1. Lung tumors & pleural lesions
Ali Al Khader, M.D.
Faculty of Medicine
Al-Balqa’ Applied University

2. A brief introduction 95% of lung tumors are carcinomas
Among the remaining 5%, we will discuss:
-Hamartoma
…the most common benign lung tumor
…spherical, “coin lesion” on x-rays
…small (1-4cm)
…consists mainly of mature cartilage admixed with fat, fibrous tissue, and
blood vessels in various proportions
-Carcinoid…a semi-benign/semi-malignant tumor…considered as malignant

3. Carcinomas, overview
The most common cause of cancer death in men & women
Decreasing among men and increasing among women
Peak incidence: 50s & 60s
Prognosis is bad in general…even if localized in the lung, the 5-year survival rate is near 45%

4. Lung cancer, 4 major histologic types
Previously: Small cell lung cancer (SCLC)
…aggressive, metastasis common since diagnosis
with median survival of 1 year
…much mitotic and apoptotic activity, necrosis, crushing
artifacts and Azzopardi effect
…always needs chemotherapy
1- Small cell carcinoma 2- Adenocarcinoma 3- Squamous cell carcinoma 4- Large cell carcinoma …others, some are “mixed”
Previously: Non-small cell lung cancer (NSCLC)
Note: Small cell carcinoma
& carcinoid are both considered
“neuroendocrine tumors”

5. The most common primary lung tumor in USA
now is:
Adenocarcinoma (replaced squamous cell carcinoma
because smoking in comparison to the past)
Smoking
Small and squamous cell carcinomas have the strongest association with smoking
…but smoking is also a risk for adenocarcinoma
Adenocarcinomas are the most common primary tumors arising in:
-women
-never-smokers
-individuals younger than 45 years of age
90% of lung cancers occurs in smokers or who stopped recently
Women are more susceptibile to carcinogens in tobacco smoke than men
Cessation of smoking decreases the risk…but never to baseline
Also passive smokers, pipes, and cigars…lesser risk

6. Molecular pathogenesis of lung cancer
Abnormalities in tumor suppressors on the short arm of chromosome 3…an early event
TP53 tumor suppressor gene mutations and KRAS oncogene mutations…later
Changes accumulate in smokers in a stepwise fashion and in large areas (field effect) forming a fertile soil for cancer to occur
A subset of adenocarcinomas (10% in whites & 30% in Asians) harbor
EGFR mutations…a receptor tyrosine kinase (oncogene)…targeted therapy
KRAS is downstream of EGFR and their mutations are mutually exclusive (do not occur at the same time)
Other tyrosine kinases that may be mutated in adenocarcinoma and can respond to their specific targeted therapies: ALK, ROS1, HER2, c-MET
…the concept of “personalized lung cancer therapy”: molecular pathogenesis guides the treatment

7. Important event sequences
Atypical adenomatous hyperplasia adenocarcinoma in situ
invasive adenocarcinoma …this is proposed for some adenocarcinomas
Squamous metaplasia squamous dysplasia squamous cell
carcinoma in situ invasive squamous cell carcinoma
These precursor lesion may last for many years

8. Other environmental & occupational risk factors
Uranium
Asbestos (alone: 5-fold increased risk, with smoking: 55-fold)
Chromium
Arsenic
Nickel
Vinyl chloride

9. Morphology of lung cancer
Adenocarcinoma…peripherally more
Squamous cell and small cell carcinomas…centrally more (in major bronchi)
Adenocarcinoma…may be glandular (acinar), papillary, mucinous or solid
Adenocarcinoma in situ…previously called: bronchioalveolar carcinoma
…characteristic growth along preexisting alveolar septa, without invasion

10. TTF-1 (thyroid transcription factor 1)…especially positive in lung
Adenocarcinoma and small cell carcinoma
Adenocarcinoma in situ
Adenocarcinoma…gland-forming

11. Squamous cell carcinoma, some notes
Necrosis with cavitation is more common
Metastasis outside thorax is slower than others
Earlier precursor events can be detected as abnormal cells in cytopathologic examination of sputum or bronchoalveolar lavage
Variable morphology (from well differentiated (much more keratin) to poorly differentiated)

12. Some clinical presentations
Involvement of left supraclavicular lymph node = Virchow node
Compression of superior vena cava with venous congestion of the face…Vena caval syndrome
Apical tumors if compressing sympathetic plexus…Horner syndrome?
…these apical neoplasms are called: Pancoast tumors

13. Paraneoplastic syndromes of lung cancer
In 3-10% of cases
Mainly:
1-Hypercalcemia (parathyroid hormone-related peptide)…squamous cell carcinoma
2-Cushing syndrome (ACTH)…small cell carcinoma…also carcinoid
3-SIADH (syndrome of inappropriate ADH secretion)…small cell carcinoma
4-Neuromuscular syndromes…small cell carcinoma
5-Clubbing of fingers and pulmonary osteoarthropathy
6-Coagulation abnormalities (migratory thrombophlebitis, DIC)
7-Carcinoid syndrome…carcinoid tumor…also small cell carcinoma

14. Carcinoid tumors Mainly intrabronchial growth, well-circumscribed
The cells contain neurosecretory granules (features of neuroendocrine tumors)
It is better to consider them as: low-grade neuroendocrine carcinomas (malignant)
May rarely secrete hormonally active polypeptides…carcinoid syndrome
Classified as typical (indolent) and atypical (worse)
Resectable and curable
Young adults (mean 40 years)
Sometimes as part of MEN syndrome
5-15% metastasize to hilar lymph nodes, but distal metastasis is rare

15. Carcinoid tumors, morphology
Typical carcinoid: nests of uniform cells that have regular round nuclei with “salt-and-pepper” chromatin, absent or rare mitoses and little pleomorphism
Atypical carcinoid: necrosis and more mitoses

16. Carcinoid tumors, clinical notes
Symptoms related to bronchial location (cough, hemoptysis, obstruction & infection)
Peripheral carcinoids are often asymptomatic and discovered incidentally
Rarely: carcinoid syndrome (intermittent attacks of diarrhea, flushing and cyanosis)
The reported 5- and 10-year survival rates for typical carcinoids are above 85%, while these rates drop to 56% and 35%, respectively, for atypical carcinoids

17. Metastases to the lung Any pattern of growth
…but remember that multiplicity is more with metastatic than primary (not always)

18. A brief note on malignant mesothelioma of the pleura
A rare cancer of mesothelial cells, usually arising in the parietal or visceral pleura; it also occurs much less commonly in the peritoneum and pericardium
80% to 90% of individuals with this cancer have a history of exposure to asbestos (shipyard workers, miners, insulators)
The latent period for developing malignant mesothelioma after the initial exposure is long, often 25 to 40 years
The combination of cigarette smoking and asbestos exposure greatly increases the risk for developing lung carcinoma, but it does not increase the risk for developing malignant mesothelioma
The lifetime risk after exposure does not diminish over time (unlike with smoking, in which the risk decreases after cessation)
BAP1 mutations are common (a tumor suppressor gene important for DNA repair)

19. Pleural effusions Transudates or exudates…transudate = hydrothorax
The most common cause of bilateral hydrothorax is: Congestive heart failure
An exudate, characterized by protein content greater than 30 g/L and, often, inflammatory cells, suggests pleuritis
The four principal causes of pleural exudate formation are: infection (suppurative pleuritis or empyema)-cancer (commonly hemorrhagic)- pulmonary infarction-viral pleuritic
…others: connective tissue diseases and uremia

20. Pneumothorax
Simple/spontaneous…without known lung disease…young healthy men
Secondary…with known thoracic or lung disorder

21. Other pleural fluid accumulations

22. Thank You