Squamous cell lung cancer is typically seen in older adult heavy smokers, characterised by centrally located cavitating lesions with keratin pearls and intercellular bridges seen histologically.
Description
Squamous cell lung carcinoma (SqCC) is a type of non-small cell lung cancer (NSCLC), accounting for about 30% of all NSCLC cases. The tumour originates from the squamous epithelium lining the bronchi and bronchioles. It is characterised by the presence of keratinising or non-keratinising malignant squamous cells, often with intercellular bridges.
Pathogenesis
SqCC arises from the metaplastic change of bronchial epithelial cells in response to chronic inflammation and injury, typically due to chronic cigarette smoke exposure. The process of carcinogenesis involves the progressive accumulation of genetic mutations that drive dysregulated cell growth. Key molecular alterations implicated in SqCC include mutations in TP53, CDKN2A, and PIK3CA genes, and amplification of SOX2 and FGFR1 genes.
Subtypes
Four main histologic subtypes of SqCC are recognised:
- Keratinising: Characterised by keratin pearl formation and intercellular bridges.
- Non-keratinising: Lacks keratin pearl formation but still exhibits intercellular bridges.
- Basaloid: Exhibits basal cell features with high mitotic activity.
- Papillary: Comprised of papillary structures lined by atypical squamous cells.
Epidemiology, Risk Factors & Associations
- Strongly associated with cigarette smoking, with a linear relationship between the number of pack-years smoked and risk of SqCC (85% of cases).
- More common in males (2:1 ratio male to female).
- Typically presents in individuals between the ages of 60 and 70.
Clinical Features
- Chronic, often productive cough, weight loss, and hemoptysis are common presentations.
- Late-stage symptoms include chest pain, dyspnea, and fatigue.
- Paraneoplastic syndromes, such as hypercalcemia and hypophosphatemia, can occur due to production of parathyroid hormone-related protein (PTHrP).
- Upper lobe (apex) or superior sulcus lesions (Pancoast Tumours) may present with Pancoast syndrome, characterised by: ipsilateral shoulder and arm pain, paresthesias, paresis and atrophy of the thenar muscles of the hand, and Horner’s syndrome (ptosis, miosis, and anhidrosis).
Complications
- Risk of locoregional invasion leading to complications such as superior vena cava syndrome, hoarseness due to recurrent laryngeal nerve involvement, and dysphagia from oesophageal compression.
- Distant metastases most commonly occur in the adrenal glands, liver, brain, and bones (up to 30% of cases at diagnosis).
Pathological Features
Histopathology
- Macroscopic: Centrally located tumour, often showing necrosis and cavitation. Tumour size can vary widely, and larger tumours often show areas of haemorrhage.
- Microscopic: Presence of atypical squamous cells with keratin pearls and intercellular bridges. Cells often show marked nuclear atypia.
Radiological Features
General Features
- Centrally located mass or consolidation, often showing cavitation in >80%.
- Post-obstructive pneumonia or atelectasis may be seen due to bronchial obstruction.
XR
- A central mass or areas of consolidation due to post-obstructive pneumonia may be visible.
- Hilar enlargement can be seen due to lymphadenopathy.
- S-sign of golden – right upper lobe collapse with fissural retraction due to Pancoast tumour.
CT
- Non-contrast: Demonstrates a centrally located mass, often with necrotic or cavitary components. Regional lymphadenopathy may be visible.
NM
- PET FDG: Tumours usually intensely metabolic, typically show increased FDG uptake, which can help differentiate malignancy from benign lesions and can be used to assess the extent of disease and response to treatment.
Grading and Staging
SqCC is graded and staged according to the TNM staging system for NSCLC. The system assesses tumour size and invasiveness (T), involvement of regional lymph nodes (N), and presence of distant metastases (M).
Diagnosis
Diagnosis is confirmed by histological examination of a biopsy specimen, usually obtained via bronchoscopy or CT-guided percutaneous biopsy.
Differential Diagnosis
- Adenocarcinoma of the lung: Typically located peripherally, demonstrating ground-glass opacities on imaging. Histologically, shows glandular differentiation.
- Small cell lung cancer: Centrally located but rarely causes cavitation. Radiographically, exhibits rapid growth over a short period. Histologically, it displays small cells with scant cytoplasm and nuclear moulding.
- Granulomatous diseases (e.g., tuberculosis): Can cause cavitation, but typically present with other radiographic signs such as lymphadenopathy and a miliary pattern. A history of exposure and positive microbiology tests can help differentiate these conditions.
Management
Management strategies depend on the stage of the disease and overall health status of the patient. Early-stage disease (stage I and II) is typically managed with surgical resection, while more advanced disease may be treated with a combination of chemotherapy, radiation, and potentially targeted therapies or immunotherapies.