Are you more of a visual learner? Check out our online video lectures and start your respiratory medicine course now for free!

Image:a lit cigarette in an ashtray by Tomasz Sienicki. License: CC BY-SA 3.0


Overview

It is important to be familiar with the following types of tumors encountered in the lung:

Type Explanation
Lung cancer Malignant cancers arising from respiratory tract epithelium
Lung metastases Malignant cancers arising outside of the lung that have spread to the lung
Mesothelioma Primary malignant cancer of the mesothelium
Rarer lung tumors Unusual benign/ malignant cancers of the lung

Lung cancer is divided into two types based on histological constitution: non-small cell (80-85% of cases) and small cell lung cancers.

Epidemiology of Lung Cancer

Lung cancer accounts for 13% of all cancers, but 90% of cases are fatal. The incidence increases with age; lung cancer is rare before 50 years of age. It is more common in individuals aged 75-79 years. The incidence of lung cancer in males is about 500/100,000 per year. In females, it has increased substantially to about 400/100,000 per year, possibly because the number of female smokers has increased.

In the UK, the lifetime risk of individuals developing lung cancer is about 1 in 14 in men and about 1 in 19 in women.

Lung cancer world map

Image : “Trachea, bronchus, lung cancers world map-Deaths per million persons-WHO2012” by Chris55. License: CC BY-SA 4.0

Histological Types of Lung Cancer

In 97% of lung cancer cases, carcinoma of the lung arises from the uncontrolled growth of epithelial cells. The various histological types of lung cancer can be mentioned as follows::

Non-small cell lung cancer

There are three predominant histological types of non-small cell lung cancer. Squamous cell carcinoma constitutes about 30% of all lung cancer cases. It is mainly a disease of the central airways. These tumors arise from the respiratory epithelium in the central region of the lungs, usually in the proximal bronchus.

Adenocarcinoma constitutes about 40% of all lung cancer cases. These are peripheral tumors arising from the mucosal glands in a peripheral location in the lung. It is seen mostly in patients who are nonsmokers.  Large cell cancer constitutes about 10% of all lung cancer cases. It affects the peripheral lung and is histologically varied in nature, consisting of atypical cells with focal necrosis.

Small cell lung cancer

About 20% of lung cancer cases are small cell, which is centrally placed and arises from the peribronchial epithelium. Small cell lung cancer grows rapidly and metastasizes early to the mediastinal lymph nodes, bones, adrenal glands, liver, and brain. Small cell lung carcinoma is sensitive to chemotherapy; however, surgery is not curative in these patients.

Pathogenesis of Lung Cancer

Sequential acquisition of multiple mutations and gene duplications affecting the tumor suppressor genes and the oncogenes, such as p53, K-ras, and EGFR ultimately culminate into lung cancer. About 90% of cases are due to cigarette smoking. Exposure to asbestos works in synergy with smoking.

Other risk factors, which act as harbingers of lung carcinoma, include:

lung cancer cell during cell division

Image: “Lung cancer cell during cell division” by the United States: National Institutes of Health. License: Public Domain

  • Radon gas exposure
  • Uranium exposure
  • Radiotherapy to the lungs
  • Family history
  • Chemical exposure, such as diesel exhaust

Intriguingly, the incidence of lung cancer in patients with COPD is increased over and above the effects of smoking. However, it is important to recognize that not all lung cancers are due to smoking alone. Adenocarcinoma, for instance, occurs in non-smoking middle-aged women.

Clinical Recognition of Lung Cancer

By United Kingdom standards, the model age group is 75 to 79 years with incidence more in males. In this scenario, radiological evidence of a patch in the left upper part of the lung is potential lung cancer. Multiple different clinical symptoms can present to different specialties.

The symptoms are mentioned below:

  • Current or previous smoking
  • Aged over 50 years
  • Lung mass on an X-ray
  • Bone pain
  • Weight loss, cachexia, anorexia, neurologic dysfunction, and fatigue

A few weeks’ history of tumor symptoms, such as lung symptoms, might be due to local invasion, distal metastases, and paraneoplastic symptoms. The primary lung disease usually presents with a short history of a few weeks’ duration.

The most frequent modes of presentation of the primary disease can be briefly touched upon as follows:

Symptom Explanation
New cough Most frequent local symptom
Haemoptysis
  • Associated with central tumors of airway origin
  • Massive and occasionally fatal in nature
Asymptomatic lung mass
  • More likely to be adenocarcinoma
  • Squamous cell carcinoma usually presents as a central mass, while a central mass with large nodes is more typical of small cell lung cancer (SCLC)
Shortness of breath
  • Slow, insidious progressive shortness of breath over weeks indicates obstruction of large airways by the tumor, either by infiltration or  compression
  • Associated clinical signs are fixed monophonic wheeze, lobar or total lung collapse, and distal pneumonia
Systemic symptoms
  • Classic systemic symptoms of malignancy: weight loss, anorexia, fatigue, and malaise can appear within a few weeks of presentation
  • Eventually; a very morbid doomed cachexic appearance sets in
Clubbing This clinical sign may or may not be present.

There is a subtle, but definite, clinical-radiological association. It is a classic presentation if present. More often than not, the tumor can be localized to a particular part of the lung.

Simple such instances can be mentioned as follows:

Radiological feature Clinical correlation
Right upper lobe collapse Mostly secondary to central tumor blocking the right upper lobe bronchus. This leads to cough with occasional hemoptysis
Right apical mass Presents with pain in arm and cough
Small right lung lesion Often seen as an incidental finding. It is helpful if one gets a previous radiological image for comparison. A new onset lesion, along with a history of smoking, is potentially a cancer lesion unless proved otherwise.

Once the tumor leaves the lung borders, local invasion affects the lymph nodes first. Hilar and mediastinal lymph nodes by obstruction secondary to compression or infiltration can affect the surrounding vital neurovascular structures leading to respective pressure manifestations.

A brief mention of the various modes in which local invasion can manifest is as follows:

Structure affected Manifestations
None Asymptomatic masses
Superior vena cava obstruction in right-sided tumors Arm and face edema with a headache, fixed engorged JVP and dilated superficial chest wall veins are the manifestations
Recurrent laryngeal nerve palsy on the left side A hoarse voice with a “bovine” cough
Phrenic nerve palsy Raised hemidiaphragm is present as seen on a chest skiagram
Oesophageal obstruction This results in dysphagia and higher frequency of aspiration
Tracheal or major bronchial obstruction Dyspnoea with the collapsed lung is seen in patients with airway obstruction

Local invasion infrequently involves chest wall infiltration. Chest wall invasion is associated with excruciating pain, radiating from shoulder to the ulnar aspect of the arm to hand, rib destruction, and palpable firm non-tender mass. Invasion of the chest wall in cases of apical tumors results in a constellation of symptoms. The tumor is then known as “Pancoast’s tumor.” They are basically squamous cell carcinomas or adenocarcinomas.

The salient features of Pancoast’s tumor are:

  • Invasion of the brachial plexus
  • Pain in the arm (T1 root)
  • Wasting of the hand small muscles
  • Horner´s syndrome (partial ptosis, meiosis, and enophthalmos)

Lung cancer can spread to a multitude of varied organs relatively quickly. Liver and brain metastases are the most common, but the adrenal glands, bones, and cervical lymph nodes may also be affected.

A short description of distal metastases is as follows:

Organ with distal metastasis Manifestations
Brain Presenting as a space-occupying lesion, the symptoms are congruent with those secondary to raised intracranial pressure, such as vomiting, nausea, headache, focal neurological signs, mental state changes, and seizures
Bone Bone metastasis is characterized by unbearable night pains, pathological fractures, and cord compression in case of vertebral body involvement with elevated alkaline phosphatase
Liver Hepatomegaly with pain, weight loss, anorexia, and nausea
Cervical nodes A palpable hard mass in the neck may be the only complaint
Lungs Lung parenchymal involvement may be seen on a CT scan. It is not always associated with symptoms
Pleura Effusion with dyspnea is seen
Adrenal glands Usually asymptomatic; adrenal metastasis is a CT scan-based diagnosis

Paraneoplastic syndromes

Non-metastatic distal effects of cancer, secondary to ectopic hormones and autoantibodies, collectively constitute paraneoplastic syndromes. The significant paraneoplastic syndromes associated with lung cancer are induced by an alteration in the immune system responding to neoplasm, and their clinical features are as follows:

Cancer type Paraneoplastic syndrome Clinical features
All
  • Systemic disturbance
  • Hypercoagulability
  • Anemia of chronic disease
  • Dermatological
  • Cachexia, anorexia, malaise, fatigue
  • DVT, PE, thrombocytosis
  • Low Hb
  • Gynaecomastia, acanthosis nigricans, dermatomyositis
SCLC SIADH

 

 

 

Cushing’s syndrome

 

Eaton Lambert syndrome

 

Neurological

  • Hyponatremia
  • Confusion
  • seizures
  • coma
Cushingoid appearance, weakness, hypokalemia
Muscle weakness
Neuropathies, cerebellar syndromes, cognitive dysfunction
NSCLC Hypertrophic pulmonary osteoarthropathy

 

Hypercalcemia

Clubbing, painful and tender wrists and ankles

Polyuria, polydipsia, confusion, and hyperreflexia

Differential Diagnosis of Suspected Lung Cancer

There are many conditions that can mimic lung cancer. The important differentials of lung masses are:

Differential Example
Lung metastases from another type of cancer
  • Breast cancer
  • Prostate cancer
Less common tumors of the lung Carcinoid
Lung infection
  • TB: active disease or healed granulomas
  • Lung abscess
  • Fungal/ parasite infections
Benign masses
  • Lung sequestration
  • Enfolded lung
  • Parenchymal scar
Lung inflammatory conditions
  • Sarcoid
  • Vasculitis

Management and Treatment of Lung Cancer

Three important questions need to be addressed before one can start treating lung cancer. These questions are focused to determine the stage and histology of the disease, which will indicate whether the tumor is curable or not.

Diagnosis

There is a multitude of diverse tests available to determine the stage of the disease. All patients with lung cancer should have a chest X-ray and CT of the chest, liver, and adrenals. One should look for size and local invasion extent, the presence of hilar and mediastinal nodes, lung and pleural metastases, and liver or adrenal gland metastases.

Blood tests are also required, such as Fbc, U+E, and LFT. One should look for raised ALP to rule out liver and bone metastases. Paraneoplastic syndromes and fitness for therapy are also related to these tests.

Chest-Xray

Image: “60-year-old male a chronic smoker presented with blood in sputum and breathlessness. Chest Xray showed a mass in the left lung and biopsy confirmed to be cancer” by Dr manikandan d. License: CC BY-SA 3.0

According to the clinical presentation, selected patients should have a neck USG in case of palpable cervical nodes. A bone scan helps in identifying bone metastases. During a spinal MRI, one should be wary of vertebral metastases or potential cord lesions to evaluate spinal cord compression. Also, a PET scan helps with a pre-operative assessment. A pleural tap helps with evaluating pleural effusion.

To obtain a histological diagnosis, there are many biopsy methods available. The least invasive and maximally safe option is recommended. Distal and safer lesions outside the lung are typically biopsied. Mediastinal nodes are important for deciding whether curative treatment is possible.

The potential biopsy methods depending on the target lesion are:

Location of the lesion Available biopsy techniques
Peripheral lung lesion CT guided percutaneous biopsy, surgical excision, sputum cytology, and bronchial washings
Proximal lung lesion Bronchoscopy with bronchial biopsy, brushings, and washings for sputum cytology
Mediastinal lymph nodes Endobronchial ultrasound-guided biopsy (EBUS) or surgical biopsy by mediastinotomy or mediastinoscopy
Cervical nodes Ultrasound-guided percutaneous biopsy
Bone CT guided percutaneous biopsy
Pleura Pleural tap for cytology, CT or ultrasound-guided percutaneous biopsy of pleura
Adrenal CT guided percutaneous biopsy
Liver CT or ultrasound-guided percutaneous

Lung cancer staging is important in determining whether it may be curable. A simplified version of the complex TNM staging is:

Score Primary Tumor size Nodal involvement Metastases
0 None None
1 < 3 cm diameter Ipsilateral hilar nodes Any
2 3 to 7 cm diameter Ipsilateral mediastinal nodes
3 > 7 cm diameter Contralateral/extrathoracic nodes
4 Invading trachea, vessels, mediastinum, or spine

Functional capacity is also measured to select patients who can tolerate resection of lung

  • 0: Fully active, able to carry on regular activity without restriction
  • 1: cannot perform physically strenuous activities but is ambulatory and able to perform light or sedentary work (e.g., light housework, office work)
  • 2: Ambulatory and capable of self-care but unable to carry out any work activities for more than 50% of waking hours
  • 3: Capable of performing only limited self-care, confined to a bed or chair for more than 50% of waking hours
  • 4: Completely disabled, totally dependent on others, incapable of performing self-care activities, totally confined to a bed or chair
  • 5: Dead

Potentially curable disease

Treatment for curable NSCLC in Stage I, II, and III involves surgery, followed by postoperative chemotherapy or radiotherapy. Stages I and II involve a minimal surgical invasive approach. If a tumor is confined to one lobe, lobectomy is offered. If the tumor has crossed the oblique fissure, pneumonectomy may be considered. If the patient is not a candidate for surgery, radical radiotherapy is used.

Treatment for incurable NSCLC involves palliative chemotherapy with a modest increase in life expectancy, by about six months, and a dismal prognosis of less than 5 % five-year survival.

Palliative radiotherapy has a definite role in the treatment of incurable NSCLC in Stage IV under the following circumstances:

  • Pain due to local invasion
  • Bronchial obstruction (can also be treated endobronchially)
  • Haemoptysis
  • Bone and brain metastases

Other relevant treatment options in incurable NSCLC can be mentioned as follows:

Treatment modality Explanation
High dose corticosteroids Brain metastases and/or bronchial obstruction call for use of steroids
Targeted chemotherapy Newer targeted chemotherapy drugs such as EGFR inhibitors are very effective for selected patients

SCLC is a high volume disease, often with metastases at presentation. SCLC is sensitive to chemotherapy and is, therefore, unsuitable for surgical resection. Treatment involves chemotherapy unless a patient has a poor performance status. Radiotherapy helps if the disease is restricted to one hemithorax. SCLC is known to relapse quickly, and median survival is around 15 months. The palliative treatment regime is the same as it is for NSCLC.

End of Life Care

About 90% of patients with lung cancer die from the disease. Therefore, end of life care is mandatory for almost all patients. A multidisciplinary dedicated team should include a palliative care physician, lung cancer nurse specialist, community palliative care nurse, respiratory physician, and oncologist. Pain control is an important aspect of end of life care.

A few salient features of pain control are:

  • Initially short-acting agents, such as Oramorph
  • Titrate up until pain is controlled
  • Then swap with long-acting agents such as MST
  • End-stage pain control may require subcutaneous opiate pumps

Mesothelioma

Mesothelioma is a primary malignant tumor of the mesothelium. It is an aggressive tumor fatal to patients. It has a very poor prognosis. It typically affects middle-aged men with a history of asbestos exposure and has a lag phase from exposure to disease onset of about 20-40 years. The risk of developing mesothelioma increases proportionately to the amount of inhaled asbestos fibers. Professions at higher risk of asbestos exposure are dock workers, engineers, shipbuilders, boilermakers, and those in building trades, such as plumbers, carpenters, and electricians.

Early warning signs of mesothelioma include exudative pleural effusion. Chest wall pain, weight loss, anemia, and malaise follow. Distinctive radiological features can be discerned only in later stages.

The same can be mentioned as follows:

  • Circumferential, irregular pleural thickening, with or without effusion
  • Mediastinal surface involvement
  • Marked loss of volume in the affected lung

Pleural effusion in a patient with asbestos exposure is potentially mesothelioma unless proven otherwise. Diagnosis requires pleural biopsies; CT guided or thoracoscopic and often needs repeating. Mesothelioma is almost impossible to cure. With a median survival of 8 to 14 months, treatment options are limited to palliative radiotherapy and chemotherapy with opiate painkillers and occasional pleurodesis to prevent recurrent effusions.

Summary

Lung cancer, consisting of malignant lesions arising from the respiratory epithelium, is the most fatal cancer. It accounts for 13 % of all cancers, but almost 90% of the cases are fatal. The incidence in females is increasing.

The major histological types of lung cancer are small-cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). NSCLC is comprised of three major groups:

  • Squamous cell carcinomas
  • Adenocarcinoma
  • Large cell tumors

About 90% of cases are due to smoking.

Lung cancer symptoms include local symptoms, such as a cough and breathlessness. Systemic features include weight loss, malaise, neurological dysfunctions, and fatigue. Radiological features vary depending on the tumor location. Once the tumor enters the lung, it invades the hilar and mediastinal lymph nodes first and then can causes pressure symptoms, either by compression or infiltration of surrounding structures, such as the esophagus, superior vena cava, and the recurrent laryngeal nerve.

Invasion of the chest wall, in cases of apical tumors, results in a constellation of symptoms. The tumor is then known as “Pancoast’s tumor.” Symptoms include pain in the arms and hands, along with Horner’s syndrome. Distal metastases can occur in diverse organs, such as liver, brain, bone, and adrenals.

Non-metastatic distal effects of cancer, secondary to ectopic hormones and autoantibodies, collectively constitute paraneoplastic syndromes. Confirming histological grade through clinical assessment of the patient and determining whether the patient is curable is essential for comprehensive and holistic management.

Treatment for curable NSCLC involves surgery, followed by postoperative chemotherapy or radiotherapy. SCLC responds to chemotherapy, assessed by functional capacity criteria and tumor stage, but it typically relapses and has a dismal prognosis. Mesothelioma is a primary malignant tumor of the mesothelium. Associated with asbestos exposure; mesothelioma is almost impossible to cure, and treatment consists of palliative care with chemoradiation.

Rate this article
1 Star2 Stars3 Stars4 Stars5 Stars (Votes: 3, average: 4.67)
Loading...