2012 EDUCATIONAL BOOK - American Society of Clinical Oncology

Fig. 2. Total number and percent distribution of the ten most frequent types of cancers projected for the year 2012 in Brazil (excluding
nonmelanoma skin cancer). 3
Abbreviation: CNS, central nervous system.
and bronchial brushings or washings. Mediastinal lymph
nodes are often sampled for staging. The pathologist provides
information about the histologic type (or subtype), the
presence and extent of tumor invasion, and surgical margins.
The presence of EGFR or EML4-ALK mutations is also
important, as it can direct treatment toward the use of
specific tyrosine kinase inhibitors (TKIs). 12
In a study performed by investigators at the Brazilian
National Cancer Institute, 162 paraffin-embedded specimens
obtained from patients with NSCLC were analyzed for
EGFR (exons 18 to 21), KRAS (exon 2), and BRAF (exons 11
and 15) mutations and for MET amplification and ALK
rearrangement (Fig. 3). 10 EGFR analysis was successful
in 150 cases, and mutations were identified in 25.3% (38
patients) of patients (6, 19, 13, and 5 mutations in exons 18,
19, 20, and 21, respectively; 5 cases encompassing mutations
in 2 different exons). These abnormalities were observed
mainly in adenocarcinomas (52.8%) but were also frequent
in SCC (36.1%).
In the above study, KRAS mutations were observed in 30
of 148 analyzed cases (20.3%), in which 76.7% were adenocarcinomas.
BRAF mutations were found in 13 of 145
patients (9.0%), mainly in squamous histology (61.5%). Notably,
mutations in exon 11 in men with SCC were identified,
although no case of V600E mutation was identified. 10
The latter observation differs from previous reports of a high
prevalence of this abnormality in patients with a BRAF
mutation. 14 MET gene–increased copy number (mean � 5
copies/cell) was observed in 21 of 152 evaluated cases
(13.8%), mostly in adenocarcinomas (73.7%). ALK rearrangement
was present in four of 161 cases (2.5%), three of
them with adenocarcinoma and one with bronchioloalveolar
histology.
During the surgical procedure, the removed tissue should
428
provide information about the status of resection margins,
involvement of regional lymph nodes and the presence of
incidental nodules. The information on the WHO histologic
type (and subtype), disease staging, and prognostic factors
are essential for treatment planning. The recognition of a
bronchioloalveolar subtype of adenocarcinoma is also relevant,
as EGFR-TKIs are beneficial for these patients. 15
Furthermore, immunohistochemistry is a critical tool in
distinguishing between primary lung cancer and other neoplasms,
such as mesothelioma, metastatic cancer of another
origin, or neuroendocrine tumors. 12
Clinical Evaluation
GILBERTO SCHWARTSMANN
The initial evaluation of a patient with NSCLC includes
medical history, physical examination, laboratory tests,
chest x-ray, abdominal ultrasound, and/or CT scans. Bronchoscopy
is recommended for the diagnosis of central lesions,
while percutaneous biopsy is usually performed in
peripheral lesions. It is recommended that the patient be
referred to a smoking cessation program. Staging includes a
chest CT with the inclusion of the upper abdomen and
adrenals.
Mediastinoscopy is the gold standard for the study of
mediastinal lymph nodes. The sampling of mediastinal
lymph nodes is essential, as CT scans have limitations to
rule out lymph node involvement. Endobronchial ultrasoundtransbronchial
needle aspiration (EBUS-TBNA) is also being
considered for the mediastinal staging of patients with
NSCLC worldwide. Unfortunately, only a small number of
cancer centers in Brazil are currently applying this technique
in the routine treatment of patients with lung cancer.
The use of PET imaging is also a valuable tool in the
current staging of patients with NSCLC. However, because
of its high cost and limited availability through the National