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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)
Funded by The Federal Ministry for Economic Affairs and Energy; Grant: 01MD19013D, Smart-MD Project, Digital Technologies
Esophageal cancer may be due to either squamous cell carcinoma (ESCC) or adenocarcinoma (EAC). SCCs tend to occur closer to the mouth, while adenocarcinomas occur closer to the stomach. Dysphagia (difficulty swallowing, solids worse than liquids) and painful swallowing are common initial symptoms. If the disease is localized, surgical removal of the affected esophagus may offer the possibility of a cure. If the disease has spread, chemotherapy and radiotherapy are commonly used.
Ninety percent of cases of head and neck cancer (cancer of the mouth, nasal cavity, nasopharynx, throat and associated structures) are due to squamous cell carcinoma.
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.
Epithelial-myoepithelial carcinoma of the lung (EMECL) is a very rare histologic form of malignant epithelial neoplasm ("carcinoma") arising from lung tissue.
Patients typically present with a non-productive cough and weight loss.
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
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. .
Cytologic features of serous carcinoma are:
- Marked intragroup nuclear pleomorphism.
- Macronucleoli.
- "Knobby" group borders (in large groups).
- Hydropic vacuoles.
Symptoms of serous carcinoma may include:
- Discomfort/pain or bloating in abdomen
- Frequent urination
- Weight loss
The symptoms of laryngeal cancer depend on the size and location of the tumour. Symptoms may include the following:
- Hoarseness or other voice changes
- A lump in the neck
- A sore throat or feeling that something is stuck in the throat
- Persistent cough
- Stridor - a high-pitched wheezing sound indicative of a narrowed or obstructed airway
- Bad breath
- Earache (""referred"")
- Difficulty swallowing
Treatment effects can include post-operative changes in appearance, difficulty eating, or loss of voice that may require learning alternate methods of speaking.
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.
Laryngeal cancer, also known as cancer of the larynx or laryngeal carcinoma, are mostly squamous cell carcinomas, reflecting their origin from the skin of the larynx.
Cancer can develop in any part of the larynx, but the cure rate is affected by the location of the tumour. For the purposes of tumour staging, the larynx is divided into three anatomical regions: the glottis (true vocal cords, anterior and posterior commissures); the supraglottis (epiglottis, arytenoids and aryepiglottic folds, and false cords); and the subglottis.
Most laryngeal cancers originate in the glottis. Supraglottic cancers are less common, and subglottic tumours are least frequent.
Laryngeal cancer may spread by direct extension to adjacent structures, by metastasis to regional cervical lymph nodes, or more distantly, through the blood stream. Distant metastases to the lung are most common. In 2013 it resulted in 88,000 deaths up from 76,000 deaths in 1990. Five year survival rates in the United States are 60%.
The differential diagnosis of serous carcinoma not otherwise specified includes:
- Ovarian serous carcinoma, a type of ovarian cancer.
- Uterine serous carcinoma, also known as "uterine papillary serous carcinoma", a type of uterine cancer.
- Fallopian tube serous carcinoma, a type of uterine tube cancer.
- Cervical serous carcinoma, a rare type of cervical cancer.
- Primary peritoneal serous carcinoma, a very rare cancer that arise from the peritoneum.
There has been the suggestion that the above diagnoses really represent one entity.
Primary peritoneal cancer or carcinoma is also known as serous surface papillary carcinoma, primary peritoneal carcinoma, extra-ovarian serous carcinoma, primary serous papillary carcinoma, psammomacarcinoma. It was historically classified under "carcinoma of unknown primary" (CUP). Primary peritoneal cancer (PPC, or PPCa) is a cancer of the cells lining the peritoneum, or abdominal cavity.
Some studies indicate that up to 15% of serous ovarian cancers are thought to be actually primary peritoneal carcinomas in origin.
Histomorphological and molecular biological characteristics suggest that serous carcinomas, which include ovarian serous carcinoma, uterine serous carcinoma, Fallopian tube serous carcinoma, cervical serous carcinoma, and primary peritoneal serous carcinoma really represent one entity.
Head and neck cancers are malignant neoplasms that arise in the head and region which comprises nasal cavity, paranasal sinuses, oral cavity, salivary glands, pharynx, and larynx. Majority of head and neck cancers histologically belong to squamous cell type and hence they are categorized as Head and Neck Squamous Cell Carcinoma (abbreviated as HNSCC)[Forastiere AA, 2003]. HNSCC are the 6th most common cancers worldwide and 3rd most common cancers in developing world. They account for ~ 5% of all malignancies worldwide (Ferlay J, 2010) and 3% of all malignancies in the United States (Siegel R, 2014).
Risk factors include tobacco consumption (chewing or smoking), alcohol consumption, Epstein-Barr virus (EBV) infection, human papilloma virus (HPV; esp. HPV 16, 18) infection, betel nut chewing, wood dust exposures, consumption of certain salted fish and others (NCI Factsheet, 2013). EBV infection has been specifically associated with nasopharyngeal cancer. Reverse smoking was considered as a risk factor for oral cancer. Interestingly, "Cis-retinoic acid" (i.e. supplements of retinoic acid) intake may increase the risk of HNSCC in active smokers. Low consumption of fruits and vegetables was associated with higher incidence of HNSCC.
HNSCC classification: Based on the HPV infection status, head and neck cancers are classified into HPV-positive and HPV-negative categories. So far, this is the only available molecular classification. Majority (>50%) of oral cancers are HPV-positive in the U.S. HPV-positive oral cancers are widely prevalent in younger patients and are associated with multiple sexual partners and oral sexual practices. HPV-positive cancers have better prognosis, especially for nonsmokers as compared to HPV-negative cancers.
Staging and grading of HNSCC: HNSCC are classified according to the tumor-node-metastasis (TNM) system of American Joint Committee on cancer. TNM staging system for HNSCC are discussed else where.
Symptoms include lump or sore, sore throat, hoarse of voice, difficulty in swallowing etc (NCI Factsheet, 2013).
Treatment for HNSCC is predominantly based on the stage of the disease. Factors such as patient fitness, baseline swallow, airway functional status, and others are considered before determining the treatment plan. Standard of care for HNSCC includes one or combination of the following: surgery, radiation, chemotherapeutic agents such as Cisplatin, 5-Flurouracil (5-FU) etc. Molecularly targeted therapies were developed since the discovery of role of epidermal growth factor receptor (EGFR) signaling in HNSCC development, progression and prognosis. These targeted therapies include monoclonal antibodies (such as cetuximab, panitumumab etc.) and tyrosine kinase inhibitors (such as erlotinib, gefitinib, etc.). Among these EGFR-targeting agents, only cetuximab has been approved by FDA in 2006 for HNSCC treatment.
Ninety percent (MacMillan, 2015) of cases of head and neck cancer (cancer of the mouth, nasal cavity, nasopharynx, throat and associated structures) are due to squamous cell carcinoma. Symptoms may include a poorly healing mouth ulcer, a hoarse voice or other persistent problems in the area. Treatment is usually with surgery (which may be extensive) and radiotherapy. Risk factors include smoking, alcohol consumption and hematopoietic stem cell transplantation (Elad S, Zadik Y, Zeevi I, et al., 2010, pp. 1243–1244). In addition, recent studies show that about 25% of mouth and 35% of throat cancers are associated with HPV. The 5 year disease free survival rate for HPV positive cancer is significantly higher when appropriately treated with surgery, radiation and chemotherapy as compared to non-HPV positive cancer, substantiated by multiple studies including research conducted by Maura Gillison, "et al." of Johns Hopkins Sidney Kimmel Cancer Center.
Throat cancer usually begins with symptoms that seem harmless enough, like an enlarged lymph node on the outside of the neck, a sore throat or a hoarse sounding voice. However, in the case of throat cancer, these conditions may persist and become chronic. There may be a lump or a sore in the throat or neck that does not heal or go away. There may be difficult or painful swallowing. Speaking may become difficult. There may be a persistent earache. Other possible but less common symptoms include some numbness or paralysis of the face muscles.
Presenting symptoms include :
- Mass in the neck
- Neck pain
- Bleeding from the mouth
- Sinus congestion, especially with nasopharyngeal carcinoma
- Bad breath
- Sore tongue
- Painless ulcer or sores in the mouth that do not heal
- White, red or dark patches in the mouth that will not go away
- Earache
- Unusual bleeding or numbness in the mouth
- Lump in the lip, mouth or gums
- Enlarged lymph glands in the neck
- Slurring of speech (if the cancer is affecting the tongue)
- Hoarse voice which persists for more than six weeks
- Sore throat which persists for more than six weeks
- Difficulty swallowing food
- Change in diet or weight loss
Histological variants of lung cancer classified as sarcomatoid carcinoma include pleomorphic carcinoma, giant cell carcinoma, spindle cell carcinoma, carcinosarcoma, and pulmonary blastoma.
Sarcomatoid carcinoma is a relatively uncommon form of cancer whose malignant cells have histological, cytological, or molecular properties of both epithelial tumors ("carcinoma") and mesenchymal tumors ("sarcoma").
Squamous cell cancers are common in the mouth, including the inner lip, tongue, floor of mouth, gingivae, and hard palate. Cancers of the mouth are strongly associated with tobacco use, especially use of chewing tobacco or "dip", as well as heavy alcohol use. Cancers of this region, particularly the tongue, are more frequently treated with surgery than are other head and neck cancers.
Surgeries for oral cancers include
- Maxillectomy (can be done with or without orbital exenteration)
- Mandibulectomy (removal of the mandible or lower jaw or part of it)
- Glossectomy (tongue removal, can be total, hemi or partial)
- Radical neck dissection
- Mohs procedure
- Combinational e.g., glossectomy and laryngectomy done together.
The defect is typically covered/improved by using another part of the body and/or skin grafts and/or wearing a prosthesis.
Like other cancers arising in the head and neck region, HPV+OPC may be an asymptomatic incidental finding of an abnormality in the mouth, by the patient or a health professional, present with local symptoms such as difficulties with speech, swallowing, and breathing as well as pain and infection, or as a swelling in the neck if the cancer has spread to lymph nodes there. These may be accompanied by more general symptoms such as loss of appetite, weight loss and weakness.
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.
Combined small cell lung carcinoma (or c-SCLC, and rarely rendered as "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 (or more) components of non-small cell lung carcinoma (NSCLC).
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.
Due to the diverse nature of salivary gland tumours, many different terms and classification systems have been used. Perhaps the most widely used currently is that system proposed by the World Health Organization in 2004, which classifies salivary neoplasms as primary or secondary, benign or malignant, and also by tissue of origin. This system defines five broad categories of salivary gland neoplasms:
Benign epithelial tumors
- Pleomorphic adenoma
- Warthin's tumor
- Myoepithelioma
- Basal cell adenoma
- Oncocytoma
- Canalicular adenoma
- Lymphadenoma
- "Sebaceous lymphadenoma"
- "Nonsebaceous lymphadenoma"
- Ductal papilloma
- "Inverted ductal papilloma"
- "Intraductal papilloma"
- "Sialadenoma papilliferum"
- Cystadenoma
- Malignant epithelial tumors
- Acinic cell carcinoma
- Mucoepidermoid carcinoma
- Adenoid cystic carcinoma
- Polymorphous low-grade adenocarcinoma
- Epithelial-myoepithelial carcinoma
- Clear cell carcinoma, not otherwise specified
- Basal cell adenocarcinoma
- Sebaceous carcinoma
- Sebaceous lymphadenocarcinoma
- Cystadenocarcinoma
- Low-grade cribriform cystadenocarcinoma
- Mucinous adenocarcinoma
- Oncocytic carcinoma
- Salivary duct carcinoma
- Salivary duct carcinoma, not otherwise specified
- Adenocarcinoma, not otherwise specified
- Myoepithelial carcinoma
- Carcinoma ex pleomorphic adenoma
- Mammary analogue secretory carcinoma
- Carcinosarcoma
- Metastasizing pleomorphic adenoma
- Squamous cell carcinoma
- Large cell carcinoma
- Lymphoepithelial carcinoma
- Sialoblastoma
- Soft tissue tumors
- Hemangioma
- Hematolymphoid tumors
- Hodgkin lymphoma
- Diffuse large B-cell lymphoma
- Extranodal marginal zone B cell lymphoma
- Secondary tumors (i.e. a tumor which has metastasized to the salivary gland from a distant location)
Others, not included in the WHO classification above, include:
- Intraosseous (central) salivary gland tumors
- Hybrid tumors (i.e. a tumor displaying combined forms of histologic tumor types)
- Hybrid carcinoma
- Others
- Others
- Keratocystoma
- Sialolipoma
Human papillomavirus-positive oropharyngeal cancer (HPV+OPC) is a subtype of oropharyngeal squamous cell carcinomas (OSCC), associated with the human papillomavirus type 16 virus (HPV16). Historically, cancer of the throat oropharynx (throat) was associated with the use of alcohol and tobacco, but the majority of cases are now associated with the HPV virus. HPV+OPC differs in a number of respects from OPC not associated with HPV (HPV-OPC), and is considered a separate disease. HPV has long been associated with cancers in the anogenital region, but in 2007 it was also recognized as a cause of oropharyngeal cancer. HPV is common among healthy adults and is largely transmitted through sexual contact, but tobacco use increases the risk of cancer.
Detection of a tumour suppressor protein, known as p16, is commonly used to diagnose an HPV associated OPC. The extent of disease is described in the standard cancer staging system, using the AJCC TNM system, based on the T stage (size and extent of tumour), N stage (extent of involvement of regional lymph nodes) and M stage (whether there is spread of the disease outside the region or not), and combined into an overall stage from I–IV. In 2016, a separate staging system was developed for HPV+OPC, distinct from HPV-OPC.
The historical treatment of OPC was surgical, with an approach through the neck and splitting of the jaw bone, which resulted in a considerable risk of death. Later, radiotherapy with or without the addition of chemotherapy, provided a less invasive alternative, and the results in terms of treating the cancer, were comparable. Newer minimally invasive surgical techniques through the mouth have improved outcomes, and surgery is often followed by radiation and or chemotherapy in high risk cases. In the absence of high quality evidence, management decisions are often based on technical factors, likely functional loss and the persons preferences. Some HPV+OPC may first appear in lymph nodes in the neck, without an obvious source (cancer of unknown primary origin) but removal of tonsil tissue from the oropharynx will often show hidden disease. The presence of HPV in the tumour is associated with a better response to treatment and a better outcome, independent of the treatment methods used and a nearly 60% reduced risk of dying from the cancer. Most recurrence occurs locally and within the first year after treatment. The use of tobacco decreases the chances of survival. While most head and neck cancer has been declining with reduced smoking rates, HPV+OPC has been increasing. Compared to HPV-OPC patients, HPV+OPC patients tend to be younger, have a higher socioeconomic status and are less likely to smoke. In addition they tend to have smaller tumours, but are more likely to have involvement of the cervical lymph nodes. In the United States and other countries, the number of cases of oropharyngeal cancer has been increasing steadily, with the incidence of HPV+OPC increasing faster than the decline in HPV-OPC. The increase is seen particularly in young men in developed countries, and HPV+OPC now accounts for the majority of all OPC cases.
Attempts are being made to reduce the incidence of HPV+OPC by introducing vaccination that includes HPV types 16 and 18, found in 95% of these cancers, prior to exposure to the virus. Early data suggest a reduction in infection rates.
Small-cell carcinoma (also known as "small-cell lung cancer", or "oat-cell carcinoma") is a type of highly malignant cancer that most commonly arises within the lung, although it can occasionally arise in other body sites, such as the cervix, prostate, and gastrointestinal tract. Compared to non-small cell carcinoma, small cell carcinoma has a shorter doubling time, higher growth fraction, and earlier development of metastases.