LUNG TUMORS

LUNG TUMORS

• Variety of tumor can arise from lung

- Carcinomas ( 90 – 95%).- Bronchial carcinoids (5%) and- Mesenchymal neoplasms (2-5%).

Lung carcinoma• Lung cancer is currently the most frequently

diagnosed major cancer in the world and the most common cause of cancer mortality worldwide.

• This is largely due to the carcinogenic effects of

cigarette smoke.

• It occurs most often between ages 40 and 70 years.

Etiopathogenesis: 1. Tobacco Smoking:• 87% of lung carcinomas occur in active smokers

or those who stopped recently.

• There was a statistical association between smoking and frequency of lung cancer- (1) The amount of daily smoking,- (2) The tendency to inhale, and- (3) The duration of the smoking habit.

• Risk of developing cancer is 10-fold greater in smoker and 60-fold greater risk in heavy smokers

• Cessation of smoking for 10 years reduces risk of carcinoma of lung.

• There is also association between cigarette smoking and carcinoma of the mouth, pharynx, larynx, esophagus, pancreas, uterine cervix, kidney, and urinary bladder.

• Secondhand smoke, or environmental tobacco smoke,

contains numerous human carcinogens for which there is no safe level of exposure.

• These sequential changes have been best documented for squamous cell carcinoma,

Respiratory coloumnar cells

Squamous metaplasia

Squamous dysplasia

Carcinoma in situ

INVASIVE SQUAMOUS CELL CARCINOMA

• More than 1200 potential carcinogens are present in the cigarette smoke.

• They include both initiators (polycyclic aromatic hydrocarbons such as benzo[a]pyrene) and promoters, such as phenol derivatives.

• Radioactive elements may also be found (polonium-210, carbon-14, potassium-40) as well as other contaminants, such as arsenic, nickel, molds, and additives.

• Bronchio-alveolar carcinomas, a type of tumor that is not strongly associated with smoking in humans.

2.Industrial Hazards• High-dose ionizing radiation is carcinogenic.

• Studies shows that there was an increased incidence of lung cancer among survivors of the Hiroshima and Nagasaki atomic bomb blasts.

• Uranium is weakly radioactive, but lung cancer rates

among nonsmoking uranium miners are 4 times higher.

• The risk of lung cancer is increased with asbestos. Among asbestos workers, one death in five is due to lung carcinoma, 1 in 10 to pleural or peritoneal mesotheliomas and 1 in 10 to gastrointestinal carcinomas

3. Air Pollution:• Radon is a ubiquitous radioactive gas that has

been linked epidemiologically to increased lung cancer in miners exposed to relatively high concentrations.

• Low-levels of indoor exposure (e.g., in homes in areas of high radon in soil) could also lead to increased incidence of lung tumors.

Molecular Genetics:• Exposures act by causing genetic alterations in lung cells,

which accumulate and eventually lead to the neoplastic phenotype.

• Dominant oncogenes- c-MYC, K-RAS, EGFR, and HER-2/neu. • Inactivated tumor suppressor genes- p53,RB, p16INK4a.

• P53- Both small and non-small cell carcinomas.

• c-MYC and RB gene- Small cell tumor.

• RAS and p16INK4a - Non small cell tumor.

Precursor lesions

• Three types of precursor epithelial lesions are recognized:

1. Squamous dysplasia and carcinoma in situ, 2. Atypical adenomatous hyperplasia, and

3.Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia.

Classification of lung carcinoma:

• Squamous cell carcinoma (25% to 40%) • Adenocarcinoma (25% to 40%)

• Small cell carcinoma (20% to 25%)• Large cell carcinoma (10% to 15%)

Histologic Classification of Malignant Epithelial Lung Tumors

• Squamous cell carcinoma• Small cell carcinoma• Combined small cell carcinoma • Adenocarcinoma:

- Acinar, papillary, bronchioloalveolar, solid, mixed subtypes

• Large cell carcinoma• Large cell neuroendocrine carcinoma

• Adenosquamous carcinoma.• Carcinomas with pleomorphic, sarcomatoid,

or sarcomatous elements.• Carcinoid tumor:

- Typical, atypical.• Carcinomas of salivary gland type.• Unclassified carcinoma.

1.Squamous Cell Carcinoma:• It is common in men and with a smoking history.

• Gross: Large grey white tumor near the hilum(central).

• Histologically, this tumor is characterized by the presence of keratinization and/or intercellular bridges.

• Keratinization may take the form of squamous pearls or individual cells with markedly eosinophilic dense cytoplasm.

• Mitotic activity is higher in poorly differentiated tumors.

• Squamous cell carcinomas show the highest frequency of p53 mutations.

• Loss of protein expression of the tumor suppressor gene RB is detected by immunohistochemistry in 15% of squamous cell carcinomas.

• The CDK-inhibitor p16INK4 is inactivated, and its protein product is lost in 65% of tumour.

• HER-2/neu is highly expressed in 30% of these cancers.

Gross – Squamous cell carcinoma

Squamous cell carcinoma

2. Adenocarcinoma:• It is common in women and nonsmokers.

• This tumor shows glandular differentiation or mucin production by the tumor cells.

• Gross – tumor is solid with more peripheral location.

• Adenocarcinomas show various growth patterns like acinar, papillary, bronchioloalveolar, and solid with mucin formation.

• Histologically shows well-differentiated tumors with obvious glandular elements to papillary lesions.

• K-RAS mutations are seen primarily in adenocarcinoma, with a much lower frequency in nonsmokers (5%) than in smokers (30%).

• p53, RB, and p16 mutations and inactivation have

the same frequency in adenocarcinoma as in squamous cell carcinoma.

Gross – Adenocarcinoma

Adenocarcinoma

Nuclear feautres

Broncho- alveolar carcinoma:• It occurs in the terminal bronchioloalveolar regions.

• Gross- It almost always occurs in the peripheral portions of the lung either as a single nodule or, more often, as multiple diffuse nodules that sometimes coalesce to produce a pneumonia-like consolidation.

• The parenchymal nodules have a mucinous, gray

translucence when secretion is present but otherwise appear as solid and gray-white

• Histologically, the key feature is their growth along preexisting structures without destruction of alveolar architecture.

• The growth pattern has been termed "lepidic," an

allusion to the neoplastic cells resembling butterflies sitting on a fence.

It has two subtypes:• 1. Nonmucinous- Columnar, peg-shaped, or cuboidal

cells. • 2. Mucinous- Tall, columnar cells with cytoplasmic and

intra-alveolar mucin, growing along the alveolar septa.

Broncho-alveolar carcinoma

3. SMALL CELL CARCINOMA:• The epithelial cells are small, with scant cytoplasm,

ill-defined cell borders, finely granular nuclear chromatin (salt and pepper pattern), and absent or inconspicuous nucleoli.

• The cells are round, oval, and spindle-shaped, and nuclear molding is prominent.

• The mitotic count is high. • Necrosis is common and often extensive.

• Electron microscopy- Dense-core neurosecretory granules 100 nm in diameter in the cytoplasm.

• IHC stain- Chromogranin, synaptophysin, and Leu-7 (in 75% of cases) and parathormone-like substances.

• It is most aggressive tumors, metastasize widely, and are virtually incurable by surgical means.

• p53 and RB tumor suppressor genes are frequently mutated (50% to 80% and 80% to 100% of small cell carcinomas, respectively).

Small cell carcinoma

4. LARGE CELL CARCINOMA:• This is an undifferentiated malignant epithelial tumor that lacks

the cytologic features of small cell carcinoma and glandular or squamous differentiation.

• The cells typically have large nuclei, prominent nucleoli, and a moderate amount of cytoplasm.

• Ultrastructurally, however, minimal glandular or squamous differentiation is common.

• One histologic variant is large cell neuroendocrine carcinoma. This is recognized by such features as organoid nesting, trabecular, rosette-like and palisading patterns - Neuroendocrine differentiation.

Large cell carcinoma

5. CARCINOID TUMOR• It represent 1% to 5% of all lung tumors.

• Most patients with these tumors are younger than 40 years of age and affects both sexes.

• Carcinoid tumors are subclassified into typical and atypical carcinoids.

• Typical carcinoids have no p53 mutations or BCL2/BAX imbalance.

• Gross:- Carcinoids may centrally or peripheral lesion.

- Central tumors grow as finger-like or spherical polypoid masses that commonly project into the lumen of the bronchus and measures 3 to 4 cm in diameter.( collarbutton lesion ).

- Peripheral tumors are solid and nodular.

- Spread to local lymph nodes is more likely with atypical carcinoid.

• Microscopy: -Tumor is composed of organoid, trabecular, palisading, ribbon, or rosette-like arrangements of cells separated by a delicate fibrovascular stroma.

-The individual cells are quite regular and have uniform round nuclei and a moderate amount of eosinophilic cytoplasm.

Typical carcinoids- 2 mitoses per 10 hpf and no necrosis.Aypical carcinoids- 2 to 10 mitoses per 10 hpf and foci of

necrosis.

Carcinoid tumors

Secondary Pathology:• Partial obstruction may cause marked focal emphysema.

• Total obstruction may lead to atelectasis. • severe suppurative or ulcerative bronchitis or

bronchiectasis. • Pulmonary abscesses. • Compression or invasion of the superior vena cava can

cause venous congestion, dusky head and arm edema, and, ultimately, circulatory compromise—the superior vena cava syndrome.

TNM STAGING:• T1- Tumor <3 cm without pleural or main stem

bronchus involvement.• T2- Tumor >3 cm or involvement of main stem

bronchus 2 cm from carina, visceral pleural involvement, or lobar atelectasis.

• T3- Tumor with involvement of chest wall, diaphragm, mediastinal pleura, pericardium, main stem bronchus 2 cm from carina, or entire lung atelectasis.

• T4- Tumor with invasion of mediastinum, heart, great vessels, trachea, esophagus, vertebral body, or carina or with a malignant pleural effusion.

• N0- No demonstrable metastasis to regional lymph nodes.

• N1- Ipsilateral hilar or peribronchial nodal involvement.

• N2- Metastasis to ipsilateral mediastinal or subcarinal lymph nodes.

• N3- Metastasis to contralateral mediastinal or hilar lymph nodes, ipsilateral or contralateral scalene, or supraclavicular lymph nodes.

• M0- No (known) distant metastasis.• M1- Distant metastasis present.

Clinical features:• Major complaints are

- Cough (75%),- Weight loss (40%),- Chest pain (40%),- Dyspnea (20%) and- Haemoptysis.

PARA-NEOPLASTIC SYNDROME• Antidiuretic hormone (ADH).• Adrenocorticotropic hormone (ACTH), producing

Cushing syndrome.• Parathormone, parathyroid hormone-related

peptide.• Calcitonin, causing hypocalcemia.• Gonadotropins, causing gynecomastia.• Serotonin and bradykinin, associated with the

carcinoid

• Lambert-Eaton myasthenic syndrome.• Acanthosis nigricans.• Apical lung cancers in the superior pulmonary

sulcus tend to invade the neural structures around the trachea, including the cervical sympathetic plexus, and produce a group of clinical findings that includes severe pain in the distribution of the ulnar nerve and Horner syndrome (enophthalmos, ptosis, miosis, and anhidrosis) on the same side as the lesion. Such tumors are also referred to as Pancoast tumors.

Metastases to lung: • The lung is the most common site of metastatic

neoplasms. • Both carcinomas and sarcomas arising anywhere

in the body may spread to the lungs via the blood or lymphatics or by direct continuity.

• Growth of contiguous tumors into the lungs occurs most often with esophageal carcinomas and mediastinal lymphomas.

• GROSS- Multiple discrete nodules (cannonball lesions) are scattered throughout all lobes.

• These discrete lesions tend to occur in the periphery of the lung rather than in the central locations of the primary lung carcinoma.

• Other patterns include solitary nodule, endobronchial, pleural, pneumonic consolidation, and mixtures of the above.

Metastases to lung

Metastases to lung

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