Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Am J Surg Pathol. 2011 Jan;35(1):127-34. doi: 10.1097/PAS.0b013e318200cf78.
The presence of mucin pools lacking neoplastic epithelium ("acellular" mucin) in resection specimens of rectal carcinoma after neoadjuvant chemoradiotherapy (CRT) is a well-recognized phenomenon. The current recommendation by the College of American Pathologists is to regard acellular mucin as a type of treatment response and not as residual tumor. However, data-based evidence for or against such an approach is incomplete. In this study, we systematically analyzed the pattern and significance of mucin pools in 108 consecutive, prospectively collected resection specimens from patients who had uT3-4 and/or uN1 rectal cancer and were treated with preoperative long-course CRT. The 108 patients, 39 female and 69 male, had a median age of 58.5 years. With every tumor entirely examined in whole-mount sections, mucin pools were identified in 33 cases (33 of 108, 31%); in 16 (15%) they were all acellular. The mucin pools were focal (10% to 50% of the entire lesion) in 25 cases and extensive (>50%) in 8 cases. Mucin pools were also noted in the lymph nodes in 6 cases (6%); 3 of these were entirely acellular. Five cases had mucin pools in both the primary site and the lymph nodes. When acellular mucin was considered as "no residual tumor," the complete pathologic response rate for the entire cohort was 22% (24 of 108). The pathologic stage of the residual tumor (ypT) was 0 or 1 for 27 cases (25%) and 2 to 4 for 81 cases. The pathologic stage of nodal disease (ypN) was 0 for 83 (77%) and 1 or 2 for 25 cases. When acellular mucin was considered as "residual tumor," the complete pathologic response rate dropped to 17%; ypT was upstaged in 10 tumors and ypN was upstaged in 2 tumors. With a median follow-up of 31 months, the 3-year recurrence-free survival (RFS) was 73% for the entire group. Advanced pathologic response and low pathologic stage of the residual tumor (determined based on the depth of only viable tumor cells) correlated significantly with better RFS. However, the correlation between pathologic response and RFS became insignificant when acellular mucin pools were considered as residual tumor. Neither the presence of mucin pools nor their extent or cellularity had an impact on RFS. Furthermore, none of the 12 patients whose ypT or ypN was upstaged by acellular mucin had recurrent disease (3-y RFS of 100%). Thus, our results suggest that mucin pools in rectal carcinoma after neoadjuvant CRT do not have a significant impact on patient outcome, supporting the College of American Pathologists recommendation that only viable tumor cells, not acellular mucin, are to be interpreted as residual disease in the tumor pathologic staging.
新辅助放化疗（CRT）后直肠腺癌切除标本中存在缺乏肿瘤上皮的粘蛋白池（“无细胞”粘蛋白）是一种公认的现象。美国病理学家学院目前的建议是将无细胞粘蛋白视为一种治疗反应，而不是残留肿瘤。然而，这种方法的基于数据的证据并不完整。在这项研究中，我们系统地分析了 108 例连续前瞻性收集的直肠腺癌切除标本中粘蛋白池的模式和意义，这些患者均患有 uT3-4 和/或 uN1 直肠癌，并接受了术前长程 CRT 治疗。这 108 例患者中，女性 39 例，男性 69 例，中位年龄为 58.5 岁。通过对所有肿瘤进行全切片检查，在 33 例（33/108，31%）中发现粘蛋白池；其中 16 例（15%）全部为无细胞。粘蛋白池在 25 例中为局灶性（整个病变的 10%至 50%），在 8 例中为广泛性（>50%）。在 6 例（6%）淋巴结中也发现粘蛋白池；其中 3 例完全无细胞。5 例在原发灶和淋巴结中均有粘蛋白池。当无细胞粘蛋白被视为“无残留肿瘤”时，整个队列的完全病理缓解率为 22%（108 例中有 24 例）。残留肿瘤的病理分期（ypT）对于 27 例（25%）为 0 或 1，对于 81 例为 2 至 4。淋巴结疾病的病理分期（ypN）对于 83 例（77%）为 0，对于 25 例为 1 或 2。当无细胞粘蛋白被视为“残留肿瘤”时，完全病理缓解率下降至 17%；10 例肿瘤 ypT 分期升高，2 例 ypN 分期升高。中位随访 31 个月后，整个组的 3 年无复发生存率（RFS）为 73%。高级别的病理反应和残留肿瘤的低病理分期（仅基于存活肿瘤细胞的深度确定）与更好的 RFS 显著相关。然而，当考虑无细胞粘蛋白池为残留肿瘤时，病理反应与 RFS 之间的相关性变得不显著。粘蛋白池的存在、其范围或细胞性均与 RFS 无关。此外，无细胞粘蛋白使 ypT 或 ypN 分期升高的 12 例患者中，均无疾病复发（3 年 RFS 为 100%）。因此，我们的结果表明，新辅助 CRT 后直肠腺癌中的粘蛋白池对患者预后没有显著影响，支持美国病理学家学院的建议，即只有存活的肿瘤细胞，而不是无细胞粘蛋白，应被解释为肿瘤病理分期中的残留疾病。
