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Uterine leiomyoma invading internal iliac vein and consequently disseminating into the right atrium is an extremely rare condition, and surgical strategy is controversial. Here, we reported a specific case with successful surgical resection through one-stage total hysterectomy, bilateral oophorectomy, and the intracardiovascular lesion. This procedure would be an optimal choice for uterine leiomyoma invading inferior vena cava and spreading to right atrium., (© 2024. The Author(s).)

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., (© 2024. The Author(s).)

To date, over 200 families with hereditary leiomyomatosis and renal cell carcinoma (HLRCC) and over 600 families with Birt-Hogg-Dubé (BHD) syndrome have been reported, with low incidence. Here, we describe a patient with suspected rare HLRCC complicated by BHD syndrome. The proband (II1) had characteristic cutaneous leiomyoma-like protrusions on the neck and back, a left renal mass and multiple right renal, liver and bilateral lung cysts. Three family members (I1, II2, II3) had a history of renal cancer and several of the aforementioned clinical features. Two family members (II1, II3) diagnosed with fumarate hydratase (FH)-deficient papillary RCC via pathological biopsy carried two heterozygous variants: FH (NM_000143.3) missense mutation c.1189G>A (p.Gly397Arg) and FLCN (NM_144997.5) frameshift mutation c.1579_1580insA (p.Arg527Glnfs*75). No family member carrying a single variant had renal tumours. In HEK293T cells transfected with mutant vectors, mRNA and protein expression after FLCN p.Arg527Glnfs*75 and FH p.Gly397Arg mutations were significantly lower than those in wild-type (WT) cells. Cell immunofluorescence showed altered protein localisation and reduced protein expression after FLCN p.Arg527Glnfs*75 mutation. The FH WT was uniformly distributed in the cytoplasm, whereas FH protein expression was reduced after the p.Gly397Arg mutation and scattered sporadically with altered cell localisation. Patients with two variants may have a significantly increased penetrance of RCC., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Heterozygous loss-of-function variants in the suppressor of fused protein gene (SUFU) can result in Gorlin syndrome, which is characterized by an increased frequency of basal cell carcinoma, medulloblastoma, odontogenic keratocysts, as well as other tumors. We describe a case of a 5-month-old female who presented with multiple intra-abdominal leiomyomata and was found to have a likely pathogenic splice site variant in the SUFU gene. This is the first reported case of leiomyomatosis secondary to a pathogenic SUFU variant in an infant and may represent an early, atypical presentation of Gorlin syndrome., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: Conflicts of Interest: The authors declare no conflicts of interest.

BACKGROUND Intravenous leiomyomatosis (IVL) is a rare benign smooth muscle tumor originating in the uterus or in the uterine vessels. It is characterized by continuous intraluminal growth that may extend through iliac veins and inferior vena cava (IVC) to right chambers of the heart and pulmonary vasculature, leading to life-threatening complications. This case report describes an uncommon cause of non-thrombotic pulmonary embolism in young woman caused by extensive IVL. CASE REPORT A 39-year-old woman was admitted after multiple syncopal episodes. She was initially found to have a bilateral pulmonary embolism and large right atrial mass believed to be a thrombus. After an unsuccessful attempt to remove the thrombus with AngioVac (AngioDynamics, Latham, NY), subsequent sternotomy revealed a large pedunculated mass extending to the infra-hepatic IVC. Further abdominal imaging showed multiple uterine masses, with the largest about 17 cm, infiltrating the parauterine vessels and extending through the right iliac vein and inferior vena cava up to the right atrium. Pathology examination of the atrial mass revealed benign leiomyoma consistent with further pathology findings after hysterectomy. The pulmonary embolism was believed to be caused by tumor tissue, and anticoagulation was abandoned. Pulmonary nodule raised a suspicion of benign pulmonary metastases, but, fortunately, remained stable during follow-up and the patient had a successful recovery. CONCLUSIONS Available information about IVL is scarce. This tumor, although benign and rare, should be included in the differential diagnosis of cardiac tumors and non-thrombotic pulmonary emboli in women with predisposing risk factors, as potential complications are life-threatening.

Understanding the mechanisms of the Warburg shift to aerobic glycolysis is critical to defining the metabolic basis of cancer. Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is an aggressive cancer characterized by biallelic inactivation of the gene encoding the Krebs cycle enzyme fumarate hydratase, an early shift to aerobic glycolysis, and rapid metastasis. We observed impairment of the mitochondrial respiratory chain in tumors from patients with HLRCC. Biochemical and transcriptomic analyses revealed that respiratory chain dysfunction in the tumors was due to loss of expression of mitochondrial DNA (mtDNA)-encoded subunits of respiratory chain complexes, caused by a marked decrease in mtDNA content and increased mtDNA mutations. We demonstrated that accumulation of fumarate in HLRCC tumors inactivated the core factors responsible for replication and proofreading of mtDNA, leading to loss of respiratory chain components, thereby promoting the shift to aerobic glycolysis and disease progression in this prototypic model of glucose-dependent human cancer., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Background: Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a tumour predisposition syndrome characterised by predisposition to cutaneous and uterine leiomyomata and renal cell carcinoma (RCC)., Objective: To define the clinical findings, molecular genetics, and prognosis in a cohort of 69 families with a fumarate hydratase (FH) pathogenic variant and/or clinical features of HLRCC., Design, Setting, and Participants: Clinical and molecular findings were obtained for 185 individuals from 69 families from four UK regional genetics clinics., Outcome Measurements and Statistical Analysis: Ages at confirmed diagnoses, last dates of follow-up, and molecular results were attained for probands and relatives. To study the effect of potential ascertainment bias, phenotypes of probands and their affected relatives were compared., Results and Limitations: A germline FH variant (19 novel and 21 known, >50% missense variants) was identified in 68/69 probands and 90 relatives. Cutaneous leiomyomata occurred in 90/185 (48.6%) individuals (mean age 45.9 yr) and uterine leiomyomata in 33/107 (30.8%) females (mean age 35.0 yr). Of 185 individuals, 23 (12.4%) had a confirmed renal tumour, and histopathology where known (n = 18) was variable: seven clear cell RCCs, nine papillary RCCs (six of type 2), one collecting duct tumour, and one tumour with oncocytic cystic morphology. Mean age at symptomatic RCC diagnosis was 44.0 yr and median survival was 21.0 mo. Eighty-one individuals underwent 187 renal imaging surveillance scans; three stage 1 RCCs were detected. Mean survival of individuals diagnosed with stage 1/2 RCC was significantly longer than those diagnosed with stage 3/4 RCC (p = 0.0004)., Conclusions: Management of HLRCC is challenging as RCC occurs in a minority of cases but is highly aggressive. This large multicentre series has identified novel features and evidence that renal screening in HLRCC detects early-stage RCCs., Patient Summary: We show that hereditary leiomyomatosis and renal cell cancer is associated with a 21% lifetime risk of renal cell carcinoma (RCC; 95% confidence interval 8.2-37.1), and renal imaging screening detects early-stage RCC., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a rare familial cancer syndrome with a germline mutation in the fumarate hydratase gene. Affected individuals are predisposed to development of cutaneous leiomyomas, uterine leiomyomas, and papillary renal cell carcinoma. We present a case of a mother and son pair affected with HLRCC, discuss clinical management, and examine potential syndromic manifestations in extended family members. Annual imaging surveillance for kidney cancer is recommended since 20-30% of individuals develop aggressive papillary type II renal cell carcinoma that can be difficult to treat once it has metastasized., (Copyright © 2020 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Introduction: Renal cell carcinoma (RCC) is a heterogeneous group of cancers that can occur sporadically or as a manifestation of various inherited syndromes. Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is one such inherited syndrome that predisposes patients to HLRCC-associated RCC. These tumors are notoriously aggressive and often exhibit early metastases. HLRCC results from germline mutations in the FH gene, which encodes the citric acid cycle enzyme fumarate hydratase (FH). FH loss leads to alterations in oxidative carbon metabolism, necessitating a switch to aerobic glycolysis, as well as a pseudohypoxic response and consequent upregulation of various pro-survival pathways. Mutations in FH also alter tumor cell migratory potential, response to oxidative stress, and response to DNA damage., Areas Covered: We review the mechanisms by which FH loss leads to HLRCC-associated RCC and how these mechanisms are being rationally targeted., Expert Opinion: FH loss results in the activation of numerous salvage pathways for tumor cell survival in HLRCC-associated RCC. Tumor heterogeneity requires individualized characterization via next-generation sequencing, ultimately resulting in HLRCC-specific treatment regimens. As HLRCC-associated RCC represents a classic Warburg tumor, targeting aerobic glycolysis is particularly promising as a future therapeutic avenue.

Background: Hereditary leiomyomatosis and renal cancer (HLRCC) is a cancer syndrome associated with a germline mutation in fumarate hydratase (FH). The syndrome is associated with cutaneous and uterine leiomyomas, and some patients develop a lethal form of kidney cancer. This study provides estimates for the FH carrier frequency and kidney cancer penetrance., Methods: Data sets containing sequencing data for the FH gene were used: the 1000 Genomes Project (1000GP) and the Exome Aggregation Consortium (ExAC). Alterations in the FH gene were characterized on the basis of different variant risk tiers: 1) ClinVar annotated variants, 2) loss-of-function alterations, and 3) highly impactful missense alterations. The cumulative incidence of FH alterations overall and by different world populations was evaluated in 1000GP and ExAC. A lifetime penetrance of HLRCC kidney cancer risk was generated with 3 estimates of the annual incidence., Results: The overall allele frequencies of tier 1 to 3 FH alterations in the ExAC and 1000GP data sets were 2.54 × 10 -3 (1 in 393) and 1.20 × 10 -3 (1 in 835), respectively. There were differences in the allele frequencies of FH alterations between world populations. Based on various estimates of the percentage of kidney cancers with FH alterations, the lifetime kidney cancer penetrance for carrier estimate 3 in ExAC was 1.7% to 5.8%., Conclusions: FH alterations are common and are carried by approximately 1 in 1000 individuals according to the more conservative estimates. The lifetime kidney cancer penetrance appears lower than previously estimated. Although databases are not population cohorts, they provide a useful quantitative estimate of rare variants with low penetrance., (© 2020 American Cancer Society.)

Competing Interests: Competing interests: None declared.

Background: Fibroids are the most common benign tumours of the female genital tract and are associated with numerous clinical problems including a possible negative impact on fertility. In women requesting preservation of fertility, fibroids can be surgically removed (myomectomy) by laparotomy, laparoscopically or hysteroscopically depending on the size, site and type of fibroid. Myomectomy is however a procedure that is not without risk and can result in serious complications. It is therefore essential to determine whether such a procedure can result in an improvement in fertility and, if so, to then determine the ideal surgical approach., Objectives: To examine the effect of myomectomy on fertility outcomes and to compare different surgical approaches., Search Methods: We searched the Cochrane Gynaecology and Fertility Group (CGFG) Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, Epistemonikos database, World Health Organization (WHO) International Clinical Trials Registry Platform search portal, Database of Abstracts of Reviews of Effects (DARE), LILACS, conference abstracts on the ISI Web of Knowledge, OpenSigle for grey literature from Europe, and reference list of relevant papers. The final search was in February 2019., Selection Criteria: Randomised controlled trials (RCTs) examining the effect of myomectomy compared to no intervention or where different surgical approaches are compared regarding the effect on fertility outcomes in a group of infertile women suffering from uterine fibroids., Data Collection and Analysis: Data collection and analysis were conducted in accordance with the procedure suggested in the Cochrane Handbook for Systematic Reviews of Interventions., Main Results: This review included four RCTs with 442 participants. The evidence was very low-quality with the main limitations being due to serious imprecision, inconsistency and indirectness. Myomectomy versus no intervention One study examined the effect of myomectomy compared to no intervention on reproductive outcomes. We are uncertain whether myomectomy improves clinical pregnancy rate for intramural (odds ratio (OR) 1.88, 95% confidence interval (CI) 0.57 to 6.14; 45 participants; one study; very low-quality evidence), submucous (OR 2.04, 95% CI 0.62 to 6.66; 52 participants; one study; very low-quality evidence), intramural/subserous (OR 2.00, 95% CI 0.40 to 10.09; 31 participants; one study; very low-quality evidence) or intramural/submucous fibroids (OR 3.24, 95% CI 0.72 to 14.57; 42 participants; one study; very low-quality evidence). Similarly, we are uncertain whether myomectomy reduces miscarriage rate for intramural fibroids (OR 1.33, 95% CI 0.26 to 6.78; 45 participants; one study; very low-quality evidence), submucous fibroids (OR 1.27, 95% CI 0.27 to 5.97; 52 participants; one study; very low-quality evidence), intramural/subserous fibroids (OR 0.80, 95% CI 0.10 to 6.54; 31 participants; one study; very low-quality evidence) or intramural/submucous fibroids (OR 2.00, 95% CI 0.32 to 12.33; 42 participants; one study; very low-quality evidence). This study did not report on live birth, preterm delivery, ongoing pregnancy or caesarean section rate. Laparoscopic myomectomy versus myomectomy by laparotomy or mini-laparotomy Two studies compared laparoscopic myomectomy to myomectomy at laparotomy or mini-laparotomy. We are uncertain whether laparoscopic myomectomy compared to laparotomy or mini-laparotomy improves live birth rate (OR 0.80, 95% CI 0.42 to 1.50; 177 participants; two studies; I 2 = 0%; very low-quality evidence), preterm delivery rate (OR 0.70, 95% CI 0.11 to 4.29; participants = 177; two studies; I 2 = 0%, very low-quality evidence), clinical pregnancy rate (OR 0.96, 95% CI 0.52 to 1.78; 177 participants; two studies; I 2 = 0%, very low-quality evidence), ongoing pregnancy rate (OR 1.61, 95% CI 0.26 to 10.04; 115 participants; one study; very low-quality evidence), miscarriage rate (OR 1.25, 95% CI 0.40 to 3.89; participants = 177; two studies; I 2 = 0%, very low-quality evidence), or caesarean section rate (OR 0.69, 95% CI 0.34 to 1.39; participants = 177; two studies; I 2 = 21%, very low-quality evidence). Monopolar resectoscope versus bipolar resectoscope One study evaluated the use of two electrosurgical systems during hysteroscopic myomectomy. We are uncertain whether bipolar resectoscope use compared to monopolar resectoscope use improves live birth/ongoing pregnancy rate (OR 0.86, 95% CI 0.30 to 2.50; 68 participants; one study, very low-quality evidence), clinical pregnancy rate (OR 0.88, 95% CI 0.33 to 2.36; 68 participants; one study; very low-quality evidence), or miscarriage rate (OR 1.00, 95% CI 0.19 to 5.34; participants = 68; one study; very low-quality evidence). This study did not report on preterm delivery or caesarean section rate., Authors' Conclusions: There is limited evidence to determine the role of myomectomy for infertility in women with fibroids as only one trial compared myomectomy with no myomectomy. If the decision is made to have a myomectomy, the current evidence does not indicate a superior method (laparoscopy, laparotomy or different electrosurgical systems) to improve rates of live birth, preterm delivery, clinical pregnancy, ongoing pregnancy, miscarriage, or caesarean section. Furthermore, the existing evidence needs to be viewed with caution due to the small number of events, minimal number of studies and very low-quality evidence., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

There has been growing concern surrounding the use of unconfined power morcellation in laparoscopic surgeries for uterine leiomyoma due to its associated risks and long-term clinical sequelae, including parasitic leiomyomas and disseminated peritoneal leiomyomatosis (DPL). We present a case of DPL resulting from previous laparoscopic morcellation and a review of the existing literature. DPL is a potentially devastating consequence of unconfined laparoscopic morcellation in the surgical management of uterine fibroids. A multidisciplinary approach is recommended in the management of DPL, especially in cases of multivisceral involvement. Clinical caution ought to be exercised when using power morcellators; when unavoidable, confined laparoscopic morcellation offers a promising mitigation and should be adopted if practicable., (Copyright: © Singapore Medical Association.)

Uterine intravenous leiomyomatosis is an uncommon tumor, usually arising from the uterus, with nodular masses which extend intravascularly over variable distances and may reach the inferior vena cava, right atrium, and pulmonary arteries. Early diagnosis and surgical intervention are crucial as intracardiac leiomyomatosis not only causes cardiac symptoms but may result in pulmonary embolism and sudden death. Complete tumor resection is key in disease management, thus rendering cardiac-extending uterine intravenous leiomyomatosis one of the most challenging conditions for surgical treatment. The use of interventional radiology procedures can facilitate the surgical approach. We report the case of a massive pelvic recurrence of uterine leiomyomatosis with intracardiac extension and pulmonary embolism, analyzing management and surgical outcomes, highlighting the role of interventional radiology during the therapeutic pathway. Nonetheless, there are currently very few data available concerning the use of interventional radiology procedures in the therapeutic strategy of uterine intravenous leiomyomatosis with intracardiac extension.

Objective: To describe laparoscopic management of a case of leyomiomatosis peritonealis disseminata associated with ovarian endometriosis., Design: Surgical video article., Setting: Academic hospital., Patient: We present a case of a 30-year-old woman referred to our clinic for abdominal and pelvic pain and dyspareunia. A hysteroscopic myomectomy was reported as previous surgical history. At ultrasound examination, a left ovarian cyst of 4 cm suspected for typical endometrioma and a mild hydroureteronephrosis of left kidney were revealed. The patient was scheduled for laparoscopic surgery., Interventions: During laparoscopy, multiple nodules were found simulating widespread metastases involving colon, small bowel, omentum, right diaphragmatic dome, gastric surface, vesico-uterine area and abdominal peritoneum. Several biopsies and a peritoneal washing were performed, suspecting a peritoneal carcinomatosis. The histological frozen section examination revealed a possible benign disease, requiring further immunohistochemical study that diagnosed leiomyomatosis peritonealis. A second laparoscopy was then performed after one month. Enucleation of the left ovarian endometriotic cyst with classic stripping technique was performed. The left ureter was compressed by a fibrotic nodule of 5 cm that was isolated and removed. Operating time was 80 minutes. The postoperative course was uneventful and the patient was discharged on postoperative day 2., Main Outcome Measures: Description of a case of leiomyomatosis peritonealis disseminata in a patient with no previous history of intra-abdominal morcellation., Results: The removal of the left ovarian endometriotic cyst and the periureteral nodule was successfully performed. The patient reported good health conditions without hydroureteronephrosis at six months follow up visit., Conclusions: Leiomyomatosis peritonealis disseminata is a rare clinical disorder characterized by proliferation of nodules, consisted by smooth muscle cells. The association of this condition with endometriosis has been described in other studies. Despite several medical therapies have been proposed (chemotherapy, aromatase inhibitor, gonadotropin-releasing hormone agonist), surgical excision remains a good option, frequently performed for symptoms palliation. Laparoscopic approach might be considered the procedure of choice in case of symptomatic women with leiomyomatosis peritonealis disseminata., (Copyright © 2019 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Diffuse esophageal leiomyomatosis is a rare esophageal tumor characterized by circumferential thickening of smooth muscle layers. Diffuse esophageal leiomyomatosis can be associated with Alport's syndrome and therefore diagnosed by skin biopsy. Alport syndrome is a hereditary disease usually defined by the association of glomerular nephropathy and perceptual deafness. Here we describe the management of a young women with a diffuse esophageal leiomyomatosis and a past history of uterine leiomyoma. The surgical treatment depends on the esophageal extent of the disease. Association between diffuse esophageal leiomyomatosis and early uterine leiomyomas could be also observed and leading to Alport's syndrome diagnosis despite the absence of renal abnormalities., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Rationale: Pulmonary embolism is a potentially devastating medical condition. Although deep-vein thrombosis is the most common etiology, a nonthrombotic pulmonary embolism is not uncommon., Patient Concerns: A 45-year-old woman was admitted to our hospital for progressive effort dyspnea for 3 weeks., Diagnosis: Echocardiography revealed a mobile mass extending from the right atrium to the bilateral proximal pulmonary artery. As the mass was no response to thrombotic therapy, intravenous leiomyomatosis was suspected. Computed tomography (CT) revealed a hypo-attenuated tumor extending from the ovarian vein to the pulmonary artery., Interventions: A 1-stage operation for the surgical removal of the tumor, right salpingo-oophorectomy and subtotal hysterectomy were performed. Surgical specimen was identified as uterine leiomyomatosis without malignant transformation., Outcomes: The patient was followed- up for 2 years and subsequent CT did not reveal any notable lesions., Lessons: Nonthrombotic pulmonary embolism is a potentially life-threatening complication. This case indicated intravenous leiomyomatosis should be considered in the differential diagnosis for certain cases. Complete surgical excision was the only curative treatment.

Renal cell carcinoma (RCC) accounts for 2-3% of all malignant disease in adults. Hereditary RCC represents 5 to 8% of kidney tumors. Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) represents an autosomal dominant syndrome that results from a germline mutation in fumarate hydratase gene (FH). HLRCC patients typically present with skin or uterine leiomyomas and renal neoplasms. HLRCC was recently recognized as a distinct renal tumor subtype by the WHO 2016 classification. Many morphological patterns such as papillary, solid, tubular, and cystic had been described as part of morphological aspects of HLRCC. In this study, we describe a case of a patient that had a history of persistence of ductus arteriosus (PDA) and cryptorchidism. In addition, the renal tumor showed a very unusual hystiocytoid morphological aspect. We confirmed the presence of a FH germline mutation both in the patient and his mother.

Background: Pulmonary lymphangioleimyomatosis (PLAM) is a rare disease involving lung. PLAM primarily affects young women, a characteristic it shares with systemic lupus erythematosus (SLE). Estrogen has long been assumed to play an important role both in PLAM and SLE. We report a menopausal woman, who was found to have PLAM 1 year after she was diagnosed with SLE. Her chest radiograph was normal in the early phase of SLE., Case Presentation: A 52-year-old Chinese woman was referred to our hospital in August 2014 because of swelling in both legs. She also reported a malar rash and intermittent generalized arthralgia. Laboratory examination showed leukopenia. Her serum albumin level was 23 g/L; 24-h urinary protein excretion was 5.3 g. She tested positive for anti-Smith (Sm) antibody and anti-SS-A antibody. Renal biopsy indicated Class V + IV(G)-A lupus nephritis (LN). The condition of SLE and LN improved on a regime of tapering prednisolone and intermittent intravenous cyclophosphamide therapy until 1 year later when she developed exertional dyspnea accompanied with frequent cough. Thoracic computed tomography revealed numerous well-defined cysts and the diagnosis of PLAM was confirmed by lung biopsy. In the follow-up period, the patient continued to be on prednisolone and mycophenolate mofetil for the treatment of SLE, but only agreed to receive symptomatic treatment for PLAM. One year after the diagnosis of PLAM, during which time the SLE was stable, she died of respiratory failure and cor pulmonale., Conclusion: We report a patient with coexisting SLE and PLAM, who was treated with immunosuppressive therapy. SLE was stable but PLAM was not improved. Although the coexistence of SLE and PLAM might be a coincidence, the occurrence of these two diseases in a menopausal woman may warrant further mechanistic exploration.

Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome is a recognized distinct phenotypic variant of multiple cutaneous and uterine leiomyomatosis. The present case reports an extremely rare case of HLRCC syndrome combined with adrenocortical carcinoma. The case suggests that HLRCC should be considered in any young patient with bulky uterine leiomyomas and renal cell cancer, and F-FDG PET/CT can help detect unexpected additional primary malignancy in a patient with known cancer.

Alport syndrome-diffuse leiomyomatosis (AS-DL, OMIM: 308940) is a rare variant of the X-linked Alport syndrome that shows overgrowth of visceral smooth muscles in the gastrointestinal, respiratory and female reproductive tracts in addition to renal symptoms. AS-DL results from deletions that encompass the 5' ends of the COL4A5 and COL4A6 genes, but deletion breakpoints between COL4A5 and COL4A6 have been determined in only four cases. Here, we characterize deletion breakpoints in five AS-DL patients and show a contiguous COL4A6/COL4A5 deletion in each case. We also demonstrate that eight out of nine deletion alleles involved sequences homologous between COL4A5 and COL4A6. Most breakpoints took place in recognizable transposed elements, including long and short interspersed repeats, DNA transposons and long-terminal repeat retrotransposons. Because deletions involved the bidirectional promoter region in each case, we suggest that the occurrence of leiomyomatosis in AS-DL requires inactivation of both genes. Altogether, our study highlights the importance of homologous recombination involving multiple transposed elements for the development of this continuous gene syndrome and other atypical loss-of-function phenotypes.

We report a case of vaginal adenosis in a woman of 42years. This is a rare congenital disorder since cessation of use of diethylstilbestrol (DES), usually of benign course, not to ignore in its tubo-endometrial histological form which may progress to atypical adenosis precursor of vaginal clear cell adenocarcinoma in patients exposed in utero to DES., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Background: Cases of women with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome developing leiomyomata are rare. A case with mitotically active leiomyomata has not previously been described to our knowledge., Case: A 43-year-old woman with MRKH syndrome found to have an incidental pelvic mass on imaging studies underwent a diagnostic laparoscopy, followed by resection of leiomyomata and uterine remnant via mini laparotomy. Histopathology revealed focal infarction associated with a mitotically active area in one of the leiomyomata but with no evidence of marked cytologic atypia or hypercellularity. Focal adenomyosis was also noted., Conclusion: Studies have shown that mitotically active smooth cell tumors of the uterus having 5-9 mitoses/10 hpf and no cellular atypia have a metastatic rate too low to be regarded as sarcomas. Although the pathology findings in this case are benign with no need for continued surveillance by gynecologic oncology, regular follow-up with a gynecologist annually may be indicated for early diagnosis of recurrence secondary to the uncommon characteristics of this benign tumor, especially in this rare category of patients with Müllerian agenesis. Mitotically active leiomyomata can occur in patients with Müllerian agenesis, but the likelihood that a pelvic mass in a patient with MRKH syndrome is a sarcoma is extremely low.

A 36-year-old woman, who had a history of myomectomy, presented with lightheadedness after changing position from sitting to standing and effort-related shortness of breath. Echocardiography demonstrated a hyperechoic elongated mobile mass extending from the inferior caval vein to the right atrium. The mass was surgically removed, and histological examination established the diagnosis of intravenous leiomyomatosis. This case caught the attention of our cardiology group to consider the diagnosis when an inferior caval vein or right atrium mass is found in a patient with a history of uterine leiomyomatosis.

Background: Intravenous leiomyomatosis (IVL) extending to inferior vena cava and heart is one of the most challenging conditions for surgical treatment. We explored the use of computerized tomography angiography (CTA) in preoperative assessment for this disease., Methods: A cohort of 31 patients with IVL extending to inferior vena cava and heart were reviewed from the year 2002 to 2014, focusing on the preoperative CTA imaging characteristics and the surgical procedures in clinical treatment., Results: All patients were diagnosed correctly combining the clinical medical history and CTA imaging. Thirteen patients had tumors confined within the inferior vena cava, and 18 patients had tumors intruding into the right heart. Furthermore, 15 tumors were located in the right atrium alone, and 3 tumors involved both the right atrium and the right ventricle. All patients had simple or multiple soft tissue masses from the pelvis, with 22 tumors extending into inferior vena cava through the iliac veins and 9 tumors through the ovarian veins. Three patients had tumors invading into lung and underwent tumor thrombus resection in the pulmonary artery. Patients received either one-stage surgery or two-stage surgery dependent on patient general condition and tumor status. All operations were successfully performed by multidisciplinary cooperation, including gynecology, cardiac surgery, and vascular surgery, without severe surgical-related complications or deaths., Conclusions: CTA imaging can present location, size, and full-scale extension pathway of IVL lesions, and can be used as first-line imaging technique in preoperative assessment, having great significance in making surgical plan and obtaining successful outcome.

There are a significant number of diseases and treatment considerations of considerable importance relating to the skin and renal systems. This emphasizes the need for dermatologists in practice or in clinical training to be aware of these associations. Part I of this 2-part continuing medical education article reviews the genetic syndromes with both renal and cutaneous involvement that are most important for the dermatologist to be able to identify, manage, and appropriately refer to nephrology colleagues. Part II reviews the inflammatory syndromes with relevant renal manifestations and therapeutic agents commonly used by dermatologists that have drug-induced effects on or require close consideration of renal function. In addition, we will likewise review therapeutic agents commonly used by nephrologists that have drug-induced effects on the skin that dermatologists are likely to encounter in clinical practice. In both parts of this continuing medical education article, we discuss diagnosis, management, and appropriate referral to our nephrology colleagues in the context of each nephrocutaneous association. There are a significant number of dermatoses associated with renal abnormalities and disease, emphasizing the need for dermatologists to be keenly aware of their presence in order to avoid overlooking important skin conditions with potentially devastating renal complications. This review discusses important nephrocutaneous disease associations with recommendations for the appropriate urgency of referral to nephrology colleagues for diagnosis, surveillance, and early management of potential renal sequelae., (Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is an autosomal dominant familial disorder due to FH mutation. Despite a considerable increase in information about the genetic background, inter- and intrafamilial phenotypic variability/penetrance are not well documented., Objective: To describe a large French HLRCC family and provide new data on penetrance and intrafamilial variability., Materials and Methods: The whole family was contacted for clinical examination, skin biopsy, uterine and kidney imagery and molecular analysis., Results: The family included 22 members in 3 generations. The second generation consisted of 13 members who were older than the expected age of onset of disease manifestations. Of the 12 available members of this second generation, 6 (1 man and 5 women, aged 44-57 years) had a novel FH mutation. All had the same mild phenotype with cutaneous asymptomatic leiomyomas, uterine fibroids (if women) and no kidney tumor. The other 6 members not bearing the familial mutation had normal clinical and radiological findings. In this second generation, the penetrance was therefore complete, and there was no intrafamilial variability in the clinical expression of the mutation., Conclusion: This study provides additional data on genotype/phenotype correlation, intrafamilial variability and penetrance that should help to improve prognosis and genetic counseling., (© 2016 S. Karger AG, Basel.)

Introduction: Leiomyomatosis peritonealis disseminata is a very rare benign condition of the peritoneal cavity that may mimic peritoneal carcinomatosis or metastatic leiomyosarcomas. It mainly develops in association with pregnancy, but is also rarely associated with endometriosis., Case Presentation: A 31-year-old Asian woman presented to our hospital with abdominal pain in the right lower quadrant. Her abdominopelvic computed tomography scan showed a 1.2cm-sized nodule at the appendiceal tip, but no other abnormal findings. We suspected acute appendicitis and performed an exploratory laparoscopy. Her appendix was enlarged at the tip portion. Also noted were blood-colored fluid collections in her pelvic cavity and bilateral ovarian cysts. Additionally, several small whitish firm solid nodules, ranging from 0.5 to 1.0cm in size, were present on her pelvic peritoneum. Her histological examination confirmed that the endometriosis of her appendix coexisted with leiomyomatosis peritonealis disseminata., Conclusions: We report a case involving a 31-year-old woman with acute symptoms of endometriosis of the appendix associated with leiomyomatosis peritonealis disseminata. Appendiceal endometriosis with leiomyomatosis peritonealis disseminata presenting as acute appendicitis is extremely rare. To the best of our knowledge, this is the first such case reported in the literature.