非小细胞肺癌病理学检查原则NCCN指南2016v4

NSCLC NCCN2016V4 PRINCIPLES OF PATHOLOGIC REVIEW
病理学检查原则

Pathologic Evaluation
病理评估

* The purpose of pathologic evaluation is to classify the histologic type of lung cancer and to determine all staging parameters as recommended by the AJCC, including tumor size, the extent of invasion (pleural and bronchial), adequacy of surgical margins, and presence or absence of lymph node metastasis.山东省肿瘤医院呼吸肿瘤内科张品良
*病理评估的目的是分类肺癌的组织学类型并确定AJCC推荐的所有分期数据，包括肿瘤大小、浸润程度（胸膜、支气管）、手术切缘是否适当以及有或无淋巴结转移。

Further, determination of the specific molecular abnormalities of the tumor is critical for predicting sensitivity or resistance to an increasing number of drugable targets, primarily tyrosine kinase inhibitors (TKIs) (see Molecular Diagnostic Studies in Lung Cancer in this section).
此外，测定肿瘤特定的分子异常是预测越来越多的drugable靶向药物敏感性或抵抗性的关键，主要是酪氨酸激酶抑制剂（TKIs）（见本节中的肺癌分子诊断研究）。

* The WHO tumor classification system has historically provided the foundation for the classification of lung tumors, including histologic types, clinical features, staging considerations, and the molecular, genetic, and epidemiologic aspects of lung cancer.
*多年来WHO肿瘤分类系统为肺肿瘤的分类提供了基础，包括组织学类型、临床特征、分期需要考虑的事项以及肺癌的分子、遗传学和流行病学特征的研究。

* The pathology diagnostic report should include the histologic classification as described by the WHO for carcinomas of the lung.
*病理诊断报告应包括WHO对肺癌描述的组织学分类。

The recently published classification of adenocarcinoma should be used for this tumor subtype in resection specimens and small biopsies.
在切除标本和小活检中对于这一肿瘤亚型应该使用最近公布的腺癌分类。

Use of bronchioloalveolar carcinoma (BAC) terminology is strongly discouraged.
强烈反对使用细支气管肺泡癌（BAC）术语。

* The generic term “non-small cell lung cancer (NSCLC)” should be avoided as a single diagnostic term.
*术语“非小细胞肺癌（NSCLC）”应避免作为一个单独的诊断术语。

In small biopsies of poorly differentiated carcinomas where immunohistochemistry (IHC) is used, the following terms are acceptable: “NSCLC favor adenocarcinoma” or “NSCLC favor squamous cell carcinoma.”
在使用免疫组化（IHC）的低分化癌小活检中，下列术语是可以接受的：“NSCLC支持腺癌”或“NSCLC支持鳞状细胞癌。”

Mutational testing (eg, epidermal growth factor receptor [EGFR]) is strongly recommended in all NSCLC favor adenocarcinomas.
在所有支持腺癌的NSCLC中强烈建议突变检测（如，表皮生长因子受体[EGFR] ）。

* Formalin-fixed paraffin-embedded tumor is acceptable for most molecular analyses.
*对于大多数的分子分析，福尔马林固定石蜡包埋的肿瘤是可以接受的。

* Limited use of IHC studies in small tissue samples is strongly recommended, thereby preserving critical tumor tissue for molecular studies, particularly in patients with advanced-stage disease.
*在小组织标本中强烈建议限制使用免疫组化研究，从而保留关键的肿瘤组织用于分子研究，尤其是在晚期疾病患者中。

A limited panel of one squamous cell carcinoma marker (eg, p63, p40) and one adenocarcinoma marker (eg, TTF-1, napsin A) should suffice for most diagnostic problems.
对于大多数诊断问题，一个鳞状细胞癌标记 （如，p63、p40） 和一个腺癌标记 （如，TTF-1、新天冬氨酸蛋白酶A） 的有限组合应该足够。

Adenocarcinoma Classification
腺癌的分类

* Adenocarcinoma in situ (AIS; formerly BAC): ≤3 cm nodule, lepidic growth, mucinous, non-mucinous, or mixed mucinous/non-mucinous types.
*原位腺癌（AIS；原名BAC）：结节≤75px、贴壁生长、黏液性、非黏液性或黏液/非黏液混合性。

* Minimally invasive adenocarcinoma (MIA): ≤3 cm nodule with ≤5 mm of invasion, lepidic growth, mucinous, non-mucinous, or mixed mucinous/non-mucinous types.
*微浸润腺癌（MIA）：结节≤75px、浸润≤5mm、贴壁生长、黏液性、非黏液性或黏液/非黏液混合性。

* Invasive adenocarcinoma, predominant growth pattern: lepidic >5 mm of invasion, acinar, papillary, micropapillary, or solid with mucin.
＊浸润腺癌，主要的生长模式：贴壁浸润> 5mm、腺泡状、乳头状、微乳头状或伴有黏液的实体瘤。

* Invasive adenocarcinoma variants: mucinous adenocarcinoma, colloid, fetal, and enteric morphologies.
*浸润腺癌：黏液腺癌、胶冻、胚胎及肠道形态。

Immunohistochemical Staining
免疫组化染色

* Judicious use of IHC is strongly recommended to preserve tissue for molecular testing.
*强烈建议明智使用IHC以保留组织用于分子检测。

IHC should be utilized only after consideration of all data including routine H&E histology, clinical findings, imaging studies, and patient’s history.
只应该在评估所有的资料包括常规H&E组织学、临床表现、影像学检查及患者的病史之后才考虑利用IHC。

* Although the concordance is generally good between the histologic subtype and the immunophenotype seen in small biopsies compared with surgical resection specimens, caution is advised in attempting to subtype small biopsies with limited material or cases with an ambiguous immunophenotype.
*与手术切除的标本相比，小活检标本的组织学亚型和免疫表型之间尽管观察到的一致性总体而言是好的，但是，建议试图对材料有限的小活检或免疫表型模棱两可的患者进行亚型诊断时应慎重。

* IHC should be used to differentiate primary pulmonary adenocarcinoma from the following: squamous cell carcinoma, large cell carcinoma, metastatic carcinoma, and malignant mesothelioma; to determine whether neuroendocrine differentiation is present.
*为鉴别原发性肺腺癌与下列疾病：鳞状细胞癌、大细胞癌、转移癌以及恶性间皮瘤，应该使用IHC以确定是否存在神经内分泌分化。

* Primary pulmonary adenocarcinoma
*原发性肺腺癌

→ In patients for whom the primary origin of the carcinoma is uncertain, an appropriate panel of immunohistochemical stains is recommended to exclude metastatic carcinoma to the lung.
→ 在肿瘤原发部位尚不明确的患者中，建议适当的免疫组化染色组合以排除肺转移性癌。

→ TTF-1 is a homeodomain-containing nuclear transcription protein of the Nkx2 gene family that is expressed in epithelial cells of the embryonal and mature lung and thyroid.
→ 甲状腺转录因子1（TTF-1）是Nkx2基因家族的一种含同源结构域的核转录蛋白，在肺和甲状腺胚胎和成熟的上皮细胞中表达。

TTF-1 immunoreactivity is seen in primary pulmonary adenocarcinoma in the majority (70%–100%) of non-mucinous adenocarcinoma subtypes.
在原发性肺腺癌中见到甲状腺转录因子1（TTF-1）免疫反应性大多数（70%–100%）为非黏液腺癌亚型。

Metastatic adenocarcinoma to the lung is virtually always negative for TTF-1 except in metastatic thyroid malignancies, in which case thyroglobulin is also positive.
肺转移性腺癌除了转移性甲状腺恶性肿瘤TTF-1几乎总是阴性，在这种情况下，甲状腺球蛋白也阳性。

→ Napsin A - an aspartic proteinase expressed in normal type II pneumocytes and in proximal and distal renal tubules - appears to be expressed in >80% of lung adenocarcinomas and may be a useful adjunct to TTF-1.
→ 新天冬氨酸蛋白酶A（Napsin A）——在正常肺泡Ⅱ型上皮细胞和肾小管近端与远端表达的一种天门冬氨酸蛋白酶——似乎在80%以上的肺腺癌中表达，因此TTF-1辅助可能是有用的。

→ The panel of TTF-1 (or alternatively napsin A) and p63 (or alternatively p40) may be useful in reining the diagnosis to either adenocarcinoma or squamous cell carcinoma in small biopsy specimens previously classified as NSCLC NOS.
→ 在既往分类为NSCLC NOS的小活检标本中，在“驾驭”腺癌或鳞状细胞癌诊断时，TTF-1（或者可选择Napsin A）和p63（或者可选择p40）组合可能是有用的。

* Neuroendocrine differentiation
*神经内分泌分化

→ CD56, chromogranin, and synaptophysin are used to identify neuroendocrine tumors.
→ CD56、嗜铬素以及突触素用于鉴别神经内分泌肿瘤。

* Malignant mesothelioma versus pulmonary adenocarcinoma
＊恶性间皮瘤与肺腺癌

→ The distinction between pulmonary adenocarcinoma and malignant mesothelioma (epithelial type) can be made by correlation of the histology with the clinical impression, imaging studies, and a limited panel of immunomarkers if needed.
→ 鉴别肺腺癌与恶性间皮瘤（上皮型）可以根据组织学与临床印象、影像检查的相互关系以及如果需要有限的免疫标记组合做出诊断。

→→Immunostains relatively sensitive and specific for mesothelioma include WT-1, calretinin, D2-40, HMBE-1, and cytokeratin 5/6 (negative in adenocarcinoma).
→→对于间皮瘤比较敏感且特异的免疫标记包括Wilm's肿瘤基因（WT-1）、钙结合蛋白，D2-40、HMBE-1和细胞角蛋白5/6（在腺癌中阴性）。

→→Antibodies immunoreactive in adenocarcinoma include CEA, B72.3, Ber-EP4, MOC31, CD15, claudin-4, and TTF-1 (negative in mesothelioma).
→→在腺癌中免疫反应性抗体包括CEA、B72.3、Ber-EP4、MOC31、CD15、紧密连接蛋白-4和TTF-1（在间皮瘤中阴性）。