Renal cell carcinoma in young FH mutation carriers: case series and review of the literature.

Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC) is an autosomal dominant syndrome caused by heterozygous pathogenic germline variants in the fumarate hydratase (FH) gene. It is characterized by cutaneous and uterine leiomyomas and an increased risk of developing renal cell carcinoma (RCC), which is usually adult-onset. HLRCC-related RCC tends to be aggressive and can metastasize even when the primary tumor is small. Data on children and adolescents are scarce. Herein, we report two patients from unrelated Dutch families, with HLRCC-related RCC at the ages of 15 and 18 years, and a third patient with an FH mutation and complex renal cysts at the age of 13. Both RCC's were localized and successfully resected, and careful MRI surveillance was initiated to monitor the renal cysts. One of the patients with RCC subsequently developed an ovarian Leydig cell tumor. A review of the literature identified 10 previously reported cases of HLRCC-related RCC in patients aged younger than 20 years, five of them presenting with metastatic disease. These data emphasize the importance of recognizing HLRCC in young patients to enable early detection of RCC, albeit rare. They support the recommendations from the 2014 consensus guideline, in which genetic testing for FH mutations, and renal MRI surveillance, is advised for HLRCC family members from the age of 8-10 years onwards.

Celiac Artery Syndrome After Correction of Kyphoscoliosis.

Compression of the celiac artery by a tight arcuate ligament of the diaphragm is a rare syndrome that can arise after correction of severe kyphosis. Symptoms include abdominal pain and ileus and liver dysfunctions. These symptoms can be easily attributed to more common causes like the superior mesenteric artery syndrome, and a delay in the diagnosis of celiac artery obstruction may result in severe ischemic disease of the gastrointestinal tract. We present a case of celiac artery syndrome after correction of a kyphoscoliosis with severe sequelae that has not been documented before.

SOX3 deletion in mouse and human is associated with persistence of the craniopharyngeal canal.

CONTEXT: SOX3 is an early developmental transcription factor involved in pituitary development. In humans, over- and underdosage of SOX3 is associated with X-linked hypopituitarism with variable phenotypes ranging from isolated GH deficiency (GHD) to panhypopituitarism, with or without mental retardation and, in most cases, with reported pituitary imaging, an ectopic/undescended posterior pituitary. PATIENT: We present a young patient with hemophilia B and developmental delay who had a 2.31-Mb deletion on Xq27 including SOX3, F9, and eight other contiguous genes. He developed GH and gonadotropin deficiency, whilst his thyroid function was in the low normal range. Magnetic resonance imaging revealed a eutopic posterior pituitary and the unusual finding of a persistent craniopharyngeal canal that has not previously been described in patients with congenital hypopituitarism. OBJECTIVE AND METHODS: To establish whether loss of SOX3 can account for the human phenotype, we examined in detail the hypothalamo-pituitary region of neonatal Sox3 null mice. RESULTS: Consistent with the patient's phenotype, Sox3 null mice exhibit a ventral extension of the anterior pituitary that penetrates, and generates a mass beneath, the sphenoid bone. This suggests that the defect results from abnormal induction of Rathke's pouch, leading to a persistent connection between Rathke's pouch and the oral ectoderm. CONCLUSIONS: Our observations expand the spectrum of phenotypes observed in association with altered SOX3 dosage and may affect the approach to genetic screening. Screening for SOX3 should be advised not only for hypopituitary patients with an ectopic posterior pituitary, but also for those with a structurally normal pituitary and additional findings, including clefts and a persistent craniopharyngeal canal, with or without mental retardation.

Systematic review and meta-analysis on the diagnostic performance of FDG-PET/CT in detecting bone marrow involvement in newly diagnosed Hodgkin lymphoma: is bone marrow biopsy still necessary?

BACKGROUND: This study aimed to systematically review and meta-analyze published data on the diagnostic performance of (18)F-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (FDG-PET/CT) in detecting bone marrow involvement in newly diagnosed Hodgkin lymphoma, and to determine whether FDG-PET/CT can replace blind bone marrow biopsy (BMB) in these patients. PATIENTS AND METHODS: The PubMed/Medline and Embase databases were systematically searched for relevant studies. Methodological quality of each study was assessed. Sensitivities and specificities of FDG-PET/CT in individual studies were calculated and underwent meta-analysis with a random effects model. A summary receiver operating characteristic curve (sROC) was constructed with the Moses-Shapiro-Littenberg method. The weighted summary proportion of FDG-PET/CT-negative patients with a positive BMB among all cases was calculated under the fixed effects model. RESULTS: Nine eligible studies, comprising a total of 955 patients with newly diagnosed Hodgkin lymphoma, were included. Overall, the studies were of moderate methodological quality. The sensitivity and specificity of FDG-PET/CT for the detection of bone marrow involvement ranged from 87.5% to 100% and from 86.7% to 100%, respectively, with pooled estimates of 96.9% [95% confidence interval (CI) 93.0% to 99.0%] and 99.7% (95% CI 98.9% to 100%), respectively. The area under the sROC curve was 0.9860. The weighted summary proportion of FDG-PET/CT-negative patients with a positive BMB among all cases was 1.1% (95% CI 0.6% to 2.0%). CONCLUSION: Although the methodological quality of studies that were included in this systematic review and meta-analysis was moderate, the current evidence suggests that FDG-PET/CT may be an appropriate method to replace BMB in newly diagnosed Hodgkin lymphoma.