NcXHF

GERBER, PAIK, AND DOWLATI
a tumor that is well differentiated and exhibits classic structural
features such as keratinization, intercellular bridges,
and pearl formation. 1,2 Histopathologic subtypes include papillary,
basaloid, clear cell, and small cell variants. Most squamous
lung cancers are marked by the expression of p40/p63, cytokeratins
5/6, high molecular weight keratin, and carcinoembryonic
antigen. Most cases do not express cytokeratin 7 and thyroid
transcription factor 1 (TTF-1). 3
There are a number of diagnostic challenges inherent to
this disease. Small biopsy specimens and poorly differentiated
tumors often lack the histologic hallmarks of squamous
differentiation. In such cases, immunohistochemical (IHC)
profıling for both p40/p63 (positive in squamous cases) and
TTF-1 (negative in squamous cases) has been established as a
useful approach for determining lineage. 1,3 A number of
studies have also addressed the issue of adenosquamous
carcinomas, tumors that have most likely arisen from a
common clone but exhibit divergence in histologic appearance.
In terms of molecular biology, these tumors appear
to be more closely aligned with adenocarcinomas
than squamous cell carcinomas, which has important
therapeutic implications as it relates to current guidelines
for EGFR and ALK testing. 1
In 2012, The Cancer Genome Atlas published a comprehensive
molecular analysis of 178 early-stage squamous lung
tumors and, from a conceptual standpoint, ushered in an era
of personalized medicine for patients with this disease. 4
These data, coupled with discoveries made by other
researchers, 5-7 crystallized the notion that a potentially actionable
oncogenic driver could be found in the majority of
squamous cases. Key targets are discussed below, and include
KEY POINTS
Although most recent lung cancer developments have been
limited to adenocarcinoma histology, numerous discoveries
for squamous, small cell, and other histologies have also
been made.
A putative oncogenic driver can be identified in the
majority of patients with squamous cell lung cancer. Key
druggable targets include FGFR1 amplification, PI3K
pathway alterations, cell cycle checkpoint disturbances,
and DDR2 mutations.
Ramucirumab, a monoclonal antibody against VEGFR-2, is
now FDA-approved in conjunction with docetaxel for the
treatment of patients with non–small cell lung cancers,
including squamous cell lung cancers, making this the first
antiangiogenesis drug available to patients with this
disease.
Comprehensive genomic analyses of small cell lung cancer
have been conducted. Current experimental treatment
approaches are focusing on targeting mitotic, cell cycle,
and DNA repair regulation, as well as immunotherapy.
Pulmonary neuroendocrine tumors represent a diverse
spectrum of diseases. Radiolabeled somatostatin analogs
and molecularly targeted agents are under investigation.
SIDEBAR 1. World Health Organization
Classification of Lung Cancers, Including
Modification by IASLC/ATS/ERS Classification of
Lung Adenocarcinoma 155
Preinvasive Lesions
Bronchial squamous dysplasia/carcinoma in situ
Atypical adenomatous hyperplasia
Adenocarcinoma in situ
Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia
Adenocarcinoma
Minimally invasive adenocarcinoma ( 3 cm lepidic
predominant tumor with 5 mm invasion)
Invasive adenocarcinoma
- Lepidic predominant (nonmucinous with 5 mm invasion)
- Acinar predominant
- Papillary predominant
- Micropapillary predominant
- Solid predominant with mucin
Adenocarcinoma Variants
Invasive mucinous adenocarcinoma
Colloid
Fetal
Enteric
Squamous Cell Carcinoma (Variants)
Papillary
Clear cell
Small cell
Basaloid
Small Cell Carcinoma (Variant)
Combined small cell carcinoma
Large Cell Carcinoma (Variants)
Large cell neuroendocrine carcinoma (LCNEC) and
Combined LCNEC
Basaloid carcinoma
Lymphoepithelioma-like carcinoma
Clear cell carcinoma
Large cell carcinoma with rhabdoid phenotype
Adenosquamous Carcinoma
Sarcomatoid Carcinoma
Pleomorphic carcinoma
Spindle cell carcinoma
Giant cell carcinoma
Carcinosarcoma
Pulmonary blastoma
Carcinoid Tumor
Typical carcinoid
Atypical carcinoid
Salivary Gland Tumors
Mucoepidermoid carcinoma
Adenoid cystic carcinoma
Epithelial-myoepithelial carcinoma
Abbreviations: IASLC, International Association for the Study of Lung Cancer; ATS,
American Thoracic Society; ERS, European Respiratory Society.
148 2015 ASCO EDUCATIONAL BOOK | asco.org/edbook