Lesions of Ductal Morphology in the Prostate/In Reply

Archives of Pathology & Laboratory Medicine,  Mar 2008  by Pickup, Michael,  Van der Kwast, Theodorus H,  Cohen, Ronald J,  Wheeler, Thomas M,  Bonkhoff, Helmut,  Rubin, Mark A

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To the Editor.-During the last few decades, lesions with ductal morphology in the prostate have raised considerable controversy. This includes the distinction of a subset of lumen-spanning neoplastic proliferations within distended prostatic ducts from the more common forms of high-grade prostatic intraepithelial neoplasia (eg, those with tufted, micropapillary, and flat architecture) and the separate categorization of ductal adenocarcinoma of the prostate. In their recent authoritative review of the subject, 4 eminent urogenital pathologists1 make a proposal on the reporting of these lesions in pathologic practice. Strikingly, the outcome of their analysis is largely in line with another review on the same topic.2 Both reviews recommend reporting intraductal carcinoma as a separate entity based on (1) the feasibility of defining histopathologic criteria that allow its distinction from high-grade prostatic intraepithelial neoplasia and adenocarcinoma and (2) its unfavorable clinical impact as compared to high-grade prostatic intraepithelial neoplasia. Furthermore, both reviews propose to include intraductal carcinoma identified in a prostate biopsy specimen in the Gleason score (as grade 4 or 5) in the rare event that prostate core biopsy specimens contain grade 3 carcinoma associated with intraductal carcinoma, resulting in at least a Gleason score 7. Although Gleason himself failed to separate intraductal carcinoma (cribri-form or comedo-type) from invasive carcinoma, the recognition of intraductal carcinioma would not impact the Gleason grading system.

The review by Cohen et al3 is somewhat contradictory with regard to their recommendation of repeat biopsies in the rare instance of an isolated intraductal carcinoma identified in prostate biopsy specimens. At one point the authors suggest that this finding should immediately lead to a radical prostatectomy without further exploration for the presence of invasive carcinoma. In their final recommendations, however, an early repeat biopsy is recommended. In our opinion the latter would be advised, as it seems that occasionally intraductal carcinoma may not be associated with invasive disease.3 It may otherwise be difficult to explain to the urologist and patient after radical prostatectomy that major surgery was performed for noninvasive disease.

A difference in opinion seems to emerge from the point of view of Cohen et al that ductal adenocarcinoma can be superseded by the unifying term intraductal carcinoma of the prostate.1 There is indeed no clear reason to consider ductal adenocarcinoma as a separate category of prostatic adenocarcinoma, as proposed in the World Health Organization classification of prostate tumors, 4 since it is generally associated with conventional (acinar) adenocarcinoma. In our opinion, ductal adenocarcinoma should be considered as a variant of prostatic adenocarcinoma, much as mucinous and clear cell carcinomas are considered variants. There are sound morphologic and clinical reasons for this view: (1) its characteristic morphology, particularly the tall columnar cell type lining true papillary formations; (2) the urinary obstructive symptoms if located centrally within the prostate; and (3) its identification late in the disease course as a consequence of the slow rise in prostate-specific antigen levels. Similar to the situation with all other adenocarcinomas, we do not see any reason to categorize the ductal adenocarcinomas within the group of intraductal carcinomas, given their generally evident invasive character.

MICHAEL PICKUP, MD

Department of Pathology

University Health Network

Toronto, Ontario, Canada M5G 2C4

THEODORUS H. VAN DER KWAST, MD

Department of Pathology and Laboratory Medicine

Mount Sinai Hospital

Toronto, Ontario, Canada M5G 1X5

1. Cohen RJ, Wheeler TM, Bonkhoff H, Rubin MA. A proposal on the identification, histological reporting, and implications of intraductal prostatic carcinoma. Arch Pathol Lab Med. 2007;131:1103-1109.

2. Pickup M, Van der Kwast TH. My approach to: intraductal lesions of the prostate gland. J Clin Pathol. 2007;60:856-865.

3. Cohen RJ, Shannon BA, Weinstein SL. In-traductal 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.

4. Yang XJ, Cheng L, Helpap B, Samaratunga H. Ductal carcinoma. In: Eble JN, Sauter G, Ep-stein JI, Sesterhenn IA, eds. Pathology and Genetics of Tumours of the Urinary System and Male Genital Organs. Lyon, France: IARC Press; 2004:199-201. World Health Organization Classification of Tumours.

The authors have no relevant financial interest in the products or companies described in this article.

In Reply.-Pickup and Van der Kwast propose that ductal adenocarcinoma of the prostate gland should be considered a variant of prostatic adeno-carcinoma, rather than incorporated within the unifying classification of intraductal carcinomas as they believe we have suggested in our review article.1 We have carefully considered this important issue but stand by our position that any lesions with so-called ductal morphology (ie, lumen-spanning neoplastic cells with papillary/trabecular, cribriform, or solid architecture) should be classified as: (1) intraductal carcinoma of the prostate (IDC-P) if surrounded by a complete or partial basal cell layer or (2) invasive adenocarcinoma if a basal cell layer is not detectable by immunostaining, assigned Gleason grade 3, 4, or 5 if comedonecrosis is present. Under our proposed system, invasive ductal adenocarcinoma, as defined by lesions with "ductal mor-phology" but no surrounding basal cell layer, would be simply classified as invasive adenocarcinoma, not IDC-P. Such cases may be recognized by some pathologists as a morphologic variant of prostatic adenocarci-noma, as with mucinous or clear-cell variants. However this "ductal" morphologic variant has not been associated with any prognostic implications independent of tumor Gleason grade or pathologic stage,2 and there is evidence that this term should no longer be used.3 We therefore see no reason to discuss it separately from other types of invasive prostatic ad-enocarcinoma. The focus of our article was on the identification, histolog-ic reporting, and clinical implications of IDC-P, and the importance of distinguishing this lesion from high-grade prostatic intraepithelial neoplasia.