Download SDL 9 Lung Cancer One of the most common cancers affecting

SDL 9 Lung Cancer
 One of the most common cancers affecting humans; most
related to tobacco smoking
 Lung cancer is the leading cause of death due to cancer in
both men and women
 Lung cancer terminology encompasses bronchogenic
carcinoma including non-small cell carcinomas and small
cell carcinomas
 Promising new screening methodologies and targeted
therapies will likely improve these statistics
 General signs & Sx:
o Hemotptysis
o Weight loss
o Fatigue
o Cough
o Hoarseness
o Pain
 Risk factors:
o Tobacco smoking
o Exposure to radiation (e.g., Radon)
o Genetic risks
o One does not have to be a tobacco smoker to develop
primarylung cancer.
o MOST COMMON type of lung cancer is metastatic
cancer from other anatomic locations.
 Carcinogens/toxins in tobacco smoke: acetaldehyde,
acrylonitrile, arsenic, benzene, formaldehyde, furan,
hydrazine, lead, polonium-210, vinyl chloride,
nitromethane, isoprene
 Radiology in Dx:
o Chest x-ray is the starting place
o Abnormal areas identified on plan x-ray of chest will
likely be followed by compute tomography scanning
(CT) which is more helpful in identifying anatomic
extent of disease; LN involvement
o CT guided needle biopsy of suspicious area helptul in
definitive Dx.
 Other Means of Dx:
o Bronchoscopy & biopsy lesion with or near bronchial
tree
o Bronchial lavage & sputum analysis by cytology
 Old Means of Dx:
o In the past: surgical biopsy with mediastinoscopy for
lung cancer staging significant morbidity/mortality
o Today, diagnosis may be established in a less invasive
way with endobronchial U/S (EBUD) by either a
specifically trained pulmonologist
 Can sample tumor w/in or near bronchial tree
 LN stations may be sampled to stage the patient
 Pathologist is on-site at procedure to interpret
cytologic preparations to help guide collection of
samples and ensure adequate material for
molecular pathology
Next step after Dx:
 PET (positron emission tomography) scanning may
be performed to help highlight metabolically active
tumor metastases
 Head CT to rule out brain/CNS metastases and initial
work-up for staging
Pathology Classification:
 Old classification: non-small cell carcinoma and
small cell carcinoma (primary bronchogenic)
 Today: must discriminate between types of primary
lung cancer
 Primary Tumors:
o Small cell carcinoma (neuroendocrine
carcinoma)
 Large cell neuroendocrine carcinoma
o Non-small cell carcinoma
 Adenocarcinoma
 Squamous cell carcinoma
 Large cell carcinoma
o Other types of lung tumors
 Carcinoid tumor (well-differentiated
neuroendocrine carcinoma)
 Sarcomas
 Pleural mesothelioma
 Incidence in U.S.:
o 40% - Adenocarcinoma
o 30% - Squamous cell carcinoma
o 15% - Large cell carcinoma
o 15% - Small cell carcinoma
 Metastatic Lung tumors
o Carcinomas: breast, liver, colon, etc
o Malignant melanoma
o Sarcoma
ADENOCARCINOMA
 Carcinoma composed of malignant glands; tends to
be more peripheral in lung (e.g., subpleural scar
carcinoma)
 Precursor lesion: AAH (atypical adenomatous
hyperplasia)
 Non-invasive types: bronchioloalveolar cell
carcinoma (BAC) or adenocarcinoma in-situ
Adenocarcinoma
A) Atypical adenomatous hyperplasia
B) Bronchioalveolar cell carcinoma; adenocarcinoma
in-situ
 Adenocarcinoma progression
o Histologically normal → Paraneoplastic →
Preinvasive → Invasive → Metastatic
(squamous cell carcinoma)
 EGF-R mutations and Alk gene rearrangement are
rarely identified in these tumors
 Overexpression of the EGF-R as assessed by
immunohistochemistry can be used as a therapeutic
agent
(Adenocarcinoma on bronchial brushing or lavage)
 Molecular pathology testing - targeted therapy
o Pts w/EGF-R (epidermal growth factor receptor)
mutations tend to have longer disease free
progression and survival than those w/out them
o Pts may be eligible for small Tyr kinase inhibitors (e.g.,
geftinib) which block EGF-R signal transduction
o Pts who harbor mutations tend to be never-smokers,
women & of Asian decent
 Alk Gene rearrangement
o Pts w/Alk gene rearrangement were documented to
have dramatic response to drug Crizotinib
o Testing for Alk gene rearrangement is by FISH
o Pts w/Alk gene rearrangement tend to be neversmokers
LARGE CELL CARCINOMA
Poorly differeniated carcinoma composed of malignant
tumor cells w/out features of either adenocarcinoma or
squamous cell carcinoma
(large cell carcinoma)
SMALL CELL CARCINOMA
Aka small cell (undifferentiated) neuroendocrine
carcinomas
 Tumor tents to be located in central location
 Precursor lesion thought to be atypical with LN or
distant metastases at the time of Dx
 Unlike non-small cell carcinoma, surgical intervention
is typically not a Tx
(FISH)
SQUAMOUS CELL CARCINOMA
 Malignant tumor of lug - tends to be in central location
 Precursor lesions: squamous metaplasia → dysplasia
 Important to document squamous characteristice
because pts w/squamous lung carcinoma are not
eligible for Tx w/bevacuzimab (Avastin), an inhibitor of
VEGF involved in angiogenesis in tumors (risk of
pulmonary hemorrhage)
(Small cell carcinoma as it may
appear on bronchial brushing or
lavage)
 Pts w/small cell carcinoma typically do not harbor
specific therapeutically exploitable genetic
abnormalities
 Pts typically have an initial dramatic response to
systemic chemotherapy which often includes platinumcontaining compounds (e.g., cisplatin, oxaliplatin)
PLEURAL MESOTHELIOMA
 Exposure to asbestos (primarily amphibole type
asbestos: crocidolite and amosite)
 Pleural based malignancy
 Few good Tx and very poor prognosis
 Encases the lung - metastatic deposits
 MOST COMMON histology is epitheloid histology
(others include sarcomatoid and biphasic types)
 Big medico-legal issues: careful documentation and
establishing the diagnosis beyond any doubt - expert
consultation
 Asbestos bodies
 Asbestos Mineral & EM
 Other pulmonary tumors
o Carcinoid tumor (well-differentiated
neuroendocrine carinoma)
o Soft tissue tumors (solitary fibrous tumor, synovial
sarcoma, leiomyosarcoma, others)
o Pediatric malrignancies (peluropulmonary
blastoma)
QUIZ QUESTIONS
 Most common pulmonary tumor? Metastatic tumors
 What mutation is associated with therapeutic
response to Tyr inhibitors such as gefitinib?
 EGF-R mutations
 Why is it important to recognize squamous
carcinoma features in pts w/lung cancer? Drug
BEVACUZIMAB/Avastin is CI for use due to risk of
pulmonary hemorrhage