Squamous Cell Lung Cancer


Continuing Education Activity

Squamous cell carcinoma (SCC) of the lung, also known as squamous cell lung cancer, is a type of non-small cell lung cancer (NSCLC). Squamous cell lung tumors often occur in the central part of the lung or in the main airway, such as the left or right bronchus. The main causative agent of cellular transformation is tobacco smoke. This activity reviews the evaluation and management of squamous cell carcinoma of the lung and highlights the role of the interprofessional team in managing patients with this condition.

Objectives:

  • Identify the etiology of squamous cell lung cancer.
  • Review the appropriate history, physical, and evaluation of squamous cell lung cancer.
  • Outline the management options available for squamous cell lung cancer.
  • Summarize interprofessional team strategies for improving care coordination and communication to enhance the care of patients with squamous cell lung cancer and improve outcomes.

Introduction

Squamous cell carcinoma (SCC) of the lung, also known as squamous cell lung cancer, is a type of non-small cell lung cancer (NSCLC). Among NSCLC, adenocarcinoma is the most common, followed by squamous cell carcinoma of the lung, especially in women. This is attributed to the change in the pattern of cigarette smoking, but there is no definitive evidence.

Etiology

Approximately 80% of lung cancer cases in men and 90% of cases in women are associated with smoking.[1][2] SCC is more strongly associated with smoking than any other type of NSCLC. Other risk factors for SCC include age, family history, exposure to second-hand smoke, mineral and metal particles, or asbestos.

Epidemiology

Lung cancer is the most common cancer and cause of cancer-related mortality worldwide.[3] Lung cancer incidence was estimated at 2,093,876 cases globally in 2018, accounting for 11.6% of the global cancer burden. Estimated mortality for lung cancer in 2018 was 1,761,007 deaths globally, constituting around 18.4% of global cancer-related mortality.[4]

The global distribution for lung cancer incidence in 2018 was: Asia (58.5%), Europe (22.4%), North America (12.1%), LAC (4.3%), Africa (1.9%), and Oceania (0.81%).[4]

Approximately 85% of all lung cancers are NSCLCs. Adenocarcinoma and squamous cell carcinoma are the most common subtypes, accounting for 50% and 30% of NSCLC cases, respectively.[3]

Pathophysiology

SCC lung disease originates from the transformation of the squamous cells lining the airways. Squamous cells are thin, flat cells that are found lining many organs of the human body. Squamous cell lung tumors often occur in the central part of the lung or in the main airway, such as the left or right bronchus. The main causative agent of cellular transformation is tobacco smoke, which contains more than 300 harmful agents and 40 potential carcinogens. Transformed squamous cells are characterized by keratinization and/or intercellular bridges and often exhibit a high degree of mutation frequency.[4]

Histopathology

A correct histologic diagnosis is becoming increasingly important because it may predict response and toxicity to therapies.[5] A diagnosis of SCC can be confirmed when a minimum of 10% of the tumor bulk of resected samples exhibits transformation features such as keratinization or intracellular bridges. If the differentiated squamous element of the tumor is minimal, a diagnosis of poorly differentiated SCC is made. An immunohistochemistry (IHC) panel, together with a mucin stain, can help identify NSCLC subtypes. SCC also shows a strong expression of squamous biomarkers, including p63 and p40 proteins.

In 2015, the World Health Organization revised classification to recognize three variants of SCC based on histological examination:[6]

  • Keratinizing
  • Non-keratinizing
  • Basaloid: basaloid component is greater than 50% of the tissue with minimal areas of squamous differentiation

History and Physical

Symptoms of NSCLCs can include cough, chest pain, shortness of breath, blood in sputum, wheezing, hoarseness, recurring chest infections (including bronchitis and pneumonia), weight loss, and loss of appetite and fatigue. However, NSCLC patients often show no symptoms in the early stages of the disease. Metastases may occur in advanced disease, and symptoms may include bone pain, spinal cord impingement, and neurologic symptoms (headache, weakness or numbness of limbs, dizziness, seizures).

Evaluation

Following the physical examination, a complete blood count (CBC), a chest X-ray or computed tomography (CT) scan may be used to evaluate SCC provided that the tumor is of sufficient size. The presence of a cavity, filled by either gas or fluid, within a tumor mass is a classic sign of SCC.[1] Further signs may include pulmonary nodules, mass, or infiltrate, mediastinal widening, atelectasis, hilar enlargement, and pleural effusion. Additional studies including CT abdomen with contrast, brain magnetic resonance imaging (MRI) with contrast, and pulmonary function tests (PFTs) can also be done once the initial diagnosis is made. Assessment of PD-L1, EGFR, ALK fusion oncogene, and other mutations are also done.

Treatment / Management

The treatment varies with the stage of cancer. Surgical resection is the first line of treatment for stages I and II. For 1A, there is no role for chemotherapy. For 1B, surgical resection with adjuvant chemotherapy is considered in some cases if the tumor size is greater than 4cm. Stage II is treated by surgery followed by chemotherapy, usually, lobectomy is preferred, but in poor surgical candidates, sub-lobar resection can be considered. In stage I and II, radiation therapy is considered if there are positive margins post-surgically, and also in poor surgical candidates.

Most of the stage III tumors are unresectable. In stage IIIA, which are definitely staged during resection surgery, can be considered followed by adjuvant chemotherapy but chemotherapy with radiation is the usual choice. For stage IIIB, combined chemotherapy and radiation are used. In stage IV chemotherapy with palliative radiation is used. Multiple randomized, controlled trials and large meta-analyses all confirm the superiority of combination chemotherapy regimens for advanced NSCLC.[2] Also, depending on mutation status, targeted therapy is used as well. In advanced NSCLC, therapy should be based on the molecular features of the tumor.

In NSCLC with somatic driven mutation, specific inhibitor therapy is indicated.[7] For epidermal growth receptor mutation, tyrosine kinase inhibitors like erlotinib, gefitinib, afatinib are used. For ALK mutation, crizotinib is the first line. NSCLC which lacks this mutation depending on programmed cell death-ligand 1 (PD-L1) expression immunotherapy alone or immunotherapy with combined chemotherapy is considered. Chemotherapy for neoadjuvant and adjuvant therapy includes cisplatin with vinorelbine or etoposide, vinblastine, gemcitabine, docetaxel, or pemetrexed are considered. In patients who cannot tolerate cisplatin, paclitaxel with carboplatin is considered. First-line systemic therapy for advanced-stage includes bevacizumab, carboplatin, and paclitaxel. Other options are cetuximab with cisplatin and vinorelbine or erlotinib with platinum-based chemotherapy.

Differential Diagnosis

SSC of the lung must be differentiated from other lung cancers, including small cell lung cancers (SCLC) and other NSCLC such as adenocarcinoma and large cell carcinoma.

Surgical Oncology

Surgery is the treatment of choice for stage I and II. For stage IIIA, surgery is considered only in individualized cases.

Radiation Oncology

Radiation therapy is considered for stage I and II with positive margins post-surgically or in poor surgical candidates in whom complete lobectomy is not possible. For stage III, radiation therapy, along with chemotherapy, is the treatment of choice. For stage IV, radiation is only for palliation.

Pertinent Studies and Ongoing Trials

The immunotherapeutic atezolizumab (anti-PDL1, RG7446, MPDL3280A monoclonal antibody against PD-L1 (programmed death-ligand 1) is being evaluated in a phase III clinical trial as a potential first-line treatment for patients with non-squamous or squamous non-small cell lung cancer whose tumors express PDL1. A phase I trial evaluating atezolizumab in combination with erlotinib or alectinib in patients with non-small cell lung cancer is also ongoing. IPA-3 or OTSSP167 and auranofin was highly synergistic in EGFR or KRAS mutant squamous cell carcinoma cell lines and decreased tumor volume in mice models.[8]

Toxicity and Side Effect Management

Platinum-based chemotherapy, along with second active cytotoxic agents, is usually considered in patients who require chemotherapy. The chance of toxicity increases beyond four to six cycles of therapy and is not recommended beyond that. In patients with no optimal response, maintenance therapy can be continued with one or more components, but typically the platinum-based therapy is discontinued, given its severe toxicity.[9] The patients should be monitored for nephrotoxicity, ototoxicity, cytopenias, and significant neuropathy. Folic acid, vitamin b12, and sometimes dexamethasone are usually considered to avoid some side effects of chemotherapy.

Staging

Staging in lung cancer is based on CT scan images according to the Tumor-Node-Metastasis (TNM) staging system. This is a summary of the 8th Edition of TNM in Lung Cancer, which is issued by the IASLC (International Association for the Study of Lung Cancer) and replaces the TNM 7th edition.[10]

 Proposed T, N, and M descriptors for the eighth edition of TNM classification for lung cancer

T: Primary tumor
Tx Primary tumor cannot be assessed or tumor proven by the presence of malignant cells in sputum or bronchial washings but not visualized by imaging or bronchoscopy
T0 No evidence of primary tumor
Tis Carcinoma in situ
T1 Tumor ≤3 cm in its greatest dimension surrounded by lung or visceral pleura without bronchoscopic evidence of invasion more proximal than the lobar bronchus (i.e., not in the main bronchus) 
  T1a(mi) Minimally invasive adenocarcinoma 
  T1a Tumor ≤1 cm in greatest dimension 
  T1b Tumor >1 cm but ≤2 cm in greatest dimension 
  T1c Tumor >2 cm but ≤3 cm in greatest dimension 
T2 Tumor >3 cm but ≤5 cm or tumor with any of the following features :
  Involves the main bronchus regardless of distance from the carina but without the involvement of the carina
  - Invades visceral pleura
  Associated with atelectasis or obstructive pneumonitis that extends to the hilar region, involving part or all of the lung
  T2a Tumor >3 cm but ≤4 cm in greatest dimension
  T2b Tumor >4 cm but ≤5 cm in greatest dimension
T3 Tumor >5 cm but ≤7 cm in greatest dimension or associated with separate tumor nodule(s) in the same lobe as the primary tumor or directly invades any of the following structures: chest wall (including the parietal pleura and superior sulcus tumors), phrenic nerve, the parietal pericardium
T4 Tumor >7 cm in greatest dimension or associated with separate tumor nodule(s) in a different ipsilateral lobe than that of the primary tumor or invades any of the following structures: diaphragm, mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral body, and carina
N: Regional lymph node involvement
Nx Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Metastasis in ipsilateral peribronchial and/or ipsilateral hilar lymph nodes and intrapulmonary nodes, including involvement by direct extension
N2 Metastasis in ipsilateral mediastinal and/or subcarinal lymph node(s)
N3 Metastasis in contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene, or supraclavicular lymph node(s)
M: Distant metastasis  
M0 No distant metastasis
M1 Distant metastasis present
 M1a Separate tumor nodule(s) in a contralateral lobe; tumor with pleural or pericardial nodule(s) or malignant pleural or pericardial effusion 
  M1b Single extrathoracic metastasis 
  M1c Multiple extrathoracic metastases in one or more organs

Note: Changes to the seventh edition are in bold.

  • a. The uncommon superficial spreading tumor of any size with its invasive component limited to the bronchial wall, which may extend proximal to the main bronchus, is also classified as T1a.
  • b. Solitary adenocarcinoma, ≤ 3cm with a predominately lepidic pattern, and ≤ 5mm invasion in any one focus.
  • c. T2 tumors with these features are classified as T2a if ≤4 cm in greatest dimension or if the size cannot be determined, and T2b if >4 cm but ≤5 cm in greatest dimension.
  • d. Most pleural (pericardial) effusions with lung cancer are due to tumors. In a few patients, however, multiple microscopic examinations of pleural (pericardial) fluid are negative for tumor, and the fluid is non-bloody and not an exudate. When these elements and clinical judgment dictate that the effusion is not related to the tumor, the effusion should be excluded as a staging descriptor.
  • e. This includes the involvement of a single distant (nonregional) lymph node.    

Proposed stage groupings for the eighth edition of the TNM classification for lung cancer

Occult carcinoma TX N0 M0
Stage 0 Tis N0 M0
Stage IA1 T1a(mi) N0 M0
  T1a N0 M0
Stage IA2 T1b N0 M0
Stage IA3 T1c N0 M0
Stage IB T2a N0 M0
Stage IIA T2b N0 M0
Stage IIB T1a–c N1 M0
  T2a N1 M0
  T2b N1 M0
  T3 N0 M0
Stage IIIA T1a–c N2 M0
  T2a b N2 M0
  T3 N1 M0
  T4 N0 M0
  T4 N1 M0
Stage IIIB T1a–c N3 M0
  T2a–b N3 M0
  T3 N2 M0
  T4 N2 M0
Stage IIIC T3 N3 M0
  T4 N3 M0
Stage IVA Any T Any N M1a
  Any T Any N M1b
Stage IVB Any T Any N M1c

Prognosis

Squamous cell lung cancer can spread to multiple sites, including the brain, spine and other bones, adrenal glands, and liver. Due to the lack of targeted therapies for SCC and the late stage of detection, the prognosis is often poor for these patients.

Complications

Complications from SCC of the lung can include:

  • Shortness of breath if the tumor obstructs the major airways or causes fluid to accumulate around the lungs (pleural effusion)
  • Bleeding in the airway, resulting in hemoptysis
  • Metastasis resulting in pain and neurological complications

Postoperative and Rehabilitation Care

Preoperative exercises and rehabilitation program has shown significant postoperative outcomes and reduced postoperative pulmonary complications.[11]. However, postoperative pulmonary rehabilitation alone without preoperative exercise showed only a small to moderate effect on postoperative exercise capacity on the short-term follow-up, but the long-term effect on functional capacity is unknown.[12]

Consultations

  • Pulmonology
  • Cardiothoracic surgery
  • Medical oncology
  • Surgical oncology
  • Palliative care
  • Psychiatry

Deterrence and Patient Education

Education on avoiding or mitigating against risk factors such as tobacco products and causes of occupational disease (such as the use of personal protective equipment) can reduce SCC development. Education about early cancer screening with low dose CT scan of the chest is important for early recognization and treatment to prevent tumor burden. Counseling patients about stages of cancers and the chance of complete cure in case of early detection and counseling on palliative care in advanced stages is very important to reduce stress both for patients and loved ones.

Enhancing Healthcare Team Outcomes

Given the complexity of care required in the treatment of this condition, an interprofessional healthcare team, including primary clinicians, cardiothoracic surgeons, medical oncologists, radiation oncologists, surgical oncologists, and palliative care, are needed. Strong collaboration and communication within the interprofessional team are vital to improving outcomes.



(Click Image to Enlarge)
Squamous cell carcinoma of lung.
Squamous cell carcinoma of lung.
New England journal of medicine. Images in Clinical Medicine. PUB MED ID:30207918. Dr.Bhanu Sabbula
Article Details

Article Author

Bhanusivakumar Sabbula

Article Editor:

Fatima Anjum

Updated:

12/4/2020 2:11:13 PM

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