Manejo clínico de la neoplasia trofoblástica gestacional: presentación de un caso / Clinical management of gestational trophoblastic neoplasia: presentation of a case

La enfermedad trofoblástica gestacional es una entidad poco frecuente que se produce por una proliferación anormal de la placenta. Engloba un diverso espectro de entidades histológicas, que conllevan a su vez diversas implicaciones clínicas. Unas son de carácter benigno (mola parcial y mola completa, placentomegalia, nódulo del sitio placentario) y otras de carácter maligno, estas últimas reciben en común la denominación de Neoplasia Tofoblástica Gestacional (NTG) y tienen un alto potencial de metastatización. Forman parte de las NTG: la mola invasiva, el tumor trofoblástico del sitio placentario, el tumor trofoblástico epitelioide y el coriocarcinoma gestacional. Lo más común es que la NTG debute tras la aparición de una gestación molar, pero también es posible que ocurra tras otro tipo de evento obstétrico como una gestación a término, o una gestación ectópica. Es pues de vital importancia realizar un correcto seguimiento tras evacuar una gestación molar, realizando una monitorización de los valores séricos de la BhcG y sospechando una enfermedad trofoblástica persistente ante los supuestos que posteriormente describiremos.La principal herramienta terapéutica para la NTG es el uso de la quimioterapia, aunque también se puede optar por la cirugía endeterminados casos. Habrá que valorar de modo individualizado en función de la histología, score pronóstico y deseos genésicos futuros de la paciente. Afortunadamente, la tasa de supervivencia y de curación de la NTG con un tratamiento y seguimiento adecuado es muy elevada. (AU)

Gestational trophoblastic disease is a rare entity that is caused by an abnormal proliferation of the placenta. It encompasses adiverse spectrum of histological entities, which carry various clinical implications. Some of them are benign (partial mole and complete mole, placentomegaly, placental site nodule) and others of a malignant nature, which are known as Gestational TrophoblasticNeoplasia (GTN) and have a high potential for metastasization. Are part of the GTN: invasive mole, trophoblastic tumor of theplacental site, trophoblastic tumor epithelioid and gestational choriocarcinoma. The most common is that NTG debuts after theappearance of a molar gestation, but it also may occur after another type of obstetric event such as a term gestation, or an ectopicgestation. It is therefore of vital importance to carry out a correct follow-up after evacuating a molar gestation, monitoring the serumvalues of BhcG and suspecting a persistent trophoblastic disease in the event that we will later describe. The main therapeutic toolfor NTG is the use of chemotherapy, although surgery can also be chosen in certain cases. It will be necessary to assess individuallyaccording to histology, prognostic score and future genetic desires of the patient. Fortunately, the survival and cure rate of NTG with proper treatment and follow-up is very high. (AU)

Caso Clínico: Mola Hidatiforme Parcial. Resolución Obstétrica / Case Report: Partial Hydatiform Mole Obstetric Resolution

INTRODUCCIÓN: La mola hidatiforme parcial es una enfermedad del tejido trofoblástico que se caracteriza por presentar sobrecrecimiento del mismo, con feto presente, sus manifestaciones tanto clínicas como de laboratorio indican que puede transformarse en tumor de características malignas. CASO CLÍNICO: Paciente de 28 años de edad de 17.1 Semanas de Gestación (SG) por fecha de última menstruación (FUM), con presencia de sangrado rojo rutilante hace 9 horas, vómitos postprandiales durante todo embarazo, niveles de hormona gonadotropina coriónica fracción B (BHCG) 90000 mUI/ml, ecografía que reporta placenta multiquística en patrón de racimo de uvas con presencia de feto vivo. EVOLUCIÓN: Paciente es sometida a un aborto terapéutico modo parto y legrado, presenta un valor de BHCG 25000 mUI/ml, se realiza evaluación periódica de BHCG, a los 15 días después del procedimiento presenta un nivel de BHCG de 470 mUI/ml, al mes presenta un valor de BHCG de 183 mUI/ml. Se optó por administrar manejo anticonceptivo mediante Drospirenona + Etinilestradiol mínimo por 6 meses, al segundo mes de BHCG disminuye a 86 mUI/ml, ecografía de control con reporte normal, a los 4 meses el valor de BHCG reportado es < 1 mUI/ml por lo cual oncología decide el alta médica definitiva. CONCLUSIONES: Según datos bibliográficos la presentación de la enfermedad es muy similar a la del caso expuesto, siendo una rara afección del tejido trofoblástico, que mediante un pronto diagnóstico y manejo, tuvo un desenlace y evolución favorable, llegando a una resolución completa de la enfermedad. (au)

BACKGROUND: The partial hydatidmole is a disease oftrophoblastic tissue characterized by trophoblastic overgrowth with a fetus present, both clinical and laboratory manifestations that indicate being able to transforminto a tumor ofmalignant characteristics. CASE REPORT A 28-year-old patient 17.1 gestation weeks, with red bleeding 9 hours ago, postprandial vomiting throughout pregnancy, BHCG 90000mUI/ml levels, ultrasound thatreports amulticystic placenta in the formof a honeycomb of bees with presence of vivid fetus. EVOLUTION: Patientis submitted to therapeutic abortion in themode of delivery and curettage presents a BHCG value of 25000 mUI/ml, a periodic evaluation of BHCG is performed, 15 days after the procedure has aBHCGlevel of 470mUI/ml, amonthlyBHCGvalue of 183 , it was decided to administer contraceptive management by means of Drospirenona + Etinilestradiol minimum for 6 months, the second month of BHCG decreases to 86 mUI/ml, control ultrasound with normal report, at 4 months the value of BHCG reported is < 1mUI/ml for which oncology decides high definitivemedical. CONCLUSIONS: According to bibliographical data the presentation of the disease is very similar to that of the exposed case, being a rare affection of the trophoblastic tissue, which through a prompt diagnosis and management had a favorable outcome and evolution, reaching a complete resolution ofthe disease.(au)

[Clinical and radiological features of gestational trophoblastic tumors]. / Tumeurs trophoblastiques gestationnelles: aspects cliniques et radiologiques.

Gestational trophoblastic disease incorporates a group of diseases which differ from each other by their regressive evolution, their evolution to metastasis and to recurrence. It is a severe disease that affects women of childbearing age. Gestational trophoblastic tumors (GTT) are the malignant forms of gestational trophoblastic diseases. They are always a result of pregnancy, more often molar pregnancy (hydatidiform mole). The most common type of gestational trophoblastic tumors (GTT) is the invasive mole because, in most cases, the diagnosis is made when cancer is still confined to the uterus. Choriocarcinoma is a more rare type of tumor, often developing distant metastases. When there is a progression to a trophoblastic tumor, the assessment of locoregional extension and distant metastases is essential to establish an appropriate treatment protocol. We here report three clinical cases of GTT by describing their clinical presentations and the use of imaging techniques in the diagnosis and management of these disorders.

Multicenter analysis of gestational trophoblastic neoplasia in Turkey.

BACKGROUND: To evaluate the incidence, diagnosis and management of GTN among 28 centers in Turkey. MATERIALS AND METHODS: A retrospective study was designed to include GTN patients attending 28 centers in the 10-year period between January 2003 and May 2013. Demographical characteristics of the patients, histopathological diagnosis, the International Federation of Gynecology and Obstetrics (FIGO) anatomical and prognostic scores, use of single-agent and multi-agent chemotherapy, surgical interventions and prognosis were evaluated. RESULTS: From 2003-2013, there were 1,173,235 deliveries and 456 GTN cases at the 28 centers. The incidence was calculated to be 0.38 per 1,000 deliveries. According to the evaluated data of 364 patients, the median age at diagnosis was 31 years (range, 15-59 years). A histopathological diagnosis was present for 45.1% of the patients, and invasive mole, choriocarcinoma and PSTTs were diagnosed in 22.3% (n=81), 18.1% (n=66) and 4.7% (n=17) of the patients, respectively. Regarding final prognosis, 352 (96.7%) of the patients had remission, and 7 (1.9%) had persistence, whereas the disease was mortal for 5 (1.4%) of the patients. CONCLUSIONS: Because of the differences between countries, it is important to provide national registration systems and special clinics for the accurate diagnosis and treatment of GTN.

Gestational trophoblastic disease: experience at Nawabshah Hospital.

BACKGROUND: Gestational Trophoblastic Disease (GTD) is a heterogeneous group of diseases that includes partial and complete hydatidiform mole, invasive mole, choriocarcinoma and placental site trophoblastic tumour. The incidence of GTD varies in different parts of the world. The malignant potential of this disease is higher in South East Asia in comparison to western countries. Objectives of study were to determine the frequency, clinical presentation and management outcomes of GTD. This retrospective, descriptive case series was conducted in the Department of Obstetric and Gynaecology Nawabshah Medical College Hospital, from 1st Jan 2007 to 30th Dec 2007. METHODS: The case records of all the gestational trophoblastic cases during study period were analysed regarding their history, clinical examination, investigations, treatment and follow-up. The main outcomes were measured in terms of duration, antecedent pregnancy, investigations, treatment and the follow-up. RESULTS: There were a total of 1056 Obstetric admissions during the study period, which included 30 cases of trophoblastic disease with a frequency of GTD was 28 per 1000 live births. Of these 30 cases, 21 (70%) patients had hydatidiform mole, 7 (23.3%) patients had invasive disease and 2 (6.6%) patients had choriocarcinoma. Twenty three patients (76.6%) received chemotherapy while 25 (83.3%) patients had suction evacuation and 4 (13.3%) patients underwent hysterectomy. Among all patients, 29 (96.7%) fully recovered and 1 (3.3%) died because of extensive disease; metastasis extending up to brain. CONCLUSION: Frequency of GTD was higher compared to national and international studies. The disease was common in extremes of ages, low para and grand multiparous women. Hydatidiform mole was the commonest type of trophoblastic disease in these patients. Most common presenting complaint was bleeding per vagina followed by pain in lower abdomen.

A case of metastasizing invasive hydatidiform mole. Is less--less good? Review of the literature with regard to adequate treatment.

BACKGROUND: Patients with invasive hydatidiform moles (IHM) have a good prognosis. Even if disease has spread, monocytostatic treatment might be sufficient if the diagnosis has been histologically confirmed. Established classifications divide gestational trophoblastic disease (GTD) including choriocarcinoma into cases with "high" and "low" risk. Without respect to histology "high-risk" cases are recommended to obtain polychemotherapy. CASE: A 40-year-old nullipara underwent hysterectomy for persistent vaginal bleeding after she had already been treated with curettage for hydatidiform mole. An IHM was pathohistologically confirmed. There were no signs of pulmonary spread or other metastases at the time of surgery. Postsurgically persistent beta-hCG levels lead to thorough staging, which revealed multiple pulmonary metastases and a vaginal metastasis. Despite metastasizing GTD with poor prognosis criteria she was treated with single agent therapy. Eight cycles of two weekly methotrexate (MTX) were administered. All sites of metastases responded and our patient is still fine after one year of follow-up. CONCLUSION: With respect to this and other reports monochemotherapy can be a reasonable primary treatment for metastatic IHM.

[Clinical analysis of 13 cases of gestational trophoblastic tumor misdiagnosed as ectopic pregnancy].

OBJECTIVE: To evaluate clinical-pathological features, diagnosis and therapy of gestational trophoblastic tumor (GTT) misdiagnosed as ectopic pregnancy. METHODS: From 1999 to 2003, a total of 13 patients with GTT misdiagnosed as ectopic pregnancy were retrospectively analyzed. RESULTS: The main symptoms were amenorrhea, abdominal pain, irregular vaginal bleeding. Serum beta-human chorionic gonadotrop in (hCG) was measured in 10 patients. Eight had hCG values above 10,000 IU/L; 3 had hCG values above 50,000 IU/L. The lesions of GTT misdiagnosed as ectopic pregnancy were fallopian tube, horn of uterus, peritoneal cavity, greater omentum, recto-uterine pouch. According to standards of the International Federation of Gynecology and Obstetrics (FIGO) the 13 patients were categorized as 6 of stage I, 2 of stage II, 3 of stage III and 5 of stage IV. Histologically they included 10 cases of choriocarcinoma and 3 of invasise mole. All patients were treated by complete surgical resection combined with subsequent adjuvant chemotherapy. CONCLUSIONS: Misdiagnosis leads to delay in therapy with resultant increased morbidity of GTT. Analysis on serial hCG is helpful to differential diagnosis between ectopic pregnancy and GTT.

Management of gestational trophoblastic disease in developing countries.

In Malaysia, the incidence of molar pregnancy and gestational trophoblastic neoplasia is 2.8 and 1.59 per 1000 deliveries, respectively; the disease is more common among the Chinese compared to the Malays and Indians. While uterine suction is the preferred method of uterine evacuation of hydatidiform mole, complete evacuation was not achieved at the first attempt in 25% of cases. Partial moles comprise 30% of all moles; these need follow up similar to that for complete moles as they are potentially malignant. In the management of invasive moles, chemotherapy should not be withheld in the presence of metastases or failure of regression of hCG. Placental site tumours are rare. Prophylactic hysterectomy and prophylactic chemotherapy are not recommended. However, in those patients with unsatisfactory hCG regression curves indicating 'at risk' in developing gestational trophoblastic neoplasia (GTN), 'selective preventive chemotherapy' appears appropriate. Chemotherapy remains the main modality of treatment for GTN. As tumour bulk and location of disease are important determinants in outcome, we categorized our patients into low, medium- and high-risk groups with survivals of 100, 98 and 61.7% respectively. Surgery and radiotherapy have a limited role.

Management of gestational trophoblastic diseases in Japan--a review.

In Japan we have a standardized protocol for the management of gestational trophoblastic diseases issued by the Japan Society of Obstetrics & Gynecology in 1988. Hydatidiform moles should be treated by evacuating the uterus. Patients must then be followed up until serial weekly serum hCG titres fall to undetectable levels. Our hCG regression curve post-evacuation is quite useful for the detection of persistent trophoblastic diseases. Persistent trophoblastic diseases develop in about 10-15 per cent of patients after molar evacuation in Japan. We classify persistent trophoblastic diseases into three groups: (1) post-molar persistent hCG; (2) invasive mole or metastatic moles; and (3) choriocarcinoma. Investigations into any possible metastases are carried out as soon as possible in affected patients. Post-molar persistent hCG presents no focus or histological findings except persistent elevated hCG, although single agent chemotherapy is required. In the other two groups with focus, it is very difficult to get histological specimens to make accurate diagnoses unless surgery is done. For the selection of the most appropriate chemotherapy, what we call a 'Diagnostic Score' is applied to differentiate choriocarcinoma from invasive moles or metastatic moles clinically in patients falling into these two groups. This unique 'Diagnostic Score' for the detection of choriocarcinoma plays an important role in initial management in our protocol.

Manejo de la enfermedad del trofoblasto: mola parcial y completa / Management of trophoblastic disease: partial and complete mole

Se comunican 67 pacientes con enfermedad del trofoblasto tratadas entre 1982 y 1998. Se incluyen 44 molas completas y 23 molas parciales. Un resultado relevante fue el diagnóstico de enfermedad del trofoblasto por hallazgo en el estudio anátomo-patológico sin la sospecha clínica en un 25,54 por ciento de los casos (mola completa 20,5 por ciento, mola parcial 34,8 por ciento). No hubo diferencias significativas en la clínica entre mola parcial y completa. La persistencia de enfermedad fue mayor en el grupo con mola completa. La respuesta al tratamiento primario con quimioterapia en enfermedad persistente usando monodroga fue 75 por ciento. Respecto de la fertilidad futura, 30 pacientes se embarazaron con un total de 45 embarazos con una tasa de aborto de 6,7 por ciento y de recurrencia para enfermedad molar de 2,2 por ciento

Angiographic-guided embolization of metastatic invasive mole.

BACKGROUND: The friable and hypervascular nature of a metastatic invasive mole places the patient at risk for significant hemorrhage. Bleeding is the chief cause of morbidity and mortality in patients with a histopathological diagnosis of invasive mole. Bleeding from vaginal metastatic lesions can be controlled by packing the vagina and local excision if necessary. Often the results are less than satisfactory. CASE: This case describes a 43-year-old Hispanic female with metastatic invasive mole to the vagina. Following chemotherapy, she underwent life-threatening hemorrhage requiring hospitalization and multiple transfusions. The metastatic lesions were successfully embolized with gelfoam by selective angiography. The patient required minimal additional chemotherapy and is currently without evidence of disease. CONCLUSIONS: The technique of angiographic embolization is emerging as a successful and minimally invasive procedure as illustrated in this presentation. Prophylactic embolization with or prior to the administration of chemotherapy in the management of metastatic invasive mole is discussed and may play a role in the primary therapy of this condition.

Current approaches to diagnosis and treatment of gestational trophoblastic disease.

Diagnosis of molar pregnancy relies on serum and urine human chorionic gonadotropin estimations in addition to characteristic appearances on histology. Approximately 92% of hydatidiform moles resolve spontaneously after evacuation, and with careful human chorionic gonadotropin follow-up, the remainder can be successfully treated with a minimum of toxicity. Non-post-mole gestational choriocarcinoma is also highly curable with modern chemotherapy, and in the rare cases when drug resistance develops, surgery can be an effective salvage treatment. In cases when doubt exists as to whether a patient has a true gestational tumor or a human chorionic gonadotropin-producing carcinoma, the origin of the tumor can sometimes be determined by DNA analysis. This determination can help to avoid inappropriate chemotherapy for patients with nongestational tumors.

Treatment of malignant trophoblastic tumors. An analysis of 209 cases.

From 1948 to 1985, a total of 630 cases of choriocarcinoma and invasive mole were treated in our hospital. The methods of treatment varied in different periods of time. In the third period (1972-1985), 5 Fu and/or KSM were the main therapeutic agents used in the treatment of 110 cases of choriocarcinoma and 99 cases of invasive mole. Metastases were observed in more than 90% of cases of choriocarcinoma and nearly 1/4 belonged to stage IV. The mortality of choriocarcinoma decreased from 84.3% to 32.7% after treatment and that of invasive mole from 32.4% to 8.1%. 43 of 80 patients treated with chemotherapy alone conceived after recovery, resulting in a total of 50 pregnancies including 31 term deliveries by 28 women. All the children are normal and healthy, the eldest being 11 years old now.

Study and treatment of gestational trophoblastic diseases at the John I. Brewer Trophoblastic Disease Center, 1962-1990.

From 1962 through 1989, 5063 patients were referred to the John I. Brewer Trophoblastic Disease Center of the Northwestern University Medical School. Among these were 564 patients treated with chemotherapy for gestational trophoblastic tumors (choriocarcinoma and invasive mole). The overall cure rate was 94%, 100% for 323 patients without evidence of metastases and 85% for 241 patients with metastatic disease. Four factors were determined to significantly influence treatment response: (1) clinicopathologic diagnosis of choriocarcinoma, (2) metastases to sites other than the lung or vagina, (3) number of metastases, and (4) previous failed chemotherapy.