Department of Pulmonary Diseases, GROW school for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, the Netherlands.
Pathology-DNA, Jeroen Bosch Hospitals', Hertogenbosch, the Netherlands.
Histopathology. 2019 Mar;74(4):555-566. doi: 10.1111/his.13800. Epub 2019 Jan 24.
Pulmonary large cell neuroendocrine carcinoma (LCNEC) is underdiagnosed on biopsy specimens. We evaluated if routine neuroendocrine immunohistochemical (IHC) stains are helpful in the diagnosis of LCNEC on biopsy specimens.
Using the Dutch pathology registry (PALGA), surgically resected LCNEC with matching pre-operative biopsy specimens were identified and haematoxylin and IHC slides (CD56, chromogranin-A, synaptophysin) requested. Subsequently, three pathologists assigned (1) the presence or absence of the WHO 2015 criteria and (2) cumulative size of all (biopsy) specimens. For validation, a tissue microarray (TMA) of non-small-cell lung cancer (NSCLC) (n = 77) and LCNEC (n = 19) was used. LCNEC was confirmed on the resection specimens in 32 of 48 re-reviewed cases. In 47% (n = 15 of 32) LCNEC was also confirmed in the paired biopsy specimens. Neuroendocrine morphology was absent in 53% (n = 17 of 32) of paired biopsy specimens, more often when smaller amounts of tissue were available for evaluation [29% < 5 mm (n = 14) versus 67% ≥5 mm (n = 18) P = 0.04]. Combined with current WHO criteria, positive staining for greater than or equal to two of three neuroendocrine IHC markers increased the sensitivity for LCNEC from 47% to 93% on paired biopsy specimens, and further validated using an independent TMA of LCNEC and NSCLC with sensitivity and specificity of 80% and 99%, respectively.
LCNEC is difficult to diagnose because neuroendocrine morphology is frequently absent in biopsy specimens. In NSCLC devoid of obvious morphological squamous or adenocarcinoma features, positive staining in greater than or equal to two of three neuroendocrine IHC stains supports the diagnosis of LCNEC.
肺大细胞神经内分泌癌（LCNEC）在活检标本中被误诊。我们评估常规神经内分泌免疫组织化学（IHC）染色是否有助于诊断活检标本中的 LCNEC。
使用荷兰病理学登记处（PALGA），确定了手术切除的 LCNEC 并匹配术前活检标本，并请求苏木精和 IHC 切片（CD56、嗜铬粒蛋白-A、突触素）。随后，三名病理学家分配（1）存在或不存在 2015 年 WHO 标准和（2）所有（活检）标本的累积大小。为了验证，使用非小细胞肺癌（NSCLC）（n=77）和 LCNEC（n=19）的组织微阵列（TMA）。在重新审查的 32 例病例中，有 32 例在切除标本中证实了 LCNEC。在 47%（n=15/32）的配对活检标本中也证实了 LCNEC。神经内分泌形态在 53%（n=32/32）的配对活检标本中缺失，当评估的组织量较少时更常见[29%（n=14）<5mm 与 67%（n=18）≥5mm，P=0.04]。与当前的 WHO 标准结合使用，大于或等于三种神经内分泌 IHC 标志物中的两种的阳性染色增加了配对活检标本中 LCNEC 的敏感性，从 47%增加到 93%，并使用 NSCLC 和 LCNEC 的独立 TMA 进一步验证，敏感性和特异性分别为 80%和 99%。
LCNEC 难以诊断，因为神经内分泌形态在活检标本中经常缺失。在缺乏明显形态学鳞癌或腺癌特征的 NSCLC 中，大于或等于三种神经内分泌 IHC 染色中的两种的阳性染色支持 LCNEC 的诊断。
