Made by DATEXIS (Data Science and Text-based Information Systems) at Beuth University of Applied Sciences Berlin
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)
Funded by The Federal Ministry for Economic Affairs and Energy; Grant: 01MD19013D, Smart-MD Project, Digital Technologies
While most carcinoids are asymptomatic through the natural lifetime and are discovered only upon surgery for unrelated reasons (so-called "coincidental carcinoids"), all carcinoids are considered to have malignant potential.
About 10% of carcinoids secrete excessive levels of a range of hormones, most notably serotonin (5-HT), causing:
- Flushing (serotonin itself does not cause flushing). Potential causes of flushing in carcinoid syndrome include bradykinins, prostaglandins, tachykinins, substance P, and/or histamine, diarrhea, and heart problems. Because of serotonin's growth-promoting effect on cardiac myocytes,[14] a serotonin-secreting carcinoid tumour may cause a tricuspid valve disease syndrome, due to the proliferation of myocytes onto the valve.
- Diarrhea
- Wheezing
- Abdominal cramping
- Peripheral edema
The outflow of serotonin can cause a depletion of tryptophan leading to niacin deficiency. Niacin deficiency, also known as pellagra, is associated with dermatitis, dementia, and diarrhea.
This constellation of symptoms is called "carcinoid syndrome" or (if acute) "carcinoid crisis". Occasionally, haemorrhage or the effects of tumor bulk are the presenting symptoms. The most common originating sites of carcinoid is the small bowel, particularly the ileum; carcinoid tumors are the most common malignancy of the appendix. Carcinoid tumors may rarely arise from the ovary or thymus.
They are most commonly found in the midgut at the level of the ileum or in the appendix. The next most common affected area is the respiratory tract, with 28% of all cases — per PAN-SEER data (1973 – 1999). The rectum is also a common site.
Some PanNETs do not cause any symptoms, in which case they may be discovered incidentally on a CT scan performed for a different purpose. Symptoms such as abdominal or back pain or pressure, diarrhea, indigestion, or yellowing of the skin and whites of the eyes can arise from the effects of a larger PanNET tumor, either locally or at a metastasis. About 40% of PanNETS have symptoms related to excessive secretion of hormones or active polypeptides and are accordingly labeled as "functional"; the symptoms reflect the type of hormone secreted, as discussed below. Up to 60% of PanNETs are nonsecretory or nonfunctional, in which there is no secretion, or the quantity or type of products, such as pancreatic polypeptide (PPoma), chromogranin A, and neurotensin, do not cause a clinical syndrome although blood levels may be elevated. In total, 85% of PanNETs have an elevated blood marker.
Functional tumors are often classified by the hormone most strongly secreted, for example:
- gastrinoma: the excessive gastrin causes Zollinger–Ellison syndrome (ZES) with peptic ulcers and diarrhea
- insulinoma: hypoglycemia occurs with concurrent elevations of insulin, proinsulin and C peptide
- glucagonoma: the symptoms are not all due to glucagon elevations, and include a rash, sore mouth, altered bowel habits, venous thrombosis, and high blood glucose levels
- VIPoma, producing excessive vasoactive intestinal peptide, which may cause profound chronic watery diarrhea and resultant dehydration, hypokalemia, and achlorhydria (WDHA or pancreatic cholera syndrome)
- somatostatinoma: these rare tumors are associated with elevated blood glucose levels, achlorhydria, cholelithiasis, and diarrhea
- less common types include ACTHoma, CRHoma, calcitoninoma, GHRHoma, GRFoma, and parathyroid hormone–related peptide tumor
In these various types of functional tumors, the frequency of malignancy and the survival prognosis have been estimated dissimilarly, but a pertinent accessible summary is available.
Carcinoid (also carcinoid tumor) is a slow-growing type of neuroendocrine tumor originating in the cells of the neuroendocrine system. In some cases, metastasis may occur. Carcinoid tumors of the midgut (jejunum, ileum, appendix, and cecum) are associated with carcinoid syndrome.
Carcinoid tumors are the most common malignant tumor of the appendix, but they are most commonly associated with the small intestine, and they can also be found in the rectum and stomach. They are known to grow in the liver, but this finding is usually a manifestation of metastatic disease from a primary carcinoid occurring elsewhere in the body. They have a very slow growth rate compared to most malignant tumors. The median age at diagnosis for all patients with neuroendocrine tumors is 63 years.
PanNETs are sometimes abbreviated as PETs or PNETs: such use should not to be confused with the primitive neuroectodermal tumor (PNET).
The majority of PanNETs are benign, while some are malignant. The World Health Organization (WHO) classification scheme places neuroendocrine tumors into three main categories, which emphasize the tumor grade rather than the anatomical origin. In practice, those tumors termed well or intermediately differentiated PanNETs in the WHO scheme are sometimes called "islet cell tumors." The high grade subtype, termed neuroendocrine cancer (NEC) in the WHO scheme, is synonymous with "islet cell carcinoma".
Most paragangliomas are either asymptomatic or present as a painless mass. While all contain neurosecretory granules, only in 1–3% of cases is secretion of hormones such as catecholamines abundant enough to be clinically significant; in that case manifestations often resemble those of pheochromocytomas (intra-medullary paraganglioma).
About 85% of paragangliomas develop in the abdomen; only 12% develop in the chest and 3% in the head and neck region (the latter are the most likely to be symptomatic). While most are single, rare multiple cases occur (usually in a hereditary syndrome). Paragangliomas are described by their site of origin and are often given special names:
- Carotid paraganglioma (carotid body tumor): Is the most common of the head and neck paragangliomas. It usually presents as a painless neck mass, but larger tumors may cause cranial nerve palsies, usually of the vagus nerve and hypoglossal nerve.
- Organ of Zuckerkandl: A collection of paraganglia near the bifurcation of the aorta, comprising a small mass of neural crest-derived chromaffin cells. Serves as a common origin of abdominal paragangliomas.
- Glomus tympanicum and Glomus jugulare: Both commonly present as a middle ear mass resulting in tinnitus (in 80%) and hearing loss (in 60%). The cranial nerves of the jugular foramen may be compressed, resulting swallowing difficulty, or ipsilateral weakness of the upper trapezius and sternocleiodomastoid muscles (from compression of the spinal accessory nerve). These patients present with a reddish bulge behind an intact ear drum. This condition is also known as the "Red drum". On application of pressure to the external ear canal with the help of a pneumatic ear speculum the mass could be seen to blanch. This sign is known as "Brown's sign". A deficient bony plate along the tympanic portion of the internal carotid artery (aberrant ICA) is a normal variant and can be mistaken with glomus jugulare.
- Vagal paraganglioma: These are the least common of the head and neck paragangliomas. They usually present as a painless neck mass, but may result in dysphagia and hoarseness.
- Pulmonary paraganglioma: These occur in the lung and may be either single or multiple.
- Other sites: Rare sites of involvement are the larynx, nasal cavity, paranasal sinuses, thyroid gland, and the thoracic inlet, as well as the bladder in extremely rare cases.
The World Health Organization (WHO) classification scheme places neuroendocrine tumors into three main categories, which emphasize the tumor grade rather than the anatomical origin:
- well-differentiated neuroendocrine tumours, further subdivided into tumors with benign and those with uncertain behavior
- well-differentiated (low grade) neuroendocrine carcinomas with low-grade malignant behavior
- poorly differentiated (high grade) neuroendocrine carcinomas, which are the large cell neuroendocrine and small cell carcinomas.
Additionally, the WHO scheme recognizes mixed tumors with both neuroendocrine and epithelial carcinoma features, such as goblet cell cancer, a rare gastrointestinal tract tumor.
Placing a given tumor into one of categories depends on well-defined histological features: size, lymphovascular invasion, mitotic counts, Ki-67 labelling index, invasion of adjacent organs, presence of metastases and whether they produce hormones.
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.
A benign tumor is a mass of cells (tumor) that lacks the ability to invade neighboring tissue or metastasize. Benign tumors do not spread into, or invade, nearby tissues. Benign tumors can sometimes be quite large, however. When removed, they usually do not grow back, whereas malignant tumors sometimes do. Unlike most benign tumors elsewhere in the body, benign brain tumors can be life threatening. Benign tumors generally have a slower growth rate than malignant tumors and the tumor cells are usually more differentiated (cells have normal features). Benign tumors are typically surrounded by an outer surface (fibrous sheath of connective tissue) or remain with the epithelium. Common examples of benign tumors include moles and uterine fibroids.
Although benign tumors will not metastasize or locally invade tissues, some types may still produce negative health effects. The growth of benign tumors produces a "mass effect" that can compress tissues and may cause nerve damage, reduction of blood to an area of the body (ischaemia), tissue death (necrosis) and organ damage. The mass effect of tumors is more prominent if the tumor is within an enclosed space such as the cranium, respiratory tract, sinus or inside bones. Tumors of endocrine tissues may overproduce certain hormones, especially when the cells are well differentiated. Examples include thyroid adenomas and adrenocortical adenomas.
Although most benign tumors are not life-threatening, many types of benign tumors have the potential to become cancerous (malignant) through a process known as tumour progression. For this reason and other possible negative health effects, some benign tumors are removed by surgery.
The colorectal adenoma is a benign glandular tumor of the colon and the rectum. It is a precursor lesion of the colorectal adenocarcinoma (colon cancer).
Some morphological variants have been described:
- tubular adenoma
- tubulovillous adenoma
- villous adenoma
- sessile serrated adenoma (SSA)
Appendix cancer or appendiceal cancers are rare malignancies of the vermiform appendix.
Gastrointestinal stromal tumors are rare tumors with malignant potential. Primary lymphomas can occur in the appendix. Breast cancer, colon cancer, and tumors of the female genital tract may metastasize to the appendix.
SSAs, generally, are asymptomatic. They are typically identified on a colonoscopy and excised for a definitive diagnosis and treatment.
Benign tumors are very diverse, and may be asymptomatic or may cause specific symptoms depending on their anatomic location and tissue type. They grow outwards, producing large rounded masses, which can cause what is known as a "mass effect". This growth can cause compression of local tissues or organs, which can cause many effects such as blockage of ducts, reduced blood flow (ischaemia), tissue death (necrosis) and nerve pain or damage. Some tumors also produce hormones that can lead to life-threatening situations. Insulinomas can produce large amounts of insulin leading to hypoglycemia. Pituitary adenomas can cause elevated levels of hormones such as growth hormone and insulin-like growth factor-1, which cause acromegaly; prolactin; ACTH and cortisol, which cause Cushings disease; TSH, which causes hyperthyroidism; and FSH and LH. Bowel intussusception can occur with various benign colonic tumors. Cosmetic effects can be caused by tumors, especially those of the skin, possibly causing psychological effects on the person with the tumor. Vascular tumors can bleed, which in some cases can be substantial, leading to anemia.
Symptoms may include coughing, an upper respiratory tract infection, shortness of breath, and chest pain. These symptoms are very non-specific, and can be caused by other types of tumor in the lung or mediastinum more generally, and by other conditions. Imaging (X-ray, CT, MRI) may be used to determine the presence and precise location of a tumor, but not a specific diagnosis of PPB or other tumor.
Doctors are unable to tell if a child has PPB right away, and not upper respiratory tract infection, until more test are taken and they show that there is no infection. Another symptom is pneumothorax.
SSAs are diagnosed by their microscopic appearance; histomorphologically, they are characterized by (1) basal dilation of the crypts, (2) basal crypt serration, (3) crypts that run horizontal to the basement membrane (horizontal crypts), and (4) crypt branching. The most common of these features is basal dilation of the crypts.
Unlike traditional colonic adenomas (e.g. tubular adenoma, villous adenoma), they do not (typically) have nuclear changes (nuclear hyperchromatism, nuclear crowding, elliptical/cigar-shaped nuclei).
Traditionally, neuroendocrine tumors have been classified by their anatomic site of origin. NETs can arise in many different areas of the body, and are most often located in the intestine, pancreas or the lungs. The various kinds of cells that can give rise to NETs are present in endocrine glands and are also diffusely distributed throughout the body, most commonly Kulchitsky cells or similar enterochromaffin-like cells, that are relatively more common in the gastrointestinal and pulmonary systems.
NETs include certain tumors of the gastrointestinal tract and of the pancreatic islet cells, certain thymus and lung tumors, and medullary carcinoma of the parafollicular cells of the thyroid. Tumors with similar cellular characteristics in the pituitary, parathyroid, and adrenomedullary glands are sometimes included or excluded.
Within the broad category of neuroendocrine tumors there are many different tumor types: this outline is presented to facilitate retrieving information. Neuroendocrine tumors are uncommon in many of these areas, and frequently represent only a very small proportion of the tumors or cancers at these locations.
- Pituitary gland: Neuroendocrine tumor of the anterior pituitary
- Thyroid gland: Neuroendocrine thyroid tumors, particularly medullary carcinoma
- Parathyroid tumors
- Thymus and mediastinal carcinoid tumors
- Pulmonary neuroendocrine tumors
- bronchus
- pulmonary carcinoid tumors: typical carcinoid (TC; low-grade); atypical carcinoid (AC; intermediate-grade)
- small-cell lung cancer (SCLC)
- large cell neuroendocrine carcinoma of the lung (LCNEC)
- Extrapulmonary small cell carcinomas (ESCC or EPSCC)
- Gastroenteropancreatic neuroendocrine tumors (GEP-NET)
- Foregut GEP-NET (foregut tumors can conceptually encompasses not only NETs of the stomach and proximal duodenum, but also the pancreas, and even thymus, lung and bronchus)
- Pancreatic endocrine tumors (if considered separately from foregut GEP-NET)
- Midgut GEP-NET (from distal half of 2nd part of the duodenum to the proximal two-thirds of the transverse colon)
- appendix, including well differentiated NETs (benign); well differentiated NETs (uncertain malignant potential); well differentiated neuroendocrine carcinoma (with low malignant potential); mixed exocrine-neuroendocrine carcinoma (goblet cell carcinoma, also called adenocarcinoid and mucous adenocarcinoid)
- Hindgut GEP-NET
- Liver and gallbladder
- Adrenal tumors, particularly adrenomedullary tumors
- Pheochromocytoma
- Peripheral nervous system tumors, such as:
- Schwannoma
- paraganglioma
- neuroblastoma
- Breast
- Genitourinary tract
- urinary tract carcinoid tumor and neuroendocrine carcinoma
- ovary
- neuroendocrine tumor of the cervix
- testes
- Merkel cell carcinoma of skin (trabecular cancer)
- Several inherited conditions:
- multiple endocrine neoplasia type 1 (MEN1)
- multiple endocrine neoplasia type 2 (MEN2)
- von Hippel-Lindau (VHL) disease
- neurofibromatosis type 1
- tuberous sclerosis
- Carney complex
A neoplasm can be benign, potentially malignant, or malignant (cancer).
- Benign tumors include uterine fibroids and melanocytic nevi (skin moles). They are circumscribed and localized and do not transform into cancer.
- Potentially-malignant neoplasms include carcinoma in situ. They are localised, do not invade and destroy but in time, may transform into a cancer.
- Malignant neoplasms are commonly called cancer. They invade and destroy the surrounding tissue, may form metastases and, if untreated or unresponsive to treatment, will prove fatal.
- Secondary neoplasm refers to any of a class of cancerous tumor that is either a metastatic offshoot of a primary tumor, or an apparently unrelated tumor that increases in frequency following certain cancer treatments such as chemotherapy or radiotherapy.
- Rarely there can be a metastatic neoplasm with no known site of the primary cancer and this is classed as a cancer of unknown primary origin
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.
The most common general classification is:
- hyperplastic,
- neoplastic (adenomatous & malignant),
- hamartomatous and,
- inflammatory.
"Tumor" (American English) or "tumour" (British English), Latin for "swelling", one of the cardinal signs of inflammation, originally meant any form of swelling, neoplastic or not. Current English, however, both medical and non-medical, uses "tumor" as a synonym for a neoplasm (a solid or fluid-filled cystic lesion that may or may not be formed by an abnormal growth of neoplastic cells) that appears enlarged in size. Some neoplasms do not form a tumor; these include leukemia and most forms of carcinoma in situ. "Tumor" is also not synonymous with "cancer." While cancer is by definition malignant, a tumor can be benign, precancerous, or malignant.
The terms "mass" and "nodule" are often used synonymously with "tumor". Generally speaking, however, the term "tumor" is used generically, without reference to the physical size of the lesion. More specifically, the term "mass" is often used when the lesion has a maximal diameter of at least 20 millimeters (mm) in greatest direction, while the term "nodule" is usually used when the size of the lesion is less than 20 mm in its greatest dimension (25.4 mm = 1 inch).
Synonyms for FA include well differentiated fetal adenocarcinoma, high-grade fetal adenocarcinoma, pulmonary adenocarcinoma
of fetal type, and pulmonary endodermal tumour resembling fetal lung.
Pulmonary neuroendocrine tumor are classified according to tumoral grade:
- Low grade pulmonary neuroendocrine tumor: Typical pulmonary carcinoid tumour (TC; low-grade);
- Intermediate-grade pulmonary neuroendocrine tumor: Atypical pulmonary carcinoid tumour (AC; intermediate-grade)
- High-grade pulmonary neuroendocrine tumor
- Small cell lung cancer (SCLC)
- Large cell neuroendocrine carcinoma (LCNEC of the lung)
Low-grade nodular neuroendocrine proliferations ≥ 0.5 cm are classified as carcinoid tumors and smaller ones are called pulmonary tumorlets.
When neuroendocrine cell hyperplasia and tumorlets are extensive, they represent the rare preinvasive lesion for carcinoids known as "diffuse idiopathic pulmonary neuroendocrine cell hyperplasia".
Both LCNEC and SCLC can demonstrate histologic heterogeneity with other major histologic types of lung carcinoma, such as pulmonary adenocarcinoma or pulmonary squamous cell carcinoma, but is not characteristic of TC or AC.
Carcinosarcomas are malignant tumors that consist of a mixture of carcinoma (or epithelial cancer) and sarcoma (or mesenchymal/connective tissue cancer). Carcinosarcomas are rare tumors, and can arise in diverse organs, such as the skin, salivary glands, lungs, the esophagus, pancreas, colon, uterus and ovaries.
Four main hypotheses have been proposed for the cellular origins of carcinosarcoma, based largely on the pathology of the disease. First, the collision tumor hypothesis, which proposes the collision of two independent tumors resulting in a single neoplasm, based on the observation that skin cancers and superficial malignant fibrous histiocytomas are commonly seen in patients with sun-damaged skin; second, the composition hypothesis, which suggests that the mesenchymal component represents a pseudosarcomatous reaction to the epithelial malignancy; third, the combination hypothesis, which suggests that both the epithelial and mesenchymal components of the tumor arise from a common pluripotential stem cell that undergoes divergent differentiation; and fourth, the conversion/divergence hypothesis, which argues that the sarcomatous component of the tumor represents a metaplastic sarcomatous transformation of the epithelial component. Despite the remaining uncertainty on the mechanisms that generate these tumors, recent immunohistochemical, ultrastructural, and molecular genetic studies suggest and favor the notion of monoclonality in carcinosarcoma. In addition, identical p53 and KRAS mutations have been identified in both epithelial and mesenchymal components of carcinosarcoma, findings that suggest an early alteration in the histogenesis of the tumor with late transformation or degeneration of the epithelial component into the sarcomatous component.
These are polyps which are associated with inflammatory conditions such as Ulcerative Colitis and Crohns disease.
Pleuropulmonary blastoma (PPB) is a rare cancer originating in the lung or pleural cavity. It occurs most often in infants and young children but also has been reported in adults. In a retrospective review of 204 children with lung tumors, pleuropulmonary blastoma and carcinoid tumor were the most common primary tumors (83% of the 204 children had secondary tumors spread from cancers elsewhere in the body). Pleuropulmonary blastoma is regarded as malignant. The male:female ratio is approximately one.