Primary Ewing sarcoma of the kidney: a rare entity with diagnostic challenges.

Ewing sarcoma is a very rare tumour with aggressive behaviour and a poor prognosis. It tends to metastasize rapidly. Renal Ewing sarcoma is extremely rare, and only 48 cases have been reported in the literature. Herein, we report the case of a 14-year-old female presenting with a painful left flank swelling. Ultrasound and magnetic resonance imaging showed a large tumour invading the left kidney, heterogeneously enhanced after injection, associated with lymph nodes and peritoneal carcinomatosis. A thoraco-abdomino-pelvic computed tomography scan revealed pulmonary nodules and osteolytic lesions. A biopsy was performed, and histology, immunohistochemistry, and molecular studies confirmed the diagnosis of retroperitoneal Ewing sarcoma. Multi-agent chemotherapy followed by radical nephrectomy was performed, confirming the renal origin, and histology showed a post-therapeutical response. After a 1-year follow-up, there was no evidence of recurrence. We report this case to highlight the rarity of this entity and its challenging clinico-pathological diagnosis when presenting as a renal tumour.

Angiomyofibroblastoma of the vulva: A case report and review of the literature.

Angiomyofibroblastoma (AMFB) represents a rare, benign mesenchymal tumor with a predilection for the vulvovaginal region. It is usually diagnosed in middle-aged women. Histopathology and immunohistochemical study remain the key to diagnosis. Like other benign mesenchymal vulval tumors, AMFB shows indolent behavior and rarely recurs after complete surgical excision. Herein, we present a case of vulvar AMFB in a 51-year-old woman to highlight the diagnostic difficulties when considering this rare entity.

Fibrothecoma a rare ovarian tumor: A case report.

INTRODUCTION AND IMPORTANCE: Fibroma, thecoma, and fibrothecoma collectively denote a range of non-cancerous sex cord-stromal tumors distinguished by the presence of fibroblastic stromal cells and/or cells resembling luteinized theca cells. CASE PRESENTATION: In this report, we present a case study of a 52-year-old patient in whom this uncommon tumor was identified via MRI, highlighting the distinctive diagnostic and treatment considerations associated with it. CLINICAL DISCUSSION: Ovarian fibrothecoma tumors are infrequent, constituting less than 4 % of all ovarian tumors. Although they may manifest at any age, they are more commonly observed in elderly and post-menopausal individuals. Diagnosis hinges on clinical and paraclinical data, yet definitive confirmation is predominantly achieved through anatomopathological examination. For younger patients, conservative surgery is usually favored, whereas peri- or post-menopausal individuals may undergo radical treatment. CONCLUSION: Ovarian Fibrothecoma, though rare, are typically benign tumors frequently found in older patients. Diagnosis primarily relies on histological examination. Fortunately, the prognosis for these tumors is generally favorable.

Cerebral large vessels vasculitis following Guillain-Barré syndrome as first clinical manifestations of primary Sjogren's syndrome: A case based - Review.

Background: Primary Sjogren's syndrome (pSS) is an autoimmune exocrinopathy in which extraglandular signs of pSS are determinant for the prognosis. Involvement of both peripheral and central nervous system (CNS) are known to be among the sites of high systemic activity in pSS. Case presentation: We, herein, report a case of a 57-year-old female patient with pSS presenting with typical Guillan-Barré syndrome (GBS), shortly followed by acute headaches accompanied by cortical blindness. Cerebral magnetic resonance imaging (MRI) demonstrated T2 signal abnormalities on the occipital region with narrowing and irregularities of the cerebral arteries, suggestive of CNS vasculitis.Subtle sicca symptoms occurring prior to neurological symptoms by 8 months together with immunological disturbances (anti-SSA, anti-SSB antibodies positivity, type II cryoglobulins positivity, and C4 hypocomplementemia) allowed us to retain the diagnosis of pSS. Recovery of motor symptoms was possible under the combined use of immunoglobulins and corticotherapy during the initial phase. A three-years follow-up confirmed progressive motor recovery and stabilization under 6-months cyclophosphamide cycles relayed by azathioprine therapy. Conclusions: Neurological complications can be inaugural in lead to urgent investigations and treatment. Peripheral and central neurological manifestations can coexist. The approach should integrate careful clinical assessment, as well as radiological and immunological findings.

A Sertoli-Leydig ovarian tumor presenting as ovarian torsion: A case report.

Torsion occurs as a complication in 10% of cases of ovarian tumors. It predominantly occurs in benign ones, while malignant tumors are less prone to torsion. Sertoli-Leydig cell tumors are highly unusual sex cord-stromal tumors of the ovary, accounting for less than 0.2% of all ovarian cancers. A 39-year-old patient presented to the emergency department with a Sertoli-Leydig cell tumor diagnosed due to ovarian torsion. The clinical presentation was characterized by abdominal pain. Ultrasound indicated signs of torsion, and torsion of the right ovary was subsequently confirmed during laparotomy. A salpingo-oophorectomy was performed, and histological examination revealed a moderately differentiated Sertoli-Leydig cell tumor. Sertoli-Leydig cell tumors often present with hormone-related or non-hormonal symptoms. Surgery plays a crucial role in both diagnosis and treatment. Postoperative treatment is not necessary for well-differentiated Sertoli-Leydig cell tumors in stage IA-IB. However, patients with grade 2-3 disease, advanced stage, or heterologous elements may consider adjuvant treatment. As these tumors are rare, this case contributes to the documentation of Sertoli-Leydig cell tumors, with a case diagnosed due to ovarian torsion. The case highlights the importance of establishing international registries of Sertoli-Leydig cell tumor cases for standardized management.

Voluminous cervical polyp delivered: a case report.

Cervical polyps are common gynecological findings, typically small and benign. However, larger polyps can mimic malignant neoplasms and pose diagnostic challenges. We present a case of a 40-year-old woman with a large cervical polyp, highlighting the critical role of radiological imaging in diagnosis and management. The lesion was successfully resected, with histological examination confirming a benign nature. This case underscores the necessity for careful evaluation of large cervical polyps to ensure accurate diagnosis and treatment.

RAB32 Ser71Arg in autosomal dominant Parkinson's disease: linkage, association, and functional analyses.

BACKGROUND: Parkinson's disease is a progressive neurodegenerative disorder with multifactorial causes, among which genetic risk factors play a part. The RAB GTPases are regulators and substrates of LRRK2, and variants in the LRRK2 gene are important risk factors for Parkinson's disease. We aimed to explore genetic variability in RAB GTPases within cases of familial Parkinson's disease. METHODS: We did whole-exome sequencing in probands from families in Canada and Tunisia with Parkinson's disease without a genetic cause, who were recruited from the Centre for Applied Neurogenetics (Vancouver, BC, Canada), an international consortium that includes people with Parkinson's disease from 36 sites in 24 countries. 61 RAB GTPases were genetically screened, and candidate variants were genotyped in relatives of the probands to assess disease segregation by linkage analysis. Genotyping was also done to assess variant frequencies in individuals with idiopathic Parkinson's disease and controls, matched for age and sex, who were also from the Centre for Applied Neurogenetics but unrelated to the probands or each other. All participants were aged 18 years or older. The sequencing and genotyping findings were validated by case-control association analyses using bioinformatic data obtained from publicly available clinicogenomic databases (AMP-PD, GP2, and 100 000 Genomes Project) and a private German clinical diagnostic database (University of Tübingen). Clinical and pathological findings were summarised and haplotypes were determined. In-vitro studies were done to investigate protein interactions and enzyme activities. FINDINGS: Between June 1, 2010, and May 31, 2017, 130 probands from Canada and Tunisia (47 [36%] female and 83 [64%] male; mean age 72·7 years [SD 11·7; range 38-96]; 109 White European ancestry, 18 north African, two east Asian, and one Hispanic] underwent whole-exome sequencing. 15 variants in RAB GTPase genes were identified, of which the RAB32 variant c.213C>G (Ser71Arg) cosegregated with autosomal dominant Parkinson's disease in three families (nine affected individuals; non-parametric linkage Z score=1·95; p=0·03). 2604 unrelated individuals with Parkinson's disease and 344 matched controls were additionally genotyped, and five more people originating from five countries (Canada, Italy, Poland, Turkey, and Tunisia) were identified with the RAB32 variant. From the database searches, in which 6043 individuals with Parkinson's disease and 62 549 controls were included, another eight individuals were identified with the RAB32 variant from four countries (Canada, Germany, UK, and USA). Overall, the association of RAB32 c.213C>G (Ser71Arg) with Parkinson's disease was significant (odds ratio [OR] 13·17, 95% CI 2·15-87·23; p=0·0055; I2=99·96%). In the people who had the variant, Parkinson's disease presented at age 54·6 years (SD 12·75, range 31-81, n=16), and two-thirds had a family history of parkinsonism. RAB32 Ser71Arg heterozygotes shared a common haplotype, although penetrance was incomplete. Findings in one individual at autopsy showed sparse neurofibrillary tangle pathology in the midbrain and thalamus, without Lewy body pathology. In functional studies, RAB32 Arg71 activated LRRK2 kinase to a level greater than RAB32 Ser71. INTERPRETATION: RAB32 Ser71Arg is a novel genetic risk factor for Parkinson's disease, with reduced penetrance. The variant was found in individuals with Parkinson's disease from multiple ethnic groups, with the same haplotype. In-vitro assays show that RAB32 Arg71 activates LRRK2 kinase, which indicates that genetically distinct causes of familial parkinsonism share the same mechanism. The discovery of RAB32 Ser71Arg also suggests several genetically inherited causes of Parkinson's disease originated to control intracellular immunity. This shared aetiology should be considered in future translational research, while the global epidemiology of RAB32 Ser71Arg needs to be assessed to inform genetic counselling. FUNDING: National Institutes of Health, the Canada Excellence Research Chairs program, Aligning Science Across Parkinson's, the Michael J Fox Foundation for Parkinson's Research, and the UK Medical Research Council.

Increased IL-22 in cerebrospinal fluid of neuro-behçet's disease patients.

Remitting-Relapsing Multiple Sclerosis (RRMS) and Neuro-Behçet Disease (NBD) are two chronic neuro-inflammatory disorders leading to brain damage and disability in young adults. Herein, we investigated in these patients the cytokine response by beads-based multiplex assays during the early stages of these disorders. Cytokine investigations were carried out on treatment-naive patients suffering from RRMS and NBD recruited at the first episode of clinical relapse. Our findings demonstrate that Cerebrospinal Fluid (CSF) cells from NBD patients, but not RRMS, secrete significant high levels of IL-22 which is associated with elevated IL-22 mRNA expression. We also observed an increase in IL-22 levels in the definite NBD subgroup as compared to the probable NBD one, indicating a clear relationship between elevated IL-22 levels and diagnostic certainty. Interestingly, we found no correlation of IL-22 secretion between CSF and serum arguing about intrathecal release of IL-22 in the CNS of NBD patients. Moreover, we showed by correlogram analysis that this cytokine doesn't correlate with IL-17A, IL-17F and IL-21 suggesting that this cytokine is secreted by Th22 cells and not by Th17 cells in the CSF of NBD patients. Finally, we found elevated levels of IL-6 and a positive correlation between IL and 6 and IL-22 in the CSF of NBD. In conclusion, these results suggest that IL-6 contributes to the production of IL-22 by T cells leading to the exacerbation of inflammation and damage within the CNS of NBD patients.

Lipoleiomyoma: a potential mimic of an ovarian dermoid cyst on MRI-a case report.

Uterine lipoleiomyomas are rare variants of uterine leiomyomas which is composed of adipocytes and smooth muscle cells. In this report, we describe the case of a 39-year-old patient who presented with persistent, isolated pelvic pain. Ultrasonography showed an oval, well-defined left ovarian mass. Computed tomography (CT) scanning showed a predominantly-fatty mass with tissular components, no calcifications and heterogeneously enhanced after injection, suggesting initially a mature teratoma. Magnetic resonance imaging (MRI) findings revealed a latero-uterine mass, suggesting the presence of a left ovarian dermoid cyst with a potentially-malignant fleshy component. A subsequent pathology report revealed a lipoleiomyoma with cartilaginous metaplasia. Most notably, despite the fatty nature of the tumour and the use of MRI, the pedunculated appearance of the lipoleiomyoma observed intraoperatively mimicked a dermoid tumour even on imaging. Improved understanding of leiomyoma variants and secondary degenerative changes can help prevent misdiagnosis.

A pathogenic variant in RAB32 causes autosomal dominant Parkinson's disease and activates LRRK2 kinase.

Background: Parkinson's disease (PD) is a progressive neurodegenerative disorder. Mendelian forms have revealed multiple genes, with a notable emphasis on membrane trafficking; RAB GTPases play an important role in PD as a subset are both regulators and substrates of LRRK2 protein kinase. To explore the role of RAB GTPases in PD, we undertook a comprehensive examination of their genetic variability in familial PD. Methods: Affected probands from 130 multi-incident PD families underwent whole-exome sequencing and genotyping, Potential pathogenic variants in 61 RAB GTPases were genotyped in relatives to assess disease segregation. These variants were also genotyped in a larger case-control series, totaling 3,078 individuals (2,734 with PD). The single most significant finding was subsequently validated within genetic data (6,043 with PD). Clinical and pathologic findings were summarized for gene-identified patients, and haplotypes were constructed. In parallel, wild-type and mutant RAB GTPase structural variation, protein interactions, and resultant enzyme activities were assessed. Findings: We found RAB32 c.213C>G (Ser71Arg) to co-segregate with autosomal dominant parkinsonism in three multi-incident families. RAB32 Ser71Arg was also significantly associated with PD in case-control samples: genotyping and database searches identified thirteen more patients with the same variant that was absent in unaffected controls. Notably, RAB32 Ser71Arg heterozygotes share a common haplotype. At autopsy, one patient had sparse neurofibrillary tangle pathology in the midbrain and thalamus, without Lewy body pathology. In transfected cells the RAB32 Arg71 was twice as potent as Ser71 wild type to activate LRRK2 kinase. Interpretation: Our study provides unequivocal evidence to implicate RAB32 Ser71Arg in PD. Functional analysis demonstrates LRRK2 kinase activation. We provide a mechanistic explanation to expand and unify the etiopathogenesis of monogenic PD. Funding: National Institutes of Health, the Canada Excellence Research Chairs program, Aligning Science Across Parkinson's, the Michael J. Fox Foundation for Parkinson's Research, and the UK Medical Research Council.

Primary cutaneous adenoid cystic carcinoma with lung metastasis: A case report with literature review.

Adenoid cystic carcinoma is a rare tumor that typically originates from secretory glands, most commonly found in the salivary glands. However, it can also develop as a primary cutaneous adenoid cystic carcinoma, which appears identical under the microscope to adenoid cystic carcinoma originating in other tissues. Distinguishing between primary cutaneous adenoid cystic carcinoma and extracutaneous adenoid cystic carcinoma with cutaneous metastases is crucial for determining the prognosis and appropriate management of the condition. In this case report, we describe a case of primary cutaneous adenoid cystic carcinoma located on the hand with lung metastases. Proper differentiation, treatment planning and regular clinical follow-up to monitor for any signs of recurrence or metastasis are essential to ensure favorable outcomes for patients with this rare neoplasm.

Genetic heterogeneity within a consanguineous family involving TTPA and SETX genes.

Autosomal recessive cerebellar ataxias (ARCA) constitute a highly heterogeneous group of progressive neurodegenerative disorders that typically occur prior to adulthood. Despite some clinical resemblance between these disorders, different genes are involved. We report in this study four Tunisian patients belonging to the same large consanguineous family, sharing autosomal recessive cerebellar ataxia phenotypes but with clinical, biological, electrophysiological, and radiological differences leading to the diagnosis of two distinct ARCA caused by two distinct gene defects. Two of our patients presented ataxia with the vitamin E deficiency (AVED) phenotype, and the other two presented ataxia with oculo-motor apraxia 2 (AOA2). Genetic testing confirmed the clinical diagnosis by the detection of a frameshift c.744delA pathogenic variant in the TTPA gene, which is the most frequent in Tunisia, and a new variant c.1075dupT in the SETX gene. In Tunisia, data suggest that genetic disorders are common. The combined effects of the founder effect and inbreeding, added to genetic drift, may increase the frequency of detrimental rare disorders. The genetic heterogeneity observed in this family highlights the difficulty of genetic counseling in an inbred population. The examination and genetic testing of all affected patients, not just the index patient, is essential to not miss a treatable ataxia such as AVED, as in the case of this family.

Diffuse cerebral edema with leukoencephalopathy revealing systemic lupus erythematosus: A case report and review of literature.

Background: Systemic lupus erythematosus (SLE) is a common autoimmune disease with various symptoms involving multiple organs. Neuropsychological manifestations are various and generally serious. Leukoencephalopathy is particularly rare but life-threatening in patients with SLE. Results: Here, we describe the case of a young woman who developed a subacute onset intracranial hypertension, papillar edema on fundus examination, diffuse cerebral edema on brain CT scan, and diffuse leukoencephalopathy on brain magnetic resonance imaging (MRI). The immunological workup was positive for antinuclear antibodies, anti-DNA and anti-extractable nuclear antigens (ENA) antibodies. She was ultimately diagnosed with SLE and experienced significant improvement after treatment with high dose of corticosteroids, acetazolamide, and immunosuppressant. We additionally review the previously reported cases of SLE with diffuse cerebral edema and leukoencephalopathy with a focus on the possible pathophysiological mechanisms of such association. Conclusions: We highlight, through this case report and the literature review, the importance of considering SLE in patients with cerebral edema and diffuse leukoencephalopathy and treating it aggressively.

Juvenile Dermatomyositis Without Skin Lesions in an Antinuclear Matrix Protein 2 Antibody Seropositive Pediatric Case.

ABSTRACT: We report a 5-year-old boy who presented with progressive weakness in 4 limbs and gait disorders over 7 months. No skin rash was observed on admission. A symmetrical proximodistal weakness was found. The creatine kinase level was normal with a slightly elevated lactate dehydrogenase level. Biopsy specimens showed infiltration of mononuclear cells, few necrotic fibers, and perifascicular atrophy. Screening for myositis-specific antibodies was positive for the antinuclear matrix protein 2 antibody, which is mainly associated with dermatomyositis. Symptoms improved on receiving corticosteroids. Our findings suggest that in cases where inflammatory muscle disease is suspected, antinuclear matrix protein 2 antibody analyses should be considered for precise diagnosis, even with the absence of dermatological symptoms. The case suggests consideration of juvenile dermatomyositis in children with no associated skin manifestations or elevated creatine kinase levels and highlights the importance of screening for myositis-specific antibodies in helping with the diagnosis, given the possible heterogeneity of its clinical presentations.

Interaction of Mitochondrial Polygenic Score and Lifestyle Factors in LRRK2 p.Gly2019Ser Parkinsonism.

BACKGROUND: A mitochondrial polygenic score (MGS) is composed of genes related to mitochondrial function and found to be associated with Parkinson's disease (PD) risk. OBJECTIVE: To investigate the impact of the MGS and lifestyle/environment on age at onset (AAO) in LRRK2 p.Gly2019Ser parkinsonism (LRRK2-PD) and idiopathic PD (iPD). METHODS: We included N = 486 patients with LRRK2-PD and N = 9259 with iPD from the Accelerating Medicines Partnership® Parkinson's Disease Knowledge Platform (AMP-PD), Fox Insight, and a Tunisian Arab-Berber founder population. Genotyping data were used to perform the MGS analysis. Additionally, lifestyle/environmental data were obtained from the PD Risk Factor Questionnaire (PD-RFQ). Linear regression models were used to assess the relationship between MGS, lifestyle/environment, and AAO. RESULTS: Our derived MGS was significantly higher in PD cases compared with controls (P = 1.1 × 10-8 ). We observed that higher MGS was significantly associated with earlier AAO in LRRK2-PD (P = 0.047, ß = -1.40) and there was the same trend with a smaller effect size in iPD (P = 0.231, ß = 0.22). There was a correlation between MGS and AAO in LRRK2-PD patients of European descent (P = 0.049, r = -0.12) that was visibly less pronounced in Tunisians (P = 0.449, r = -0.05). We found that the MGS interacted with caffeinated soda consumption (P = 0.003, ß = -5.65) in LRRK2-PD and with tobacco use (P = 0.010, ß = 1.32) in iPD. Thus, patients with a high MGS had an earlier AAO only if they consumed caffeinated soda or were non-smokers. CONCLUSIONS: The MGS was more strongly associated with earlier AAO in LRRK2-PD compared with iPD. Caffeinated soda consumption or tobacco use interacted with MGS to predict AAO. Our study suggests gene-environment interactions as modifiers of AAO in LRRK2-PD. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.