Serial Imaging Studies Research Articles

RARE TUMORS OF POSTERIOR CRANIAL FOSSA IN ADULTS

Objectives Tumors arising in the posterior cranial fossa pertain to a special category of neoplasm in the manner that they can cause cerebellar syndrome, obstructive hydrocephalus, brainstem compression – cranial nerve dysfunction – and herniation. In the cerebellopontine angle, the most common tumors are acoustic neuromas followed by meningiomas. Among the petroclival tumors, the most common benign tumors are meningiomas and the most common malign tumors are chordomas and metastases. Among jugular foramen tumors, the common tumors are schwannomas, paragangliomas and meningiomas. We report our unit’s experience with the neurosurgical management of rare posterior cranial fossa tumors as compared to the main literature results, taking into consideration the clinical, radiological aspects and the outcome. Materials and Methods Retrospective analysis of a single unit cohort of patients diagnosed with rare posterior cranial fossa tumors, who underwent surgical treatment in the Neurosurgery I Department of the University Emergency Hospital Bucharest between 2017 and 2024. Relevant literature review was analyzed, as well as serial clinical examinations, imaging studies, and operative records were taken into consideration. Conclusions Depending on the location, size, and pathology of the posterior cranial fossa tumors, there are different treatment options, which include microsurgical resection, observation, stereotactic radiotherapy. These type of lesions still represent a challenge and require electing the most suitable approach whilst preserving the neurologic function of the patient.

MIRD Pamphlet No. 30: MIRDfit-A Tool for Fitting of Biodistribution Time-Activity Data for Internal Dosimetry.

In nuclear medicine, estimating the number of radioactive decays that occur in a source organ per unit administered activity of a radiopharmaceutical (i.e., the time-integrated activity coefficient [TIAC]) is an essential task within the internal dosimetry workflow. TIAC estimation is commonly derived by least-squares fitting of various exponential models to organ time-activity data (radiopharmaceutical biodistribution). Rarely, however, are methods used to objectively determine the model that best characterizes the data. Additionally, the uncertainty associated with the resultant TIAC is generally not evaluated. As part of the MIRDsoft initiative, MIRDfit has been developed to offer a biodistribution fitting software solution that provides the following essential features and advantages for internal dose assessment: nuclear medicine-appropriate fit functions; objective metrics for guiding best-fit selection; TIAC uncertainty calculation; quality control and data archiving; integration with MIRDcalc software for dose calculation; and a user-friendly Excel-based interface. For demonstration and comparative validation of MIRDfit's performance, TIACs were derived from serial imaging studies involving 18F-FDG and 177Lu-DOTATATE using MIRDfit. These TIACs were then compared with TIAC estimates obtained using other software. In most cases, the TIACs agreed within approximately 10% between MIRDfit and the other software. MIRDfit has been endorsed by the MIRD Committee of the Society of Nuclear Medicine and Molecular Imaging and has been integrated into the MIRDsoft suite of free dosimetry software; it is available for download at no user cost (https://mirdsoft.org/).

Serial MRI to monitor the progression of a case of sphenoid bone osteomyelitis in a dog (Canis familiaris)

AbstractA 2‐year‐5‐month‐old, male, neutered, crossbreed dog presented with third eyelid protrusion, right eye exophthalmos and facial hyperaesthesia. Neurological examination was suggestive of a lesion affecting the right optic nerve. Magnetic resonance imaging allowed a presumptive diagnosis of sphenoid bone osteomyelitis, meningitis and right‐sided optic neuritis. The dog was discharged with clindamycin (13 mg/kg/8 h), amoxicillin–clavulanate (25 mg/kg/8 h), gabapentin (10 mg/kg/8 h), paracetamol (15 mg/kg/8 h) and prednisolone (0.5 mg/kg/24 h). Paracetamol, gabapentin and prednisolone were gradually stopped. A 3‐month follow‐up revealed right‐eye blindness. Magnetic resonance imaging showed improvement in changes compatible with osteomyelitis and meningitis resolution, prompting clindamycin cessation. At the 6‐month follow‐up, magnetic resonance imaging indicated only right optic nerve atrophy. Amoxicillin–clavulanate was stopped. There had been no relapses at 12‐month follow‐up. Serial magnetic resonance imaging studies were pivotal in adjusting antibiotic therapy, and instilled confidence for treatment cessation upon lesion resolution. This marked the first use of serial magnetic resonance imaging to modulate sphenoid bone osteomyelitis treatment in dogs.

Lack of mitochondrial complex I assembly factor NDUFAF2 results in a distinctive infantile-onset brainstem neurodegenerative disease with early lethality

BackgroundCongenital disorders of the mitochondrial respiratory chain are a heterogeneous group of inborn errors of metabolism. Among them, NADH:ubiquinone oxidoreductase (complex I, CI) deficiency is the most common. Biallelic pathogenic variants in NDUFAF2, encoding the nuclear assembly CI factor NDUFAF2, were initially reported to cause progressive encephalopathy beginning in infancy. Since the initial report in 2005, less than a dozen patients with NDUFAF2-related disease have been reported.MethodsClinical, biochemical, and neuroradiological features of four new patients residing in Northern Israel were collected during 2016–2022 at Emek Medical Center. Enzymatic activities of the five respiratory-chain complexes were determined in isolated fibroblast mitochondria by spectrophotometric methods. Western blot analyses were conducted with anti-human NDUFAF2 antibody; antibody against the mitochondrial marker VDAC1 was used as a loading control. Genetic studies were performed by chromosome microarray analysis using Affymetrix CytoScan 750 K arrays.ResultsAll four patients presented with infantile-onset growth retardation, ophthalmological impairments with nystagmus, strabismus (starting between 5 and 9 months), and further progressed to life-threatening episodes of apnea usually triggered by trivial febrile illnesses (between 10 and 18 months) with gradual loss of acquired developmental milestones (3 of 4 patients). Serial magnetic-resonance imaging studies in two of the four patients showed a progressive pattern of abnormal T2-weighted hyperintense signals involving primarily the brainstem, the upper cervical cord, and later, the basal ganglia and thalami. Magnetic-resonance spectroscopy in one patient showed an increased lactate peak. Disease progression was marked by ventilatory dependency and early lethality. 3 of the 4 patients tested, harbored a homozygous 142-kb partial interstitial deletion that omits exons 2–4 of NDUFAF2. Mitochondrial CI activity was significantly decreased in the only patient tested. Western blot analysis disclosed the absence of NDUFAF2 protein compared to normal controls. In addition, we reviewed all 10 previously reported NDUFAF2-deficient cases to better characterize the disease.ConclusionsBiallelic loss-of-function mutations in NDUFAF2 result in a distinctive phenotype in the spectrum of Leigh syndrome with clinical and neuroradiological features that are primarily attributed to progressive brainstem damage.

Prenatal diagnosis of Fetal Cardiac Rhabdomyoma associated with Familial Tuberous Sclerosis

Introduction: Of the fetal heart tumors, the most common are rhabdomyomas. Its prevalence is based on 11,000 autopsies performed on children and is 0.027%.1 Its diagnosis in the prenatal stage is a challenge, however, it has been reported in the second and third trimesters of gestation.Clinical case: 19-year-old female patient with a history of presenting with lipothymia at 2 years of age. Given these manifestations, she underwent different studies, including Cranial Magnetic Resonance (MRI), which concluded as a diagnosis of Tuberous Sclerosis. In its current state of gestation, at week 33, a finding is seen that corresponds to unilateral pulmonary agenesis; at 35 weeks, liver and kidney ultrasounds are performed on the mother and fetal ultrasound. Serial ultrasound findings revealed maternal hepatic and renal hemangiolipoma. Fetal biventicular rhabdomyoma with probable transposition of the great vessels and pulmonary artery stenosis.Discussion: Rhabdomyomas are the most common fetal cardiac tumors. In our clinical case, the pregnant woman had a history of Bourneville Tuberous Sclerosis. The definitive diagnosis of maternal pathologies was made in the 3rd trimester. It was complicated to manage due to suspicion of additional heart disease of the Classical Transposition of the Great Vessels type, evidenced by imaging studies. He was subsequently referred to a more complex center for better follow-up and definitive treatment.Conclusions: Fetal rhabdomyoma diagnosed prenatally is complex, requiring serial imaging studies and multidisciplinary follow-up. It is important to monitor the hemodynamic status and any cardiovascular repercussions of the pregnant woman. In addition, fetal structures including the central nervous system, heart and renal parenchyma must be carefully evaluated to avoid significant sequelae in those affected.

Large intradiploic arachnoid cyst of the skull in child—a case report and new terminology proposition

We present a rare finding of the arachnoid matter invaginating into the base of middle cranial fossa and creating an abnormal space. Presented entity was incidentally found in head CT scan of 12-year-old male. Based on the radiological characteristics in CT scans and MR images, the diagnosis of intradiploic arachnoid cyst (AC) was suggested. After surgical intervention and histopathological analysis of the specimen, the diagnosis was confirmed. We assume this is the first description of large intrasphenoid AC without any traumatic or iatrogenic cause. The literature provides many different terms for the phenomenon. We are proposing the term intradiploic arachnoid diverticulum as the more accurate for capturing the essence of the phenomenon. It provides clear differentiation of the entities from classical arachnoid cysts since they are of different anatomical localization (intradural vs. extradural) and etiopathogenesis. Management with arachnoid diverticulum is not yet established, but observation with serial imaging studies should be recommended as primary management in case of asymptomatic cyst. When cyst is symptomatic, surgical treatment may be required.

Diagnosis and management of mediastinal extragonadal germ cell tumors

SummaryExtragonadal germ cell tumors (EGCT) are rare and comprise only 2–3% of all testicular germ cell tumors. The majority of EGCT are located in the mediastinum, followed by the retroperitoneum. Although histologically similar to germ cell tumors (GCT), EGCT have distinct histological patterns which result in a biologically aggressive variant of GCT with the need for interdisciplinary care in highly specialized centers. The majority of mediastinal EGCT harbor teratoma or yolk sac tumor elements. Treatment usually consists of a combination of systemic cytotoxic therapy and aggressive postchemotherapeutic surgery. First-line treatment for extragonadal seminomas and nonseminomas consists of three and four cycles of PEB or PEI, respectively. In patients with significantly elevated markers, a personalized approach based on adequate marker decline can be used, and in poor-risk patients, first-line high-dose chemotherapy might be discussed. Postchemotherapeutic surgery remains an integral part of the multidisciplinary treatment for nonseminomatous EGCT and it is of utmost importance that all residual masses, independent of size and location, are resected completely. Residual masses in seminomatous EGCTs rarely harbor vital cancer and might be followed by serial imaging studies or FDG-PET/CT. The prognosis of nonseminomatous EGCT is poor, with 5‑year overall survival rates of 17%, 60–70%, and 90% for poor, intermediate, and excellent prognosis, respectively. Prognosis for seminomatous EGCT is excellent, with 5‑year overall survival rates of 95% and 88% for good and intermediate prognosis, respectively. Salvage chemotherapy consists of high-dose chemotherapy or targeted therapy in very selected patients.

Mediastinal perigraft seroma after thoracic aortic surgery.

We investigated pertinent factors associated with mediastinal perigraft seroma (PGS) after thoracic aortic surgery. In addition, we provided a clinical review of this entity, as reports reviewing abundant mediastinal PGS cases are rare. Eighty-two patients who underwent either ascending aortic replacement or aortic arch replacement between 2016 and 2022 in our institution were enrolled in the present study. Postoperative computed tomography scans were scanned to detect fluid capsules with a diameter ≥ 3.0 cm and radiodensity ≤ 25 Hounsfield units (HU). Patients who did and who did not develop PGS formation were compared. Variables with a statistically significant difference between these groups were included in a multiple logistic regression analysis along with other factors associated with PGS in the literature. The incidence rate of PGS was 14.6% (12/82). The average radiodensity of the mass was 16.6 ± 6.3 HU. The average onset of PGS was 8.5 months post-surgery. Multivariate logistic regression analysis revealed that ejection fraction (odds ratio [OR]: 1.25, 95% confidence interval [CI]: 1.03-1.50, P = 0.021), aortic dissection (versus degenerative aortic aneurysm) (OR: 6.61, 95% CI: 1.35-32.4, P = 0.02), and warfarin use (OR: 6.67, 95% CI: 1.19-37.1, P = 0.03) significantly contributed to mediastinal PGS after thoracic aortic surgery. High ejection fraction, warfarin use, and aortic dissection (versus degenerative aortic aneurysm) contributed significantly to mediastinal PGS formation after thoracic aortic surgery. Careful serial postoperative imaging studies and fluid analysis can be used to guide treatment plans.

Locoregional Recurrence of Esophageal Cancer Treated with Curative Intent Local Salvage Therapy: A Single Center Experience.

Locoregional recurrence of esophageal carcinoma after neoadjuvant therapy and en bloc esophagectomy, although uncommon, is challenging to manage. Currently, there are no standard treatment approaches prompting many health care providers to adopt a palliative approach. We describe our experience and outcomes of treating this specific group of patients with a focus on salvage curative intent local therapy. All patients undergoing en bloc esophagectomy following neoadjuvant therapy between 2007 and 2017 at the McGill University Health Centre, a tertiary referral center for esophageal cancer, were identified. Patient follow-up included a structured surveillance protocol with serial endoscopic and cross-sectional imaging studies. Local recurrence was defined as histologically confirmed recurrences at the anastomosis. Regional recurrence was defined as radiological evidence of celiac, mediastinal, or para-esophageal/conduit lymphadenopathy. Demographic, pathologic, therapeutic variables were extracted as well as disease free and overall survival. Of 755 patients identified, locoregional recurrences occurred in 27 patients (3.6%) of whom 18 were included in the analysis. The median disease-free survival post index operation was 15months (IQR 10-23). The sites of recurrence were local (6/18, 33.3%); regional (8/18, 44.4%); and locoregional (4, 22.2%). Chemoradiation was the most common modality used to treat recurrence (10/18, 55.6%) whilst 4 (22.2%) underwent surgery. Following treatment for locoregional recurrence, 1-year overall survival was 61.1% and at 5years was 22.2%. Consolidative salvage local therapy for locoregional recurrence after en bloc esophagectomy is feasible and can entail prolonged survival in a subset of patients.

Isolated pulmonary langerhans cell histiocytosis: A diagnostic challenge in oncologic patients.

Isolated pulmonary langerhans cell histiocytosis: A diagnostic challenge in oncologic patients.

Abstract OT3-11-01: TK IMPACT: Treatment Monitoring of Hormone Receptor Positive (HR+), HER2 Negative (HER2-) Metastatic Breast Cancer (MBC) Patients Receiving CDK 4/6 Inhibitors (CDK4/6i) with DiviTum® Thymidine Kinase 1 Activity

Abstract Background: CDK 4/6i have altered the therapeutic landscape of HR+, HER2- MBC, improving progression free and overall survival (PFS and OS) compared to endocrine therapy (ET) alone. Despite durable responses to CDK 4/6i in a large majority of patients, treatment response monitoring in this population has historically included numerous serial blood-based and imaging studies at frequent time points. There is a growing global interest in utilizing novel non-invasive biomarker-driven disease monitoring assessments to improve patient outcomes and reduce health care costs. Thymidine kinase 1 (TK1), a key cell-cycle regulated enzyme important for nucleotide metabolism during DNA synthesis, is regulated by the E2F pathway, downstream of CDK 4/6. Studies have shown that DiviTum® TK1 activity (TKa) may serve as both a prognostic and predictive biomarker of CDK 4/6i treatment response (McCartney et al, Clin Canc Res, 2020; Malorni et al, Eur J Cancer, 2022; Bagegni et al, Breast Cancer Res, 2017). Early TKa suppression within 2 weeks (wk) post CDK 4/6i therapy initiation is associated with improved PFS, suggesting a subgroup of patients who may be able to de-escalate imaging frequency. Elevated TKa at baseline and post CDK 4/6i may identify patients with CDK 4/6i-resistant disease and disease progression (PD) requiring early therapy modification. TK IMPACT is a prospective, single-arm trial designed to assess the impact of incorporation of DiviTum® TKa on a physician’s decision regarding subsequent timing of routine disease monitoring modalities in patients with advanced HR+, HER2- MBC receiving ET plus CDK 4/6i (NCT04968964). Methods: Blood sample collections will be analyzed using DiviTum® TKa at baseline (bl), wk 2, 4, 6, 8, and Q 4 wks thereafter beginning at wk 8 during the first 24-wk time period of study enrollment (+/- 3 days); followed by Q 12 wks thereafter, until PD or 36 months, whichever occurs first. Optional repeat TKa within 2-4 wks (+/-3 days) is permitted in case of rising TKa. Research blood (bl, wk 2, 12, 24, 48, and PD) and optional archival tumor tissue collection at diagnosis and PD will be obtained for correlatives. The investigator will record intended imaging modalities and timing prior to receipt of TKa, followed by documentation of any changes in imaging testing interval after receipt of TKa. Key eligibility criteria include postmenopausal women age ≥18 years with HR+, HER2- MBC, to initiate (Cohort 1) or are currently receiving (≤24 months, Cohort 2) any FDA approved first line ET plus CDK 4/6i with a life expectancy > 6 months. The primary endpoint is any physician-reported intended change in imaging testing interval post TKa by study cohort, within the first 48-wk period of study participation. Key secondary endpoints are concordance rate between TKa values and progression status at first on-study imaging and longitudinal TKa dynamics. Key exploratory endpoints include plasma and tumor tissue-based biomarkers of CDK 4/6i response and resistance. A total of 40 patients will be enrolled (n=20/Cohort). The expected change rate is 20% with a 95% Wilson confidence interval of 0.105~0.248 across all patients and if within each cohort, with a 95% Wilson confidence interval of 0.081~0.416 for N=20. N=40 allows the lower limit of the 95% CI > 10% and that of the N=20 in Cohort 1 to be ~10%, indicating some clinically meaningful influence of TKa progression on patient management. The study is open to accrual and has presently enrolled 5 patients. Citation Format: Nusayba A. Bagegni, Isabella Grigsby, Leslie Nehring, Jingqin Luo, Jennifer Powers Carson, David W. Gibson, Meghan Horvath, Katherine K. Clifton, Foluso O. Ademuyiwa, Rama Suresh, Ashley Frith, Andrew A. Davis, Lindsay L. Peterson, Ron Bose, Amy Williams, Mattias Bergqvist, Cynthia Ma. TK IMPACT: Treatment Monitoring of Hormone Receptor Positive (HR+), HER2 Negative (HER2-) Metastatic Breast Cancer (MBC) Patients Receiving CDK 4/6 Inhibitors (CDK4/6i) with DiviTum® Thymidine Kinase 1 Activity [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT3-11-01.

Modifiable vascular risk factors in patients with cerebral and spinal cavernous malformations: a complete 10-year follow-up study.

The aim was to investigate the effect of modifiable vascular risk factors on the risk of first and recurrent bleeding for patients with a cavernous malformation (CM) of the central nervous system (CNS) over a 10-year period. A retrospective review of our CM institutional database was performed spanning from 2003 to 2021. The inclusion criteria were non-missing serial magnetic resonance imaging studies and clinical baseline metrics such as vascular risk factors. The exclusion criteria were patients who underwent surgical CM removal and patients with less than a decade of follow-up. Kaplan-Meier and Cox regression analyses were performed to determine the cumulative risk (10 years) of hemorrhage. Eighty-nine patients with a CM of the CNS were included. Our results showed a non-significant increased risk of hemorrhage during 10 years of follow-up in patients using nicotine (hazard ratio 2.11, 95% confidence interval 0.86-5.21) and in patients with diabetes (hazard ratio 3.25, 95% confidence interval 0.71-14.81). For the presence of modifiable vascular risk factors at study baseline different cumulative 10-year risks of bleeding were observed: arterial hypertension 42.9% (18.8%-70.4%); diabetes 66.7% (12.5%-98.2%); hyperlipidemia 30% (8.1%-64.6%); active nicotine abuse 50% (24.1%-76%); and obesity 22.2% (4%-59.8%). Overall cumulative (10-year) hemorrhage risk was 30.3% (21.3%-41.1%). The probability of hemorrhage in untreated CNS CM patients increases progressively within a decade of follow-up. None of the modifiable vascular risk factors showed strong indication for an influence on hemorrhage risk, but our findings may suggest a more aggressive course in patients with active nicotine abuse or suffering from diabetes.

Is the Lifetime Malignancy Risk in United States Military Personnel Sustaining Combat-related Trauma Increased Because of Radiation Exposure From Diagnostic Imaging?

Patients with complex polytrauma in the military and civilian settings are often exposed to substantial diagnostic medical radiation because of serial imaging studies for injury diagnosis and subsequent management. This cumulative radiation exposure may increase the risk of subsequent malignancy. This is particularly true for combat-injured servicemembers who receive care at a variety of facilities worldwide. Currently, there is no coordinated effort to track the amount of radiation exposure each servicemember receives, nor a surveillance program to follow such patients in the long term. It is important to assess whether military servicemembers are exposed to excessive diagnostic radiation to mitigate or prevent such occurrences and monitor for carcinogenesis, when necessary. The cumulative amount of radiation exposure for combat-wounded and noncombat-wounded servicemembers has not been described, and it remains unknown whether diagnostic radiation exposure meets thresholds for an increased risk of carcinogenesis. We performed this study to (1) quantify the amount of exposure for combat-wounded servicemembers based on medical imaging in the first year after injury and compare those exposures with noncombat-related trauma, and (2) determine whether the cumulative dose of radiation correlates to the Injury Severity Score (ISS) across the combat-wounded and noncombat-wounded population combined. We performed a retrospective study of servicemembers who sustained combat or noncombat trauma and were treated at Walter Reed National Military Medical Center from 2005 to 2018. We evaluated patients using the Department of Defense Trauma Registry. After consolidating redundant records, the dataset included 3812 unique servicemember encounters. Three percent (104 of 3812) were excluded because of missing radiation exposure data in the electronic medical record. The final cohort included 3708 servicemembers who had combat or noncombat injury trauma, with a mean age at the time of injury of 26 ± 6 years and a mean ISS of 18 ± 12. The most common combat trauma mechanisms of injury were blast (in 65% [2415 of 3708 patients]), followed by high-velocity gunshot wounds (in 22% [815 of 3708 patients]). We calculated the cumulative diagnostic radiation dose exposure at 1 year post-traumatic injury in patients with combat-related trauma and those with noncombat trauma. We did this by multiplying the number of imaging studies by the standardized effective radiation dose for each imaging study type. We then performed analysis of variance for four data subsets (battle combat trauma, nonbattle civilian trauma, high ISS, and high radiation exposure [> 50 mSv]) independently. To evaluate whether the total number of imaging studies, radiation exposure, and ISS values differed between battle-wounded and nonbattle-wounded patients, we performed a pairwise t-test. The mean radiation exposure for combat-related injuries was 35 ± 26 mSv while the mean radiation exposure for noncombat-related injuries was 22 ± 33 mSv in the first year after injury. In the first year after trauma, 44% of patients (1626 of 3708) were exposed to high levels of radiation that were greater than 20 mSv, and 23% (840 of 3708) were exposed to very high levels of radiation that were greater than 50 mSv. Servicemembers with combat trauma-related injuries had eight more imaging studies than those who sustained noncombat injuries. Servicemembers with combat trauma injuries (35 ± 26 mSv) were exposed to more radiation (approximately 4 mSv) than patients treated for noncombat injuries (22 ± 33 mSv) (p = 0.01). We found that servicemembers with combat injuries had a higher ISS than servicemembers with noncombat trauma (p < 0.001). We found a positive correlation between radiation exposure and ISS for servicemembers. The positive relationship between radiation exposure and ISS held for combat trauma (r 2 = 0.24; p < 0.001), noncombat trauma (r 2 = 0.20; p < 0.001), servicemembers with a high ISS (r 2 = 0.10; p < 0.001), and servicemembers exposed to high doses of radiation (r 2 = 0.09; p < 0.001). These data should be used during clinical decision-making and patient counseling at military treatment facilities and might provide guidance to the Defense Health Agency. These recommendations will help determine whether the benefits of further imaging outweigh the risk of carcinogenesis. If not, we need to develop interdisciplinary clinical practice guidelines to reduce or minimize radiation exposure. It is important for treating physicians to seriously weigh the risk and benefits of every imaging study ordered because each test does not come without a cumulative risk. Level III, therapeutic study.

13-year Old Male Child Patient with a known Case of Necrotizing Encephalopathy

ANCE (Acute necrotizing encephalopathy of childhood) is a disease that affects children with a high fever, a respiratory or gastrointestinal infection, rapid changes in awareness, and seizures. Almost all Asian newborns and children who were previously in good health are affected by this illness. According to serial magnetic resonance imaging studies, the thalami, cerebellum, brainstem, and white matter all showed symmetric lesions in this disease. The condition has a poor prognosis with high morbidity and mortality rates. Amir Kola Children's Hospital is evaluating an A.N.E.C. in a 22-month-old kid Missense mutations were also detected in the gene that codes for the nuclear pore protein- Ran Binding Protein 2 (RANBP2). Though the clinical course and prognosis of ANE differ, the characteristic of neuro radiology manifestation of ANE is multifocal symmetric brain lesions visible on computed tomography (C.T.) or magnetic resonance imaging (M.R.I.).The treatment of ANCE is still under particular observation. We provide the most up-to-date information on ANCE, emphasizing early detection and successful consultation and treatment of this rare but deadly disease.

ODP024 Adrenocortical Carcinoma Identified in a Patient With Familial Adenomatous Polyposis Syndrome

Abstract Background Numerous extracolonic manifestations are associated with familial adenomatous polyposis (FAP), including benign thyroid and adrenal nodules, less commonly thyroid and adrenal cancers. We describe a case of a patient with history of FAP who was found to have malignant lesions both in the thyroid and adrenal glands. Clinical Case A 54 year-old female with familial adenomatous polyposis (FAP) underwent partial colectomy at age 16. Known extracolonic manifestation at initial presentation was limited to a dermoid tumor of the right breast. Upon evaluation by endocrinology, she was found to have a dominant thyroid nodule in the right lobe that eventually doubled in size and was positive for papillary thyroid cancer with a BRAF V600E mutation. Successful total thyroidectomy with central neck lymph node dissection was completed, and she is now undergoing routine surveillance for ATA low risk PTC. She maintained annual endoscopic surveillance with gastroenterology and underwent serial abdominal imaging studies for complaints of abdominal discomfort. Right adrenal adenoma was first identified in August 2017 and screening for functionality, to include pheochromocytoma, was negative. Repeat abdominal imaging in 2020 showed the lesion increased in size by 30%. CT imaging identified the nodule as indeterminate based on the washout characteristics (HU 27 pre-contrast, absolute washout = 13% and relative washout = 8%). A 2cm left adrenal mass was also noted with radiographic features consistent with a lipid poor, benign, adenoma (HU 33 pre-contrast, absolute washout = 58%, relative washout = 39%). PET-CT was performed to further characterize the right sided lesion, which was vividly FDG avid at 8.7 SUV (high probability of malignancy). The left adrenal nodule was mildly FDG avid with an SUV of 2.4. CT-guided biopsy of the right adrenal gland was performed and immunohistochemistry did not stain for chromogranin, inhibin, pankeratin or calretinin. Positive staining for MART-1 was seen, which is a typically associated with adrenal cortical cells. There was a high index of suspicion for malignancy given her hereditary cancer syndrome, and the decision was made to proceed with right adrenalectomy. Final surgical pathology confirmed a low grade adrenocortical carcinoma with two nodular lesions, both staining CD10 positive with the mitotic marker (Ki-67) 2-3% positive. The patient's left adrenal gland remains functionally intact, and there were no indications to pursue postoperative treatment or adjuvant therapy. Conclusion The patient presented here is representative of incidentally discovered nonfunctional adrenocortical carcinoma in the setting of a hereditary cancer syndrome. The available literature suggests that adrenocortical tumors should be considered FAP tumors, and sporadic mutations leading to adrenocortical carcinoma are less likely related to germline APC gene mutations Presentation: No date and time listed

PNEUMORACHIS FROM ASTHMA EXACERBATION: A RARE COMPLICATION

PNEUMORACHIS FROM ASTHMA EXACERBATION: A RARE COMPLICATION

S1767 Metastatic Solid Pseudopapillary Neoplasm of the Pancreas, Rare Presentation of an Uncommon Tumor

Introduction: Solid pseudopapillary neoplasms (SPN) make up less than 3% of all diagnosed pancreatic neoplasms. Abdominal CT or MRI are the imaging modalities most utilized, and biopsy is necessary to confirm the diagnosis. Resection of the mass is standard of care and the prognosis is quite good, with 5-year survival rates of over 95%. Both recurrence and metastasis of the tumor are exceedingly rare, occurring in only 1-4% of patients. Case Description/Methods: A 26-year-old female presented with several years of abdominal pain. CT scan revealed a 10cm mass in the neck and body of the pancreas and patient underwent a hybrid resection including subtotal pancreatectomy, splenectomy, and cholecystectomy. Pathology showed a neoplasm extending to the inked margins with positive beta-catenin and CD10 nuclear staining with no evidence of metastasis. At the age of 32, the patient presented again with abdominal pain. A CT and PET scan showed numerous LUQ, perirenal, pancreatic, and periadrenal soft tissue densities. Laparoscopic resection of a 3.5x3 cm soft tissue mass near the remnant pancreas was performed, showing fibrous stroma with angulated islands of epithelioid cells with cystic degeneration and positive staining for vimentin, CD56, and beta-catenin. Resection of multiple abdominal soft tissue tumors, in bulk measuring more than 10 cm, as well as complete omentectomy, left adrenalectomy, bilateral salpingo-oophorectomy, appendectomy, and hyperthermic intraperitoneal chemotherapy with cisplatin was performed. Pathology showed multiple metastatic tumors all consistent with SPN. The appendix, left adrenal gland, bilateral ovaries, and all lymph nodes were negative for any tumor. Two years later, MRI revealed 3.0 x 2.1 cm hyperintense lesion in the caudate lobe of the liver. EUS with biopsy was performed, revealing clusters of uniform, bland cells with ovoid nuclei and associated fibrillary stroma circumscribing vessels with a background of hemorrhagic debris (Figure). Immunohistochemistry showed cells positive for vimentin, LEF1, and beta-catenin, again consistent with SPN. Discussion: This is one of the few cases of multiple instances of both recurrence and metastasis of SPN documented in the literature. This case report shows that serial imaging studies and close follow-up are needed even years after resection and that, although rare, recurrence and metastasis can occur more than one time after the initial diagnosis.Figure 1.: Biopsy of the caudate liver lesion showing clusters of uniform, bland cells with ovoid nuclei and associated fibrillary stroma and hemorrhagic debris, consistent with SPN.

S3056 Immune-Mediated Hepatitis: A Single Drug or a Class Effect?

Introduction: While the rates of diagnosis and death due to non small cell lung cancer are decreasing, the five year relative survival rate remains 20%. Treatment of lung cancer is rapidly evolving, particularly in the metastatic setting. Immunotherapies, most notably PD-1 inhibitors, have drastically changed the landscape of treatment. Immune Hepatitis can, unfortunately, be a reason for discontinuation of the drugs. Immune Hepatitis has been generally thought to be associated with all drugs of a particular class, not specific drug agents. Case Description/Methods: We present a case of an 84 year old female with metastatic non small cell lung cancer with a PD-1 expression of 100%. She was started on single agent Pembrolizumab due to inability to tolerate chemotherapy limiting therapeutic options. Shortly after starting therapy she developed immune hepatitis requiring steroid therapy and withdrawal of the drug with multiple drug interruptions. Ultimately, the drug was discontinued due to worsening elevation in her liver enzymes with resumption of the drug. Standard of practice in such cases is to avoid all drugs in the PD-1 inhibitor family due to similar toxicity profiles and mechanism of action observed. Given the fact that she did not have any other treatment options, she was started on Nivolumab, a different PD-1 inhibitor. Patient was able to tolerate Nivolumab without elevation of her liver enzymes or development of immune hepatitis. She has been on the drug for approximately 10 months with serial monitoring and no evidence of liver injury has been observed. Discussion: While PD-1 inhibitors have revolutionized the treatment of metastatic NSCLC and the drugs are overall well tolerated, a small percentage of patients develop immune mediated liver injury due to reactive cytotoxic T lymphocytes as the reactivated T cells attack other tissues, including the liver. Generally, this has been seen consistently across the entire drug class, not specific to single agents. We present a rare case of immune mediated liver toxicity specific to Pembrolizumab that was subsequently not observed with Nivolumab, despite both drugs having identical mechanisms of actions. Patient has had multiple serial labs and imaging studies showing no progression of her disease, stable on Nivolumab. This case highlights the need for further investigation regarding the mechanism of Immune mediated liver toxicity/injury that may be specific to single agents and not necessarily a drug class.

Bone Densities Assessed by Hounsfield Units at L5 in Computed Tomography Image Independently Predict Hepatocellular Carcinoma Development in Cirrhotic Patients.

A previous study identified that bone density (BD) assessed by Hounsfield unit (HU) at T12 in computed tomography (CT) image was a predictor for hepatocellular carcinoma (HCC) development in cirrhotic patients. Here, we conducted a verification study, where clinical variables together with BDs (assessed from three different bone areas: T12, L5, and femur trochanter) were assessed for their predictive values for time-to-HCC development in cirrhotic patients. Univariate Cox proportional hazard analysis showed that age (p = 0.017), T12 BD (p = 0.013) and L5 BD (p = 0.005), but not femur BD, were significant predictors. Multivariate analysis revealed that L5 BD was the only independent factor associated with time-to-HCC development (adjusted p = 0.007). Kaplan-Meier analysis confirmed that BD which was lower than median HU was associated with a shorter time-to-HCC development for both T12 BD and L5 BD (p = 0.001 each). Longitudinal follow-ups for BDs in HCC patients having received serial CT imaging studies unveiled a significantly rapid reduction in BD, right before HCC was diagnosed (p = 0.025 when compared with the average BD reduction rate). In conclusion, BD assessed by HU at L5 was an independent predictor for HCC development in cirrhotic patients. Rapid BD reduction during CT scan follow-ups could serve as a warning sign for HCC development.

P1051: A PHASE 2 STUDY OF IMG-7289 (BOMEDEMSTAT) IN PATIENTS WITH ADVANCED MYELOFIBROSIS

Background: Lysine-specific demethylase-1 (LSD1) is an activity critical for the self-renewal of malignant myeloid cells and maturation of megakaryocytes, cells central to the pathogenesis of MF. Bomedemstat is an orally active LSD1 inhibitor that in mouse models ameliorated the hallmarks of MPNs and improved survival (Kleppe et al. 2015; Jutzi et al. 2018). Aims: IMG-7289-CTP-102 is an ongoing, global, open-label Phase 2 study evaluating bomedemstat dosed QD in MF patients (NCT03136185). Key eligibility criteria include patients intolerant, refractory, resistant, or inadequately controlled by approved therapy, and platelet count ≥100 x 109/L. Key objectives are safety and reduction of spleen volume (SVR) by MRI/CT and total symptoms scores (TSS) using the MPN-SAF instrument. Methods: Serial bone marrow (BM) biopsies and imaging studies are read centrally. 261 genes are serially sequenced to quantify changes in the allelic frequencies of mutations (MAF) and identify new mutations. The starting dose is 0.6 mg/kg/d titrating, as needed, to a platelet count of 50-75x109/L. Results: At 89 patients, the study is now fully enrolled: 46% primary MF, 33% post-essential thrombocythaemia-MF, 21% post-polycythaemia vera-MF. Median age is 68 (35-88) with 52% males. Prior treatment with ruxolitinib was reported in 83% (74/89); 46% had also received at least 1 additional treatment. 30% of patients (27/89) had received ≥1 RBC transfusion prior to dosing. By IPSS, 53% were high-risk, 40% int.-2, and 7% int.-1. At screening (N=103), sequencing to a mean depth of >1000 bp, JAK2 was mutated in 69%, CALR in 21%, MPL in 6%; 59% had ≥2 mutations of which 71% were high-molecular risk mutations in ASXL1, IDH1/2, EZH2, U2AF1, TP53 and/or SRSF2. At data cutoff (3 Feb 2022), the median duration of treatment is 28 weeks (2-131). Of patients for whom TSS data is available at 24 weeks in those with baseline values ≥20, 72% (18/25) had a reduction in TSS; 24% (6/25) reported a ≥50% reduction. Of patients evaluable for SVR (N=50), 64% had a reduction in spleen volume from baseline; in 28%, SVR was ≥20%. Of evaluable patients (N=41), 90% had stable (∆ <±1.0 g/dL) or improved (≥1.0 g/dL) hemoglobin. Of patients with BM fibrosis scoring post-baseline (N=52), 31% improved by 1 grade and 50% were stable. CCL5 and S100A8/A9 cytokines were elevated at baseline in 50% (16/32) and 78%, respectively; at Day 84, 81% and 68%, respectively, showed reductions of at least 10% and of those, 100% (CCL5) and 47% (S100A8/A9) normalized. In follow-up sequencing at around Week 24, of 60 mutant alleles in 32 patients, the mean MAF fell by 39% in 48%. JAK2 MAFs fell by 31% [SD 5%] in 46% (N=24); ASXL1 MAFs fell 40% in 71%. Clones with JAK2 and/or ASXL1 mutations were most affected. No new mutations have been identified and no patient has transformed to AML. The most common non-hematologic AEs reported by patients was dysgeusia in 36% (32/90) and diarrhoea in 34% (31/90). All dysgeusia events were grade 1/2 and 1 led to treatment discontinuation. Of 14 related SAEs, 4 were Grade 2, 9 Grade 3 and 1 Grade 4 (thrombocytopenia). Twenty-nine patients remain on bomedemstat. Early terminations due to AEs occurred in 18 (20%) patients (9 related to bomedemstat), and 13 discontinued for other reasons. There have been no safety signals, DLTs, or deaths related to drug. Summary/Conclusion: In patients with advanced MF, bomedemstat alone had an acceptable tolerability profile, relieved symptoms, reduced spleen volume and mutation burden while improving fibrosis and anemia without safety signals.