LUNG TUMORSAlthough lungs are frequently the site of metastases from cancers in extrathoracic organs, primary lung cancer is also a common disease.
Ninety-five percent of primary lung tumors arise from the bronchial epithelium (bronchogenic carcinomas); the remaining 5% are a miscellaneous group that includes bronchial carcinoids, &other.
The number one cause of cancer-related deaths in male and female.
The number of new cases of lung cancer occurring in 2008 in the United States is estimated to be 215 (note that in 1950 it was 18,000), accounting for about 15% of cancer diagnoses and 29% of cancer-related deaths.
Age: Peak between 55 and 65 years.
Sex: currently, the male-to-female ratio is about 2:1 but the rate of increase among males is slowing down, but it continues to accelerate among females, WHY?
At diagnosis, greater than 50% of patients already have distant metastatic disease.Classification (WHO 2015):1- Adenocarcinoma:- lepidemic adenocarcinoma- Acinar adenocarcinoma-Papillary adenocarcinoma-Others2- Squamous cell carcinoma3-Neuroendocrine tumors:- Small (oat) cell carcinoma- Neuroendocrine carcinoma- Carcinoid tumors4- Large cell carcinoma5- Others as adenosquamous, sarcomatoid,…
For reasons not entirely understood, adenocarcinoma has replaced squamous cell carcinoma as the most common primary lung tumor in recent years.
Adenocarcinomas are also by far the most common primary tumors arising in:
In lifetime nonsmokers.
Patients younger than 45 years.
For therapeutic purposes, bronchogenic carcinomas are classified into two broad groups: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). WHY?
Etiology and PathogenesisBronchogenic carcinomas, similar to cancers at many other anatomic sites, arise by a stepwise accumulation of genetic abnormalities that result in transformation of benign bronchial epithelium into neoplastic tissue.
Mining (various radioactive particles)
Dusts containing arsenic, chromium, uranium, nickel, vinyl chloride, and mustard gas
SMOKING:Statistical, clinical, and experimental evidence incriminates cigarette smoking.
About 90% of lung cancers occur in active smokers or those who stopped recently.
There is a nearly linear correlation between the frequency of lung cancer and pack-years of cigarette smoking. The risk becomes 60 times greater among habitual heavy smokers (two packs a day for 20 years) compared with nonsmokers.
For reasons not entirely clear, women have a higher susceptibility to tobacco carcinogens than men.
Cessation of smoking decreases the risk of developing lung cancer over time, but it may never return to baseline levels.
Passive smoking increases the risk of developing lung cancer to approximately twice that of nonsmokers.
Smoking results in progressive alterations in the lining epithelium of the respiratory tract: basal cell hyperplasia and squamous metaplasia and progress to squamous dysplasia and carcinoma in situ, culminating in invasive cancer.
Squamous and small cell carcinomas show the strongest association with tobacco exposure.
Squamous cell carcinomasMen > women.
Preceded for years by squamous metaplasia or dysplasia in the bronchial epithelium, which then transforms to carcinoma in situ.
Gross:Typically central in location (major bronchi), frequently presenting with bronchial obstruction, and may undergo central necrosis, giving rise to cavitation.
Histologically:These tumors range from well-differentiated squamous cell neoplasms showing keratin pearls and intercellular bridges to poorly differentiated neoplasms having only minimal residual squamous cell features.
AdenocarcinomasThey have the weakest association with a previous history of smoking.
Female & young.
Mostly peripheral in location, sometimes originating in areas of pre-existing lung scarring ("scar carcinomas").
In general, these tumors grow slowly and form smaller masses.
They tend to metastasize widely at an early stage.
Histologically:They assume a variety of forms, including acinar (gland forming), papillary, and solid types.
LipidemicA subtype of adenocarcinomas.
They involve peripheral parts of the lung, either as a single nodule or, more often, as multiple diffuse nodules that may produce pneumonia-like consolidation.
Bronchoalveolar carcinoma;Pneumonic-like consoidation
Large cell carcinomasThe lesions may be central or peripheral.
Histological features: insufficiently differentiated to permit further classification by light microscope; pleomorphic cells, frequently very large.
SMALL CELL CARCINOMA (oat cell carcinoma)Usually centrally located with early involvement of the hilar and mediastinal nodes.
These tumors are derived from neuroendocrine cells of the lung, and hence they express a variety of neuroendocrine markers and secrete a host of polypeptide hormones that may result in paraneoplastic syndromes.
Oat cell carcinoma. The cut surface of this tumor has a white appearance. The tumor seen here has caused obstruction of the main bronchus to left lung so that the distal lung is collapsed.
Histologically:Tumor cells are round to oval, and have little cytoplasm; and finely granular chromatin.
Clinical presentation of lung cancer:Clinical presentation of lung cancer:
Silent, features of metastasis.
Haemoptysis (ulceration of tumour in bronchus).
Chest pain (involvement of pleura and chest wall).
Wheeze (narrowing of airway).
weight loss, anemia, anorexia, malaise.
Paraneoplastic syndromes (10% of cases) include:
Hypercalcemia why?Cushing syndrome why?
Syndrome of inappropriate secretion of antidiuretic hormone (SIADH).
Neuromuscular syndromes, including a myasthenic-like syndrome, peripheral neuropathy, and polymyositis.
Clubbing of the fingers and hypertrophic pulmonary osteoarthropathy.Hematologic manifestations, including migratory thrombophlebitis, nonbacterial endocarditis, and disseminated intravascular coagulation.
Hypercalcemia is most often encountered with squamous cell neoplasms, the hematologic syndromes with adenocarcinomas. The remaining syndromes are much more common with small cell neoplasms.
Diagnosis:History and examination
- Positive in 80% of central tumors.
- Positive in 50% of peripheral tumors.
Biopsy - a number of ways:
- Bronchoscopy (very good for central tumors)
- Needle (very good for peripheral tumors)
PrognosisThe prognosis of lung cancer is dismal: the 5-year survival rate for all stages of lung cancer combined is about 14%; even patients with disease localized to the lung have a 5-year survival of approximately 45%.
SCC: relative good - slow growing and often resectable.
Adenocarcinoma: poor, because most tumors do not present signs of airway obstruction (because of there peripheral location) and therefore are highly advanced before presentation; bronchioloalveolar carcinoma has a good prognosis.
Oat cell carcinoma: poor, because tumors are fast growing and highly malignant.
Large cell carcinoma: poor; tumors usually widely disseminated at time of diagnosis.
Secondary tumors of the lung
Etiology: any malignancy may reach lung from lymph spread or vascular spread.
Clinical presentation: same as primary lesions
There are 3 common patterns:
Miliary pattern (many small neoplasms)
Cannon ball pattern (one large, spherical, well demarcated neoplasm).
Lymphangitis carcinomatosis (spread along lymphatics - white lines through lungs instead of black lines marking lymphatics.
Poor, except if local resection is possible
Bronchial carcinoid:Account for 5% of all pulmonary neoplasms.
Arise from the Kulchitsky cells (neuroendocrine cells that line the bronchial mucosa).
The neoplastic cells may rarely secrete hormones & polypeptides and may induce carcinoid syndrome.
Affect adult of both sexes.
Originate in mainstem bronchi, protrude into lumen and often present with early airways obstruction.
Histologically, composed of nests of uniform cells that have regular round nuclei, rare mitoses, and little pleomorphism.
Prognosis:Slowly growing may spread to the hilar nodes but distant metastasis is rare. The reported 5- to 10-year survival rate ranges from 50% to 95%.
Pleural lesions:Lesions of the pleura may be inflammatory or neoplastic.
Malignant mesotheliomaA rare cancer of mesothelial cells, arising in the pleura, & much less commonly in the peritoneum and pericardium.
It is related to occupational exposure to asbestos in the air. (50% of the patients have a history of exposure to asbestos).
The latent period for developing malignant mesotheliomas is long, often 25 to 40 years after initial asbestos exposure.
The combination of cigarette smoking and asbestos exposure greatly increases the risk of bronchogenic carcinoma, but it does not increase the risk of developing malignant mesotheliomas.
Asbestos is not removed or metabolized from the lung, and hence the fibers remain in the body for life. Asbestos fibers gather near the mesothelial cell layer, where they generate reactive oxygen species that cause DNA damage and potentially oncogenic mutations.
Morphology:The affected lung is typically ensheathed by a yellow-white, firm, sometimes gelatinous layer of tumor that obliterates the pleural space
The neoplasm may directly invade the thoracic wall or the subpleural lung tissue.
Distant metastasis is rare.
The dense white encircling tumor mass is arising from the visceral pleura and is a mesothelioma