Rossi Giulio, Pelosi Giuseppe, Barbareschi Mattia, Graziano Paolo, Cavazza Alberto, Papotti Mauro
Azienda Arcispedale S Maria Nuova/IRCCS, Reggio Emilia, Italy.
Int J Surg Pathol. 2013 Aug;21(4):326-36. doi: 10.1177/1066896913489346. Epub 2013 Jun 5.
Morphology still remains the cornerstone in lung cancer classification and cytology and small biopsy samples should be interpreted by morphology, whenever feasible, according to shared and widely agreed-upon diagnostic schemes. However, as novel therapy strategies are being offered on the basis of the diverse tumor characteristics, pathologists are now challenged by the need to offer clinicians more detailed typing of non-small cell lung cancer, not otherwise specified (NSCLC-NOS), especially when dealing with limited diagnostic material or poorly differentiated tumors. Close integration of morphology, immunohistochemistry, and clinical data is highly warranted according to a multidisciplinary approach to limit the category of NSCLC-NOS as much as possible or exclude unsuspected metastases, so rendering more definite and clinically useful diagnoses. Among the many proposed immunohistochemical markers, which as a whole are more practical and diagnostically useful than cumbersome and expensive molecular assays, a 2-hit model including thyroid transcription factor-1 (TTF-1) and p40 (the latter more specific for squamous differentiation than p63) seems to be the most effective to basically highlight adenocarcinoma (positivity for TTF-1 regardless of p63) and squamous (always strongly and diffusely positive for p40 or p63 and negative for TTF-1) differentiation. This minimalist 2-hit diagnostic approach paves the way to novel perspectives in clinical trials on lung cancer, and it is also in keeping with the need of strategically preserving diagnostic material for molecular assays that are essential for personalizing therapies.
形态学仍然是肺癌分类的基石，只要可行，细胞学和小活检样本都应根据共同且广泛认可的诊断方案，通过形态学进行解读。然而，由于基于不同肿瘤特征提供了新的治疗策略，病理学家现在面临着挑战，即需要为临床医生提供更详细的非小细胞肺癌（未另行指定，NSCLC-NOS）分型，尤其是在处理有限的诊断材料或低分化肿瘤时。根据多学科方法，将形态学、免疫组织化学和临床数据紧密结合非常必要，以尽可能限制NSCLC-NOS的类别或排除意外转移，从而做出更明确且对临床有用的诊断。在众多提出的免疫组织化学标志物中，整体而言，它们比繁琐且昂贵的分子检测更实用且对诊断更有帮助，一种包括甲状腺转录因子-1（TTF-1）和p40（后者比p63对鳞状分化更具特异性）的双靶点模型似乎是最有效的，基本上可以突出腺癌（无论p63如何，TTF-1呈阳性）和鳞状细胞癌（p40或p63始终呈强阳性且弥漫性阳性，TTF-1呈阴性）的分化。这种极简的双靶点诊断方法为肺癌临床试验开辟了新视角，也符合战略性保留用于个性化治疗所必需的分子检测诊断材料的需求。
