Trophoblastic neoplasm

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Trophoblastic neoplasm
Intermediate trophoblast 3 - low mag.jpg
Micrograph of intermediate trophoblast and a hydatidiform mole (bottom of image). H&E stain.
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Gestational trophoblastic neoplasia (GTN) is group of rare diseases related to pregnancy and included in gestational trophoblastic disease (GTD) in which abnormal trophoblast cells grow in the uterus. [1] GTN can be classified into benign and malignant lesions. Benign lesions include placental site nodule and hydatidiform moles while malignant lesions have [2] four subtypes including invasive mole, gestational choriocarcinoma, placental site trophoblastic tumor (PSTT) and epithelioid trophoblastic tumor (ETT). [3] The choriocarcinoma has 2 significant subtypes including gestational and non-gestational and they are differentiated by their different biological feature and prognosis. [4] Signs and symptoms of GTN will appear vary from person to person and depending upon the type of the disease. They may include uterine bleeding not related to menstruation, pain or pressure in pelvis, large uterus and high blood pressure during pregnancy. The cause of this disease is unknown but the identification of the tumor based on total beta-human chorionic gonadotropin (β-hCG) in the serum.

Contents

Management of GTN requires pathology review, treatment options and monitoring of hCG. Therefore, it can be treated with curettage, hysterectomy and single agent or multi agent chemotherapy. [4] Although this group of diseases are highly susceptible to chemotherapy, prognosis depends on the type of GTN and whether the tumor has spread to other areas of the body. [5]

Cause and Risk factors

The exact cause of gestational trophoblastic neoplasia (GTN) is unknown. GTN often arises after molar pregnancies but can also occur after any gestation including miscarriages and term pregnancies. [6] Although risk factors may impact on the development of the tumor, most do not directly cause of disease. According to some studies, the risk of complete molar pregnancy is highest in women over age 35 and younger than 20. The risk is even higher for women over age 45. [7] [8]

Signs and Symptoms

The symptoms of GTN will vary from person to person. People with the same disease may not have all the symptoms listed.[ citation needed ]

Diagnosis

Initial screening tests for GTN include:

Tumor staging

FIGO (International Federation of Gynecology and Obstetrics) 2000 Anatomical staging is commonly used to evaluate stage of GTN.

Stage I - Disease confined to the uterus

Stage II - GTN extends outside of the uterus, but is limited to the genital structures (adnexa, vagina, broad ligament)

Stage III - GTN extends to the lungs, with or without known genital tract involvement

Stage IV - All other metastatic sites [14]

Pathophysiology

High magnification micrograph of choriocarcinoma. H&E stain. Choriocarcinoma -2- high mag.jpg
High magnification micrograph of choriocarcinoma . H&E stain.

All types of gestational trophoblastic neoplasia originate from the placenta. A placenta develops in the uterus during pregnancy and becomes first site of nutrient and gas exchange between mother and fetus. It has two components such as fetal component and mother component. A fetal component is composed of cytotrophoblast and syncytiotrophoblast. [15] The exact pathogenesis of choriocarcinoma has not been fully understood, but studies have shown cytotrophoblast cells function as stem cells and transform into malignant form. The neoplastic cytotrophoblast further differentiates into either intermediate trophoblasts or syncytiotrophoblast.[ citation needed ]

Treatment

Several treatment methods are available for GTN that include surgery, chemotherapy or combination of these. Surgery treatment is most common initial method for some types of the disease but it depends on the stage of the tumor. Common surgical options include dilation and curettage, and hysterectomy.

Prognosis

FIGO modified Prognostic Scoring System. The system evaluates the patients to those with GTN as low-risk and high-risk based on several risk factors such as age, pregnancy or interval of pregnancies, size or metastases of tumor and prior chemotherapy. Each risk factors are rated at levels 0-4 scores. The numbers are then added up, and the overall score determines a woman's risk level.

Therefore, some studies have shown that the condition is harder to cure if the cancer has spread to the liver or brain or β-hCG level is higher than 40,000 mIU/mL when treatment begins, cancer returns after having chemotherapy or symptoms/ pregnancy occurred for more than 4 months before treatment. [17]

Epidemiology

According to studies, GTN is found more frequently in Asia compared to North America or Europe. [15] As of 2020, the reported incidence of choriocarcinoma ranges from 1 in 40 000 pregnancies in North America and Europe, to 9.2 and 3.3 per 40 000 pregnancies in Southeast Asia and Japan, respectively. Epidemiological studies have reported that hydatidiform mole appears to be caused by abnormal gametogenesis and fertilization more frequent at the extremes of reproductive age of younger than 15 and older than 45 years of age and pregnancies at these ages are a risk factor for hydatidiform mole. The risk increases after age 35 and there is a 5–10 times increased risk after 45 years. [18]

Research

Recently, in order to provide more comprehension tools of GTN pathogenesis, epigenetic modifications and molecular biology techniques could be applied for proper diagnosis, management, and treatment of such neoplasia. The progression of anti-angiogenesis therapy and molecular targeted cancer therapies would be capable of improving the therapeutic perspective among patients with drug resistance. [19] Although chemotherapy and hysterectomy are currently used in a clinical setting, the use of diverse treatments including anti-body and gene therapy also being attempted to cure GTN. In addition, gene delivery tools using genetically engineered neural stem cells are presently being examined for the treatment of GTN and previous studies have indicated a significant inhibitory effect on tumor growth. [20]

Related Research Articles

<span class="mw-page-title-main">Ectopic pregnancy</span> Female reproductive system health issue

Ectopic pregnancy is a complication of pregnancy in which the embryo attaches outside the uterus. Signs and symptoms classically include abdominal pain and vaginal bleeding, but fewer than 50 percent of affected women have both of these symptoms. The pain may be described as sharp, dull, or crampy. Pain may also spread to the shoulder if bleeding into the abdomen has occurred. Severe bleeding may result in a fast heart rate, fainting, or shock. With very rare exceptions, the fetus is unable to survive.

<span class="mw-page-title-main">Testicular cancer</span> Medical condition

Testicular cancer is cancer that develops in the testicles, a part of the male reproductive system. Symptoms may include a lump in the testicle or swelling or pain in the scrotum. Treatment may result in infertility.

<span class="mw-page-title-main">Human chorionic gonadotropin</span> Hormone

Human chorionic gonadotropin (hCG) is a hormone for the maternal recognition of pregnancy produced by trophoblast cells that are surrounding a growing embryo, which eventually forms the placenta after implantation. The presence of hCG is detected in some pregnancy tests. Some cancerous tumors produce this hormone; therefore, elevated levels measured when the patient is not pregnant may lead to a cancer diagnosis and, if high enough, paraneoplastic syndromes, however, it is not known whether this production is a contributing cause, or an effect of carcinogenesis. The pituitary analog of hCG, known as luteinizing hormone (LH), is produced in the pituitary gland of males and females of all ages.

<span class="mw-page-title-main">Trophoblast</span> Early embryonic structure that gives rise to the placenta

The trophoblast is the outer layer of cells of the blastocyst. Trophoblasts are present four days after fertilization in humans. They provide nutrients to the embryo and develop into a large part of the placenta. They form during the first stage of pregnancy and are the first cells to differentiate from the fertilized egg to become extraembryonic structures that do not directly contribute to the embryo. After blastulation, the trophoblast is contiguous with the ectoderm of the embryo and is referred to as the trophectoderm. After the first differentiation, the cells in the human embryo lose their totipotency because they can no longer form a trophoblast. They become pluripotent stem cells.

<span class="mw-page-title-main">Molar pregnancy</span> Abnormal form of pregnancy (human disorder)

A molar pregnancy, also known as a hydatidiform mole, is an abnormal form of pregnancy in which a non-viable fertilized egg implants in the uterus. It falls under the category of gestational trophoblastic diseases. During a molar pregnancy, the uterus contains a growing mass characterized by swollen chorionic villi, resembling clusters of grapes. The occurrence of a molar pregnancy can be attributed to the fertilized egg lacking an original maternal nucleus. As a result, the products of conception may or may not contain fetal tissue. These molar pregnancies are categorized into two types: partial moles and complete moles, where the term 'mole' simply denotes a clump of growing tissue or a ‘growth'.

<span class="mw-page-title-main">Choriocarcinoma</span> Malignant, trophoblastic cancer, usually of the placenta

Choriocarcinoma is a malignant, trophoblastic cancer, usually of the placenta. It is characterized by early hematogenous spread to the lungs. It belongs to the malignant end of the spectrum in gestational trophoblastic disease (GTD). It is also classified as a germ cell tumor and may arise in the testis or ovary.

<span class="mw-page-title-main">Gestational trophoblastic disease</span> Pregnancy-related tumours

Gestational trophoblastic disease (GTD) is a term used for a group of pregnancy-related tumours. These tumours are rare, and they appear when cells in the womb start to proliferate uncontrollably. The cells that form gestational trophoblastic tumours are called trophoblasts and come from tissue that grows to form the placenta during pregnancy.

Gestational choriocarcinoma is a form of gestational trophoblastic neoplasia, which is a type of gestational trophoblastic disease (GTD), that can occur during pregnancy. It is a rare disease where the trophoblast, a layer of cells surrounding the blastocyst, undergoes abnormal developments, leading to trophoblastic tumors. The choriocarcinoma can metastasize to other organs, including the lungs, kidney, and liver. The amount and degree of choriocarcinoma spread to other parts of the body can vary greatly from person to person.

<span class="mw-page-title-main">Complications of pregnancy</span> Medical condition

Complications of pregnancy are health problems that are related to, or arise during pregnancy. Complications that occur primarily during childbirth are termed obstetric labor complications, and problems that occur primarily after childbirth are termed puerperal disorders. While some complications improve or are fully resolved after pregnancy, some may lead to lasting effects, morbidity, or in the most severe cases, maternal or fetal mortality.

<span class="mw-page-title-main">Cytotrophoblast</span>

"Cytotrophoblast" is the name given to both the inner layer of the trophoblast or the cells that live there. It is interior to the syncytiotrophoblast and external to the wall of the blastocyst in a developing embryo.

Ovarian diseases refer to diseases or disorders of the ovary.

<span class="mw-page-title-main">Placental disease</span> Medical condition

A placental disease is any disease, disorder, or pathology of the placenta.

<span class="mw-page-title-main">Interstitial pregnancy</span> Medical condition

An interstitial pregnancy is a uterine but ectopic pregnancy; the pregnancy is located outside the uterine cavity in that part of the fallopian tube that penetrates the muscular layer of the uterus. The term cornual pregnancy is sometimes used as a synonym, but remains ambiguous as it is also applied to indicate the presence of a pregnancy located within the cavity in one of the two upper "horns" of a bicornuate uterus. Interstitial pregnancies have a higher mortality than ectopics in general.

<span class="mw-page-title-main">Placental site trophoblastic tumor</span> Medical condition

Placental site trophoblastic tumor is a form of gestational trophoblastic disease, which is thought to arise from intermediate trophoblast.

Theca lutein cyst is a type of bilateral functional ovarian cyst filled with clear, straw-colored fluid. These cysts result from exaggerated physiological stimulation due to elevated levels of beta-human chorionic gonadotropin (beta-hCG) or hypersensitivity to beta-hCG. On ultrasound and MRI, theca lutein cysts appear in multiples on ovaries that are enlarged.

<span class="mw-page-title-main">Min Chiu Li</span> American physician

Min Chiu Li was a Chinese-American oncologist and cancer researcher. Li was the first scientist to use chemotherapy to cure widely metastatic, malignant cancer.

Early pregnancy bleeding refers to vaginal bleeding before 14 weeks of gestational age. If the bleeding is significant, hemorrhagic shock may occur. Concern for shock is increased in those who have loss of consciousness, chest pain, shortness of breath, or shoulder pain.

Epithelioid trophoblastic tumor (ETT) is a gestational trophoblastic disease with about 110 case reports in the literature. It is a trophoblastic tumor of neoplastic chorionic type associated with the intermediate trophoblast.

<span class="mw-page-title-main">Extracranial germ cell tumor</span> Type of tumor

An extracranial germ cell tumor (EGCT) occurs in the abnormal growth of germ cells in the gonads and the areas other than the brain via tissue, lymphatic system, or circulatory system. The tumor can be benign or malignant (cancerous) by its growth rate. According to the National Cancer Institute and St. Jude Children's Research Hospital, the chance of children who are under 15 years old having EGCTs is 3%, in comparison to adolescents, a possibility of 14% with aged 15 to 19 can have EGCTs. There is no obvious cut point in between children and adolescents. However, common cut points in researches are 11 years old and 15 years old.

Ovarian germ cell tumors (OGCTs) are heterogeneous tumors that are derived from the primitive germ cells of the embryonic gonad, which accounts for about 2.6% of all ovarian malignancies. There are four main types of OGCTs, namely dysgerminomas, yolk sac tumor, teratoma, and choriocarcinoma.

References

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  19. Sharami SR, Saffarieh E (March 2020). "A review on management of gestational trophoblastic neoplasia". Journal of Family Medicine and Primary Care. 9 (3): 1287–1295. doi: 10.4103/jfmpc.jfmpc_876_19 . PMC   7266251 . PMID   32509606.
  20. Kim GS, Hwang KA, Choi KC (March 2019). "A promising therapeutic strategy for metastatic gestational trophoblastic disease: Engineered anticancer gene-expressing stem cells to selectively target choriocarcinoma". Oncology Letters. 17 (3): 2576–2582. doi:10.3892/ol.2019.9911. PMC   6396211 . PMID   30867726.