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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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Bone tumors may be classified as "primary tumors", which originate in bone or from bone-derived cells and tissues, and "secondary tumors" which originate in other sites and spread (metastasize) to the skeleton. Carcinomas of the prostate, breasts, lungs, thyroid, and kidneys are the carcinomas that most commonly metastasize to bone. Secondary malignant bone tumors are estimated to be 50 to 100 times as common as primary bone cancers.
The most common symptom of bone tumors is pain, which will gradually increase over time. A person may go weeks, months, and sometimes years before seeking help; the pain increases with the growth of the tumor. Additional symptoms may include fatigue, fever, weight loss, anemia, and/or unexplained bone fractures. Many patients will not experience any symptoms, except for a painless mass. Some bone tumors may weaken the structure of the bone, causing pathologic fractures.
Many patients first complain of pain that may be worse at night, may be intermittent and of varying intensity and may have been occurring for some time. Teenagers who are active in sports often complain of pain in the lower femur, or immediately below the knee. If the tumor is large, it can present as overt localised swelling. Sometimes a sudden fracture is the first symptom, because affected bone is not as strong as normal bone and may fracture abnormally with minor trauma. In cases of more deep-seated tumors that are not as close to the skin, such as those originating in the pelvis, localised swelling may not be apparent.
Bone metastases are a major clinical concern that can cause severe pain, bone fractures, spinal cord compression, hypercalcemia, anemia, spinal instability, decreased mobility, and rapid degradation in the quality of life for patients. Patients have described the pain as a dull ache that grows worse over time, with intermittent periods of sharp, jagged pain. Even under controlled pain management, these periods of breakthrough pain can occur rapidly, without warning, several times a day. Pain may be worse at night and partially relieved by activity. Metastases to weightbearing bones may become symptomatic early in the course of disease as compared to metastases to the flat bones of the rib or sternum.
- Effects of bone metastasis
- severe pain
- bone fractures
- spinal cord compression
- hypercalcemia
- anemia
- spinal instability
- decreased mobility
An osteosarcoma (OS) or osteogenic sarcoma (OGS) is a cancerous tumor in a bone. Specifically, it is an aggressive malignant neoplasm that arises from primitive transformed cells of mesenchymal origin (and thus a sarcoma) and that exhibits osteoblastic differentiation and produces malignant osteoid.
Osteosarcoma is the most common histological form of primary bone cancer. It is most prevalent in teenagers and young adults.
Bone metastases, or metastatic bone disease, is a class of cancer metastases that results from primary tumor invasion to bone. Bone-originating primary tumors such as osteosarcoma, chondrosarcoma, and Ewing's sarcoma are rare. Unlike hematological malignancies that originate in the blood and form non-solid tumors, bone metastases generally arise from epithelial tumors and form a solid mass inside the bone. Bone metastases cause severe pain, characterized by a dull, constant ache with periodic spikes of incident pain.
Individuals with an enchondroma often have no symptoms at all. The following are the most common symptoms of an enchondroma. However, each individual may experience symptoms differently. Symptoms may include:
- Pain that may occur at the site of the tumor if the tumor is very large, or if the affected bone has weakened causing a fracture of the affected bone
- Enlargement of the affected finger
- Slow bone growth in the affected area
The symptoms of enchondroma may resemble other medical conditions or problems. Always consult your physician for a diagnosis.
Brown tumours consist of fibrous tissue, woven bone and supporting vasculature, but no matrix. The osteoclasts consume the trabecular bone that osteoblasts lay down and this front of reparative bone deposition followed by additional resorption can expand beyond the usual shape of the bone, involving the periosteum thus causing bone pain. The characteristic brown coloration results from hemosiderin deposition into the osteolytic cysts. Hemosiderin deposition is not a distinctive feature of brown tumors; it may also be seen in giant cell tumors of the bone.
Brown tumors may be rarely associated with ectopic parathyroid adenomas or end stage renal osteodystrophy.
For SPB the most common presenting symptom is that of pain in the affected bone. Back pain and other consequences of the bone lesion may occur such as spinal cord compression or pathological fracture. Around 85% of extramedullary plasmacytoma presents within the upper respiratory tract mucosa, causing possible symptoms such as epistaxis, rhinorrhoea and nasal obstruction. In some tissues it may be found as a palpable mass.
An enchondroma is a cartilage cyst found in the bone marrow. Typically, enchondroma is discovered on an X-ray scan. Enchondromas have a characteristic appearance on Magnetic Resonance Imaging (MRI) as well. They have also been reported to cause increased uptake on PET examination.
An osteolytic lesion (from the Greek words for "bone" (ὀστέον), and "to unbind" (λύειν)) is a softened section of a patient's bone formed as a symptom of specific diseases, including breast cancer and multiple myeloma. This softened area appears as a hole on X-ray scans due to decreased bone density. Osteolytic lesions can cause pain, increased risk of bone fracture, and spinal chord compression. These lesions can be treated using biophosphonates or radiation, though new solutions are being tested in clinical trials.
The afflicted may have relatively small amounts of pain that will quickly increase in severity over a time period of 6–12 weeks. The skin temperature around the bone may increase, a bony swelling may be evident, and movement may be restricted in adjacent joints.
Spinal lesions may cause quadriplegia and patients with skull lesions may have headaches.
The brown tumor is a bone lesion that arises in settings of excess osteoclast activity, such as hyperparathyroidism. It is not a true neoplasm, as the term "tumor" suggests; however, it may mimic a true neoplasm. It most commonly affects the maxilla and mandible, though any bone may be affected. Brown tumours are radiolucent on x-ray.
Individuals presenting with fibrosarcoma are usually adults aged thirty to fifty five years, often presenting with pain. In adults, males have a higher incidence for fibrosarcoma than females.
Plasmacytoma is a plasma cell dyscrasia in which a plasma cell tumour grows within soft tissue or within the axial skeleton.
The International Myeloma Working Group lists three types: solitary plasmacytoma of bone (SPB); extramedullary plasmacytoma (EP), and multiple plasmacytomas that are either primary or recurrent. The most common of these is SPB, accounting for 3–5% of all plasma cell malignancies. SPBs occur as lytic lesions within the axial skeleton and extramedullary plasmacytomas most often occur in the upper respiratory tract (85%), but can occur in any soft tissue. Approximately half of all cases produce paraproteinemia. SPBs and extramedullary plasmacytomas are mostly treated with radiotherapy, but surgery is used in some cases of extramedullary plasmacytoma. The skeletal forms frequently progress to multiple myeloma over the course of 2–4 years.
Due to their cellular similarity, plasmacytomas have to be differentiated from multiple myeloma. For SPB and extramedullary plasmacytoma the distinction is the presence of only one lesion (either in bone or soft tissue), normal bone marrow (<5% plasma cells), normal skeletal survey, absent or low paraprotein and no end organ damage.
In infants, fibrosarcoma (often termed congenital infantile fibrosarcoma) is usually congenital. Infants presenting with this fibrosarcoma usually do so in the first two years of their life. Cytogenetically, congenital infantile fibrosarcoma is characterized by the majority of cases having a translocation between chromosomes 12 and 15 (notated as t(12;15)(p13;q25)) that results in formation of the fusion gene, "ETV6-NTRK3", plus individual cases exhibiting trisomy for chromosomes 8, 11, 17, or 20. The histology, association with the "ETV6-NRTK3" fusion gene as well as certain chromosome trisomies, and the distribution of markers for cell type (i.e. cyclin D1 and Beta-catenin) within this tumor are similar to those found in the cellular form of mesoblastic nephroma. Indeed, mesoblastic nephroma and congenital infantile sarcoma appear to be the same disease with the exception that mesoblastic lymphoma originates in the kidney whereas congenital infantile sarcoma originates in non-renal tissues.
Aneurysmal bone cyst, abbreviated ABC, is an osteolytic bone neoplasm characterized by several sponge-like blood or serum filled, generally non-endothelialized spaces of various diameters.
The term is a misnomer, as the lesion is neither an aneurysm nor a cyst.
Fibrous dysplasia is a mosaic disease that can involve any part or combination of the craniofacial, axillary, and/or appendicular skeleton. The type and severity of the complications therefore depend on the location and extent of the affected skeleton. The clinical spectrum is very broad, ranging from an isolated, asymptomatic monostotic lesion discovered incidentally, to severe disabling disease involving practically the entire skeleton and leading to loss of vision, hearing, and/or mobility.
Individual bone lesions typically manifest during the first few years of life and expand during childhood. The vast majority of clinically significant bone lesions are detectable by age 10 years, with few new and almost no clinically significant bone lesions appearing after age 15 years. Total body scintigraphy is useful to identify and determine the extent of bone lesions, and should be performed in all patients with suspected fibrous dysplasia.
Children with fibrous dysplasia in the appendicular skeleton typically present with limp, pain, and/or pathologic fractures. Frequent fractures and progressive deformity may lead to difficulties with ambulation and impaired mobility. In the craniofacial skeleton, fibrous dysplasia may present as a painless “lump” or facial asymmetry. Expansion of craniofacial lesions may lead to progressive facial deformity. In rare cases patients may develop vision and/or hearing loss due to compromise of the optic nerves and/or auditory canals, which is more common in patients with McCune-Albright syndrome associated growth hormone excess. Fibrous dysplasia commonly involves the spine, and may lead to scoliosis, which in rare instances may be severe. Untreated, progressive scoliosis is one of the few features of fibrous dysplasia that can lead to early fatality.
Bone pain is a common complication of fibrous dysplasia. It may present at any age, but most commonly develops during adolescence and progresses into adulthood.
Bone marrow stromal cells in fibrous dysplasia produce excess amounts of the phosphate-regulating hormone fibroblast growth factor-23 (FGF23), leading to loss of phosphate in the urine. Patients with hypophosphatemia may develop rickets/osteomalacia, increased fractures, and bone pain.
Leiomyosarcoma, also referred to as LMS, is a malignant (cancerous) smooth muscle tumor. A benign tumor originating from the same tissue is termed leiomyoma. It is also important to note that while it has been believed that leiomyosarcomas do not arise from leiomyomas, there are leiomyoma variants for which classification is evolving.
About 1 person in 100,000 gets diagnosed with LMS each year. Leiomyosarcoma is one of the more common types of soft-tissue sarcoma, representing 10 percent to 20 percent of new cases. (Leiomyosarcoma of the bone is more rare.) Sarcoma is rare, consisting of only 1 percent of cancer cases in adults. Leiomyosarcomas can be very unpredictable. They can remain dormant for long periods of time and recur after years. It is a resistant cancer, meaning generally not very responsive to chemotherapy or radiation. The best outcomes occur when it can be removed surgically with wide margins early, while small and still in situ.
RMS can occur in almost any soft-tissue site in the body; the most common primary sites are genitourinary (24%), parameningeal (16%), extremity (19%), orbit (9%), other head and neck (10%), and miscellaneous other sites (22%). RMS often presents as a mass, but signs and symptoms can vary widely depending on the site of the primary tumor. Genitourinary tumors may present with hematuria, urinary tract obstruction, and/or a scrotal or vaginal mass. Tumors that arise in the retroperitoneum and mediastinum can become quite large before producing signs and symptoms. Parameningeal tumors may present with cranial nerve dysfunction, symptoms of sinusitis, ear discharge, headaches, and facial pain. Orbital tumors often present with orbital swelling and proptosis. Extremity tumors generally present as a rapidly enlarging, firm mass in the relevant tissue. The cancer's prevalence in the head, face, and neck will often allow for earlier signs of the disease simply due to the obvious nature of tumors in these locations. Despite the varying presentation and typically aggressive nature of the disease, RMS has the potential to be diagnosed and treated early. The fourth IRSG study found that 23% of patients were diagnosed in time for a complete resection of their cancer, and 15% had resection with only minimal remnants of the diseased cells.
Smooth muscle cells make up the involuntary muscles, which are found in most parts of the body, including the uterus, stomach and intestines, the walls of all blood vessels, and the skin. It is therefore possible for leiomyosarcomas to appear at any site in the body. They are most commonly found in the uterus, stomach, small intestine and retroperitoneum.
Uterine leiomyosarcomas come from the smooth muscle in the muscle layer of the uterus. Cutaneous leiomyosarcomas derive from the pilo-erector muscles in the skin. Gastrointestinal leiomyosarcomas might come from smooth muscle in the GI tract or, alternatively, also from a blood vessel. At most other primary sites—retroperitoneal extremity (in the abdomen, behind the intestines), truncal, abdominal organs, etc.—leiomyosarcomas appear to grow from the muscle layer of a blood vessel (the tunica media). Thus a leiomyosarcoma can have a primary site of origin anywhere in the body where there is a blood vessel.
The tumors are usually hemorrhagic and soft and microscopically marked by pleomorphism, abundant (15–30 per 10 high power fields) abnormal mitotic figures, and coagulative tumor cell necrosis. There is a wide differential diagnosis, which includes spindle cell carcinoma, spindle cell melanoma, fibrosarcoma, malignant peripheral nerve sheath tumor and even biphenotypic sinonasal sarcoma.
Monostotic fibrous dysplasia (or monostotic osteitis fibrosa) is a form of fibrous dysplasia where only one bone is involved. It comprises a majority of the cases of fibrous dysplasia.
A rare bone disorder characterized by benign bone growths which can cause very painful swellings and bone deformities and makes bone prone to fractures.
Myosarcoma is a malignant muscle tumor. People with myosarcoma often wake up with the feeling as if they had a cramp during their sleep.
Leiomyosarcoma is sarcoma of smooth muscle, and rhabdomyosarcoma is sarcoma of striated muscle. However, the term myosarcoma itself still appears in the literature.
Bone lesions are caused by an imbalance of regulatory factors, characterized by an increased depletion and resorption of old bone tissue and a decrease in bone rebuilding, known as bone remodeling. This imbalance is due to a flooding of regulatory factors released by specific tumors, thus overwhelming the tissue repair system and resulting in these lesions. The over-activity of osteoclasts can also cause hypercalcemia, which can cause damage to the kidneys and requires additional medication and monitoring.
In multiple myeloma, an increased number of myeloma cells block osteoblasts from creating new bone, while these cancerous cells also release factors that cause an upregulation on osteoclasts, causing an increasing in bone tissue resorption and an overall breakdown of bone integrity. This breakdown often begins in the bone marrow near tumor sites and spreads outward to the surface of the implicated bone.
The most common cancers that metastasize to osteolytic lesions are prostate, thyroid, lung and breast, though any cancer can cause bone lesions. Lesions are most often found in larger bones, such as the skull, pelvis, radius, and femur.
Fibrous dysplasia is a disorder where normal bone and marrow is replaced with fibrous tissue, resulting in formation of bone that is weak and prone to expansion. As a result, most complications result from fracture, deformity, functional impairment, and pain. Disease occurs along a broad clinical spectrum ranging from asymptomatic, incidental lesions to severe disabling disease. Disease can affect one bone (monostotic) or multiple (polyostotic), and may occur in isolation or in combination with cafe-au-lait skin macules and hyperfunctioning endocrinopathies, termed McCune-Albright syndrome. More rarely, fibrous dysplasia may be associated with intramuscular myxomas, termed Mazabraud's syndrome. Fibrous dysplasia is very rare, and there is no known cure. Fibrous dysplasia is not a form of cancer.