Abstract：
BACKGROUND: Prostatic adenocarcinoma can occasionally display urothelial carcinoma morphology, which prompts immunohistochemistry (IHC) studies to determine its lineage. Typically, prostate cancer is characterized by the lack of cytokeratin (CK) 7, CK20 and high molecular weight keratin (HMWK) expression, as opposed to bladder cancer.
METHODS: We report a series of 12 prostatic adenocarcinoma cases with unusual urothelial-like morphology, diagnosed at two academic institutions in Toronto between 2018 and 2023, and analyzed by immunohistochemistry for prostatic, urothelial, and neuroendocrine marker expression. We collected patient age, androgen deprivation therapy (ADT) status, tumour site, histomorphology, Grade group (GG) and results of genetic testing.
RESULTS: The median age of the 12 patients included in this case series was 75.5 years (range 41-85). A history of prostatic cancer was noted in 7/12 (58%) patients. Five of nine (56%) patients had elevated serum PSA level at diagnosis. Six of eleven (55%) patients had prior ADT. Tumour sites were prostate (n = 6), bladder (n = 3), liver metastases (n = 2), and lung metastasis (n = 1). GGs of the primary tumours were GG3 (n = 1) and GG5 (n = 8). The observed urothelial-like morphology was diffuse in ten cases, and focal in two cases. CK7 was strong/diffuse in 8/11 tested cases, and focal weak in one case. CK20, HMWK, p63 and GATA3 were patchy/focal/weak/moderate in 3/6, 4/7, 4/8 and 2/9 cases, respectively. Ten (83%) cases were positive for at least one prostatic marker; eight (67%) cases had loss/weak staining of at least one prostatic marker. AR loss was seen in 2/7 (29%) cases. Seven of ten (70%) cases had diffuse/strong expression of at least one neuroendocrine marker. No trend was evident between prior ADT/AR status and any IHC result. Molecular analyses for DNA damage repair (DDR) genes (n = 6) demonstrated one ATM deletion (bladder). In addition, one TMPRSS2:ERG fusion (lung metastasis) was identified.
CONCLUSIONS: This series comprises high-grade and/or metastatic prostatic adenocarcinoma cases with distinctive urothelial-like morphology and frequent aberrant CK7/CK20/HMWK expression. Their histomorphology, highly suggestive of an urothelial origin, represents a diagnostic pitfall that can lead to considerable management repercussions. The fact that a high proportion of the reported cases had loss/weak expression of at least one of the tested prostatic-specific markers, and occasionally a diffuse positivity for neuroendocrine markers highlights the importance of (1) clinical history and (2) utilization of broad IHC panels to correctly diagnose such unusual prostate cancer cases.
METHODS: We report a series of 12 prostatic adenocarcinoma cases with unusual urothelial-like morphology, diagnosed at two academic institutions in Toronto between 2018 and 2023, and analyzed by immunohistochemistry for prostatic, urothelial, and neuroendocrine marker expression. We collected patient age, androgen deprivation therapy (ADT) status, tumour site, histomorphology, Grade group (GG) and results of genetic testing.
RESULTS: The median age of the 12 patients included in this case series was 75.5 years (range 41-85). A history of prostatic cancer was noted in 7/12 (58%) patients. Five of nine (56%) patients had elevated serum PSA level at diagnosis. Six of eleven (55%) patients had prior ADT. Tumour sites were prostate (n = 6), bladder (n = 3), liver metastases (n = 2), and lung metastasis (n = 1). GGs of the primary tumours were GG3 (n = 1) and GG5 (n = 8). The observed urothelial-like morphology was diffuse in ten cases, and focal in two cases. CK7 was strong/diffuse in 8/11 tested cases, and focal weak in one case. CK20, HMWK, p63 and GATA3 were patchy/focal/weak/moderate in 3/6, 4/7, 4/8 and 2/9 cases, respectively. Ten (83%) cases were positive for at least one prostatic marker; eight (67%) cases had loss/weak staining of at least one prostatic marker. AR loss was seen in 2/7 (29%) cases. Seven of ten (70%) cases had diffuse/strong expression of at least one neuroendocrine marker. No trend was evident between prior ADT/AR status and any IHC result. Molecular analyses for DNA damage repair (DDR) genes (n = 6) demonstrated one ATM deletion (bladder). In addition, one TMPRSS2:ERG fusion (lung metastasis) was identified.
CONCLUSIONS: This series comprises high-grade and/or metastatic prostatic adenocarcinoma cases with distinctive urothelial-like morphology and frequent aberrant CK7/CK20/HMWK expression. Their histomorphology, highly suggestive of an urothelial origin, represents a diagnostic pitfall that can lead to considerable management repercussions. The fact that a high proportion of the reported cases had loss/weak expression of at least one of the tested prostatic-specific markers, and occasionally a diffuse positivity for neuroendocrine markers highlights the importance of (1) clinical history and (2) utilization of broad IHC panels to correctly diagnose such unusual prostate cancer cases.
摘要：
背景：前列腺腺癌偶尔可以显示尿路上皮癌的形态，提示免疫组织化学（IHC）研究以确定其谱系。通常,前列腺癌的特点是缺乏细胞角蛋白（CK）7，CK20和高分子量角蛋白（HMWK）的表达，而不是膀胱癌。
方法：我们报告了一系列12例前列腺腺癌的尿路上皮样形态异常，2018年至2023年在多伦多的两个学术机构诊断，并通过免疫组织化学分析前列腺，尿路上皮,和神经内分泌标志物表达。我们收集了病人的年龄,雄激素剥夺治疗（ADT）状态，肿瘤部位，组织形态学,等级组（GG）和基因检测结果。
结果：纳入本病例系列的12名患者的中位年龄为75.5岁（范围41-85岁）。7/12（58％）患者有前列腺癌病史。9名患者中有5名（56％）在诊断时血清PSA水平升高。11名患者中有6名（55％）患有ADT。肿瘤部位为前列腺（n=6），膀胱（n=3），肝转移（n=2），和肺转移（n=1）。原发性肿瘤的GGs为GG3(n=1)和GG5(n=8)。10例观察到的尿路上皮样形态为弥漫性，和焦点在两个案例中。在8/11测试病例中CK7强/弥漫性，在一种情况下，焦点较弱。CK20,HMWK,p63和GATA3在3/6、4/7、4/8和2/9例中呈斑片状/局灶性/弱/中度，分别。10例(83%)对至少一种前列腺标记物呈阳性;8例(67%)对至少一种前列腺标记物具有缺失/弱染色。AR丢失见于2/7(29%)例。10例中的7例(70%)具有至少一种神经内分泌标志物的弥漫性/强表达。在先前的ADT/AR状态和任何IHC结果之间没有明显的趋势。DNA损伤修复（DDR）基因的分子分析（n=6）证明了一个ATM缺失（膀胱）。此外,鉴定出一个TMPRSS2:ERG融合(肺转移)。
结论：本系列包括高级别和/或转移性前列腺腺癌病例，具有独特的尿路上皮样形态和频繁的异常CK7/CK20/HMWK表达。他们的组织形态学,高度暗示尿路上皮起源，代表了一个诊断缺陷，可能导致相当大的管理影响。事实上，报告的病例中有高比例的至少一种被测试的前列腺特异性标志物缺失/弱表达，偶尔神经内分泌标志物的弥漫性阳性强调了(1)临床病史和(2)利用广泛的IHC面板正确诊断此类不寻常前列腺癌病例的重要性。
方法：我们报告了一系列12例前列腺腺癌的尿路上皮样形态异常，2018年至2023年在多伦多的两个学术机构诊断，并通过免疫组织化学分析前列腺，尿路上皮,和神经内分泌标志物表达。我们收集了病人的年龄,雄激素剥夺治疗（ADT）状态，肿瘤部位，组织形态学,等级组（GG）和基因检测结果。
结果：纳入本病例系列的12名患者的中位年龄为75.5岁（范围41-85岁）。7/12（58％）患者有前列腺癌病史。9名患者中有5名（56％）在诊断时血清PSA水平升高。11名患者中有6名（55％）患有ADT。肿瘤部位为前列腺（n=6），膀胱（n=3），肝转移（n=2），和肺转移（n=1）。原发性肿瘤的GGs为GG3(n=1)和GG5(n=8)。10例观察到的尿路上皮样形态为弥漫性，和焦点在两个案例中。在8/11测试病例中CK7强/弥漫性，在一种情况下，焦点较弱。CK20,HMWK,p63和GATA3在3/6、4/7、4/8和2/9例中呈斑片状/局灶性/弱/中度，分别。10例(83%)对至少一种前列腺标记物呈阳性;8例(67%)对至少一种前列腺标记物具有缺失/弱染色。AR丢失见于2/7(29%)例。10例中的7例(70%)具有至少一种神经内分泌标志物的弥漫性/强表达。在先前的ADT/AR状态和任何IHC结果之间没有明显的趋势。DNA损伤修复（DDR）基因的分子分析（n=6）证明了一个ATM缺失（膀胱）。此外,鉴定出一个TMPRSS2:ERG融合(肺转移)。
结论：本系列包括高级别和/或转移性前列腺腺癌病例，具有独特的尿路上皮样形态和频繁的异常CK7/CK20/HMWK表达。他们的组织形态学,高度暗示尿路上皮起源，代表了一个诊断缺陷，可能导致相当大的管理影响。事实上，报告的病例中有高比例的至少一种被测试的前列腺特异性标志物缺失/弱表达，偶尔神经内分泌标志物的弥漫性阳性强调了(1)临床病史和(2)利用广泛的IHC面板正确诊断此类不寻常前列腺癌病例的重要性。
