Glioblastoma, IDH-Wildtype With Epithelioid Morphology and a BCR::NTRK2 Fusion.

Glioblastoma, IDH-wildtype (GBM) is a high-grade astrocytic glioma that accounts for the majority of malignant brain tumors in adults. Within this entity, epithelioid GBM represents a histological subtype characterized by a loosely cohesive aggregate of large cells with abundant cytoplasm, and vesicular nuclei that usually harbors the BRAF V600E mutation. Molecular alterations in GBMs are frequent and play an important role in the diagnosis of this entity. Among the many genetic alterations reported, NTRK fusions are rare and account for <2% of gliomas. Furthermore, NTRK2 fusions are most seen in pediatric populations. Recent approval of the TRK inhibitor larotrectinib by the Food and Drug Administration (FDA) has brought interest in the study and recognition of NTRK fusions in multiple types of tumors. Trials that assess the response to this drug in cancers carrying NTRK fusions have yielded favorable results. We discuss a rare presentation of an adult-type GBM with epithelioid morphology and a BCR::NTRK2 gene fusion.

Endoscopic Evaluation of PET/CT Abnormalities in the Gastrointestinal Tract: Yield and Approach.

BACKGROUND: Unexpected hypermetabolic activity is often encountered in the gastrointestinal tract when PET/CT is performed for various indications, prompting endoscopic evaluation. Our aim was to characterize the types of lesions seen in segments of the gastrointestinal tract with unexpected PET/CT abnormalities as well as clinically significant lesions seen on endoscopy which did not produce a PET/CT abnormality to guide the endoscopist tasked with evaluating these imaging findings. METHODS: We retrospectively reviewed a database of endoscopies performed at City of Hope Comprehensive Cancer Center between January 1, 2016 and September 30, 2021 for an indication of "abnormal PET." We divided the gastrointestinal tract into segments and defined categories of endoscopic/histologic findings for each segment. We counted the number of segments with an abnormal PET/CT finding and corresponding endoscopic/histologic abnormality as well as the number of segments with an endoscopic/histologic abnormality but normal PET/CT. RESULTS: PET/CT identified 209 segments with hypermetabolic activity, 109 of which had corresponding endoscopic/histologic abnormalities. In the jejunum and ileum, all corresponding lesions were malignant. Seventy-three percent of corresponding lesions in the stomach were H. pylori positive. PET/CT failed to detect 34.7% of clinically significant lesions diagnosed endoscopically, including 1 malignancy in the transverse colon and many inflammatory or low-risk premalignant lesions. CONCLUSION: PET/CT abnormalities seen in the small bowel should be evaluated urgently as nearly all correlates were malignant, while abnormalities in the stomach should prompt workup for H. pylori. Most lesions missed by PET/CT were inflammatory or low-risk premalignant yet clinically significant, confirming the need to inspect the entirety of the upper or lower gastrointestinal tract during endoscopy.

Defining MRI Superiority over CT for Colorectal and Neuroendocrine Liver Metastases.

BACKGROUND: We compared CT and MRI for staging metastatic colorectal or neuroendocrine liver metastases (CRLMs and NELMs, respectively) to assess their impact on tumor burden. METHODS: A prospectively maintained database was queried for patients who underwent both imaging modalities within 3 months, with two blinded radiologists (R1 and R2) independently assessing the images for liver lesions. To minimize recall bias, studies were grouped by modality, and were randomized and evaluated separately. RESULTS: Our query yielded 76 patients (42 CRLMs; 34 NELMs) with low interrater variability (intraclass correlation coefficients: CT = 0.941, MRI = 0.975). For CRLMs, there were no significant differences in lesion number or size between CT and MRI. However, in NELMs, Eovist®-enhanced MRI detected more lesions (R1: 14.3 vs. 12.1, p = 0.02; R2: 14.4 vs. 12.4, p = 0.01) and smaller lesions (R1: 5.7 vs. 4.4, p = 0.03; R2: 4.8 vs. 2.9, p = 0.02) than CT. CONCLUSIONS: CT and MRI are equivalent for CRLMs, but for NELMs, MRI outperforms CT in detecting more and smaller lesions, potentially influencing treatment planning and surgery.

Metastatic Testicular Sex Cord Tumor Harboring a EWSR1::ATF1 Gene Fusion-A Case Report of a Novel Neoplasm: "Inflammatory and Nested Testicular Sex Cord Tumor".

We present a case report of a 54-year-old male with a metastatic testicular sex cord tumor harboring a EWSR1::ATF1 gene fusion. The tumor displayed a solid and nested architecture with sclerotic stroma and variable inflammatory infiltrate, and was positive for SF-1, inhibin, EMA, CD30, and WT1 expression. Further genetic analysis identified a EWSR1::ATF1 gene fusion. Overall findings were consistent with an "inflammatory and nested testicular sex cord tumor," a recently described testicular neoplasm characterized by EWSR1::ATF1 gene fusion and aggressive clinical behavior. Due to the aggressive nature of this entity and the limited response to current treatment options available, identification of potential biomarkers for early diagnosis and targeted therapies are critical. This case report provides important insights into the genomic landscape of testicular sex cord-stromal tumors, especially within the CTNNB1-negative subset of patients with an aggressive clinical course, and further supports the distinction of "inflammatory and nested testicular sex cord tumor" as a separate entity from Sertoli cell tumors due to its characteristic morphological, immunohistochemical and molecular, features and clinical behavior.

Long-Term Outcomes of Patients on a Phase II Prospective Trial of Oligometastatic Hormone-Sensitive Prostate Cancer Treated With Androgen Deprivation and External Beam Radiation.

PURPOSE: External beam radiation therapy (EBRT) to oligometastases may improve outcomes in patients with oligometastatic hormone-sensitive prostate cancer (oHSPC). Follow-up on this cohort has been limited to <5 years and prospective data on de novo patients with oHSPC are lacking. We reviewed the long-term outcomes of patients with oHSPC treated with EBRT and androgen deprivation therapy on a prospective trial. METHODS AND MATERIALS: From 2006 to 2011, patients with oHSPC with 1 to 5 metastases received 36 weeks of androgen deprivation therapy (luteinizing hormone-releasing hormone agonist + bicalutamide) and up to 53 Gy to all visible metastases. When indicated, the primary tumor or prostate bed was treated with EBRT up to 78 or 66 Gy, respectively. RESULTS: Twenty-nine patients were treated: 15 de novo, 14 oligorecurrent, and 21 patients (72.4%) had bone metastases. Median number of metastases per patient was 1 (range, 1-5). EBRT was administered to 52 lesions (38 bone, 12 pelvic lymph nodes [LNs], 2 nonpelvic LNs) up to 53 Gy (range, 47-66). Median follow-up was 9.9 years (years; range, 0.2-14.4). Median overall survival was 9.7 years (95% confidence interval [CI], 5.8-not reached). Median progression-free survival was 1.9 years (95% CI, 1.6-2.2). Patients who presented with prostate cancer-defined de novo metastases had significantly improved (P = .04) median progression-free survival (2.0 years; 95% CI, 1.3-6.0) compared with oligorecurrent patients (1.8 years; 95% CI, 1.0-2.0). Patients who presented with LN-only metastases had numerically improved (P = .13) median PFS (5.8 years; 95% CI, 1.2-not reached) compared with patients with bony metastases (1.8 years; 95% CI, 1.3-2.0). At last follow-up, 17 patients (58.6%) had local control of all EBRT-treated metastases. The metastases that locally progressed had previously been controlled for median 3.5 years (range, 1.7-10.5). CONCLUSIONS: Our results compare favorably with other reported studies of patients with oHSPC and provide new insights into their long-term outcomes.

Exercise training and NR supplementation to improve muscle mass and fitness in adolescent and young adult hematopoietic cell transplant survivors: a randomized controlled trial {1}.

BACKGROUND: Advances in hematopoietic cell transplantation (HCT) have led to marked improvements in survival. However, adolescents and young adults (AYAs) who undergo HCT are at high risk of developing sarcopenia (loss of skeletal muscle mass) due to the impact of HCT-related exposures on the developing musculoskeletal system. HCT survivors who have sarcopenia also have excess lifetime risk of non-relapse mortality. Therefore, interventions that increase skeletal muscle mass, metabolism, strength, and function are needed to improve health in AYA HCT survivors. Skeletal muscle is highly reliant on mitochondrial energy production, as reflected by oxidative phosphorylation (OXPHOS) capacity. Exercise is one approach to target skeletal muscle mitochondrial OXPHOS, and in turn improve muscle function and strength. Another approach is to use "exercise enhancers", such as nicotinamide riboside (NR), a safe and well-tolerated precursor of nicotinamide adenine dinucleotide (NAD+), a cofactor that in turn impacts muscle energy production. Interventions combining exercise with exercise enhancers like NR hold promise, but have not yet been rigorously tested in AYA HCT survivors. METHODS/DESIGN: We will perform a randomized controlled trial testing 16 weeks of in-home aerobic and resistance exercise and NR in AYA HCT survivors, with a primary outcome of muscle strength via dynamometry and a key secondary outcome of cardiovascular fitness via cardiopulmonary exercise testing. We will also test the effects of these interventions on i) muscle mass via dual energy x-ray absorptiometry; ii) muscle mitochondrial OXPHOS via an innovative non-invasive MRI-based technique, and iii) circulating correlates of NAD+ metabolism via metabolomics. Eighty AYAs (ages 15-30y) will be recruited 6-24 months post-HCT and randomized to 1 of 4 arms: exercise + NR, exercise alone, NR alone, or control. Outcomes will be collected at baseline and after the 16-week intervention. DISCUSSION: We expect that exercise with NR will produce larger changes than exercise alone in key outcomes, and that changes will be mediated by increases in muscle OXPHOS. We will apply the insights gained from this trial to develop individualized, evidence-supported precision initiatives that will reduce chronic disease burden in high-risk cancer survivors. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05194397. Registered January 18, 2022, https://clinicaltrials.gov/ct2/show/NCT05194397 {2a}.

Episodic, severe abdominal pain due to isolated jejunal Crohn's disease.

Small bowel Crohn's disease can present with episodic, relapsing, and remitting symptoms and delays in the diagnosis are common. We present a case of a young woman with three years of intermittent abdominal pain and nausea with negative previous evaluations. On presentation, inflammatory markers were elevated, and repeat imaging showed jejunal inflammation, with histopathological examination showing non-caseating granulomas of the small bowel consistent with Crohn's disease. This case highlights the importance of gastroenterologist recognizing the alarm signs in a patient with unexplained symptoms and adds to the literature on the clinical presentation of a rare diagnosis of isolated jejunal Crohn's disease.

Comprehensive imaging manifestations of tuberous sclerosis.

OBJECTIVE: The purposes of this article are to describe the abdominal manifestations of tuberous sclerosis, including renal and hepatic angiomyolipomas, splenic hamartomas, and renal cysts; the differentiation of renal angiomyolipomas from renal cell carcinoma by use of various imaging modalities; and the key imaging findings of intracranial subependymal nodules, giant cell astrocytomas, cortical tubers, lymphangioleiomyomatosis, cardiac rhabdomyomas, and osseous lesions. CONCLUSION: Tuberous sclerosis is an autosomal dominant neurocutaneous syndrome characterized by various abnormalities, including multisystemic hamartomas. Correct diagnosis of this syndrome is imperative, not only by detecting cutaneous manifestations at physical examination but also by recognizing the characteristic multimodality imaging findings. Patients can present with a variety of symptoms, ranging from seizures to acute abdomen with life-threatening hemorrhage. The mortality rate is as high as 40% by the age of 35 years.