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Deep Learning Technology: Sebastian Arnold, Betty van Aken, Paul Grundmann, Felix A. Gers and Alexander Löser. Learning Contextualized Document Representations for Healthcare Answer Retrieval. The Web Conference 2020 (WWW'20)
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Patients typically present with a non-productive cough and weight loss.
FA can produce repeated hemoptysis, possibly related to cavitation of the tumor.
Other presenting symptoms described have included: flu-like syndrome with cough and fever,
Lung cancer is an extremely heterogeneous family of malignant neoplasms, with well over 50 different histological variants recognized under the 4th revision of the World Health Organization (WHO) typing system ("WHO-2004"), currently the most widely used lung cancer classification scheme. Because these variants have differing genetic, biological, and clinical properties, including response to treatment, correct classification of lung cancer cases are necessary to assure that lung cancer patients receive optimum management.
The WHO-2004 scheme groups lung carcinomas into 8 major types:
- Squamous cell carcinoma
- Small cell carcinoma
- Adenocarcinoma
- Large cell carcinoma
- Adenosquamous carcinoma
- Sarcomatoid carcinoma
- Carcinoid tumor
- Salivary gland-like carcinoma
EMECL is considered a subtype of salivary gland-like carcinoma, tumors so named because their histological appearance and characteristics closely resemble malignant neoplasms arising in the major and minor salivary glands.
In WHO-2004, BACs are one of four specific histologic subtypes of lung adenocarcinoma, along with acinar adenocarcinoma, papillary adenocarcinoma, and solid adenocarcinoma with mucin production. However, approximately 80% of adenocarcinomas are found to contain two (or more) of these four subtypes. Multiphasic tumors such as these are classified into a fifth "subtype", termed adenocarcinoma with mixed subtypes.
There are other classification systems that have been proposed for lung cancers, including BACs and other forms of adenocarcinoma. The Noguchi classification system for small adenocarcinomas has received considerable attention, particularly in Japan, but has not been nearly as widely applied and recognized as the WHO system.
Like other forms of lung carcinoma, BAC possesses unique clinical and pathological features, prognosis, and responses to different treatments.
Lung cancers have been historically classified using two major paradigms. Histological classification systems group lung cancers according to the appearance of the cells and surrounding tissues when they are viewed under a microscope. Clinical classification systems divide lung cancers into groups based on medical criteria, particularly their response to different treatment regimens.
Before the mid-1900s, lung cancer was considered to be a single disease entity, with all forms treated similarly. In the 1960s, small cell lung carcinoma (SCLC) was recognized as a unique form of lung cancer, based both on its appearance (histology) and its clinical properties, including much greater susceptibility to chemotherapy and radiation, more rapid growth rate, and its propensity to metastasize widely early on in its course. Since then, most oncologists have based patient treatment decisions on a dichotomous division of lung cancers into SCLC and non-small cell lung carcinomas (NSCLC), with the former being treated primarily with chemoradiation, and the latter with surgery.
An explosion of new knowledge, accumulated mainly over the last 20 years, has proved that lung cancers should be considered an extremely heterogeneous family of neoplasms with widely varying genetic, biological, and clinical characteristics, particularly their responsiveness to the large number of newer treatment protocols. Well over 50 different histological variants are now recognized under the 2004 revision of the World Health Organization ("WHO-2004") typing system, currently the most widely used lung cancer classification scheme. Recent studies have shown beyond doubt that the old clinical classification paradigm of "SCLC vs. NSCLC" is now obsolete, and that correct "subclassification" of lung cancer cases is necessary to assure that lung cancer patients receive optimum management.
Approximately 98% of lung cancers are carcinoma, which are tumors composed of cells with epithelial characteristics. LCLC's are one of 8 major groups of lung carcinomas recognized in WHO-2004:
- Squamous cell carcinoma
- Small cell carcinoma
- Adenocarcinoma
- Large cell carcinoma
- Adenosquamous carcinoma
- Sarcomatoid carcinoma
- Carcinoid tumor
- Salivary gland-like carcinoma
In situ pulmonary adenocarcinoma (AIS), previously called "Bronchioloalveolar carcinoma" (BAC), is a term describing certain variants of lung cancer arising in the distal bronchioles or alveoli that initially exhibit a specific non-invasive growth pattern. BAC is a type of non-small-cell lung cancer (NSCLC). AIS is defined as a small (≤3 cm) solitary tumour with pure alveolar epithelial appearance (lepidic growth), lacking any invasion of the interstitium. If completely resected, the prognosis of surgically treated AIS is 100%.
Synonyms for FA include well differentiated fetal adenocarcinoma, high-grade fetal adenocarcinoma, pulmonary adenocarcinoma
of fetal type, and pulmonary endodermal tumour resembling fetal lung.
Large-cell carcinoma (LCC) 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 (Non-Small Cell Carcinoma) which originates from epithelial cells of the lung.
Lung cancer is a large and exceptionally heterogeneous family of malignancies. Over 50 different histological variants are explicitly recognized within the 2004 revision of the World Health Organization (WHO) typing system ("WHO-2004"), currently the most widely used lung cancer classification scheme. Many of these entities are rare, recently described, and poorly understood. However, since different forms of malignant tumors generally exhibit diverse genetic, biological, and clinical properties — including response to treatment — accurate classification of lung cancer cases are critical to assuring that patients with lung cancer receive optimum management.
Under WHO-2004, lung carcinomas are divided into 8 major taxa:
- Squamous cell carcinoma
- Small cell carcinoma
- Adenocarcinoma
- Large cell carcinoma
- Adenosquamous carcinoma
- Sarcomatoid carcinoma
- Carcinoid tumor
- Salivary gland-like carcinoma
Pulmonary neuroendocrine tumors are neuroendocrine tumors localized to the lung: bronchus or pulmonary parenchyma.
Pulmonary neuroendocrine tumors include a spectrum of tumors from the low-grade typical pulmonary carcinoid tumor and intermediate-grade atypical pulmonary carcinoid tumor to the high-grade pulmonary large cell neuroendocrine carcinoma (LCNEC) and pulmonary small cell carcinoma (SCLC), with significant clinical, epidemiologic and genetic differences.
Giant-cell carcinoma of the lung (GCCL) is a rare histological form of large-cell lung carcinoma, a subtype of undifferentiated lung cancer, traditionally classified within the non-small-cell lung carcinomas (NSCLC).
The characteristic feature of this highly lethal malignancy is the distinctive light microscopic appearance of its extremely large cells, which are bizarre and highly pleomorphic, and which often contain more than one huge, misshapen, pleomorphic nucleus ("syncytia"), which result from cell fusion.
Although it is common in the lung cancer literature to refer to histologically mixed tumors containing significant numbers of malignant giant cells as "giant-cell carcinomas", technically a diagnosis of "giant-cell carcinoma" should be limited strictly to neoplasms containing "only" malignant giant cells (i.e. "pure" giant-cell carcinoma).
Aside from the great heterogeneity seen in lung cancers (especially those occurring among tobacco smokers), the considerable variability in diagnostic and sampling techniques used in medical practice, the high relative proportion of individuals with suspected GCCL who do not undergo complete surgical resection, and the near-universal lack of complete sectioning and pathological examination of resected tumor specimens prevent high levels of quantitative accuracy.
Adenosquamous lung carcinoma (AdSqLC) is a biphasic malignant tumor arising from lung tissue that is composed of at least 10% by volume each of squamous cell carcinoma (SqCC) and adenocarcinoma (AdC) cells.
Adenocarcinomas are highly heterogeneous tumors. Several major histological subtypes are currently recognized by the WHO and IASLC/ATS/ERS
- Non-invasive or minimally invasive adenocarcinoma
- Adenocarcinoma in situ of the lung (Bronchioalveolar carcinoma)
- Minimally invasive adenocarcinoma of the lung
- Invasive adenocarcinoma
- Acinar predominant adenocarcinoma
- Papillary predominant adenocarcinoma
- Micropapillary predominant adenocarcinoma
- Solid predominant adenocarcinoma
- Invasive mucinous adenocarcinoma
In as many as 80% of tumors that are extensively sampled, components of more than one of these subtypes will be recognized. In such cases, resected tumors should be classified by comprehensive histological subtyping. Using increments of 5% to describe the amount of each subtype present, the predominant subtype is used to classify the whole tumor. The predominant subtype is prognostic for survival after complete resection.
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.
Some variants are not clearly recognized by the WHO and IASLC/ATS/ERS classification:
- Enteric adenocarcinoma of the lung
- Cribriform adenocarcinoma of the lung
Salivary gland–like carcinomas of the lung generally refers a class of rare cancers that arise from the uncontrolled cell division (mitosis) of mutated cancer stem cells in lung tissue. They take their name partly from the appearance of their abnormal cells, whose structure and features closely resemble those of cancers that form in the major salivary glands (parotid glands, submandibular glands and sublingual glands) of the head and neck. Carcinoma is a term for malignant neoplasms derived from cells of epithelial lineage, and/or that exhibit cytological or tissue architectural features characteristically found in epithelial cells.
This class of primary lung cancers contains several histological variants, including mucoepidermoid carcinoma of the lung, adenoid cystic carcinoma of the lung, epithelial-myoepithelial carcinoma of the lung, and other (even more rare) variants. .
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.
In carcinoma in situ, atypical cells may be identified by cytologic smear test of sputum, bronchoalveolar lavage or samples from endobronchial brushings. However, squamous-cell carcinoma in situ is asymptomatic and undetectable on X-ray radiographs.
Eventually, it becomes symptomatic, usually when the tumor mass begins to obstruct the lumen of a major bronchus, often producing distal atelectasis and infection. Simultaneously, the lesion invades into the surrounding pulmonary substance. On histopathology, these tumors range from well differentiated, showing keratin pearls and cell junctions, to anaplastic, with only minimal residual squamous-cell features.
Nearly 40% of lung cancers in the US are adenocarcinoma, which usually originates in peripheral lung tissue. Most cases of adenocarcinoma are associated with smoking; however, among people who have smoked fewer than 100 cigarettes in their lifetimes ("never-smokers"), adenocarcinoma is the most common form of lung cancer. Its incidence has been increasing in many developed Western nations in the past few decades, where it has become the most common major type of lung cancer in smokers (replacing squamous cell lung carcinoma) and in lifelong nonsmokers. According to the Nurses' Health Study, the risk of adenocarcinoma of the lung increases substantially after a long duration of previous tobacco smoking, with a previous smoking duration of 30 to 40 years giving a relative risk of approximately 2.4 compared to never-smokers, and a duration of more than 40 years giving a relative risk of approximately 5.
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, although it may also occur as central lesions. 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. The adenocarcinoma has an increased incidence in smokers, and is the most common type of lung cancer seen in non-smokers and women. The peripheral location of adenocarcinoma in the lungs may be due to the use of filters in cigarettes which prevent the larger particles from entering the lung. Deeper inhalation of cigarette smoke results in peripheral lesions that are often the case in adenocarcinomas of the lung. Generally, adenocarcinomas grow more slowly and form smaller masses than the other subtypes. However, they tend to form metastases widely at an early stage. Adenocarcinoma is a non-small cell lung carcinoma, and as such, it is not as responsive to radiation therapy as is small cell lung carcinoma, but is rather treated surgically, for example by pneumonectomy or lobectomy.
Lung cancer is a large and exceptionally heterogeneous family of malignancies. Over 50 different histological variants are explicitly recognized within the 2004 revision of the World Health Organization (WHO) typing system ("WHO-2004"), currently the most widely used lung cancer classification scheme. Many of these entities are rare, recently described, and poorly understood. However, since different forms of malignant tumors generally exhibit diverse genetic, biological, and clinical properties — including response to treatment — accurate classification of lung cancer cases are critical to assuring that patients with lung cancer receive optimum management.
Approximately 99% of lung cancers are carcinoma, a term that indicates that the malignant neoplasm is composed of, or descended from, cells of epithelial lineage (i.e. derived from embryonic endoderm, as is the case in lung carcinomas, or from ectoderm), and/or that the malignant cells exhibit tissue architectural, cytological, or molecular features characteristically found in epithelial cells. Under WHO-2004, lung carcinomas are divided into 8 major taxa:
- Squamous cell carcinoma
- Small cell carcinoma
- Adenocarcinoma
- Large cell carcinoma
- Adenosquamous carcinoma
- Sarcomatoid carcinoma
- Carcinoid tumor
- Salivary gland-like carcinoma
SCLC is generally considered to be the most aggressive of these major forms of lung cancer, with the worst long term prognosis and survival rates. As a result, it is recommended that all multiphasic malignant lung tumors (i.e. those with more than one histological pattern) that are found to contain "any" proportion of SCLC cells should be classified as c-SCLC, and "not" as combined forms of any of the other histological variants present in the tumor. Currently, the only exception to this recommendation occurs in cases where anaplastic large cell lung carcinoma (LCLC) is the second histological component. In these instances, a minimum of 10% of the viable malignant cells present must be identified as LCLC before the tumor is considered to be a c-SCLC. Under the WHO-2004 classification scheme, c-SCLC is the only recognized variant of SCLC.
Pulmonary neuroendocrine tumor are classified according to tumoral grade:
- Low grade pulmonary neuroendocrine tumor: Typical pulmonary carcinoid tumour (TC; low-grade);
- Intermediate-grade pulmonary neuroendocrine tumor: Atypical pulmonary carcinoid tumour (AC; intermediate-grade)
- High-grade pulmonary neuroendocrine tumor
- Small cell lung cancer (SCLC)
- Large cell neuroendocrine carcinoma (LCNEC of the lung)
Low-grade nodular neuroendocrine proliferations ≥ 0.5 cm are classified as carcinoid tumors and smaller ones are called pulmonary tumorlets.
When neuroendocrine cell hyperplasia and tumorlets are extensive, they represent the rare preinvasive lesion for carcinoids known as "diffuse idiopathic pulmonary neuroendocrine cell hyperplasia".
Both LCNEC and SCLC can demonstrate histologic heterogeneity with other major histologic types of lung carcinoma, such as pulmonary adenocarcinoma or pulmonary squamous cell carcinoma, but is not characteristic of TC or AC.
Epithelial-myoepithelial carcinoma of the lung (EMECL) is a very rare histologic form of malignant epithelial neoplasm ("carcinoma") arising from lung tissue.
For several decades, primary lung cancers were consistently dichotomously classified for treatment and research purposes into small-cell lung carcinomas (SCLCs) and non-small-cell lung carcinomas (NSCLCs), based on an oversimplified approach that is now clearly outmoded. The new paradigm recognizes that lung cancers are a large and extremely heterogeneous family of malignant neoplasms, with over 50 different histological variants included in the 4th (2004) revision of the World Health Organization typing system, the most widely used lung cancer classification scheme ("WHO-2004"). These variants are increasingly appreciated as having different genetic, biological, and clinical properties, including prognoses and responses to treatment regimens, and therefore, that correct and consistent histological classification of lung cancers are necessary to validate and implement optimum management strategies.
About 1% of lung cancers are sarcomas, germ cell tumors, and hematopoietic tumors, while 99% of lung cancers are carcinoma. Carcinomas are tumors composed of transformed, abnormal cells with epithelial tissue architecture and/or molecular characteristics, and which derive from embryonic endoderm. Eight major taxa of lung carcinomas are recognized within the WHO-2004 classification:
1. Small-cell carcinoma
2. Squamous cell carcinoma
3. Adenocarcinoma
4. Large-cell carcinoma
5. Adenosquamous carcinoma
6. Sarcomatoid carcinoma
7. Carcinoid
8. Salivary gland-like carcinoma
The subclassification of GCCL among these major taxa has undergone significant changes in recent decades. Under the 2nd revision (1981) of the WHO classification, it was considered a subtype of large-cell carcinoma. In the 3rd (1999) revision, it was placed within a taxon called "Carcinomas with Pleomorphic, Sarcomatoid, or Sarcomatous Elements", along with pleomorphic carcinoma, spindle cell carcinoma, carcinosarcoma, and pulmonary blastoma, which are (arguably) related variants. While the 4th revision ("WHO-2004") retained the same grouping of lesions as the 3rd revision, the name of the major taxon was shortened to "sarcomatoid carcinomas".
The current rules for classifying lung cancers under WHO-2004, while useful and improved, remain to some extent fairly complex, ambiguous, arbitrary, and incomplete. Although it is fairly common for mixed tumors that are seen to contain malignant giant cells to be called "giant-cell carcinomas", "accurate" classification of a pulmonary tumor as a GCCL requires that the "entire tumor" consists "only" of malignant giant cells. Therefore, complete sampling of the entire tumor — obtained via a surgical resection — is absolutely necessary for a definitive diagnosis of GCCL to be made.
Many of the symptoms of NSCLC can be signs of other diseases, but having chronic or overlapping symptoms may be a signal of the presence of the disease. Some symptoms are indicators of less advanced cases while some may signal that the cancer has spread. Some of the symptoms of less advanced cancer include chronic cough, coughing up blood, chest pain, hoarseness, shortness of breath, wheezing, chest pain, weight loss, and loss of appetite. A few more symptoms associated with the early progression of the disease are feeling weak, being very tired, having trouble swallowing, swelling in the face or neck, and continuous or recurring infections like bronchitis or pneumonia. Signs of more advanced cases include bone pain, nervous system changes (headache, weakness, dizziness, balance problems, seizures), jaundice, lumps near the surface of the body, numbness of extremities due to Pancoast Syndrome, and nausea, vomiting and constipation brought on by hypercalcemia. Some more of the symptoms that indicate further progression of the cancer include shortness of breath, superior vena cava syndrome, trouble swallowing, large amounts of mucus, weakness, fatigue, and hoarseness.
"Lung tumors" are neoplastic tumors of the lung These include:
Primary tumors of the lung/pulmonary system:
- Bronchial leiomyoma, a rare, benign tumor
- Lung cancer, the term commonly used to refer to "carcinoma of the lung"
- Pulmonary carcinoid tumor
- Pleuropulmonary blastoma
- Neuroendocrine tumors of the lung
- Lymphomas of the lung.
- Sarcomas of the lung.
- Some rare vascular tumors of the lung
Non-lung tumors which may grow into the lungs:
- Mediastinal tumors
- Pleural tumors
Metastasis or secondary tumors/neoplasms with other origin:
- Metastasis to the lung
Small-cell carcinoma of the lung usually presents in the central airways and infiltrates the submucosa leading to narrowing of bronchial airways. Common symptoms include cough, dyspnea, weight loss, and debility. Over 70% of patients with small-cell carcinoma present with metastatic disease; common sites include liver, adrenals, bone, and brain.
Due to its high grade neuroendocrine nature, small-cell carcinomas can produce ectopic hormones, including adrenocorticotropic hormone (ACTH) and anti-diuretic hormone (ADH). Ectopic production of large amounts of ADH leads to syndrome of inappropriate antidiuretic hormone hypersecretion (SIADH).
Lambert-Eaton myasthenic syndrome (LEMS) is a well-known paraneoplastic condition linked to small-cell carcinoma.
Acinic cell carcinoma of the lung is a very rare malignant neoplasm originating from bronchial glands. It is classified as a salivary gland-like carcinoma under the most widely used lung cancer classification system.
Squamous-cell carcinoma (SCC) of the lung is a type of non-small-cell lung carcinoma and is more common in men than in women. It 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. 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.