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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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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.
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.
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.
Cancer can be considered a very large and exceptionally heterogeneous family of malignant diseases, with squamous cell carcinomas comprising one of the largest subsets.
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.
Symptoms of cancer in dogs may include:
- Lumps (which are not always malignant, but should always be examined by a vet)
- Swelling
- Persistent sores
- Abnormal discharge from any part of the body
- Bad breath
- Listlessness/lethargy
- Rapid, often unexplained weight loss
- Sudden lameness
- Offensive odor
- Black, tarry stools (a symptom of ulcers, which can be caused by mast cell tumors)
- Decreased or loss of appetite
- Difficulty breathing, urinating or defecating
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.
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.
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.
Typical signs of acral lentiginous melanoma include the following
- Longitudinal tan, black, or brown streak on a finger
- Pigmentation of proximal nail fold
- Areas of dark pigmentation (on palms of hands)
Warning signs are new areas of pigmentation, or existing pigmentation that shows change. If caught early, acral lentiginous melanoma has a similar cure rate as the other types of superficial spreading melanoma.
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.
There are a variety of different skin cancer symptoms. These include changes in the skin that do not heal, ulcering in the skin, discolored skin, and changes in existing moles, such as jagged edges to the mole and enlargement of the mole.
Uveal melanomas, often referred to by the media and in the general population as ocular melanomas, may arise from any of the three parts of the uvea, and are sometimes referred to by their location, as choroidal melanoma, ciliary body melanoma, or iris melanoma. Large tumors often encompass multiple parts of the uvea and can be named accordingly. True iris melanomas, originating from within the iris as opposed to originating elsewhere and invading the iris, are distinct in their etiology and prognosis, such that the other tumors are often referred to collectively as Posterior uveal melanomas.
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.
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.
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"
Uveal tumors can originate from melanocytes residing within the iris. Benign melanocytic tumors, such as iris freckles and moles (nevi), are common and pose no health risks, unless they show signs of malignancy, in which case they are classified as iris melanomas. Though derived from uveal melanocytes, iris melanomas share more in common with cutaneous (skin) melanomas, in that they frequently harbor BRAF mutations associated with ultraviolet damage. Iris melanomas are much less likely to metastasize than other uveal melanomas, and less likely to impair vision if detected and treated early. Approximately 5% of uveal melanomas involve the iris.
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.
These tumors are usually benign, but can become malignant over time. They vary in size, and can be found as singles or multiples. They are most commonly found in mature grey horses (less than 15 years old) and are typically found under the tail, around the anus, and on the external genitalia.
Acral lentiginous melanoma is a kind of lentiginous skin melanoma. Melanoma is a potentially serious skin cancer that arises from pigment cells (melanocytes). Although acral lentiginous melanoma is rare in people with lighter skin types, it is the most common subtype in people with darker skins. Acral lentiginous melanoma is observed on the palms, soles, under the nails and in the oral mucosa. It occurs on non-hair-bearing surfaces of the body, which may or may not be exposed to sunlight. It is also found on mucous membranes. It is the most common form of melanoma diagnosed amongst Asian and sub-Saharan African ethnic groups. The average age at diagnosis is between sixty and seventy years.
These tumors are frequently malignant and have a high tendency to spread to other organs. They are most commonly found in grey horses who are over the age of 15 and are found as a large coalescing mass under the tail, around the anus, on the external genitalia, or the parotid salivary gland.
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.
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.
Around 95% of penile cancers are squamous cell carcinomas. They are classified into the following types:
- basaloid (4%)
- warty (6%)
- mixed warty-basaloid (17%)
- verrucous (8%)
- papillary (7%)
- other SCC mixed (7%)
- sarcomatoid carcinomas (1%)
- not otherwise specified (49%)
Other types of carcinomas are rare and may include small cell, Merkel cell, clear cell, sebaceous cell or basal cell tumors. Non-epithelial malignancies such as melanomas and sarcomas are even more rare.
Like many malignancies, penile cancer can spread to other parts of the body. It is usually a primary malignancy, the initial place from which a cancer spreads in the body. Much less often it is a secondary malignancy, one in which the cancer has spread to the penis from elsewhere. The staging of penile cancer is determined by the extent of tumor invasion, nodal metastasis, and distant metastasis.
The T portion of the AJCC TNM staging guidelines are for the primary tumor as follows:
- TX: Primary tumor cannot be assessed.
- T0: No evidence of primary tumor.
- Tis: Carcinoma "in situ".
- Ta: Noninvasive verrucous carcinoma.
- T1a: Tumor invades subepithelial connective tissue without lymph vascular invasion and is not poorly differentiated (i.e., grade 3–4).
- T1b: Tumor invades subepithelial connective tissue with lymph vascular invasion or is poorly differentiated.
- T2: Tumor invades the corpus spongiosum or cavernosum.
- T3: Tumor invades the urethra or prostate.
- T4: Tumor invades other adjacent structures.
Anatomic Stage or Prognostic Groups of penile cancer are as follows:
- Stage 0—Carcinoma "in situ".
- Stage I—The cancer is moderately or well differentiated and only affects the subepithelial connective tissue.
- Stage II—The cancer is poorly differentiated, affects lymphatics, or invades the corpora or urethra.
- Stage IIIa—There is deep invasion into the penis and metastasis in one lymph node.
- Stage IIIb—There is deep invasion into the penis and metastasis into multiple inguinal lymph nodes.
- Stage IV—The cancer has invaded into structures adjacent to the penis, metastasized to pelvic nodes, or distant metastasis is present.