肺癌 Lung Cancer 2019.1.1 頃最終更新

京大では最初は伝統的？に
Organ, laterality-tumor site, procedure:
- Histologic type.
で初めて，あとは synoptic風 に記載（原則）。

【記載例】
Lung, left upper lobectomy:
- Papillary adenocarcinoma, G2.
    Immunohistochemistry:
        ALK (D5F3): Negative
        ROS1: Positive
    Tumor size: 2.8 x 2.5 x 2.0 cm (invasive 1.6 cm)
    Pattern: papillary 60%, acinar 30%, lepidic 10%
    Spread through air spaces (STAS): Not idenfied
    Others: pm0, pl0, Ly0, V0, br-, pa-, pv-
    Stage: pT1c pN0
Lymph node, dissection:
- No evidence of malignancy.

上記の記載法だと，intrapulmonary metastasis (pm), pleural invasion (pl), lymphovascular invasion (Ly, V), bronchial/vascular margin (br, pa, pv) は others に入れている。

Grade は必須ではないかも
G1 = lepidic
G2 = papillary, acinar, invasive mucinous
G3 = solid, micropapillary

リンパ節はN1 が Station 10〜14 (それぞれ Hilar nodes, Interlobar nodes, Lobar nodes, Segmental nodes,  Subsegmental nodes）。N2 が Station 1〜9 (それぞれ Lower cervical, supraclavicular, and sternal notch nodes, Upper paratracheal nodes, Prevascular and retrotracheal nodes, Lower paratracheal nodes, Subaortic nodes (aorto-pulmonary window), Paraaortic nodes (ascending aorta or phrenic), Subcarinal nodes, Paraesophageal nodes (below carina), Pulmonary ligament nodes)。

肺腫瘍の分類

WHO Classification of tumors of the lung (2015)	ICD-O code
Epithelial tumors	* = new
Adenocarcinoma	8140/3
Lepidic adenocarcinoma	8250/3*
Acinar adenocarcinoma	8551/3*
Papillary adenocarcinoma	8260/3
Micropapillaryadenocarcinoma	8265/3
Solid adenocarcinoma	8230/3
Invasive mucinous adenocarcinoma	8253/3*
Mixed invasive mucinous and non-mucinous adenocarcinoma	8254/3*
Colloid adenocarcinoma	8480/3
Fetal adenocarcinoma	8333/3
Enteric adenocarcinoma	8144/3
Minimally invasive adenocarcinoma, non-mucinous	8250/2*
Minimally invasive adenocarcinoma, mucinous	8257/3*
Preinvasive lesions	8250/0*
Atypical adenomatous hyperplasia	8140/2
Adenocarcinoma in situ, non-mucinous	8410/2
Adenocarcinoma in situ, mucinous	8253/2
Squamous cell carcinoma	8070/3
Keratinizing squamous cell carcinoma	8071/3
Non-keratinizing squamous cell carcinoma	8072/3
Basaloid squamous cell carcinoma	8083/3
Preinvasive lesion
Squamous cell carcinoma in situ	8070/2
Neuroendocrine tumours
Small cell carcinoma	8041/3
Combined small cell carcinoma	8045/3
Large cell neuroendocrine carcinoma	8013/3
Combined large cell neuroendocrine carcinoma	8013/3
Carcinoid tumours
Typical carcinoid	8240/3
Atypical carcinoid	8249/3
Preinvasive lesion
Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia	8040/0*
Large cell carcinoma	8012/3
Adenosquamous carcinoma	8560/3
Pleomorphic carcinoma	8022/3
Spindle cell carcinoma	8032/3
Giant cell carcinoma	8031/3
Carcinosarcoma	8980/3
Pulmonary blastoma　肺芽腫	8972/3
Other and unclassified carcinomas
Lymphoepithelioma-like carcinoma	8082/3
NUT carcinoma	8023/3*
Salivary gland-type tumours
Mucoepidermoid carcinoma	8430/3
Adenoid cystic carcinoma	8200/3
Epithelial-myoepithelial carcinoma	8562/3
Pleomorphic adenoma	8940/0
Papillomas 乳頭腫
Squamous cell papilloma	8052/0
Exophytic	8052/0
Inverted	8053/0
Glandular papilloma	8260/0
Mixed squamous cell and glandular papilloma	8560/0
Adenomas 　腺腫
Sclerosing pneumocytoma (硬化性肺細胞腫 = sclerosing hemangioma)	8832/0
Alveolar adenoma	8251/0
Papillary adenoma	8260/0
Mucinous cystadenoma	8470/0
Mucous gland adenoma	8480/0
Mesenchymal tumours
Pulmonary hamartoma	8992/0
Chondroma	9220/0
PEComatous tumours
Lymphangioleiomyomatosis	9174/1
PEComa, benign	8714/0
Clear cell tumour	8005/0
PEComa, malignant	8714/3
Congenital peribronchial myofibroblastic tumour	8827/1
Diffuse pulmonary lymphangiomatosis
Inflammatory myofibroblastic tumour	8825/1
Epithelioid haemangioendothelioma	9133/3
Pleuropulmonary blastoma	8973/3
Synovial sarcoma	9040/3
Pulmonary artery intimal sarcoma	9137/3
Pulmonary myxoid sarcoma with EWSR1-CREB1 translocation	8842/3*
Myoepithelial tumours
Myoepithelioma	8982/0
Myoepithelial carcinoma	8982/3
Lymphohistiocytic tumours
Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma)	9699/3
Diffuse large B-cell lymphoma	9680/3
Lymphomatoid granulomatosis	9766/1
Intravascular large B-cell lymphoma	9712/3
Pulmonary Langerhans cell histiocytosis	9751/1
Erdheim-Chester disease	9750/1
Tumours of ectopic origin
Germ cell tumours
Teratoma, mature	9080/0
Teratoma, immature	9080/1
Intrapulmonary thymoma	8580/3
Melanoma	8720/3
Meningioma, NOS	9530/0
Metastatic tumours

Lepidic の由来

ラテン語の lepra (鱗状の) に由来する造語 らしい
         lepidic = relating to scales or a scaly covering layer  (THE FREE DICTIONARY)
類語
        Lepidodendron =リンボク（鱗木）
        leprosy = ライ（癩）

Arch Pathol Lab Med. 2013;137:1822–1824; doi: 10.5858/arpa.2013-0144-HP)

John George Adami, MD is first chair of pathology at McGill University (Montreal, Canada) and creator of the term lepidic.
In the early 1990s the erroneous belief that the term lepidic came from the etymologic origin ‘‘butterfly’’ became prevalent. The changing definition of the term is highlighted in the AFIP’s third series by Colby, Koss, and Travis published in 1995. In this text, lepidic is defined in one instance as meaning ‘‘scale-like’’ and in another as ‘‘calling forth the image of a butterfly (genus: Lepidoptera) alighting on intact alveolar walls.’’ Similar to Monarch butterflies migrating across the continent, the term lepidic migrated throughout the pulmonary literature. Lepidic did not have an entomologic etymology.

In fact this word is a neologism, a new word invented in Canada in the early 1900s. Adami was a prolific writer, and he first used the term lepidic in an address to the Toronto Pathological Society on January 4, 1902. He proposed 2 new terms that would be used to classify all neoplasms. The term lepidic (from λεπιδοζ, meaning a rind, skin, or membrane) was applied to tumors that appeared to be derived from surface-lining cells.

肺の切り出し

B3bにprobeを通してCT断の目安とする（出典不明）。
太い気管支の粘膜内病変は展開固定後に切り出し。


主な遺伝子変異

EGFR遺伝子変異（コバス，オンコマイン）

 (日本肺癌学会, 第1.7版, 2009年5月)
リガンド結合→HER2などと二量体形成→RAS-RAF-MAPK, PI3K-AKT経路

EGFR/HER1の遺伝子変異はチロシンキナーゼ阻害剤(TKI)の治療対象になりうる。
2007年6月1日よりD004-13の悪性腫瘍遺伝子検査が算定できるようになった。

Terminal respiratory unit 型，non-smoker → EGFR変異
Central airway compartment 型，smoker → KRAS変異 (mucinous BAC)

ゲフィチニブの場合，奏功率およそ
    Exon 21 L858R (71%),
    Exon 19 欠失 (81%),
    Exon 18 G719X (56%),
    Exon 21 L861Q (39%)
    Exon 20 挿入 (0%)。
Exon 20 の変異は大体 TKI 治療に抵抗性
耐性変異: Exon 20 T790M  (→ osimertinib) など。

EML4-ALK融合遺伝子陽性肺癌

肺腺癌の3-7%。mucinous cribriform carcinoma, solid growth, signet ring cell の 形態が多い。
免疫組織化学やFISH法で判定できる．


その他の遺伝子変異（オンコマイン）
ROS1 fusion　免疫染色も可能
BRAF mutation　免疫染色？
HER2 mutation　免疫染色？
KRAS mutation
PIK3CA mutation
MET mutation
RET fusion
MAP2K1 mutation
NRAS mutation
AKT mutation

LCNEC  の定義

小細胞癌と同様の化学療法が奏効する可能性がある。そしてすぐに耐性になり小細胞癌と同様に予後が悪い。

配列：類器官型胞巣，索状，ロゼット，索状構造
核所見：核小体明瞭，広い細胞質
分裂像：>10 / 2 mm^2 (average 75, rarely less than <30); Ki-67 index 40-80%
壊死：通常は広い
IHC: クロモグラニン or シナプトフィジン or CD56のいずれかが10%以上陽性

SCC - pemetrexed (Alimta)の効果低い

野口の分類 (Cancer 1995)