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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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Initially, nearby lymph nodes are struck early. The lungs, liver, brain, and bones are the most common metastasis locations from solid tumors.
- In lymph nodes, a common symptom is lymphadenopathy
- Lungs: cough, hemoptysis and dyspnea (shortness of breath)
- Liver: hepatomegaly (enlarged liver), nausea and jaundice
- Bones: bone pain, fracture of affected bones
- Brain: neurological symptoms such as headaches, seizures, and vertigo
Although advanced cancer may cause pain, it is often not the first symptom.
Some patients, however, do not show any symptoms.
When the organ gets a metastatic disease it begins to shrink until its lymph nodes burst, or undergo lysis.
Most cancers typically present as a single primary tumor. Over the course of time—particularly if the primary tumor is left untreated—smaller "satellite" tumors will appear at other places in the body, a phenomenon known as metastasis. Less commonly, a metastatic tumor is found first; but in most such cases, the primary tumor can then be located via examination and testing. Rarely (3-5% of the time), the primary tumor cannot be found because it is too small, or because it has regressed due to immune system activity or other factors. In such situations a diagnosis of cancer of unknown primary origin (CUP) is made.
CUP usually comes to attention because of masses or swellings found somewhere in the body, either by physical examination or on medical imaging performed for another indication. The disease typically develops rapidly, and metastases may occur in places in the body that are otherwise unusual. Comprehensive physical examination is part of the process to identify a possible primary source of cancer; this should include the breasts, lymph nodes, the skin, external genitals, as well as an internal examination of the rectum and of the pelvic organs.
The location of metastases may be a clue as to the underlying source, even if this cannot be found on investigations. For instance, a woman in whom there is axillary lymphadenopathy (swelling in the lymph nodes of the armpit) it is likely that the cancer originated in the breast, and men with lymph node deposits in the mediastinum of the chest and/or retroperitoneal space of the abdomen may have a germ cell tumor.
Cancer of unknown primary origin (CUP, "occult cancer") is a cancer that is determined to be at the metastatic stage at the time of diagnosis, but a primary tumor cannot be identified. A diagnosis of CUP requires a clinical picture consistent with metastatic disease and one or more biopsy results inconsistent with a primary tumor.
CUP is found in about 3 to 5% of all people diagnosed with invasive cancer, and carries a poor prognosis in most (80 to 85%) of those circumstances. The other 15 to 20% of patients, however, have a relatively long survival with appropriate treatment.
The symptoms produced by metastatic breast cancer vary by the location of the metastases. For instance:
- Metastatic disease to the bone causes severe, progressive pain, and, less commonly, pathological fracture, erythema over the affected bone, and swelling.
- Metastatic breast cancer to the brain causes the following symptoms: persistent, progressively worsening headache, visual changes, seizures, nausea or vomiting, vertigo, behavioral and personality changes, and increased intracranial pressure.
- Metastatic disease to the liver causes jaundice, elevated liver enzymes, abdominal pain, loss of appetite, nausea, and vomiting
- Metastatic breast cancer to the lung or pleura causes chronic cough, dyspnea, abnormal chest X-ray, and chest pain.
- Other nonspecific systemic symptoms of metastatic breast cancer include fatigue, malaise, weight loss, and poor appetite.
Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; it is typically spoken of as such spread by a cancerous tumor. The newly pathological sites, then, are metastases (mets).
Cancer occurs after cells are genetically altered to proliferate rapidly and indefinitely. This uncontrolled proliferation by mitosis produces a primary heterogeneic tumour. The cells which constitute the tumor eventually undergo metaplasia, followed by anaplasia then dysplasia, resulting in a malignant phenotype. This malignancy allows for invasion into the circulation, followed by invasion to a second site for tumorigenesis.
Some cancer cells known as circulating tumor cells acquire the ability to penetrate the walls of lymphatic or blood vessels, after which they are able to circulate through the bloodstream to other sites and tissues in the body. This process is known (respectively) as "lymphatic" or "hematogenous" spread. After the tumor cells come to rest at another site, they re-penetrate the vessel or walls and continue to multiply, eventually forming another clinically detectable tumor. This new tumor is known as a metastatic (or "secondary") tumor. Metastasis is one of the hallmarks of cancer, distinguishing it from benign tumors. Most cancers can metastasize, although in varying degrees. Basal cell carcinoma for example rarely metastasizes.
When tumor cells metastasize, the new tumor is called a "secondary" or "metastatic" tumor, and its cells are similar to those in the original or primary tumor. This means that if breast cancer metastasizes to the lungs, the secondary tumor is made up of abnormal breast cells, not of abnormal lung cells. The tumor in the lung is then called "metastatic breast cancer", not "lung cancer". Metastasis is a key element in cancer staging systems such as the TNM staging system, where it represents the "M". In overall stage grouping, metastasis places a cancer in Stage IV. The possibilities of curative treatment are greatly reduced, or often entirely removed, when a cancer has metastasized.
The symptoms of laryngeal cancer depend on the size and location of the tumour. Symptoms may include the following:
- Hoarseness or other voice changes
- A lump in the neck
- A sore throat or feeling that something is stuck in the throat
- Persistent cough
- Stridor - a high-pitched wheezing sound indicative of a narrowed or obstructed airway
- Bad breath
- Earache (""referred"")
- Difficulty swallowing
Treatment effects can include post-operative changes in appearance, difficulty eating, or loss of voice that may require learning alternate methods of speaking.
There are few early warning signs that a patient has a DSRCT. Patients are often young and healthy as the tumors grow and spread uninhibited within the abdominal cavity. These are rare tumors and symptoms are often misdiagnosed by physicians. The abdominal masses can grow to enormous size before being noticed by the patient. The tumors can be felt as hard, round masses by palpating the abdomen.
First symptoms of the disease often include abdominal distention, abdominal mass, abdominal or back pain, gastrointestinal obstruction, lack of appetite, ascites, anemia, and/or cachexia.
Other reported symptoms include unknown lumps, thyroid conditions, hormonal conditions, blood clotting, kidney or urological problems, testicle, breast, uterine, vaginal, or ovarian masses.
Carcinomatosis is often restricted to tumors of epithelial origin, adenocarcinomas, while sarcomatosis describes the dissemination of tumors of mesenchymal origin, sarcomas.
When most tumors metastasize to the lung, they form distinct nodules, but about 7% spread through the lymph vessels of the lung. They may impair breathing in several ways; the lung becomes stiffer; blood vessels traveling alongside the distended lymph vessels become compressed.
Carcinoma is a type of cancer that develops from epithelial cells. Specifically, a carcinoma is a cancer that begins in a tissue that lines the inner or outer surfaces of the body, and that arises from cells originating in the endodermal, mesodermal and ectodermal germ layer during embryogenesis.
Carcinomas occur when the DNA of a cell is damaged or altered and the cell begins to grow uncontrollably and become malignant. It is from the Greek καρκίνωμα 'karkinoma' meaning sore, ulcer, or cancer, itself derived from "karkinos" 'crab'.
Metastatic breast cancer, also referred to as metastases, advanced breast cancer, secondary tumours, secondaries or stage 4 breast cancer, is a stage of breast cancer where the disease has spread to distant sites beyond the axillary lymph nodes. There is no cure for metastatic breast cancer. There is no stage after IV.
It usually occurs several years after the primary breast cancer, although it is sometimes diagnosed at the same time as the primary breast cancer or, rarely, before the primary breast cancer has been diagnosed.
Metastatic breast cancer cells frequently differ from the preceding primary breast cancer in properties such as receptor status. The cells have often developed resistance to several lines of previous treatment and have acquired special properties that permit them to metastasize to distant sites. Metastatic breast cancer can be treated, sometimes for many years, but it cannot be cured. Distant metastases are the cause of about 90% of deaths due to breast cancer.
Breast cancer can metastasize anywhere in body but primarily metastasizes to the bone, lungs, regional lymph nodes, liver and brain, with the most common site being the bone. Treatment of metastatic breast cancer depends on location of the metastatic tumours and includes surgery, radiation, chemotherapy, biological, and hormonal therapy.
Typical environmental barriers in a metastatic event include physical (a basement membrane), chemical (reactive oxygen species or ROS, hypoxia and low pH) and biological (immune surveillance, inhibitory cytokines and regulatory extra-cellular matrix (ECM) peptides) components. Organ-specific anatomic considerations also influence metastasis; these include blood-flow patterns from the primary tumor and the homing ability of cancer cells to certain tissues. The targeting by cancer cells of specific organs is probably regulated by chemo-attractant factors and adhesion molecules produced by the target organ, along with cell-surface receptors expressed by the tumor cells.
Adenocarcinoma (; plural adenocarcinomas or adenocarcinomata ) is a type of cancerous tumor that can occur in several parts of the body. It is defined as neoplasia of epithelial tissue that has glandular origin, glandular characteristics, or both. Adenocarcinomas are part of the larger grouping of carcinomas, but are also sometimes called by more precise terms omitting the word, where these exist. Thus invasive ductal carcinoma, the most common form of breast cancer, is adenocarcinoma but does not use the term in its name—however, esophageal adenocarcinoma does to distinguish it from the other common type of esophageal cancer, esophageal squamous cell carcinoma. Several of the most common forms of cancer are adenocarcinomas, and the various sorts of adenocarcinoma vary greatly in all their aspects, so that few useful generalizations can be made about them.
In the most specific usage (narrowest sense), the glandular origin or traits are exocrine; endocrine gland tumors, such as a VIPoma, an insulinoma, or a pheochromocytoma, are typically not referred to as adenocarcinomas but rather are often called neuroendocrine tumors. Epithelial tissue sometimes includes, but is not limited to, the surface layer of skin, glands, and a variety of other tissue that lines the cavities and organs of the body. Epithelial tissue can be derived embryologically from any of the germ layers (ectoderm, endoderm, or mesoderm). To be classified as adenocarcinoma, the cells do not necessarily need to be part of a gland, as long as they have secretory properties. Adenocarcinoma is the malignant counterpart to adenoma, which is the benign form of such tumors. Sometimes adenomas transform into adenocarcinomas, but most do not.
Well differentiated adenocarcinomas tend to resemble the glandular tissue that they are derived from, while poorly differentiated adenocarcinomas may not. By staining the cells from a biopsy, a pathologist can determine whether the tumor is an adenocarcinoma or some other type of cancer. Adenocarcinomas can arise in many tissues of the body owing to the ubiquitous nature of glands within the body, and, more fundamentally, to the potency of epithelial cells. While each gland may not be secreting the same substance, as long as there is an exocrine function to the cell, it is considered glandular and its malignant form is therefore named adenocarcinoma.
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.
Laryngeal cancer, also known as cancer of the larynx or laryngeal carcinoma, are mostly squamous cell carcinomas, reflecting their origin from the skin of the larynx.
Cancer can develop in any part of the larynx, but the cure rate is affected by the location of the tumour. For the purposes of tumour staging, the larynx is divided into three anatomical regions: the glottis (true vocal cords, anterior and posterior commissures); the supraglottis (epiglottis, arytenoids and aryepiglottic folds, and false cords); and the subglottis.
Most laryngeal cancers originate in the glottis. Supraglottic cancers are less common, and subglottic tumours are least frequent.
Laryngeal cancer may spread by direct extension to adjacent structures, by metastasis to regional cervical lymph nodes, or more distantly, through the blood stream. Distant metastases to the lung are most common. In 2013 it resulted in 88,000 deaths up from 76,000 deaths in 1990. Five year survival rates in the United States are 60%.
Desmoplastic small-round-cell tumor is an aggressive and rare cancer that primarily occurs as masses in the abdomen. Other areas affected may include the lymph nodes, the lining of the abdomen, diaphragm, spleen, liver, chest wall, skull, spinal cord, large intestine, small intestine, bladder, brain, lungs, testicles, ovaries, and the pelvis. Reported sites of metastatic spread include the liver, lungs, lymph nodes, brain, skull, and bones.
The tumor is classified as a soft tissue sarcoma. It is considered a childhood cancer that predominantly strikes boys and young adults. The disease rarely occurs in females, but when it does the tumors can be mistaken for ovarian cancer.
In dogs, mast cell tumors are the most frequent round cell tumor.
Small-cell carcinoma (also known as "small-cell lung cancer", or "oat-cell carcinoma") is a type of highly malignant cancer that most commonly arises within the lung, although it can occasionally arise in other body sites, such as the cervix, prostate, and gastrointestinal tract. Compared to non-small cell carcinoma, small cell carcinoma has a shorter doubling time, higher growth fraction, and earlier development of metastases.
Primary peritoneal cancer or carcinoma is also known as serous surface papillary carcinoma, primary peritoneal carcinoma, extra-ovarian serous carcinoma, primary serous papillary carcinoma, psammomacarcinoma. It was historically classified under "carcinoma of unknown primary" (CUP). Primary peritoneal cancer (PPC, or PPCa) is a cancer of the cells lining the peritoneum, or abdominal cavity.
Some studies indicate that up to 15% of serous ovarian cancers are thought to be actually primary peritoneal carcinomas in origin.
Histomorphological and molecular biological characteristics suggest that serous carcinomas, which include ovarian serous carcinoma, uterine serous carcinoma, Fallopian tube serous carcinoma, cervical serous carcinoma, and primary peritoneal serous carcinoma really represent one entity.
Small-cell carcinoma of the lung usually presents in the central airways and infiltrates the submucosa leading to narrowing of bronchial airways. Common symptoms include cough, dyspnea, weight loss, and debility. Over 70% of patients with small-cell carcinoma present with metastatic disease; common sites include liver, adrenals, bone, and brain.
Due to its high grade neuroendocrine nature, small-cell carcinomas can produce ectopic hormones, including adrenocorticotropic hormone (ACTH) and anti-diuretic hormone (ADH). Ectopic production of large amounts of ADH leads to syndrome of inappropriate antidiuretic hormone hypersecretion (SIADH).
Lambert-Eaton myasthenic syndrome (LEMS) is a well-known paraneoplastic condition linked to small-cell carcinoma.
Mucinous cystadenocarcinoma of the lung (MCACL) is a very rare malignant mucus-producing neoplasm arising from the uncontrolled growth of transformed epithelial cells originating in lung tissue.
This particular variant of lung cancer is usually asymptomatic and is found after chest x-rays are taken for other reasons. Hemoptysis is seen occasionally and, in some cases, distal obstruction of bronchi by blood clots or mucus plugs produces cough and/or infection. Lesions often enlarge and progress slowly, over many years.
The 1999 World Health Organization classification system defined MCACL as a cystic adenocarcinoma with copious mucin production that, histologically, resembles (the more common) mucus-producing cystadenocarcinomas originating in the ovary, breast and pancreas. The 2004 revision of the WHO classification noted that the tumors tend to be well circumscribed by a partial fibrous tissue capsule with central cystic change and copious mucin pooling. The thin, fibrous wall circumscribing the tumor is highly characteristic of this lesion. It can sometimes occur within a pulmonary bronchocele, and this tumor entity should be kept in mind after identification of a bronchocele with suspicious or non-prototypical imaging characteristics.
Microscopically, the neoplastic epithelial cells tend to grow along the alveolar walls, in a fashion similar to the mucinous variant of bronchioloalveolar carcinoma, a more common form of adenocarcinoma.
Hemoptysis is seen occasionally.
Positron Emission Tomography (PET) scanning can be of assistance in diagnosing MCACL, as these lesions show intense uptake, typically in the wall of the tumor.
CA 19-9 has been reported to be elevated in MCACL.
Differential diagnosis of MCACL includes secondary metastatic cystadenocarcinomatous lesions, particularly from the pancreas or ovary, mucoepidermoid carcinoma, and pulmonary mucinous bronchioloalveolar carcinoma. The mouse monoclonal antibody 1D3, developed to detect a high molecular weight mucin found in a number of cystic malignancies of various organs, may be of use in differentiating primary mucinous cystadenocarcinoma of the lung from metastatic lung tumors due to mucinous cystic lesions of the uterus and pancreas, as well as those primary in the colon and stomach.
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.
Krukenberg tumors often come to the attention when they cause abdominal or pelvic pain, bloating, ascites, or pain during sexual intercourse. Krukenberg tumors can occasionally provoke a reaction of the ovarian stroma which leads to hormone production, that results in vaginal bleeding, a change in menstrual habits, or hirsutism, or occasionally virilization as a main symptom.
All these symptoms are non-specific and can also arise with a range of problems other than cancer, and a diagnosis can only be made following confirmatory investigations such as computed tomography (CT) scans, laparotomy and/or a biopsy of the ovary.
As of 2004, no simple and comprehensive classification system has been devised and accepted within the scientific community. Traditionally, however, malignancies have generally been classified into various types using a combination of criteria, including:
the cell type from which they start, specifically:
1. Epithelial cells ⇨ carcinoma
2. Non-hematopoietic mesenchymal cells ⇨ sarcoma
3. Hematopoietic cells
1. bone marrow-derived cells that normally mature in the bloodstream ⇨ Leukemia
2. bone marrow-derived cells that normally mature in the lymphatic system ⇨ Lymphoma
4. Germ cells ⇨ Germinoma
Other criteria that play a role in a cancer diagnosis include:
- The degree to which the malignant cells resemble their normal, untransformed counterparts
- the appearance of the local tissue and stromal architecture
- the anatomical location from which tumors arise
- genetic, epigenetic, and molecular features
Symptoms may include:
- Swelling in the extremities (arms or legs), also called peripheral edema; the swelling often is painless.
- Difficulty in moving the extremity that has the tumor, including a limp.
- Soreness localized to the area of the tumor or in the extremity.
- Neurological symptoms.
- Pain or discomfort: numbness, burning, or "pins and needles."
- Dizzyness and/or loss of balance.
Tumors in the eye and orbit can be benign like dermoid cysts, or malignant like rhabdomyosarcoma and retinoblastoma.