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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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MCC usually presents as a firm, painless, nodule (up to 2 cm diameter) or mass (>2 cm diameter). These flesh-colored, red, or blue tumors typically vary in size from 0.5 cm (less than one-quarter of an inch) to more than 5 cm (2 inches) in diameter, and usually enlarge rapidly. Although MCC's may arise almost anywhere on the body, about half originate on sun-exposed areas of the head and neck, one-third on the legs, and about one-sixth on the arms. In about 12% of cases, no obvious anatomical site of origin ("primary site") can be identified.
Merkel-cell cancers tend to invade locally, infiltrating the underlying subcutaneous fat, fascia, and muscle, and typically metastasize early in their natural history, most often to the regional lymph nodes. MCCs also spread aggressively through the blood vessels, particularly to liver, lung, brain, and bone.
A Mixed tumor is a tumor that derives from multiple tissue types.
For example, a "Chondroid syringoma" is a cutaneous condition characterized histologically by nests of cuboidal or polygonal epithelial cells in the dermis.
There are two types: one derived from a single germ cell layer that differentiates into more than one cell type, and one derived from more than one germ cell layer (totipotent cells).
These terms are related since they represent the steps of the progression toward cancer:
- Dysplasia is the earliest form of precancerous lesion recognizable in a biopsy. Dysplasia can be low-grade or high-grade. High-grade dysplasia may also be referred to as carcinoma "in situ".
- Invasive carcinoma, usually simply called cancer, has the potential to invade and spread to surrounding tissues and structures, and may eventually be lethal.
It presents as a slow growing mass that especially affects tendons and aponeuroses and it is deeply situated. Patients often perceive it as a lump or hard mass. It causes either pain or tenderness but only until it becomes large enough. This kind of tumor is commonly found in the extremities especially around the knee, feet and ankle. Patients diagnosed with clear cell sarcoma are usually between the ages of 20 and 40.
Carcinoma "in situ (CIS), also known as in situ" neoplasm, is a group of abnormal cells. While they are a form of neoplasm there is disagreement over whether CIS should be classified as cancer. This controversy also depends on the exact CIS in question (i.e. cervical, skin, breast). Some authors do not classify them as cancer, however, recognizing that they can potentially become cancer. Others classify certain types as a non-invasive form of cancer. The term "pre-cancer" has also been used.
These abnormal cells grow in their normal place, thus ""in situ"" (from Latin for "in its place"). For example, carcinoma "in situ" of the skin, also called Bowen's disease, is the accumulation of dysplastic epidermal cells within the epidermis only, that has failed to penetrate into the deeper dermis. For this reason, CIS will usually not form a tumor. Rather, the lesion is flat (in the skin, cervix, etc.) or follows the existing architecture of the organ (in the breast, lung, etc.). Exceptions include CIS of the colon (polyps), the bladder (preinvasive papillary cancer), or the breast (ductal carcinoma "in situ" or lobular carcinoma "in situ").
Many forms of CIS have a high probability of progression into cancer, and therefore removal may be recommended; however, progression of CIS is known to be highly variable and not all CIS becomes invasive cancer.
In the TNM classification, carcinoma "in situ" is reported as TisN0M0 (stage 0).
Skin cancer, or neoplasia, is the most common type of cancer diagnosed in horses, accounting for 45 to 80% of all cancers diagnosed. Sarcoids are the most common type of skin neoplasm and are the most common type of cancer overall in horses. Squamous-cell carcinoma is the second-most prevalent skin cancer, followed by melanoma. Squamous-cell carcinoma and melanoma usually occur in horses greater than 9-years-old, while sarcoids commonly affect horses 3 to 6 years old. Surgical biopsy is the method of choice for diagnosis of most equine skin cancers, but is contraindicated for cases of sarcoids. Prognosis and treatment effectiveness varies based on type of cancer, degree of local tissue destruction, evidence of spread to other organs (metastasis) and location of the tumor. Not all cancers metastasize and some can be cured or mitigated by surgical removal of the cancerous tissue or through use of chemotherapeutic drugs.
Often, this disease evolves from a precursor lesion, usually a dysplastic nevus. Otherwise it arises in previously normal skin. A prolonged radial growth phase, where the lesion remains thin, may eventually be followed by a vertical growth phase where the lesion becomes thick and nodular. As the risk of spread varies with the thickness, early SSM is more frequently cured than late nodular melanoma.
The microscopic hallmarks are:
- Large melanocytic cells with nest formation along the dermo-epidermal junction.
- Invasion of the upper epidermis in a pagetoid fashion (discohesive single cell growth).
- The pattern of rete ridges is often effaced.
- Invasion of the dermis by atypical, pleomorphic melanocytes
- Absence of the 'maturation' typical of naevus cells
- Mitoses
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.
Bowen's disease typically presents as a gradually enlarging, well-demarcated red colored plaque with an irregular border and surface crusting or scaling. Bowen's disease may occur at any age in adults, but is rare before the age of 30 years; most patients are aged over 60. Any site may be affected, although involvement of palms or soles is uncommon. Bowen's disease occurs predominantly in women (70–85% of cases). About 60–85% of patients have lesions on the lower leg, usually in previously or presently sun-exposed areas of skin.
This is a persistent, progressive, unelevated, red, scaly or crusted plaque which is due to an intraepidermal carcinoma and is potentially malignant. The lesions may occur anywhere on the skin surface, including on mucosal surfaces. Freezing, cauterization, or diathermy coagulation is often effective treatment. Pathomorphologic study of tissue sampling revealed: polymorphism of spiny epithelial cells has progressed into atypism; increased mitosis; giant and multinucleate cells; acanthosis; hyperkeratosis and parakeratosis; basal membrane and basal layer are retained.
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.
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.
Early signs of melanoma are changes to the shape or color of existing moles or, in the case of nodular melanoma, the appearance of a new lump anywhere on the skin. At later stages, the mole may itch, ulcerate or bleed. Early signs of melanoma are summarized by the mnemonic "ABCDE":
- Asymmetry
- Borders (irregular with edges and corners)
- Color (variegated)
- Diameter (greater than , about the size of a pencil eraser)
- Evolving over time
These classifications do not, however, apply to the most dangerous form of melanoma, nodular melanoma, which has its own classifications:
- Elevated above the skin surface
- Firm to the touch
- Growing
Metastatic melanoma may cause nonspecific paraneoplastic symptoms, including loss of appetite, nausea, vomiting and fatigue. Metastasis of early melanoma is possible, but relatively rare: less than a fifth of melanomas diagnosed early become metastatic. Brain metastases are particularly common in patients with metastatic melanoma. It can also spread to the liver, bones, abdomen or distant lymph nodes.
Merkel-cell carcinoma (MCC) is a rare and highly aggressive skin cancer, which, in most cases, is caused by the Merkel cell polyomavirus (MCV) discovered by scientists at the University of Pittsburgh in 2008. It is also known as cutaneous APUDoma, primary neuroendocrine carcinoma of the skin, primary small cell carcinoma of the skin, and trabecular carcinoma of the skin.
Approximately 80% of Merkel-cell carcinomas are caused by MCV. The virus is clonally integrated into the cancerous Merkel cells. In addition, the virus has a particular mutation only when found in cancer cells, but not when it is detected in healthy skin cells. Direct evidence for this oncogenetic mechanism comes from research showing that inhibition of production of MCV proteins causes MCV-infected Merkel carcinoma cells to die but has no effect on malignant Merkel cells that are not infected with this virus. MCV-uninfected tumors, which account for approximately 20% of Merkel-cell carcinomas, appear to have a separate and as-yet unknown cause. These tumors tend to have extremely high genome mutation rates, due to ultraviolet light exposure, whereas MCV-infected Merkel cell carcinomas have low rates of genome mutation. No other cancers have been confirmed so far to be caused by this virus. Because of the viral origin for this cancer, immunotherapies are a promising avenue for research to treat virus-positive Merkel-cell carcinoma.
This cancer is considered to be a form of neuroendocrine tumor. While patients with a small tumor (less than 2 cm) that has not yet metastasized to regional lymph nodes have an expected 5-year survival rate of more than 80 percent, once a lesion has metastasized regionally, the rate drops to about 50 percent. Up to half of patients that have been seemingly treated successfully (i.e. that initially appear cancer-free) subsequently suffer a recurrence of their disease. Recent reviews cite an overall 5-year survival rate of about 60% for all MCC combined.
Merkel-cell carcinoma occurs most often on the sun-exposed face, head, and neck.
Bowen's disease, also known as squamous cell carcinoma" in situ" is a neoplastic skin disease. It can be considered as an early stage or intraepidermal form of squamous cell carcinoma. It was named after John T. Bowen.
Erythroplasia of Queyrat is a particular type of Bowen's disease that can arise on the glans or prepuce in males, and, on the vulva in females, and may be induced by human papilloma virus. It is reported to occur in the corneoscleral limbus.
Giant-cell fibroblastoma is a rare type of soft-tissue tumor marked by painless nodules in the dermis (the inner layer of the two main layers of tissue that make up the skin) and subcutaneous (beneath the skin) tissue. These tumors may come back after surgery, but they do not spread to other parts of the body. They occur mostly in boys and are related to dermatofibrosarcoma protuberans.
Visual inspection is the most common diagnostic technique. Moles that are irregular in color or shape are typically treated as candidates. To detect melanomas (and increase survival rates), it is recommended to learn to recognize them (see "ABCDE" mnemonic above), to regularly examine moles for changes (shape, size, color, itching or bleeding) and to consult a qualified physician when a candidate appears.
In general, epithelioid sarcoma is a slow-growing and relatively painless tumor, often resulting in a lengthy period of time between presentation and diagnosis. Due to its ambiguity, it is often misdiagnosed, mistaken as a persistent wart or cyst. It most commonly presents itself in the distal limbs (fingers, hands, forearms, or feet) as a small, soft mass or a series of bumps. It is most often described as a firm-to-hard palpable mass, either in the deep soft tissue or in the dermis. Often, superficial lesions will ulcerate causing a mistaken diagnosis of a poorly healing traumatic wound or wart. About 13% of patients will present with multifocal tumors, and about 13% of patients will present with metastatic disease.
Epithelioid sarcoma is a rare soft tissue sarcoma arising from Mesenchyme tissue and characterized by epithelioid-like features. It accounts for less than 1% of all soft tissue sarcomas. It was first clearly characterized by F.M. Enzinger in 1970. It commonly presents itself in the distal limbs (fingers, hands, forearms, or feet) of young adults as a small, soft mass or a series of bumps. A proximal version has also been described, frequently occurring in the upper extremities. Rare cases have been reported in the pelvis, vulva, penis, and spine.
Histologically, epithelioid sarcoma forms nodules with central necrosis surrounded by bland, polygonal cells with eosinophilic cytoplasm and peripheral spindling. Epithelioid sarcomas typically express vimentin, cytokeratins, epithelial membrane antigen, and CD34, whereas they are usually negative for S100, desmin, and FLI-1. They typically stain positive for CA125.
Epithelioid sarcoma most commonly strikes young adults, yet no age group is immune. The disease has a tendency to develop local recurrences and metastasis thereafter to regional lymph nodes, lung, bone, brain, and other locations, including the scalp. Generally speaking, epithelioid sarcoma has a high rate of relapse after initial treatment and tends to recur locally (at or near the original tumor site). Epithelioid sarcoma also demonstrates lymphatic spread (in 22-48% of cases), and metastasis (in 21-63% of cases). These events, as well as advanced stage (progression) and grade (aggressiveness), are predictive of an overall worse outcome. The overall five-year survival rate for epithelioid sarcoma is anywhere from 25 to 78%. Importantly, the 10-year and 15-year survival rate drops off significantly. Associated with a more positive outcome are younger age, female vs. male sex, distal vs. proximal location, smaller tumor size, and negative margins upon tumor resection.
Multiple cutaneous leiomyomas, also known as Pilar leiomyomas, arise from the arrectores pilorum muscles, and are made up of a poorly circumscribed proliferation of haphazardly arranged smooth muscle fibers located in the dermis that appear to infiltrate the surrounding tissue and may extend into the subcutis.
Sometimes associated with uterine leiomyomas (a combination known as multiple cutaneous and uterine leiomyomatosis, MCUL), these lesions may also be a manifestation of the hereditary leiomyomatosis and renal cell cancer syndrome.
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
A Spitz nevus (also known as an epithelioid and spindle-cell nevus, benign juvenile melanoma, and "Spitz's juvenile melanoma") is a benign melanocytic nevus, a type of skin lesion, affecting the epidermis and dermis.
The name "juvenile melanoma" is generally no longer used as it is misleading: it is not a melanoma, it is a benign lesion; and it can also occur in adults, not only in children.
The cause of Spitz nevi is not yet known. There is an association with sunburn, but causation is not established. Genetic studies of Spitz nevi have shown that most cells have the normal number of chromosomes, however a minority (25%) of cells have been shown to contain extra copies of parts of some chromosomes, such as the short arm of chromosome 11 (11p).
Spitz nevi characteristically have vertically arranged nests of nevus cells that have both a spindled and an morphology. Apoptotic cells may be seen at the dermoepidermal junction. The main histologic differential diagnoses are pigmented spindle cell nevus and malignant melanoma.
Basal-cell skin cancer (BCC) usually presents as a raised, smooth, pearly bump on the sun-exposed skin of the head, neck or shoulders. Sometimes small blood vessels (called telangiectasia) can be seen within the tumor. Crusting and bleeding in the center of the tumor frequently develops. It is often mistaken for a sore that does not heal. This form of skin cancer is the least deadly and with proper treatment can be completely eliminated, often without scarring.
Squamous-cell skin cancer (SCC) is commonly a red, scaling, thickened patch on sun-exposed skin. Some are firm hard nodules and dome shaped like keratoacanthomas. Ulceration and bleeding may occur. When SCC is not treated, it may develop into a large mass. Squamous-cell is the second most common skin cancer. It is dangerous, but not nearly as dangerous as a melanoma.
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.