Pulmonary Neoplasms - MedPath

What does this refer to

• ______ : are abnormal tissue growths; may be benign or malignant

Neoplasms

What does this refer to

• Primary vs. metastatic lung tumors

• Lung cancer is the leading cause of cancer-related deaths worldwide

Pulmonary neoplasms

What does this refer to

• Benign vs. Malignant

• Primary vs. Secondary (metastatic)

• Non-small cell lung cancer (NSCLC) vs. Small cell lung cancer (SCLC)

Classification of Pulmonary Tumors

What does this refer to

• Tobacco smoke: primary risk factor

• Environmental exposures: radon, asbestos, pollution

• Genetic predispositions

Etiologic factors

What does this refer to

• Most common: Hamartomas (contain cartilage, fat, connective tissue)

• Usually peripheral and asymptomatic

• Detected incidentally on imaging

• Slow growing

Benign Pulmonary Tumors

What does this refer to

• They consist of a mixture of normal lung tissue elements, including cartilage, fat, connective tissue, and smooth muscle, with entrapped respiratory epithelium.

Composition of Hamartomas

What does this refer to

• They often appear as well-defined, coin-shaped nodules on imaging, sometimes with characteristic "popcorn-like" calcification or fat.

Appearance of Hamartomas

What does this refer to

• Non-Small Cell Lung Cancer (NSCLC) ~85%

• Small Cell Lung Cancer (SCLC) ~15%

• Other: carcinoid tumors, mesothelioma, lymphomas

Malignant Pulmonary Tumors

What does this refer to

• Smoking: responsible for ~90% of lung cancer cases

  • Heavy smokers have 20 times’ greater chance of lung cancer than nonsmokers

  • Smoking is related to cancers of the larynx, oral cavity, esophagus, and urinary bladder

• Environmental or occupational exposures: radon, asbestos, air pollution

• Genetic mutations: inherited or acquired

Etiologic factors

What Non small cell lung cancer (NSCLC) subtype does this refer to

• peripheral, most common in non-smokers

Adenocarcinoma

What Non small cell lung cancer (NSCLC) subtype does this refer to

• : central, associated with smoking

Squamous cell carcinoma

What Non small cell lung cancer (NSCLC) subtype does this refer to

• : undifferentiated, poor prognosis

Large cell carcinoma

What does this refer to

• Accounts for ~15% of cases

• Highly aggressive and rapidly growing

• Strongly associated with smoking

Small cell lung cancer (SCLC)

What does this refer to

• Driver mutations: EGFR, KRAS, ALK, BRAF (NSCLC); TP53, RB1 (SCLC)

• Promote proliferation, evade apoptosis, enhance survival

• Targetable mutations guide therapy decisions

Molecular Pathogenesis

What does this refer to

• ______ mutation → increased tyrosine kinase activity

• Downstream signaling: RAS-RAF-MEK, PI3K-AKT pathways

• Targeted by _______ inhibitors: erlotinib, osimertinib

EGFR Pathway in NSCLC

What mutation is the following

• _______ : associated with poor response to therapy

• Found in younger, non-smoking populations

KRAS

What mutation is the following

• _______ rearrangement: targetable with crizotinib, alectinib

• Found in younger, non-smoking populations

ALK

What does this refer to

• Initiation: DNA damage (carcinogens)

• Promotion: clonal expansion

• Progression: acquisition of malignant phenotype

Multistep Carcinogenesis

What does this refer to

• Metaplasia → Dysplasia → Carcinoma in situ → Invasive cancer

• Loss of differentiation and architecture

• Increased mitotic activity and pleomorphism

Histopathological Changes

What does this refer to

• Composed of stromal cells, immune cells, extracellular matrix

• Supports tumor growth, angiogenesis, immune evasion

• Dynamic and interactive system

Tumor Microenvironment

What does this refer to

• Tumors secrete vascular endothelial growth factor (VEGF) to promote blood vessel formation

• New vessels are leaky and irregular

• Targeted by anti-VEGF therapies (e.g., bevacizumab)

Angiogenesis in lung cancer

What does this refer to

• PD-L1 (Programmed Death-Ligand1) expression on tumor cells binds PD-1 on T cells

• Suppresses immune response

• Checkpoint inhibitors restore T-cell activity

Immune evasion mechanisms

What does this refer to

• Tumor cells degrade extracellular matrix via proteases

• Enter blood/lymphatic vessels

• Seed distant organs: brain, bone, liver, adrenals

Invasion and Metastasis

What does this refer to

• Occur due to ectopic hormone/cytokine production

• SCLC: SIADH, ectopic ACTH (Cushing), neurologic syndromes

• NSCLC: hypercalcemia (parathyroid hormone related protein-PTHrP), hypertrophic osteoarthropathy

Paraneoplastic syndrome

What paraneoplastic syndrome is associated with SCLC

SIADH, ectopic ACTH (Cushing), neurologic syndromes

What paraneoplastic syndrome is associated with NSCLC

NSCLC

What does this refer to

• Cough, hemoptysis, wheezing, chest pain, weight loss

• Recurrent pneumonia, hoarseness (recurrent laryngeal nerve)

• Superior vena cava syndrome in central tumors

Symptoms of Lung Cancer

What does this refer to

• CXR: mass, atelectasis, pleural effusion

• CT: defines size, lymph node involvement, metastases

• PET: identifies metabolically active disease

Radiologic Appearance

What does this refer to

• Bronchoscopy: visual and biopsy of central lesions

• Endobronchial ultrasound (EBUS): guides lymph node sampling

• Transthoracic needle biopsy for peripheral nodules

Bronchoscopy and Biopsy

What radiology technique tells you “: mass, atelectasis, pleural effusion”

CXR

What radiology technique tells you “: defines size, lymph node involvement, metastases”

CT

What radiology technique tells you “: identifies metabolically active disease”

PET

What is used to “visual and biopsy of central lesions”?

Bronchoscopy

What is used to “guides lymph node sampling”

Endobronchial ultrasound (EBUS)

What is used for for peripheral nodules

Transthoracic needle biopsy

Given the cytologic and histologic information below, what would you diagnose the patient with

• “glandular structures, mucin production”

Adenocarcinoma

Given the cytologic and histologic information below, what would you diagnose the patient with

• “keratin pearls, intercellular bridges”

Squamous

Given the cytologic and histologic information below, what would you diagnose the patient with

• “small blue cells, nuclear molding, necrosis”

SCLC

What does this refer to

• T: tumor size and local invasion

• N: nodal involvement

• M: presence of distant metastases

Stage guides prognosis and treatment

What does this refer to

• Surgical resection (stages I-IIIA)

• Adjuvant chemotherapy, radiation

• Targeted therapies and immunotherapies for advanced stages

NSCLC Treatment Strategies

What does this refer to

• Chemo-radiotherapy mainstay of treatment

• Limited stage: curative intent

• Extensive stage: palliative, often rapid relapse

SCLC Treatment Strategies

What does this refer to

• EGFR, ALK, ROS1 inhibitors for mutation-positive tumors

• Improved survival and reduced toxicity

• Resistance mutations (e.g., T790M) can develop

Targeted Therapy in NSCLC

What does this refer to

• Checkpoint inhibitors (PD-1/PD-L1 blockers)

• Effective in high PD-L1 expression

• Improves overall survival in NSCLC

Role of Immunotherapy

What does this refer to

• Checkpoint inhibitors (PD-1/PD-L1 blockers)

• Effective in high PD-L1 expression

• Improves overall survival in NSCLC

Surveillance and Follow-Up

What does this refer to

• 5-year survival depends on stage and histology

• Early-stage NSCLC: ~60-70%

• SCLC and late-stage NSCLC: <15%

Prognosis

What does this refer to

• Rare, aggressive cancer of pleura

• Strongly linked to asbestos exposure

• Long latency period (20–50 years)

• More common in men and older individuals

• Asbestos fibers cause chronic inflammation

• DNA damage leads to mesothelial cell mutation

• Tumor spreads along pleural surfaces

• Invades chest wall, diaphragm, and pericardium

Mesothelioma

What does this refer to

• Neuroendocrine tumors (NETs) of the lung

• Classified as typical or atypical

• Less aggressive than small cell carcinoma

• May secrete hormones (e.g., serotonin)

• Origin from neuroendocrine Kulchitsky cells

• Uncontrolled proliferation due to mutations (e.g., MEN1)

• Tumor may produce bioactive amines

• Can cause carcinoid syndrome if metastasized

Carcinoid tumors

What does this refer to

• : asbestos-related, pleural origin, aggressive

• Importance of early recognition and pathology

• Both require multidisciplinary management

Mesothelioma

What does this refer to

• “neuroendocrine tumors, variable behavior, hormone-secreting”

• Importance of early recognition and pathology

• Both require multidisciplinary management

Carcinoid Tumors