OBJECTIVES: Hysterectomy remains the only definitively effective treatment for diffuse uterine leiomyomatosis (DUL). However, no standardized management strategy exists for DUL patients wishing to preserve fertility. This study summarizes and analyzes 5 cases of individualized treatment in DUL patients desiring fertility preservation, aiming to provide a clinical reference for personalized management of similar patients. METHODS: We retrospectively analyzed the clinical data of 5 DUL patients with fertility intentions admitted to the Department of Obstetrics and Gynecology at Third Xiangya Hospital of Central South University. To preserve fertility, individualized treatment plans were selected based on clinical manifestations and fibroid distribution. One patient received high-intensity focused ultrasound (HIFU); one underwent hysteroscopic myomectomy (HM) combined with laparoscopic myomectomy (LRM); one underwent HIFU combined with HM and LRM; one received drug therapy combined with staged HM; and one underwent HIFU combined with staged HM and drug therapy. Treatment outcomes and pregnancy results were analyzed. RESULTS: After treatment, all 5 patients showed marked improvement in menstrual volume or dysmenorrhea symptoms and significant reduction in uterine volume; mild intrauterine adhesions occurred in 3 cases. All 5 patients achieved successful pregnancy. One patient with chronic hypertension developed severe preeclampsia at 34 weeks and underwent cesarean section, while the remaining 4 delivered at term by cesarean section. Three cases of placenta accreta and 2 cases of postpartum hemorrhage occurred. During long-term follow-up, one patient underwent hysterectomy 2 years postpartum due to increased menstrual volume, while the other 4 remained stable. CONCLUSIONS Individualized treatment tailored to DUL patients' conditions can preserve fertility, support successful pregnancy, and achieve favorable pregnancy outcomes.
Humans ; Female ; Pregnancy ; Leiomyomatosis/therapy* ; Uterine Neoplasms/therapy* ; Adult ; Retrospective Studies ; Fertility Preservation/methods* ; Hysterectomy ; Uterine Myomectomy/methods* ; High-Intensity Focused Ultrasound Ablation ; Pregnancy Outcome

Humans ; Female ; Fumarate Hydratase/genetics* ; Kidney Neoplasms ; Carcinoma, Renal Cell ; Leiomyomatosis ; Uterine Neoplasms

Objective: To investigate the clinicopathologic and molecular characteristics of fumarate hydratase (FH) deficient uterine leiomyoma. Methods: Eighty cases of FH deficient uterine leiomyoma were diagnosed from April 2018 to September 2022 in Department of Pathology, Peking University Third Hospital. Sanger sequencing of FH gene exons (exon 1-10) were performed on tumor tissues and matched non-tumor tissues/peripheral blood for all cases. FH immunohistochemistry were performed in 74 cases; S-(2-succino)-cysteine (2SC) were also detected by immunohistochemistry in five cases. Results: Patients' age ranged from 18 to 54 (36.0±7.5) years, with more than 60% exhibiting clinical symptoms of multiple and large leiomyomas (the median diameter was 70 mm). More than four histologic features, including staghorn vasculature, alveolar-pattern edema, bizarre nuclei, oval nuclei arranged in chains, prominent eosinophilic nucleoli with perinucleolar haloes and eosinophilic intracytoplasmic globules were observed in 98.5% (67/68) patients. The immunohistochemical sensitivity of FH and 2SC were 97.3% and 100%, respectively. Based on the Sanger sequencing results, the cases were divided into germline variant group (31 cases), somatic variant group (29 cases) and no variant group (20 cases). Sixty-nine percent (20/29) of the patients with FH germline variation had clear family history. Conclusions: Clinical features, histological morphology, FH and 2SC immunohistochemistry and Sanger sequencing have their own significance and limitations in differential diagnosis of FH deficient uterine leiomyoma. In clinical practice, the above information should be fully integrated and studied for accurate pathologic diagnosis and selection of patients with FH germline variation.
Female ; Humans ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Fumarate Hydratase/genetics* ; Uterine Neoplasms/pathology* ; Leiomyoma/pathology* ; Germ-Line Mutation ; Diagnosis, Differential ; Leiomyomatosis/pathology* ; Carcinoma, Renal Cell/diagnosis*

Humans ; Consensus ; Leiomyomatosis/surgery* ; Pelvis/diagnostic imaging* ; China

OBJECTIVE: To analyze clinical phenotype and genetic variants in a Chinese pedigree of hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome. METHODS: Whole exome sequencing was carried out for the proband from the pedigree. Suspected FH gene variants were validated by Sanger sequencing. Clinical manifestation and histopathological examination were used to analyze the pedigree comprehensively. RESULTS: The pedigree met the clinical diagnostic criteria for HLRCC syndrome. The whole exome sequencing showed that the FH gene of the proband had a heterozygous missense variant of c.1490T>C (p.F497S), which was consistent with the Sanger sequencing. The mother, daughter and son of the proband all had the heterozygous missense variant of c.1490T>C (p.F497S). According to the American Society of Medical Genetics and Genomics Classification Standards and Guidelines for Genetic Variations, c.1490T>C (p.F497S) (PM2+PP1-M+PP3+PP4) was a possible pathogenic variant. Based on our literature search, this variant was a new variant that had not been reported. CONCLUSION The FH gene missense variant of c.1490T>C (p.F497S) may be the cause of the HLRCC syndrome pedigree, which provides a basis for the genetic diagnosis and genetic counseling of the HLRCC syndrome.
Carcinoma, Renal Cell/genetics* ; Humans ; Kidney Neoplasms/genetics* ; Leiomyomatosis/pathology* ; Mutation ; Neoplastic Syndromes, Hereditary ; Pedigree ; Phenotype ; Skin Neoplasms ; Uterine Neoplasms

Carcinoma, Renal Cell/surgery* ; Fumarate Hydratase ; Humans ; Kidney Neoplasms/surgery* ; Leiomyomatosis/pathology*

Female ; Heart Atria ; diagnostic imaging ; surgery ; Heart Neoplasms ; diagnostic imaging ; surgery ; Humans ; Leiomyomatosis ; diagnostic imaging ; surgery ; Magnetic Resonance Imaging ; Middle Aged ; Ultrasonography

For the modern practice of cancer surgery, the concept of oncovascular surgery (OVS), defined as cancer resection with concurrent ligation or reconstruction of a major vascular structure, can be very important. OVS for advanced cancers requires specialized procedures performed by a specialized multidisciplinary team. Roles of oncovascular surgeons are summarized as: a primary surgeon in vessel-origin tumors, a rescue surgeon treating complications during cancer surgery, and a consultant surgeon as a multidisciplinary team for cancer surgery. Vascular surgeons must show leadership in cancer surgery in cases of complex advanced diseases, such as angiosarcoma, leiomyosarcoma, intravenous leiomyomatosis, retroperitoneal soft tissue sarcoma, iatrogenic injury of the major vessels during cancer surgery, pancreatic cancer with vascular invasion, extremity soft tissue sarcoma, melanoma and others.
Consultants ; Extremities ; Hemangiosarcoma ; Humans ; Leadership ; Leiomyomatosis ; Leiomyosarcoma ; Ligation ; Melanoma ; Pancreatic Neoplasms ; Sarcoma ; Surgeons

PURPOSE: Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is a rare genetic syndrome resulting from germline mutations in fumarate hydratase. The combination of bevacizumab plus erlotinib showed promising interim results for HLRCC-associated RCC. Based on these results, we analyzed the outcome of bevacizumab plus erlotinib in Korean patients with HLRCC-associated RCC. MATERIALS AND METHODS: We retrospectively reviewed the efficacy and safety of bevacizumab plus erlotinib in patients with HLRCC-associated RCC who were confirmed to have germline mutations in fumarate hydratase. The primary endpoint was the objective response rate (ORR), while the secondary endpoints were progression-free survival (PFS) and overall survival (OS). RESULT: We identified 10 patients with advanced HLRCC-associated RCC who received bevacizumab plus erlotinib. Median age at diagnosis was 41 years, and five of the patients had received the combination as first- or second-line treatments. The ORR was 50% and the median PFS and OS were 13.3 and 14.1 months, respectively. Most adverse events were predictable and manageable by conventional measures, except for one instance where a patient died of gastrointestinal bleeding. CONCLUSION: This is the first real-world outcome of the treatment of advanced HLRCC-associated RCC. Bevacizumab plus erlotinib therapy showed promising activity with moderate toxicity. We should be increasingly aware of HLRCC-associated RCC and bevacizumab plus erlotinib should be a first-line treatment for this condition, unless other promising data are published.
Bevacizumab ; Carcinoma, Renal Cell ; Diagnosis ; Disease-Free Survival ; Erlotinib Hydrochloride ; Fumarate Hydratase ; Germ-Line Mutation ; Hemorrhage ; Humans ; Leiomyomatosis ; Retrospective Studies

OBJECTIVE: Intravenous leiomyomatosis (IVL) and benign metastasizing leiomyoma (BML) are uncommon variants of benign uterine leiomyomas with extrauterine manifestations. Categorizing the extent of disease allows clinicians to delineate the clinical spectrum and the level of sophistication for complete surgical resection. METHODS: Twelve patients with IVL and BML were reviewed. They were divided into early versus late stage disease groups, and initial manifestation, clinical characteristics, laboratory values, surgical pathology, and follow up data were summarized. RESULTS: Patients were mostly pre- or peri-menopausal and parous. Patients with late stage disease were more likely to present with cardiac symptoms or abnormal findings on chest X-ray, whereas those with early stage disease presented with classical leiomyoma symptoms including heavy menstrual bleeding, increased myoma size, or lower abdominal discomfort. Tumor marker levels were within normal ranges. A trend of higher neutrophil to leukocyte ratio was observed in the late versus the early stage group (10.4 vs. 1.51, P=0.07); the platelet leukocyte ratio was statistically higher in patients with late stage IVL (0.23 vs. 0.13, P=0.04). The overall recurrence rate was 25%. No recurrence was observed in stage I or stage III IVL groups, while 50% of the stage II IVL group showed recurrence in the pelvic cavity. CONCLUSION: IVL and BML are benign myoma variants with paradoxically metastatic clinical presentation. Careful inquiry of systemic symptoms, the presence of underlying systemic inflammation, and a high index of suspicion are required for preoperative diagnosis. Furthermore, a multidisciplinary approach is necessary to improve outcomes of surgical resection.
Blood Platelets ; Diagnosis ; Follow-Up Studies ; Hemorrhage ; Humans ; Inflammation ; Leiomyoma* ; Leiomyomatosis* ; Leukocytes ; Myoma ; Neoplasm Metastasis ; Neutrophils ; Pathology, Surgical ; Recurrence ; Reference Values ; Smooth Muscle Tumor ; Thorax