Department of Pathology, University of Massachusetts, UMass Memorial Medical Center, 1 Innovation Dr., Biotech 3 Bldg., 2nd Floor, Worcester, MA, USA.
Ann Diagn Pathol. 2021 Aug;53:151758. doi: 10.1016/j.anndiagpath.2021.151758. Epub 2021 May 8.
Anal squamous cell carcinoma (SqCC) is a morphologically heterogeneous entity. Basaloid and non-keratinizing anal SqCC may be confused with other tumors including neuroendocrine carcinoma due to morphologic overlap, and expression of neuroendocrine markers is not well-studied in anal SqCC. Prompted by a case of anal SqCC that was initially misdiagnosed as neuroendocrine carcinoma on the basis of morphology and CD56 expression, we retrospectively examined the expression of neuroendocrine markers CD56, synaptophysin, and chromogranin in 48 cases of basaloid anal SqCC, with clinicopathologic correlation. HPV16 was identified in 46 cases, HPV33 in one case, and one case was HPV-negative. Three (6.3%) cases demonstrated CD56 expression, including two with diffuse and one with focal expression. Two CD56-positive cases demonstrated basaloid morphology with peripheral palisading and the other demonstrated adenoid cystic/cylindroma-like morphology. None of the cases showed significant synaptophysin or chromogranin expression. The three cases expressing CD56 were HPV16-positive, and one demonstrated a CTNNB1 mutation. There was no difference in clinicopathologic features including stage, outcome, or HPV status, between CD56-positive and negative groups. Our findings support that CD56 expression is infrequently expressed in anal SqCC and is not indicative of neuroendocrine differentiation in the absence of expression of more specific neuroendocrine markers such as synaptophysin and chromogranin. Pathologists should be aware that CD56 expression may occur in basaloid anal SqCC and is a diagnostic pitfall due to morphologic overlap with neuroendocrine carcinoma and other tumors including basal cell carcinoma.
分析鳞状细胞癌（SqCC）是一种形态上具有异质性的实体。基底细胞样和非角化性肛门 SqCC 可能由于形态学重叠而与其他肿瘤（包括神经内分泌癌）混淆，并且神经内分泌标志物在肛门 SqCC 中的表达尚未得到充分研究。基于形态学和 CD56 表达，我们最初误诊为神经内分泌癌的肛门 SqCC 病例促使我们回顾性检查了 48 例基底细胞样肛门 SqCC 中神经内分泌标志物 CD56、突触素和嗜铬粒蛋白的表达，并进行了临床病理相关性分析。在 46 例病例中检测到 HPV16，1 例病例中检测到 HPV33，1 例病例 HPV 阴性。有 3 例（6.3%）病例表达 CD56，其中 2 例弥漫性表达，1 例局灶性表达。2 例 CD56 阳性病例表现为基底细胞样形态，伴有外周栅栏状排列，另 1 例表现为腺样囊性/圆柱瘤样形态。无明显突触素或嗜铬粒蛋白表达。表达 CD56 的 3 例病例均为 HPV16 阳性，其中 1 例存在 CTNNB1 突变。CD56 阳性和阴性组在临床病理特征（包括分期、预后或 HPV 状态）方面无差异。我们的研究结果表明，CD56 在肛门 SqCC 中的表达频率较低，在缺乏更特异性的神经内分泌标志物（如突触素和嗜铬粒蛋白）表达的情况下，并不提示神经内分泌分化。病理学家应该意识到，CD56 表达可能发生在基底细胞样肛门 SqCC 中，并且由于与神经内分泌癌和其他肿瘤（包括基底细胞癌）的形态学重叠，是一个诊断陷阱。
