SPECIAL SELECTED TOPICS- RESPIRATORY SYSTEM DISORDERS-SSTRSDO-QAA 028
1. What
are the main characteristics of bronchogenic carcinomas?

Bronchogenic carcinoma is the most common primary malignant
tumor of the lung and a leading cause of cancer-related death worldwide. Most
cases are strongly associated with cigarette smoking. The tumor usually arises
from the bronchial epithelium after progressive dysplastic and malignant
transformation.
Bronchogenic carcinomas are aggressive tumors with early
local invasion and distant metastasis. Patients commonly present with cough,
hemoptysis, chest pain, dyspnea, or recurrent pneumonia. Some tumors produce
paraneoplastic syndromes due to ectopic hormone secretion. Histologically, they
are classified into several major subtypes.
Early diagnosis is often difficult because symptoms appear
late. Prognosis depends mainly on histological type and clinical stage.
2. Which
etiologic agents have been known to promote lung cancers?
Cigarette smoking is the single most important etiological
factor responsible for lung cancer. Passive smoking also increases the risk.
Occupational exposure to asbestos, arsenic, chromium, nickel, beryllium, and
uranium contributes significantly. Radon gas exposure is an important cause,
especially in underground miners and poorly ventilated buildings.
Air pollution and diesel exhaust increase the incidence of
lung cancer. Previous pulmonary fibrosis and chronic lung disease predispose to
malignant transformation. Ionizing radiation is another recognized carcinogenic
factor.
Genetic susceptibility influences individual risk. Smoking
combined with asbestos exposure produces a synergistic increase in lung cancer
risk.
Avoidance of tobacco remains the most effective preventive
measure.
3. List
the main histologic types of bronchogenic carcinomas.
Bronchogenic carcinomas are classified into four major
histological types. Squamous cell carcinoma arises from bronchial epithelium
and often shows keratinization. Adenocarcinoma originates from gland-forming
epithelial cells and is the most common type overall.
Small cell carcinoma is a highly malignant neuroendocrine
tumor with early metastasis. Large cell carcinoma is an undifferentiated
malignant epithelial tumor lacking features of the other types.
Additional less common variants include adenosquamous
carcinoma and sarcomatoid carcinoma. Histological classification guides
treatment decisions.
Molecular testing is especially important in adenocarcinoma.
Accurate pathological diagnosis is essential for prognosis and therapy.
4. What
is the most common histologic type of lung cancer?
Adenocarcinoma is currently the most common histologic type
of lung cancer worldwide. It occurs in both smokers and non-smokers but is
particularly common among non-smokers and women. The tumor usually arises in
the peripheral parts of the lung.
Histologically, it forms glands or produces mucin. Many
tumors harbor mutations involving EGFR, ALK, KRAS, or other molecular pathways.
Molecular testing is essential because targeted therapy improves survival in
selected patients.
Adenocarcinoma may invade the pleura and metastasize early.
Clinical presentation includes cough, dyspnea, chest pain, or incidental
radiological detection.
Prognosis depends primarily on tumor stage at diagnosis.
5. How
are lung cancers divided according to their response to chemotherapy?
Lung cancers are broadly divided into small cell lung
carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC) according
to their biological behavior and response to treatment. Small cell carcinoma
responds well initially to chemotherapy and radiotherapy because of its high
mitotic activity.
However, recurrence is common, and long-term survival remains
poor. Non-small cell carcinomas include squamous cell carcinoma,
adenocarcinoma, and large cell carcinoma. These tumors respond less effectively
to chemotherapy than small cell carcinoma.
Surgical resection is the preferred treatment for localized
NSCLC. Targeted therapy and immunotherapy have significantly improved outcomes
in selected patients.
Accurate classification is essential for choosing appropriate
treatment.
6. Which
types of carcinomas are most closely related to smoking?
Squamous cell carcinoma and small cell carcinoma show the
strongest association with cigarette smoking. Nearly all patients with small
cell carcinoma have a significant smoking history.
Squamous cell carcinoma develops through squamous metaplasia
and dysplasia induced by tobacco smoke. Large cell carcinoma also has a strong
association with smoking. Adenocarcinoma is associated with smoking but also
commonly occurs in non-smokers.
Tobacco smoke contains numerous carcinogens that produce
genetic mutations in bronchial epithelial cells. The risk increases with the
duration and intensity of smoking.
Smoking cessation substantially reduces future cancer risk.
Tobacco control remains the most effective preventive strategy.
7. In
which parts of the lung do most bronchogenic carcinomas arise?
The site of origin varies according to the histological
subtype of bronchogenic carcinoma. Squamous cell carcinoma usually arises
centrally in the main, lobar, or segmental bronchi. Small cell carcinoma also
commonly originates in the central bronchi.
Adenocarcinoma most frequently develops in the peripheral
lung parenchyma, often near the pleura. Large cell carcinoma may arise either
centrally or peripherally. Peripheral tumors may invade the pleura and chest
wall.
Central tumors commonly produce bronchial obstruction,
atelectasis, and recurrent pneumonia. Knowledge of tumor location assists
radiological diagnosis and biopsy planning.
Tumor site also influences clinical presentation and surgical
management.
8.
Describe the most common pathways of lung cancer spread.
Lung carcinoma spreads by direct invasion, lymphatic
dissemination, hematogenous metastasis, and transcoelomic extension. Direct
invasion involves the pleura, chest wall, mediastinum, diaphragm, or
pericardium. Lymphatic spread first involves hilar and mediastinal lymph nodes.
Hematogenous spread commonly affects the brain, liver,
adrenal glands, bones, and opposite lung. Pleural involvement may produce
malignant pleural effusion.
Tumor cells may invade major blood vessels and bronchi. Small
cell carcinoma metastasizes particularly early and extensively. Distant
metastases are often present at the time of diagnosis. The extent of metastatic
spread is a major determinant of prognosis.
9. What
are the main pathologic features of squamous cell carcinoma of the lung?

Squamous cell carcinoma usually arises centrally from the
major bronchi and is strongly associated with cigarette smoking. It develops
through a sequence of squamous metaplasia, dysplasia, carcinoma in situ, and
invasive carcinoma.
Grossly, the tumor forms a firm gray-white mass that may
obstruct the bronchial lumen. Central necrosis frequently produces cavitation.
Microscopically, malignant squamous cells show keratinization and intercellular
bridges.
Tumor differentiation varies from well differentiated to
poorly differentiated forms. Local invasion commonly involves adjacent bronchi
and mediastinal structures.
Hypercalcemia may occur due to ectopic production of
parathyroid hormone-related peptide (PTHrP). Surgical resection offers the best
outcome in localized disease.
10. What
are the main pathologic features of adenocarcinoma of the lung?

Adenocarcinoma is the most common primary lung cancer and
usually arises in the peripheral lung parenchyma. It originates from glandular
epithelial cells or type II pneumocytes. Grossly, it appears as a firm
gray-white peripheral mass, often associated with pleural retraction.
Microscopically, the tumor forms glands or produces
intracellular or extracellular mucin. Several histological patterns, including
acinar, papillary, micropapillary, solid, and lepidic, may be present.
Molecular abnormalities involving EGFR, ALK, ROS1, and KRAS
are common. The tumor invades pleura, lymphatics, and blood vessels in advanced
stages. Regional lymph node and distant metastases may occur early.
Histological subtype and molecular profile guide targeted
therapy and prognosis.
11. What
are the main morphologic characteristics of bronchioloalveolar carcinoma?

Bronchioloalveolar carcinoma is now classified as adenocarcinoma
in situ or lepidic-predominant adenocarcinoma. The tumor
usually arises in the peripheral lung and may appear as a solitary nodule or
diffuse pneumonic-type consolidation.
Microscopically, neoplastic cells grow along intact alveolar
septa in a lepidic pattern without destroying the underlying
lung architecture in early lesions. Mucin-producing and non-mucinous variants
are recognized.
Stromal, vascular, and pleural invasion are absent in
adenocarcinoma in situ but appear in invasive forms. Multiple bilateral lesions
may occur. The surrounding alveolar framework is initially preserved.
Prognosis is excellent for non-invasive lesions after
complete surgical excision. Invasive lesions behave like conventional
adenocarcinoma.
12.
Discuss the clinical symptoms caused by bronchioloalveolar carcinoma.
Patients commonly present with persistent cough and gradually
progressive dyspnea. Copious watery sputum (bronchorrhea) is a
characteristic feature in mucinous tumors. Hemoptysis may occur but is usually
mild.
Chest pain is uncommon unless pleural invasion develops.
Fever may lead to confusion with pneumonia. Weight loss and fatigue occur in
advanced disease. Chest radiographs may show a solitary peripheral nodule or
diffuse infiltrative shadows resembling pneumonia.
The tumor often responds poorly to antibiotics because it
mimics infection. Early diagnosis depends on imaging, bronchoscopy, biopsy, and
histopathological examination.
Prognosis is favorable in localized adenocarcinoma in situ
but less favorable in diffuse invasive disease.
13. What
are the main pathologic features of small cell carcinoma of the lung?

Small cell carcinoma is a highly malignant neuroendocrine
tumor strongly associated with cigarette smoking. It usually arises centrally
near the main bronchi. Grossly, it forms a soft gray-white infiltrative mass
with extensive necrosis.
Microscopically, the tumor consists of small round or
spindle-shaped cells with scant cytoplasm, finely granular chromatin, and
numerous mitotic figures. Nuclear molding is a characteristic feature.
The tumor shows extensive vascular invasion and early
metastasis. Neuroendocrine markers such as chromogranin, synaptophysin, and
CD56 are typically positive. Ectopic hormone production commonly causes
paraneoplastic syndromes.
sBecause dissemination occurs early, surgery is rarely
useful, and chemotherapy with radiotherapy is the primary treatment.
14.
Discuss the origin of large cell carcinoma of the lung.
Large cell carcinoma is an undifferentiated malignant
epithelial tumor that lacks the histological features of squamous cell
carcinoma, adenocarcinoma, or small cell carcinoma. It probably arises from
primitive bronchial epithelial stem cells capable of multidirectional
differentiation.
The tumor may occur in either central or peripheral parts of
the lung. Grossly, it forms a large soft mass with areas of hemorrhage and
necrosis. Microscopically, it contains large pleomorphic cells with abundant
cytoplasm, prominent nucleoli, and frequent mitoses. Gland formation and
keratinization are absent.
SThe tumor grows rapidly and metastasizes early. Prognosis is
generally poor because most patients present with advanced disease. Treatment
follows the principles used for non-small cell lung carcinoma.
15. How
do lung carcinomas present clinically?
Lung carcinoma often remains asymptomatic during its early
stages. Persistent cough is the most common presenting symptom. Hemoptysis,
chest pain, dyspnea, and recurrent pneumonia occur because of airway
obstruction or local invasion.
Constitutional symptoms include weight loss, anorexia,
fatigue, and fever. Hoarseness results from recurrent laryngeal nerve
involvement. Superior vena cava obstruction causes facial swelling and venous
congestion. Pancoast tumors produce shoulder pain and Horner syndrome due to
brachial plexus involvement.
Many patients present with symptoms caused by distant
metastases involving the brain, bones, liver, or adrenal glands. Early
detection through imaging significantly improves survival.
16.
Describe the importance of histologic type and clinical stage in the prognosis
and therapy of patients with lung cancer.
Histological classification determines the biological
behavior and treatment strategy of lung cancer. Small cell carcinoma is highly
aggressive and is treated mainly with chemotherapy and radiotherapy because
surgery is rarely beneficial.
Non-small cell carcinomas are managed primarily by surgical
resection when localized. Clinical staging using the TNM system is the most
important prognostic factor. Early-stage tumors have significantly better
survival than advanced metastatic disease.
Molecular testing identifies patients suitable for targeted
therapies such as EGFR or ALK inhibitors. Immunotherapy has improved outcomes
in selected advanced tumors.
Histological type predicts response to specific treatments.
Accurate staging and pathological diagnosis are essential for individualized
management and prognosis.
17. What
are the most frequent paraneoplastic syndromes in patients with lung cancer?
Paraneoplastic syndromes result from ectopic hormone
production or immune-mediated mechanisms rather than direct tumor invasion.
Small cell carcinoma commonly produces ACTH, causing Cushing
syndrome, and ADH, causing syndrome of inappropriate antidiuretic
hormone secretion (SIADH).
Squamous cell carcinoma frequently secretes parathyroid
hormone-related peptide (PTHrP), resulting in hypercalcemia. Neurological
syndromes include Lambert-Eaton myasthenic syndrome and peripheral neuropathy.
Hypertrophic pulmonary osteoarthropathy and digital clubbing
are well-recognized manifestations. Hypercoagulability may lead to migratory
thrombophlebitis. Dermatomyositis and polymyositis occur occasionally.
Recognition of paraneoplastic syndromes may facilitate early
diagnosis of occult lung cancer. Successful treatment of the primary tumor
often improves these manifestations.
18. List
the main histologic subtypes of neuroendocrine tumors of the lungs.
Pulmonary neuroendocrine tumors are classified into four
major histological subtypes based on differentiation and biological
behavior. Typical carcinoid tumor is a low-grade
neuroendocrine neoplasm with an excellent prognosis.
Atypical carcinoid tumor is an intermediate-grade tumor with increased
mitotic activity and focal necrosis. Large cell neuroendocrine
carcinoma is a high-grade malignant tumor with aggressive clinical
behavior. Small cell carcinoma is the most aggressive
neuroendocrine carcinoma and metastasizes early.
All neuroendocrine tumors express markers such as
chromogranin, synaptophysin, and CD56. Prognosis worsens progressively from
typical carcinoid to small cell carcinoma. Histological grading guides
treatment and predicts survival.
19. What
are the main clinical and pathologic characteristics of bronchial carcinoids?

Bronchial carcinoids are well-differentiated neuroendocrine
tumors arising from Kulchitsky cells of the bronchial mucosa. They account for
a small proportion of primary lung tumors and usually occur in younger
patients.
Most tumors arise centrally within the major bronchi and
produce cough, wheezing, recurrent pneumonia, or hemoptysis because of
bronchial obstruction. Grossly, they appear as well-circumscribed, highly
vascular, polypoid masses projecting into the bronchial lumen. Microscopically,
uniform neuroendocrine cells are arranged in nests, trabeculae, or rosettes.
Typical carcinoids have few mitoses and no necrosis, whereas
atypical carcinoids show increased mitotic activity and focal necrosis.
Carcinoid syndrome is uncommon because vasoactive substances are usually
metabolized in the lungs. Surgical excision is the treatment of choice.
The prognosis is excellent for typical carcinoids and
intermediate for atypical carcinoids.
20. List
the usual features of metastatic tumors in the lungs.

The lungs are one of the most common sites of metastatic
spread because they receive the entire cardiac output through the pulmonary
circulation. Metastases commonly arise from cancers of the breast, colon,
kidney, thyroid, prostate, liver, and malignant melanoma.
Grossly, metastatic tumors usually appear as multiple,
well-circumscribed, rounded nodules of varying sizes scattered throughout both
lungs. Some tumors produce diffuse lymphangitic spread or pleural involvement.
Histologically, the metastatic tumor resembles the primary
malignancy. Patients may be asymptomatic or present with cough, dyspnea, chest
pain, or hemoptysis. Chest CT is highly sensitive for detecting pulmonary
metastases.
Treatment depends on the primary tumor, extent of metastasis,
and patient's clinical condition. Pulmonary metastases generally indicate
advanced-stage malignancy and carry a guarded prognosis.
DR.C.GANESAN M.D
PROFESSOR OF MEDICINE