Double Trisomy 16 and 22 Clinically Mimic Partial Hydatidiform Mole in a Case of Subsequent Pregnancy Loss.

A case of double trisomy 16 and 22 in the second pregnancy loss is presented. DNA analyses (short tandem repeats genotyping) of miscarriage specimen was indicated because of ultrasound suspicion of partial hydatidiform mole. After the partial hydatidiform mole exclusion, further DNA analyses focused on the most common aneuploidies causing pregnancy loss, detected double trisomy 16 and 22 in the product of conception. The couple was referred to clinical genetic consultation and normal parental karyotypes were proved. For further explanatory purposes, archived material from the first pregnancy loss was analyzed and trisomy of chromosome 18 was detected. By comparison of allelic profiles of the mother, father, and both losses, the maternal origin of all aneuploidies was proven what can be attributed to frequent meiosis errors, probably due to advanced maternal age (44 years at the first loss and 45 years at the second loss). In conclusion, aneuploidies can mimic partial hydatidiform mole. Genetic analysis is helpful on the one hand to rule out partial hydatidiform mole and on the other hand to identify aneuploidies and in this way to determine the cause of miscarriage.

PTEN mutations as predictive marker for the high-grade endometrial cancer development in slovak women.

Endometrial carcinoma (ECa) is one of the most common neoplasia of the female genital tract. The phosphatase and tensin (PTEN) homolog is the most frequently mutated tumor suppressor gene in endometrial carcinoma. PTEN encodes a phosphatase, a key regulatory enzyme involved in a signal transduction pathway that regulates cell growth, migration and apoptosis. The study evaluates an association between the morphological appearance of endometrial hyperplasia and ECa, and the presence of PTEN variations, PTEN protein´s level and intracellular localization. A total of 67 archived formalin-fixed and paraffin-embedded human biopsy tissue specimens with normal proliferative and secretory endometrium, endometrial hyperplasia without atypia and endometrial atypical hyperplasia, endometrioid the grade G1 and G3 and serous subtype of ECa were evaluated by sequencing for the presence of mutations in coding regions of PTEN gene of endometrial epithelial cells. The PTEN gene expression and intercellular localization of PTEN protein were evaluated immunohistochemically by immunoreactive score (IRS). PTEN mutation spectrum in endometrial carcinoma was identified for Slovak population. 28 non-silent mutations were identified in PTEN, twelve of them were novel, not annotated in Catalogue of Somatic Mutations in Cancer. Higher frequency of PTEN mutations was observed in serous carcinoma compared to global average. No correlation was observed between samples´ IRS, PTEN cellular localization and identified mutations. PTEN sequencing can be beneficial for patients considering prognosis of disease and sensitivity to treatment.

Importance of the genetics in the diagnostics of hydatidiform mole.

OBJECTIVE: To summarize the possibilities of the genetic analysis of hydatidiform moles and point out its perspectives in the diagnostics of this disease. DESIGN: Review. SETTING: Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University in Bratislava, Slovak Republic. METHODS: Analysis of published literature data from the internet databases PubMed, ScienceDirect, Scopus and printed literature from the period 1963-2019. RESULTS: This review refers on karyotyping, flow cytometry, FISH (Fluorescent in Situ Hybridization), VNTR-RFLP analysis (Variable Number of Tandem Repeats-Restriction Fragment Length Polymorphism), VNTR-PCR analysis (Variable Number of Tandem Repeats-Polymerase Chain Reaction) and STR (Short Tandem Repeat) genotyping of hydatidiform moles. The article summarizes possible application of these methods in the differential diagnostics of molar pregnancy (partial and complete hydatidiform moles) and nonmolar hydropic abortions. CONCLUSION: Genetic analyses offer precise identification of types of molar pregnancies when histopathological diagnosis is not clear during early stages of pathology.

[Results of gestational trophoblastic neoplasia treatment in the Slovak Republic in the years from 1993 to 2012]. / Výsledky liecby gestacnej trofoblastovej neoplázie v Slovenskej republike v rokoch 1993 az 2012.

OBJECTIVE: Analysis and epidemiology of gestational trophoblastic neoplasia treatment in the Slovak Republic in the years 1993-2012. DESIGN: Retrospective epidemiological national study. SETTING: Centre for gestational trophoblastic disease Ministry of Health the Slovak Republic, Bratislava. METHODS: Retrospective analysis results of gestational trophoblastic neoplasia treatment according to prognostic scoring and staging system FIGO/WHO in Centre for gestational trophoblastic disease Ministry of Health the Slovak Republic Bratislava in the years 1993-2012. RESULTS: The treatment of gestational trophoblastic neoplasia (GTN) in the Czech and Slovak Republics started in 1955 and lasted till 1993. After the split of the former Czechoslovakia the Centre for gestational trophoblastic disease was created in Slovakia. 75 patients were treated in this Centre in the years 1993-2012. According to prognostic scoring and staging system FIGO/WHO 56 (75%) patients had low-risk gestational trophoblastic neoplasia and 19 (25%) of patients had high-risk gestational trophoblastic neoplasia. There were 41 patients (55%), 2 (3%), 24 (32%) and 8 (11%) in stage I., II., III. and IV. respectively. Total curability rate was 94.7% and mortality rate was 5.3%. Curability rate 100% was achieved in stage I & II and all placental site trophoblastic tumours (PSTT), 98.3% in stage III and 50% stage IV. In the years 1993-2012 the incidence of choriocarcinoma was one in 76 273 pregnancies and one in 53 203 deliveries. The incidence of other gestational trophoblastic neoplasia in the same years was for PSTT one in 533 753 pregnancies and one in 372 422 deliveries, invasive mole one in 145 611 pregnancies and one in 101 569 deliveries, and persistent GTN one in 40 043 pregnancies and one in 27 932 deliveries. 225-241 patients were treated in the same period of time in the Czech Republic with curability rate 98.2-98. 3%. CONCLUSION: Early detection and treatment in the centre for trophoblastic disease are crucial points in the manage-ment of gestational trophoblastic neoplasia, because the effective therapy of gestational trophoblastic neoplasia with high curability rate is available.

[Expression of p57 marker in differential diagnosis of complete and partial mole - correlation with DNA analysis]. / Expresia markeru p57 v diferenciálnej diagnostike kompletnej a parciálnej moly - korelácia s DNA analýzou.

Nowadays valid classification of gestational trophoblastic disease, according to the World Health Organisation from the year 2003, divides gestational trophoblastic disease into three groups - molar pregnancies, non-neoplastic non-molar changes of trophoblast and tumours of trophoblast. To the molar pregnancies belong complete, partial, invasive and metastatic hydatidiform mole. In the differential diagnosis it is important to distinguish the complete hydatidiform mole from other forms of gestational trophoblastic disease, because there is an increased risk of malignant transformation of trophoblast cells in complete hydatidiform mole. 10 cases of genetically confirmed diploid complete mole and 10 cases of genetically confirmed triploid partial mole were included into our retrospective study. All cases were examined microscopically in the basic haematoxillin and eosin staining and immunohistochemically with the use of antibodies against human choriogonadotropin hormone, placental alkaline phosfatase and protein p57. Villous cytotrophoblast, stromal villous cells, extravillous trophoblast and decidual cells were p57 positive in all cases of partial hydatidiform mole. All 10 cases of complete hydatidiform mole were p57 negative in stromal villous cells and villous cytotrophoblast. P57 protein is a marker distinguishing complete hydatidiform moles from partial moles.

[DNA analysis in gestational trophoblastic disease]. / DNA analýza gestacnej trofoblastovej choroby.

OBJECTIVE: DNA analysis of different forms of gestational trophoblastic disease. DESIGN: Retrospective clinical study. SETTING: Slovak Center of Trophoblastic Disease, Bratislava, Slovak Republic. METHODS: In the period of September 1993 to April 2003, eighty-nine cases of gestational trophoblastic disease were analysed. There were 22 cases of partial hydatidiform moles, 58 cases of complete hydatidiform mole, 5 cases of invasive mole and 4 cases of gestational choriocarcinomas. Southern hybridization and polymerase chain reaction were used for DNA analysis. RESULTS: From 22 analyzed cases of partial hydatidiform moles 19 (86.4%) were triploid and 3 (13.6%) diploid ones. There were 58 cases of complete hydatidiform mole and out of them 29 (50%) were homozygous, 28 (48.3%) heterozygous, and in one case (1.7%) both paternal and maternal genome was detected. In 8 cases of heterozygous and in one case of homozygous complete hydatidiform mole occurred a malignant transformation to gestational choriocarcinoma. CONCLUSIONS: Molecular analysis can determine the nuclear DNA origin of complete hydatidiform mole and allow us to define the patients with higher risk of malignant transformation usually to gestational choriocarcinoma.

Management of intracavitary left atrium tumors during pregnancy - two case reports.

OBJECTIVE: Authors documented an individual management of intracavitary left atrium tumors diagnosed during pregnancy. SUBJECT: Two case reports were presented. Brain embolisation was supposed in the case one of intracavitary left atrium tumor. An urgent cardiosurgery at 24 weeks' gestation was performed on the cardiopulmonary bypass. In case two (multiple pregnancy - twins) cardiac tumor in left atrium was detected in third trimester of pregnancy. The mother was without any serious cardiac and systemic complications during the last trimester. Surgical approach was different - removal of tumor after delivery. CONCLUSION: The surgical approach should be determined by clinical behavior of left atrial cardiac tumors.

[Laparoscopic findings in women with chronic pelvic pain]. / Laparoskopické nálezy u zien s chronickou panvovou bolest'ou.

Chronic pelvic pain afflicts 5-10% of women. The diagnosis of its cause is predominantly assessed by means of laparoscopy which in 60-70% reveals various organic causes of pain. The retrospective study analyses the results of 43 laparoscopic examinations indicated due to chronic pelvic pain. The average age of patients was 29.97 years. Organic findings on internal genitals were found in 36 cases (83.7%). Endometriosis was diagnosed in 11 cases (25.6%). According to the criteria of American Fertility Society, 4 patients (36.4%) suffered from stage I, 6 patients (54.5%) suffered from stage II, and only one case (9.1%) was caused by stage III. Chronic inflammatory process was diagnosed in 12 cases (18.6%), adhesions without any other pathologic findings in 8 cases (18.6%), and ovarial cysts in 3 cases (7.0%). Varicose pelvic veins and uterine myoma occurred in one case (2.3%), respectively. In 7 cases, no pathological change was revealed. Laparoscopy in coincidence with chronic pelvic pain is a significant examination which helps to reveal the organic origin of disturbance. An early decision of applying this invasive examination contributes to fast assessment of the diagnose and commencement of treatment. (Tab. 2, Fig. 1, Ref. 32.)

[Papillomavirus infection of the uterine cervix in women using contraception]. / Papilomavírusová infekcia krcka maternice u zien s antikoncepciou.

OBJECTIVE: The authors analyze the prevalence of the anogenital form of HPV infection as one of the most frequent STD, in the female population using different types of contraception. METHODS: Using the method of DNA hybridization, the authors examined for HPV infection of the uterine cervix 245 users of contraception, incl. 127 women using hormonal contraception and 118 women with IUD. 112 women of this group were examined before they started to use contraception and one year after started to use it. The control group was formed by 143 using no contraception. RESULTS: The authors found a significantly higher incidence of HPV infection of the uterine cervix in the group of women using contraception (24.1%) than in the control group (15.4%). On analysis of the group of women using contraception, as compared with the control group, they found a significantly higher incidence of HPV in women with hormonal contraception (26.0%) while the higher prevalence of HPV (by 6.6%) in women with IUD as compared with the control group was not significant. However the differences in the incidence of HPV (4%) between the two groups of women taking hormonal preparations (26.0%) or having a IUD (22%) were not significant. On examination of women before the onset of contraception and after one year of its use the authors found that candidates of contraception had as compared with the control group an insignificantly (by 3.3%) higher prevalence of HPV already before the beginning of contraception. After one year of contraception it increased by another 3.6%. CONCLUSION: With regard to the higher incidence of HPV in women using contraception and with regard to the oncogenic effect of HPV the authors emphasize the importance of regular detailed gynaecological examinations of these women focused on early diagnosis of precancerous conditions of the uterine cervix.

Mola invasiva--special form of GTD.

Invasive hydatidiform mole is a relative rare form of gestational trophoblastic disease (GTD). Most of hydatidiform moles remit after evacuation but some of them have the tendency to invade the myometrium. In some rare cases the trophoblastic tissue can be found in other tissues like lungs, vulva, vagina or broad ligament. The aim of the study was to demonstrate some of clinical, immunohistochemical and DNA analysis findings of a patient with a previous diagnosis of a complete hydatidiform mole.

[Diagnosis of partial hydatidiform mole using molecular genetics]. / Molekulárno genetická diagnostika parciálnej moly hydatidózy.

The aim of our study was to confirm the diagnosis of partial hydatidiform mole (PMH) and to determine mechanism of PMH development by chromosomal DNA analysis. In our study we analysed 8 cases of morphologically and histologically confirmed PMH. Their karyotype was determined by using methods of direct, 24-hour and a long-term tissue culture. The restriction fragment length polymorphisms (RFLP) method was used for DNA analysis of PMH chorionic villi and from progenitor lymphocytes in peripheral blood. All cases were triploid. DNA analysis revealed in six cases one maternal and two paternal RFLP bands, and in two cases two maternal and one paternal RFLP bands.

[Personal experience with diagnosis of complete hydatidiform mole based on DNA]. / Nase skúsenosti s diagnostikou kompletnej moly hydatidózy na úrovni DNA.

In our study we analyzed 13 cases of histologically defined complete hydatidiform mole (CHM), by using cytogenetic and molecular genetic methods. There were seven homozygous and six heterozygous CHM. In one case of heterozygous CHM we found a biparental contribution to genomic DNA. This is evidence of a more heterogeneous etiopathogenesis of hydatidiform mole.

[Extrauterine choriocarcinoma--a rare form of gestational trophoblastic disease]. / Extrauternný choriokarcinóm--zriedkavá forma gestacnej trofoblastovej choroby.

Choriocarcinoma represents the most serious form of trophoblast gestation disease. In the majority of cases the carcinomatous tissues fill out the uterine cavity, or they grow in a form of nodes deep in the uterine wall. The primary extrauterine localization of this tumour is very rare. The authors describe two cases of choriocarcinomas with tubal or ovarian localization. (Fig. 4, Ref. 19.)

Origin of choriocarcinoma in previous molar pregnancy proved by DNA analysis.

A 17-year old woman had in a short time period (seven months) a very exciting reproduction history. Molar pregnancy in December 1993, choriocarcinoma in January 1994 and induced abortion in June 1994. DNA analysis proved the origin of the choriocarcinoma in the previous molar pregnancy.