Histology: A poorly differentiated adenocarcinoma is present on the prostate biopsy. The tumor cells are pleomorphic, in that they not uniform one to another. Numerous mitotic figures and apoptotic bodies are identified. Large areas of cellular necrosis are present. In addition, Gleason score 4+3=7 (Grade Group 3) adenocarcinoma is present with cytologically bland cells arranged in acini and cribriform structures. Immunohistochemical stains for CDX2 are diffusely positive.
Answer: C.
Discussion. The poorly differentiated tumor does not resemble Grade Group 5 adenocarcinoma of the prostate. First, the tumor is more pleomorphic without prominent nucleoli, whereas typical high grade prostate cancer has a more uniform appearance where each nucleus is enlarged with prominent nucleoli yet not significant variation in size and shape. Second, there is extensive necrosis, which also differs from usual high grade prostate cancer. Grade Group 5 prostate cancer can show uncommonly rounded nests of carcinoma with central necrosis, which in most cases represents intraductal carcinoma but can also on occasion be invasive carcinoma with necrosis. However, one does not see sheets of tumor with large areas of necrosis in Grade Group 5 prostate adenocarcinoma. Third, it would be exceptional for high grade prostate cancer to be negative for NKX3.1 and P501S with positivity for PSAP, given the greater sensitivity and specificity of the NKX3.1 and P501S. At our institution, the tumor was confirmed to be negative for NKX3.1, P501S, PSA, and GATA3. The tumor was strongly diffusely positive for CDX2, SATB2, CK20, and CK7. These findings along with the morphology is typical of a gastrointestinal tumor, although uncommonly prostate adenocarcinoma can express CDX2. Although CK7 and CK20 positivity is more usual for an upper GI or pancreaticobiliary primary, colorectal carcinoma can express both of these cytokeratins in approximately 15% of cases. Given that the morphology of the tumor in the prostate looks more like a lower than upper GI tumor and that colorectal carcinoma involves the prostate much more commonly than an upper GI/pancreaticobiliary carcinoma, the most likely diagnosis is spread from the lower GI tract. A bladder or prostatic urethral adenocarcinoma would have identical morphology and immunoexpression, but the negative cystoscopy virtually rules out this possibility. A misleading finding in the case was the presence of usual prostate adenocarcinoma, which in part lead the outside institution to consider a unifying diagnosis of prostate adenocarcinoma involving all the parts. However, prostate adenocarcinoma is common, such that occasionally there may be both usual prostate adenocarcinoma and a tumor from another site co-existing in the prostate.