Answer: A - Prostate adenocarcinoma, grade group 1 and intraductal carcinoma

Prostate carcinoma (PCa) commonly shows an indolent clinical course, and the management and outcome of the disease is closely dependent on grade (reported as Gleason score/grade group system) and tumor stage (TNM system).

Intraductal carcinoma of prostate (IDC-P) is extension of neoplastic cells in dilated prostate glands which maintain normal architecture (including intact basal layer/basement membrane). The morphological features of IDC-P includes identification of enlarged glands with overtly populated neoplastic cells forming cribriform structures, papillary/micropapillary structures or solid sheets, with or without central necrosis. Neoplastic cells often show marked nuclear atypia (defined as 6 times the size of normal cells). By definition, IDC-P is not invasive carcinoma and should not be included in the grading (Based on the current guidelines by the Genitourinary Pathology Society (GUPS), Gleason grading is used only for invasive prostate adenocarcinoma). However, IDC-P is commonly associated with invasive carcinoma of high grade.

In the current case, the large cellular cribriform clusters reveal intact basilar layer (highlighted by P63 and HMWCK in PIN4 stain); therefore they represent IDC-P. Adjacent to the IDC-P, there are clusters of small back-to-back glands predominantly showing open lumina, and a minority of poorly-formed glands. These neoplastic glands do not have basilar layer (negative for P63). Aberrant expression of HMWCK (as seen in some neoplastic glands) has been reported in prostate adenocarcinoma, and does not confer the malignant diagnosis. Having few (<5) poorly formed glands admixed with well-formed glands should not be interpreted as Gleason pattern 4; therefore Gleason score for the case is 3+3=6 (Grade Group 1).

It is very important that presence of IDC-P is included in the final report, with a note that almost all cases with similar morphology have been associated with infiltrating high-grade aggressive adenocarcinoma and definitive treatment (with radical surgery or radiation therapy) is recommended.

Choice #2 is not correct because IDC-P is not included in Gleason score. Choice #3 is not correct because the large clusters are highly cellular and do not represent HGPIN.

References

Khani F, Epstein JI. Prostate Biopsy Specimens With Gleason 3+3=6 and Intraductal Carcinoma: Radical Prostatectomy Findings and Clinical Outcomes. Am J Surg Pathol. 2015 Oct;39(10):1383-9

Amin A. Prostate Ductal Adenocarcinoma. Appl Immunohistochem Mol Morphol. 2018 Aug;26(7):514-521.

Epstein JI, Hirsch MS. A Comparison of Genitourinary Pathology Society (GUPS) and International Society of Urological Pathology (ISUP) Prostate Cancer Grading Guidelines. Am J Surg Pathol. 2021 Jul 1;45(7):1005-1007.