LUNG TUMORS

• 95% of primary lung tumors are carcinomas

04/22/2025 1
Carcinomas
• Leading cause of cancer deaths
• The peak incidence is in fifties and sixties.
• At diagnosis, more than 50% of patients already have distant metastasis
• One fourth have disease in the regional lymph nodes.
• The prognosis remains dismal
• The 5-year survival rate for all stages of lung cancer combined is about
16%
• Localized to the lung, the 5-year survival rate is only 45%.
• Most common visceral malignancy
04/22/2025 2
 The four major histologic types
• Adenocarcinoma
• Squamous cell carcinoma
• Small cell carcinoma (a subtype of neuroendocrine carcinoma)
• Large cell carcinoma
• Squamous cell and small cell carcinomas have the strongest association
with smoking
• Adenocarcinomas is the most common primary tumors arising in
women, in never-smokers, and in individuals younger than 45 years of
age.
04/22/2025 3
04/22/2025 4
Etiology and pathogenesis
• Cigarette smoking is the main culprit responsible for the mutations
that give rise to lung cancers.
• About 90% of lung cancers occur in active smokers
• The increased risk is 60 times greater among habitual heavy smokers
(two packs a day for 20 years) than among nonsmokers
• For unclear reasons, women are more susceptibile to carcinogens in
tobacco smoke than men

04/22/2025 5
 • Passive smoking increases the risk ,albeit only modestly.
• Exposure to asbestos in nonsmokers increases the risk for developing lung
cancer 5-fold
• Heavy smokers exposed to asbestos ,the risk is elevated approximately 55-
fold.
• Inactivation of the putative tumor suppressor genes located on the short arm
of chromosome 3 (3p) is a very common early event
• Mutations in the TP53 tumor suppressor gene and the KRAS oncogene occur
relatively late
• Some invasive adenocarcinomas of the lung arise through an atypical
adenomatous hyperplasia–adenocarcinoma in situ–invasive adenocarcinoma
sequence.
• The sequential changes leading development of squamous cell carcinomas
are well documented
• i.e. basal cell hyperplasia and squamous metaplasia and progress to
04/22/2025
squamous dysplasia and carcinoma in situ, before culminating in invasive 6
cancer.
• Depends on duration, amount of daily smoking & deep inhaling.
• 10 fold greater risk than non smokers.
• 20 fold risk if >40 cigarettes per day
• It is very likely that the mutagenic effect of carcinogens is modified by hereditary
(genetic) factors.
• Atypical cells in 96.7% of smokers compared to 0.9% in non smokers.
• Significant proportion of over 1200 substances in smoke are carcinogenic. (not
nicotine)
• Initiaters – Benzo[o]pyrenes
• Promoters – Phenol derivatives
• Radioactive substances – Polonium, C14, K40
04/22/2025 7
MORPHOLOGY
• Lung carcinomas most often arise in small mucosal lesions that are
usually firm and gray-white
• About three fourth take their origin from bronchi (primary, secondary
or segmental)
• A small percentage from the alveolar septal cells or terminal
bronchioles – predominantly adenocarcinoma
• More distant spread can occur via the lymphatics or the
hematogenous route.

04/22/2025 8
Adenocarcinoma
• Malignant epithelial tumor with glandular differentiation or mucin
production by tumor cell
• May have acinar, papillary, bronchioalveolar, & solid pattern
• Most common in women & non smokers
• Lesions more peripherally located, & tend to be smaller
• Grow more slowly than SCC but tend to metastasize early & widely
• Are less frequently associated with smoking, K-RAS mutations are
primarily seen

04/22/2025 9
04/22/2025 10
04/22/2025 11
Squamous cell carcinoma
• Most commonly seen in men
• Closely related with smoking history
• Characterized by the presence of keratinization & /or intercellular
bridges
• The highest frequency of p53 mutation
• Tend to arise centrally in major bronchi and eventually spread to local
hilar nodes, but they disseminate outside the thorax later than do
other histologic types

04/22/2025 12
04/22/2025 13
04/22/2025 14
Large cell carcinomas
• Undifferentiated malignant epithelial tumor
• Cells typically have large nuclei, prominent nucleoli, & a moderate
amount of cytoplasm
• Peripheral lesion
• Wastebasket group of tumors that do not fit the criteria of a
squamous cell carcinoma, adenocarcinoma, or small cell carcinoma

04/22/2025 15
Small cell lung carcinomas
• Epithelial cells are small with scant cytoplasm & less than resting
lymphocytes
• Cells are round, oval, & spindle shaped, & nuclear molding is
prominent
• Mitotic count is high
• Have a strong relation ship to cigarette smoking
• Necrosis is invariably present and may be extensive
• The tumor cells are fragile and often show fragmentation and “crush
artifact” in small biopsy specimens

04/22/2025 16
• The most aggressive of lung tumors
• Pale gray, centrally located masses that extend into the lung
• p53 & RB genes are frequently mutated
• May secrete a host of polypeptide hormones that may result in
paraneoplastic syndromes
• By the time of diagnosis, most will have metastasized to hilar and
mediastinal lymph nodes.

04/22/2025 17
04/22/2025 18
• Each of these lung cancer subtypes tends to spread to lymph nodes in
the carina, the mediastinum, and the neck (scalene nodes) and
clavicular regions, and, sooner or later, to distant sites.
• Involvement of the left supraclavicular node (Virchow node) is
particularly characteristic and sometimes calls attention to an occult
primary tumor.

04/22/2025 19
• May compress or infiltrate the superior vena cava to
cause venous congestion or the vena caval
syndrome.
• Apical neoplasms may invade the brachial or cervical
sympathetic plexus, causing severe pain in the
distribution of the ulnar nerve or horner syndrome
(ipsilateral enophthalmos, ptosis, miosis, and anhidrosis).
• Such apical neoplasms are sometimes called pancoast tumors
• Clinical findings is known as pancoast syndrome

04/22/2025 20
Clinical Features
• Cough, weight loss, chest pain, dyspnea
• Paraneoplastic syndrome
• Apical lung cancers (pancoast tumor) tend to invade neural structures
around the trachea
• 5 year survival rate is 15%
• Hoarseness
• Superior vena cava syndrome
• Pericardial or pleural effusion
• Persistent segmental atelectasis or pneumonitis
04/22/2025 21
• Overall, squamous cell carcinoma and adenocarcinoma carry a more
favorable prognosis than SCLC-the median survival even with
treatment remains only 1 year, and only 5% are alive at 10 years

04/22/2025 22
Paraneoplastic syndrome
• 3-10% incidence
• Inappropriate secretion of ACTH & ADH occur predominantly in small cell
carcinoma
• Neuromuscular syndromes, including a myasthenic syndrome, peripheral
neuropathy, and polymyositis
• Clubbing of the fingers and hypertrophic pulmonary osteoarthropathy
• Coagulation abnormalities, including migratory thrombophlebitis, nonbacterial
endocarditis, and disseminated intravascular coagulation
• Hypercalcemia most often is encountered with squamous cell neoplasms
• The hematologic syndromes with adenocarcinomas
• The neurologic syndromes with small cell neoplasms
04/22/2025 23
Carcinoid Tumors
Bronchial Carcinoids
• Represent 1-5% of all lung carcinoma
• Most patients are younger than 40yrs & both sexes are affected equally
• May arise centrally or peripherally
• They are best thought of a low-grade neuroendocrine carcinomas
• Are of two types ( typical & atypical)
• 5- and 10-year survival rates for typical carcinoids are above 85%, while
these rates drop to 56% and 35%, respectively, for atypical carcinoids

04/22/2025 24
 Clinical presentation
• Due to intraluminal growth
• Persistent cough
• Hemoptysis
• Impairment of respiratory drainage with secondary bacterial infection
• Elaboration of vasoactive amines
 Intermittent attacks of diarrhea
 Flushing
 Cyanosis
• They are amenable for treatment
• Distant metastases are rare
• Typical carcinoid, atypical carcinoid, and large cell neuroendocrine and small cell carcinoma can be viewed as a
continuum of increasing histologic aggressiveness and malignant potential within the spectrum of pulmonary
neuroendocrine neoplasms
04/22/2025 25
 Morphology
• bronchial carcinoids originate in main-stem bronchi and grow in one
of two patterns:
(1) an obstructing polypoid, spherical, intraluminal mass
(2) a mucosal plaque penetrating the bronchial wall to fan out in the
peribronchial tissue-the so-called collar-button lesion

04/22/2025 26
04/22/2025 27
04/22/2025 28
Metastatic tumors
• The lung is the most common site of metastasis for both carcinomas
& sarcomas
• Usually metastatic tumors involve the periphery of the lung with a
cannonball appearance
• Other patterns of these tumors include solitary nodule, pneumonic
consolidation, endobronchial or pleural nodule
• The subpleural lymphatics may be outlined by the contained tumor
producing a gross appearance known as lymphangitis carcinomatosa

04/22/2025 29
PLEURAL LESIONS
• Disease of the pleura usually is a complication of an underlying pulmonary disease
• Normally there is 15ml of lubricating fluid in the cavity
Pleural Effusion and Pleuritis
• Pleural effusions can be either transudates or exudates.
• When the effusion is a transudate,the condition is termed hydrothorax.
• Congestive heart failure is the most common cause of bilateral hydrothorax.
• 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
(1) microbial invasion through either direct extension of a
pulmonary infection or blood-borne seeding (suppurative
pleuritis or empyema)
(2) cancer (lung carcinoma, metastatic neoplasms to the lung or pleural surface,
mesothelioma)
(3) pulmonary infarction
04/22/2025 (4) viral pleuritis 30
 • Malignant effusions characteristically are large and
frequently bloody (hemorrhagic pleuritis).
• Cytologic examination may reveal the malignant cells
• Transudates and serous exudates usually are resorbed
without residual effects if the inciting cause is
controlled or remits.
• By contrast, fibrinous, hemorrhagic, and suppurative
exudates may lead to fibrous organization, yielding
adhesions or fibrous pleural thickenings that
sometimes undergo calcification.

04/22/2025 31
Empyema
• Mostly results from contagious dissemination of infection from
intrapulmonary infection
• Sometimes from hematogenous & lymphatic dissemination or from
subdiaphragmatic sites
• Characterized by loculated, yellow creamy pus composed of
neutrophils & organism
• It usually results in fibrosis of the pleural cavity by organization of the
exudate less commonly it can resolve

04/22/2025 32
Pneumothorax
• Air or gas in the pleural cavities
• Spontaneous, traumatic, therapeutic
• Most commonly associated with emphysema, asthma, & TB
• Causes compression, collapse of the lung & may be responsible for
marked respiratory distress

04/22/2025 33
• Hemothorax is the collection of whole blood (in contrast with bloody effusion) in
the pleural cavity
• May be a complication of a ruptured intrathoracic aortic aneurysm, an event that
is almost always fatal.
• With hemothorax, in contrast with bloody pleural effusions, the blood clots within
the pleural cavity.
• Chylothorax is a pleural collection of a milky lymphatic fluid containing
microglobules of lipid.
• The total volume of fluid may not be large, but chylothorax is always significant
because it implies obstruction of the major lymph ducts, usually by an
intrathoracic cancer (e.g., a primary or secondary mediastinal neoplasm, such as a
lymphoma).
04/22/2025 34
Mesothelioma
• Malignant tumor of mesothelial cells
• Usually arising in the parietal or visceral pleura
• Highly malignant neoplasm with short survival
• Most patients (70%) have an asbestos exposure history
• Asbestos exposure also increases the risk of pulmonary cancer
• Smoking is not related to mesothelioma

04/22/2025 35
 Mesotheliomas conform to one of three patterns:
1. epithelial, in which cuboidal cells line tubular and microcystic
spaces, into which small papillary buds project; this is the most
common pattern and also the one most likely to be confused with a
pulmonary adenocarcinoma
2. sarcomatoid, in which spindled and sometimes fibroblastic-
appearing cells grow in nondistinctive sheets
3. biphasic, having both sarcomatoid and epithelioid areas.

04/22/2025 36
04/22/2025 37