RÉSUMÉ
Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a rare autosomal dominant syndrome caused by a germline mutation in the fumarate hydratase (FH) gene that manifests with cutaneous leiomyomas, uterine fibroids, and renal cell cancer (RCC). Patients with HLRCC-associated RCC (HLRCC-RCC) have aggressive clinical courses, but there is no standardized therapy for advanced HLRCC-RCC. In this study, we described a case of aggressive HLRCC in a 33-year-old female who exhibited a novel heterozygous germline insertion mutation in exon 8 of the FH gene (c.1126 C > T; p.Q376*). The patient underwent laparoscopic resection of the right kidney, but metastases appeared within 3 months after surgery. Histological staining of the resected tumor revealed high expression levels of programmed cell death-ligand 1 (PD-L1). Therefore, the patient was treated with immunotherapy. The patient achieved a partial response to immunotherapy, and the treatment of metastatic lesions has continued to improve. A thorough literature review pinpointed 76 historical cases of HLRCC-RCC that had undergone immunotherapy. From this pool, 46 patients were selected for this study to scrutinize the association between mutations in the FH gene and the effectiveness of immunotherapy. Our results indicate that immunotherapy could significantly improve the overall survival (OS) of patients with HLRCC-RCC. However, no influence of different mutations in the FH germline gene on the therapeutic efficacy of immunotherapy was observed. Therefore, our study suggested that immunotherapy was an effective therapeutic option for patients with HLRCC regardless of the type of FH germline mutation.
Sujet(s)
Fumarate hydratase , Immunothérapie , Léiomyomatose , Syndromes néoplasiques héréditaires , Tumeurs cutanées , Tumeurs de l'utérus , Humains , Femelle , Léiomyomatose/génétique , Léiomyomatose/anatomopathologie , Léiomyomatose/thérapie , Fumarate hydratase/génétique , Adulte , Syndromes néoplasiques héréditaires/génétique , Syndromes néoplasiques héréditaires/thérapie , Syndromes néoplasiques héréditaires/complications , Syndromes néoplasiques héréditaires/anatomopathologie , Tumeurs de l'utérus/génétique , Tumeurs de l'utérus/anatomopathologie , Tumeurs de l'utérus/thérapie , Tumeurs cutanées/génétique , Tumeurs cutanées/anatomopathologie , Tumeurs cutanées/thérapie , Mutation germinale , Tumeurs du rein/génétique , Tumeurs du rein/anatomopathologie , Tumeurs du rein/thérapie , Néphrocarcinome/génétique , Néphrocarcinome/anatomopathologie , Néphrocarcinome/thérapieRÉSUMÉ
Diffuse oesophageal leiomyomatosis is a rare benign disease in the paediatric population. This report highlights a recent clinical case, together with a narrative review of current world literature.An early middle childhood girl with recurrent lower respiratory tract infections for 2 years was noted to have a retrocardiac lesion on chest X-ray, later confirmed to be an oesophageal mass on CT imaging. She underwent an Ivor-Lewis oesophagogastrectomy and a Heineke-Mikulicz pyloroplasty. Pathology examination revealed type I diffuse oesophageal leiomyomatosis. Alport syndrome was later confirmed following an episode of postoperative haematuria, which was corroborated by electron microscopy examination following renal biopsy.With an oesophageal mass lesion and Alport syndrome, oesophageal leiomyomatosis should be suspected in any patient with a clinical history of dysphagia and/or respiratory symptoms. Endoscopic ultrasound-guided tissue biopsy is valuable for diagnosis of all suspected lesions. Surgical resection is mandatory to effect cure.
Sujet(s)
Tumeurs de l'oesophage , Léiomyomatose , Néphropathie familiale avec surdité , Humains , Femelle , Léiomyomatose/chirurgie , Léiomyomatose/anatomopathologie , Léiomyomatose/imagerie diagnostique , Léiomyomatose/diagnostic , Néphropathie familiale avec surdité/complications , Néphropathie familiale avec surdité/diagnostic , Tumeurs de l'oesophage/anatomopathologie , Tumeurs de l'oesophage/diagnostic , Tumeurs de l'oesophage/chirurgie , Enfant , Tomodensitométrie , OesophagectomieRÉSUMÉ
Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome is an autosomal-dominant disorder that results from a germline pathogenic variant in the fumarate hydratase (FH) gene on chromosome 1, characterised by renal cell carcinoma (RCC), cutaneous leiomyoma and uterine leiomyoma. Leiomyosarcomas are reported in less than 1% of those with HLRCC. We report a case of a man in his 30s who had a long-standing plaque excised from the left upper arm after undergoing a radical nephrectomy for a fumarate-deficient RCC, with histological exam revealing a grade 1 leiomyosarcoma. Genetic testing confirmed a heterozygous pathogenic variant in the FH gene. This is a rare case of leiomyosarcoma associated with HLRCC, and our patient remains under surveillance with interval abdominal imaging and skin examination. Leiomyosarcomas are difficult to distinguish clinically from their benign counterpart; therefore, histopathological examination is paramount with a low threshold for excision.
Sujet(s)
Fumarate hydratase , Léiomyomatose , Léiomyosarcome , Syndromes néoplasiques héréditaires , Tumeurs cutanées , Tumeurs de l'utérus , Humains , Léiomyomatose/génétique , Léiomyomatose/anatomopathologie , Léiomyomatose/chirurgie , Léiomyomatose/diagnostic , Mâle , Tumeurs cutanées/génétique , Tumeurs cutanées/diagnostic , Tumeurs cutanées/anatomopathologie , Léiomyosarcome/génétique , Léiomyosarcome/diagnostic , Léiomyosarcome/chirurgie , Léiomyosarcome/anatomopathologie , Syndromes néoplasiques héréditaires/génétique , Syndromes néoplasiques héréditaires/diagnostic , Syndromes néoplasiques héréditaires/chirurgie , Syndromes néoplasiques héréditaires/anatomopathologie , Tumeurs de l'utérus/génétique , Tumeurs de l'utérus/anatomopathologie , Tumeurs de l'utérus/diagnostic , Tumeurs de l'utérus/chirurgie , Adulte , Fumarate hydratase/génétique , Néphrectomie , Tumeurs du rein/génétique , Tumeurs du rein/anatomopathologie , Tumeurs du rein/diagnostic , Tumeurs du rein/chirurgieRÉSUMÉ
Disseminated peritoneal leiomyomatosis (DPL) is a rare and benign clinical entity. It is also known as leiomyomatosis peritonealis disseminata (LPD). Here, we report and discuss a case of a primiparous woman in her early 40s who presented with heavy, prolonged, painful menses and heaviness in her lower abdomen. She underwent a laparoscopic myomectomy for a fibroid uterus, 12 months ago for similar complaints. On workup, she was diagnosed with DPL. We performed a total abdominal hysterectomy with bilateral salpingectomy, low anterior resection with stapled colorectal anastomosis and excision of peritoneal tumour deposits in consortium with the gastrosurgery team. Her postoperative period was uneventful, and the patient was discharged on postop day 6. Her histopathology report was consistent with leiomyoma; the follow-up period was uneventful.
Sujet(s)
Hystérectomie , Tumeurs du péritoine , Humains , Femelle , Tumeurs du péritoine/diagnostic , Tumeurs du péritoine/chirurgie , Tumeurs du péritoine/anatomopathologie , Adulte , Léiomyome/chirurgie , Léiomyome/diagnostic , Léiomyome/anatomopathologie , Léiomyomatose/chirurgie , Léiomyomatose/anatomopathologie , Léiomyomatose/diagnostic , Tumeurs de l'utérus/chirurgie , Tumeurs de l'utérus/diagnostic , Tumeurs de l'utérus/anatomopathologie , Diagnostic différentiel , Myomectomie de l'utérus , SalpingectomieRÉSUMÉ
Leiomyoma is the most prevalent benign tumor of the female reproductive system. Benign metastasizing leiomyoma (BML) is a rare phenomenon that presents at distant sites, typically the lungs, exhibiting histopathological features similar to the primary uterine tumor in the absence of malignancy features in both. Fumarate hydratase-deficient uterine leiomyoma (FH-d UL) is an uncommon subtype among uterine smooth muscle tumors (0.5-2%), showing distinctive histomorphology and FH inactivation. The majority of FH-d ULs are sporadic, caused by somatic FH inactivation, while a minority of cases occur in the context of the hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome caused by germline FH inactivation. Metastasizing FH-d UL has not been well documented and might be under-reported. Here, we present two cases (21- and 34-year-old females) who presented with metastasizing FH-d UL after myomectomy/hysterectomy with histologically proven multiple lung metastases in both, in addition to multi-organ involvement in one case (cervical-thoracic lymph nodes, left kidney, perihepatic region, left zygomatic bone, and soft tissues). Pathological examination confirmed FH-d leiomyomas in the primary/recurrent uterine tumors, multiple lung lesions, and a renal mass. The minimal criteria for diagnosis of leiomyosarcoma were not fulfilled. Genetic testing revealed germline pathogenic FH variants in both cases (c.1256C > T; p.Ser419Leu in Case 1 and c.425A > G; p.Gln142Arg in Case 2). These novel cases highlight a rare but possibly under-recognized presentation of FH-d BML. Our study suggests that FH-d BML cases might be enriched for the HLRCC syndrome.
Sujet(s)
Fumarate hydratase , Léiomyome , Tumeurs du poumon , Tumeurs de l'utérus , Humains , Femelle , Tumeurs de l'utérus/anatomopathologie , Tumeurs de l'utérus/génétique , Fumarate hydratase/déficit , Fumarate hydratase/génétique , Adulte , Léiomyome/anatomopathologie , Léiomyome/génétique , Tumeurs du poumon/anatomopathologie , Tumeurs du poumon/génétique , Jeune adulte , Léiomyomatose/anatomopathologie , Léiomyomatose/génétique , Myomectomie de l'utérus , HystérectomieRÉSUMÉ
Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an autosomal dominant cancer predisposition syndrome characterized by cutaneous leiomyomas, uterine leiomyomas, and aggressive renal cancer. Germline variants in the fumarate hydratase (FH) gene predispose to HLRCC. Identifying germline pathogenic FH variants enables lifetime renal cancer screening and genetic testing for family members. In this report, we present a FH missense variant (c.1039T>C (p.S347P)), initially classified as a variant of uncertain significance. Clinical assessment, histopathological findings, molecular genetic studies, and enzymatic activity studies support the re-classification of the FH c.1039T>C variant to "pathogenic" based on ACMG/AMP criteria. Further insights into pathological recognition of FH-deficient renal cancer are discussed and should be recognized. This study has shown how (a) detailed multi-disciplinary analyses of a single variant can reclassify rare missense variants in FH and (b) careful pathological review of renal cancers is obligatory when HLRCC is suspected.
Sujet(s)
Fumarate hydratase , Léiomyomatose , Mutation faux-sens , Syndromes néoplasiques héréditaires , Tumeurs cutanées , Tumeurs de l'utérus , Humains , Fumarate hydratase/génétique , Léiomyomatose/génétique , Léiomyomatose/anatomopathologie , Femelle , Tumeurs cutanées/génétique , Tumeurs cutanées/anatomopathologie , Tumeurs de l'utérus/génétique , Tumeurs de l'utérus/anatomopathologie , Syndromes néoplasiques héréditaires/génétique , Syndromes néoplasiques héréditaires/anatomopathologie , Tumeurs du rein/génétique , Tumeurs du rein/anatomopathologie , Pedigree , Mutation germinale , Mâle , Adulte , Prédisposition génétique à une maladie , Adulte d'âge moyenRÉSUMÉ
Women with germline pathogenic variants (PV) in the fumarate hydratase (FH) gene develop cutaneous and uterine leiomyomata and have an increased risk of developing aggressive renal cell carcinomas. Many of these women are unaware of their cancer predisposition until an atypical uterine leiomyoma is diagnosed during a myomectomy or hysterectomy, making a streamlined genetic counseling process after a pathology-based atypical uterine leiomyoma diagnosis critical. However, the prevalence of germline pathogenic/likely PVs in FH among atypical uterine leiomyomata cases is unknown. To better understand FH germline PV prevalence and current patterns of genetic counseling and germline genetic testing, we undertook a retrospective review of atypical uterine leiomyomata cases at a single large center. We compared clinical characteristics between the FH PV, FH wild-type (WT), and unknown genetic testing cohorts. Of the 144 cases with atypical uterine leiomyomata with evaluable clinical data, only 49 (34%) had documented genetic test results, and 12 (8.3%) had a germline FH PV. There were 48 IHC-defined FH-deficient cases, of which 41 (85%) had FH testing and nine had a germline FH PV, representing 22% of the tested cohort and 18.8% of the FH-deficient cohort. Germline FH PVs were present in 8.3% of evaluable patients, representing 24.5% of the cohort that completed genetic testing. These data highlight the disconnect between pathology and genetic counseling, and help to refine risk estimates that can be used when counseling patients with atypical uterine leiomyomata. PREVENTION RELEVANCE: Women diagnosed with fumarate hydratase (FH)-deficient uterine leiomyomata are at increased risk of renal cancer. This work suggests a more standardized pathology-genetic counseling referral pathway for these patients, and that research on underlying causes of FH-deficient uterine leiomyomata in the absence of germline FH pathogenic/likely pathogenic variants is needed.
Sujet(s)
Fumarate hydratase , Dépistage génétique , Mutation germinale , Léiomyome , Tumeurs de l'utérus , Humains , Femelle , Fumarate hydratase/génétique , Fumarate hydratase/déficit , Tumeurs de l'utérus/génétique , Tumeurs de l'utérus/anatomopathologie , Tumeurs de l'utérus/diagnostic , Adulte d'âge moyen , Études rétrospectives , Adulte , Léiomyome/génétique , Léiomyome/anatomopathologie , Léiomyome/diagnostic , Prédisposition génétique à une maladie , Conseil génétique , Léiomyomatose/génétique , Léiomyomatose/anatomopathologie , Léiomyomatose/diagnosticRÉSUMÉ
BACKGROUND: Intravenous leiomyomatosis (IVL), pulmonary benign metastatic leiomyomatosis (PBML), and leiomyomatosis peritonealis disseminata (LPD) are leiomyomas with special growth patterns and high postoperative recurrence rates. We report the safety and efficacy of a pilot study of sirolimus in the treatment of recurrent IVL, PBML, and recurrent LPD. METHODS: This was a pilot study to evaluate the safety and efficacy of sirolimus in the treatment of leiomyomatosis (ClinicalTrials.gov identifier NCT03500367) conducted in China. Patients received oral sirolimus 2 mg once a day for a maximum of 60 months or until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to stop. The primary end point of this study was the objective response rate. Secondary end points included safety and tolerability, disease control rate, and progression-free survival. RESULTS: A total of 15 patients with leiomyomatosis were included in the study, including five with recurrent IVL, eight with PBML and two with recurrent LPD. The median follow-up time was 15 months (range 6-54 months), nine patients (60%) had treatment-related adverse events (including all levels), and two patients had treatment-related grade 3 or 4 adverse events. The objective response rate was 20.0% (95% CI, 7.1-45.2%), and the disease control rate was 86.7% (95% CI, 62.1-96.3%). Partial response was achieved in three patients. The median response time in the three partial response patients was 33 months (range 29-36 months), and the sustained remission time of these three patients reached 0, 18, and 25 months, respectively. CONCLUSIONS: Sirolimus was safe and effective in the treatment of recurrent IVL, PBML, and recurrent LPD. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03500367. Registered on 18 April 2018.
Sujet(s)
Léiomyomatose , Tumeurs du péritoine , Humains , Évolution de la maladie , Léiomyomatose/traitement médicamenteux , Léiomyomatose/complications , Léiomyomatose/anatomopathologie , Tumeurs du péritoine/complications , Tumeurs du péritoine/anatomopathologie , Tumeurs du péritoine/chirurgie , Projets pilotes , Sirolimus/effets indésirablesRÉSUMÉ
OBJECTIVE: To analyse the risk factors for post-operative recurrence or progression of intravenous leiomyomatosis and explore the impact of different treatment strategies on patient prognosis. METHODS: Patients with intravenous leiomyomatosis who underwent surgery from January 2011 to December 2020 and who were followed for ≥3 months were included. The primary endpoint was recurrence (for patients with complete resection) or progression (for patients with incomplete resection). Kaplan-Meier survival analysis was used to analyse the factors affecting recurrence. RESULTS: A total of 114 patients were included. The median age was 45 years old (range 24-58). The tumors were confined to the uterus and para-uterine vessels in 48 cases (42.1%), while in 66 cases (57.9%) it involved large vessels (iliac vein or genital vein and/or proximal large veins). The median follow-up time was 24 months (range 3-132). Twenty-nine patients (25.4%) had recurrence or progression. The median recurrence or progression time was 16 months (range 3-60). Incomplete tumor resection (p=0.019), involvement of the iliac vein or genital vein (p=0.042), involvement of the inferior vena cava (p=0.025), and size of the pelvic tumor ≥15 cm (p=0.034) were risk factors for recurrence and progression. For intravenous leiomyomatosis confined to the uterus or para-uterine vessels, no post-operative recurrence after hysterectomy and bilateral oophorectomy occurred in this cohort. Compared with hysterectomy and bilateral oophorectomy, the risk of recurrence after tumorectomy (with the uterus and ovaries retained) was significantly greater (p=0.009), while the risk of recurrence after hysterectomy was not significantly increased (p=0.058). For intravenous leiomyomatosis involving the iliac vein/genital vein and the proximal veins, post-operative aromatase inhibitor treatment (p=0.89) and two-stage surgery (p=0.86) were not related to recurrence in patients with complete tumor resection. CONCLUSION: Incomplete tumor resection, extent of tumor lesions and size of the pelvic tumor were risk factors for post-operative recurrence and progression of intravenous leiomyomatosis.
Sujet(s)
Évolution de la maladie , Léiomyomatose , Récidive tumorale locale , Tumeurs de l'utérus , Humains , Femelle , Adulte d'âge moyen , Adulte , Léiomyomatose/chirurgie , Léiomyomatose/anatomopathologie , Récidive tumorale locale/anatomopathologie , Récidive tumorale locale/chirurgie , Facteurs de risque , Tumeurs de l'utérus/chirurgie , Tumeurs de l'utérus/anatomopathologie , Études rétrospectives , Jeune adulte , Tumeurs vasculaires/anatomopathologie , Tumeurs vasculaires/chirurgieRÉSUMÉ
BACKGROUND: To compare clinicopathologic, molecular features, and treatment outcome between fumarate hydratase-deficient renal cell carcinoma (FH-dRCC) and type 2 papillary renal cell carcinoma (T2 pRCC). METHODS: Data of T2 pRCC patients and FH-dRCC patients with additional next-generation sequencing information were retrospectively analyzed. The cancer-specific survival (CSS) and disease-free survival (DFS) were primary endpoint. RESULTS: A combination of FH and 2-succino-cysteine (2-SC) increased the rate of negative predictive value of FH-dRCC. Compared with T2 pRCC cases, FH-dRCC cases displayed a greater prevalence in young patients, a higher frequency of radical nephrectomy. Seven FH-dRCC and two T2 pRCC cases received systemic therapy. The VEGF treatment was prescribed most frequently, with an objective response rate (ORR) of 22.2% and a disease control rate (DCR) of 30%. A combined therapy with VEGF and checkpoint inhibitor reported an ORR of 40% and a DCR of 100%. FH-dRCC cases showed a shortened CSS (P = 0.042) and DFS (P < 0.001). The genomic sequencing revealed 9 novel mutations. CONCLUSIONS: Coupled with genetic detection, immunohistochemical biomarkers (FH and 2-SC) can distinguish the aggressive FH-dRCC from T2 pRCC. Future research is awaited to illuminate the association between the novel mutations and the clinical phenotypes of FH-dRCC in the disease progression.
Sujet(s)
Néphrocarcinome , Tumeurs du rein , Léiomyomatose , Tumeurs cutanées , Tumeurs de l'utérus , Humains , Femelle , Néphrocarcinome/traitement médicamenteux , Néphrocarcinome/génétique , Néphrocarcinome/métabolisme , Tumeurs du rein/traitement médicamenteux , Tumeurs du rein/génétique , Tumeurs du rein/diagnostic , Fumarate hydratase/génétique , Fumarate hydratase/métabolisme , Études rétrospectives , Facteur de croissance endothéliale vasculaire de type A , Léiomyomatose/diagnostic , Léiomyomatose/génétique , Léiomyomatose/anatomopathologie , Résultat thérapeutique , Tumeurs de l'utérus/génétique , Tumeurs de l'utérus/anatomopathologie , Tumeurs cutanées/génétiqueRÉSUMÉ
RATIONALE: Intravascular/intravenous leiomyomatosis (IVL) is a peculiar variant of uterine leiomyoma that is classified as a histologically benign smooth muscle tumor with a biological behavior similar to that of a malignant tumor. It is characterized by the proliferation of leiomyomas spreading along the uterine and extrauterine venous circulation. PATIENT CONCERNS: Herein, we present 2 cases of IVL who had completely different clinical manifestations to stress the need for constant vigilance of IVL diagnosis and the understanding of uterine leiomyoma heterogenicity. Case 1 was registered for fever without specific triggering factors, irregular menstruation and clinically diagnosed uterine diverticula, while no information about fibroids was mentioned. Case 2 was characterized by an aggressively growing abdominal mass. With a large space-occupying lesion in the right abdominopelvic cavity and no imaging evidence of involvement of the iliac vein or above vein, the patient was initially diagnosed with multiple myomata. DIAGNOSES: Both patients' diagnoses were confirmed as IVL by histopathology. To our knowledge, the mass of case 1 is the minimum IVL in the English literature. INTERVENTIONS: Subtotal hysterectomy with bilateral salpingectomy was performed on the former, while total hysterectomy with bilateral salpingectomy was performed on the latter. OUTCOMES: Both patients were comfortable, and no relapse occurred. LESSONS: Two cases in the study showed 2 different proceeding stages of the same disease and corroborated multiple pathogeneses, which have been mentioned in the available literature on IVL. Our work provides both supplement for clinical data to facilitate further research and better understanding of special types of fibroids to clinicians.
Sujet(s)
Léiomyomatose , Myome , Tumeurs de l'utérus , Maladies vasculaires , Femelle , Humains , Léiomyomatose/diagnostic , Léiomyomatose/chirurgie , Léiomyomatose/anatomopathologie , Tumeurs de l'utérus/diagnostic , Tumeurs de l'utérus/chirurgie , Tumeurs de l'utérus/anatomopathologie , Récidive tumorale locale , Veine iliaque commune/anatomopathologieRÉSUMÉ
OBJECTIVES: The aim was to explore the magnetic resonance imaging (MRI) features of stage-I intravenous leiomyomatosis (IVL). MATERIALS AND METHODS: From January 2019 to January 2023, clinical, pathological, and MRI data were collected from 19 cases confirmed by surgical pathology. Two radiologists retrospectively measured the tumor sizes, T1WIs, T2WIs, and ADC values and evaluated contrast-enhanced T1WIs, DWIs, complications and parauterine infiltrations. The number of tumor cells and the total nuclear area were measured. The percentage of tumor cell area out of the total area was used as the tumor cell density. RESULTS: Nineteen patients with stage-I IVL aged 33 to 66 years (mean age: 46 ± 7.6 years) were included in this study. All 19 cases were located in the myometrium or parametrium, with a mean diameter of 11.2 ± 4.8 cm. Among these cases, 14 (73.6%) were associated with leiomyoma, and six (31.6%) involved the broad ligament. Isointensity was observed in the T1WIs of 12 cases (63.2%), while slight hypointensity was seen in five patients (26.3%). Isointensity was observed in the on T2WIs of four cases (21.1%), and iso- or slight hyperintensity was observed in 15 cases (78.9%). A significant difference was detected between the normalized T2WIs of IVL and myometrium (p < 0.001). A Pearson correlation test showed demonstrated a negative correlation between the ADC and tumor cell density values (r = - 0.946, p < 0.001). Tortuous vessels were present in 17 cases (89.5%) within or next to the lesions, and multiple winding cord-like filling defects were seen in 11 cases (57.9%) within the tortuous vessels on the T2WIs. CONCLUSION: Identifying the characteristic MRI features of stage-I IVL helped improve the diagnostic accuracy achieves for this rare tumor. Stage-I IVL often presents as a large mass accompanied by leiomyoma, and it easily invades the broad ligament. TIWI signals exhibited isointensity, and T2WI signals contained iso- or slight hyperintensity. Tortuous vessels were present within or next to the lesions, and multiple winding cord-like filling defects were observed within the tortuous vessels on the T2WIs.
Sujet(s)
Léiomyomatose , Maladies vasculaires , Femelle , Humains , Adulte , Adulte d'âge moyen , Léiomyomatose/imagerie diagnostique , Léiomyomatose/chirurgie , Léiomyomatose/anatomopathologie , Études rétrospectives , Imagerie par résonance magnétique , Imagerie par résonance magnétique de diffusionRÉSUMÉ
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.
Sujet(s)
Néphrocarcinome , Tumeurs du rein , Léiomyomatose , Syndromes néoplasiques héréditaires , Tumeurs cutanées , Tumeurs de l'utérus , Femelle , Humains , Léiomyomatose/génétique , Léiomyomatose/anatomopathologie , Tumeurs du rein/génétique , Tumeurs cutanées/anatomopathologie , Mutation/génétique , SyndromeSujet(s)
Léiomyomatose , Tumeurs du péritoine , Humains , Léiomyomatose/anatomopathologie , Léiomyomatose/diagnostic , Tumeurs du péritoine/diagnostic , Tumeurs du péritoine/anatomopathologie , Femelle , Tomodensitométrie , Histocytochimie , Tumeurs du foie/diagnostic , Tumeurs du foie/anatomopathologie , Radiographie abdominale , Foie/anatomopathologie , Foie/imagerie diagnostique , Adulte d'âge moyen , Microscopie , AdulteRÉSUMÉ
OBJECTIVE: This study provides a concise overview of diagnostic and treatment strategies for intravenous leiomyomatosis (IVL), a rare disease with nonspecific clinical manifestations, based on cases from a tertiary referral hospital in China. METHODS: We retrospectively analyzed 11 premenopausal patients with confirmed IVL between 2018 and 2022. Clinical data from Ultrasound, Enhanced CT, and MRI were studied, along with surgical details, postoperative pathology, and follow-up information. RESULTS: Premenopausal patients showed no disease-specific symptoms, with 90.9% having a history of gynecological or obstetric surgery, and 72.7% having prior uterine fibroids. Cardiac involvement was evident in two cases, with echocardiography detecting abnormal floating masses from the inferior vena cava. Pelvic ultrasound indicated leiomyoma in 90.9% of cases, with ≥ 50 mm size. Surgery was the primary treatment, and lesions above the internal iliac vein resulted in significantly higher intraoperative blood loss (median 1300 ml vs. 50 ml, p = 0.005) and longer hospital stays (median 10 days vs. 4 days, p = 0.026). Three patients with lesions above the inferior vena cava required combined surgery with cardiac specialists. Recurrence occurred in 2 out of 11 patients with incomplete lesion resection. CONCLUSIONS: IVL mainly affects premenopausal women with uterine masses, primarily in the pelvic cavity (Stage I). Pelvic ultrasound aids early screening, while Enhanced CT or MR assists in diagnosing and assessing venous lesions. Complete resection is crucial to prevent recurrence. Lesions invading the internal iliac vein and above pose higher risks during surgery. A multidisciplinary team approach is essential for patients with lesions above the inferior vena cava, with simultaneous surgery as a potential treatment option.
Sujet(s)
Tumeurs du coeur , Léiomyomatose , Tumeurs de l'utérus , Tumeurs vasculaires , Humains , Femelle , Études rétrospectives , Léiomyomatose/imagerie diagnostique , Léiomyomatose/chirurgie , Léiomyomatose/anatomopathologie , Tumeurs du coeur/imagerie diagnostique , Tumeurs du coeur/chirurgie , Tumeurs du coeur/anatomopathologie , Veine cave inférieure/imagerie diagnostique , Veine cave inférieure/chirurgie , Veine cave inférieure/anatomopathologie , Échographie , Tumeurs de l'utérus/imagerie diagnostique , Tumeurs de l'utérus/chirurgie , Tumeurs de l'utérus/anatomopathologie , Tumeurs vasculaires/imagerie diagnostique , Tumeurs vasculaires/chirurgie , Tumeurs vasculaires/anatomopathologieRÉSUMÉ
BACKGROUND: Fumarate hydratase-deficient uterine leiomyomas (FH-dUL) are rare, accounting for only 0.4-1.6% of uterine leiomyomas. FH germline mutation gene is associated with hereditary leiomyomatosis and renal cell carcinoma syndrome (HLRCC). METHODS: In this study, we aim to investigate Clinicopathological features and FH mutation in FH-dUL. We performed a retrospective analysis of 300 cases of uterine leiomyoma, diagnosed from January 2017 to December 2021, within the archives of the Department of Pathology at Peking University People's Hospital. In our review of the immunohistochemical(IHC) staining was performed on 300 uSMTs to detect FH deficiency. RESULTS: We identified 21cases (21/300,7%) of FH-dUL. Nineteen cases (6.33%) displayed negative FH. Twenty-one cases (7%) displayed 2SC diffuse plasma and nuclear staining. The most common FH-d morphological features included staghorn vasculature ( 100%,21/21), alveolar-pattern oedema (71.43%, 15/21), scattered bizarre nuclei (23.81%, 5/21), eosinophilic cytoplasmic (rhabdoid) inclusions (47.62%, 10/21), significant eosinophilic nucleolus with peri-nucleolus hollowing (23.81%, 5/21), ovoid nuclei sometimes arranged in chains (9.52%, 2/21). DNA sequencing for the 21 cases was performed using Next Generation Sequencing (NGS). 6 cases were detected significant variations for the FH gene, 11 cases were detected FH gene mutation forvariants of uncertain significance (VUS), and 2 cases were detected a TP53 gene mutation. No related mutations were detected in the other two cases. CONCLUSIONS: FH-dUL is rare. The combination of predictive Clinicopathological evaluation,FH and 2SC IHC test, and molecular test were helpful for the screening of FH-dUL from uSMTs,or even the screening of HLRCC.
Sujet(s)
Néphrocarcinome , Tumeurs du rein , Léiomyomatose , Syndromes néoplasiques héréditaires , Tumeurs cutanées , Tumeurs de l'utérus , Femelle , Humains , Fumarate hydratase/génétique , Fumarate hydratase/analyse , Immunohistochimie , Études rétrospectives , Tumeurs de l'utérus/diagnostic , Tumeurs de l'utérus/génétique , Tumeurs de l'utérus/anatomopathologie , Léiomyomatose/diagnostic , Léiomyomatose/génétique , Léiomyomatose/anatomopathologie , Tumeurs cutanées/anatomopathologie , Syndrome , Néphrocarcinome/génétique , Tumeurs du rein/génétiqueRÉSUMÉ
Intravenous leiomyomatosis is a rare type of tumor that is histologically benign but biologically invasive. It originates from the smooth muscle of the uterine or the uterine vein. It can grow through the uterus and extend into the pelvic cavity, or grow along the veins without invading the wall of the venous vessel itself. The tumors are estrogen-dependent and can metastasize through the bloodstream. Thus, in addition to continuous growth, some tumors exhibit isolated growths in the venous system and heart chambers or show disseminated growth in the lungs, although distant metastasis to other regions usually do not occur. Currently, there is limited research on this disease, the majority of which are case reports, surgical experience summaries, and differentiation from ordinary gynecological myomas in terms of pathogenesis and radiological diagnostic experience. There are two main theories on the origin of the disease: uterine smooth muscle and smooth muscle of the uterine veins. Some studies have verified the role of estrogen, progesterone receptor-related pathways, and angiogenesis in the development of the disease. The clinical symptoms of this disease are varied, depending on the affected area. In the early stages, when the tumor only affects the pelvic cavity, patients show mild symptoms resulting from pelvic organ compression. When it progresses to the inferior vena cava and heart, patients show more complex symptoms resulting from venous return obstruction, cardiac obstruction, and hemodynamics appearing. Different institutions have proposed different disease staging and classification strategies for different clinical purposes. Some are based on the affected area of the lesion; others are based on the size of the tumor. Although surgery remains the main treatment for this disease, the specific surgical approach, adjuvant drug therapy, and prognosis still need further exploration.