the lung are by far the most common malignancies of this organ and
constitute the leading cause of cancer morbidity and mortality worldwide.
Histologically, adenocarcinomas appear
to be the most common histologic type of lung cancer diagnosed, while
squamous cell carcinoma appears to be more commonly associated with
Bronchogenic carcinoma constitutes 90 to
95% of lung tumours.
It is the most common cause of cancer death
in both men and women.
relevance for clinical practice and clinical trials. J
Clin Oncol. 2013
We summarize significant changes in
resulting from the 2011 International Association for the Study of
Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS)
was developed by an international core panel of experts representing
IASLC, ATS, and ERS with oncologists/pulmonologists, pathologists,
radiologists, molecular biologists, and thoracic surgeons. Because 70%
of patients with
lung cancer present with advanced stages, a
to small biopsies and cytology with specific terminology and criteria
focused on the need for distinguishing squamous cell carcinoma from
and on molecular testing for EGFR mutations and ALK rearrangement.
Tumors previously classified as non-small-cell carcinoma, not
otherwise specified, because of the lack of clear squamous or
morphology should be classified further by using a limited
immunohistochemical workup to preserve tissue for molecular testing.
The terms "bronchioloalveolar carcinoma" and "mixed subtype
have been discontinued. For resected adenocarcinomas,
in situ and minimally invasive
define patients who, if they undergo complete resection, will have
100% disease-free survival. Invasive adenocarcinomas are now
classified by predominant pattern after using comprehensive histologic
subtyping with lepidic, acinar, papillary, and solid patterns;
micropapillary is added as a
histologic subtype with poor prognosis. Former mucinous
bronchioloalveolar carcinomas are now called "invasive mucinous
Because the lung
cancer field is now rapidly evolving with
occurring on a frequent basis, particularly in the molecular arena,
provides a much needed standard for pathologic diagnosis not only for
patient care but also for clinical trials and TNM
smoking is well established as the most important and common etiologic
factor in the development of lung cancer.
- Statistically, there is an unequivocal link between the
frequency of lung cancer and the number of pack-years of smoking.
- Clinically, hyperplastic and atypical changes can be
seen in the bronchial epithelium of smokers and in the vicinity of
there are numerous known carcinogens in cigarette smoke (Eg., polycyclic
Other etiologic factors
include exposure to radiation (atomic bomb survivors, uranium miners),
asbestos (especially combined with smoking), air pollution (radon, particulates), and
miscellaneous occupational inhaled substances (Example: Nickel, chromates,
Genetic mechanisms implicated include
dominant oncogenes (Example: K-ras, in adenocarcinomas) and loss of
from a clinical perspective: current concepts and future prospects.
J Thorac Dis.
International Association for the Study of
Lung Cancer (IASLC)/the
American Thoracic Society (ATS)/the European Respiratory Society (ERS)
has markedly changed the pathologic diagnosis of
deals with many aspects that directly affect clinical practice, and
gateways for future research. By means of a multidisciplinary
approach, it differs significantly from the former 2004 the World
Health Organization (WHO)
which was mainly written by pathologist. The present review, in line
with the consensus article, is divided in two components: the
in resection specimens and the diagnosis of
in small biopsies and cytology. Resection specimens are currently
classified according to the predominant histologic pattern after
comprehensive subtyping in 5% increments. This approach has led to the
addition of new
pathologic subtypes [adenocarcinoma
in situ (AIS), minimally invasive
(MIA) and micropapillary predominant
and to the discontinuation of some heterogeneous entities included in
the former 2004 WHO
classification (mixed subtype
and bronchioloalveolar carcinoma). Overall, these changes have
resulted in a better stratification of
tumors in more homogeneous morphologic, clinical and biological
subgroups. Pathologic subtyping has demonstrated prognostic utility in
resected stage I-III patients, and recent data support their
predictive role for the benefit of adjuvant chemotherapy. Moreover,
comprehensive pathologic subtyping may potentially affect TNM staging
and surgical management or early-stage tumors. On the other hand, for
the first time, the novel pathologic
provides standardized terminology and diagnostic criteria of small
biopsies and cytology. Criteria are proposed not only for
but also for other histologies, but special emphasis was put on the
adenocarcinoma and squamous-cell carcinoma due to its major
Clinical features of
They usually occur in the sixth to
seventh decades of life.
The clinical symptoms depend largely on the
anatomic location of the tumour and its size.
Tumours with a central
location are more likely to produce early symptoms such as cough, dyspnea,
wheezing, hemoptysis, and pneumonia.
Tumours that are located in the periphery of the lung need to attain a
relatively large size before they become symptomatic.
Some types of symptoms may be correlated with certain
types of malignancy. For instance, bronchorrhea (expectoration of large
amounts of mucus) is more commonly seen in invasive mucinous
In other instances, symptoms such as pleuritic pain,
Pancoast syndrome, or superior vena cava syndrome develop when there is
extensive tumour burden within the thorax.
In addition, non–small cell carcinomas may also be
associated with other conditions such as bronchiectasis, pulmonary
fibrosis, tuberculosis and other infectious processes.
carcinomas usually present with cough, weight loss, chest pain, and
syndromes associated with bronchogenic carcinoma often occur due to release
of the following hormones:
- Antidiuretic hormone (syndrome
of inappropriate antidiuretic hormone release).
hormone (Cushing’s syndrome).
- Parathormone or
prostaglandin E (hypercalcemia)
- Calcitonin (hypocalcemia)
- Gonadotropin (gynecomastia)
syndromes include myopathy, peripheral neuropathy, acanthosis nigricans,
and hypertrophic osteoarthropathy (Example: clubbing of fingers).
Overall 5-year survival is
approximately 9%. Surgical resection of solitary (non-small cell) tumours
offers some improved survival (30 to 40% - 5-year survival) for a minority
of patients with localized disease.
The use of more advanced radiological techniques such as magnetic
resonance imaging and computerized tomography has greatly improved the
detection of lung cancer.