Sophie FERLICOT,
Sophie FERLICOT
Institution: Université Paris-Saclay Faculté de Médecine: Universite Paris-Saclay Faculte de Medecine
Email:
Pierre-Alexandre Just,
Pierre-Alexandre Just
Institution: APHP: Assistance Publique - Hopitaux de Paris
Email:
Eva Compérat,
Eva Compérat
Institution: APHP: Assistance Publique - Hopitaux de Paris
Email:
Etienne Rouleau,
Etienne Rouleau
Institution: Gustave Roussy Institute: Gustave Roussy
Email:
Frédérique Tissier,
Frédérique Tissier
Institution: APHP: Assistance Publique - Hopitaux de Paris
Email:
Christophe Vaessen,
Christophe Vaessen
Institution: APHP: Assistance Publique - Hopitaux de Paris
Email:
Stéphane Richard
Stéphane Richard
Institution: EPHE: Ecole Pratique des Hautes Etudes
Email:
Background: Hereditary papillary renal cell carcinoma (HPRCC) is a rare autosomal dominant disease characterized by the development of multiple and bilateral papillary type I renal cell carcinomas (RCC) and papillary adenomas caused by activating mutations in the MET proto-oncogene. Classically, dis...
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Background: Hereditary papillary renal cell carcinoma (HPRCC) is a rare autosomal dominant disease characterized by the development of multiple and bilateral papillary type I renal cell carcinomas (RCC) and papillary adenomas caused by activating mutations in the MET proto-oncogene. Classically, distinctive histological features of RCC are described according to the familial renal cell carcinoma syndrome. To date, no clear cell RCC has been reported in HPRCC syndrome. Case presentation: We describe the case of a 51-year-old man with a germline MET mutation, who developed numerous papillary tumors but also unexpectedly clear cell renal cell carcinomas. During the follow-up, an adrenal metastasis was observed seven years after the initial diagnosis corresponding to a clear cell RCC metastasis. Using FISH, the metastatic tumor presented a trisomy of chromosomes 7 and 17. These genomic alterations are usually detected in papillary RCC, highlighting the potential link between both histological subtypes of tumors and the HPRCC syndrome.
Conclusions: The pathologist must be aware that the presence of a non-papillary RCC associated with numerous papillary tumors should not exclude the diagnostic suspicion of HPRCC and thus to perform a thorough genomic study.
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3 weeks ago
Ichiro Tsuboi,
Ichiro Tsuboi
Institution: Shimane University Faculty of Medicine Department of Urology, , Izumo, Japan
Email:
Momoko Araki,
Momoko Araki
Institution: Shimane University Faculty of Medicine Department of Clinical Genetics Unit, , Izumo, Japan
Email:
Shuhei Yokoyama,
Shuhei Yokoyama
Institution: Shimane University Faculty of Medicine Department of Urology, , Izumo, Japan
Email:
Gen Tanaka,
Gen Tanaka
Institution: Shimane University Faculty of Medicine Department of Urology, , Izumo, Japan
Email:
Kazutaka Mitani,
Kazutaka Mitani
Institution: Shimane University Faculty of Medicine Department of Urology, , Izumo, Japan
Email:
Saori Yosioka,
Saori Yosioka
Institution: Shimane University Faculty of Medicine Department of Urology, , Izumo, Japan
Email:
Yusuke Kobayashi,
Yusuke Kobayashi
Institution: Shimane University Faculty of Medicine Department of Urology, , Izumo, Japan
Email:
Hirochika Nakajima,
Hirochika Nakajima
Institution: Shimane University Faculty of Medicine Department of Urology, , Izumo, Japan
Email:
Taichi Nagami,
Taichi Nagami
Institution: Shimane University Faculty of Medicine Department of Urology, , Izumo, Japan
Email:
Kohei Ogawa,
Kohei Ogawa
Institution: Shimane University Faculty of Medicine Department of Urology, , Izumo, Japan
Email:
Chiaki Koike,
Chiaki Koike
Institution: Shimane University Faculty of Medicine Department of Urology, , Izumo, Japan
Email:
Koichiro Wada
Koichiro Wada
Institution: Shimane University Faculty of Medicine Department of Urology, , Izumo, Japan
Email:
Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a rare autosomal-dominant disorder caused by a heterozygous germline mutation in the fumarate hydratase (FH) gene. HLRCC is clinically characterized by the development of three tumors: uterine leiomyomata, cutaneous leiomyomata, and renal ce...
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Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a rare autosomal-dominant disorder caused by a heterozygous germline mutation in the fumarate hydratase (FH) gene. HLRCC is clinically characterized by the development of three tumors: uterine leiomyomata, cutaneous leiomyomata, and renal cell carcinoma (RCC). HLRCC-associated RCC is aggressive and diagnosed at a much earlier age than sporadic RCC. It is essential for carriers of HLRCC to undergo annual renal screening by magnetic resonance imaging to detect early stage RCCs. Metastatic HLRCC-associated RCC must be treated by systemic therapy; however, it is unclear which medicines are most effective in treating this cancer owing to its low incidence rate. Immune checkpoint inhibitor (ICI) combinations or ICIs plus tyrosine kinase inhibitors are administered as systemic therapy for clear cell RCC. Here, we report a patient with HLRCC-associated RCC treated with sequential therapy, including ipilimumab plus nivolumab combination and cabozantinib, after diagnosis of HLRCC-associated RCC using FoundationOne Liquid CDx and single-site analysis. We also investigated familial FH mutations and describe a new family pedigree for HLRCC.
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3 weeks ago
Akihiro Ohmoto,
Akihiro Ohmoto
Institution: NULL
Email:
Naomi Hayashi,
Naomi Hayashi
Institution: NULL
Email:
Shunji Takahashi,
Shunji Takahashi
Institution: NULL
Email:
Arisa Ueki
Arisa Ueki
Institution: NULL
Email:
Adrenocortical carcinoma (ACC) and pheochromocytoma/paraganglioma (PPGL) are two rare types of adrenal gland malignancies. Regarding hereditary tumors, some patients with ACC are associated with with Li-Fraumeni syndrome (LFS), and those with PPGL with multiple endocrine neoplasia type 2. Recent stu...
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Adrenocortical carcinoma (ACC) and pheochromocytoma/paraganglioma (PPGL) are two rare types of adrenal gland malignancies. Regarding hereditary tumors, some patients with ACC are associated with with Li-Fraumeni syndrome (LFS), and those with PPGL with multiple endocrine neoplasia type 2. Recent studies have expanded this spectrum to include other types of hereditary tumors, such as Lynch syndrome or familial adenomatous polyposis. Individuals harboring germline TP53 pathogenic variants that cause LFS have heterogeneous phenotypes depending on the respective variant type. As an example, R337H variant found in Brazilian is known as low penetrant. While 50–80% of pediatric ACC patients harbored a LFS, such a strong causal relationship is not observed in adult patients, which suggests different pathophysiologies between the two populations. As for PPGL, because multiple driver genes, such as succinate dehydrogenase (SDH)-related genes, RET, NF1, and VHL have been identified, universal multi-gene germline panel testing is warranted as a comprehensive and cost-effective approach. PPGL pathogenesis is divided into three molecular pathways (pseudohypoxia, Wnt signaling, and kinase signaling), and this classification is expected to result in personalized medicine based on genomic profiles. It remains unknown whether clinical characteristics differ between cases derived from genetic predisposition syndromes and sporadic cases, or whether the surveillance strategy should be changed depending on the genetic background or whether it should be uniform. Close cooperation among medical genomics experts, endocrinologists, oncologists, and early investigators is indispensable for improving the clinical management for multifaceted ACC and PPGL.
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3 weeks ago
Annmarie Taheny,
Annmarie Taheny
Institution: NULL
Email:
Haylie McSwaney,
Haylie McSwaney
Institution: NULL
Email:
Julia Meade
Julia Meade
Institution: NULL
Email:
Current National Comprehensive Cancer Network ® (NCCN ®) guidelines for Colorectal Genetic/Familial High-Risk Assessment provide limited guidance for genetic testing for individuals with already diagnosed hereditary cancer conditions. We are presenting the case of a 36-year-old woman who was diagn...
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Current National Comprehensive Cancer Network ® (NCCN ®) guidelines for Colorectal Genetic/Familial High-Risk Assessment provide limited guidance for genetic testing for individuals with already diagnosed hereditary cancer conditions. We are presenting the case of a 36-year-old woman who was diagnosed with Lynch Syndrome at age 23 after genetic testing for a familial variant (c.283del) in the MLH1 gene. The patient had a previous history of Hodgkin Lymphoma at the time of familial variant testing, and she would later develop stage IIIa cecal adenocarcinoma at age 33 and metastatic papillary thyroid carcinoma at age 35. The patient’s family history included a first-degree relative who was diagnosed with colorectal cancer at age 39, multiple second-degree relatives with colorectal, endometrial, and stomach cancer, and third and fourth-degree relatives with breast cancer. In light of her personal and family history, a comprehensive cancer panel was recommended. This panel found a second hereditary cancer predisposition syndrome: a likely pathogenic variant (c. 349 A G) in the CHEK2 gene. This specific CHEK2 variant was recently reported to confer a moderately increased risk for breast cancer. The discovery of this second cancer predisposition syndrome had important implications for the patient’s screening and risk management. While uncommon, the possibility of an individual having multiple cancer predisposition syndromes is important to consider when evaluating patients and families for hereditary cancer, even when a familial variant has been identified.
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3 weeks ago
Fangfang Gao,
Fangfang Gao
Institution: NULL
Email:
Dejian Gu,
Dejian Gu
Institution: NULL
Email:
He Zhang,
He Zhang
Institution: NULL
Email:
Chao Shi,
Chao Shi
Institution: NULL
Email:
Feng Du,
Feng Du
Institution: NULL
Email:
Bo Zheng,
Bo Zheng
Institution: NULL
Email:
Huijuan Wu,
Huijuan Wu
Institution: NULL
Email:
Yanqiu Zhao
Yanqiu Zhao
Institution: NULL
Email:
Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a rare autosomal dominant syndrome caused by a germline mutation in the fumarate hydratase (FH) gene that manifests with cutaneous leiomyomas, uterine fibroids, and renal cell cancer (RCC). Patients with HLRCC-associated RCC (HLRCC-RCC) have...
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Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a rare autosomal dominant syndrome caused by a germline mutation in the fumarate hydratase (FH) gene that manifests with cutaneous leiomyomas, uterine fibroids, and renal cell cancer (RCC). Patients with HLRCC-associated RCC (HLRCC-RCC) have aggressive clinical courses, but there is no standardized therapy for advanced HLRCC-RCC. In this study, we described a case of aggressive HLRCC in a 33-year-old female who exhibited a novel heterozygous germline insertion mutation in exon 8 of the FH gene (c.1126 C > T; p.Q376*). The patient underwent laparoscopic resection of the right kidney, but metastases appeared within 3 months after surgery. Histological staining of the resected tumor revealed high expression levels of programmed cell death-ligand 1 (PD-L1). Therefore, the patient was treated with immunotherapy. The patient achieved a partial response to immunotherapy, and the treatment of metastatic lesions has continued to improve. A thorough literature review pinpointed 76 historical cases of HLRCC-RCC that had undergone immunotherapy. From this pool, 46 patients were selected for this study to scrutinize the association between mutations in the FH gene and the effectiveness of immunotherapy. Our results indicate that immunotherapy could significantly improve the overall survival (OS) of patients with HLRCC-RCC. However, no influence of different mutations in the FH germline gene on the therapeutic efficacy of immunotherapy was observed. Therefore, our study suggested that immunotherapy was an effective therapeutic option for patients with HLRCC regardless of the type of FH germline mutation.
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3 weeks ago
Stuart S Berr,
Stuart S Berr
Institution: NULL
Email:
Antonio Gonzalez
Antonio Gonzalez
Institution: NULL
Email:
Glioblastoma (GB) is the most common brain cancer and has limited survivability with a mean survival time of 15 months and an overall survival of less than 7 % after 5 years. Impediments to delivery of large molecule (e.g. antibodies) and cell therapeutics to a tumor include the blood–brain barrie...
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Glioblastoma (GB) is the most common brain cancer and has limited survivability with a mean survival time of 15 months and an overall survival of less than 7 % after 5 years. Impediments to delivery of large molecule (e.g. antibodies) and cell therapeutics to a tumor include the blood–brain barrier (BBB) and the blood‐tumor barrier (BTB) which prevent large solutes from crossing from circulating blood into the extracellular fluid of the central nervous system. Recently, methodology has been developed to use focused ultrasound (FUS) in conjunction with microbubbles to temporarily disrupt the BBB/BTB. FUS units have been developed that can be used in the high magnetic fields that are part of a MRI scanners. The MRI is used to locate the brain tumor to determine where FUS energy will be applied to open the BBB/BTB. However, it is difficult using current technologies to determine the optimum relative timing and dosages of drugs/cells and application of FUS. We have previously shown using PET imaging of a [89Zr]‐mCD47 to GB in a mouse model, that antibody binding by a tumor is significantly enhanced if the mCD47 antibody is injected 15 min after BBB/BTB disruption, rather than injection before BBB/BTB disruption.1 However, this study was done using two fixed time points. The animals had to be transported between different scanners which prevented us from a continuous measurement of tumor uptake and washout of antibody. We propose to build a unique trimodal MRI/FUS/PET system that would permit real‐time measurement of influx of radiolabeled therapeutic antibodies or cells and allow us to optimize the timing of FUS relative to injection of therapeutics. It will allow whole‐body mouse imaging so we will be able to measure in vivo biodistribution as well. To the best of our knowledge, no such system exists anywhere. However, our group has previously published simulation studies that show that it is feasible to use a PET insert in conjunction with MRI and FUS in the setting of tumor ablation in the brain
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3 weeks ago
Amena Ali Hussain,
Amena Ali Hussain
Institution: NULL
Email:
Eva Forssell-Aronsson,
Eva Forssell-Aronsson
Institution: NULL
Email:
Tobias Rosholm,
Tobias Rosholm
Institution: NULL
Email:
Esmaeil Mehrara
Esmaeil Mehrara
Institution: NULL
Email:
PET/CT and PET/MRI are valuable multimodality imaging techniques for visualizing both functional and anatomical information. The most used PET reconstruction algorithm is Ordered Subset Expectation Maximization (OSEM). In OSEM, the image noise increases with increased number of iterations, and the r...
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PET/CT and PET/MRI are valuable multimodality imaging techniques for visualizing both functional and anatomical information. The most used PET reconstruction algorithm is Ordered Subset Expectation Maximization (OSEM). In OSEM, the image noise increases with increased number of iterations, and the reconstruction needs to be stopped before complete convergence. The Bayesian penalized likelihood (BPL) algorithm, recently introduced, uses a noise penalty factor (β) to achieve full convergence while controlling noise. This study aims to evaluate how reconstruction algorithms and lesion radioactivity levels affect PET image quality and quantitative accuracy across three different PET systems. Materials and Methods: A NEMA phantom was filled with 18F and scanned by one PET/MRI and two PET/CT systems with sphere-to-background concentration ratio (SBR) of 2:1, 4:1, or 10:1. PET images were reconstructed with OSEM or BPL with TOF. The number of iterations and β-values were varied, while the matrix size, number of subsets, and filter size remained constant. Contrast recovery (CR) and background variability (BV) were measured in images. Results: CR increased with increased sphere size and SBR. CR and BV decreased with increased β for the 10mm sphere. Increased number of iterations in OSEM showed increased BV with limited variation in CR. BPL gave higher CR and lower BV values than OSEM. The optimal reconstruction was BPL with β between 150 and 350, where BPL was available, and OSEM with two iterations and 21 subsets for the PET/CT without BPL. Conclusion: BPL outperforms OSEM, and SBR significantly influences tracer uptake quantification in small lesions. Future studies should explore the clinical implications of these findings on diagnosis, staging, prognosis, and treatment follow-up.
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3 weeks ago
Ilaria Proietti,
Ilaria Proietti
Institution: Dermatology Unit “Daniele Innocenzi”, “A. Fiorini” Hospital, Via Firenze, 1, 04019 Terracina, Italy
Email:
Chiara Battilotti,
Chiara Battilotti
Institution: Dermatology Unit “Daniele Innocenzi”, “A. Fiorini” Hospital, Via Firenze, 1, 04019 Terracina, Italy
Email:
Francesca Svara,
Francesca Svara
Institution: Dermatology Unit “Daniele Innocenzi”, “A. Fiorini” Hospital, Via Firenze, 1, 04019 Terracina, Italy
Email:
Ersilia Tolino,
Ersilia Tolino
Institution: Dermatology Unit “Daniele Innocenzi”, “A. Fiorini” Hospital, Via Firenze, 1, 04019 Terracina, Italy
Email:
Nicoletta Bernardini,
Nicoletta Bernardini
Institution: Dermatology Unit “Daniele Innocenzi”, “A. Fiorini” Hospital, Via Firenze, 1, 04019 Terracina, Italy
Email:
Nevena Skroza,
Nevena Skroza
Institution: Dermatology Unit “Daniele Innocenzi”, “A. Fiorini” Hospital, Via Firenze, 1, 04019 Terracina, Italy
Email:
Luca Filippi,
Luca Filippi
Institution: Nuclear Medicine Unit, Department of Oncohaematology, Fondazione PTV Policlinico Tor Vergata University Hospital, Viale Oxford 81, 00133 Rome, Italy
Email:
Concetta Potenza
Concetta Potenza
Institution: Dermatology Unit “Daniele Innocenzi”, “A. Fiorini” Hospital, Via Firenze, 1, 04019 Terracina, Italy
Email:
The use of hyaluronic acid (HA) fillers in oncology patients undergoing PET-CT scans is a topic of debate due to potential interference with imaging accuracy. A 54-year-old female, postmelanoma metastasectomy in the parotid region with subsequent facial nerve palsy (FNP), received HA filler injectio...
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The use of hyaluronic acid (HA) fillers in oncology patients undergoing PET-CT scans is a topic of debate due to potential interference with imaging accuracy. A 54-year-old female, postmelanoma metastasectomy in the parotid region with subsequent facial nerve palsy (FNP), received HA filler injections for facial symmetry and functional restoration. Follow-up PET-CT scans showed no interference or artifacts attributable to HA injection, allowing for accurate imaging results. This case suggests that HA fillers administered in oncology patients may not universally pose challenges or disrupt PET-CT imaging interpretation. Due to the possible false positives induced by fillers, the inclusion of aesthetic treatments in patients’ anamnesis is a crucial step to accurately interpret PET-CT images. Although maintaining high level of caution in interpreting PET-CT results after filler injection is essential, our case emphasizes the safety of this procedure in oncology patients undergoing follow-up PET-CT scans.
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3 weeks ago
<jats:p>Effective management of the COVID-19 pandemic requires widespread and frequent testing of the population for SARS-CoV-2 infection. Saliva has emerged as an attractive alternative to nasopharyngeal samples for surveillance testing as it does not require specialized personnel or materials for ...
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<jats:p>Effective management of the COVID-19 pandemic requires widespread and frequent testing of the population for SARS-CoV-2 infection. Saliva has emerged as an attractive alternative to nasopharyngeal samples for surveillance testing as it does not require specialized personnel or materials for its collection and can be easily provided by the patient. We have developed a simple, fast, and sensitive saliva-based testing workflow that requires minimal sample treatment and equipment. After sample inactivation, RNA is quickly released and stabilized in an optimized buffer, followed by reverse transcription loop-mediated isothermal amplification (RT-LAMP) and detection of positive samples using a colorimetric and/or fluorescent readout. The workflow was optimized using 1,670 negative samples collected from 172 different individuals over the course of 6 months. Each sample was spiked with 50 copies/μL of inactivated SARS-CoV-2 virus to monitor the efficiency of viral detection. Using pre-defined clinical samples, the test was determined to be 100% specific and 97% sensitive, with a limit of detection of 39 copies/mL. The method was successfully implemented in a CLIA laboratory setting for workplace surveillance and reporting. From April 2021-February 2022, more than 30,000 self-collected samples from 755 individuals were tested and 85 employees tested positive mainly during December and January, consistent with high infection rates in Massachusetts and nationwide.</jats:p>
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2 months ago
