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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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The ultraviolet radiation from tanning beds increases the risk of melanoma. The International Agency for Research on Cancer finds that tanning beds are "carcinogenic to humans" and that people who begin using tanning devices before the age of thirty years are 75% more likely to develop melanoma.
Those who work in airplanes also appear to have an increased risk, believed to be due to greater exposure to UV.
Ultraviolet UVB light (wavelengths between 315 – 280 nm) from the sun is absorbed by skin cell DNA and results in a type of direct DNA damage called cyclobutane pyrimidine dimers (CPDs). Thymine-thymine, cytosine-cytosine or cytosine-thymine dimers are formed by the joining of two adjacent pyrimidine bases within a DNA strand. Somewhat similarly to UVB, UVA light (longer wavelengths between 400 – 315 nm) from the sun or from tanning beds can also be directly absorbed by skin DNA (at about 100 to 1000 fold lower efficiency than UVB is absorbed).
Studies suggest that exposure to ultraviolet radiation (UVA and UVB) is one of the major contributors to the development of melanoma. Occasional extreme sun exposure (resulting in "sunburn") is causally related to melanoma. Melanoma is most common on the back in men and on legs in women (areas of intermittent sun exposure). The risk appears to be strongly influenced by socio-economic conditions rather than indoor versus outdoor occupations; it is more common in professional and administrative workers than unskilled workers. Other factors are mutations in or total loss of tumor suppressor genes. Use of sunbeds (with deeply penetrating UVA rays) has been linked to the development of skin cancers, including melanoma.
Possible significant elements in determining risk include the intensity and duration of sun exposure, the age at which sun exposure occurs, and the degree of skin pigmentation. Melanoma rates tend to be highest in countries settled by migrants from northern Europe that have a large amount of direct, intense sunlight that the skin of the settlers is not adapted to, most notably Australia. Exposure during childhood is a more important risk factor than exposure in adulthood. This is seen in migration studies in Australia.
Having multiple severe sunburns increases the likelihood that future sunburns develop into melanoma due to cumulative damage. The sun and tanning beds are the main sources of UV radiation that increase the risk for melanoma and living close to the equator increases exposure to UV radiation.
This type of cancer occurs most often in Caucasians between 60 and 80 years of age, and its rate of incidence is about twice as high in males as in females. There are roughly 1,500 new cases of MCC diagnosed each year in the United States, as compared to around 60,000 new cases of melanoma and over 1 million new cases of nonmelanoma skin cancer. MCC is sometimes mistaken for other histological types of cancer, including basal cell carcinoma, squamous cell carcinoma, malignant melanoma, lymphoma, and small cell carcinoma, or as a benign cyst. Researchers believe that exposure to sunlight or ultraviolet light (such as in a tanning bed) may increase the risk of developing this disease. Similar to melanoma, the incidence of MCC in the US is increasing rapidly.
Immunosuppression can profoundly increase the odds of developing Merkel-cell carcinoma. Merkel-cell carcinoma occurs 30 times more often in people with chronic lymphocytic leukemia and 13.4 times more often in people with advanced HIV as compared to the general population; solid organ transplant recipients have a 10-fold increased risk compared to the general population.
Melanomas are usually caused by DNA damage resulting from exposure to ultraviolet light from the sun. Genetics also plays a role.
Having more than fifty moles indicates an increased risk melanoma might arise. A weakened immune system makes it easier for cancer to arise due to the body’s weakened ability to fight cancer cells.
The incidence of squamous cell carcinoma continues to rise around the world. A recent study estimated that there are between 180,000 and 400,000 cases of SCC in the United States in 2013. Risk factors for squamous cell carcinoma varies with age, gender, race, geography, and genetics. The incidence of SCC increases with age and the peak incidence is usually around 60 years old. Males are affected with SCC at a ratio of 2:1 in comparison to females. Caucasians are more likely to be affected, especially those with fair Celtic skin and chronically exposed to UV radiation. Squamous cell carcinoma of the skin is the most common among all sites of the body. Solid organ transplant recipients (heart, lung, liver, pancreas, among others) are also at a heightened risk of developing aggressive, high-risk SCC. There are also a few rare congenital diseases predisposed to cutaneous malignancy. In certain geographic locations, exposure to arsenic in well water or from industrial sources may significantly increase the risk of SCC.
Lymphoma is the most common type of blood-related cancer in horses and while it can affect horses of all ages, it typically occurs in horses aged 4–11 years.
People who have received solid organ transplants are at a significantly increased risk of developing squamous cell carcinoma due to the use of chronic immunosuppressive medication. While the risk of developing all skin cancers increases with these medications, this effect is particularly severe for SCC, with hazard ratios as high as 250 being reported, versus 40 for basal cell carcinoma. The incidence of SCC development increases with time posttransplant. Heart and lung transplant recipients are at the highest risk of developing SCC due to more intensive immunosuppressive medications used. Squamous cell cancers of the skin in individuals on immunotherapy or suffering from lymphoproliferative disorders (i.e. leukemia) tend to be much more aggressive, regardless of their location. The risk of SCC, and non-melanoma skin cancers generally, varies with the immunosuppressive drug regimen chosen. The risk is greatest with calcineurin inhibitors like cyclosporine and tacrolimus, and least with mTOR inhibitors, such as sirolimus and everolimus. The antimetabolites azathioprine and mycophenolic acid have an intermediate risk profile.
Squamous cell carcinoma of eye tissues is one of the most frequent neoplasms of cattle.
It has been demonstrated that acral lentiginous melanoma has a poorer prognosis compared to that of cutaneous malignant melanoma (CMM).
A newly discovered virus called Merkel cell polyomavirus (MCV) likely contributes to the development of the majority of MCC. Approximately 80% of MCC have this virus integrated in a monoclonal pattern, indicating that the infection was present in a precursor cell before it became cancerous. At least 20% of MCC tumors are not infected with MCV, suggesting that MCC may have other causes as well.
Polyomaviruses have been known to be oncogenic (cancer-causing) viruses in animals since the 1950s, but MCV is the first polyomavirus strongly suspected to cause tumors in humans. Like other tumor viruses, most people who are infected with MCV probably do not develop MCC. It is currently unknown what other steps or co-factors are required for MCC-type cancers to develop. MCC can also occur together with other sun exposure-related skin cancers that are not infected with MCV (i.e. basal cell carcinoma, squamous cell carcinoma, melanoma). Intriguingly, most MCV viruses obtained so far from tumors have specific mutations that render the virus uninfectious. It is unknown whether these particular mutations result from sun exposure. MCC also occurs more frequently than would otherwise be expected among immunosuppressed patients, such as transplant patients, AIDS patients, and the elderly persons, suggesting that the initiation and progression of the disease is modulated by the immune system.
While infection with MCV is common in humans, MCC patients whose tumors contain MCV have higher antibody levels against the virus than similarly infected healthy adults. A recent study of a large patient registry from Finland suggests that individuals with MCV-positive MCC's have better prognoses than do MCC patients without MCV infection. While MCV-positive MCC may be a less aggressive form of the disease, the results of the aforementioned study may instead be due to significant differences in other confounding factors, including tumor stage at the time of diagnosis, the age of the patient, or the location of the tumor rather than any intrinsic difference in disease aggressiveness or response to therapy.
Therapies for metastatic melanoma include the biologic immunotherapy agents ipilimumab, pembrolizumab, and nivolumab; BRAF inhibitors, such as vemurafenib and dabrafenib; and a MEK inhibitor trametinib.
Ultraviolet radiation from sun exposure is the primary environmental cause of skin cancer. Other risk factors that play a role include:
- Smoking tobacco
- HPV infections increase the risk of squamous-cell skin cancer.
- Some genetic syndromes including congenital melanocytic nevi syndrome which is characterized by the presence of nevi (birthmarks or moles) of varying size which are either present at birth, or appear within 6 months of birth. Nevi larger than 20 mm (3/4") in size are at higher risk for becoming cancerous.
- Chronic non-healing wounds. These are called Marjolin's ulcers based on their appearance, and can develop into squamous-cell skin cancer.
- Ionizing radiation such as X-rays, environmental carcinogens, artificial UV radiation (e.g. tanning beds), aging, and light skin color. It is believed that tanning beds are the cause of hundreds of thousands of basal and squamous-cell skin cancer. The World Health Organization now places people who use artificial tanning beds in its highest risk category for skin cancer. Alcohol consumption, specifically excessive drinking increase the risk of sunburns.
- The use of many immunosuppressive medications increases the risk of skin cancer. Cyclosporin A, a calcineurin inhibitor for example increases the risk approximately 200 times, and azathioprine about 60 times.
Acral lentiginous melanoma is due as a result of malignant melanocytes. This occurs at the membrane of the skin (outer layers). It should be noted that the pathogenesis of acral lentiginous melanoma remains unknown at this time.
Skin cancers result in 80,000 deaths a year as of 2010, 49,000 of which are due to melanoma and 31,000 of which are due to non-melanoma skin cancers. This is up from 51,000 in 1990.
More than 3.5 million cases of skin cancer are diagnosed annually in the United States, which makes it the most common form of cancer in that country. One in five Americans will develop skin cancer at some point of their lives. The most common form of skin cancer is basal-cell carcinoma, followed by squamous cell carcinoma. Unlike for other cancers, there exists no basal and squamous cell skin cancers registry in the United States.
Keratoacanthoma usually occurs in older individuals. As with squamous cell cancer, it seems likely that ultraviolet light from the sun causes the development of KA. As with squamous cell cancer, sporadic cases have been found co-infected with the human papilloma virus (HPV).
Many new treatments for Melanoma are also known to increase the rate of Keratoacanthoma, such as the B-Raf inhibitor drugs Vemurafenib and Dabrafenib.
Equine melanoma results from abnormal proliferation and accumulation of melanocytes, pigmented cells within the dermis. Gray horses over 6-years-old are especially prone to developing melanoma. The prevalence of melanoma in gray horses over 15 years old has been estimated at 80%. One survey of Camargue-type horses found an overall population prevalence of 31.4%, with prevalence increasing to 67% in horses over 15 years old. Up to 66% of melanomas in gray horses are benign, but melanotic tumors in horses with darker hair-coats may be more aggressive and are more often malignant. One retrospective study of cases sent to a referral hospital reported a 14% prevalence of metastatic melanoma within the study population. However, the actual prevalence of metastatic melanoma may be lower due to infrequent submission of melanotic tumors for diagnosis. Common sites for metastasis include lymph nodes, the liver, spleen, lung, skeletal muscle, blood vessels and parotid salivary gland.
Lentigo maligna melanoma is a melanoma that has evolved from a lentigo maligna. They are usually found on chronically sun damaged skin such as the face and the forearms of the elderly. The nomenclature is very confusing to both patients and physicians alike.
Lentigo maligna is the non-invasive skin growth that some pathologists consider to be a melanoma-in-situ. A few pathologists do not consider lentigo maligna to be a melanoma at all, but a precursor to melanomas. Once a lentigo maligna becomes a lentigo maligna melanoma, it is treated as if it were an invasive melanoma.
Conjunctival Squamous Cell Carcinoma (Conjunctival SCC) and corneal intraepithelial neoplasia comprise what are called Ocular Surface Squamous Cell Neoplasias. SCC is the most common malignancy of the conjunctiva in the US, with a yearly incidence of 1-2.8 per 100,000. Risk factors for the disease are exposure to sun (specifically occupational), exposure to UVB, and light-colored skin. Other risk factors include radiation, smoking, HPV, arsenic, and exposure to polycyclic hydrocarbons.
Conjunctival SCC is often asymptomatic at first, but it can present with the presence of a growth, red eye, pain, itching, burning, tearing, sensitivity to light, double vision, and decreased vision.
Spread of conjunctival SCC can occur in 1-21% of cases, with the first site of spread being the regional lymph nodes. Mortality for conjunctival SCC ranges from 0-8%.
Diagnosis is often made by biopsy, as well as CT (in the case of invasive SCC).
Treatment of Conjunctival SCC is usually surgical excision followed by cryotherapy. After this procedure, Conjunctival SCC can recur 8-40% of the time. Radiation treatment, topical Mitomycin C, and removal of the contents of the orbit, or exenteration, are other methods of treatment. Close follow-up is recommended, because the average time to recurrence is 8–22 months.
Nodular melanoma (NM) is the most aggressive form of melanoma. It tends to grow more rapidly in thickness (penetrate the skin) than in diameter. Instead of arising from a pre-existing mole, it may appear in a spot where a lesion did not previously exist . Since NM tends to grow in depth more quickly than it does in width, and can occur in a place that did not have a previous lesion, the prognosis is often worse because it takes longer for a person to be aware of the changes. NM is most often darkly pigmented; however, some NM lesions can be light brown, multicolored or even colorless (non-pigmented). A light-colored or non-pigmented NM lesion may escape detection because the appearance is not alarming, however an ulcerated and/or bleeding lesion is common. Polypoid melanoma is a virulent variant of nodular melanoma.
The microscopic hallmarks are:
- Dome-shaped at low power
- Epidermis thin or normal
- Dermal nodule of melanocytes with a 'pushing' growth pattern
- No "radial growth phase"
When the tumor is large and there is presence of necrosis and local recurrence, the prognosis is poor. Presence of metastasis occurs in more than 50% cases and the common places of its occurrence are the bone, lymph node and lungs. Five-year survival rates, which are reported to be between 50-65%, can be misleading because the disease is prone to late metastasis or recurrence. Ten and twenty-year survival rates are 33% and 10%, respectively.
Treatment depends on the thickness of the invasive component of the lentigo maligna. Treatment is essentially identical to other melanomas of the same thickness and stage.
The treatment protocol for uveal melanoma has been directed by many clinical studies, the most important being The Collaborative Ocular Melanoma Study (COMS). The treatment varies depending upon many factors, chief among them, the size of the tumor and results from testing of biopsied material from the tumor. Primary treatment can involve removal of the affected eye (enucleation); however, this is now reserved for cases of extreme tumor burden or other secondary problems. Advances in radiation therapies have significantly decreased the number of patients treated by enucleation in developed countries. The most common radiation treatment is plaque brachytherapy, in which a small disc-shaped shield (plaque) encasing radioactive seeds (most often Iodine-125, though Ruthenium-106 and Palladium-103 are also used) is attached to the outside surface of the eye, overlying the tumor. The plaque is left in place for a few days and then removed. The risk of metastasis after plaque radiotherapy is the same as that of enucleation, suggesting that micrometastatic spread occurs prior to treatment of the primary tumor. Other modalities of treatment include transpupillary thermotherapy, external beam proton therapy, resection of the tumor, Gamma Knife stereotactic radiosurgery or a combination of different modalities. Different surgical resection techniques can include trans-scleral partial choroidectomy, and transretinal endoresection.
Benign melanocytic tumors of the choroid, such as choroidal freckles and nevi, are very common and pose no health risks, unless they show signs of malignancy, in which case they are considered melanomas. Uveal melanoma is distinct from most skin melanomas associated with ultraviolet exposure; however, it shares several similarities with non-sun-exposed melanomas, such as acral melanomas and mucosal melanomas. BRAF mutations are extremely rare in posterior uveal melanomas; instead, uveal melanomas frequently harbor GNAQ/GNA11 mutations, a trait shared with blue nevi, Nevus of Ota, and Ocular melanosis. As seen in BRAF, mutations in GNAQ/GNA11 are early events in tumorigenesis and are not prognostic for tumor stage or later metastatic spread. In contrast, mutations in the gene BAP1 are strongly linked to metastatic spread and patient survival. Incidence of posterior uveal melanoma is highest among people with light skin and blue eyes. Other risk factors, such as blue light exposure and arc welding have been put forward, but are still debated in the field. Mobile phone use is not a risk factor for uveal melanoma.
Florid cutaneous papillomatosis is almost twice as common in men than in women, and is usually diagnosed in individuals aged 53–72 years (mean patient age, 58.5 years).
Spitz nevi are uncommon. Their annual incidence was estimated in a coastal population of sub-tropical Queensland to be 1.4 cases per 100,000 people. For comparison, the annual incidence of melanoma in the same population, which is high by world standards is 25.4 cases per 100,000 people.
Although they are most commonly found on people in their first two decades of life, the age range for people with Spitz nevi is from 6 months to 71 years, with a mean age of 22 years and a median age of 19 years.
Clear-cell sarcoma (formerly known as malignant melanoma of the soft parts) is a rare form of cancer called sarcoma. It is known to occur mainly in the soft tissues and dermis. Rare forms were thought to occur in the gastrointestinal tract before they were discovered to be different and redesignated as GNET.
Recurrence is common.
It has been associated with both EWSR1-ATF1 and EWSR1-CREB1 fusion transcripts.
Clear cell sarcoma of the soft tissues in adults is not related to the pediatric tumor known as clear cell sarcoma of the kidney.