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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
In its early stages, it can go unnoticed. It can be painless with slight physical changes. But the precursor tissue changes, can be noticed by the doctors.
Early stage symptoms can include persistent red or white patches, a non-healing ulcer, progressive swelling or enlargement, unusual surface changes, sudden tooth mobility without apparent cause, unusual oral bleeding or epitaxis and prolonged hoarseness.
Late stage symptoms can include an indurated area, paresthesia or dysesthesia of the tongue or lips, airway obstruction, chronic serous otitis media, otalgia, trismus, dysphagia, cervical lymphadenopathy, persistent pain or referred pain and altered vision.
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.
Vaginal squamous cell carcinoma spreads slowly and usually stays near the vagina, but may spread to the lungs and liver. This is the most common type of vaginal cancer.
Oral cancer, also known as mouth cancer, is a type of head and neck cancer and is any cancerous tissue growth located in the oral cavity.
It may arise as a primary lesion originating in any of the tissues in the mouth, by metastasis from a distant site of origin, or by extension from a neighboring anatomic structure, such as the nasal cavity. Alternatively, the oral cancers may originate in any of the tissues of the mouth, and may be of varied histologic types: teratoma, adenocarcinoma derived from a major or minor salivary gland, lymphoma from tonsillar or other lymphoid tissue, or melanoma from the pigment-producing cells of the oral mucosa. There are several types of oral cancers, but around 90% are squamous cell carcinomas, originating in the tissues that line the mouth and lips. Oral or mouth cancer most commonly involves the tongue. It may also occur on the floor of the mouth, cheek lining, gingiva (gums), lips, or palate (roof of the mouth). Most oral cancers look very similar under the microscope and are called squamous cell carcinoma, but less commonly other types of oral cancer occur, such as Kaposi's sarcoma.
In 2013 oral cancer resulted in 135,000 deaths up from 84,000 deaths in 1990. Five-year survival rates in the United States are 63%.
Although often the terms "erythroplasia" and "erythroplakia" are used synonymously, some sources distinguish them, stating that the latter is maccular (flat) while the former is papular (bumpy).
Erythroplakia of the genital mucosae is often referred to as erythroplasia of Queyrat.
The most common areas in the mouth where erythroplakia is found are the floor of the mouth, buccal vestibule, the tongue, and the soft palate. It appears as a red macule or plaque with well-demarcated borders. The texture is characterized as soft and velvety. An adjacent area of leukoplakia may be found along with the erythroplakia.
Erythroplasia may also occur on the laryngeal mucosa, or the anal mucosa.
In the context of lesions of the mucous membrane lining of the bladder, leukoplakia is a historic term used to describe a visualized white patch which histologically represents keratinization in an area of squamous metaplasia. The symptoms may include frequency, suprapubic pain (pain felt above the pubis), hematuria (blood in the urine), dysuria (difficult urination or pain during urination), urgency, and urge incontinence. The white lesion may be seen during cystoscopy, where it appears as a whitish-gray or yellow lesion, on a background of inflamed urothelium and there may be floating debris in the bladder. Leukoplakia of the bladder may undergo cancerous changes, so biopsy and long term follow up are usually indicated.
Most cases of leukoplakia cause no symptoms, but infrequently there may be discomfort or pain. The exact appearance of the lesion is variable. Leukoplakia may be white, whitish yellow or grey. The size can range from a small area to much larger lesions. The most common sites affected are the buccal mucosa, the labial mucosa and the alveolar mucosa, although any mucosal surface in the mouth may be involved. The clinical appearance, including the surface texture and color, may be homogenous or non-homogenous (see: classification). Some signs are generally associated with a higher risk of cancerous changes (see: prognosis).
Leukoplakia may rarely be associated with esophageal carcinoma.
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
There are many other conditions that are similar in appearance and must be ruled out before a diagnosis of erythroplakia is made (see table). Sometimes, a diagnosis is delayed for up to two weeks in order to see if the lesion spontaneously regresses on its own or if another cause can be found. Erythroplakia frequently is associated with dysplasia, and is thus a precancerous lesion.
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.
STK typically occurs in the buccal sulcus (inside the cheek) or the labial sulcus (between the lips and the teeth) and corresponds to the site where the tobacco is held in the mouth. It is painless.
The appearance of the lesion is variable depending upon the type of tobacco used, and the frequency and duration of use. It takes about 1-5 years of smokeless tobacco use for the lesion to appear. Early lesions may appear as thin, translucent and granular or wrinkled mucosa. The later lesion may appear thicker, more opaquely white and hyperkeratotic with fissures and folds. Oral snuff causes more pronounced changes in the oral mucosa than tobacco chewing. Snuff dipping is associated more with verrucous keratosis.
As well as the white changes of the oral mucosa, there may be gingival recession (receding gums) and staining of tooth roots in the area where the tobacco is held.
Salivary gland tumours usually present as a lump or swelling in the affected gland which may or may not have been present for a long time. The lump may be accompanied by symptoms of duct blockage (e.g. xerostomia). Usually, in their early stages it is not possible to distinguish a benign tumour from a malignant one. One of the key differentiating symptoms of a malignant growth is nerve involvement. For example signs of facial nerve damage (e.g facial palsy) are associated with malignant parotid tumours. Facial pain, and paraesthesia are also very often associated with a malignant tumours. Other red flag symptoms which may suggest malignancy and warrant further investigation are fixation of the lump to the overlying skin, ulceration and induration of the mucosa.
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.
SCC of the skin begins as a small nodule and as it enlarges the center becomes necrotic and sloughs and the nodule turns into an ulcer.
- The lesion caused by SCC is often asymptomatic
- Ulcer or reddish skin plaque that is slow growing
- Intermittent bleeding from the tumor, especially on the lip
- The clinical appearance is highly variable
- Usually the tumor presents as an ulcerated lesion with hard, raised edges
- The tumor may be in the form of a hard plaque or a papule, often with an opalescent quality, with tiny blood vessels
- The tumor can lie below the level of the surrounding skin, and eventually ulcerates and invades the underlying tissue
- The tumor commonly presents on sun-exposed areas (e.g. back of the hand, scalp, lip, and superior surface of pinna)
- On the lip, the tumor forms a small ulcer, which fails to heal and bleeds intermittently
- Evidence of chronic skin photodamage, such as multiple actinic keratoses (solar keratoses)
- The tumor grows relatively slowly
It presents itself in the mouth, most frequently as a thick, bilateral, symmetrical white plaques with a spongy, corrugated or velvety texture. Most usually, the lesions are on the buccal mucosa, but sometimes on the labial mucosa, alveolar ridge, floor of the mouth, ventral surface of the tongue or soft palate. The gingival margin and dorsum of the tongue are almost never affected. Less commonly, sites outside the mouth are affected, including the nasal, esophageal, laryngeal, anal and genital mucosae. It usually is present from birth, or develops during childhood. Rarely, the lesions may develop during adolescence. Apart from the appearance of the affected areas, there are usually no other signs or symptoms.
Smokeless tobacco keratosis (abbreviated to STK, also termed snuff dippers' keratosis, smokeless tobacco-associated keratosis, snuff pouch, snuff dipper's lesion, tobacco pouch keratosis, or spit tobacco keratosis) is a condition which develops on the oral mucosa (the lining of the mouth) in response to smokeless tobacco use. Generally it appears as a white patch, located at the point where the tobacco is held in the mouth. The condition usually disappears once the tobacco habit is stopped. It is associated with slightly increased risk of mouth cancer.
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
There is a diffuse, gray-white, milky opalescent appearance of the mucosa which usually occurs bilaterally on the buccal mucosa. Less often, the labial mucosa, the palate or the floor of mouth may be affected. The surface of the area is folded, creating a wrinkled, white streaked lesion. Apart from the appearance, the lesion is entirely asymptomatic.
Rarely is any soreness associated with the condition. Apart from the appearance of the lesion, there are usually no other signs or symptoms. The typical appearance of the lesion is an oval or rhomboid shaped area located in the midline of the dorsal surface of the tongue, just anterior (in front) of the sulcus terminalis. The lesion is usually symmetric, well demarcated, erythematous and depapillated, which has a smooth, shiny surface. Less typically, the lesion may be hyperplastic or lobulated and exophytic. There may be candidal lesions at other sites in the mouth, which may lead to a diagnosis of chronic multifocal oral candidiasis. Sometimes an approximating erythematous lesion is present on the palate as the tongue touches the palate frequently. The lesion is typically 2–3 cm in its longest dimension.
Squamous-cell carcinoma (SCC) is the most common cancer of the eye, periorbital area and penis, and it is the second most common cancer overall in horses, accounting for 12 to 20% of all cancers diagnosed. While SCC has been reported in horses aged 1 to 29-years, most cases occur in 8 to 15-year-old horses, making it the most common neoplasm reported in older horses. Carcinomas are tumors derived from epithelial cells and SCC results from transformation and proliferation of squames, epidermal skin cells that become keratinized. Squamous-cell carcinomas are often solitary, slow-growing tumors that cause extensive local tissue destruction. They can metastasize to other organs, with reported rates as high as 18.6%, primarily to the lymph nodes and lung.
The appearance and number of sarcoids can vary, with some horses having single or multiple lesions, usually on the head, legs, ventrum and genitalia or around a wound. The distribution pattern suggests that flies are an important factor in the formation of sarcoids. Sarcoids may resemble warts (verrucous form), small nodules (nodular form), oval hairless or scaly plaques (occult form) or very rarely, large ulcerated masses (fibroblastic form). The occult form usually presents on skin around the mouth, eyes or neck, while nodular and verrucous sarcoids are common on the groin, penile sheath or face. Fibroblastic sarcoids have a predilection for the legs, groin, eyelid and sites of previous injury. Multiple forms may also be present on an individual horse (mixed form). Histologically, sarcoids are composed of fibroblasts (collagen producing cells) that invade and proliferate within the dermis and sometimes the subcutaneous tissue but do not readily metastasize to other organs. Surgical biopsy can definitively diagnose sarcoids, but there is a significant risk of making sarcoids worse. Therefore, diagnosis based solely on clinical signs, fine-needle aspiration or complete excisional biopsy are safer choices.
Squamous-cell skin cancer, also known as cutaneous squamous-cell carcinoma (cSCC), is one of the main types of skin cancer along with basal cell cancer, and melanoma. It usually presents as a hard lump with a scaly top but can also form an ulcer. Onset is often over months. Squamous-cell skin cancer is more likely to spread to distant areas than basal cell cancer.
The greatest risk factor is high total exposure to ultraviolet radiation from the Sun. Other risks include prior scars, chronic wounds, actinic keratosis, lighter skin, Bowen's disease, arsenic exposure, radiation therapy, poor immune system function, previous basal cell carcinoma, and HPV infection. Risk from UV radiation is related to total exposure, rather than early exposure. Tanning beds are becoming another common source of ultraviolet radiation. It begins from squamous cells found within the skin. Diagnosis is often based on skin examination and confirmed by tissue biopsy.
Decreasing exposure to ultraviolet radiation and the use of sunscreen appear to be effective methods of preventing squamous-cell skin cancer. Treatment is typically by surgical removal. This can be by simple excision if the cancer is small otherwise Mohs surgery is generally recommended. Other options may include application of cold and radiation therapy. In the cases in which distant spread has occurred chemotherapy or biologic therapy may be used.
As of 2015, about 2.2 million people have cSCC at any given time. It makes up about 20% of all skin cancer cases. About 12% of males and 7% of females in the United States developed cSCC at some point in time. While prognosis is usually good, if distant spread occurs five-year survival is ~34%. In 2015 it resulted in about 51,900 deaths globally. The usual age at diagnosis is around 66. Following the successful treatment of one case of cSCC people are at high risk of developing further cases.
Predisposing factors include smoking, denture wearing, use of corticosteroid sprays or inhalers and human immunodeficiency virus (HIV) infection. "Candida" species even in healthy people mainly colonizes the posterior dorsal tongue. Median rhombiod glossitis is thought to be a type of chronic atrophic (or erythematous) candidiasis. Microbiological culture of the lesion usually shows "Candida" mixed with bacteria.
A ranula usually presents as a translucent blue, dome-shaped, swelling in the tissues of the floor of the mouth. If the lesion is deeper, then there is a greater thickness of tissue separating from the oral cavity and the blue translucent appearance may not be a feature. A ranula can develop into a large lesion many centimeters in diameter, with resultant elevation of the tongue and possibly interfering with swallowing (dysphagia). The swelling is not fixed, may not show blanching and is non-painful unless it becomes secondarily infected. The usual location is usually lateral to the midline, which may be used to help distinguish it from a midline dermoid cyst. A cervical ranula presents as a swelling in the neck, with or without a swelling in the mouth. In common with other mucoceles, ranulas may rupture and then cause recurrent swelling. Ranulas may be asymptomatic, although they can fluctuate rapidly in size, shrinking and swelling, making them hard to detect.
Leukoedema lesions disappear when the mucosa is stretched, which helps to differentiate it from other white lesions in the mouth. The differential diagnosis is with leukoplakia, oral candidiasis, oral lichen planus, white sponge nevus, morsicatio buccarum, hereditary benign intraepithelial dyskeratosis and dyskeratosis congenita. Tissue biopsy is not indicated, but when taken, the histologic appearance is one of increased epithelial thickness, broadening and eleongation of the rete ridges, parakeratosis and intracellular edema of the spinous layer. The cells of the spinous later are vacuolated, large and possess pyknotic nuclei. The superficial squamous cells have a clear, seemingly empty cytoplasm but it has not been shown that there is an increase in intracellular water, possibly making the term edema misleading. The histologic appearance is thought to be caused by water within the cells of the spinous layer causing the light to reflect back as whitish. The diagnosis is usually made based on the clinical appearance alone, but oral exfoliative cytology has been used as a diagnostic aid.