Squamous-cell carcinoma of the lung

Last updated
Squamous-cell carcinoma of the lung
Squamous cell carcinoma (3922611335).jpg
A squamous-cell lung carcinoma developing in the bronchius
Specialty Oncology

Squamous-cell carcinoma (SCC) of the lung is a histologic type of non-small-cell lung carcinoma (NSCLC). It is the second most prevalent type of lung cancer after lung adenocarcinoma and it originates in the bronchi. Its tumor cells are characterized by a squamous appearance, similar to the one observed in epidermal cells. Squamous-cell carcinoma of the lung is strongly associated with tobacco smoking, more than any other forms of NSCLC. [1]

Contents

Signs and symptoms

Squamous-cell lung carcinoma share most of the signs and symptoms with other forms of lung cancer. These include worsening cough, including hemoptysis, chest pain, shortness of breath and weight loss. Symptoms may result from local invasion or compression of adjacent thoracic structures such as compression involving the esophagus causing dysphagia, compression involving the laryngeal nerves causing change in voice, or compression involving the superior vena cava causing facial edema. Distant metastases may also cause pain and show symptoms related to other organs. [1]

Causes

Risk factors

Squamous-cell carcinoma of the lung is closely correlated with a history of tobacco smoking, more so than most other types of lung cancer. According to the Nurses' Health Study, the relative risk of SCC is approximately 5.5, both among those with a previous duration of smoking of 1 to 20 years, and those with 20 to 30 years, compared to never-smokers. [2] The relative risk increases to approximately 16 with a previous smoking duration of 30 to 40 years, and approximately 22 with more than 40 years. [2]

Mechanism

Pathogenesis

It most often arises centrally in larger bronchi, and while it often metastasizes to locoregional lymph nodes (particularly the hilar nodes) early in its course, it generally disseminates outside the thorax somewhat later than other major types of lung cancer. Large tumors may undergo central necrosis, resulting in cavitation. A squamous-cell carcinoma is often preceded for years by squamous-cell metaplasia or dysplasia in the respiratory epithelium of the bronchi, which later transforms to carcinoma in situ.[ citation needed ]

Large scale studies such as The Cancer Genome Atlas (TCGA) have systematically characterized recurrent somatic alterations likely driving lung squamous-cell carcinoma initiation and development. [3] [4]

Gene mutations and copy number alterations

Squamous-cell lung carcinoma is one of the tumor types with the highest number of mutations since smoking, the main driver of the disease, is a strong mutagenic factor. [5]

Inactivating mutations in lung SCC affect many tumor suppressor genes such as TP53 (mutated in 81% of cases), MLL2 (20%), CDKN2A (15%), KEAP1 (12%) and PTEN (8%). Recurrent loss-of-function mutations have been observed also in NOTCH1 (8%), suggesting a tumor suppressive role in lung SCC for this gene, that has also been implicated as an oncogene in haematological cancers. [3] On the other hand, recurrent gain-of-function mutations have been found in oncogenes such as PIK3CA (16%) and NFE2L2 (15%).

Common oncogene copy number amplifications have been found in SOX2, PDGFRA, EGFR, FGFR1 and CCND1. Deletions were observed in tumor suppressors such as CDKN2A, PTEN and NF1. [3]

Some alterations such as the ones affecting TP53 and CDKN2A are shared by lung SCC and the other most common type of NSCLC, lung adenocarcinoma. Conversely, the two main driver oncogenes of the latter, EGFR and KRAS, are rarely mutated in lung SCC. [4]

Somatically altered pathways

Many of the gene mutations and copy number alterations occur in pathways whose deregulation seems to be important for the initiation and progression of the tumor. Specifically, KEAP1 and NFE2L2 belong to the oxidative stress response pathways; alterations in these genes tend to occur in a mutually exclusive fashion, and therefore this pathway is overall altered in more than 30% of the cases. [3] Similarly, the squamous cell differentiation pathway, whose components include SOX2, TP63 and NOTCH1, is altered in 44% of the tumors.

Alterations in the receptor tyrosine kinase pathway are also common but not as widespread as for the adenocarcinoma type.[ citation needed ]

RNA expression profiles

Recently, four mRNA expression subtypes (primitive, basal, secretory, and classical) were identified and validated within squamous-cell carcinoma. The primitive subtype correlates with worse patient survival. These subtypes, defined by intrinsic expression differences, provide a possible foundation for improved patient prognosis and research into individualized therapies. [6]

Diagnosis

Early squamous-cell carcinoma of the lung (generally as squamous-cell carcinoma in situ) is asymptomatic and may only appear as an incidental imaging finding on CT scan or magnetic resonance imaging as a lung nodule. Eventually, it becomes symptomatic, usually when the tumor mass begins to obstruct the lumen of a major bronchus, often producing distal atelectasis and infection.

Cytopathology may detect atypical cells from cytologic smear test of sputum, bronchoalveolar lavage, or samples from endobronchial brushings.

Histopathology requires at least a lung biopsy. On such exams, these tumors range from well differentiated, showing keratin pearls and cell junctions, to anaplastic, with only minimal residual squamous-cell features. [7]

Classification

The 2015 WHO classification of lung tumors [8] divided squamous cell lung carcinomas into 3 categories: keratinizing, non-keratinizing and basaloid. Keratinizing SCC harbor features of keratinization; non-keratinizing SCC lack such features but show other squamous markers, such as p40 and p63; finally, basaloid SCC is a rare subset of poorly differentiated squamous cell lung carcinoma. Previous variants such as papillary, small-cell and clear-cell SCC were discarded from the current classification as these subtypes are very uncommon. There is no clear evidence of prognostic significance to the subtyping of lung squamous cell carcinoma. [8]

Treatment

Treatment of lung squamous-cell carcinoma depends on many factors including stage, resectability, performance status and genomic alterations acquired by the individual tumor.[ citation needed ]

Therapy of early-stage SCC mimics that of other histologic types of NSCLC. Early stage (I, II and IIIA) lung SCC are typically resected surgically, and cytotoxic chemotherapy and/or radiation may be used as an adjuvant therapy following surgery. On the other hand, advanced, metastatic or recurrent lung SCC are given first-line systemic therapy with a palliative (i.e., noncurative) intent consisting of cytotoxic chemotherapy, most commonly a platinum-based doublet. Either cisplatin or carboplatin is used as the platinum backbone. [9]

Development of targeted therapies has been less rapid for lung SCC with respect to adenocarcinoma, as ALK rearrangements and EGFR mutations targetable with receptor tyrosine kinase inhibitors are much less frequent in the former compared to the latter. [10]

Immunotherapy is showing promising results for NSCLC, and anti-PD-1 agent nivolumab has been approved by the US Food and Drug Administration (FDA) for lung SCC.

Epidemiology

Lung squamous-cell carcinoma is the second most common histologic type of lung cancer after adenocarcinoma, reaching 22.6% of all lung cancer cases as of 2012. [11] The relative incidence of the former has been steadily decreasing in favor of the latter due to the decreasing smoking rates in the last few years. [9]

As much as 91% of lung SCC has been found to be attributable to cigarette smoking. Incidence is greater in men than in women. [10]

Related Research Articles

<span class="mw-page-title-main">Lung cancer</span> Malignant tumor characterized by uncontrolled cell growth in lung tissue

Lung cancer, also known as lung carcinoma, is a malignant tumor that begins in the lung. Lung cancer is caused by genetic damage to the DNA of cells in the airways, often caused by cigarette smoking or inhaling damaging chemicals. Damaged airway cells gain the ability to multiply unchecked, causing the growth of a tumor. Without treatment, tumors spread throughout the lung, damaging lung function. Eventually lung tumors metastasize, spreading to other parts of the body.

<span class="mw-page-title-main">Carcinoma</span> Malignancy that develops from epithelial cells

Carcinoma is a malignancy that develops from epithelial cells. Specifically, a carcinoma is a cancer that begins in a tissue that lines the inner or outer surfaces of the body, and that arises from cells originating in the endodermal, mesodermal or ectodermal germ layer during embryogenesis.

<span class="mw-page-title-main">Gefitinib</span> Drug used in fighting breast, lung, and other cancers

Gefitinib, sold under the brand name Iressa, is a medication used for certain breast, lung and other cancers. Gefitinib is an EGFR inhibitor, like erlotinib, which interrupts signaling through the epidermal growth factor receptor (EGFR) in target cells. Therefore, it is only effective in cancers with mutated and overactive EGFR, but resistances to gefitinib can arise through other mutations. It is marketed by AstraZeneca and Teva.

<span class="mw-page-title-main">Non-small-cell lung cancer</span> Any type of epithelial lung cancer other than small-cell lung carcinoma

Non-small-cell lung cancer (NSCLC), or non-small-cell lung carcinoma, is any type of epithelial lung cancer other than small-cell lung cancer (SCLC). NSCLC accounts for about 85% of all lung cancers. As a class, NSCLCs are relatively insensitive to chemotherapy, compared to small-cell carcinoma. When possible, they are primarily treated by surgical resection with curative intent, although chemotherapy has been used increasingly both preoperatively and postoperatively.

p16 Mammalian protein found in Homo sapiens

p16, is a protein that slows cell division by slowing the progression of the cell cycle from the G1 phase to the S phase, thereby acting as a tumor suppressor. It is encoded by the CDKN2A gene. A deletion in this gene can result in insufficient or non-functional p16, accelerating the cell cycle and resulting in many types of cancer.

<span class="mw-page-title-main">Adenocarcinoma in situ of the lung</span> Medical condition

Adenocarcinoma in situ (AIS) of the lung —previously included in the category of "bronchioloalveolar carcinoma" (BAC)—is a subtype of lung adenocarcinoma. It tends to arise in the distal bronchioles or alveoli and is defined by a non-invasive growth pattern. This small solitary tumor exhibits pure alveolar distribution and lacks any invasion of the surrounding normal lung. If completely removed by surgery, the prognosis is excellent with up to 100% 5-year survival.

<span class="mw-page-title-main">ROS1</span> Protein-coding gene in the species Homo sapiens

Proto-oncogene tyrosine-protein kinase ROS is an enzyme that in humans is encoded by the ROS1 gene.

<span class="mw-page-title-main">CDKN2A</span> Protein-coding gene in the species Homo sapiens

CDKN2A, also known as cyclin-dependent kinase inhibitor 2A, is a gene which in humans is located at chromosome 9, band p21.3. It is ubiquitously expressed in many tissues and cell types. The gene codes for two proteins, including the INK4 family member p16 and p14arf. Both act as tumor suppressors by regulating the cell cycle. p16 inhibits cyclin dependent kinases 4 and 6 and thereby activates the retinoblastoma (Rb) family of proteins, which block traversal from G1 to S-phase. p14ARF activates the p53 tumor suppressor. Somatic mutations of CDKN2A are common in the majority of human cancers, with estimates that CDKN2A is the second most commonly inactivated gene in cancer after p53. Germline mutations of CDKN2A are associated with familial melanoma, glioblastoma and pancreatic cancer. The CDKN2A gene also contains one of 27 SNPs associated with increased risk of coronary artery disease.

<span class="mw-page-title-main">Afatinib</span> Chemical compound

Afatinib, sold under the brand name Gilotrif among others, is a medication which is used to treat non-small cell lung carcinoma (NSCLC). It belongs to the tyrosine kinase inhibitor family of medications. It is taken by mouth.

Large-cell lung carcinoma (LCLC), or large-cell carcinoma (LCC) in short, is a heterogeneous group of undifferentiated malignant neoplasms that lack the cytologic and architectural features of small cell carcinoma and glandular or squamous differentiation. LCC is categorized as a type of NSCLC which originates from epithelial cells of the lung.

<span class="mw-page-title-main">Combined small-cell lung carcinoma</span> Medical condition

Combined small cell lung carcinoma is a form of multiphasic lung cancer that is diagnosed by a pathologist when a malignant tumor, arising from transformed cells originating in lung tissue, contains a component of;small cell lung carcinoma (SCLC), admixed with one components of any histological variant of non-small cell lung carcinoma (NSCLC) in any relative proportion.

Treatment of lung cancer refers to the use of medical therapies, such as surgery, radiation, chemotherapy, immunotherapy, percutaneous ablation, and palliative care, alone or in combination, in an attempt to cure or lessen the adverse impact of malignant neoplasms originating in lung tissue.

Large cell lung carcinoma with rhabdoid phenotype (LCLC-RP) is a rare histological form of lung cancer, currently classified as a variant of large cell lung carcinoma (LCLC). In order for a LCLC to be subclassified as the rhabdoid phenotype variant, at least 10% of the malignant tumor cells must contain distinctive structures composed of tangled intermediate filaments that displace the cell nucleus outward toward the cell membrane. The whorled eosinophilic inclusions in LCLC-RP cells give it a microscopic resemblance to malignant cells found in rhabdomyosarcoma (RMS), a rare neoplasm arising from transformed skeletal muscle. Despite their microscopic similarities, LCLC-RP is not associated with rhabdomyosarcoma.

Targeted therapy of lung cancer refers to using agents specifically designed to selectively target molecular pathways responsible for, or that substantially drive, the malignant phenotype of lung cancer cells, and as a consequence of this (relative) selectivity, cause fewer toxic effects on normal cells.

HOHMS is the medical acronym for "Higher-Order HistoMolecular Stratification", a term and concept which was first applied to lung cancer research and treatment theory.

Mucinous cystadenocarcinoma of the lung (MCACL) is a very rare malignant mucus-producing neoplasm arising from the uncontrolled growth of transformed epithelial cells originating in lung tissue.

<span class="mw-page-title-main">Adenocarcinoma of the lung</span> Medical condition

Adenocarcinoma of the lung is the most common type of lung cancer, and like other forms of lung cancer, it is characterized by distinct cellular and molecular features. It is classified as one of several non-small cell lung cancers (NSCLC), to distinguish it from small cell lung cancer which has a different behavior and prognosis. Lung adenocarcinoma is further classified into several subtypes and variants. The signs and symptoms of this specific type of lung cancer are similar to other forms of lung cancer, and patients most commonly complain of persistent cough and shortness of breath.

Sarcomatoid carcinoma of the lung is a term that encompasses five distinct histological subtypes of lung cancer, including (1) pleomorphic carcinoma, (2) spindle cell carcinoma, (3) giant cell carcinoma, (4) carcinosarcoma, or (5) pulmonary blastoma.

Basaloid squamous cell carcinoma (Bas-SqCC) is an uncommon histological variant of lung cancer composed of cells exhibiting cytological and tissue architectural features of both squamous cell lung carcinoma and basal cell carcinoma.

<span class="mw-page-title-main">Squamous-cell carcinoma</span> Carcinoma that derives from squamous epithelial cells

Squamous-cell carcinoma (SCC), also known as epidermoid carcinoma, comprises a number of different types of cancer that begin in squamous cells. These cells form on the surface of the skin, on the lining of hollow organs in the body, and on the lining of the respiratory and digestive tracts.

References

  1. 1 2 "Non-Small Cell Lung Cancer Treatment". National Cancer Institute. 1980-01-01. Retrieved 2019-02-28.
  2. 1 2 Kenfield SA, Wei EK, Stampfer MJ, Rosner BA, Colditz GA (June 2008). "Comparison of aspects of smoking among the four histological types of lung cancer". Tobacco Control. 17 (3): 198–204. doi:10.1136/tc.2007.022582. PMC   3044470 . PMID   18390646.
  3. 1 2 3 4 Cancer Genome Atlas Research Network (September 2012). "Comprehensive genomic characterization of squamous cell lung cancers". Nature. 489 (7417): 519–25. Bibcode:2012Natur.489..519T. doi:10.1038/nature11404. PMC   3466113 . PMID   22960745.
  4. 1 2 Campbell JD, Alexandrov A, Kim J, Wala J, Berger AH, Pedamallu CS, et al. (June 2016). "Distinct patterns of somatic genome alterations in lung adenocarcinomas and squamous cell carcinomas". Nature Genetics. 48 (6): 607–16. doi:10.1038/ng.3564. PMC   4884143 . PMID   27158780.
  5. ↑ Ellrott K, Bailey MH, Saksena G, Covington KR, Kandoth C, Stewart C, et al. (March 2018). "Scalable Open Science Approach for Mutation Calling of Tumor Exomes Using Multiple Genomic Pipelines". Cell Systems. 6 (3): 271–281.e7. doi:10.1016/j.cels.2018.03.002. PMC   6075717 . PMID   29596782.
  6. ↑ Wilkerson MD, Yin X, Hoadley KA, Liu Y, Hayward MC, Cabanski CR, et al. (October 2010). "Lung squamous cell carcinoma mRNA expression subtypes are reproducible, clinically important, and correspond to normal cell types". Clinical Cancer Research. 16 (19): 4864–75. doi:10.1158/1078-0432.CCR-10-0199. PMC   2953768 . PMID   20643781.
  7. ↑ Entire section, if not else specified, is taken from Mitchell RS, Kumar V, Abbas AK, Fausto N (2007). "Ch. 13, box on morphology of squamous cell carcinoma". Robbins Basic Pathology (8th ed.). Philadelphia: Saunders. ISBN   978-1-4160-2973-1.
  8. 1 2 Travis WD, Brambilla E, Nicholson AG, Yatabe Y, Austin JH, Beasley MB, et al. (September 2015). "The 2015 World Health Organization Classification of Lung Tumors: Impact of Genetic, Clinical and Radiologic Advances Since the 2004 Classification". Journal of Thoracic Oncology. 10 (9): 1243–1260. doi: 10.1097/JTO.0000000000000630 . PMID   26291008.
  9. 1 2 Gandara DR, Hammerman PS, Sos ML, Lara PN, Hirsch FR (May 2015). "Squamous cell lung cancer: from tumor genomics to cancer therapeutics". Clinical Cancer Research. 21 (10): 2236–43. doi:10.1158/1078-0432.CCR-14-3039. PMC   4862209 . PMID   25979930.
  10. 1 2 Derman BA, Mileham KF, Bonomi PD, Batus M, Fidler MJ (October 2015). "Treatment of advanced squamous cell carcinoma of the lung: a review". Translational Lung Cancer Research. 4 (5): 524–32. doi:10.3978/j.issn.2218-6751.2015.06.07. PMC   4630512 . PMID   26629421.
  11. ↑ "Browse the Tables and Figures - SEER Cancer Statistics Review (CSR) 1975-2012". SEER. Retrieved 2019-02-28.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.