Lung Tumors Pathology Notes

Pathology of Lung Tumors

Objectives

  • Understand the relationship between respiratory tract malignancies and cigarette smoking.

  • Identify the major histologic forms of lung cancer and their biologic behavior patterns in relation to prognosis.

  • Recognize the importance of distinguishing between non-small cell lung carcinoma and small cell lung carcinoma.

  • Describe the modes of spread of lung carcinoma and their possible clinical manifestations.

  • Acknowledge the lung as a common site for metastatic spread of tumors from elsewhere.

  • Identify the tumors that frequently metastasize to the lung.

  • Understand paraneoplastic syndromes and list the types associated with lung carcinoma.

  • Describe the common location, typical histology, clinical manifestations, and cell of origin of bronchial carcinoid tumors.

Carcinoma of the Lung

  • Most common cancer worldwide.

  • Leading cause of cancer death.

  • Accounts for 1/3 of cancer deaths in the USA.

  • More prevalent in men, but incidence in women is increasing.

  • Overall 5-year survival rate is approximately 15%.

Etiology of Lung Cancer

Tobacco Smoking

  • Strongest association with squamous cell carcinoma and small cell carcinoma.

  • Habitual smokers have a 60 times higher risk compared to non-smokers.

  • Passive smokers have twice the risk compared to non-smokers.

  • Smoking pipes and cigars also increases the risk.

Industrial Exposure

  • Radioactive substances like Uranium.

  • Asbestos workers.

  • Inhaled chemicals: nickel, chromium, arsenic, beryllium, etc.

Scarring

  • Scar cancer (adenocarcinoma).

Clinical Presentation

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

  • Local compression and obstruction

  • Distant metastasis

  • Paraneoplastic syndromes

Manifestations of Lung Cancer Based on Location

  • Central Lung Cancer

    • Ulceration, cough, hemoptysis

    • Obstruction leading to pneumonia, lung abscess, bronchiectasis, collapse

  • Apical Lung Cancer

    • Pancoast syndrome

    • Thoracic duct involvement leading to chylothorax

  • Hilar Lymph Node Enlargement

  • Pleural Involvement

    • Pain, effusion

  • Pericardial Involvement

    • Pain, effusion

  • Peripheral Lung Cancer

  • Lower Cervical Lymph Node Enlargement

  • SVC Obstruction

  • Recurrent Laryngeal Nerve Palsy

    • Hoarseness

  • Esophagus Compression

    • Fistula, dysphagia

Bronchial Carcinoma - Modes of Spread

  • Local Spread to:

    • Pleural surface

    • Pleural cavity

    • Chest wall

    • Adjacent thoracic structures

  • Lymphatic Spread to:

    • Hilar, tracheal, and mediastinal lymph nodes

  • Hematogenous Spread to:

    • Liver, bones, brain, and adrenals

Secondary Pathological Changes in Lung Carcinoma

  • Total obstruction of bronchus with atelectasis

  • Suppurative bronchitis and pneumonia

  • Bronchiectasis

Paraneoplastic Syndromes

  • Collections of symptoms resulting from substances produced by the tumor, occurring remotely from the tumor itself.

  • Symptoms can be endocrine, neuromuscular, musculoskeletal, cardiovascular, cutaneous, hematologic, gastrointestinal, renal, or miscellaneous.

Hormones and Hormone-like Factors:

  • ADH - hyponatremia (Small cell carcinoma)

  • ACTH - Cushing's Syndrome (Small cell carcinoma)

  • Parathormone, prostaglandin E - Hypercalcaemia (Mostly squamous cell carcinoma)

  • Calcitonin - hypocalcaemia

  • Gonadotrophins - gynecomastia

  • Serotonin - Carcinoid Syndrome (Bronchial carcinoid tumor)

Lung Carcinoma Diagnosis

Radiological Investigations:

  • Chest X-ray

  • CT scan

    • May show cavitation

Bronchoscopy:

  • To visualize central lesions

  • Bronchial brushings, bronchial washings, biopsy.

CT Guided Biopsy:

  • For peripheral lesions

Cytology:

  • Sputum

  • Bronchial brushings, washings, lavage

  • Pleural fluid

  • FNAC of lymph nodes

Histology:

  • Biopsy

Bronchial Washings:

  • Saline is flushed and retrieved from airways during bronchoscopy.

Bronchoalveolar Lavage (BAL):

  • Saline is instilled deep into the lung and aspirated; analyzed for tumor cells.

Cytology

Malignant Cells:

  • Large nucleus

  • Necrosis

  • Diathetic

Biopsy

Carcinoma:

  • Abnormal

Adenocarcinoma:

  • Busy (crowded glands)

  • Highly malignant tumor

Lung Tumors

  • Tumors arising from bronchial epithelium are carcinomas (95%)

  • Others include bronchial carcinoids, mesenchymal malignancies, lymphomas, and hamartomas (5%)

Histological Types of Lung Carcinomas

  1. Non-small cell carcinomas (treated with surgery)

  2. Small cell carcinomas (treated with chemotherapy, poor prognosis)

Non-Small Cell Carcinomas

  1. Squamous cell carcinoma

  2. Adenocarcinoma

  3. Large cell carcinoma

  • Early-stage carcinomas are best treated by surgery.

Squamous Cell Carcinoma

  • More common in men.

  • Closely correlated with smoking.

  • Arises centrally in major bronchi.

  • Large tumors show necrosis and cavitation.

  • Dissemination outside the thorax is less common than with other types.

  • Well-differentiated tumors produce keratin and show intercellular bridges.

  • Less well-differentiated tumors show minimal squamous features.

  • Adjacent bronchi may show squamous metaplasia, dysplasia, and carcinoma in situ.

Adenocarcinoma

  • Most common type of lung cancer in women and non-smokers.

  • May arise in relation to peripheral scars.

  • Peripherally located; smaller tumors grow more slowly than SCC.

  • Metastasize widely at an early stage.

  • Identified by establishing glandular differentiation and mucin production by cells.

  • Many histological patterns: acinar, papillary, solid, micropapillary, invasive mucinous.

  • Molecular testing is now routine to facilitate targeted therapy.

  • Common mutations include EGFR, KRAS and BRAF, translocation of ALK.

  • Acinar (gland) formation by atypical malignant cells produce mucin.

Large Cell Carcinoma

  • Anaplastic carcinoma with large cells, large vesicular nuclei and prominent nucleoli.

  • Some have giant cells, mucin-producing cells, and some have clear cells.

Small Cell Carcinoma

  • Highly malignant tumor.

  • Strong relationship to cigarette smoking.

  • Arises from neuroendocrine cells.

  • Most often hilar or central.

  • Shows early lymph node spread.

  • Most common lung cancer type associated with ectopic hormone production.

  • Small, round, or fusiform cells with scanty cytoplasm.

  • Frequent mitoses and necrosis.

  • EM- Neurosecretory granules

  • Immunohistochemistry- Neuroendocrine markers (chromogranin, synaptophysin, neuron specific enolase, CD56).

  • Median survival, even with treatment, is about one year.

  • Almost all have metastasized at the time of diagnosis.

Bronchial Carcinoid Tumor

  • Arises from neuroendocrine cells which line the bronchial mucosa.

  • Represents about 5% of all pulmonary neoplasms.

  • Macroscopy: intraluminal mass or tumor with intrabronchial and extrabronchial components (collar-button lesions).

  • Nests of uniform cells showing round regular nuclei with salt and pepper chromatin.

  • Tumors with increased mitosis and necrosis are called atypical carcinoids.

  • Immunohistochemistry- Neuroendocrine markers (chromogranin, synaptophysin, neuron specific enolase, CD56).

  • Some tumors cause carcinoid syndrome characterized by diarrhea, flushing, and cyanosis.

  • Patients with typical carcinoid tumors have a 10-year survival of >85%.

TNM Staging of Lung Cancer (AJCC 8th edition)

T1

  • Tumor <= 3 cm

T2

  • Tumor > 3 cm to <= 5 cm

  • Involves main bronchus, without main carinal involvement, with atelectasis and/or obstructive pneumonia of part or all of lung

  • Invades visceral pleura

  • Extends across fissure or involves two adjacent lobes

T3

  • Tumor > 5 cm to <= 7 cm

  • Parietal pericardium or phrenic nerve invasion

  • Invades parietal pleura

  • Separate tumor nodules in the same lobe as the primary tumor

T4

  • Tumor > 7 cm

  • Invades trachea, recurrent laryngeal nerve, great vessels, diaphragm, esophagus, and/or vertebral body

  • Involves main carina

  • Separate tumor nodules in a different ipsilateral lobe

N1

  • Ipsilateral hilar, intrapulmonary, and/or peribronchial

N2

  • Subcarinal, ipsilateral mediastinal

N3

  • Contralateral mediastinal and hilar, ipsilateral or contralateral supraclavicular or scalene

M1a

  • Tumor in contralateral lung or pleural nodule or malignant pleural effusion

M1b

  • Single extrathoracic metastasis

M1c

  • Multiple extrathoracic metastases in one or more organs

Metastatic Tumors to the Lung

  • 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.

  • Usually multiple, bilateral, sharply outlined, rapidly growing, more pleomorphic and necrotic than lung primaries.

Blood Borne:

  • Multiple, peripheral discrete nodules (cannon balls).

Lymphatics:

  • Subpleural lymphatic involvement (Lymphangitis carcinomatosis).