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| {{Infobox medical condition (new) | | {{Short description|A type of non-small cell lung cancer}} |
| | name = <!--{{PAGENAME}} by default--> | | {{Use dmy dates|date=October 2023}} |
| | synonym = '''Pulmonary adenocarcinoma''' | |
| | image = Adenocarcinoma of the lung.jpg|
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| | caption = A gross pathological specimen of a pulmonary adenocarcinoma, removed in a [[lobectomy]].
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| '''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.<ref name="who2004">{{cite book |title=Pathology and Genetics of Tumours of the Lung, Pleura, Thymus and Heart |editor1-last=Travis |editor1-first=William D |editor2-last=Brambilla |editor2-first=Elisabeth |editor3-last=Müller-Hermelink |editor3-first=H Konrad |editor4-last=Harris |editor4-first=Curtis C |name-list-format=vanc |publisher=IARC Press |location=Lyon |year=2004 |series=World Health Organization Classification of Tumours |isbn=978-92-832-2418-1 |url=http://www.iarc.fr/en/publications/pdfs-online/pat-gen/bb10/bb10-cover.pdf |access-date=27 March 2010 |archive-url=https://web.archive.org/web/20090823210304/http://www.iarc.fr/en/publications/pdfs-online/pat-gen/bb10/bb10-cover.pdf |archive-date=2009-08-23 |url-status=dead }}</ref> It is classified as one of several [[Non-small-cell lung carcinoma|non-small cell lung cancers]] (NSCLC), to distinguish it from [[Small-cell carcinoma|small cell lung cancer]] which has a different behavior and prognosis. Lung adenocarcinoma is further classified into several subtypes and variants.<ref name=":4" /> 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. | | '''Adenocarcinoma of the lung''' is a type of [[lung cancer]] that originates in the glandular cells of the [[lung]]. It is the most common form of [[non-small cell lung cancer]] (NSCLC) and is characterized by its glandular differentiation and mucin production. |
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| Adenocarcinoma is more common in patients with a history of cigarette smoking, and is the most common form of lung cancer in younger women and Asian populations. The pathophysiology of adenocarcinoma is complicated, but generally follows a histologic progression from cells found in healthy lungs to distinctly dysmorphic, or irregular cells. There are several distinct molecular and genetic pathways that contribute to this progression. Like many lung cancers, adenocarcinoma of the lung is often advanced by the time of diagnosis. Once a lesion or tumor is identified with various imaging modalities, such as [[CT scan|computed tomography (CT)]] or [[X-ray]], a biopsy is required to confirm the diagnosis. | | ==Pathophysiology== |
| | Adenocarcinoma of the lung arises from the epithelial cells that line the alveoli and the bronchioles. These cells undergo genetic mutations that lead to uncontrolled cell growth and tumor formation. The mutations often involve genes such as [[EGFR]], [[KRAS]], and [[ALK]], which are critical in cell signaling pathways that regulate cell proliferation and survival. |
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| Treatment of this lung cancer is based upon the specific subtype and the extent of spread from the primary tumor. Surgical resection, [[chemotherapy]], [[Radiation therapy|radiotherapy]], [[targeted therapy]] and [[Cancer immunotherapy|immunotherapy]] are used in attempt to eradicate the cancerous cells based upon these factors.<ref name=":5">{{Cite journal|last=Boshoff|first=Chris|last2=Morgensztern|first2=Daniel|last3=Herbst|first3=Roy S.|date=2018-01-24|title=The biology and management of non-small cell lung cancer|journal=Nature|volume=553|issue=7689|pages=446–454|doi=10.1038/nature25183|pmid=29364287|issn=1476-4687|bibcode=2018Natur.553..446H}}</ref>
| | ==Clinical Presentation== |
| | Patients with adenocarcinoma of the lung may present with a variety of symptoms, including persistent [[cough]], [[hemoptysis]] (coughing up blood), [[dyspnea]] (shortness of breath), and [[chest pain]]. In some cases, the cancer may be asymptomatic and discovered incidentally on imaging studies performed for other reasons. |
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| ==Signs and symptoms== | | ==Diagnosis== |
| The majority of patients who are diagnosed with lung cancer usually present with locally advanced or metastatic disease. Only about one third of patients have [[Lung cancer staging#Staging|stage I]] disease when diagnosed.<ref name=":3" /> The symptoms that the patient exhibits usually reflect the extent of the cancer's spread. Lung cancers that are discovered early may cause symptoms localized to the respiratory system. However, lung cancer that is advanced will cause patients to experience additional signs and symptoms secondary to the cancer spreading to other organ systems.<ref name="Harrison">{{cite book|title=Harrison's Principles of Internal Medicine|vauthors=Horn L, Pao W, Johnson DH|publisher=McGraw-Hill|year=2012|isbn=978-0-07-174889-6|veditors=Longo DL, Kasper DL, Jameson JL, Fauci AS, Hauser SL, Loscalzo J|edition=18th|chapter=Chapter 89}}</ref> In order of highest frequency, the most common signs of lung cancer include:<ref name=":0">{{Cite web|url=https://www.cancer.org/cancer/non-small-cell-lung-cancer/detection-diagnosis-staging/signs-symptoms.html|title=Non-Small Cell Lung Cancer Signs and Symptoms|last=|first=|date=May 16, 2016|website=Cancer.org|publisher=American Cancer Society|access-date=March 11, 2018}}</ref> | | The diagnosis of adenocarcinoma of the lung typically involves imaging studies such as [[chest X-ray]] and [[CT scan]] to identify the presence of a tumor. A definitive diagnosis is made through a [[biopsy]], where a sample of the tumor tissue is examined histologically. Immunohistochemical staining and molecular testing are often performed to identify specific genetic mutations that may guide treatment. |
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| * cough that does not go away or gets worse
| | ==Staging== |
| * weight loss
| | Staging of lung adenocarcinoma is based on the [[TNM classification]] system, which assesses the size and extent of the primary tumor (T), the involvement of regional lymph nodes (N), and the presence of distant metastasis (M). Staging helps determine the prognosis and guides treatment decisions. |
| *dyspnea (shortness of breath or difficulty breathing)
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| *chest pain, which may be aggravated by deep breathing, coughing, or laughing
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| *hemoptysis (coughing up blood or rust-colored phlegm)<ref name=":1">{{Cite web|url=https://www.cancer.org/cancer/non-small-cell-lung-cancer/detection-diagnosis-staging/how-diagnosed.html|title=Tests for Non-Small Cell Lung Cancer|last=|first=|date=June 23, 2017|website=|publisher=American Cancer Society|access-date=March 11, 2018}}</ref>
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| * bone pain
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| *clubbing
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| *fever
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| *generally feeling tired or weak
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| *superior vena cava obstruction- facial, neck, upper torso swelling. This is caused by compression of vasculature by the lung tumor that restricts blood return from the upper body.<ref name=":3" />
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| *dysphagia (trouble swallowing or the sensation that something is caught in the throat) and hoarseness
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| * new onset of wheezing without history of asthma
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| Clinicians should have a high level of suspicion for lung cancer, especially in patients with a smoking history. Patients with recurring or unresolving lung infections (e.g. bronchitis and pneumonia) that are unresponsive to antibiotics should also be further evaluated for lung cancer. In nonsmokers, women and East Asians are more likely to present with symptoms of an underlying lung cancer at younger ages.<ref name="Harrison" />
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| Importantly, many of these signs are commonly due to other causes which are not cancer.<ref name=":0" /> A detailed medical history should be obtained from each patient to determine the relevance of further diagnostic workup and management.
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| === Extrapulmonary manifestations ===
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| Adenocarcinoma, like other forms of lung cancer, is usually advanced or metastatic at time of diagnosis. Patients may complain of signs or symptoms outside of the respiratory tract that represent a hematologic or metabolic complication of the malignancy without, however, resulting necessarily from obstruction or metastasis. These go under the name of [[paraneoplastic syndrome]]s, which often indicate advanced disease and worse prognosis. The most common paraneoplastic syndromes associated with adenocarcinoma of the lung are described below:
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| *'''Hypercalcemia of malignancy''' is more common in squamous cell carcinoma of the lung, but can occur in adenocarcinoma as well. Parathyroid hormone-related peptide (PTHrP) is produced by tumor cells and functions similarly to parathyroid hormone (PTH). The production of this hormonally active peptide by cancer cells causes increased bone resorption via upregulation of osteoclasts, one of the cells responsible for bone remodeling. When bone is broken down, calcium is released into the bloodstream, resulting in hypercalcemia. The signs and symptoms of elevated calcium in the blood include: thirst, fatigue, constipation, polyuria (increased urination), and nausea. It is important to rule out boney metastases in patients with NSCLC because they also present with hypercalcemia.
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| *'''Hypertrophic pulmonary osteoarthropathy (HPO)''' is fairly rare in adenocarcinoma. Less than 1% of patients with adenocarcinoma of the lung will exhibit this finding, but when it does occur, it is a poor prognostic factor. The exact mechanism of HPO is unknown but it thought to be hormonal or neurogenic in etiology. The triad of HPO includes distal clubbing, arthritis, and bilateral symmetrical periosteal formation.<ref name=":3" />
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| == Causes ==
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| === Risk factors ===
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| According to the [[Nurses' Health Study]], the risk of pulmonary adenocarcinoma increases substantially after a long duration of [[tobacco smoking]]: smokers with a previous smoking duration of 30–40 years are more than twice as likely to develop lung adenocarcinoma compared to never-smokers ([[relative risk]] of approximately 2.4); a duration of more than 40 years increases relative risk to 5.<ref>{{cite journal | vauthors = Kenfield SA, Wei EK, Stampfer MJ, Rosner BA, Colditz GA | title = Comparison of aspects of smoking among the four histological types of lung cancer | journal = Tobacco Control | volume = 17 | issue = 3 | pages = 198–204 | date = June 2008 | pmid = 18390646 | pmc = 3044470 | doi = 10.1136/tc.2007.022582 }}</ref>
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| This cancer usually is seen peripherally in the lungs, as opposed to [[small cell lung cancer]] and [[squamous cell]] lung cancer, which both tend to be more centrally located,<ref name="Travis95">{{cite journal | vauthors = Travis WD, Travis LB, Devesa SS | title = Lung cancer | journal = Cancer | volume = 75 | issue = 1 Suppl | pages = 191–202 | date = January 1995 | pmid = 8000996 | doi = 10.1002/1097-0142(19950101)75:1+<191::AID-CNCR2820751307>3.0.CO;2-Y }}</ref><ref name="Kumar-adenocarcinoma">{{cite book |chapter=Chapter 13, box on morphology of adenocarcinoma | last1 = Mitchell | first1 = Richard Sheppard | last2 = Kumar | first2 = Vinay | last3 = Abbas | first3 = Abul K. | last4 = Fausto | first4 = Nelson | name-list-format = vanc |title=Robbins Basic Pathology|publisher=Saunders |location=Philadelphia |isbn=978-1-4160-2973-1 |edition=8th| year = 2007 }}</ref> although it may also occur as central lesions.<ref name="Kumar-adenocarcinoma" /> For unknown reasons, it often arises in relation to peripheral lung scars. The current theory is that the scar probably occurred secondary to the tumor, rather than causing the tumor.<ref name="Kumar-adenocarcinoma" /> The adenocarcinoma has an increased incidence in smokers, and is the most common type of lung cancer seen in non-smokers and women.<ref name="Kumar-adenocarcinoma" /> Deeper inhalation of cigarette smoke results in peripheral lesions that are often the case in adenocarcinomas of the lung. Generally, adenocarcinoma grows more slowly and forms smaller masses than the other subtypes.<ref name="Kumar-adenocarcinoma" /> However, it tends to [[metastase|metastasize]] at an early stage.<ref name="Kumar-adenocarcinoma" />
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| == Mechanism ==
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| === Pathogenesis ===
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| [[Image:ALK_positive_lung_adenocarcinoma_-_ALK_IHC_--_high_mag.jpg|thumb|right|[[Micrograph]] showing an [[ALK positive lung cancer|ALK positive adenocarcinoma of the lung]]. ALK [[immunostain]].]]
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| [[Image:Adenocarcinoma_-_ROS1_positive_-_ROS1_--_high_mag.jpg|thumb|right|[[Micrograph]] showing a [[ROS1|ROS1 positive adenocarcinoma of the lung]]. ROS1 [[immunostain]].]]
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| Large scale studies such as [[The Cancer Genome Atlas|The Cancer Genome Atlas (TCGA)]] have systematically characterized recurrent [[Somatic evolution in cancer|somatic alterations]] likely driving lung adenocarcinoma initiation and development.<ref name=":6">{{Cite journal|last=The Cancer Genome Atlas Research Network|date=July 2014|title=Comprehensive molecular profiling of lung adenocarcinoma|journal=Nature|volume=511|issue=7511|pages=543–550|bibcode=2014Natur.511..543T|doi=10.1038/nature13385|issn=1476-4687|pmc=4231481|pmid=25079552}}</ref>
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| ==== Gene mutations and copy number alterations ====
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| Since smoking is a strong mutagenic factor, lung adenocarcinoma is one of the tumor types with the highest number of mutations.<ref>{{Cite journal|last=Mariamidze|first=Armaz|last2=Aredes|first2=Natália D.|last3=Lee|first3=Jung Il|last4=Rubin|first4=Mark A.|last5=Westervelt|first5=Peter|last6=Tine|first6=Brian Van|last7=Ley|first7=Timothy|last8=Heath|first8=Sharon|last9=Govindan|first9=Ramaswamy|date=2018-03-28|title=Scalable Open Science Approach for Mutation Calling of Tumor Exomes Using Multiple Genomic Pipelines|url=https://www.cell.com/cell-systems/abstract/S2405-4712(18)30096-6|journal=Cell Systems|language=English|volume=6|issue=3|pages=271–281.e7|doi=10.1016/j.cels.2018.03.002|issn=2405-4712|pmc=6075717|pmid=29596782}}</ref> Common somatic mutations in lung adenocarcinoma affect many [[oncogene]]s and [[Tumor suppressor|tumor suppressor genes]], including [[P53|TP53]] (mutated in 46% of cases), [[epidermal growth factor receptor|EGFR]] (27%), [[KRAS]] (32%), [[KEAP1]], [[STK11]] and [[Neurofibromin 1|NF1]].<ref name=":5" /> EGFR and KRAS mutations tend to appear in a mutually exclusive fashion. KRAS mutations are associated with smoking habits, whereas EGFR mutations occur more frequently in females, people of Asian ethnicity and never-smokers.<ref name=":4" />
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| Copy number amplifications in oncogenes such as [[Telomerase reverse transcriptase|TERT]], [[Mdm2|MDM2]], EGFR, [[C-Met|MET]], and [[Myc|MYC]] have been reported, as well as deletions of tumor suppressor genes such as [[CDKN2A]].<ref name=":6" />
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| Frequent alterations occur in genes belonging to the [[receptor tyrosine kinase]] pathway, of which EGFR is the most prominent example. This pathway is involved in cell proliferation and survival and it is often deregulated in cancer. As a consequence, targeted therapies have been developed to inhibit mutant pathway components.<ref name=":6" /><ref>{{Cite web|url=https://ghr.nlm.nih.gov/condition/lung-cancer|title=Lung cancer|last=Reference|first=Genetics Home|website=Genetics Home Reference|language=en|access-date=2019-05-06}}</ref>
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| ==== Chromosomal rearrangements====
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| Three membrane associated tyrosine kinase receptors are recurrently involved in [[Fusion gene|fusions]] or rearrangements in [[adenocarcinomas]]: [[Anaplastic lymphoma kinase|ALK]], [[ROS1]], and [[RET proto-oncogene|RET]], and more than eighty other translocations have also been reported in adenocarcinomas of the lung.<ref>http://atlasgeneticsoncology.org/Tumors/TranslocLungAdenocarcID6751.html</ref>
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| In ALK rearrangements, the most common partner gene is EML4.<ref name=":5" /> EML4-ALK fusions tend to occur in tumors that do not carry EGFR or KRAS mutations and have also a lower frequency of TP53 mutations. ALK and ROS fusions offer opportunities for targeted therapies with tyrosine kinase inhibitors.
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| === Pathophysiology ===
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| The respiratory tract can be divided into two main components: the conducting airways and the gas exchange airways. The gas exchange airways are made of alveoli, or small microscopic air sacs, that are responsible for the exchange of oxygen and carbon dioxide during normal respiration. Alveoli are composed of two cell types, type I and type II pneumocytes. Type I pneumocytes cover 95% of alveolar surfaces, and are not able to regenerate. Type II pneumocytes are more common, making up 60% of the cells within alveolar epithelium, but constitute only 3% of the alveolar surface.<ref name=":2" />
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| There are several factors that contribute to the transformation of normal alveolar epithelium into dysplastic, or pre-cancerous, lesions. Adenocarcinoma of the lung develops in a step-wise progression as type II pneumocytes undergo consecutive molecular changes that disrupt normal cell regulation and turnover. Atypical adenomatous hyperplasia (AAH) is considered a pre-cancerous lesion, and is thought to further progress to adenocarcinoma in situ and invasive adenocarcinoma of the lung. The lesions of AAH are <5 mm, can be single or multiple, and have a ground glass appearance on CT imaging. As more genetic mutations and disregulation of normal cell signaling pathways accumulate, AAH can progress to adenocarcinoma in situ (AIS). AIS lesions are classified as small tumors <3 cm with abnormal type II pneumocyte cell growth that is limited to the alveolar spaces i.e. without invasion into the stroma, pleura, or vasculature. This type of growth is termed "lepidic" and is characteristic of adenocarcinoma of the lung in its earliest stages.<ref name=":2" />
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| == Diagnosis ==
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| A diagnosis of lung cancer may be suspected on the basis of [[#Signs and symptoms|typical symptoms]], particularly in a person with smoking history. Symptoms such as coughing up blood and unintentional weight loss may prompt further investigation, such as [[medical imaging]].
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| ===Classification===
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| [[File:Adenocarcinoma - CT scan (5499628365).jpg|thumb|CT scan- adenocarcinoma of the left lung]]
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| The majority of lung cancers can be characterized as either small cell lung cancer (SCLC) or non-small cell lung cancer (NSCLC). Lung adenocarcinoma is one of the three major subtypes of NSCLC, which also include [[Squamous-cell carcinoma of the lung|squamous carcinoma]] and [[Large-cell lung carcinoma|large cell carcinoma]].<ref name=":2" />
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| Historically, there has been much debate in the most accurate method of describing adenocarcinoma of the lung and several revisions of classification systems have been published. Most recently, the International Multidisciplinary Classification of Lung Adenocarcinoma was published in 2011 and represents the consensus of several organizations to more accurately describe this specific type of lung cancer.<ref name=":4" /> The current classification system aims to more reliably predict prognosis and determination of therapeutic management.<ref name=":3">{{Cite book|title=Fishman's pulmonary diseases and disorders|last=editor.|first=Grippi, Michael A.|isbn=9780071807289|oclc=898053564|date = 2015-04-14}}</ref>
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| The tumor size, pattern of cell growth, and depth of cell invasion into normal lung tissue are considered in determining classification. The following names represent a step-wise pathologic progression in the natural course of adenocarcinoma development; Adenocarcinoma in situ (AIS), Minimally invasive adenocarcinoma (MIA), and Invasive adenocarcinoma.<ref name=":2">{{Cite book|title=Schwartz's Principles of Surgery, 10e|last=Brunicardi.|date=2014|publisher=McGraw-Hill|oclc=941117341}}</ref> Invasive adenocarcinoma of the lung includes a heterogenous mixture of subtypes and variants.
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| The 2011 consensus describes '''five subtypes''' of invasive adenocarcinomas based on the cell pattern that is most predominant. These subtypes are described below:
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| [[File:Histopathology of lepidic predominant adenocarcinoma.jpg|thumb|Histopathology of lepidic predominant adenocarcinoma.]]
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| * lepidic predominant
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| * acinar predominant
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| * papillary predominant
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| * micropapillary predominant
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| * solid predominant with mucin production
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| Cell patterns identifying subtypes are associated with prognosis, ranging from favorable (lepidic) to intermediate (acinar and papillary) to poor (micropapillary and solid).<ref name=":4" />
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| '''Four discrete variants''' of invasive adenocarcinomas not assignable to these five subtypes are also included in the current classification:
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| * invasive mucinous adenocarcinoma
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| * colloid adenocarcinoma
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| * fetal adenocarcinoma
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| * enteric adenocarcinoma<ref name=":3" />
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| === Imaging ===
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| A chest x-ray ([[Radiography|radiograph]]) is often the first imaging test performed when a person presents with cough or chest pain, particularly in the primary care setting. A chest radiograph may detect a lung nodule/mass that is suggestive of cancer, although sensitivity and specificity are limited.
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| [[CT scan|CT imaging]] provides better evaluation of the lungs, with higher sensitivity and specificity for lung cancer compared to chest radiograph (although still significant false positive rate<ref>{{cite journal | vauthors = Gossner J | title = Lung cancer screening-don't forget the chest radiograph | journal = World Journal of Radiology | volume = 6 | issue = 4 | pages = 116–8 | date = April 2014 | pmid = 24778773 | pmc = 4000607 | doi = 10.4329/wjr.v6.i4.116 }}</ref>). [[CT scan|Computed tomography (CT)]] that is specifically aimed at evaluating lung cancer includes the chest and the upper abdomen. This allows for evaluation of other relevant anatomic structures such as nearby lymph nodes, adrenal glands, liver, and bones which may show evidence of metastatic spread of disease.<ref name=":3" /> Indeed, the US Preventative Services Task Force recommends annual screening with low-dose CT in adults aged 55 to 80 years who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years, with certain caveats (see [[Lung cancer screening]]).<ref>{{cite web | url = https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/lung-cancer-screening | title = Final Recommendation Statement: Lung Cancer: Screening. | author = U.S. Preventive Services Task Force | date = December 2016 | access-date = 2018-03-10}}</ref>
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| Nuclear medicine imaging, such as [[PET-CT|PET/CT]] and [[Bone scintigraphy|bone scan]], may also be helpful to diagnose and detect metastatic disease elsewhere in the body.<ref name=":1" /> PET/CT uses a metabolically active tracer that allows clinicians to identify areas of the body that are hypermetabolic. Increased uptake of the tracer occurs in malignant cells and areas of inflammation or infection. Integrating the imaging reflective of metabolic activity with normal [[CT scan|CT imaging]] allows for higher sensitivity and specificity compared to [[Positron emission tomography|PET]] alone.<ref name=":3" />
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| MRI is reserved for patients with advanced disease where intracranial, or brain, involvement is likely. It is also helpful for evaluating the extent of chest wall, diaphragmatic, brachial plexus (such as in the case of [[Pancoast tumor|superior sulcus tumors]]), or spine involvement.<ref name=":3" />
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| === Histopathology ===
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| If possible, a [[biopsy]] of any suspected lung tumor is performed in order to make a microscopic evaluation of the cells involved and is ultimately required to confirm diagnosis.<ref name=":1" /> Biopsy should be attempted in distant lesions first to establish a histologic diagnosis and to simultaneously confirm metastatic staging. The biopsy material is also used to analyze whether the tumor express any specific mutations suitable for tageted therapy (eg. EGFR mutation or ALK mutation). Biopsy can be accomplished via bronchoscopy, transthoracic needle biopsy, and video-assisted thorascopic surgery (VATS).<ref name=":3" />
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| While sputum cytology has been shown to have limited utility, [[thoracentesis]], or aspiration of pleural fluid with an [[ultrasound]]-guided needle, should be performed when [[pleural effusion]] is present. When malignant cells are identified in the pleural aspirate of patients highly suspect for lung cancer, a definitive diagnosis and staging (stage IV adenocarcinoma of the lung) is established.<ref name=":3" />
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| Adenocarcinoma of the lung tends to stain [[mucin]] positive as it is derived from the mucus-producing glands of the lungs. Similar to other adenocarcinoma, if this tumor is well differentiated (low grade) it will resemble the normal glandular structure. Poorly differentiated adenocarcinoma will not resemble the normal glands (high grade) and will be detected by seeing that they stain positive for mucin (which the glands produce). Adenocarcinoma can also be distinguished by staining for [[TTF-1]], a [[cell marker]] for adenocarcinoma.<ref name="WCR20145.1">{{cite book|title=World Cancer Report 2014|date=2014|publisher=World Health Organization|isbn=978-9283204299|pages=Chapter 5.1}}</ref>
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| As discussed previously, the category of adenocarcinoma includes are range of subtypes, and any one tumor tends to be heterogeneous in composition. Several major subtypes are currently recognized by the World Health Organization (WHO)<ref name="who2004" /> and the [[International Association for the Study of Lung Cancer]] (IASLC) / [[American Thoracic Society]] (ATS) / [[European Respiratory Society]] (ERS):<ref name="pmid21828029">{{cite journal | vauthors = Van Schil PE, Asamura H, Rusch VW, Mitsudomi T, Tsuboi M, Brambilla E, Travis WD | title = Surgical implications of the new IASLC/ATS/ERS adenocarcinoma classification | journal = The European Respiratory Journal | volume = 39 | issue = 2 | pages = 478–86 | date = February 2012 | pmid = 21828029 | doi = 10.1183/09031936.00027511 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Travis WD, Brambilla E, Van Schil P, Scagliotti GV, Huber RM, Sculier JP, Vansteenkiste J, Nicholson AG | title = Paradigm shifts in lung cancer as defined in the new IASLC/ATS/ERS lung adenocarcinoma classification | journal = The European Respiratory Journal | volume = 38 | issue = 2 | pages = 239–43 | date = August 2011 | pmid = 21804158 | doi = 10.1183/09031936.00026711 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Vazquez M, Carter D, Brambilla E, Gazdar A, Noguchi M, Travis WD, Huang Y, Zhang L, Yip R, Yankelevitz DF, Henschke CI | title = Solitary and multiple resected adenocarcinomas after CT screening for lung cancer: histopathologic features and their prognostic implications | journal = Lung Cancer | volume = 64 | issue = 2 | pages = 148–54 | date = May 2009 | pmid = 18951650 | pmc = 2849638 | doi = 10.1016/j.lungcan.2008.08.009 | author12 = International Early Lung Cancer Action Program Investigators }}</ref> ''lepidic predominant adenocarcinoma, acinar predominant adenocarcinoma, papillary predominant adenocarcinoma, micropapillary predominant adenocarcinoma, solid predominant adenocarcinoma, and solid predominant with mucin production.'' In as many as 80% of these tumors, components of more than one subtype will be recognized. Surgically resected tumors should be classified by comprehensive histological subtyping, describing patterns of involvement in increments of 5%. The predominant histologic subtype is then used to classify the tumor overall.<ref name=":4">{{cite journal|display-authors=6|vauthors=Travis WD, Brambilla E, Noguchi M, Nicholson AG, Geisinger KR, Yatabe Y, Beer DG, Powell CA, Riely GJ, Van Schil PE, Garg K, Austin JH, Asamura H, Rusch VW, Hirsch FR, Scagliotti G, Mitsudomi T, Huber RM, Ishikawa Y, Jett J, Sanchez-Cespedes M, Sculier JP, Takahashi T, Tsuboi M, Vansteenkiste J, Wistuba I, Yang PC, Aberle D, Brambilla C, Flieder D, Franklin W, Gazdar A, Gould M, Hasleton P, Henderson D, Johnson B, Johnson D, Kerr K, Kuriyama K, Lee JS, Miller VA, Petersen I, Roggli V, Rosell R, Saijo N, Thunnissen E, Tsao M, Yankelewitz D|date=February 2011|title=International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma|journal=Journal of Thoracic Oncology|volume=6|issue=2|pages=244–85|doi=10.1097/JTO.0b013e318206a221|pmc=4513953|pmid=21252716}}</ref> The predominant subtype is prognostic for survival after complete resection.<ref>{{cite journal|vauthors=Russell PA, Wainer Z, Wright GM, Daniels M, Conron M, Williams RA|date=September 2011|title=Does lung adenocarcinoma subtype predict patient survival?: A clinicopathologic study based on the new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society international multidisciplinary lung adenocarcinoma classification|journal=Journal of Thoracic Oncology|volume=6|issue=9|pages=1496–504|doi=10.1097/JTO.0b013e318221f701|pmid=21642859}}</ref>
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| To reveal the adenocarcinomatous lineage of the solid variant, demonstration of intracellular mucin production may be performed. Foci of squamous metaplasia and dysplasia may be present in the epithelium proximal to adenocarcinomas, but these are not the precursor lesions for this tumor. Rather, the precursor of peripheral adenocarcinomas has been termed ''atypical adenomatous hyperplasia'' (AAH).<ref name="Kumar-adenocarcinoma" /> Microscopically, AAH is a well-demarcated focus of epithelial proliferation, containing cuboidal to low-columnar cells resembling [[club cells]] or [[type II pneumocyte]]s.<ref name="Kumar-adenocarcinoma" /> These demonstrate various degrees of cytologic atypia, including [[hyperchromasia]], [[pleomorphism (cytology)|pleomorphism]], prominent [[nucleoli]].<ref name="Kumar-adenocarcinoma" /> However, the atypia is not to the extent as seen in frank adenocarcinomas.<ref name="Kumar-adenocarcinoma" /> Lesions of AAH are monoclonal, and they share many of the molecular aberrations (like [[KRAS]] mutations) that are associated with adenocarcinomas.<ref name="Kumar-adenocarcinoma" />
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| Signet ring and clear cell adenocarcinoma are no longer histological subtypes, but rather cytological features that can occur in tumour cells of multiple histological subtypes, most often solid adenocarcinoma.<ref name="pmid21828029" />
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| ==Treatment== | | ==Treatment== |
| The treatment of adenocarcinoma of the lung depends on several factors including [[Cancer staging|stage]], resectability, [[performance status]], histology and genomic alterations acquired by the individual tumor.<ref name=":7">{{Cite journal|last=Zappa|first=Cecilia|last2=Mousa|first2=Shaker A.|date=2016-06-23|title=Non-small cell lung cancer: current treatment and future advances|journal=Translational Lung Cancer Research|language=en|volume=5|issue=3|pages=288–300–300|issn=2226-4477|doi=10.21037/tlcr.2016.06.07|pmid=27413711|pmc=4931124}}</ref> As in most cancer types, treatment approaches can be broadly divided into 5 categories: surgery, chemotherapy, radiotherapy, targeted therapy and immunotherapy.
| | Treatment options for adenocarcinoma of the lung depend on the stage of the disease and the presence of specific genetic mutations. Early-stage disease may be treated with surgical resection, while advanced stages may require a combination of [[chemotherapy]], [[radiation therapy]], and targeted therapies. Targeted therapies, such as [[tyrosine kinase inhibitors]], are used in patients with specific genetic mutations like EGFR or ALK. |
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| === Surgery ===
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| Early stage (I, II and IIIA) lung adenocarcinomas are typically treated surgically to remove the tumor with [[pneumonectomy]] or [[lobectomy]], if it is found to be resectable with imaging studies and biopsies and if the patient is considered able to tolerate surgery.<ref name="Kumar-adenocarcinoma" /> Video-assisted thorascopic surgery (VATS) is often adopted, which consists in the insertion of a thorascope inside a small incision made in the chest; a lobe can be removed via the scope through this small incision.<ref name=":7" /> [[File:Pie chart of lung cancers.svg|thumb|160px|Incidence of adenocarcinoma of the lung (in yellow) as compared to other [[lung cancer]] types, with fractions of non-smokers versus smokers shown for each type.<ref>Smokers defined as current or former smoker of more than 1 year of duration. See [[Commons:File:Pie chart of lung cancers.svg|image page in Commons]] for percentages in numbers. Reference:
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| *[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3044470/table/T2/ Table 2] in: {{cite journal | vauthors = Kenfield SA, Wei EK, Stampfer MJ, Rosner BA, Colditz GA | title = Comparison of aspects of smoking among the four histological types of lung cancer | journal = Tobacco Control | volume = 17 | issue = 3 | pages = 198–204 | date = June 2008 | pmid = 18390646 | pmc = 3044470 | doi = 10.1136/tc.2007.022582 }}</ref>]]
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| === Chemotherapy ===
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| For advanced (stage IV) and unresectable lung tumors, the first-line therapy is platinum-based doublet chemotherapy, combining [[cisplatin]] or [[carboplatin]] with another cytotoxic agent.<ref name=":5" /> Regimens strongly depend on each patient performance status and response, and when the risk of adverse events could worsen quality of life significantly, basic supportive care is more recommended. Chemotherapy is also used as an adjuvant therapy following surgery to kill remaining cancer cells in patients with stage IIA, IIB and IIIA NSCLC.<ref name=":7" />
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| === Radiotherapy ===
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| Adenocarcinoma is a [[non-small cell lung carcinoma]], and it is not as responsive to [[radiation therapy]] compared to [[small cell lung carcinoma]].<ref name="Kumar-adenocarcinoma" /> However, radiotherapy may be used as an adjuvant therapy for patients who have undergone a resection surgery to reduce the risk of lung cancer relapse. It may also benefit inoperable tumors that are localized to the chest and be part of palliative care to improve quality of life in patients not responding to surgery or chemotherapy.<ref name=":7" />
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| === Targeted therapy ===
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| [[Targeted therapy]] is available for lung adenocarcinomas with certain molecular characteristics. [[Protein kinase inhibitor|Tyrosine kinase inhibitors]] (TKIs) have been developed to target mutant components of the receptor tyrosine kinase pathway such as EGFR, ALK<ref>{{Cite journal|last=Arbour|first=Kathryn C.|last2=Riely|first2=Gregory J.|date=February 2017|title=Diagnosis and Treatment of ALK Positive NSCLC|journal=Hematology/Oncology Clinics of North America|volume=31|issue=1|pages=101–111|doi=10.1016/j.hoc.2016.08.012|issn=0889-8588|pmc=5154547|pmid=27912826}}</ref> and ROS1, which show frequent alterations in lung adenocarcinomas.
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| First-generation EGFR TKIs, including [[gefitinib]] and [[erlotinib]], have been shown to be more effective in treating EGFR-mutated patients with respect to cytotoxic chemotherapy. Second-generation inhibitors such as [[afatinib]] and [[dacomitinib]] provided a broader scope of application as they are able to target not only the protein [[Epidermal growth factor receptor|EGFR]] itself but also other members of the [[EGFR family]], such as [[HER2/neu|HER2]] and [[ERBB4|HER4]] (also known as ERBB2 and ERBB4), and they have shown improved [[progression-free survival]] compared to gefitinib. As the most common cause of acquired resistance to first-generation TKIs is a second EGFR mutation on codon 790, a third-generation EGFR TKI, [[osimertinib]], has been developed to target this new mutation as well.<ref name=":5" /> MET amplification is another known mechanism of acquired resistance.<ref name=":4" />
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| ALK inhibitors such as [[crizotinib]] showed to be effective against tumors harboring ALK fusions. Most patients previously treated with crizotinib benefited from second-generation ALK inhibitors including [[ceritinib]], [[alectinib]] and [[brigatinib]]. Resistance to ALK inhibitors can occur with novel acquired ALK mutations or amplifications.<ref name=":5" />
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| Also ROS1-positive tumors have shown high sensitivity to ALK inhibitors due to the high [[Sequence homology|homology]] between the kinase domains of ROS1 and ALK.<ref name=":5" />
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| === Immunotherapy ===
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| Immune response can be prevented via activation of [[immune checkpoint]]s, which consist in the binding of a ligand protein (e.g. [[PD-L1]]) to a receptor (e.g. [[Programmed cell death protein 1|PD-1]]) on the immune cell surface. As a consequence, cancer cells expressing PD-L1 can inactivate [[T cell]]s thus fostering tumor growth. [[Cancer immunotherapy|Immune checkpoint inhibitors]] have been developed to restore T cell-mediated antitumor immunity by blocking either the ligand or the receptor.
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| Immune checkpoint inhibitors have been approved for NSCLC, including anti-PD-1 [[nivolumab]] and [[pembrolizumab]]. Anti-PD-1 agents are used for patients with advanced NSCLC whose tumors progress after first-line cytotoxic chemotherapy. Pembrolizumab was established as a new standard of care for patients with advanced or metastatic NSCLC with high PD-L1 expression levels, and responses are even more pronounced for tumor with a high mutational burden (i.e. having an elevated number of mutations).<ref name=":5" />
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| Therapeutic approaches combining multiple immune checkpoint inhibitors or one immune checkpoint inhibitors and a cytotoxic agent are undergoing clinical trials as of 2018.<ref name=":5" /><ref>{{Cite journal|last=Hellmann|first=Matthew D.|last2=Ciuleanu|first2=Tudor-Eliade|last3=Pluzanski|first3=Adam|last4=Lee|first4=Jong Seok|last5=Otterson|first5=Gregory A.|last6=Audigier-Valette|first6=Clarisse|last7=Minenza|first7=Elisa|last8=Linardou|first8=Helena|last9=Burgers|first9=Sjaak|date=2018-05-31|title=Nivolumab plus Ipilimumab in Lung Cancer with a High Tumor Mutational Burden|journal=New England Journal of Medicine|language=en|volume=378|issue=22|pages=2093–2104|doi=10.1056/NEJMoa1801946|pmid=29658845|issn=0028-4793|doi-access=free}}</ref> The potential role of anti-PD-1 agents as neoadjuvant therapy in resectable NSCLCs is also being investigated.<ref>{{Cite journal|last=Forde|first=Patrick M.|last2=Chaft|first2=Jamie E.|last3=Smith|first3=Kellie N.|last4=Anagnostou|first4=Valsamo|last5=Cottrell|first5=Tricia R.|last6=Hellmann|first6=Matthew D.|last7=Zahurak|first7=Marianna|last8=Yang|first8=Stephen C.|last9=Jones|first9=David R.|date=2018-05-24|title=Neoadjuvant PD-1 Blockade in Resectable Lung Cancer|journal=New England Journal of Medicine|language=en|volume=378|issue=21|pages=1976–1986|doi=10.1056/NEJMoa1716078|issn=0028-4793|pmc=6223617|pmid=29658848}}</ref>
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| ==Epidemiology==
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| As for other lung cancer subtypes, lung adenocarcinoma incidence is strongly associated with smoking.
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| Incidence of pulmonary adenocarcinoma has been increasing in many developed Western nations in the past few decades, with a share reaching 43.3% of all lung cancers in the US as of 2012,<ref>{{Cite web|url=https://seer.cancer.gov/archive/csr/1975_2012/browse_csr.php?sectionSEL=15&pageSEL=sect_15_table.28.html|title=Browse the Tables and Figures - SEER Cancer Statistics Review (CSR) 1975-2012|website=SEER|language=en|access-date=2019-02-22}}</ref> thus replacing [[Squamous cell lung carcinoma#Squamous cell lung carcinoma|squamous cell lung carcinoma]] as the most common type of lung cancer. This can be largely attributed to the decreasing smoking rates, which favors the adenocarcinoma histology. Indeed, although smoking is still its strongest risk factor, lung adenocarcinoma is by far the most common among lifelong non-smokers (<100 cigarettes in a lifetime).<ref>{{Cite journal|last=Gandara|first=D. R.|last2=Hammerman|first2=P. S.|last3=Sos|first3=M. L.|last4=Lara|first4=P. N.|last5=Hirsch|first5=F. R.|date=2015-05-15|title=Squamous Cell Lung Cancer: From Tumor Genomics to Cancer Therapeutics|journal=Clinical Cancer Research|language=en|volume=21|issue=10|pages=2236–2243|doi=10.1158/1078-0432.CCR-14-3039|issn=1078-0432|pmc=4862209|pmid=25979930}}</ref><br />{{clear}}
| | ==Prognosis== |
| | The prognosis for patients with adenocarcinoma of the lung varies based on the stage at diagnosis and the presence of specific genetic mutations. Early-stage disease has a better prognosis, while advanced-stage disease is associated with a poorer outcome. The development of targeted therapies has improved survival rates for patients with certain genetic mutations. |
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| == References == | | ==Prevention== |
| {{reflist|30em}}
| | Preventive measures for adenocarcinoma of the lung include smoking cessation, as smoking is a major risk factor for lung cancer. Avoiding exposure to environmental carcinogens, such as asbestos and radon, can also reduce the risk of developing lung cancer. |
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| {{Epithelial neoplasms}}
| | ==Related pages== |
| {{Respiratory neoplasia}}
| | * [[Lung cancer]] |
| | * [[Non-small cell lung cancer]] |
| | * [[EGFR]] |
| | * [[KRAS]] |
| | * [[ALK]] |
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| {{DEFAULTSORT:Adenocarcinoma Of The Lung}}
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| [[Category:Lung cancer]] | | [[Category:Lung cancer]] |
| {{dictionary-stub1}}
| | [[Category:Oncology]] |
| | [[Category:Respiratory system]] |
A type of non-small cell lung cancer
Adenocarcinoma of the lung is a type of lung cancer that originates in the glandular cells of the lung. It is the most common form of non-small cell lung cancer (NSCLC) and is characterized by its glandular differentiation and mucin production.
Pathophysiology
Adenocarcinoma of the lung arises from the epithelial cells that line the alveoli and the bronchioles. These cells undergo genetic mutations that lead to uncontrolled cell growth and tumor formation. The mutations often involve genes such as EGFR, KRAS, and ALK, which are critical in cell signaling pathways that regulate cell proliferation and survival.
Clinical Presentation
Patients with adenocarcinoma of the lung may present with a variety of symptoms, including persistent cough, hemoptysis (coughing up blood), dyspnea (shortness of breath), and chest pain. In some cases, the cancer may be asymptomatic and discovered incidentally on imaging studies performed for other reasons.
Diagnosis
The diagnosis of adenocarcinoma of the lung typically involves imaging studies such as chest X-ray and CT scan to identify the presence of a tumor. A definitive diagnosis is made through a biopsy, where a sample of the tumor tissue is examined histologically. Immunohistochemical staining and molecular testing are often performed to identify specific genetic mutations that may guide treatment.
Staging
Staging of lung adenocarcinoma is based on the TNM classification system, which assesses the size and extent of the primary tumor (T), the involvement of regional lymph nodes (N), and the presence of distant metastasis (M). Staging helps determine the prognosis and guides treatment decisions.
Treatment
Treatment options for adenocarcinoma of the lung depend on the stage of the disease and the presence of specific genetic mutations. Early-stage disease may be treated with surgical resection, while advanced stages may require a combination of chemotherapy, radiation therapy, and targeted therapies. Targeted therapies, such as tyrosine kinase inhibitors, are used in patients with specific genetic mutations like EGFR or ALK.
Prognosis
The prognosis for patients with adenocarcinoma of the lung varies based on the stage at diagnosis and the presence of specific genetic mutations. Early-stage disease has a better prognosis, while advanced-stage disease is associated with a poorer outcome. The development of targeted therapies has improved survival rates for patients with certain genetic mutations.
Prevention
Preventive measures for adenocarcinoma of the lung include smoking cessation, as smoking is a major risk factor for lung cancer. Avoiding exposure to environmental carcinogens, such as asbestos and radon, can also reduce the risk of developing lung cancer.
Related pages
