Department of Pathology, Johns Hopkins University, Baltimore, MD, USA.
Am J Surg Pathol. 2010 Jul;34(7):965-9. doi: 10.1097/PAS.0b013e3181dc5e8a.
Collecting duct carcinoma (CDC) is a relatively rare but aggressive type of renal malignancy with variable morphologic features. One of the World Health Organization diagnostic criteria for CDC is the exclusion of urothelial carcinoma of renal pelvis from the differential diagnosis. PAX8 is a novel lineage restricted transcription factor expressed in renal tubules. We investigated the expression pattern of PAX8 in CDC and its utility, in combination with p63, in resolving the differential diagnosis of CDC versus upper tract urothelial carcinoma (UUC).
Archival tissues from 21 CDC and 34 UUC were retrieved from our institutional files. Immunohistochemistry for PAX8 and p63 were performed on routine and tissue microarray sections using standard immunohistochemistry protocol. Intensity of nuclear staining was evaluated for each marker and assigned an incremental 0, 1+, 2+, and 3+ score. Extent of staining was categorized as focal (<25%), nonfocal (25% to 75%), or diffuse (>75%).
CDC: All 21 (100%) CDC were positive for PAX8. Intensity of expression was moderate to strong (2+/3+) in 19 cases (90%). Extent of staining was diffuse in 13 of 21 tumors. The p63 was positive in 3 of 21 (14%) CDC cases (PAX8+/p63+). UUC: The 34 UUC included 5 pT1, 4 pT2, and 25 pT3/pT4 tumors. Thirty-one of 34 (91.2%) UUC were negative for PAX8, whereas 33 of 34 (97%) were p63 positive. Staining intensity was moderate in 15 cases (44%), of which 12 were nonfocal or diffuse. The unique p63-negative UUC was a pT1 tumor that was also negative for PAX8 (PAX8-/p63-).
We propose the use of the combination of PAX8 and p63 in the diagnosis of poorly differentiated renal sinus epithelial neoplasms where the differential diagnosis includes CDC versus UUC. The immunoprofile of PAX8+/p63- supports the diagnosis of CDC with a sensitivity of 85.7% and a specificity of 100%. In contrast, a (PAX8-/p63+) profile supports the diagnosis of UUC with a sensitivity of 88.2% and a specificity of 100%. The inverse PAX8/p63 expression seen in CDC and UUC supports a renal tubular rather than an urothelial differentiation in CDC given the nephric lineage restriction of PAX8.
集合管癌（CDC）是一种相对罕见但具有侵袭性的肾恶性肿瘤，其形态特征存在差异。世界卫生组织诊断 CDC 的标准之一是排除肾盂尿路上皮癌的鉴别诊断。PAX8 是一种新型的组织特异性转录因子，在肾小管中表达。我们研究了 PAX8 在 CDC 中的表达模式及其与 p63 联合应用于解决 CDC 与上尿路尿路上皮癌（UUC）鉴别诊断的作用。
从我院档案中检索到 21 例 CDC 和 34 例 UUC 的存档组织。使用标准免疫组织化学方案，在常规和组织微阵列切片上进行 PAX8 和 p63 的免疫组织化学染色。评估每个标志物的核染色强度，并分配递增的 0、1+、2+和 3+评分。染色程度分为局灶性（<25%）、非局灶性（25%至 75%）或弥漫性（>75%）。
CDC：所有 21 例（100%）CDC 均为 PAX8 阳性。19 例（90%）的表达强度为中度至强（2+/3+）。21 例肿瘤中有 13 例弥漫性染色。PAX8+/p63+在 3 例（14%）CDC 病例中为阳性。UUC：34 例 UUC 中包括 5 例 pT1、4 例 pT2 和 25 例 pT3/pT4 肿瘤。34 例 UUC 中有 31 例（91.2%）PAX8 阴性，而 34 例中有 33 例（97%）p63 阳性。15 例（44%）的染色强度为中度，其中 12 例为非局灶性或弥漫性。唯一的 p63 阴性 UUC 是 pT1 肿瘤，也为 PAX8 阴性（PAX8-/p63-）。
我们建议在诊断分化不良的肾窦上皮肿瘤时，使用 PAX8 和 p63 的组合来进行诊断，包括 CDC 与 UUC 的鉴别诊断。PAX8+/p63-的免疫组化表现支持 CDC 的诊断，其敏感性为 85.7%，特异性为 100%。相反，（PAX8-/p63+）表现支持 UUC 的诊断，其敏感性为 88.2%，特异性为 100%。CDC 和 UUC 中 PAX8 和 p63 的反向表达支持 CDC 中肾小管而非尿路上皮分化，因为 PAX8 受到肾系的限制。
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