molar pregnancy

Gestational Trophoblastic Diseases (GTD)

Gestational trophoblastic diseases (GTDs) originate from the placental tissue and are rare tumors with a current cure rate of more than 90% with the correct diagnosis and clinical treatment. GTDs, as a rule, fall into two main categories: a) hydatidiform moles, representing abnormal hairy proliferation with chromosomal aberrations and b) rare gestational trophoblastic neoplasms (GTNs), including choriocarcinoma, trophoblastic tumors of the placental region and epithelioid trophoblastic tumor. Persistent gestational trophoblastic disease/tumor most often occurs after molar pregnancy; however, it can follow any GTD.

The hydatidiform mole was previously diagnosed in the second trimester; but it is currently diagnosed in first trimester samples, based on the availability of accurate and sensitive tests for the detection of hCG and the use of early ultrasound. Often the diagnosis is made before the appearance of classical clinical signs and symptoms. In everyday practice, histological diagnosis of GTD still has some degree of diagnostic error classification with a high degree of inter- and intra- observer variability. Studies evaluating the simultaneous use of histology with immunohistochemistry and/or genotyping, further clarified the diagnosis of hydatidiform mole. In addition to the hydrate mole, even the rarer tumors of the GTN family require a wide knowledge of clinical and histological signs, as well as the use of immunohistochemical markers aimed at various types of trophoblasts, to achieve the correct diagnosis.

Molar Pregnancies

Classification of the gestational trophoblastic disease (GTD) of WHO includes neoplasms, molar pregnancies, non-tumor lesions and abnormal (non-molar) fleecy lesions. Molar pregnancies includes a full hydrated mole (CM), a partial hydatidiform mole (PM) and an invasive mole. Hydatidiform mole is an abnormal placenta with fleecy algae and varying degrees of abnormal trophoblastic hyperplasia, which can be distinguished by means of gross morphological and histopathological examination along with cytogenetic analyzes.

The prevalence of hydatidiform mole varies depending on the country, with the highest incidence in Southeast Asia and the lowest incidence in the United States and Europe.

Significant risk factors are maternal age >40 years, previous spontaneous abortions and the previous history of the hydatidiform mole. Vitamin A deficiency and nutritional and socioeconomic factors can increase the risk of molar pregnancy.

Permanent GTD is determined by the values of hCG, which have a plateau or increase after curettage for the hydatidiform mole. Further clinical and imaging studies show that exclude invasive moles or high-risk GTD, including choriocarcinoma. Cases of constant GTD are 15-29% following CM and 0-4% after PM. It is extremely important to separate diagnostic non-molar, hypotrophic abortion from hydatidiform moles for the purposes of prognostic and clinical management.

The clinical presentation of CM has significantly changed over the past three decades. CM was once easily diagnosed in the second trimester, and some of the symptoms were common during the presentation, including a noticeable uterine enlargement, anemia, toxemia, hyperemesis, hyperthyroidism and respiratory insufficiency. However, the diagnosis is now usually done in the first trimester often before the onset of classic clinical symptoms. This is based on the availability of accurate and sensitive tests for hCG and widespread use of both transabdominal and transvaginal ultrasound.

Despite the fact that in general, gynecological pathology usually contains copies of abortions with hydropic chorionic villi, histological features of early CM (less than 12 weeks of gestational age), PM and abortion hypotrophy often overlap and have low sensitivity and specificity, especially for PM.

Development of methods for ancillary diagnostic testing, including immunohistochemical detection of imprinted genes/products, DNA ploidy analysis and, more recently, genotyping of short tandem DNA repeats (STR), has advanced the GTD research for the last three decades. Diagnostic algorithms were proposed for the pathological diagnosis of PTD with the simultaneous use of traditional histopathological evaluation and ancillary studies to improve the accuracy of diagnosis.

Gestational Trophoblastic Neoplasms

Gestational trophoblastic neoplasms (GTNs) include choriocarcinoma, trophoblastic placental tumor (PSTT), and epithelioid trophoblastic tumor (ETT). GTNs arise from different trophoblast subtypes and have unique clinical, pathological and genetic characteristics.

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