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Dermatofibrosarcoma protuberans

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Dermatofibrosarcoma protuberans ( DFSP ) is a rare locally aggressive malignant cutaneous soft-tissue sarcoma . DFSP develops in the connective tissue cells in the middle layer of the skin (dermis). Estimates of the overall occurrence of DFSP in the United States are 0.8 to 4.5 cases per million persons per year. In the United States, DFSP accounts for between 1 and 6 percent of all soft-tissue sarcomas and 18 percent of all cutaneous soft-tissue sarcomas. In the Surveillance, Epidemiology and End Results (SEER) tumor registry from 1992 through 2004, DFSP was second only to Kaposi sarcoma .

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123-472: Dermatofibrosarcoma protuberans begins as a minor firm area of skin most commonly about to 1 to 5 cm in diameter. It can resemble a bruise, birthmark, or pimple. It is a slow-growing tumor and is usually found on the torso but can occur anywhere on the body. About 90% of DFSPs are low-grade sarcomas. About 10% are mixed, containing a high-grade sarcomatous component (DFSP-FS); therefore, they are considered to be intermediate-grade sarcomas. DFSPs rarely lead to

246-484: A metastasis (fewer than 5% metastasize), but DFSPs can recur locally. DFSPs most often arise in patients who are in their thirties but this may be due to diagnostic delay. Commonly located on the chest and shoulders, the following is the site distribution of DFPS as was observed in Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2010. The World Health Organization in 2020 classified

369-579: A portable MRI scanner approved by the FDA in 2020. Recently, MRI has been demonstrated also at ultra-low fields, i.e., in the microtesla-to-millitesla range, where sufficient signal quality is made possible by prepolarization (on the order of 10–100 mT) and by measuring the Larmor precession fields at about 100 microtesla with highly sensitive superconducting quantum interference devices ( SQUIDs ). Each tissue returns to its equilibrium state after excitation by

492-455: A primary heterogeneic tumour . The cells which constitute the tumor eventually undergo metaplasia , followed by dysplasia then anaplasia , 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 (CTCs), are able to penetrate the walls of lymphatic or blood vessels , and circulate through

615-540: A T 2 -weighted image, magnetization is allowed to decay before measuring the MR signal by changing the echo time (TE). This image weighting is useful for detecting edema and inflammation, revealing white matter lesions , and assessing zonal anatomy in the prostate and uterus . The information from MRI scans comes in the form of image contrasts based on differences in the rate of relaxation of nuclear spins following their perturbation by an oscillating magnetic field (in

738-537: A TED Talk in February 2020 on the topic. R. W. Taylor, in 1890, first identified DFSP as a keloid sarcoma. Later in 1924, Ferdinand-Jean Darier and Ferrand identified it as a progressive recurrent dermatofibroma. In 1925, E. Hoffmann coined the term dermatofibrosarcoma protuberans . Bednar tumor was first described by Bednar in 1957. The following are the ICD-10 medical codes: Metastasis Metastasis

861-436: A canalicular system are one metastatic process or in fact independent tumors caused by the same agent ( field cancerization ). There is a propensity for certain tumors to seed in particular organs. This was first discussed as the seed and soil theory by Stephen Paget in 1889. The propensity for a metastatic cell to spread to a particular organ is termed 'organotropism'. For example, prostate cancer usually metastasizes to

984-490: A cancer in Stage IV. The possibilities of curative treatment are greatly reduced, or often entirely removed when a cancer has metastasized. Initially, nearby lymph nodes are struck early. The lungs , liver , brain , and bones are the most common metastasis locations from solid tumors. Although advanced cancer may cause pain , it is often not the first symptom. Some patients, however, do not show any symptoms. When

1107-425: A clinical diagnosis of ADHD. Cardiac MRI is complementary to other imaging techniques, such as echocardiography , cardiac CT , and nuclear medicine . It can be used to assess the structure and the function of the heart. Its applications include assessment of myocardial ischemia and viability , cardiomyopathies , myocarditis , iron overload , vascular diseases, and congenital heart disease . Applications in

1230-418: A dozen are known. Human cells exhibit different kinds of motion: collective motility , mesenchymal -type movement, and amoeboid movement . Cancer cells often opportunistically switch between different kinds of motion. Some cancer researchers hope to find treatments that can stop or at least slow down the spread of cancer by somehow blocking some necessary step in one or more kinds of motion. All steps of

1353-446: A drug safety communication that new warnings were to be included on all gadolinium-based contrast agents (GBCAs). The FDA also called for increased patient education and requiring gadolinium contrast vendors to conduct additional animal and clinical studies to assess the safety of these agents. Although gadolinium agents have proved useful for patients with kidney impairment, in patients with severe kidney failure requiring dialysis there

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1476-419: A macroscopic polarized radiation that is detected by the antennas. Hydrogen atoms are naturally abundant in humans and other biological organisms, particularly in water and fat . For this reason, most MRI scans essentially map the location of water and fat in the body. Pulses of radio waves excite the nuclear spin energy transition, and magnetic field gradients localize the polarization in space. By varying

1599-504: A more malignant form (DFSP-FS). The lungs are most frequently affected, but metastases to the brain, bone, and other soft tissues are reported. DFSP is not extensively studied due to its rarity and low mortality. The majority of studies are small size case studies or meta-analysis. The most extensive research study to date was Perspectives of Patients With Dermatofibrosarcoma Protuberans on Diagnostic Delays, Surgical Outcomes, and Nonprotuberance . The lead researcher, Jerad Gardner, spoke at

1722-546: A net nuclear spin could potentially be imaged with MRI. Such nuclei include helium-3 , lithium-7 , carbon-13 , fluorine -19, oxygen-17 , sodium -23, phosphorus -31 and xenon-129 . Na and P are naturally abundant in the body, so they can be imaged directly. Gaseous isotopes such as He or Xe must be hyperpolarized and then inhaled as their nuclear density is too low to yield a useful signal under normal conditions. O and F can be administered in sufficient quantities in liquid form (e.g. O -water) that hyperpolarization

1845-542: A number of early suggestions for using arrays of detectors to accelerate imaging went largely unremarked in the MRI field, parallel imaging saw widespread development and application following the introduction of the SiMultaneous Acquisition of Spatial Harmonics (SMASH) technique in 1996–7. The SENSitivity Encoding (SENSE) and Generalized Autocalibrating Partially Parallel Acquisitions (GRAPPA) techniques are

1968-458: A patient's likelihood of death. Some cancers—such as some forms of leukemia , a cancer of the blood, or malignancies in the brain —can kill without spreading at all. Once a cancer has metastasized it may still be treated with radiosurgery , chemotherapy , radiation therapy , biological therapy , hormone therapy , surgery , or a combination of these interventions ("multimodal therapy"). The choice of treatment depends on many factors, including

2091-547: A primary cancerous source to nearby tissues was Ibn Sina . He described a case of breast cancer and metastatic condition in The Canon of Medicine . His hypothesis was based on clinical course of the patient. In March 2014 researchers discovered the oldest complete example of a human with metastatic cancer. The tumors had developed in a 3,000-year-old skeleton found in 2013 in a tomb in Sudan dating back to 1200 BC. The skeleton

2214-430: A primary tumor may appear later. The use of immunohistochemistry has permitted pathologists to give an identity to many of these metastases. However, imaging of the indicated area only occasionally reveals a primary. In rare cases (e.g., of melanoma ), no primary tumor is found, even on autopsy . It is therefore thought that some primary tumors can regress completely, but leave their metastases behind. In other cases,

2337-512: A radio frequency coil and thereby be detected. In other words, the nuclear magnetic spin of protons in the hydrogen nuclei resonates with the RF incident waves and emit coherent radiation with compact direction, energy (frequency) and phase. This coherent amplified radiation is easily detected by RF antennas close to the subject being examined. It is a process similar to masers . In clinical and research MRI, hydrogen atoms are most often used to generate

2460-414: A rate that is higher than expected by statistical chance alone. Breast cancer, for example, tends to metastasize to the bones and lungs. This specificity seems to be mediated by soluble signal molecules such as chemokines and transforming growth factor beta . The body resists metastasis by a variety of mechanisms through the actions of a class of proteins known as metastasis suppressors , of which about

2583-410: A role in the detection of large polyps in patients at increased risk of colorectal cancer. Magnetic resonance angiography (MRA) generates pictures of the arteries to evaluate them for stenosis (abnormal narrowing) or aneurysms (vessel wall dilatations, at risk of rupture). MRA is often used to evaluate the arteries of the neck and brain, the thoracic and abdominal aorta, the renal arteries, and

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2706-431: A slow infiltrative growth and a high rate of local recurrence if not completely excised. Sclerosing DFSP is a variant in which the cellularity is low, and the tumor consists of uniform bundles of collagen interspersed with more typical DFSP cells. Granular cell variant is a rare type in which spindle cells are mingled with richly granular cells, the granules being lysosomal, with prominent nucleoli. Fibrosarcomatous DFSP

2829-406: A total magnetization M z . This magnetization along z is defined as the equilibrium magnetization; magnetization is defined as the sum of all magnetic dipoles in a sample. Following the equilibrium magnetization, a 90° radiofrequency (RF) pulse flips the direction of the magnetization vector in the xy-plane, and is then switched off. The initial magnetic field B 0 , however, is still applied. Thus,

2952-852: A typical field strength for clinical MRI, the difference between high and low energy states is approximately 9 molecules per 2 million. Improvements to increase MR sensitivity include increasing magnetic field strength and hyperpolarization via optical pumping or dynamic nuclear polarization. There are also a variety of signal amplification schemes based on chemical exchange that increase sensitivity. To achieve molecular imaging of disease biomarkers using MRI, targeted MRI contrast agents with high specificity and high relaxivity (sensitivity) are required. To date, many studies have been devoted to developing targeted-MRI contrast agents to achieve molecular imaging by MRI. Commonly, peptides, antibodies, or small ligands, and small protein domains, such as HER-2 affibodies, have been applied to achieve targeting. To enhance

3075-445: Is intraoperative MRI , in which an MRI is used in surgery. Some specialized MRI systems allow imaging concurrent with the surgical procedure. More typically, the surgical procedure is temporarily interrupted so that MRI can assess the success of the procedure or guide subsequent surgical work. In guided therapy, high-intensity focused ultrasound (HIFU) beams are focused on a tissue, that are controlled using MR thermal imaging. Due to

3198-559: Is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, are metastases ( mets ). It is generally distinguished from cancer invasion , which is the direct extension and penetration by cancer cells into neighboring tissues. Cancer occurs after cells are genetically altered to proliferate rapidly and indefinitely. This uncontrolled proliferation by mitosis produces

3321-410: Is a particular setting of radiofrequency pulses and gradients, resulting in a particular image appearance. The T1 and T2 weighting can also be described as MRI sequences. edit This table does not include uncommon and experimental sequences . Standard foundation and comparison for other sequences Standard foundation and comparison for other sequences Magnetic resonance spectroscopy (MRS)

3444-456: Is a rare variant of DFSP involving greater aggression, high rates of local occurrences, and higher metastatic potential. DFSP-FS are considered to be intermediate-grade sarcomas, although they rarely metastasize (fewer than 5 percent of cases). More than 90% of DFSP tumors have the chromosomal translocation t(17;22). The translocation fuses the collagen gene ( COL1A1 ) with the platelet-derived growth factor ( PDGF ) gene. The fibroblast ,

3567-543: Is a risk of a rare but serious illness, nephrogenic systemic fibrosis , which may be linked to the use of certain gadolinium-containing agents. The most frequently linked is gadodiamide , but other agents have been linked too. Although a causal link has not been definitively established, current guidelines in the United States are that dialysis patients should only receive gadolinium agents where essential and that dialysis should be performed as soon as possible after

3690-689: Is a similar procedure that is used to image veins. In this method, the tissue is now excited inferiorly, while the signal is gathered in the plane immediately superior to the excitation plane—thus imaging the venous blood that recently moved from the excited plane. MRI for imaging anatomical structures or blood flow do not require contrast agents since the varying properties of the tissues or blood provide natural contrasts. However, for more specific types of imaging, exogenous contrast agents may be given intravenously , orally , or intra-articularly . Most contrast agents are either paramagnetic (e.g.: gadolinium, manganese, europium), and are used to shorten T1 in

3813-422: Is a term that would be used by medical specialists to describe regional lymph nodes that tested positive for malignancy. It is common medical practice to test by biopsy at least one lymph node near a tumor site when carrying out surgery to examine or remove a tumor. This lymph node is then called a sentinel lymph node . Lymphatic spread is the most common route of initial metastasis for carcinomas . In contrast, it

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3936-550: Is applied, and the remaining spatial information is filled in by combining signals from various coils, based on their known spatial sensitivity patterns. The resulting acceleration is limited by the number of coils and by the signal to noise ratio (which decreases with increasing acceleration), but two- to four-fold accelerations may commonly be achieved with suitable coil array configurations, and substantially higher accelerations have been demonstrated with specialized coil arrays. Parallel MRI may be used with most MRI sequences . After

4059-561: Is attempted first. If clear margins are not achieved RT, or chemotherapy is recommended. DFSP was previously regarded and nonresponsive to standard chemotherapy. In 2006 the US FDA approved ( imatinib mesylate ) for the treatment of DFSP. As is true for all medicinal drugs with name ending in "ib," imatinib is a small molecular pathway inhibitor; imatinib inhibits tyrosine kinase . It may be able to induce tumor regression in patients with recurrent DFSP, unresectable DFSP, or metastatic DFSP. There

4182-679: Is clinical evidence that imatinib , which inhibits PDGF-receptors , may be effective for tumors positive for the t(17;22) translocation. It is suggested that imatinib may be a treatment for challenging, locally advanced disease and in the rare metastatic cases. It was approved for use by adult patients with unresectable, recurrent and/or metastatic dermatofibrosarcoma protuberans (DFSP). Distant hematogenous metastases are extremely rare. Metastases to regional lymph nodes are rarer and are most likely in patients who have had multiple local recurrences after inadequate surgical resection. Repeatedly recurring tumors have an increased risk for transformation into

4305-434: Is disputed in certain cases. MRI is the investigation of choice in the preoperative staging of rectal and prostate cancer and has a role in the diagnosis, staging, and follow-up of other tumors, as well as for determining areas of tissue for sampling in biobanking. MRI is the investigative tool of choice for neurological cancers over CT, as it offers better visualization of the posterior cranial fossa , containing

4428-401: Is distinguished by the dispersal of melanin -rich dendritic cells of the skin. It represents 1–5 percent of all DFSP occurring in people rich in melanin pigments. Bednar is characterized by a dermal spindle cell proliferation like DFSP but distinguished by the additional presence of melanocytic dendritic cells. It occurs at the same rate as DFSP on fairer skin and should be considered to have

4551-445: Is involved in signaling pathways which upregulate EMT in melanoma thereby directly stimulates metastasis. Recently, a series of high-profile experiments suggests that the co-option of intercellular cross-talk mediated by exosome vesicles is a critical factor involved in all steps of the invasion-metastasis cascade. Metastasis occurs by the following four routes: The spread of a malignancy into body cavities can occur via penetrating

4674-402: Is more sensitive addressing the depth of the invasion on some types of DFSP, particularly large or recurring tumors, though MRI is less accurate for identifying infiltration to head and neck tumors. Due to the rarity, initial presentation of flat plaque (skin hardening) and the slow-growing nature of DFSP, it may be months to years without a protuberance (bump). The dissonance between the name of

4797-408: Is not a necessity. Using helium or xenon has the advantage of reduced background noise, and therefore increased contrast for the image itself, because these elements are not normally present in biological tissues. Moreover, the nucleus of any atom that has a net nuclear spin and that is bonded to a hydrogen atom could potentially be imaged via heteronuclear magnetization transfer MRI that would image

4920-452: Is often positive for CD34 . DFSP is a malignant tumor diagnosed with a biopsy , when a portion of the tumor is removed for examination. In order to ensure that enough tissue is removed to make an accurate diagnosis, the initial biopsy of a suspected DFSP is usually done with a core needle or a surgical incision. Clinical palpation is not entirely reliable for ascertaining the depth of a DFSP infiltration. Magnetic resonance imaging (MRI)

5043-457: Is primarily surgical , with chemotherapy and radiation therapy used if clear resection margins are not acquired. The type of surgical treatment chosen is dependent on the location of the DFSP occurrence and possible size. Mohs micrographic surgery (MMS) has a high cure rate and lowers the recurrence reduction of DFSP if negative resection margins are achieved. Wide local excision (WLE)

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5166-453: Is processed to form an image of the body in terms of the density of those nuclei in a specific region. Given that the protons are affected by fields from other atoms to which they are bonded, it is possible to separate responses from hydrogen in specific compounds. To perform a study, the person is positioned within an MRI scanner that forms a strong magnetic field around the area to be imaged. First, energy from an oscillating magnetic field

5289-463: Is suggested that DFSPs may enlarge more rapidly during pregnancy. Immunohistochemical stains for CD34, S-100 protein, factor XIIIa, and estrogen and progesterone receptors were performed on biopsy specimens. The tumors showed the expression of the progesterone receptor. As with many other stromal neoplasms, DFSPs appear to express low levels of hormone receptors, which may be one factor that accounts for their accelerated growth during pregnancy. Treatment

5412-411: Is temporarily applied to the patient at the appropriate resonance frequency. Scanning with X and Y gradient coils causes a selected region of the patient to experience the exact magnetic field required for the energy to be absorbed. The atoms are excited by a RF pulse and the resultant signal is measured by a receiving coil . The RF signal may be processed to deduce position information by looking at

5535-417: Is the lower incidence of nephrotoxicity, compared with iodinated agents, when given at usual doses—this has made contrast-enhanced MRI scanning an option for patients with renal impairment, who would otherwise not be able to undergo contrast-enhanced CT . Gadolinium-based contrast reagents are typically octadentate complexes of gadolinium(III) . The complex is very stable (log K > 20) so that, in use,

5658-468: Is uncommon for a sarcoma to metastasize via this route. Localized spread to regional lymph nodes near the primary tumor is not normally counted as a metastasis, although this is a sign of a worse outcome . The lymphatic system does eventually drain from the thoracic duct and right lymphatic duct into the systemic venous system at the venous angle and into the brachiocephalic veins , and therefore these metastatic cells can also eventually spread through

5781-595: Is used to measure the levels of different metabolites in body tissues, which can be achieved through a variety of single voxel or imaging-based techniques. The MR signal produces a spectrum of resonances that corresponds to different molecular arrangements of the isotope being "excited". This signature is used to diagnose certain metabolic disorders, especially those affecting the brain, and to provide information on tumor metabolism . Magnetic resonance spectroscopic imaging (MRSI) combines both spectroscopic and imaging methods to produce spatially localized spectra from within

5904-501: Is widely accepted to be the result of the tumor cells migration, there is a hypothesis saying that some metastases are the result of inflammatory processes by abnormal immune cells. The existence of metastatic cancers in the absence of primary tumors also suggests that metastasis is not always caused by malignant cells that leave primary tumors. The research done by Sarna's team proved that heavily pigmented melanoma cells have Young's modulus about 4.93, when in non-pigmented ones it

6027-471: Is widely used in hospitals and clinics for medical diagnosis , staging and follow-up of disease. Compared to CT , MRI provides better contrast in images of soft tissues, e.g. in the brain or abdomen. However, it may be perceived as less comfortable by patients, due to the usually longer and louder measurements with the subject in a long, confining tube, although "open" MRI designs mostly relieve this. Additionally, implants and other non-removable metal in

6150-487: The Inhibitor of DNA Binding 1 (ID1). This novel finding meant that investigators gained the ability to track endothelial progenitor cells from the bone marrow to the blood to the tumor-stroma and even incorporated in tumor vasculature. Endothelial progenitor cells incorporated in tumor vasculature suggests that this cell type in blood-vessel development is important in a tumor setting and metastasis. Furthermore, ablation of

6273-536: The anatomy and the physiological processes inside the body. MRI scanners use strong magnetic fields , magnetic field gradients, and radio waves to generate images of the organs in the body. MRI does not involve X-rays or the use of ionizing radiation , which distinguishes it from computed tomography (CT) and positron emission tomography (PET) scans. MRI is a medical application of nuclear magnetic resonance (NMR) which can also be used for imaging in other NMR applications , such as NMR spectroscopy . MRI

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6396-448: The brainstem and the cerebellum . The contrast provided between grey and white matter makes MRI the best choice for many conditions of the central nervous system , including demyelinating diseases , dementia , cerebrovascular disease , infectious diseases , Alzheimer's disease and epilepsy . Since many images are taken milliseconds apart, it shows how the brain responds to different stimuli, enabling researchers to study both

6519-466: The cancer exodus hypothesis , which posits that maintaining this cluster structure contributes to a higher metastatic potential. 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

6642-470: The cell of origin of this tumor, expresses the fusion gene in the belief that it codes for collagen. However, the resulting fusion protein is processed into a mature platelet-derived growth factor which is a potent growth factor . Fibroblasts contain the receptor for this growth factor. Thus the cell "thinks" it is producing a structural protein , but it creates a self-stimulatory growth signal . The cell divides rapidly and tumor forms. The tissue

6765-416: The equilibrium state . Exogenous contrast agents may be given to the person to make the image clearer. The major components of an MRI scanner are the main magnet , which polarizes the sample, the shim coils for correcting shifts in the homogeneity of the main magnetic field, the gradient system which is used to localize the region to be scanned and the RF system, which excites the sample and detects

6888-499: The joints and the heart . In many cases MRI examinations become easier and more comfortable for patients, especially for the patients who cannot calm their breathing or who have arrhythmia . The lack of harmful effects on the patient and the operator make MRI well-suited for interventional radiology , where the images produced by an MRI scanner guide minimally invasive procedures. Such procedures use no ferromagnetic instruments. A specialized growing subset of interventional MRI

7011-507: The ability to metastasize through the development of somatic mutations. According to this theory, diagnosis of metastatic cancers is only possible after the event of metastasis. Traditional means of diagnosing cancer (e.g. a biopsy ) would only investigate a subpopulation of the cancer cells and would very likely not sample from the subpopulation with metastatic potential. The somatic mutation theory of metastasis development has not been substantiated in human cancers. Rather, it seems that

7134-456: The advantages of having very high spatial resolution and is very adept at morphological imaging and functional imaging. MRI does have several disadvantages though. First, MRI has a sensitivity of around 10 mol/L to 10 mol/L, which, compared to other types of imaging, can be very limiting. This problem stems from the fact that the population difference between the nuclear spin states is very small at room temperature. For example, at 1.5 teslas ,

7257-743: The application of a denoising system. The record for the highest spatial resolution of a whole intact brain (postmortem) is 100 microns, from Massachusetts General Hospital. The data was published in NATURE on 30 October 2019. Though MRI is used widely in research on mental disabilities, based on a 2024 systematic literature review and meta analysis commissioned by the Patient-Centered Outcomes Research Institute (PCORI), available research using MRI scans to diagnose ADHD showed great variability. The authors conclude that MRI cannot be reliably used to assist in making

7380-510: The blood vessel cells (endothelial cells), immune cells or stromal cells. The growth of a new network of blood vessels, called tumor angiogenesis , is a crucial hallmark of cancer. It has therefore been suggested that angiogenesis inhibitors would prevent the growth of metastases. Endothelial progenitor cells have been shown to have a strong influence on metastasis and angiogenesis. Endothelial progenitor cells are important in tumor growth, angiogenesis and metastasis, and can be marked using

7503-404: The bloodstream to other sites and tissues in the body. This process, known respectively as lymphatic or hematogenous spread, allows not only single cells but also groups of cells, or CTC clusters , to travel. Evidence suggests that CTC clusters may retain their multicellular configuration throughout metastasis, enhancing their ability to establish secondary tumors. This perspective aligns with

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7626-540: The bloodstream, via the lymphatic system, or by direct extension. To do so, malignant cells break away from the primary tumor and attach to and degrade proteins that make up the surrounding extracellular matrix (ECM), which separates the tumor from adjoining tissues. By degrading these proteins, cancer cells are able to breach the ECM and escape. The location of the metastases is not always random, with different types of cancer tending to spread to particular organs and tissues at

7749-417: The body can pose a risk and may exclude some patients from undergoing an MRI examination safely. MRI was originally called NMRI (nuclear magnetic resonance imaging), but "nuclear" was dropped to avoid negative associations . Certain atomic nuclei are able to absorb radio frequency (RF) energy when placed in an external magnetic field ; the resultant evolving spin polarization can induce an RF signal in

7872-578: The bones. In a similar manner, colon cancer has a tendency to metastasize to the liver. Stomach cancer often metastasises to the ovary in women, when it is called a Krukenberg tumor . According to the seed and soil theory, it is difficult for cancer cells to survive outside their region of origin, so in order to metastasize they must find a location with similar characteristics. For example, breast tumor cells, which gather calcium ions from breast milk, metastasize to bone tissue, where they can gather calcium ions from bone. Malignant melanoma spreads to

7995-404: The brain, presumably because neural tissue and melanocytes arise from the same cell line in the embryo . In 1928, James Ewing challenged the seed and soil theory, and proposed that metastasis occurs purely by anatomic and mechanical routes. This hypothesis has been recently utilized to suggest several hypotheses about the life cycle of circulating tumor cells (CTCs) and to postulate that

8118-420: The central focus of the tumor in a "tentacle-like" fashion. This fact, coupled with diagnostic delay, may lead to inadequate initial resection. Inadequate initial treatment results in larger, deeper recurrent lesions, but these can be managed by appropriate wide excision. DFSP is a radioresponsive tumor; radiation therapy (RT) is not used as the first choice for treatment. Conservative resection through MMS or WLE

8241-420: The changes in RF level and phase caused by varying the local magnetic field using gradient coils . As these coils are rapidly switched during the excitation and response to perform a moving line scan, they create the characteristic repetitive noise of an MRI scan as the windings move slightly due to magnetostriction . The contrast between different tissues is determined by the rate at which excited atoms return to

8364-406: The circulation system, making CTCs an unlikely source of metastasis. Moreover, understanding how cancer cells adapt to the metastatic niche and remain dormant (tumor dormancy) for extended periods presents difficult questions that require further investigation. Metastasis involves a complex series of steps in which cancer cells leave the original tumor site and migrate to other parts of the body via

8487-463: The concentration of the un-complexed Gd ions should be below the toxicity limit. The 9th place in the metal ion's coordination sphere is occupied by a water molecule which exchanges rapidly with water molecules in the reagent molecule's immediate environment, affecting the magnetic resonance relaxation time . In December 2017, the Food and Drug Administration (FDA) in the United States announced in

8610-413: The continuous monitoring of moving objects in real time. Traditionally, real-time MRI was possible only with low image quality or low temporal resolution. An iterative reconstruction algorithm removed limitations. Radial FLASH MRI (real-time) yields a temporal resolution of 20 to 30 milliseconds for images with an in-plane resolution of 1.5 to 2.0 mm. Real-time MRI adds information about diseases of

8733-406: The cytosol leading to the chronic activation of innate immune pathways, which are hijacked by cancer cells to spread to distant organs. Expression of this metastatic signature has been correlated with a poor prognosis and has been shown to be consistent in several types of cancer. Prognosis was shown to be worse for individuals whose primary tumors expressed the metastatic signature. Additionally,

8856-524: The distribution of air spaces within the lungs. Injectable solutions containing C or stabilized bubbles of hyperpolarized Xe have been studied as contrast agents for angiography and perfusion imaging. P can potentially provide information on bone density and structure, as well as functional imaging of the brain. Multinuclear imaging holds the potential to chart the distribution of lithium in the human brain, this element finding use as an important drug for those with conditions such as bipolar disorder. MRI has

8979-422: The endothelial progenitor cells in the bone marrow can lead to a significant decrease in tumor growth and vasculature development. Therefore, endothelial progenitor cells are important in tumor biology and present novel therapeutic targets. The immune system is typically deregulated in cancer and affects many stages of tumor progression, including metastasis. Epigenetic regulation also plays an important role in

9102-405: The expression of these metastatic-associated genes was shown to apply to other cancer types in addition to adenocarcinoma . Metastases of breast cancer , medulloblastoma and prostate cancer all had similar expression patterns of these metastasis-associated genes. The identification of this metastasis-associated signature provides promise for identifying cells with metastatic potential within

9225-422: The fibro sarcomatous DFSP (DFSP-FS) variant (also termed dermatofibrosarcoma protuberans, fibro sarcomatous ) of the dermatofibrosarcoma protuberans as a specific form of the intermediate (rarely metastasizing) fibroblastic and myofibroblastic tumors and other variants of this disorder as a specific form of the intermediate (locally aggressive) fibroblastic and myofibroblastic tumors . Bednar, or pigmented DFSP,

9348-400: The form of radiofrequency pulses through the sample). The relaxation rates are a measure of the time it takes for a signal to decay back to an equilibrium state from either the longitudinal or transverse plane. Magnetization builds up along the z-axis in the presence of a magnetic field, B 0 , such that the magnetic dipoles in the sample will, on average, align with the z-axis summing to

9471-405: The formation of cancer fusion cells (CFCs). Understanding the enigma of cancer cell spread to distant sites, which accounts for over 90% of cancer-related deaths, necessitates comprehensive investigation. Key outstanding questions revolve around the survival and migration of cancer cells, such as the nucleus, as they face challenges in passage through capillary valves and hydrodynamic shear forces in

9594-516: The functional and structural brain abnormalities in psychological disorders. MRI also is used in guided stereotactic surgery and radiosurgery for treatment of intracranial tumors, arteriovenous malformations, and other surgically treatable conditions using a device known as the N-localizer . New tools that implement artificial intelligence in healthcare have demonstrated higher image quality and morphometric analysis in neuroimaging with

9717-455: The genetic state of the primary tumor reflects the ability of that cancer to metastasize. Research comparing gene expression between primary and metastatic adenocarcinomas identified a subset of genes whose expression could distinguish primary tumors from metastatic tumors, dubbed a "metastatic signature." Up-regulated genes in the signature include: SNRPF , HNRPAB , DHPS and securin . Actin , myosin and MHC class II down-regulation

9840-463: The haematogenous route. This is typical route of metastasis for sarcomas, but it is also the favored route for certain types of carcinoma, such as renal cell carcinoma originating in the kidney and follicular carcinomas of the thyroid. Because of their thinner walls, veins are more frequently invaded than are arteries, and metastasis tends to follow the pattern of venous flow . That is, hematogenous spread often follows distinct patterns depending on

9963-567: The heart can be reduced by timing the MRI pulse according to heart cycles. Blood vessels flow artifacts can be reduced by applying saturation pulses above and below the region of interest. Hepatobiliary MR is used to detect and characterize lesions of the liver , pancreas , and bile ducts . Focal or diffuse disorders of the liver may be evaluated using diffusion-weighted , opposed-phase imaging and dynamic contrast enhancement sequences. Extracellular contrast agents are used widely in liver MRI, and newer hepatobiliary contrast agents also provide

10086-407: The high energy at the focus, the temperature rises to above 65 °C (150 °F) which completely destroys the tissue. This technology can achieve precise ablation of diseased tissue. MR imaging provides a three-dimensional view of the target tissue, allowing for the precise focusing of ultrasound energy. The MR imaging provides quantitative, real-time, thermal images of the treated area. This allows

10209-540: The high-gyromagnetic-ratio hydrogen nucleus instead of the low-gyromagnetic-ratio nucleus that is bonded to the hydrogen atom. In principle, heteronuclear magnetization transfer MRI could be used to detect the presence or absence of specific chemical bonds. Multinuclear imaging is primarily a research technique at present. However, potential applications include functional imaging and imaging of organs poorly seen on H MRI (e.g., lungs and bones) or as alternative contrast agents. Inhaled hyperpolarized He can be used to image

10332-417: The image contrast in a typical scan. The standard display of MR images is to represent fluid characteristics in black-and-white images, where different tissues turn out as follows: MRI has a wide range of applications in medical diagnosis and around 50,000 scanners are estimated to be in use worldwide. MRI affects diagnosis and treatment in many specialties although the effect on improved health outcomes

10455-413: The immune contexture, so as to foster a favourable microenvironment for secondary tumour growth. It is theorized that metastasis always coincides with a primary cancer, and, as such, is a tumor that started from a cancer cell or cells in another part of the body. However, over 10% of patients presenting to oncology units will have metastases without a primary tumor found. In these cases, doctors refer to

10578-578: The independent relaxation processes of T 1 ( spin-lattice ; that is, magnetization in the same direction as the static magnetic field) and T 2 ( spin-spin ; transverse to the static magnetic field). To create a T 1 -weighted image, magnetization is allowed to recover before measuring the MR signal by changing the repetition time (TR). This image weighting is useful for assessing the cerebral cortex, identifying fatty tissue, characterizing focal liver lesions, and in general, obtaining morphological information, as well as for post-contrast imaging. To create

10701-567: The legs (called a "run-off"). A variety of techniques can be used to generate the pictures, such as administration of a paramagnetic contrast agent ( gadolinium ) or using a technique known as "flow-related enhancement" (e.g., 2D and 3D time-of-flight sequences), where most of the signal on an image is due to blood that recently moved into that plane (see also FLASH MRI ). Techniques involving phase accumulation (known as phase contrast angiography) can also be used to generate flow velocity maps easily and accurately. Magnetic resonance venography (MRV)

10824-462: The location of the primary tumor. For example, colorectal cancer spreads primarily through the portal vein to the liver. Some tumors, especially carcinomas may metastasize along anatomical canalicular spaces. These spaces include for example the bile ducts, the urinary system, the airways and the subarachnoid space . The process is similar to that of transcoelomic spread. However, often it remains unclear whether simultaneously diagnosed tumors of

10947-430: The metastatic cascade involve a number of physical processes. Cell migration requires the generation of forces, and when cancer cells transmigrate through the vasculature, this requires physical gaps in the blood vessels to form. Besides forces, the regulation of various types of cell-cell and cell-matrix adhesions is crucial during metastasis. The metastatic steps are critically regulated by various cell types, including

11070-723: The metastatic outgrowth of disseminated tumor cells. Metastases display alterations in histone modifications, such as H3K4-methylation and H3K9-methylation, when compared to matching primary tumors. These epigenetic modifications in metastases may allow the proliferation and survival of disseminated tumor cells in distant organs. A recent study shows that PKC-iota promotes melanoma cell invasion by activating Vimentin during EMT. PKC-iota inhibition or knockdown resulted in an increase in E-cadherin and RhoA levels while decreasing total Vimentin, phosphorylated Vimentin (S39) and Par6 in metastatic melanoma cells. These results suggested that PKC-ι

11193-453: The metastatic pathway of cancer: the epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) hypothesis (1), the cancer stem cell hypothesis (2), and the macrophage–cancer cell fusion hybrid hypothesis (3). Some new hypotheses were suggested as well, i.e., under the effect of particular biochemical and/or physical stressors, cancer cells can undergo nuclear expulsion with subsequent macrophage engulfment and fusion, with

11316-405: The most streamlined of MRI sequences , there are physical and physiologic limits to the rate of gradient switching. Parallel MRI circumvents these limits by gathering some portion of the data simultaneously, rather than in a traditional sequential fashion. This is accomplished using arrays of radiofrequency (RF) detector coils, each with a different 'view' of the body. A reduced set of gradient steps

11439-486: The musculoskeletal system include spinal imaging , assessment of joint disease, and soft tissue tumors . Also, MRI techniques can be used for diagnostic imaging of systemic muscle diseases including genetic muscle diseases. Swallowing movement of throat and oesophagus can cause motion artifact over the imaged spine. Therefore, a saturation pulse applied over this region the throat and oesophagus can help to avoid this artifact. Motion artifact arising due to pumping of

11562-608: The neoplasm and its clinical presentations may cause a majority of patients to experience a diagnostic delay. A 2019 research study found out of 214 patients a range between less than a year to 42 years before diagnosis (median, four years) from patients noticing a symptom to diagnosis. Currently, a majority of patients (53%) receive a misdiagnosis by health care providers. The most frequent prebiopsy clinical suspicion included cyst (101 [47.2%]), lipoma (30 [14.0%]), and scar (17 [7.9%]). It has been suggested an alternative term for DFSP should be dermatofibrosarcoma, often protuberant. It

11685-414: The opportunity to perform functional biliary imaging. Anatomical imaging of the bile ducts is achieved by using a heavily T2-weighted sequence in magnetic resonance cholangiopancreatography (MRCP). Functional imaging of the pancreas is performed following administration of secretin . MR enterography provides non-invasive assessment of inflammatory bowel disease and small bowel tumors. MR-colonography may play

11808-414: The organ gets a metastatic disease it begins to shrink until its lymph nodes burst, or undergo lysis . Metastatic tumors are very common in the late stages of cancer. The spread of metastasis may occur via the blood or the lymphatics or through both routes. The most common sites of metastases are the lungs , liver , brain , and the bones Currently, three main theories have been proposed to explain

11931-480: 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

12054-717: The parallel imaging methods in most common use today. The advent of parallel MRI resulted in extensive research and development in image reconstruction and RF coil design, as well as in a rapid expansion of the number of receiver channels available on commercial MR systems. Parallel MRI is now used routinely for MRI examinations in a wide range of body areas and clinical or research applications. Most MRI focuses on qualitative interpretation of MR data by acquiring spatial maps of relative variations in signal strength which are "weighted" by certain parameters. Quantitative methods instead attempt to determine spatial maps of accurate tissue relaxometry parameter values or magnetic field, or to measure

12177-466: The parameters of the pulse sequence , different contrasts may be generated between tissues based on the relaxation properties of the hydrogen atoms therein. Since its development in the 1970s and 1980s, MRI has proven to be a versatile imaging technique. While MRI is most prominently used in diagnostic medicine and biomedical research, it also may be used to form images of non-living objects, such as mummies . Diffusion MRI and functional MRI extend

12300-499: The patterns of spread could be better understood through a 'filter and flow' perspective. However, contemporary evidences indicate that the primary tumour may dictate organotropic metastases by inducing the formation of pre-metastatic niches at distant sites, where incoming metastatic cells may engraft and colonise. Specifically, exosome vesicles secreted by tumours have been shown to home to pre-metastatic sites, where they activate pro-metastatic processes such as angiogenesis and modify

12423-441: The physician to ensure that the temperature generated during each cycle of ultrasound energy is sufficient to cause thermal ablation within the desired tissue and if not, to adapt the parameters to ensure effective treatment. Hydrogen has the most frequently imaged nucleus in MRI because it is present in biological tissues in great abundance, and because its high gyromagnetic ratio gives a strong signal. However, any nucleus with

12546-457: The primary tumor and hope for improving the prognosis of these metastatic-associated cancers. Additionally, identifying the genes whose expression is changed in metastasis offers potential targets to inhibit metastasis. Treatment and survival is determined, to a great extent, by whether or not a cancer remains localized or spreads to other locations in the body. If the cancer metastasizes to other tissues or organs it usually dramatically increases

12669-440: The primary tumor as "unknown" or "occult," and the patient is said to have cancer of unknown primary origin (CUP) or unknown primary tumors (UPT). It is estimated that 3% of all cancers are of unknown primary origin. Studies have shown that, if simple questioning does not reveal the cancer's source (coughing up blood—"probably lung ", urinating blood—"probably bladder "), complex imaging will not either. In some of these cases

12792-403: The quality of life of people with major illness, has been recommended as part of management programs for metastasis. Results from a systematic review of the literature on radiation therapy for brain metastases found that there is little evidence to inform comparative effectiveness and patient-centered outcomes on quality of life, functional status, and cognitive effects. Although metastasis

12915-1012: The resulting NMR signal. The whole system is controlled by one or more computers. MRI requires a magnetic field that is both strong and uniform to a few parts per million across the scan volume. The field strength of the magnet is measured in teslas – and while the majority of systems operate at 1.5 T, commercial systems are available between 0.2 and 7 T. 3T MRI systems, also called 3 Tesla MRIs, have stronger magnets than 1.5 systems and are considered better for images of organs and soft tissue. Whole-body MRI systems for research applications operate in e.g. 9.4T, 10.5T, 11.7T. Even higher field whole-body MRI systems e.g. 14 T and beyond are in conceptual proposal or in engineering design. Most clinical magnets are superconducting magnets, which require liquid helium to keep them at low temperatures. Lower field strengths can be achieved with permanent magnets, which are often used in "open" MRI scanners for claustrophobic patients. Lower field strengths are also used in

13038-629: The same chances of metastasis. Myxoid DFSP has areas of myxoid degeneration in the stroma . Giant cell fibroblastoma contains giant cells , and is also known as juvenile DFSP. Giant cell fibroblastomas are skin and soft-tissue tumors that usually arise in childhood. They are sometimes seen in association with dermatofibrosarcoma protuberans (DFSP, hybrid lesions) or may transform or recur as DFSP. Atrophic DFSP resemble other benign lesions such as morphea , idiopathic atrophoderma, atrophic scar, anetoderma or lipoatrophy . It behaves like classic DFSP. It commonly favours young to middle-aged adults. It has

13161-487: The same whether they are found in the breast or have spread to another part of the body. So, if a tissue sample taken from a tumor in the lung contains cells that look like breast cells, the doctor determines that the lung tumor is a secondary tumor. Still, the determination of the primary tumor can often be very difficult, and the pathologist may have to use several adjuvant techniques, such as immunohistochemistry , FISH ( fluorescent in situ hybridization ), and others. Despite

13284-680: The sample or patient. The spatial resolution is much lower (limited by the available SNR ), but the spectra in each voxel contains information about many metabolites. Because the available signal is used to encode spatial and spectral information, MRSI requires high SNR achievable only at higher field strengths (3 T and above). The high procurement and maintenance costs of MRI with extremely high field strengths inhibit their popularity. However, recent compressed sensing -based software algorithms ( e.g. , SAMV ) have been proposed to achieve super-resolution without requiring such high field strengths. Real-time magnetic resonance imaging (RT-MRI) refers to

13407-403: The scan to remove the agent from the body promptly. In Europe, where more gadolinium-containing agents are available, a classification of agents according to potential risks has been released. In 2008, a new contrast agent named gadoxetate , brand name Eovist (US) or Primovist (EU), was approved for diagnostic use: This has the theoretical benefit of a dual excretion path. An MRI sequence

13530-668: The sensitivity of the contrast agents, these targeting moieties are usually linked to high payload MRI contrast agents or MRI contrast agents with high relaxivities. A new class of gene targeting MR contrast agents has been introduced to show gene action of unique mRNA and gene transcription factor proteins. These new contrast agents can trace cells with unique mRNA, microRNA and virus; tissue response to inflammation in living brains. The MR reports change in gene expression with positive correlation to TaqMan analysis, optical and electron microscopy. It takes time to gather MRI data using sequential applications of magnetic field gradients. Even for

13653-604: The size of certain spatial features. Examples of quantitative MRI methods are: Quantitative MRI aims to increase the reproducibility of MR images and interpretations, but has historically require longer scan times. Quantitative MRI (or qMRI) sometimes more specifically refers to multi-parametric quantitative MRI, the mapping of multiple tissue relaxometry parameters in a single imaging session. Efforts to make multi-parametric quantitative MRI faster have produced sequences which map multiple parameters simultaneously, either by building separate encoding methods for each parameter into

13776-455: The spin magnetization vector will slowly return from the xy-plane back to the equilibrium state. The time it takes for the magnetization vector to return to its equilibrium value, M z , is referred to as the longitudinal relaxation time, T 1 . Subsequently, the rate at which this happens is simply the reciprocal of the relaxation time: 1 T 1 = R 1 {\displaystyle {\frac {1}{T1}}=R1} . Similarly,

13899-405: The surface of the peritoneal , pleural , pericardial, or subarachnoid spaces. For example, ovarian tumors can spread transperitoneally to the surface of the liver. Lymphatic spread allows the transport of tumor cells to regional lymph nodes near the primary tumor and ultimately, to other parts of the body. This is called nodal involvement, positive nodes, or regional disease. "Positive nodes"

14022-484: The time in which it takes for M xy to return to zero is T 2 , with the rate 1 T 2 = R 2 {\displaystyle {\frac {1}{T2}}=R2} . Magnetization as a function of time is defined by the Bloch equations . T 1 and T 2 values are dependent on the chemical environment of the sample; hence their utility in MRI. Soft tissue and muscle tissue relax at different rates, yielding

14145-551: The tissue they accumulate in, or super-paramagnetic (SPIONs), and are used to shorten T2 and T2* in healthy tissue reducing its signal intensity (negative contrast agents). The most commonly used intravenous contrast agents are based on chelates of gadolinium , which is highly paramagnetic. In general, these agents have proved safer than the iodinated contrast agents used in X-ray radiography or CT. Anaphylactoid reactions are rare, occurring in approx. 0.03–0.1%. Of particular interest

14268-415: The tumor might just be too small and/or in an unusual location to be diagnosed. The cells in a metastatic tumor resemble those in the primary tumor. Once the cancerous tissue is examined under a microscope to determine the cell type, a doctor can usually tell whether that type of cell is normally found in the part of the body from which the tissue sample was taken. For instance, breast cancer cells look

14391-476: The type of primary cancer, the size and location of the metastases, the patient's age and general health, and the types of treatments used previously. In patients diagnosed with CUP it is often still possible to treat the disease even when the primary tumor cannot be located. Current treatments are rarely able to cure metastatic cancer though some tumors, such as testicular cancer and thyroid cancer , are usually curable. Palliative care , care aimed at improving

14514-447: The use of techniques, in some cases the primary tumor remains unidentified. Metastatic cancers may be found at the same time as the primary tumor, or months or years later. When a second tumor is found in a patient that has been treated for cancer in the past, it is more often a metastasis than another primary tumor. It was previously thought that most cancer cells have a low metastatic potential and that there are rare cells that develop

14637-400: The utility of MRI to capture neuronal tracts and blood flow respectively in the nervous system, in addition to detailed spatial images. The sustained increase in demand for MRI within health systems has led to concerns about cost effectiveness and overdiagnosis . In most medical applications, hydrogen nuclei, which consist solely of a proton , that are in tissues create a signal that

14760-487: Was also associated with the signature. Additionally, the metastatic-associated expression of these genes was also observed in some primary tumors, indicating that cells with the potential to metastasize could be identified concurrently with diagnosis of the primary tumor. Recent work identified a form of genetic instability in cancer called chromosome instability (CIN) as a driver of metastasis. In aggressive cancer cells, loose DNA fragments from unstable chromosomes spill in

14883-475: Was analyzed using radiography and a scanning electron microscope. These findings were published in the Public Library of Science journal. Metastasis is a Greek word meaning "displacement", from μετά, meta , "next", and στάσις, stasis , "placement". Magnetic resonance imaging Magnetic resonance imaging ( MRI ) is a medical imaging technique used in radiology to form pictures of

15006-439: Was only 0.98. In another experiment they found that elasticity of melanoma cells is important for its metastasis and growth: non-pigmented tumors were bigger than pigmented and it was much easier for them to spread. They showed that there are both pigmented and non-pigmented cells in melanoma tumors , so that they can both be drug-resistant and metastatic. The first physician to report the possibility of local metastasis from

15129-484: Was the gold standard for treating DFSP but is currently under reevaluation. Presently in the United States, WLE may be suggested after the recurrence of MMS. Larger resection margins are suggested for WLE than MMS. Recurrence rate with WLE is about 8.5% with a lower recurrence rate related to wider excision. DFSP characteristic features are its capacity to invade surrounding tissues, to a considerable distance from

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