A 55-Year-Old Woman Presenting with a Second Diagnosis of Craniopharyngioma Following Diagnosis and Successful Treatment of Craniopharyngioma as a 5-Year-Old Child.

BACKGROUND Craniopharyngioma is a rare, partly cystic embryonic malformation of the sellar and parasellar region and is usually benign. This report is of a 55-year-old woman presenting with a second diagnosis of craniopharyngioma following diagnosis and successful treatment of craniopharyngioma as a 5-year-old child. CASE REPORT Our patient was diagnosed with craniopharyngioma at age 5 when she presented with headaches accompanied by nausea and vomiting, decreased visual acuity, polyurea, and polydipsia for 6 months. She was found to have diplopia and grade II papilledema. A skull X-ray showed separation of the sutures and a calcified mass in the suprasellar region. A pneumoencephalogram showed extension of the tumor into the third ventricle. Surgery was performed via transcallosal approach followed by radiotherapy at 5000 rays. She was followed up clinically and radiologically and had been disease-free until age 55, when she presented with headache and facial numbness. On examination, she had right-eye Horner syndrome, decreased sensation in the right side of the face, diplopia, and grade 2 facial palsy. An MRI revealed interval significant recurrence of the craniopharyngioma at the sellar/suprasellar mass with extension to the right Meckel's cave and the right posterior fossa. On April 6, 2023, she underwent surgical resection through a right-sided craniotomy and Kawase approach. This was followed by CyberKnife radiation therapy. CONCLUSIONS This report has presented a rare recurrence of craniopharyngioma with a 50-year interval and has highlighted the challenges in the diagnosis and the multidisciplinary approach to patient diagnosis and management.

A New Sarcoma Shortly after Treatment for High-Grade Glioma with Adjuvant Chemoradiation: A Case Report.

Introduction: High-grade gliomas are central nervous system tumors conventionally treated with surgery followed by adjuvant chemoradiotherapy. Secondary cancer due to radiation therapy is a rare yet established phenomenon that typically occurs years after radiation therapy. Case Presentation: In this case, we discuss an early presentation of a second cancer adjacent to the radiation field. This case report is of a 52-year-old male who developed a new scalp sarcoma at the site of primary surgery 8 months after radiation therapy. Genetic testing revealed a heterozygous missense variant in the NF1 gene, a variant of uncertain significance. The report highlights that this case does not conform to the expected criteria for postradiation sarcoma in terms of timing. Conclusion: Secondary cancers may arise earlier than expected, even in phenotypically normal patients, as they may have unmanifested variants of relevant mutations. The question of pre-radiotherapy screening for radiosensitivity syndromes and diseases requires further study, as current data are limited and do not provide enough insight into the significance of different genetic variants.

Embryonal tumor with multilayered rosettes: a report of a rare case.

The authors report a case of an embryonal tumor with multilayered rosettes (ETMR) in an 18-month-old female infant who presented with gait imbalance and progressive left-sided weakness for 2 months. ETMR is a rare small round blue cell aggressive tumor of the central nervous system characterized by the amplification of the C19MC region on chromosome 19 (Chr19q13.42). This report in detail the clinical-radiologic and histopathological workup and diagnosis. Because ETMRs are newly described rare pediatric central nervous system tumors with only a few reported cases, we aim to document this typical case to add to the existing data on these tumors.

Adenoid cystic carcinoma of the orbit with bilateral cavernous sinus extension: A case report.

INTRODUCTION AND IMPORTANCE: Adenoid cystic carcinoma (ACC) is an uncommon malignant epithelial tumor of the salivary and lacrimal glands. Orbital ACC is rare, originating commonly from the lacrimal gland, with only a few cases reported without lacrimal gland involvement. Deep orbital ACC may be associated with extension into skull base structures, and further intracranial invasion. CASE PRESENTATION: We report a 47-year-old gentleman who presented with insidious onset of bilateral proptosis, left ophthalmoplegia, and loss of vision. Imaging revealed left orbital infiltrative mass with intracranial invasion and bilateral cavernous sinus extension. The lacrimal gland was not involved clinically nor radiologically. Histopathology showed ACC with classical cribriform pattern. There was no evidence of primary source of tumor or metastasis. DISCUSSION: ACC of the orbit commonly originates from the lacrimal gland. Only a few cases of orbital ACC without lacrimal gland involvement were found in English literature. Workup for our patient did not reveal a primary source of tumor. Tumor may have risen from ectopic orbital lacrimal gland tissue, extension from non-orbital sites, or through perineural or hematogenous spread. Only one case of bilateral cavernous sinus extension has been previously reported. Treatment for advanced orbital ACC is exenteration in most cases. However, due to the advanced nature of disease in our patient, palliative radiotherapy was the treatment of choice. CONCLUSION: Orbital ACC of non-lacrimal origin is rare and is associated with high morbidity and mortality. Early recognition and treatment are key for preventing organ and life-threatening complications such as advanced intracranial spread.

Ten-year survival in glioblastoma patient with neurofibromatosis type 1: illustrative case.

BACKGROUND: Gliomas are commonly detected in patients with neurofibromatosis type 1 (NF1) at an early age. Few patients with NF1 are diagnosed with glioblastoma. The course of management, response to therapy, and prognosis of such patients are unknown. Few reports have shown longer-than-average survival rates for patients with NF1 with glioblastoma. OBSERVATIONS: A 27-year-old man with NF1 presented with symptoms of high intracranial pressure. Imaging and pathology showed left frontotemporal glioblastoma. Gross total resection was achieved, and concurrent chemoradiotherapy was administered. Recurrence of tumor was detected 48 months later, and the patient underwent tumor debulking and concurrent chemoradiotherapy. The patient received first-, second-, and third-line chemotherapy (temozolomide, bevacizumab, bevacizumab/irinotecan) with good tolerance and has survived >10 years since then with good functional status. LESSONS: This case demonstrates >10 years overall survival of glioblastoma in a patient with NF1. Reports of patients with NF1 with longer survival may be attributed to the young age at diagnosis and relatively better tolerance for therapy. It might also support the growing evidence of a unique subset of glioblastoma associated with NF1 and opens the door for a more molecular targeted therapy in the future.

Genomic, Proteomic, and Phenotypic Spectrum of Novel O-Sialoglycoprotein Endopeptidase Variant in Four Affected Individuals With Galloway-Mowat Syndrome.

Galloway-Mowat syndrome is a rare autosomal recessive disease characterized by a unique combination of renal and neurological manifestations, including early-onset steroid-resistant nephrotic syndrome, microcephaly, psychomotor delay, and gyral abnormalities of the brain. Most patients die during early childhood. Here, we identified a novel homozygous O-sialoglycoprotein endopeptidase (OSGEP) variant, NM_017807.3:c.973C>G (p.Arg325Gly), in four affected individuals in an extended consanguineous family from Saudi Arabia. We have described the detailed clinical characterization, brain imaging results, and muscle biopsy findings. The described phenotype varied from embryonic lethality to early pregnancy loss or death at the age of 9. Renal disease is often the cause of death. Protein modeling of this OSGEP variant confirmed its pathogenicity. In addition, proteomic analysis of the affected patients proposed a link between the KEOPS complex function and human pathology and suggested potential pathogenic mechanisms.

Early onset of capsular contracture after breast augmentation with implant: report of two cases & review of literature.

Capsular contracture (CC) is a local complication caused by an inflammatory reaction that leads to fibrosis. CC commonly occurs after one year of surgery. Hence, there has been no previously reported early onset of CC. Therefore, we report two unusual cases of early onset of post-breast reconstruction capsular contracture.

Finger Flexor Weakness in Myasthenia Gravis.

Myasthenia gravis (MG) affects the ocular, bulbar, and proximal limb muscles. The involvement of distal limb muscles is uncommon. MG-related weakness that severely affects the finger flexors and spares finger extensors and intrinsic hand muscles have never been reported. Here, we report a 35-year-old woman with acetylcholine receptor-antibody positive generalised MG who presented with severe bilateral asymmetric (left worse than right) finger flexor weakness during an MG relapse. The remaining muscles including the median and ulnar intrinsic hand muscles were normal. Repetitive nerve stimulation test showed decremental responses of more than 10%. Magnetic resonance imaging showed short-T1 inversion recovery sequences and increased signal intensities in the volar forearm muscles. Needle electromyography revealed fibrillations and positive sharp waves, small amplitude, short-duration, and polyphasic early recruiting motor unit action potentials. Myositis-specific autoantibodies were negative. Muscle biopsy showed neurogenic features. The patient had a good recovery with immunotherapy. We conclude that clinicians should be aware that marked weakness of the finger flexors can occur as a result of an MG relapse and may require early aggressive therapy. Key Words: Electromyography, Finger flexors, Muscle, Biopsy, Myasthenia gravis.

Exome Sequencing Reveals Novel TTN Variants in Saudi Patients with Congenital Titinopathies.

Aim: Our goal was to determine the genetic basis of early-onset myopathy in patients from two unrelated families. Materials and Methods: Whole-exome sequencing, autozygosity mapping, and confirmatory targeted Sanger sequencing were performed using genomic DNA extracted from blood samples from three myopathic patients of two unrelated families. Variant filtering and pathogenicity analyses were evaluated according to standard protocols and up-to-date pipelines applied at the King Faisal Specialist Hospital and Research Center. Results: A novel homozygous variant was detected in TTN gene within the first three M-line-encoding exons in a 9-year-old female in the first family who had delayed motor development and proximal weakness. Her 4-year-old affected brother, with the same homozygous variant, could not yet walk without help. This pathogenic nonsense variant is predicted to cause a premature stop during translation. In the second family we identified two novel variants as compound heterozygosites (a deletion and a variant affecting a canonical splice site) in an affected 9-year-old female with weakness that developed at age 3, in the second family. SpliceAI predicted the variants being splice-altering with high probability. These variants were fully segregated in the family. The deletion was found to be on the paternal allele, whereas the splicing variant was on the maternal allele. The patient's echocardiography revealed mitral valve prolapse with mild mitral regurgitation. Muscle histology showed minicores that were also confirmed by electron microscopy. Conclusion: Our study identified novel pathogenic variants in the TTN gene that are likely responsible for the phenotype of early-onset myopathy; hence, expanding genotype-phenotype relationship of titinopathies.

Clival simple bone cyst: Rare pathological entity (case report).

BACKGROUND: Clival cystic lesions are not frequently seen in neurosurgery. Cystic lesion in the clivus can be part of a neoplastic process such as chordoma, chondrosarcoma, plasmacytoma, or metastasis. Rare types of pure cystic clival lesions include simple bone cysts and arachnoid cysts, which are asymptomatic most of the time and do not cause symptoms until they reach a large size. CASE DESCRIPTION: This is a case report of a healthy 53-year-old male patient with a clival cystic lesion. The patient underwent surgical drainage and wall resection of the clival lesion with no postoperative complications. Intraoperative finding raised the possibility of the diagnosis of an arachnoid cyst. However, the pathology findings indicated a simple bone cyst. CONCLUSION: Simple bone cyst and arachnoid cyst in the clivus are rare, they should be considered in the diagnosis of clival cystic lesions.

Atypical Imaging of Hemorrhagic Lumbosacral Myxopapillary Ependymoma with Histopathological Correlation: A Case Report.

BACKGROUND Spinal myxopapillary ependymoma (MPE) is a slow-growing tumor arising from ependymal cells of the central nervous system. MPE rarely presents with acute neurological compromise and most commonly occur in the filum terminale or conus medullaris region. To date, only a few cases have been reported of patients presenting acutely because of hemorrhagic MPE. CASE REPORT A 16-year-old boy without previous medical problems presented with a sudden onset of severe pain in the low back radiating to the thighs. He could not walk owing to the severity of the pain. Neurological examination revealed an unsteady gait, but the rest of the motor and sensory examination was normal. Lumbosacral spine magnetic resonance imaging revealed an intradural hemorrhagic mass extending from L5 to S2. The encapsulated hemorrhagic tumor was resected, and the pathology was consistent with MPE grade I. The patient made a significant recovery postoperatively. It is extremely rare for MPE to present with spontaneous hemorrhage in the lumbosacral region. Prompt diagnosis and management led to a favorable outcome. This case report is intended to highlight the atypical presentation and imaging features of hemorrhagic MPE. CONCLUSIONS We described a rare case of MPE in the lumbosacral region of a patient who presented with acute neurological compromise and atypical imaging features.

Validating candidate biomarkers for different stages of non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is a common chronic condition caused by the accumulation of fat in the liver. NAFLD may range from simple steatosis to advanced cirrhosis, and affects more than 1 billion people around the world. To date, there has been no effective treatment for NAFLD. In this study, we evaluated the expression of 4 candidate NAFLD biomarkers to assess their possible applicability in the classification and treatment of the disease.Twenty-six obese subjects, who underwent bariatric surgery, were recruited and their liver biopsies obtained. Expression of 4 candidate biomarker genes, PNPLA3, COL1A1, PPP1R3B, and KLF6 were evaluated at gene and protein levels by RT-qPCR and enzyme-linked immunosorbent assay (ELISA), respectively.A significant increase in the levels of COL1A1 protein (P = .03) and PNPLA3 protein (P = .03) were observed in patients with fibrosis-stage NAFLD compared to that in patients with steatosis-stage NAFLD. However, no significant differences were found in abundance of PPP1R3B and KLF6 proteins or at the gene level for any of the candidate.This is the first study, to our knowledge, to report on the expression levels of candidate biomarker genes for NAFLD in the Saudi population. Although PNPLA3 and PPP1R3B had been previously suggested as biomarkers for steatosis and KLF6 as a possible marker for the fibrosis stage of NAFLD, our results did not support these findings. However, other studies that had linked PNPLA3 to fibrosis in advanced NAFLD supported our current finding of high PNPLA3 protein in patients with fibrosis. Additionally, our results support COL1A1 protein as a potential biomarker for the fibrosis stage of NAFLD, and indicate its use in the screening of patients with NAFLD. Further studies are required to validate the use of COL1A1 as a biomarker for advanced NAFLD in a larger cohort.

Phenotypic and genotypic analysis of limb-Girdle muscular dystrophy type 2B.

Dysferlinopathies are rare autosomal recessive muscular dystrophies caused by mutation in the dysferlin (DYSF) gene, resulting in varied phenotype. In this case report, we review a 26-year-old diabetic male patient who presented to hospital suffering from progressive muscle weakness. We confirmed the diagnosis of dysferlinopathy with phenotype of limb girdle muscular dystrophy, followed by a muscle biopsy, immunohistochemistry and a molecular technique, exome sequencing. The specific homozygous mutations in DYSF and heterozygous mutation PSAP genes identified in the present case of LGMD-2B are found in the Saudi population.

Endothelial dysfunction in nonalcoholic steatohepatitis with low cardiac disease risk.

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. We prospectively evaluated endothelial function by assessing flow-mediated dilatation (FMD) of the brachial artery in patients with biopsy-proven NAFLD. This prospective study included 139 patients (50 healthy controls, 47 patients with steatosis and 42 patients with steatohepatitis), all of whom were nondiabetic. Patients with long-standing or uncontrolled hypertension, smokers, and morbidly obese patients were excluded. The medians (ranges) for vascular FMD in the steatohepatitis, steatosis, and control groups were 6% (0-37.5%), 10.8% (0-40%) and 13.6% (0-50%), respectively. The control group had a higher average FMD than the NAFLD group (15.13% vs 10.46%), and statistical significance was reached when the control and steatohepatitis groups were compared (13.6% vs 6%, p = 0.027). Average alanine aminotransferase was significantly higher in the steatohepatitis group than in the steatosis and control groups (54 (U/L) vs 31 (U/L), p = 0.008). Cholesterol levels were similar between all groups. In the multivariate analysis, FMD (OR = 0.85, p = 0.035) and high triglycerides (OR = 76.4, p = 0.009) were significant predictors of steatohepatitis. In the absence of major cardiac risk factors, we demonstrated better endothelial function in healthy controls, evidenced by a higher FMD of the brachial artery than that of patients with steatohepatitis.

Neuronal Differentiation in a Pituitary Macroadenoma with Focal Small Blue Round Cell Morphology: Report of a Rare Pattern.

Ganglion cell-containing pituitary adenomas that are neurofilament protein-positive are the exceedingly rare form of pituitary ganliocytomas. We report a case of a 23-year-old male patient who presented with a clinical picture of acromegaly in addition to raised prolactin level. Histopathology showed areas exhibiting pseudopapillary and solid proliferation of round and monotonous blue cells. The immunohistochemistry showed strong reactivity for synaptophysin and growth hormone and focal reactivity to prolactin. Fibrous bodies are confirmed using cytokeratin immunostain, in keeping with sparsely granulated somatotroph component. The patient remained free of recurrence after one year of radiological follow-up.

Prevalence of biopsy-proven nonalcoholic fatty liver among patients with gallstone disease.

BACKGROUND/AIM: Gallstone disease (GD) and nonalcoholic fatty liver disease (NAFLD) are associated with metabolic syndrome. Despite the benign nature of NAFLD, 10% of patients may develop advanced fibrosis and cirrhosis. We aimed to identify the prevalence and factors associated with NAFLD among GD patients in the Saudi population. PATIENTS AND METHODS: This is a single-center, observational cohort study that included patients seen in general surgery clinics at our institution from 2011 to 2017. All liver biopsies were taken at the same time as the cholecystectomy. Demographical and clinical data were prospectively collected from the study population. RESULTS: Of the 301 GD patients in the study, 15% had a normal body mass index (BMI), 29% were overweight, and 56% were obese. There were 143 (47.8%) patients with NAFLD, of which 125 (41.8%) showed steatosis and 18 (6%) had nonalcoholic steatohepatitis. There was a significant positive correlation between NAFLD and age (r = 0.243; P < 0.0001), and BMI (r = 0.242; P < 0.0001). Obese patients with BMI 30-40 kg/m[2] were 2.403 (P = 0.039) more likely to have NAFLD compared with normal BMI patients, and this value increased to 6.145 (P = 0.002) in patients with BMI >40 kg/m[2]. Additionally, patients with T2DM were 2.839 times (P = 0.015) more likely to have NAFLD compared with those who did not. CONCLUSIONS: The prevalence of NAFLD among GD patients is high. High BMI and diabetes are independent factors associated with NAFLD in GD patients. The results suggest that there may be a need for routine liver biopsy in selected patients during cholecystectomy.

Next generation DNA sequencing of atypical choroid plexus papilloma of brain: Identification of novel mutations in a female patient by Ion Proton.

Choroid plexus papilloma (CPP) is a rare benign tumor of the central nervous system that is usually confined to the cerebral ventricles. According to the World Health Organization, CPP corresponds to a grade I atypical CPP (a-CPP); however, it can become more aggressive and reach grade II, which can rarely undergo malignant transformation into a choroid plexus carcinoma (grade III). To the best of our knowledge, identification of these tumors mutations by next generation DNA sequencing (NGS) has not been yet reported. In the present study, NGS analysis of an a-CPP case was performed. Data were analyzed using Advaita Bioinformatics i-VariantGuide and Ion Reporter 5.6 programs. The results from NGS identified 12 novel missense mutations in the following genes: NOTCH1, ATM, STK36, MAGI1, DST, RECQL4, NUMA1, THBS1, MYH11, MALT1, SMARCA4 and CDH20. The PolyPhen score of six variants viz., DST, RECQL4, NUMA1, THBS1, MYHI1 and SMARCA4 were high, which suggested these variants represents pathogenic variants. Two novel insertions that caused frameshift were also found. Furthermore, two novel nonsense mutations and 14 novel intronic variants were identified in this tumor. The novel missense mutation detected in ATM gene was situated in c.5808A>T; p. (Leu1936Phe) in exon 39, and a known ATM mutation was in c.5948A>G; p. (Asn1983Ser). These novel mutations had not been reported in previous database. Subsequently, the quality statistics of these variants, including allele coverage, allele ratio, P-value, Phred quality score, sequencing coverage, PolyPhen score and alleles frequency was performed. For all variants, P-value was highly significant and the Phred quality score was high. In addition, the results from sequencing coverage demonstrated that 97.02% reads were on target and that 97.88% amplicons had at least 500 reads. These findings may serve at determining new strategies to distinguish the types of choroid plexus tumor, and at developing novel targeted therapies. Development of NGS technologies in the Kingdom of Saudi Arabia may be used in molecular pathology laboratories.

Endoscopic Transnasal Resection of Suprasellar Teratoma.

BACKGROUND: Intracranial teratomas are rare tumors that usually present during the second decade of life. Among intracranial teratomas, suprasellar germ cell tumors in particular are extremely rare. We present the case of an 18-year-old girl who underwent a successful endoscopic transnasal resection of a suprasellar teratoma with a mixed germ cell component. CASE DESCRIPTION: An 18-year-old girl presented with progressive visual disturbance, headache, weight loss, and fatigue for 2 weeks. She had decreased vision in her right eye and double vision when looking to the right side. On examination, she had right-side complete abducens nerve palsy and partial oculomotor nerve palsy bilaterally. Brain imaging revealed a large suprasellar lesion consistent with a germ cell tumor. The patient underwent a transnasal endoscopic resection of the lesion. Pathology showed a mixed germ cell tumor (80% mature cystic teratoma, 18% yolk sac tumor, and 2% germinoma). The mature teratomatous elements identified included skin with sebaceous material, hair, cartilage, acini, colonic mucosa, muscle, nerve bundles, and adipose tissue. Postoperative magnetic resonance imaging (MRI) showed residual tumor in the left cavernous sinus and anterior clinoid process superiorly. At a 1-year follow-up, the double vision had resolved, and her vision showed progressive improvement. The patient was maintained on treatment for diabetes insipidus, hypothyroidism, and adrenal insufficiency. Her last MRI showed no signs of tumor progression. CONCLUSIONS: The present case demonstrates a safe endoscopic transnasal surgical resection of a rare suprasellar tumor, mixed teratoma, with intra-axial extension. The endoscopic transnasal approach can be considered a valid option for a suprasellar lesion.

The histological spectrum of tubulo-reticular inclusion positive renal biopsies: a tertiary hospital experience and review of the literature.

AIM: To identify the underlying diseases with TRI-positive kidney biopsies, and describe the histological pattern and spectrum of TRI-positive kidney biopsies. METHODS: A retrospective analysis of all patients' chart that underwent renal biopsy at King Saud University Medical City between 2012 and 2017 was done. Kidney biopsies that indicated a positive result for tubuloreticular inclusions (TRI's) on electron microscopy were reviewed and the underlying disease and histological pattern was extracted. RESULTS: Of 1,473 native kidney biopsies reviewed, 96 (6.5%) were TRI-positive. Of the 96 TRI-positive kidney biopsies, 87 (90.6%) were TRI-positive lupus nephritis (LN); of which 10 (11.5%) were Class V, 49 (56.3%) were active LN, and 28 (32.2%) were inactive LN. The underlying diseases of the nine non-LN TRI-positive cases included diabetic nephropathy, connective tissue disorders, immune complex mediated Glomerulonephritis (GN), acute thrombotic microangiopathy, rhabdomyolysis, and Wegener's disease. CONCLUSION: LN is a very common finding in TRI-positive kidney biopsies. Active LN and chronic LN are the more common classes of TRI-positive LN kidney biopsies, than pure membranous (Class V) LN. TRI positive kidney biopsies without LN are commonly found in diabetic nephropathy, connective tissue disorders and immune mediated GN's. This study highlights this finding in our patients cohort in opposition to what has been reported in the literature.