Squamous cell carcinoma of the lung overview

# Overview
Squamous cell carcinoma of the lung ( also known as "Squamous cell lung cancer") is a type of non-small cell carcinoma of the lung. It is the second most commonly encountered lung cancer after lung adenocarcinoma. Squamous cell carcinoma accounts for 30-35% of all lung cancers and has a strong association with smoking. Squamous cell carcinoma of the lung may be classified according to the WHO histological classification system into 4 main types: papillary, clear cell, small cell, and basaloid. Squamous cell carcinoma of the lung arises from the epithelial cells of the lung from the central bronchi to the terminal alveoli, which are normally involved in the protection of the airways. Squamous cell carcinoma of the lung has a central location and usually appears as a hiliar or perihiliar mass. Squamous cell carcinoma of the lung is a rapidly growing cancer which may metastasize to various organs of the body. Genes involved in the pathogenesis of squamous cell carcinoma include EGFR, EML-4, KRAS, HER2, and ALK. Common causes of squamous cell carcinoma of the lung include precursor lesions, such as metaplasia or dysplasia induced by smoking, asbestos exposure, ionizing radiation, atmospheric pollution, and chronic interstitial pneumonitis. Less common causes of non-small cell lung cancer include chromium and nickel exposure, vinyl chloride exposure, and inorganic arsenic exposure. The optimal treatment management of squamous cell carcinoma of the lung will depend on several characteristics, such as pre-treatment evaluation (performance status), location, and adequate staging. Common medical treatment options for the management of squamous cell carcinoma of the lung include chemotherapy (neoadjuvant/adjuvant) and radiation therapy. Surgery is the mainstay of treatment for squamous cell carcinoma of the lung. Common surgical procedures for the treatment of squamous cell carcinoma of the lung include pulmonary lobectomy, pneumonectomy, lung resection with lobectomy, or lung resection with pneumonectomy with or without lymph node dissection. The preferred surgical procedure is thoracotomy with removal of the entire lung or lobe (lobectomy) along with regional lymph nodes and contiguous structures. Prognosis of  squamous cell carcinoma of the lung is generally regarded as poor, with the average survival rate ranging from 16% to 49%.

# Historical Perspective
In 1929, Fritz Lickint, a German physican, first described the association between smoking and squamous cell carcinoma of the lung.

# Classification
Squamous cell carcinoma of the lung may be classified according to the WHO histological classification system into 4 main types: papillary, clear cell, small cell, and basaloid.

# Pathophysiology
Squamous cell carcinoma of the lung arises from the epithelial cells from the central bronchi to the terminal alveoli, which are normally involved in the protection of the airways. The pathological irritation caused by cigarette smoke causes the mucus-secreting ciliated pseudostratified columnar respiratory epithelial cells that line the airways to be replaced by stratified squamous epithelium. Squamous cell carcinoma of the lung has a central location and usually appears as a hiliar or perihiliar mass. Squamous cell carcinoma of the lung is a rapidly growing cancer which may metastasize to various organs of the body. Genes involved in the pathogenesis of squamous cell carcinoma include several oncogenes, such as EGFR, EML-4, KRAS, HER2, and ALK. On gross pathology, findings include central necrosis, cavitation, and invasion of peribronchial soft tissue. On microscopic histopathological analysis squamous cell carcinoma of the lung demonstrate large polygonal malignant cells containing keratin and intercellular bridges. On inmunohistochemistry, findings associated with squamous cell carcinoma of the lung include the presence of p53 and high-molecular weight keratins for squamous cell carcinoma. Other squamous immunomarkers include CK5/6, CEA, 34BE12, TTF-1, and CK7.

# Causes
Common causes of squamous cell carcinoma of the lung include precursor lesions, such as metaplasia or dysplasia induced by smoking, asbestos exposure, ionizing radiation, atmospheric pollution, and chronic interstitial pneumonitis. Less common causes of non-small cell lung cancer include chromium and nickel exposure, vinyl chloride exposure, and inorganic arsenic exposure.

# Differentiating Squamous Cell Carcinoma of the Lung from other Diseases
Squamous cell carcinoma must be differentiated from other diseases that cause chronic cough, weight loss, hemoptysis, and dyspnea among adults such as tuberculosis, pulmonary fungal disease, and secondary metastases.

# Epidemiology and Demographics
Squamous cell carcinoma of the lung accounts for 30% to 35% of all lung cancers and is the second most commonly encountered lung cancer after lung adenocarcinoma.Squamous cell carcinoma of the lung accounts for approximately 27% of all cancer deaths. The incidence of lung squamous cell carcinoma increases with age; the median age at diagnosis is approximately 70 years (usually ranging from 65 to 74 years). Males are more commonly affected with squamous cell carcinoma of the lung than females. The male to female ratio is approximately 1.8 to 1. Squamous cell carcinoma of the lung usually affects black individuals more frequently. Black race is associated with a higher incidence of squamous cell carcinoma compared with White race.

# Risk Factors
Common risk factors in the development of squamous cell carcinoma of the lung include smoking, family history of lung cancer, high levels of air pollution, radiation therapy to the chest, radon gas, asbestos, occupational exposure to chemical carcinogens, and previous lung disease.

# Screening
According to the U.S. Preventive Services Task Force (USPSTF), screening for lung cancer by low-dose computed tomography is recommended every year among smokers who are between 55 to 80 years old and who have history of smoke 30 pack-years or more and either continue to smoke or have quit within the past 15 years (grade B recommendation).

# Natural History, Complications and Prognosis
If left untreated, squamous cell carcinoma of the lung progression occurs slowly and is then followed by local invasion to lymph nodes and distant metastasis. Squamous cell carcinoma of the lung is a locally aggressive tumor, which commonly occurs among adult patients between 65 to 74 years. Common sites of metastasis include liver, adrenal gland, bone, and brain. Complications of squamous cell carcinoma of the lung include development of pneumonia, pleural effusion, metastasis, and Horner's syndrome. The 5-year survival rate of patients with squamous cell carcinoma of the lung depends on the stage at diagnosis. Prognosis is generally regarded as poor, and the average survival rate ranges from 16% to 49%. Features associated with worse prognosis are the presence of genetic and histologic factors (such as presence of necrosis), performance status, tumor size, presence of lymphatic invasion, invasion to the pulmonary artery, presence of satellite lesions, and presence of regional or distant metastases. The 5-year recurrence rate of squamous cell carcinoma of the lung is approximately 24%.

# Diagnosis

## Staging
According to the American Joint Committee on Cancer (AJCC) staging system, there are  4 stages squamous cell carcinoma of the lung, based on 3 factors: tumor size, lymph node invasion, and metastasis. Each stage is assigned a letter and a number  that designate T for tumor size, N for node invasion, and M for metastasis.

## Diagnostic study of choice
Computed tomography is the method of choice for the diagnosis of squamous cell carcinoma of the lung. On CT, findings of squamous cell carcinoma of the lung will depend on the location of the tumor, characteristic findings include: ground-glass opacity, rounded or spiculated mass, local nodal involvement, intraluminar obstruction, and lobar collapse.

## History and Symptoms
The hallmark of squamous cell carcinoma of the lung is chronic cough, weight loss, and hemoptysis. A positive history of smoking may be suggestive of squamous cell carcinoma of the lung. Symptoms related to squamous cell carcinoma of the lung will vary depending on the size and location of the tumor. Common symptoms of squamous cell carcinoma of the lung may also include shortness of breath, fatigue, and chest pain. Less common symptoms of  squamous cell carcinoma of the lung include bone pain, fatigue, dizziness, dysphagia, and numbness in the extremities.

## Physical Examination
Physical examination findings of squamous cell carcinoma of the lung will depend on the location of the tumor. Non-small cell lung cancer with central location may cause crackling sounds, focal wheezing, voice hoarseness, and tachypnea. Peripheral location can present with pleurisy findings, such as reduced chest expansion. Common physical examination of patients with squamous cell carcinoma of the lung include crackling or bubbling noises, decreased/absent breath sounds, whispered pectoriloquy, and tachypnea.

## Laboratory Findings
Laboratory findings associated with squamous cell carcinoma of the lung include elevation of LDH or serum tumor markers. Routine laboratory studies for squamous cell carcinoma of the lung include complete blood count, electrolytes, calcium, alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, creatinine, albumin, and lactate dehydrogenase.

## Chest X Ray
On chest X ray,  characteristic findings of squamous cell carcinoma of the lung include rounded or spiculated mass, bulky hilum (representing the tumor and local nodal involvement) and lobar collapse.

## CT
Computed tomography is the imaging modality of choice for the diagnosis of squamous cell carcinoma of the lung. On chest CT, findings of squamous cell carcinoma of the lung will depend on the location of the tumor, characteristic findings include ground-glass opacity, rounded or spiculated mass, local nodal involvement, intraluminar obstruction, and lobar collapse.

## MRI
On MRI, the diagnosis of squamous cell carcinoma of the lung requires pleural effusion assessment, as well as guidance for biopsy to detect either a peripheral or mediastinal mass.

## Ultrasound
On endobronchial and endoscopic ultrasound, characteristic findings of non-small cell lung cancer include: enlarged lymph nodes and local invasion to adjacent bronchial structures and mediastinum. Endobronchial ultrasound is a first-line diagnostic modality for mediastinal staging.

## Other Imaging Findings
Other imaging findings of squamous cell carcinoma of the lung include: PET/CT and pulmonary angiography.

## Other Diagnostic Studies
Other diagnostic modalities for squamous cell carcinoma of the lung include thoracotomy, bronchoscopy, mediastinoscopy, and  transthoracic percutaneous fine needle aspiration. Common biopsy findings associated with squamous cell carcinoma of the lung include prominent nucleoli, eosinophilic cytoplasm, and intracellular bridges. Different types of lung tissue biopsy include bronchoscopy biopsy, open biopsy, and video-assisted thoracoscopic surgery.

## Biopsy
Biopsy findings associated with squamous cell carcinoma of the lung include prominent nucleoli, eosinophilic cytoplasm, and intracellular bridges. Different sub-types of lung tissue biopsy for squamous cell carcinoma of the lung include needle biopsy, open biopsy, and video-assisted thoracoscopic surgery.

# Treatment

## Medical Therapy
The optimal treatment management of squamous cell carcinoma of the lung will depend on several characteristics, such as pre-treatment evaluation (performance status), location, and adequate staging. Common medical treatment options for the management of squamous cell carcinoma of the lung include chemotherapy (neoadjuvant/adjuvant) and radiation therapy.

## Chemotherapy
Combination chemotherapy regimens using platinum-based chemotherapy and specific-inhibitors is the treatment of choice for the management of patients with squamous cell carcinoma of the lung. Chemotherapy may be required depending on the histological subtype of the squamous cell carcinoma of the lung, molecular testing (presence of genetic mutations), and staging. In the majority of cases, the predominant treatment of choice for squamous cell carcinoma of the lung is either neoadjuvant chemotherapy or adjuvant chemotherapy, which is either followed or preceded by surgical resection. Commonly used chemotherapeutic agents include cisplatin, erlotinib, paclitaxel, docetaxel, carboplatin, etoposide or vinorelbine.

## Radiation Therapy
Radiation therapy is recommended as palliative care either among patients who are diagnosed at an advanced stage of squamous cell carcinoma of the lung or among symptomatic patients with local involvement (pain, vocal cord paralysis, and hemoptysis). Curative radiation therapy may be indicated in patients who are not suitable for surgery with early stage squamous cell carcinoma of the lung. The main goal of radiation therapy for squamous cell carcinoma of the lung is maximum tumor control with minimal tissue toxicity. There are 2 main types of radiation therapy for squamous cell carcinoma of the lung: external beam radiation therapy and brachytherapy (internal radiation therapy).

## Surgery
Surgery is the mainstay of treatment for squamous cell carcinoma of the lung. Common surgical procedures for the treatment of squamous cell carcinoma of the lung include pulmonary lobectomy, pneumonectomy, lung resection with lobectomy, lung resection with pneumonectomy with or without lymph node dissection. The preferred surgical procedure is thoracotomy with removal of the entire lung or lobe (lobectomy) along with regional lymph nodes and contiguous structures. Common complications of squamous cell carcinoma of the lung surgery, include: atelectasis, nosocomial pneumonia, prolonged mechanical ventilation, respiratory failure, bronchospasm, pulmonary embolism.

# Primary Prevention
Primary preventive measures of squamous cell carcinoma of the lung include avoidance of smoking, smoking exposure, exposure to asbestos, and other high risk occupational jobs.

# Secondary Prevention
Secondary prevention of squamous cell carcinoma of the lung depends on the stage of squamous cell carcinoma of the lung at diagnosis. Secondary prevention routine follow-up using chest CT imaging along with periodic evaluation of alert signs in second-hand smokers or active smokers.