for cancer progression. Prostate. 2000;43:11-19. Dawkins HJ, Sellner LN, Turbett GR, et al.: Distinction between intraductal carcinoma of the prostate (IDC-P), high-grade dysplasia (PIN), and invasive prostatic adenocarcinoma, using molecular markers of cancer progression. Prostate. 2000;44:265-270. Reyes AO, Swanson PE, Carbone JM et al.: Unusual histologic types of high grade Prostatic intraepithelial Neoplasia. Am. J. Surg. Pathol. 1997; 21: 1215-1222. Weinstein MH.: Digital image analysis of proliferativo index: two distinct populations of high grade Prostatic intraepithelial Neoplasia in close proximity to adenocarcinoma of the prostate. Hum. Pathol. 1998; 29: 620-626. Bishara T, Ramnani DM, Epstein JI.: High-grade prostatic intraepithelial neoplasia on needle biopsy: risk of cancer on repeat biopsy related to number of involved cores and morphologic pattern. Am J Surg Pathol. 2004 ;28:629-633. Mosquera JM, Perner S, Demichelis F, Kim R, Hofer MD, Mertz KD, Paris PL, Simko J, Collins C, Bismar TA, Chinnaiyan AM, Rubin MA.: Morphological features of TMPRSS2-ERG gene fusion prostate cancer. J Pathol. 2007 ;212:91-101. Cohen RJ, Wheeler TM, Bonkhoff H, Rubin MA.: A proposal on the identification, histologic reporting, and implications of intraductal prostatic carcinoma. Arch Pathol Lab Med. 2007;131:1103-1109. Rubin MA, de La Taille A, Bagiella E, Olsson CA, O'Toole KM.: Cribriform carcinoma of the prostate and cribriform prostatic intraepithelial neoplasia: incidence and clinical implications. Am J Surg Pathol. 1998 ;22:840-848. Cohen RJ, Shannon BA, Weinstein SL.: Intraductal carcinoma of the prostate gland with transmucosal spread to the seminal vesicle: a lesion distinct from high-grade prostatic intraepithelial neoplasia. Arch Pathol Lab Med. 2007 ;131:1122-1125. Guo CC, Epstein JI.: Intraductal carcinoma of the prostate on needle biopsy: Histologic features and clinical significance. Mod Pathol. 2006 ;19:1528-1535.