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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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It has been demonstrated that acral lentiginous melanoma has a poorer prognosis compared to that of cutaneous malignant melanoma (CMM).
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.
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.
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.
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.
Squamous cell carcinoma of eye tissues is one of the most frequent neoplasms of cattle.
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.
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.
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.
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.
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.
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"
Lentigo maligna (also known as "lentiginous melanoma on sun-damaged skin") is a melanoma "in situ" that consists of malignant cells but does not show invasive growth. Lentigo maligna is not the same as lentigo maligna melanoma, and should be discussed separately. It typically progresses very slowly and can remain in a non-invasive form for years. The transition to true melanoma is marked by the appearance of a bumpy surface (itself a marker of vertical growth and invasion), at which point it is called lentigo maligna melanoma. It is normally found in the elderly (peak incidence in the 9th decade), on skin areas with high levels of sun exposure like the face and forearms. Some authors do not consider lentigo maligna to be a melanoma. It is commonly thought of as a melanoma precursor. Incidence of evolution to lentigo maligna melanoma is very low, about 2.2% to 5% in elderly patients.
It is also known as "Hutchinson's melanotic freckle". This is named for Jonathan Hutchinson.
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).
The etiology of florid cutaneous papillomatosis is unknown. It is likely directly induced by an underlying neoplasm secreting a growth factor. One candidate may be alpha-transforming growth factor, structurally related to epidermal growth factor, but antigenically distinct from it. The underlying cancer is most often gastric adenocarcinoma but also with breast cancer, bladder cancer, hepatobiliary cancer, ovarian cancer, uterine cancer, prostate cancer, lung cancer and cervical cancer. Other associated underlying malignancies include squamous cell carcinomas and lymphomas.
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.
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.
Characteristics include a blue/black stain of skin initially. Skin is thin, about 4-5 cell layers thick, which is often related to aging. Histological features include epidermal atrophy and increased number of melanocytes.
An invasive tumor arising from a classical lentigo maligna. Usually a darkly pigmented raised papule or nodule, arising from a patch of irregularly pigmented flat brown to dark brown lesion of sun exposed skin of the face or arms in an elderly patient.
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.
Ultraviolet light from the sun causes premature aging of the skin and skin damage that can lead to melanoma. Some scientists hypothesize that overexposure to UV, including excessive sunlight, may play a role in the formation of acquired moles. However, more research is needed to determine the complex interaction between genetic makeup and overall exposure to ultraviolet light. Some strong indications that this is so (but falling short of proof), are:
- The relative lack of moles on the buttocks of people with dysplastic nevi.
- Freckles (spots of melanin on the skin, and distinct from moles) are known to be influenced by sunlight.
Studies have found that sunburns and too much time in the sun can increase the risk factors for melanoma. This is "in addition to" those who have dysplastic nevi being at higher risk of this cancer (the uncertainty is in regard to acquiring "benign" moles). To prevent and reduce the risk of melanoma caused by UV radiation, the American Academy of Dermatology and the National Cancer Institute recommends staying out of the sun between 10 a.m. and 4 p.m. standard time (or whenever one's shadow is shorter than one's height). The National Cancer Institute also recommends wearing long sleeves and trousers, hats with a wide brim, sunscreens, and sunglasses that have UV-deflecting lenses.
Desmoplastic melanoma (also known as a "Neurotropic melanoma," or "Spindled melanoma") is a rare cutaneous condition characterized by a deeply infiltrating type of melanoma with an abundance of fibrous matrix. It usually occurs in the head and neck region of older people with sun-damaged skin. Diagnosis can be difficult as it has a similar appearance to sclerosing melanocytic nevi as well as some nonmelanocytic skin lesions such as scars, fibromas, or cysts.
Desmoplastic melanomas tend to recur locally, with distant metastasis being less common.
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.
Superficial spreading melanoma (also known as "superficially spreading melanoma") (SSM) is usually characterized as the most common form of cutaneous melanoma in Caucasians. The average age at diagnosis is in the fifth decade, and it tends to occur on sun-exposed skin, especially on the backs of males and lower limbs of females.
A lentigo () (plural lentigines, ) is a small pigmented spot on the skin with a clearly defined edge, surrounded by normal-appearing skin. It is a harmless (benign) hyperplasia of melanocytes which is linear in its spread. This means the hyperplasia of melanocytes is restricted to the cell layer directly above the basement membrane of the epidermis where melanocytes normally reside. This is in contrast to the "nests" of multi-layer melanocytes found in moles (melanocytic nevi). Because of this characteristic feature, the adjective "lentiginous" is used to describe other skin lesions that similarly proliferate linearly within the basal cell layer.
Lentigines are distinguished from freckles (ephelis) based on the proliferation of melanocytes. Freckles have a relatively normal number of melanocytes but an increased "amount" of melanin. A lentigo has an increased "number" of melanocytes. Freckles will increase in number and darkness with sunlight exposure, whereas lentigines will stay stable in their color regardless of sunlight exposure.
Lentigines by themselves are benign, however one might desire the removal or treatment of some of them for cosmetic purposes. In this case they can be removed surgically, or lightened with the use of topical depigmentation agents. Some common depigmentation agents such as azelaic acid and kojic acid seem to be inefficient in this case, however other agents might work well (4% hydroquinone, 5% topical cysteamine, 10% topical ascorbic acid).
Conditions characterized by lentigines include:
- Lentigo simplex
- Solar lentigo (Liver spots)
- PUVA lentigines
- Ink spot lentigo
- LEOPARD syndrome
- Mucosal lentigines
- Multiple lentigines syndrome
- Moynahan syndrome
- Generalized lentiginosis
- Centrofacial lentiginosis
- Carney complex
- Inherited patterned lentiginosis in black persons
- Partial unilateral lentiginosis
- Peutz-Jeghers syndrome
- Lentigo maligna
- Lentigo maligna melanoma
- Acral lentiginous melanoma