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Teratoma

From Wikipedia, the free encyclopedia
Teratoma
A small (4 cm)dermoid cystof an ovary, discovered duringcesarean section
SpecialtyGynecology,oncology
SymptomsMinimal, painless lump[1][2]
ComplicationsOvarian torsion,testicular torsion,hydrops fetalis[1][2][3]
TypesMature, immature[4]
CausesUnknown[2]
Diagnostic methodTissue biopsy[2]
Differential diagnosisLipoma,dermoid,myelomeningocele[5]
TreatmentSurgery,chemotherapy[5][6]
Frequency1 in 30,000 newborns (coccyx)[7]

Ateratomais atumormade up of several different types oftissue,such ashair,muscle,teeth,orbone.[4]Teratomata typically form in thetailbone(where it is known as asacrococcygeal teratoma),ovary,ortesticle.[4]

Symptoms

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Symptoms may be minimal if the tumor is small.[2]A testicular teratoma may present as a painless lump.[1]Complications may includeovarian torsion,testicular torsion,orhydrops fetalis.[1][2][3]

They are a type ofgerm cell tumor(a tumor that begins in the cells that give rise tospermoreggs).[4][8]They are divided into two types: mature and immature.[4]Mature teratomas includedermoid cystsand are generallybenign.[8]Immature teratomas may becancerous.[4][9]Most ovarian teratomas are mature.[10]In adults, testicular teratomas are generally cancerous.[11]Definitive diagnosis is based on atissue biopsy.[2]

Treatment of coccyx, testicular, and ovarian teratomas is generally by surgery.[5][6][12]Testicular and immature ovarian teratomas are also frequently treated withchemotherapy.[6][10]

Teratomas occur in the coccyx in about one in 30,000 newborns, making them one of the most common tumors in this age group.[5][7]Females are affected more often than males.[5]Ovarian teratomas represent about a quarter ofovarian tumorsand are typically noticed during middle age.[10]Testicular teratomas represent almost half oftesticular cancers.[13]They can occur in both children and adults.[14]The term comes from the Greek word for "monster"[15]plus the "-oma" suffix used for tumors.

Types

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Mature teratoma

[edit]
Ovarian teratoma with hair inside
Mature teratoma of the mediastinum: A horizontal slice of the resected tumor reveals fibrofatty tissue, calcified areas, and a few cystic spaces lined with smooth membrane and containing a hair. In the left lower corner, the involved B5 bronchus is evident.

A mature teratoma is a grade 0 teratoma. They are highly variable in form and histology, and may be solid, cystic, or a combination of the two. A mature teratoma often contains several different types of tissue such asskin,muscle,andbone.Skin may surround a cyst and grow abundanthair(seedermoid cyst). Mature teratomas generally are benign, with 0.17-2% of mature cystic teratomas becoming malignant.[16]

Immature teratoma

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Immature teratoma is the malignant counterpart of the mature teratoma and contains immature tissues which typically showprimitive or embryonalneuroectodermalhistopathology. Immature teratoma has one of the lowest rates ofsomatic mutationof any tumor type and results from one of five mechanisms ofmeiotic failure.[17]

Gliomatosis peritoneii

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Gliomatosis peritoneii, which presents as a deposition of mature glial cells in the peritoneum, is almost exclusively seen in conjunction with cases of ovarian teratoma. Through genetic studies of exome sequence, it was found that gliomatosis is genetically identical to the parent ovarian tumor and developed from cells that disseminate from the ovarian teratoma.[17]

Dermoid cyst

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Adermoid cystis a mature cystic teratoma containing hair (sometimes very abundant) and other structures characteristic of normal skin and other tissues derived from theectoderm.The term is most often applied to teratoma on the skull sutures and in the ovaries of females.[citation needed]

Fetusin fetuand fetiform teratoma

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Fetusin fetuand fetiform teratoma are rare forms of mature teratomas that include one or more components resembling a malformed fetus. Both forms may contain or appear to contain complete organ systems, even major body parts, such as a torso or limbs. Fetusin fetudiffers from fetiform teratoma in having an apparentspineandbilateral symmetry.[18]

Most authorities agree that fetiform teratomas are highly developed mature teratomas; the natural history of fetusin fetuis controversial.[18]It has been noted that fetiform teratoma is reported more often (by gynecologists) in ovarian teratomas, and fetusin fetuis reported more often (by general surgeons) in retroperitoneal teratomas. Fetusin fetuhas often been interpreted as afetusgrowing within itstwin.As such, this interpretation assumes a special complication oftwinning,one of several grouped under the termparasitic twin.In many cases, the fetusin fetuis reported to occupy a fluid-filled cyst within a mature teratoma.[19][20][21][22]Cysts within mature teratomas may have partially-developed organ systems: reports include cases of partialcranial bones,long bonesand a rudimentary, beating heart.[23][24]

Regardless of whether fetusin fetuand fetiform teratoma are one entity or two, they are distinct from and not to be confused withectopic pregnancy.

Struma ovarii

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Main article:Struma ovarii

A struma ovarii (also known asgoitreof the ovary or ovarian goiter) is a rare form of mature teratoma that contains mostlythyroidtissue.[25]

Epignathus

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Main article:Epignathus

Epignathus is a rare teratoma originating in the oropharyngeal area that occursin utero.It presents with a mass protruding from the mouth at birth. Untreated, breathing is impossible. AnEXIT procedureis the recommended initial treatment.

Signs and symptoms

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Teratomas may be found in babies, children, and adults. Teratomas of embryonal origin are most often found in babies at birth, in young children, and, since the advent ofultrasound imaging,in fetuses.

The most diagnosed fetal teratomas aresacrococcygeal teratoma(Altman types I, II, and III) and cervical (neck) teratoma. Because these teratomas project from the fetal body into the surroundingamniotic fluid,they can be seen during routine prenatal ultrasound exams. Teratomas within the fetal body are less easily seen with ultrasound; for these, MRI of the pregnant uterus is more informative.[26][27]

Complications

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Teratomas are not dangerous for the fetus unless either amass effectoccurs or a large amount of blood flows through the tumor (known as vascular steal). The mass effect frequently consists of obstruction of normal passage of fluids from surrounding organs. The vascular steal can place a strain on the growing heart of the fetus, even resulting in heart failure, thus must be monitored by fetalechocardiography.

Teratomas can cause an autoimmune illness called N-methyl-D-aspartate (NMDA) receptor encephalitis. In this condition, the teratomas may contain B cells with NMDA-receptor specificities.[28]

After teratoma removal surgery, a risk exists of regrowth in place, or in nearby organs.[29]

Pathophysiology

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Main article:Germ cell tumor

Teratomas belong to a class of tumors known asnonseminomatousgerm cell tumor.All tumors of this class are the result of abnormal development ofpluripotentcells:germ cellsandembryonal cells.Teratomas of embryonic origin arecongenital;teratomas of germ cell origin may or may not be congenital. The kind of pluripotent cell appears to be unimportant, apart from constraining the location of the teratoma in the body.

Teratomas derived from germ cells occur in thetesticleandovaries.Teratomas derived from embryonic cells usually occur on the subject's midline: in the brain, elsewhere in theskull,in the nose, in the tongue, under the tongue, and in theneck(cervical teratoma),mediastinum,retroperitoneum,and attached to thecoccyx.Teratomas may also occur elsewhere: very rarely in solid organs (most notably the heart and liver) and hollow organs (such as the stomach and bladder), and more commonly on theskull sutures.

Teratoma rarely include more complicated body parts such asteeth,brain matter,[30]eyes,[31][32]ortorso.[33]

Hypotheses of origin

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Concerning the origin of teratomas, numerous hypotheses exist.[18]These hypotheses are not to be confused with the unrelated hypothesis that fetusin fetu(see below) is not a teratoma at all, but rather aparasitic twin.

Diagnosis

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CT showing a teratoma of the ovary: fatty formation with a smooth boundary, with a dense part, possibly a tooth.
Micrographof a teratoma showing tissue from all threegerm layers:mesoderm(immaturecartilage- left-upper),endoderm(gastrointestinal glands - center-bottom) andectoderm(epidermis - right)

Teratomas are thought to originatein utero,so can be consideredcongenitaltumors. Many teratomas are not diagnosed until much later in childhood or in adulthood. Large tumors are more likely to be diagnosed early on. Sacrococcygeal and cervical teratomas are often detected by prenatalultrasound.Additional diagnostic methods may include prenatalmagnetic resonance imaging.In rare circumstances, the tumor is so large that the fetus may be damaged or die. In the case of large sacrococcygeal teratomas, a significant portion of the fetus'blood flowis redirected toward the teratoma (a phenomenon calledsteal syndrome), causingheart failure,orhydrops,of the fetus. In certain cases,fetal surgerymay be indicated.

Beyond the newborn period, symptoms of a teratoma depend on its location and organ of origin. Ovarian teratomas often present with abdominal orpelvic pain,caused bytorsionof the ovary or irritation of its ligaments. A recently discovered condition where ovarian teratomas cause encephalitis associated with antibodies against theN-methyl-D-aspartatereceptor antibody (NMDAR) - often referred to as "anti-NMDA receptor encephalitis",was identified as a serious complication. Patients develop a multistage illness that progresses from psychosis, memory deficits, seizures, and language disintegration into a state of unresponsiveness with catatonic features often associated with abnormal movements, and autonomic and breathing instability.[34]Testicular teratomas present as a palpable mass in the testis;mediastinalteratomas often cause compression of the lungs or the airways and may present withchest painand/or respiratory symptoms.

Some teratomas containyolk sacelements, which secreteAlpha -fetoprotein.Its detection may help to confirm the diagnosis and is often used as a marker for recurrence or treatment efficacy, but is rarely the method of initial diagnosis. (Maternal serumAlpha -fetoproteinis a usefulscreening testfor other fetal conditions, includingDown syndrome,spina bifida,andabdominal walldefects such asgastroschisis.)

Classification

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Regardless of location in the body, a teratoma is classified according to acancer stagingsystem. This indicates whetherchemotherapyorradiation therapymay be needed in addition to surgery. Teratomas commonly are classified using theGonzalez-Crussi[18]grading system: 0 or mature (benign); 1 or immature, probably benign; 2 or immature, possiblymalignant(cancerous); and 3 or frankly malignant. If frankly malignant, the tumor is a cancer for which additional cancer staging applies.[citation needed]

Teratomas are also classified by their content; a solid teratoma contains only tissues (perhaps including more complex structures); a cystic teratoma contains only pockets of fluid or semifluid such ascerebrospinal fluid,sebum,or fat; a mixed teratoma contains both solid and cystic parts. Cystic teratomas usually are grade 0 and, conversely, grade 0 teratomas usually are cystic.

Grades 0, 1, and 2 pure teratomas have the potential to become malignant (grade 3), and malignant pure teratomas have the potential tometastasize.These rare forms of teratoma with malignant transformation may contain elements of somatic (not germ cell) malignancy such asleukemia,carcinoma,orsarcoma.[35] A teratoma may contain elements of other germ cell tumors, in which case it is not a pure teratoma, but rather is a mixedgerm cell tumorand is malignant. In infants and young children, these elements usually areendodermal sinus tumor,followed bychoriocarcinoma.Finally, a teratoma can be pure and not malignant yet highly aggressive; this is exemplified by growing teratoma syndrome, in which chemotherapy eliminates the malignant elements of a mixed tumor, leaving pure teratoma, which paradoxically begins to grow very rapidly.[36]

Malignant transformation

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A "benign" grade 0 (mature) teratoma nonetheless has a risk of malignancy. Recurrence with malignantendodermal sinus tumorhas been reported in cases of formerly benign mature teratoma,[37][38]even in fetiform teratoma and fetus in fetu.[39][40]Squamous cell carcinomahas been found in a mature cystic teratoma at the time of initial surgery.[41]A grade 1 immature teratoma that appears to be benign (e.g., because AFP is not elevated) has a much higher risk of malignancy, and requires adequate follow-up.[42][43][44][45] This grade of teratoma also may be difficult to diagnose correctly. It can be confused with other small round cell neoplasms such as neuroblastoma, small cell carcinoma of hypercalcemic type, primitive neuroectodermal tumor, Wilm's tumor, desmoplastic small round cell tumor, and non-Hodgkinlymphoma.[46]

A teratoma with malignant transformation is a very rare form of teratoma that may contain elements of somatic malignant tumors such as leukemia, carcinoma, or sarcoma.[35]Of 641 children with pure teratoma, nine developed TMT:[47]five carcinoma, twoglioma,and two embryonal carcinoma (here, these last are classified among germ cell tumors).

Extraspinal ependymoma

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Extraspinalependymoma,usually considered to be a glioma (a type of nongerm cell tumor), may be an unusual form of mature teratoma.[48]

Treatment

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Surgery

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The treatment of choice is complete surgical removal (i.e.,complete resection).[49][50]Teratomas are normally well-encapsulated and noninvasive of surrounding tissues, hence they are relatively easy to resect from surrounding tissues. Exceptions include teratomas in the brain, and very large, complex teratomas that have pushed into and become interlaced with adjacent muscles and other structures.

Prevention of recurrence does not requireen blocresection of surrounding tissues.

Chemotherapy

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For malignant teratomas, usually, surgery is followed by chemotherapy.

Teratomas that are in surgically inaccessible locations, or are very complex, or are likely to be malignant (due to late discovery and/or treatment) sometimes are treated first with chemotherapy.[citation needed]

Follow-up

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Although often described as benign, a teratoma does have malignant potential. A UK study of 351 infants and children diagnosed with "benign" teratoma reported 227 with MT, 124 with IT. Five years after surgery, event-free survival was 92.2% and 85.9%, respectively, and overall survival was 99% and 95.1%.[51]A similar study in Italy reported on 183 infants and children diagnosed with teratoma. At 10 years after surgery, event-free and overall survival were 90.4% and 98%, respectively.[52]

Depending on which tissue(s) it contains, a teratoma may secrete a variety of chemicals with systemic effects. Some teratomas secrete the "pregnancy hormone"human chorionic gonadotropin(βhCG), which can be used in clinical practice to monitor the successful treatment or relapse in patients with a known HCG-secreting teratoma. This hormone is not recommended as a diagnostic marker, because most teratomas do not secrete it. Some teratomas secretethyroxine,in some cases to such a degree that it can lead to clinicalhyperthyroidismin the patient. Of special concern is the secretion ofAlpha -fetoprotein(AFP); under some circumstances, AFP can be used as a diagnostic marker specific for the presence ofyolk saccells within the teratoma. These cells can develop into a frankly malignant tumor known asyolk sac tumororendodermal sinus tumor.

Adequate follow-up requires close observation, involving repeated physical examination, scanning (ultrasound, MRI, or CT), and measurement of AFP and/or βhCG.[53][54]

Epidemiology

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Ovarian tumorsbyincidenceand risk ofovarian cancer,with mature cystic teratoma at bottom andimmature teratomaat right.[55]

Embryonal teratomas most commonly occur in the sacrococcygeal region;sacrococcygeal teratomais the single most common tumor found in newborn humans.

Of teratomas on the skull sutures, about 50% are found in or adjacent to theorbit.[56]Limbal dermoid is achoristoma,not a teratoma.

Teratoma qualifies as arare disease,but is not extremely rare. Sacrococcygeal teratoma alone is diagnosed at birth in one out of 40,000 humans. Given the current human population and birth rate, this equals five per day or 1800 per year. Add to that number sacrococcygeal teratomas diagnosed later in life, and teratomas in other locales, and theincidenceapproaches 10,000 new diagnoses of teratoma per year.[citation needed]

Other animals

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Ovarian teratomas have been reported inmares,[57] mountain lions,[58][59]and canines.[60]Teratomas also occur, rarely, in other species.[61]

Use in stem cell research

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Pluripotent stem cells including human induced pluripotent stem cells have a unique property of being able to generate teratomas when injected in rodents in the research laboratory.[62]The roots of this observation has been attributed toLeroy Stevensof theJackson Laboratory.[63]In 1970, Stevens noticed that the cell populations that gave rise to teratomas were very similar to the cells of very early embryos. For this reason, the so-called "teratoma assay" is one of the gold-standard validation assays for pluripotent stem cells.[64]Because differentiated human pluripotent stem cells are being developed as the basis for numerous regenerative medicine therapies, there is concern that residual undifferentiated stem cells could lead to teratoma formation in injected patients, and researchers are working to develop methods to address this concern.[65]

New research has looked at utilizing the human teratoma in chimeric animal studies as a promising platform for modeling multi-lineage human development, pan-tissue functional genetic screening, and tissue engineering.[66]

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Public DomainThis article incorporatespublic domain materialfromDictionary of Cancer Terms.U.S. National Cancer Institute.

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