A phantom human chorionic gonadotropin in the case of molar pregnancy.

Accurately interpreting persistent, low human chorionic gonadotropin (hCG) levels is essential for managing gestational trophoblastic disease. Erroneous interpretation can lead to inappropriate interventions, including unnecessary chemotherapy or hysterectomy, or unjustified changes in chemotherapeutic regimens due to misidentification of a false-positive hCG as a true positive. The predominant etiology of phantom hCG is the presence of heterophilic antibodies. Consequently, screening for urine hCG is indispensable for its diagnosis because immunoglobulin is not generally present in urine. Here, we report about phantom hCG after a complete hydatidiform mole. Initial urine hCG evaluations were negative, although the serum hCG levels remained positive, leading to the diagnosis of phantom hCG. After subsequent delivery, urine hCG levels persisted at diminished levels. However, a different assay yielded negative hCG results for both serum and urine samples. The patient subsequently gave birth. The absence of hCG was consistently confirmed over five years.

Single-nucleotide polymorphism array and fluorescence in situ hybridization analysis to decode the cytogenetic profile of atypical partial hydatidiform moles diagnosed by short tandem repeat polymorphism analysis.

Accurate diagnosis of partial hydatidiform moles (PHMs) is crucial for improving outcomes of gestational trophoblastic neoplasia. The use of short tandem repeat (STR) polymorphism analysis to distinguish between PHM and hydropic abortuses is instrumental; however, its diagnostic power has not been comprehensively assessed. Herein, we evaluated the diagnostic efficacy of STR in differentiating between PHM and hydropic abortus, thus providing an opportunity for early measurement of human chorionic gonadotropin for PHMs. We reviewed charts of STR polymorphism analysis performed on fresh villous specimens and patient blood samples using a commercial kit for 16 loci. The genetic classification of 79 PHMs was confirmed. STR was reliable in differentiating PHMs when at least 15 loci were available. Typically, PHMs are characterized by their triploidy, including two paternal and one maternal haploid contribution. In our sample, seven PHMs lacked the three-allelic loci, requiring fluorescence in situ hybridization (FISH) analysis to investigate imbalanced biparental conceptus and single-nucleotide polymorphism array analysis to reveal cytogenetic details. Of these PHMs, two, three, and one were identified as androgenetic/biparental mosaics (diploids), monospermic diandric monogynic triploids, and a typical dispermic diandric monogynic triploid, respectively. The remaining case was monospermic origin, but its ploidy details could not be available. Therefore, STR differentiated PHM from a biparental diploid abortus in most cases. However, PHM diagnosis may be compromised when STR is used as the sole method for cases displaying distinct cytogenetic patterns lacking the three-allelic loci, including androgenetic/biparental mosaicism. Therefore, FISH should be considered to confirm the diagnosis.

Therapy-related myeloid neoplasms after treatment for ovarian cancer: A retrospective single-center case series.

OBJECTIVE: Therapy-related myeloid neoplasms (t-MNs) are often fatal and arise as late complications of previous anticancer drug treatment. No single-center case series has examined t-MNs in epithelial ovarian cancer (EOC). METHODS: All patients with EOC treated at Chiba University Hospital between 2000 and 2021 were included. We retrospectively analyzed the characteristics, clinical course, and outcomes of patients who developed t-MNs. RESULTS: Among 895 cases with EOC, 814 cases were treated with anticancer drugs. The median follow-up period was 45 months (interquartile range, 27-81) months. Ten patients (1.2%) developed t-MNs (FIGO IIIA in one case, IIIC in three, IVA in one, and IVB in five). Nine patients were diagnosed with myelodysplastic syndrome and one with acute leukemia. One patient with myelodysplastic syndrome developed acute leukemia. The median time from the first chemotherapy administration to t-MN onset was 42 months (range, 21-94 months), with t-MN diagnoses resulting from pancytopenia in four cases, thrombocytopenia in three, and blast or abnormal cell morphology in four. The median number of previous treatment regimens was four (range, 1-7). Paclitaxel + carboplatin therapy was administered to all patients, gemcitabine and irinotecan combination therapy to nine, bevacizumab to eight, and olaparib to four. Six patients received chemotherapy for t-MN. All patients died (eight cancer-related deaths and two t-MN-related deaths). None of the patients was able to restart cancer treatment. The median survival time from t-MN onset was 4 months. CONCLUSIONS: Patients with EOC who developed t-MN were unable to restart cancer treatment and had a significantly worse prognosis.

Removal of an Intrauterine Polypoid Lesion Resolved Chemotherapy-resistant Gestational Trophoblastic Neoplasia: A Case Report.

Background/Aim: Single-agent chemotherapy typically has curative outcomes in patients with low-risk gestational trophoblastic neoplasia (GTN). Although surgical intervention is a potential alternative, its efficacy in these patients remains unclear. This report describes a case in which surgical excision of a uterine polypoid lesion resolved chemotherapy-resistant low-risk GTN. Case Report: A 43-year-old patient received pulse actinomycin D treatment for post-molar low-risk GTN without extrauterine metastasis. However, the patient showed resistance to the chemotherapy regimen. There was no initial evidence of protrusion of GTN into the uterine cavity; however, a polypoid lesion grew into the uterine cavity during therapy. This growth was successfully excised via a transvaginal approach using forceps with minimal blood loss. There was a postoperative decrease in human chorionic gonadotropin levels, which ultimately reached the predetermined threshold without the need for changing the therapeutic protocol. Conclusion: Surgical resection should be considered a viable therapeutic strategy for uterine polypoid growth in chemotherapy-resistant low-risk GTN.

Evaluation of Combined p57KIP2 Immunohistochemistry and Fluorescent in situ Hybridization Analysis for Hydatidiform Moles Compared with Genotyping Diagnosis.

Immunostaining with p57KIP2 is a widely used diagnostic technique to differentiate complete hydatidiform moles (CHMs) from partial hydatidiform moles (PHM) and non-molar hydropic abortion. However, distinguishing between PHMs and non-molar hydropic abortions using histopathology alone is often challenging. This study aimed to evaluate the technical validity and additional benefits of using fluorescence in situ hybridization (FISH) in combination with p57KIP2 immunostaining to diagnose molar and non-molar conceptuses. The study involved 80 specimens, which underwent genetic diagnosis using short tandem repeat analysis, including 44 androgenetic CHMs, 20 diandric monogynic PHMs, 14 biparental non-molar hydropic abortions, 1 monoandric digynic triploid abortion, and 1 vaginal specimen of gestational trophoblastic neoplasia. Two pathologists independently diagnosed the cases based on morphology and p57KIP2 immunostaining while the clinical information was masked. FISH analysis was performed using 3 probes (CEP17, CEPX, and CEPY), which revealed that all androgenetic CHM and biparental diploid non-molar hydropic abortion specimens were diploid. Among the 20 diandric monogynic PHM cases examined by analyzing short tandem repeat polymorphisms, 18 were triploid, and the remaining 2 were diploid. These two specimens were possibly androgenetic/biparental mosaics based on FISH analysis, where the three-signal ratios counting 50 cells were clearly within the diploid ranges. Eight of the 20 genetic PHMs and 2 of the 14 genetically confirmed non-molar hydropic abortions that were falsely diagnosed based on morphology and immunohistochemistry by at least 1 pathologist were correctly diagnosed as PHM and non-molar hydropic abortion, respectively, by FISH analysis. However, 1 monoandric digynic villus was classified as triploid by FISH analysis, leading to a false PHM diagnosis. In conclusion, the combination of FISH analysis with p57KIP2 immunostaining helps in diagnosing molar and non-molar conceptuses in numerous cases; nevertheless, exceptional cases should be considered.

Total human chorionic gonadotropin is a more suitable diagnostic marker of gestational trophoblastic diseases than the free ß-subunit of human chorionic gonadotropin.

Objectives: Human chorionic gonadotropin (hCG) levels are essential for the management of trophoblastic diseases. This study aimed to compare the sensitivities and relationships of two hCG measurement methods (total hCG and the free ß-subunit of hCG) in managing gestational trophoblastic disease (GTD). Design and Methods: We analyzed data from patients treated for GTD at Chiba University Hospital between 2008 and 2019. We focused on cases where both total hCG (mIU/mL) and the free ß-subunit of hCG (ng/mL) were measured on the same day. Results: Out of 80 patients (mean age 38.9 ± 11.7 years) and 158 measurements, 26 had values below the sensitivity threshold for both tests. Fifty-nine measurements were positive for total hCG but below the sensitivity threshold for the free ß-subunit of hCG, whereas only two showed the opposite. Seventy-one measurements were positive for both total hCG and the free ß-subunit of hCG. There was a significant correlation between total hCG and the free ß-subunit of hCG with both positive values, (r = 0.94, p < 0.001; Spearman's correlation test). Of the 85 measurements with undetectable free ß-subunit levels, 26 also had undetectable total hCG levels. However, total hCG was detectable in 59 patients from these cases, with a median value (interquartile range) of 2.9 (1.75-4.9) mIU/mL. Conclusions: In the management of GTD, the use of the free ß-subunit system alone cannot be recommended.

A Phase Ib Study of Durvalumab (MEDI4736) in Combination with Carbon-Ion Radiotherapy and Weekly Cisplatin for Patients with Locally Advanced Cervical Cancer (DECISION Study): The Early Safety and Efficacy Results.

We conducted a phase Ib study to examine the safety of a combination of carbon-ion RT (CIRT) with durvalumab (MEDI4736; AstraZeneca) in patients with locally advanced cervical cancer. This was an open-label, single-arm study with a modified 3 + 3 design. Patients with newly diagnosed histologically proven locally advanced cervical cancer were enrolled. All patients received 74.4 Gy of CIRT in 20 fractions and concurrent weekly cisplatin (chemo-CIRT) at a dose of 40 mg/m2. Durvalumab was administered (1500 mg/body) at weeks two and six. The primary endpoint was the incidence of adverse events (AEs) and serious AEs (SAEs), including dose-limiting toxicity (DLT). All three enrolled patients completed the treatment without interruption. One patient developed hypothyroidism after treatment and was determined to be an SAE. No other SAEs were observed. The patient recovered after levothyroxine sodium hydrate treatment. None of the AEs, including hypothyroidism, were associated with DLT in the present study. All three patients achieved complete responses within the CIRT region concerning treatment efficacy. This phase 1b trial demonstrates the safety of combining chemo-CIRT and durvalumab for locally advanced cervical cancer in the early phase. Further research is required as only three patients were included in this study.

Prognosis prediction of uterine cervical cancer using changes in the histogram and texture features of apparent diffusion coefficient during definitive chemoradiotherapy.

OBJECTIVES: We investigated prospectively whether, in cervical cancer (CC) treated with concurrent chemoradiotherapy (CCRT), the Apparent diffusion coefficient (ADC) histogram and texture parameters and their change rates during treatment could predict prognosis. METHODS: Fifty-seven CC patients treated with CCRT at our institution were included. They underwent MRI scans up to four times during the treatment course (1st, before treatment [n = 41], 2nd, at the start of image-guided brachytherapy (IGBT) [n = 41], 3rd, in the middle of IGBT [n = 27], 4th, after treatment [n = 53]). The entire tumor was manually set as the volume of interest (VOI) manually in the axial images of the ADC map by two radiologists. A total of 107 image features (morphology features 14, histogram features 18, texture features 75) were extracted from the VOI. The recurrence prediction values of the features and their change rates were evaluated by Receiver operating characteristics (ROC) analysis. The presence or absence of local and distant recurrence within two years was set as an outcome. The intraclass correlation coefficient (ICC) was also calculated. RESULTS: The change rates in kurtosis between the 1st and 3rd, and 1st and 2nd MRIs, and the change rate in grey level co-occurrence matrix_cluster shade between the 2nd and 3rd MRIs showed particularly high predictive powers (area under the ROC curve = 0.785, 0.759, and 0.750, respectively), which exceeded the predictive abilities of the parameters obtained from pre- or post-treatment MRI only. The change rate in kurtosis between the 1st and 2nd MRIs had good reliability (ICC = 0.765). CONCLUSIONS: The change rate in ADC kurtosis between the 1st and 2nd MRIs was the most reliable parameter, enabling us to predict prognosis early in the treatment course.

Delayed postrenal failure due to progression of asymptomatic hydronephrosis following hysterectomy.

Asymptomatic hydronephrosis following hysterectomy is generally transient. Here, we present the case of a 52-year-old woman who underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy for benign indications. Computed tomography (CT) to examine bleeding on the second postoperative day incidentally revealed bilateral grade II hydronephrosis. Asymptomatic hydronephrosis was not reevaluated, and gynecological outpatient follow-up was terminated with a normal creatinine level on postoperative day 43. On postoperative day 107, the patient noticed weight gain of 10 kg, decreased urine output, and generalized edema. The serum creatinine level was elevated to 5.4 mg/dL, and CT revealed bilateral grade III hydronephrosis. Urgent bilateral ureteral stenting was performed to treat stenosis of the distal ureters that caused postrenal failure. Ureteroneocystostomy was performed for strict stenosis of the right ureter at 10 months postoperatively. Histological examination of the resected distal ureter showed inflammation and fibrosis. Asymptomatic hydronephrosis developing after hysterectomy progress to delayed postrenal failure.

Suppressor-type TERT mutations associated with recurrence in ovarian clear cell carcinoma.

Several cancers harbor "enhancer-type" mutations of the telomerase reverse transcriptase (TERT) promoter for immortalization. Here, we report that 8.6% (8/93) of ovarian clear cell carcinomas (OCCCs) possess the "suppressor-type" TERT promoter mutation. The recurrence rate of OCCCs with "suppressor-type" TERT promoter mutations was 62.5% (5/8) and was significantly higher than that of the "unaffected-type" with no mutation (20.8%, 15/72) or "enhancer-type" TERT promoter mutations (7.7%, 1/13). Our findings show that the acquired suppression of TERT is closely associated with OCCC development and recurrence, indicating the need for further research on telomerase suppression in cancers.

Auxiliary and experimental diagnostic techniques for hydatidiform moles.

Hydatidiform moles are classified into complete hydatidiform moles (CHMs), which are androgenetic and diploid, and partial hydatidiform moles (PHM), which are triploid with two paternal chromosomes and one maternal chromosome. The incidence of gestational trophoblastic neoplasia differs substantially between CHM and PHM. However, they are occasionally difficult to diagnose. In this review, auxiliary and experimental methods based on cytogenetic features and advanced molecular detection techniques applied to the diagnosis and analysis of hydatidiform moles are summarized, including basic principles, characteristics, and clinical implications. Short tandem repeat polymorphism analysis is considered the gold standard for the genetic diagnosis of hydatidiform moles. In clinical settings, immunohistochemical analyses of p57KIP2 , an imprinted gene product, are widely used to differentiate CHMs from other conceptuses, including PHMs. Recently, new molecular genetic techniques, such as single nucleotide polymorphism arrays, have been applied to research on hydatidiform moles. In addition to insights from classical methods, such as chromosome analysis, recently developed approaches have yielded novel findings related to the mechanism underlying the development of androgenetic CHMs.

Short tandem repeat polymorphism analysis for primary peritoneal choriocarcinoma: A case report and literature review.

The peritoneum is an extremely rare site for primary choriocarcinoma development. Primary peritoneal choriocarcinoma could be either gestational or nongestational, whereas it is straightforward to ascribe uterine or tubal choriocarcinoma to the gestational origin. Herein, we report a case of primary peritoneal choriocarcinoma that is genetically diagnosed as a gestational subtype originating from an occult complete hydatidiform mole. A 46-year-old female patient with two-time induced abortion histories underwent emergency laparotomy under clinical suspicion of ruptured tubal pregnancy. Laparotomy revealed a hemorrhagic tumor in the left mesosalpinx with apparently intact left ovary and fallopian tube. The excised tumor was pathologically diagnosed as choriocarcinoma. Multiplex short tandem repeat polymorphism analysis revealed an androgenetic/homozygous genotype tumor, identifying its origin as a complete hydatidiform mole. Our literature review of nine primary peritoneal choriocarcinoma cases, including ours, highlighted the importance of tumor genotyping in differentiating between gestational and non-gestational subtypes and identifying the causative pregnancy.

The effect of steep head-down tilt on respiratory status in endometrial cancer patients with obesity during robot-assisted hysterectomy.

Objective: To evaluate the effect of head-down tilt on airway pressure in gynecologic patients with obesity during robot-assisted hysterectomy. Methods: We retrospectively reviewed the records of 27 patients with body mass index (BMI) ≥ 25 kg/m2 who underwent robot-assisted hysterectomy for endometrial cancer and endometrial atypical hyperplasia using the da Vinci Xi system. Mechanical ventilation was performed using pressure-controlled ventilation (PCV). Surgery was performed at 20° (group A, n = 17) or 25° head-down tilt (group B, n = 10). Respiratory parameters, including positive end-expiratory pressure (PEEP), tidal volume (TV), mean airway pressure (P mean), and peak airway pressure (P peak), were measured before (T1) and after the head-down tilt at 1 h (T2) and 2 h (T3) during anesthesia. Results: The median BMI was 37.5 (range 28-51) kg/m2, with no between-group variation. Oxygenation was maintained intraoperatively for all patients. The expiratory carbon dioxide partial pressure was 43.6 (95% confidence interval (CI) 42.2-45.0) mmHg. The P mean peak at T2 in group B was significantly higher than in group A (P < 0.011); however, other parameters at T2 and T3 did not differ significantly between the groups. Patients with BMI ≥ 40 kg/m2 had significantly higher respiratory parameters than those with BMI < 40 kg/m2. In patients with BMI ≥ 40 kg/m2, the mean P means and P peaks at T3 were 17.3 cmH2O (95% CI 16.3-18.3) and 29.4 cmH2O (95% CI 27.1-31.7), respectively. Discussion: With careful anesthetic management during PCV, robot-assisted surgery with a head-down tilt of 25° or below may be safe, even in patients with class III obesity.

Phase Ib study of durvalumab (MEDI4736) in combination with carbon-ion radiotherapy and weekly cisplatin for patients with locally advanced cervical cancer (DECISION study): study protocol for a prospective open-label single-arm study.

INTRODUCTION: Concurrent chemoradiotherapy is considered the standard treatment strategy for locally advanced cervical cancer. Most recent reports indicate that patients with bulky tumours or adenocarcinoma subtypes have poorer local control. Carbon-ion radiotherapy (CIRT) with the concurrent use of chemotherapy has shown promising results in such cases of difficult-to-treat uterine cervical cancer. Programmed death-ligand 1 (PD-L1) upregulation was observed in tumour tissue samples from patients who had undergone CIRT. Thus, a combination of CIRT and anti-PD-L1 antibody may suppress metastasis by activating antitumour immune response, in addition to exhibiting strong local effects. OBJECTIVE: We will assess the safety and tolerability (primary endpoint) of the concomitant use of durvalumab, an anti-PD-L1 antibody, with CIRT and weekly cisplatin for locally advanced cervical cancer. METHODS AND ANALYSIS: This study is a non-randomised, open-label, prospective phase 1b study. Up to 10 patients with histologically proven uterine cervical cancer at stage IIB, IIIA, IIIB, IIIC1 or IVA as per International Federation of Gynecology and Obstetrics (2018) staging will be enrolled. All patients will receive CIRT of 74.4 Gy relative biological effectiveness in 20 fractions over 5 weeks (four fractions per week). Weekly cisplatin at a dose of 40 mg/m2 will be administrated up to five times. Durvalumab at a dose of 1500 mg/body will be administrated at weeks 2 and 6. Safety and tolerability will be evaluated based on the frequency of dose-limiting toxicities until 92 days after CIRT starts. Patients will be followed-up strictly as per the scheduled protocol for 1 year after CIRT initiation. ETHICS AND DISSEMINATION: The Human Research Ethics Committees of QST Hospital (#C21-002) and Chiba University (#2021006) have approved this study protocol. The findings will be published in peer-reviewed journals and presented at scientific conferences. TRIAL REGISTRATION NUMBER: Japan Registry of Clinical Trials (jRCT2031210083), registered on 12 May 2021.

Discrepancies in pathological diagnosis of endometrial stromal sarcoma: a multi-institutional retrospective study from the Japanese clinical oncology group.

Endometrial stromal sarcoma (ESS) is a rare uterine malignancy that requires accurate pathological diagnosis for proper treatment. This study aimed to clarify the discrepancies in the pathological diagnosis of ESS and obtain practical clues to improve diagnostic accuracy. Between 2002 and 2015, 148 patients with low-grade ESS (LGESS), high-grade ESS (HGESS), undifferentiated endometrial sarcoma (UES), or undifferentiated uterine sarcoma (UUS) diagnosed at 31 institutions were included. We performed immunohistochemistry, real-time polymerase chain reaction for JAZF1-SUZ12 and YWHAE-NUTM2A/B, and break-apart fluorescent in situ hybridization for JAZF1, PHF1, and YWHAE. Central pathology review (CPR) was performed by six pathologists. After CPR, LGESS, HGESS, UES/UUS, and other diagnoses were confirmed in 72, 25, 16, and 31 cases, respectively. Diagnostic discrepancies were observed in 19.6% (18/92) of LGESS and 34% (18/53) of HGESS or UUS/UES. Adenosarcomas, endometrial carcinomas, carcinosarcomas, and leiomyosarcomas were common diagnostic pitfalls. JAZF1-SUZ12 transcript, PHF1 split signal, and YWHAE-NUTM2A/B transcript were mutually exclusively detected in 23 LGESS, 3 LGESS, and 1 LGESS plus 3 HGESS, respectively. JAZF1-SUZ12 and YWHAE-NUTM2A/B transcripts were detected only in cases with CPR diagnosis of LGESS or HGESS. The CPR diagnosis of LGESS, HGESS, and UUS was a significant prognosticator, and patients with LGESS depicted a favorable prognosis, while those with UUS showed the worst prognosis. Pathological diagnosis of ESS is often challenging and certain tumors should be carefully considered. The accurate pathological diagnosis with the aid of molecular testing is essential for prognostic prediction and treatment selection.

High prevalence of pulmonary embolism prior to cancer therapies in patients with ovarian and endometrial cancers detected by contrast-enhanced CT using D-dimer as an index.

OBJECTIVE: We aimed to evaluate the prevalence of pulmonary embolism (PE) before cancer therapies in patients with ovarian and endometrial cancers with enhanced computed tomography (CT) using D-dimer (DD), and determine the optimal cut-off level of DD. METHODS: Since 2009, we have performed preoperative venous thromboembolism (VTE) screening of patients with ovarian and endometrial cancer. For patients with DD levels of more than 1.0 µg/ml, enhanced CT images were obtained from the pulmonary apex to the foot to detect PE and deep venous thrombosis (DVT) simultaneously. RESULTS: Among patients with ovarian cancer, 84 of 413 (20.3%) had VTEs (DVT alone, n = 31 [7.5%]; PE with or without DVT, n = 53 [12.8%]; PE alone, n = 12 [2.9%]). Among patients with endometrial cancer, 50 of 455 (11.0%) had VTEs (DVT alone, n = 19 [4.2%]; PE with or without DVT, n = 31 [6.8%], PE alone, n = 14 [3.1%]). The optimal cut-off level of DD was estimated to be ≥1.5 and ≥1.2 µg/ml in ovarian and endometrial cancers, respectively. CONCLUSION: Our study revealed a high prevalence of PE before cancer therapies in patients with ovarian and endometrial cancers by enhanced CT using DD.

Spermatogonium-Derived Complete Hydatidiform Mole.

A complete hydatidiform mole (CHM) is a conceptus with only sperm-derived chromosomes. Here, we report on a CHM with genomic DNA identical to that of the paternal somatic cells. The CHM developed in a woman who had undergone intrauterine implantation of a blastocyst obtained through in vitro injection of a presumed round spermatid into one of her oocytes. The CHM was genetically identical to peripheral white cells of her husband and contained no maternally derived nuclear DNA. We hypothesize that a spermatogonium, rather than a round spermatid, was inadvertently selected for the procedure. The CHM developed into a gestational trophoblastic neoplasia, which resolved after chemotherapy. (Funded by the Japan Society for the Promotion of Science.).

Surgical margin status and recurrence pattern in invasive vulvar Paget's disease: A Japanese Gynecologic Oncology Group study.

OBJECTIVE: To examine the association between surgical margin status and recurrence pattern in invasive vulvar Paget's disease. METHODS: This is a preplanned secondary analysis of a previously organized nationwide retrospective study in Japan (JGOG-1075S). Women with stage I-IV invasive vulvar Paget's disease who received surgical treatment from 2001-2010 were examined (n=139). Multivariable analysis was performed to assess local-recurrence, distant-recurrence, and all-cause mortality based on surgical margin status. RESULTS: The median age was 70 years. The majority had stage I disease (61.2%), and the median tumor size was 5.0cm. Nodal metastasis was observed in 15.1%. Simple vulvectomy (46.0%) was the most common surgery type followed by radical vulvectomy (28.1%). More than half received vulvar reconstructive surgery (59.0%). Positive surgical margin was observed in 35.3%, and close margin <1cm was observed in 29.5%. Vulvectomy type was not associated with surgical margin status (P=0.424). The median follow-up was 5.8 years. Positive surgical margin was associated with increased local-recurrence (5-year cumulative rates for positive versus negative margin: 35.8% versus 15.0%, P=0.010) but not distant-recurrence (18.3% versus 16.0%, P=0.567). Positive surgical margin was also associated with increased all-cause mortality (5-year overall survival rates for positive versus negative margin: 72.6% versus 88.2%, P=0.032). In multivariable analysis, positive surgical margin remained an independent factor associated with increased risk of local-recurrence (hazard ratio 2.80, 95% confidence interval 1.18-6.63) and all-cause mortality (hazard ratio 2.87, 95% confidence interval 1.20-6.83). CONCLUSION: Positive surgical margin appears to be common in invasive vulvar Paget's disease that is associated with increased local-recurrence and all-cause mortality risks. Role of alternative surgical technique or adjuvant therapy merits further investigation to improve local disease control.

Parental contribution to trisomy in heterozygous androgenetic complete moles.

Complete hydatidiform moles (CHMs) comprise a proliferative trophoblastic disorder and are known to be androgenetic and diploid. Androgenetic CHMs are classified as having monospermic and dispermic origins. Rarely, some CHMs have other genetic constitutions, such as biparental diploid or tetraploid. Previous studies have shown the possibility that androgenetic heterozygous CHMs have an additional chromosome with high frequency. This study aimed to comprehensively analyse the molecular karyotyping of androgenetic dispermic CHMs and the parental contribution of their additional chromosomes. Single-nucleotide polymorphism arrays were performed with the genomic DNA of CHMs and patients. The B allele frequency and selected B allele frequency plotting of CHM were visualised. Among the 31 dispermic CHMs, eight showed trisomy and one showed double trisomy; of the 10 additional chromosomes, seven were of maternal original and three were of paternal origin. In addition, three disomic chromosomes comprised one maternal and one paternal chromosome, although these should theoretically have had two paternal chromosomes in the case of androgenetic CHMs. The subclassification of heterozygous CHMs, with or without maternal contribution, is a new approach and could be a candidate indicator of gestational trophoblastic neoplasia risk.