Orphanet Journal of Rare Diseases

The prognosis of recurrent low-grade endometrial stromal sarcoma: a retrospective cohort study

AbstractBackgroundThe prognosis of recurrent low-grade endometrial stromal sarcoma (LGESS) is little known. This study was to investigate the survival outcomes of a cohort of patients with recurrent LGESS.MethodsPatients with primary LGESS diagnosed and treated for first recurrence confirmed by histology in the study center from February 2012 to June 2019 were retrospectively included. The progression-free interval (PFI) after the last treatment for first recurrence and overall survival (OS) since the diagnosis of first recurrence, which were followed up to June 1, 2020, were compared between groups of various therapy modalities.ResultsFifty-six patients were included, and 43 patients (76.8%) had definite follow-up outcomes. The 5-year PFI and OS rates were 30.0% (95% confidence interval [95% CI] 29.2–30.8) and 75.0% (68.0–82.0), respectively. In univariate analysis, only fertility-sparing treatment, ovarian preservation and surgical treatment had a significant impact on the PFI (hazard ratio [HR] 4.5, 3.1, and 0.2; 95% CI 1.5–13.1, 1.3–7.3, and 0.1–0.7; andp = 0.006, 0.009 and 0.006, respectively), but no factor was found to be associated with increased mortality risk. After adjusted with hormone treatment or chemotherapy, surgical treatment had significant effectiveness on OS (HR 0.3 and 0.3, 95% CI 0.1–1.0 and 0.1–1.0,p = 0.045 and 0.049, respectively). None of the patients with fertility-sparing treatment had successful conception, and all experienced repeated relapse.ConclusionFor patients with recurrent LGESS, fertility-sparing treatment or ovarian preservation should not be provided. Surgery is the treatment of choice, and hormone treatment and/or chemotherapy was effective for the survival benefits of surgical treatment.

The clinical practice and outcomes of minimally invasive surgery in primary malignant melanoma of the vagina and cervix patients: a retrospective cohort study

Abstract Background Primary malignant melanoma of the vagina (PMMV) and cervix (PMMC) are extremely rare tumors with a poor prognosis, lacking well-defined protocols or standardized treatment guidelines. While the preferred management for early-stage PMMV and PMMC is surgery, comprehensive reports on the impact of various surgical techniques on cancer outcomes are scarce. Objective This study aimed to compare outcomes between open and minimally invasive surgery (MIS) in PMMV and PMMC, and concurrently evaluated prognostic risk factors for these conditions. Methods We conducted a single-center retrospective cohort study of PMMV and PMMC patients treated surgically from January 2000 to July 2021. Clinicopathological features and surgical outcomes were assessed retrospectively. Patients underwent either open surgery or MIS. Disease-Free Survival (DFS) rates were compared. Results Of 45 eligible patients, the MIS group showed a higher rate of total vaginectomy (P = 0.022), reduced median intraoperative blood loss (P = 0.031), shorter median hospital stay (P = 0.042), and no significant increase in perioperative complications (P = 0.867). The incidence of negative margins < 1 cm was significantly lower in the MIS group (P = 0.032). Cox proportional hazards regression identified microsatellites (HR = 2.893 [1.042–8.029]; P = 0.042), surgical negative margin distance (HR = 0.042 [0.008–0.217]; P < 0.001), and total vaginectomy (HR = 0.042 [0.008–0.217]; P < 0.001) as independent prognostic factors for DFS. MIS was linked to a significant difference in 2-year DFS (P = 0.030), but there was no notable difference in overall survival (OS) compared to open surgery (P = 0.078). The outcomes are validated through sensitivity analysis and hierarchical assessment, leading to the development of a novel nomogram simultaneously. Conclusions Total vaginectomy may improve DFS in PMMV and PMMC patients. A combination of MIS and radical vaginal resection can effectively manage PMMV and PMMC as an initial surgical strategy.

Long-term outcome and fertility results of intraplacental choriocarcinoma: a retrospective study of 14 patients and literature review

Abstract Backgrounds Intraplacental choriocarcinoma (IC) is an extremely rare subtype of gestational choriocarcinoma. The long-term follow-up and reproductive outcomes of IC patients remain unclear. Here, we report a series of 14 cases and conduct a literature review to assess the fertility and recurrence results of this rare disease. Results Fourteen patients with pathologically confirmed IC treated in Peking Union Medical College Hospital between January 2002 and July 2022 were included in this study. Half of them had metastatic IC and were treated by chemotherapy with or without surgery. Only 1 patient had chemoresistant disease, but she achieved complete remission after immunotherapy. The median follow-up time was 45.5 months (range 4-192), and no recurrence occurred. One metastatic IC patient who achieved remission after chemotherapy had a full-term delivery. Among the 5 patients with fertility demands, 3 abandoned their pursuit of pregnancy because of “fear and worry about choriocarcinoma recurrence”. We reviewed a total of 89 cases of IC in English and Chinese literature from 1963 to 2022, and only 5 cases with subsequent pregnancy were reported, all of them were nonmetastatic IC cases. Conclusions IC is sensitive to chemotherapy and has good long-term remission and a low recurrence rate. Patients with metastatic or nonmetastatic IC can have good pregnancy results after treatment. Doctors should pay more attention to the psychology of these patients. Clinical trial registration N/A.

Genetic and clinical characterization of a novel FH founder mutation in families with hereditary leiomyomatosis and renal cell cancer syndrome

Abstract Background Hereditary leiomyomatosis and renal cell cancer syndrome is a rare autosomal dominant hereditary syndrome. Previously, we published the largest cohort of FH mutation carriers in Spain and observed a highly recurrent missense heterozygous variant, FH(NM_000143.4):c.1118A > G p.(Asn373Ser), in 104 individuals from 31 apparently unrelated families. Here, we aimed to establish its founder effect and characterize the associated clinical phenotype. Results Haplotype analysis confirmed that families shared a common haplotype (32/38 markers) spanning 0.61–0.82 Mb, indicating this recurrent variant was inherited from a founder ancestor. Cutaneous and uterine leiomyomatosis were diagnosed in 64.6% (64/99) and 98% (50/51) of patients, respectively, and renal cell cancer was present in 10.4% (10/96). The pathogenic FH_c.1118A > G variant is a Spanish founder mutation that originated 12–26 generations ago. We estimate that the variant may have appeared between 1370 and 1720. Individuals carrying this founder mutation had similar frequency of renal cell cancer and a higher frequency of renal cysts and leiomyomas than those in other cohorts of this syndrome. Conclusions In the Spanish province of Alicante there is a high prevalence of HLRCC because of the founder mutation FH c.1118A > G; p.(Asn373Ser). The characterization of founder mutations provides accurate and specific information regarding their penetrance and expressivity. In individuals with suspected HLRCC from the province of Alicante, genetic testing by direct analysis of the founder FH c.1118A > G; p.(Asn373Ser) mutation may be a faster and more efficient diagnostic tool compared with complete gene sequencing.

Clinical and ultrasound characteristics of virilizing ovarian tumors in pre- and postmenopausal patients: a single tertiary center experience

Abstract Background A virilizing ovarian tumor (VOT) is a rare cause of hyperandrogenism in pre- and postmenopausal women. Although transvaginal ultrasound is considered as the first-line imaging method for ovarian tumors, it is examiner-dependent. We aimed to summarize the clinical and ultrasound manifestations of VOTs to help establish the diagnosis with emphasis on those causing diagnostic difficulty. Method We retrospectively identified 31 patients with VOTs who underwent surgery at Peking Union Medical College Hospital. Results Patients with VOTs were predominantly premenopausal. All patients showed androgenic manifestations with serum testosterone levels elevated to varying degrees. The tumor size of VOTs was significantly correlated with age (P < 0.001). The VOTs in the postmenopausal group were significantly smaller than those in the premenopausal group (median 1.8 cm [range, 1.3–4.8 cm] vs 4.5 cm [range, 0.7–11.9 cm]; P = 0.018). Twenty-seven out of 31 VOTs were successfully identified by ultrasound. On ultrasound, VOTs are mostly solid and hypoechoic masses with enhanced vascularity. Four VOTs (0.7–1.5 cm) were radiologically negative, and they were the smallest among all patients. Conclusion Patients with VOTs showed androgenic manifestations with varying degrees of hyperandrogenemia. Older patients tend to have smaller VOTs. Ultrasound is an effective method for the detection of VOTs. Some VOTs can be very small and difficult to visualize radiologically, especially in postmenopausal patients. Examiners must remain vigilant about very small VOTs on the basis of endocrine symptoms.

Clinical features of a Chinese female nongestational choriocarcinoma cohort: a retrospective study of 37 patients

Abstract Background Choriocarcinoma is a rare malignant neoplasm, which is classified as either gestational choriocarcinoma or nongestational choriocarcinoma. The purpose of this study was to examine the clinical characteristics of Chinese female nongestational choriocarcinoma patients and discuss our experience in treating this rare disease. Results We conducted a single-center retrospective study on a sample of 37 nongestational choriocarcinoma patients who were diagnosed and treated at Peking Union Medical College Hospital from March 1982 to March 2020. Their demographic, clinical, laboratory, and therapeutic data were collected. Detailed information was available for all 37 individuals in our sample. The primary lesions included 34 in the ovaries, 2 in the pituitary and 1 in the stomach. The median age of onset was 22 years, and the median follow-up period spanned 41 months. The lungs (40.5%) were the most commonly observed metastatic site. All subjects were treated with surgery and multidrug chemotherapies, and a median of 4.0 courses was required to achieve complete remission. The overall complete response rate, relapse rate, and 3-year and 5-year survival rates were 81.1%, 16.7%, 80.0%, and 75.5%, respectively. Conclusions Nongestational choriocarcinoma can be managed well using surgery and multidrug chemotherapies, but the overall outcome of nongestational choriocarcinoma is still worse than that of gestational choriocarcinoma. Mixed nongestational choriocarcinoma seems to have similar therapeutic outcomes as pure tumors.

Clinical characteristics and treatment outcomes of women with recurrent uterine leiomyosarcoma

Abstract Objective To determine the clinical characteristics and treatment outcomes of women with recurrent uterine leiomyosarcoma (uLMS). Methods We conducted a retrospective cohort study to evaluate the clinical characteristics and survival of women with recurrent uLMS and identify prognostic factors. Results Overall, 71 patients with first recurrence of uLMS were included in our study. 19 patients (26.8%) received systemic therapy and 52 patients (73.2%) received secondary cytoreductive surgery (SCS). In SCS subgroup (n = 52), a complete resection with no residual disease was performed in 47 patients (90.4%). 38.5% (20/52) patients received non-reproductive organ surgeries. 10 (19.2%) patients had received thoracic surgery because of lung-only recurrence. Bowel, bladder surgery was performed in 8 (15.4%), 3 (5.8%) patients, respectively. 1 (1.9%) patient had received liver surgery. The median follow-up duration was 38.7 months (range: 2.7-317.6 months). 41 (57.7%) patients died during follow-up. 5-year OS for the entire cohort was 52.9%. Patients experienced first recurrence after initial diagnoses within 12 months (n = 24) had a worse 5-year OS than those after 12 months (n = 47) (17.0% vs. 69.1%, P < 0.001). 5-year OS for the SCS and non-SCS subgroup was 62.0% and 28.0%, respectively (P < 0.001). Multivariate analysis showed time to fist recurrence within 12 months (HR = 4.60, 95% CI: 1.49–14.4, P = 0.008) was an independent predictor of decreased 5-year OS in SCS subgroup. Conclusions SCS is an important treatment choice for recurrent uLMS and seems to have benefited patients. Time to fist recurrence within 12 months is an independent predictor of decreased 5-year OS in SCS subgroup.

Intravenous leiomyomatosis presenting as Budd–Chiari syndrome: a case report and literature review

Abstract Background Budd–Chiari syndrome (BCS) caused by intravenous leiomyomatosis (IVL) is rare. Further reports and thorough evaluation are needed to identify and manage this disease. Method We described the case of a 49-year-old lady, exhibiting features of BCS secondary to IVL, and reviewed three other previous cases of BCS caused by IVL. Results The mean onset age of these four patients was 54.8 years. All but one (Patient No. 2) had a history of myoma, myomectomy, or hysterectomy. Abdominal pain, bloating or increasing abdominal circumference, and bilateral lower extremity edema were common symptoms. The establishment of clinical diagnoses of IVL and BCS mainly depends on clinical presentations and imaging, such as ultrasonography, computed tomography, and magnetic resonance imaging. Surgical intervention to alleviate the hepatic veins outflow obstruction is the most important treatment. Conclusions BCS caused by IVL should be considered when the inferior vena cava and right atrium lesions were detected in a patient with characteristics of BCS and a history of uterine myoma or hysterectomy. Complete tumor resection is the only curative treatment and should be performed as soon as possible.

Gestational trophoblastic neoplasia with pancreatic metastasis: clinical characteristics, treatment strategies, and outcomes

Abstract Objective Pancreatic metastasis of gestational trophoblastic neoplasia (GTN) is extremely rare, with only a few reported cases. Methods A retrospective analysis was conducted on GTN patients with pancreatic metastasis at Peking Union Medical College Hospital (2000–2024) and a literature review was performed. A descriptive analysis was carried out on the clinical characteristics, treatment strategies, and outcomes of patients who met the inclusion criteria. Fisher's exact test was used to analyze differences in metastatic patterns and clinical outcomes among patients with different clinical characteristics. Results A total of 24 cases were identified (7 from our institute, 17 from literature): 18 choriocarcinomas, 5 placental-site trophoblastic tumors, and 1 epithelioid trophoblastic tumor. Pancreatic metastasis led to organ-specific symptoms. Treatments included chemotherapy (single/multi-agent), immunotherapy, and targeted therapy. Six patients underwent surgical or localized interventions. Outcomes varied: 9 (37.5%) achieved disease-free survival, 5 (20.8%) had partial remission, and 10 (41.7%) died. Surgical or invasive interventions were associated with significantly improved outcomes (P = 0.024). Conclusion Pancreatic invasion in GTN is a high-risk condition often associated with poor outcomes. Advanced imaging techniques enhance diagnostic accuracy, while endoscopic ultrasound-guided fine-needle biopsy provides essential histopathological confirmation. Multi-agent chemotherapy remains the cornerstone of treatment, with surgical interventions carefully tailored to the individual patient’s condition. For better management and prognosis, an initial treatment strategy integrating multi-agent chemotherapy, immunotherapy, and targeted therapies may offer benefits; however, further investigation is warranted.

Monozygotic twin cases of endometriosis with Glanzmann thrombasthenia: a case report and review of literature

AbstractBackgroundGlanzmann thrombasthenia (GT) is a rare bleeding disorder with a high prevalence in communities where consanguineous marriages are mainstream. Endometriosis is a chronic inflammatory disease, and its risk increases in women with menstrual periods of longer than six days. The phenotypic expression of endometriosis is determined by the frequency and rate of the menstrual flow, as well as genetic and environmental factors.Result and case presentation14-year-old monozygotic twin sisters with GT who developed ovarian endometriosis were referred to Hazrat Rasoul Hospital due to severe dysmenorrhea. In ultrasonic examination, endometrioma cysts were reported in both patients. They both went under endometrioma cystectomy, and the bleeding was managed using antifibrinolytic drugs, followed by recombinant activated coagulation factor VII. Both were discharged after 3 days. In the ultrasound examination performed one year after the surgery, ovaries were normal in the first twin, while the second twin had a 28 × 30 hemorrhagic cyst in the left ovary.Discussion and conclusionMenstrual bleeding and genetic factors are two theories that could be related to GT and endometriosis association, and GT could be considered a risk factor for endometriosis.