Evidence Of Metastatic Disease Research Articles

Severe atypical iliac wing fracture associated with long-term bisphosphonate use.

Bisphosphonate use is associated with atypical non-traumatic fractures, which are most commonly seen in the femur. We report a 63-year-old postmenopausal woman who presented acutely with progressively worsening lumbar pain radiating to her left hip for 10days. There was no antecedent trauma. On examination, the patient could not bear weight on her left leg due to the severity of the pain. Radiography and computed tomography of the pelvis demonstrated an iliac wing fracture which was treated conservatively. The patient had a significant past medical history of breast cancer and intense bisphosphonate use for several years which was discontinued 3years previously. No discrete bone lesion was seen at the fracture site on computed tomography, and there was no evidence of metastatic disease elsewhere. A dual-energy X-ray absorptiometry scan showed the lowest bone mineral density T-score of - 1.2. A diagnosis of an atypical fracture related to long-term bisphosphonate therapy was made. To the best of our knowledge, this is the first reported case of an isolated iliac wing fracture associated with long-term bisphosphonate therapy in the literature. Whilst the incidence of such fractures is exceedingly rare, it is an important differential in patients with atypical fractures on long-term bisphosphonates.

Performance of O-RADS MRI Score in Differentiating Benign From Malignant Ovarian Teratomas: MR Feature Analysis for Differentiating O-RADS 4 From O-RADS 2.

The aim of the study is to evaluate the performance of the ovarian-adnexal reporting and data system magnetic resonance imaging (O-RADS MRI) score and perform individual MRI feature analysis for differentiating between benign and malignant ovarian teratomas. In this institutional review board-approved retrospective study, consecutive patients with a pathology-proven fat-containing ovarian mass imaged with contrast-enhanced MRI (1.5T or 3T) from 2013 to 2022 were included. Two blinded radiologists independently evaluated masses per the O-RADS MRI lexicon, including having a "characteristic" or "large" Rokitansky nodule (RN). Additional features analyzed included the following: nodule size/percentage volume relative to total teratoma volume, presence of bulk/intravoxel fat in the nodule, diffusion restriction in the nodule, angular interface, nodule extension through the teratoma border, presence/type of nodule enhancement pattern (solid versus peripheral), and evidence for metastatic disease. An overall O-RADS MRI score was assigned. Patient and lesion features associated with malignancy were evaluated and used to create a malignant teratoma score. χ2, Fisher's exact tests, receiver operating characteristic curve, and κ analysis was performed. One hundred thirty-seven women (median age 34, range 9-84 years) with 123 benign and 14 malignant lesions were included. Mean teratoma size was 7.3 cm (malignant: 14.4 cm, benign: 6.5 cm). 18/123 (14.6%) of benign teratomas were assigned an O-RADS 4 based on the presence of a "large" (11/18) or "noncharacteristic" (12/18) RN. 12/14 malignant nodules occupied >25% of the total teratoma volume (P = 0.09). Features associated with malignancy included the following: age <18 years, an enhancing noncharacteristic RN, teratoma size >12 cm, irregular cystic border, and extralesional extension; these were incorporated into a malignant teratoma score, with a score of 2 or more associated with area under the curve of 0.991 for reviewer 1 and 0.993 for reviewer 2. Peripheral enhancement in a RN was never seen with malignancy (64/123 benign, 0/14 malignant) and would have appropriated downgraded 9/18 overcalled O-RADS 4 benign teratomas. O-RADS MRI overcalled 15% (18/123) benign teratomas as O-RADS 4 but correctly captured all malignant teratomas. We propose defining a "characteristic" RN as an intravoxel or bulk fat-containing nodule. Observation of a peripheral rim of enhancement in a noncharacteristic RN allowed more accurate prediction of benignity and should be added to the MRI lexicon for improved O-RADS performance.

GCT-26. INTRACRANIAL NON-GERMINOMATOUS GERM CELL TUMOR WITH MALIGNANT TRANSFORMATION TO EMBRYONAL RHABDOMYSARCOMA

Abstract BACKGROUND Non-germinomatous germ cell tumors (NGGCT) constitute 35%- 45% of intracranial germ cell tumors. Growing teratoma syndrome has been observed in patients with NGGCTs after starting chemotherapy. While growing teratomas are typically benign, this process can rarely involve malignant transformation and result in poor prognosis. We present the case of a patient with pineal NGGCT and growing teratoma syndrome with malignant transformation to embryonal rhabdomyosarcoma. CASE REPORT A 13-year-old male presented with headaches and vision changes. An MRI brain demonstrated a 26 x 25 x 19 mm (AP X TR X CC) mixed solid and cystic pineal mass with no evidence of metastatic disease. Due to elevated alpha fetoprotein levels in the serum and cerebrospinal fluid, he was diagnosed with intracranial NGGCT. Treatment was initiated with alternating cycles of Carboplatin/Etoposide and Ifosfamide/Etoposide. After 2 cycles of chemotherapy, a complete biochemical response was noted but MRI showed increased tumor size (presumed growing teratoma syndrome). The patient underwent complete tumor resection. Histology showed embryonal rhabdomyosarcoma as a somatic malignancy arising in a mature teratoma. Further molecular characterization revealed somatic NF1 and KRAS pathogenic mutations that are consistent with the primary diagnosis. Methylation profiling, however, did not exhibit a match with any known malignancies. Continued complete response was noted following two additional chemotherapy cycles. The patient is planned for six total chemotherapy cycles followed by high-dose craniospinal radiation with boost to the primary tumor. CONCLUSIONS Malignant transformation is a rare phenomenon in NGGCT. There is no standard of care for these patients. Further studies are needed to define ideal therapy for this patient population.

MDB-24. SHH MEDULLOBLASTOMA WITH SMO MUTATION BEFORE THE AGE OF 5YEARS OLD

Abstract BACKGROUND SHH medulloblastomas represent around 30% of MB’s and occur mostly in infants and adults with an intermediate prognosis. The driving mutations concern mostly PTCH1(43%), SUFU(10%) or SMO(9%). SMO activating mutations have been described almost exclusively in adults, and is extremely rare in infants. The features and outcome of SMO mutated infant MB are not known so far. PATIENTS AND METHODS We did a national retrospective analysis of children under 5 years with a SHH medulloblastoma and a somatic SMO mutation. We collected clinical, radiological and biological data (centralised reviews) with addition of methyloma, aiming to depict the clinico-molecular features and the outcome of these rare MB. RESULTS We identified 6 patients from 2014 to 2020. The median age at diagnosis was 3.2years. No evidence of metastatic disease was found for 5/6 patients and one had a positive CSF cytology. All patients underwent a complete removal. All had an extensive nodularity histologic subtype, no specific alterations in CGH apart from gains of all chromosomes 2,7 and,15. Methyloma classified 4/6 in subgroup SHH-1 and 2 in subgroup SHH-2. One patient had a second cerebellar lesion with a different radiological aspect; histological analysis and methylation profiling revealed a subependymoma, sharing the same SMO mutation than the MB ((c.1604G&amp;gt;T/p.(Trp535Leu)), suggesting a mosaicism. Another patient presented a polymalformative disorder diagnosed as a Curry-Jones syndrome, in agreement with the finding of mosaic SMO variant (c.1234C&amp;gt;T(p.Leu412Phe)). All patients received several cycles of chemotherapy, and no radiotherapy. With a median follow-up of 3.9 years, all patients were alive in complete remission with no relapse. CONCLUSION This data suggests that an underlying mosaicism must be sought in these very rare patients, and that the outcome seems overall similar to other infants with SHH medulloblastoma and more classical SUFU or PTCH1 mutations.

Focal leptomeningeal vascular anomalies on brain MRI: A mimic of leptomeningeal metastatic disease

Abstract Background The diagnosis of leptomeningeal metastatic disease has major prognostic and therapeutic implications. We report 13 patients with a radiologically distinct kind of focal, enhancing leptomeningeal lesion on brain MRI that mimics leptomeningeal metastatic disease. Methods These patients were assessed at University Health Network (Toronto, Canada) between January 2001 and December 2023. Results Median age was 68 years (range, 55–78 years) and 10 patients were women. All patients had brain magnetic resonance imaging (MRI) including contrast-enhanced T2-weighted fluid attenuation inversion recovery (FLAIR) and T1-weighted spin echo sequences. MRI in all 13 patients showed a focal enhancing lesion located along the leptomeningeal surface of the brain. The MRI exams were reported as possible or likely leptomeningeal metastatic disease for the majority (9/13) of patients. Each lesion was curvilinear rather than sheet-like, and some lesions consisted of multiple connected/branching curvilinear structures with the appearance of abnormal vessels. The lesions were distinct from normal blood vessels. Some lesions had a visible connection with a nearby cortical vein. Follow-up contrast-enhanced brain MRI for 8/13 (62%) patients at a median of 3.9 years (IQR 2.4–6.6 years) showed all lesions were unchanged over time. Another 2/13 (15%) patients had clinical and CT brain follow-up after one year with no evidence of metastatic disease. Conclusions We describe a distinct kind of focal, enhancing leptomeningeal lesion on brain MRI that mimics metastatic disease. These lesions are likely a type of low-flow vascular anomaly. Their curvilinear/branching shape and intense enhancement particularly on T2-weighted FLAIR images distinguish these lesions from tumors.

EVOLVE-HNSCC: A global phase 3 study of volrustomig as sequential therapy for unresected locally advanced head and neck squamous cell carcinoma (LA-HNSCC) following definitive concurrent chemoradiotherapy (cCRT).

TPS6120 Background: Currently there are no approved maintenance therapies for patients (pts) with unresected LA-HNSCC following definitive cCRT. The PD-1 inhibitors pembrolizumab and nivolumab are licensed for treatment of pts with recurrent or metastatic HNSCC who have progressed on or after a platinum-based therapy. Dual inhibition of CTLA-4 and PD-L1 is approved in solid tumors including renal cell carcinoma (RCC), NSCLC, and melanoma, and has shown a numerical trend towards improved survival in first-line pts with recurrent/metastatic HNSCC whose tumors express PD-L1. Volrustomig (MEDI5752) is a monovalent, PD-1/CTLA-4 bispecific, humanized IgG1 monoclonal antibody engineered to specifically inhibit PD-1, with increased CTLA-4 blockade on PD-1+ activated T cells compared to PD-1– resting peripheral T cells. In a first-in-human phase 1/2 study (NCT03530397), volrustomig monotherapy showed promising efficacy with acceptable tolerability in advanced clear cell RCC and in combination with chemotherapy in advanced NSCLC. The phase 3, randomized, open-label, multicenter, eVOLVE-HNSCC study will evaluate the efficacy and safety of sequential therapy with volrustomig compared with observation in pts with unresected LA-HNSCC who have not progressed after receiving definitive cCRT (NCT06129864). Methods: Key eligibility criteria include histologically or cytologically confirmed, unresected LA-HNSCC with no evidence of metastatic disease, i.e. AJCC 8th edition (TNM staging system) stage IVA/B cancers of the hypopharynx, oral cavity, larynx or HPV-negative oropharynx, or stage III HPV-positive oropharynx cancer; age ≥18 years; WHO/ECOG performance score of 0 or 1; and adequate organ and bone marrow function. Key exclusion criteria include requiring further treatment with curative intent after definitive cCRT, resected LA-HNSCC, recurrent/metastatic disease, and &gt;1 primary tumor. Following initial screening and definitive cCRT (cisplatin or carboplatin + paclitaxel or carboplatin + 5-FU, plus concomitant radiotherapy), approximately 1145 pts whose disease has not progressed within 12 weeks of the last dose of cCRT will be randomized 1:1 to Arm A or B. Arm A will receive volrustomig intravenously every 3 weeks for a maximum of 12 months or 18 cycles, or until RECIST v1.1-defined radiological progressive disease (PD) or unacceptable toxicity. Arm B will undergo observation for a maximum of 12 months or until PD. The primary endpoint is PFS in pts with PD-L1-expressing tumors. Secondary endpoints include PFS in all randomized pts, OS in pts with PD-L1-expressing tumors and in all randomized pts, PFS2, safety, patient-reported outcomes, pharmacokinetics, and immunogenicity. Exploratory biomarker analyses will also be conducted. Enrollment began in December 2023. Clinical trial information: NCT06129864 .

Exploring the Diagnostic Dilemma of Indeterminate Pulmonary Nodules in Patients with Primary Sarcoma of Bone.

Bone sarcomas are known to have a predilection for pulmonary metastasis. Surveillance protocols are thus focused on periodic chest imaging, typically with CT scan. Pulmonary nodules can be easily identified with this modality, but smaller nodules are not readily biopsied and may not represent metastatic disease. These are called indeterminate. The natural history of indeterminate nodules in a bone sarcoma population and factors associated with progression to true metastatic disease are not clearly defined. All bone sarcoma patients treated at a single institution from 2010 to 2020 were eligible for inclusion. We treated 327 patients over this period; 119 were excluded for age less than 16 years, 31 were excluded for evident metastatic disease at presentation, and 60 were excluded for incomplete clinical follow-up or CT chest imaging either at staging or in surveillance. We assessed chest CT images for presence of pulmonary nodules and selected variables both at the staging and on surveillance images. Nodules were considered metastatic if proven histologically with a biopsy or by clinical interpretation by the multidisciplinary sarcoma team. Clinical and imaging factors were assessed for the association of indeterminate nodule progression to true metastatic disease. Seventy three of the 117 patients had indeterminate nodules on their staging CT scan; 41.1% of those patients progressed to metastatic disease compared to 43.2% of the patients that did not have indeterminate nodules on staging CT. Fifty eight of the 117 patients developed indeterminate nodules on surveillance chest CT, and 55.2% of those patients progressed to metastatic disease. There were no clinical or imaging factors that predicted the development of metastatic disease in the group that had indeterminate nodules at presentation; however, the number and size of nodules did correlate with progression to metastasis in those that developed indeterminate nodules on surveillance. Indeterminate pulmonary nodules are common on staging CT scans in patients with a bone sarcoma. The presence or absence of these indeterminate nodules was not predictive of progression to true metastatic disease in this cohort. However, the development of indeterminate nodules on surveillance imaging was associated with progression to metastatic disease with the size and number of nodules being important factors.

Endoscopic Resection for Duodenal Neuroendocrine Neoplasms between 10 and 20 mm-A Systematic Review and Meta-Analysis.

Background. The optimal management of duodenal neuroendocrine neoplasms (dNENs) sized 10-20 mm remains controversial and although endoscopic resection is increasingly performed instead of surgery, the therapeutic approach in this setting is not fully standardized. We performed a systematic review of the literature and a meta-analysis to clarify the outcomes of endoscopic resection for 10-20 mm dNENs in terms of efficacy (i.e., recurrence rate) and safety. Methods. A computerized literature search was performed using relevant keywords to identify pertinent articles published until January 2023. Results. Seven retrospective studies were included in this systematic review. The overall recurrence rate was 14.6% (95%CI 5.4-27.4) in 65 patients analyzed, without significant heterogeneity. When considering studies specifically focused on endoscopic mucosal resection, the recurrence rate was 20.5% (95%CI 10.7-32.4), without significant heterogeneity. The ability to obtain the free margin after endoscopic resection ranged between 36% and 100%. No complications were observed in the four studies reporting this information. Conclusions. Endoscopic resection could be the first treatment option in patients with dNENs sized 10-20 mm and without evidence of metastatic disease. Further studies are needed to draw more solid conclusions, particularly in terms of superiority among the available endoscopic techniques.

Vascular, adipose tissue, and/or calyceal invasion in clear cell tubulopapillary renal cell tumour: potentially problematic diagnostic scenarios.

The 2022 WHO classification for kidney tumours recently downgraded clear cell tubulopapillary (also known as clear cell papillary) renal cell carcinoma (RCC) to a benign neoplasm (i.e. clear cell tubulopapillary renal cell tumour) based on the overwhelmingly banal nature of this neoplasm. However, it has been recognized that some clear cell tubulopapillary renal cell tumours demonstrate vascular, adipose or pelvicalyceal invasion, raising the possibility of more aggressive behaviour. The goal of this study was to determine if these 'high stage' features have an effect on tumour prognosis, warranting a carcinoma designation. After excluding cases with tissue artefact (i.e. prior core biopsy track changes) and other RCC subtypes with next-generation sequencing, nine clear cell tubulopapillary renal cell tumours with these so-called 'high stage' features, and otherwise classic morphologic and immunophenotypic findings, including low-grade cytology and 'cup-like' CA9 expression, were evaluated. Median tumour size was 2.2 cm with a range of 0.8 to 6.7 cm. Eight cases (89%) demonstrated perinephric or hilar adipose tissue invasion, although most of these cases showed a bulging (in contrast to an infiltrative) growth pattern. One case demonstrated renal vascular invasion in addition to hilar adipose tissue invasion, and one case demonstrated extension into the pelvicalyceal system. There were no recurrences or evidence of metastatic disease. These overall findings continue to support the benign designation for clear cell tubulopapillary renal cell tumours, despite morphologic features that might raise the possibility of a 'higher stage' neoplasm.

Abstract B002: Phase I study of endoscopic ultrasound (EUS)-guided NBTXR3 delivery activated by radiotherapy (RT) for locally advanced or borderline resectable pancreatic cancer (LAPC or BRPC)

Abstract Patients with LAPC or BRPC often receive radiation therapy (RT) after chemotherapy (chemo) if no metastatic progression has occurred. Historically, CA19-9 normalizes in ~20 to 30% of patients after all therapy. While escalated dose radiotherapy (EDR) has shown promising survival in selected patients, extending use of EDR to all patients is challenging due to RT dose limitations of the bowel. To overcome this limitation, we are investigating NBTXR3, composed of functionalized hafnium oxide nanoparticles administered by a single intratumoral injection, locally amplifying the RT dose. In this phase 1 trial, the primary objective is to determine the NBTXR3 recommended phase 2 dose (RP2D). Secondary objectives are to measure anti-tumor effects. The study uses a Bayesian optimal interval design (BOIN) and has two parts: dose-finding (NBTXR3 at [level 1] 33% of gross tumor volume [GTV] or [level 2] at 42% of GTV) and cohort expansion at RP2D. In part 1, eligibility criteria included only LAPC patients with no evidence of metastatic disease after 2-6 months of chemo, part 2 allows BRPC. NBTXR3 was administered once prior to RT via an EUS-guided intratumoral injection. All patients received 45 Gy in 15 fractions with intensity modulated radiation therapy (IMRT). Patients were followed up to 1 year. Dose-limiting toxicities (DLTs) were defined as any grade ≥ 3 adverse events definitely or possibly related to NBTXR3 and/or RT. Target tumor response was per RECIST v1.1 criteria. CA19-9 was measured serially. We defined CA19-9 normalization as a value of 37 U/ml after finishing NBTXR3/RT. We compared rates of CA19-9 normalization in this phase 1 trial to a historical cohort of patients who received modern chemo/RT without NBTXR3. As of July 12, 2023, 15 LAPC patients have been treated with NBTXR3/RT. The median age was 63 years [range 43-81], 8 males, 7 females. The first patient (level 1) and subsequent 14 patients (level 2) had no injection complications. Level 2 had 1 non-serious DLT related to RT. At 4 weeks post RT, 13 had stable disease (SD) locally (2 had progressive disease [PD] overall), 1 had PD locally, and 1 had radiographic complete response (CR). At 3 months post RT, 11 had SD locally (1 PD overall), 1 PD locally, and 1 had surgery with negative margins and no residual viable tumor. 9 patients had elevated CA19-9 before NBTXR3/RT, 7 of these 9 (78%) had a decrease in CA19-9 subsequently, and 2 of these 9 (22%) had CA19-9 normalization eventually. 12 patients had elevated CA19-9 at diagnosis, and 5 out of 12 patients (42%) had normalization of CA19-9 after all therapy. We reviewed 455 patients with LAPC/BRPC between 2015-2019 who were treated at our institution as a comparison cohort for CA19-9 normalization rates. Out of 307 patients with elevated CA19-9 at diagnosis and normal bilirubin, 95 normalized (31%) and 212 did not normalize (69%) within 6 months of receiving cytotoxic therapy. The RP2D of NBTXR3 is 42% of GTV. The responses and CA19-9 results in comparison to historical data suggest promising anti-tumor efficacy of NBTXR3/RT. Citation Format: Gabriela Fuentes, Maria J. Rodriguez, Matthew H.G. Katz, Naruhiko Ikoma, Ching-Wei D. Tzeng, Michael Overman, Shubham Pant, Michael S. Lee, Robert A. Wolff, Milind Javle, Cullen M. Taniguchi, Emma B. Holliday, Ethan B. Ludmir, Prajnan Das, Albert C. Koong, Omar I. Vivar, Suyu Liu, Eric P. Tamm, Leonard A. Farber, Manoop S. Bhutani, Eugene J. Koay. Phase I study of endoscopic ultrasound (EUS)-guided NBTXR3 delivery activated by radiotherapy (RT) for locally advanced or borderline resectable pancreatic cancer (LAPC or BRPC) [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr B002.

Concurrent Isolated Hypoglossal Nerve Palsy Induced by Jugular Vein Thrombosis, Cervical Plexus Masses, and Vestibular Schwannoma: A Complex Case Report Highlighting Anatomical Pathways and Clinical Challenges

Background: Hypoglossal nerve palsy is typically observed alongside other cranial nerve impairments, with isolated cases being infrequent and posing diagnostic complexities. Originating intracranially, the nerve traverses the skull and neck, governing tongue motility. Lesions are classified as supranuclear, nuclear, or infranuclear, engendering tongue deviation towards the affected side. Due to its proximity to crucial structures, hypoglossal nerve palsy often coincides with supplementary symptoms. Etiologies encompass skull base metastases, carotid artery pathologies, and trauma. This study explores less conventional triggers such as hypoglossal nerve palsy following thyroidectomy, jugular vein thrombosis, cervical plexus masses, and Vestibular Schwannoma. Case Description: A 38-year-old female presented to the Neurology outpatient clinic with leftward tongue deviation and left-sided neck and shoulder pain accompanied by stiffness that had begun several months prior. In addition to the tongue deviation, she reported minor dysphagia, blurry vision, and intermittent numbness on the left side of her scalp. MRI and duplex ultrasound verified the presence of left internal jugular vein (IJV) thrombosis. The patient was initially prescribed Eliquis and acetazolamide, with slight improvements in symptoms, though medication use ceased due to side effects. During a subsequent follow-up visit, persistent tongue deviation and worsening left shoulder pain prompted additional cervical imaging. A new cervical spine MRI revealed a 15x14 mm nodular dural enhancement with a paraspinal soft tissue mass at the C2 level. Concurrently, multiple cranial nerve palsies were detected during the physical examination. Unfortunately, the patient was subsequently diagnosed with breast cancer. To rule out brain metastases related to her breast cancer, an additional brain MRI was performed, revealing a newly formed 2.3x1.6x1.2 cm left cerebellopontine angle mass adjacent to the internal auditory canal (IAC), suggestive of a vestibular schwannoma but without evidence of metastatic disease. The patient's care involved a multidisciplinary team, including hematologist-oncologists, neurosurgeons, and neurologists. Conclusion: This case report highlights the less common causes of hypoglossal nerve palsy, such as jugular vein thrombosis, cervical plexus masses, and Vestibular Schwannoma. The persistence of the patient's palsy is attributed to the cumulative impact of these anatomical factors on the hypoglossal nerve. This underscores the diagnostic challenges posed by isolated hypoglossal nerve palsy and emphasizes the importance of comprehensive clinical evaluation and imaging for accurate diagnosis.

A Rare Case of Incidental Primary Follicular Lymphoma Co-Existing With Grade Group 5 Prostatic Adenocarcinoma

Abstract Introduction/Objective Primary lymphoma of the prostate is an exceedingly rare entity comprising less than 0.1% of all prostatic cancers with follicular lymphoma making up only 12% of primary prostatic lymphomas. There is very limited literature owing to their rarity and underdiagnosis. To the best of our knowledge, prostatic adenocarcinoma with an incidental follicular lymphoma presenting as a prostate imaging reporting and data system 4 (PI-RADS 4) lesion on multiparametric magnetic resonance imaging (mpMRI) with mildly elevated serum prostate specific antigen (PSA) has not been previously described. Methods/Case Report A 73 year old male presented to Danbury Hospital for follow up on benign prostatic hyperplasia (BPH) diagnosed in 2020. The patient was experiencing nocturia and had a serum PSA of 4.8. Multiparametric MRI revealed an enlarged, 5.5 x 4.1 x 3.3 cm, prostate gland (estimate weight of 45.5 grams) with a 1.2 cm PI-RADS 4 lesion in the right anterior mid gland. There was no evidence of metastatic disease on his most recent body imaging. He was subsequently scheduled for prostate needle biopsy. Histopathology showed a high grade prostatic adenocarcinoma, with a Gleason score 4 + 5=9, along with a focally prominent dense lymphoid infiltrate in four of four cores from the same area of abnormality that was detected on mpMRI. The latter comprised of ill defined follicles and sheets of small cleaved atypical lymphoid cells consistent with centrocytes and very few centroblasts. By immunohistochemical staining, the atypical cells in lymphoid follicles and interfollicular areas were positive for CD20, CD10 and BCL2 and negative for cyclin D1. CD21 stain highlighted the follicular dendritic cell meshwork in the germinal centers with a low Ki67 proliferation index. A final diagnosis of low grade follicular lymphoma (grade1-2) coexisting with the prostatic adenocarcinoma was rendered. The patient is currently undergoing lymphoma staging as the treatment for adenocarcinoma is planned. Results (if a Case Study enter NA) NA Conclusion Primary lymphoma of the prostate usually presents with non specific obstructive voiding symptoms and normal or near normal PSA levels which makes it challenging for physicians to suspect lymphomas. The lymphocytic infiltrate, originally thought to be prostatitis, underwent further evaluation with immunohistochemistry due to its monotonous appearance, which clinched the final diagnosis. Careful evaluation of prostate core needle biopsies is necessary even after spotting carcinoma in order to rule out low grade lymphomas.

Magnetic Resonance Imaging Features and Prognostic Indicators of Local Recurrence after Curettage and Cementation of Atypical Cartilaginous Tumour in the Appendicular Skeleton.

Objective: The aim of this study is to determine MRI features that may be prognostic indicators of local recurrence (LR) in patients treated with curettage and cementation of atypical cartilaginous tumours (ACTs) in the appendicular skeleton. Materials and Methods: This study is a retrospective review of adult patients with histologically confirmed appendicular ACT. The data collected included age, sex, skeletal location and histology from curettage, the presence of LR and oncological outcomes. The pre-operative MRI characteristics of the ACT reviewed by a specialist MSK radiologist included lesion location, lesion length, degree of medullary filling, bone expansion, cortical status and the presence of soft tissue extension. Results: A total of 43 patients were included, including 9 males and 34 females with a mean age of 42.8 years (range: 25-76 years). Tumours were located in the femur (n = 19), humerus (n = 15), tibia (n = 5), fibula (n = 2) and radius and ulna (n = 1 each). A total of 19 lesions were located in the diaphysis, 12 in the metadiaphysis, 6 in the metaphysis and 6 in the epiphysis. The mean tumour length was 61.0 mm (range: 12-134 mm). The mean follow up was 97.7 months (range: 20-157 months), during which 10 (23.3%) patients developed LR, 7 (70%) of which were asymptomatic and 3 (30%) of which presented with pain. Four patients required repeat surgery with no associated death or evidence of metastatic disease. LR was significantly commoner with tumours arising in the epiphysis or metadiaphysis, but no MRI features were predictive of LR. Conclusions: No relationship was found between the apparent 'aggressiveness' of an ACT of the appendicular skeleton on MRI and the development of LR following treatment with curettage and cementation.

Survival Outcomes by Race and Ethnicity in Veterans With Nonmetastatic Castration-Resistant Prostate Cancer

Racial and ethnic disparities in prostate cancer are poorly understood. A given disparity-related factor may affect outcomes differently at each point along the highly variable trajectory of the disease. To examine clinical outcomes by race and ethnicity in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) within the US Veterans Health Administration. A retrospective, observational cohort study using electronic health care records (January 1, 2006, to December 31, 2021) in a nationwide equal-access health care system was conducted. Mean (SD) follow-up time was 4.3 (3.3) years. Patients included in the analysis were diagnosed with prostate cancer from January 1, 2006, to December 30, 2020, that progressed to nmCRPC defined by (1) increasing prostate-specific antigen levels, (2) ongoing androgen deprivation, and (3) no evidence of metastatic disease. Patients with metastatic disease or death within the landmark period (3 months after the first nmCRPC evidence) were excluded. The primary outcome was time from the landmark period to death or metastasis; the secondary outcome was overall survival. A multivariate Cox proportional hazards model, Kaplan-Meier estimates, and adjusted survival curves were used to evaluate outcome differences by race and ethnicity. Of 12 992 patients in the cohort, 826 patients identified as Hispanic (6%), 3671 as non-Hispanic Black (28%; henceforth Black), 7323 as non-Hispanic White (56%; henceforth White), and 1172 of other race and ethnicity (9%; henceforth other, including American Indian or Alaska Native, Asian, Native Hawaiian or Other Pacific Islander, unknown by patient, and patient declined to answer). Median time elapsed from nmCRPC to metastasis or death was 5.96 (95% CI, 5.58-6.34) years for Black patients, 5.62 (95% CI, 5.11-6.67) years for Hispanic patients, 4.11 (95% CI, 3.96-4.25) years for White patients, and 3.59 (95% CI, 3.23-3.97) years for other patients. Median unadjusted overall survival was 6.26 (95% CI, 6.03-6.46) years among all patients, 8.36 (95% CI, 8.0-8.8) years for Black patients, 8.56 (95% CI, 7.3-9.7) years for Hispanic patients, 5.48 (95% CI, 5.2-5.7) years for White patients, and 4.48 (95% CI, 4.1-5.0) years for other patients. The findings of this cohort study of patients with nmCRPC suggest that differences in outcomes by race and ethnicity exist; in addition, Black and Hispanic men may have considerably improved outcomes when treated in an equal-access setting.

OR08-06 Adjuvant Radiation Therapy Is Not Associated With A Survival Benefit After R0 Resection In Non-Metastatic Adrenocortical Carcinoma

Abstract Disclosure: Y.J. Lee-Saxton: None. C.E. Egan: None. T.E. Marshall: None. A. Tumati: None. T. Beninato: None. R. Zarnegar: None. T.J. Fahey: None. B.M. Finnerty: None. Introduction: The benefit of adjuvant radiation therapy (RT) in adrenocortical carcinoma (ACC) is not well characterized, particularly for those who undergo initial R0 surgical resection without evidence of metastatic disease. We aimed to identify factors associated with administration of adjuvant RT in these patients, and to determine the association between adjuvant RT and overall survival in patients with non-metastatic ACC who underwent R0 surgical resection. Methods: The National Cancer Database was queried for histologic codes denoting ACC from 2004-2018. Patients who underwent R0 resection without evidence of metastatic disease were included and placed into two cohorts - those who underwent adjuvant RT and those who did not. Patients with incomplete or unknown data regarding clinically relevant variables were excluded from analysis. A multivariable logistic regression was performed to identify predictors of adjuvant RT administration. A multivariable Cox regression was performed to identify factors associated with overall survival (OS). Kaplan-Meier survival estimates and log-rank test were also performed to assess the impact of adjuvant RT on OS. Results: 388 patients were identified: 51 (13.1%) patients received adjuvant RT, while 337 (86.9%) did not. Adjuvant chemotherapy administration was the only factor associated with administration of adjuvant RT (OR 6.45, 95% CI 3.02 - 13.8, p&amp;lt;0.001). No significant difference was observed between the Kaplan-Meier survival estimates of the two cohorts (p=0.54). After adjusting for patient characteristics including age, sex, co-morbidity index, race, receipt of chemotherapy, and tumor characteristics including tumor size, tumor grade, pathologic tumor stage, and pathologic nodal stage, adjuvant RT was not associated with improved OS in patients who underwent R0 resection (HR 1.01, 95% CI 0.63 - 1.60, p=0.98). However, tumor size &amp;gt;6cm (HR 1.54, 95% CI 1.03 - 2.32, p=0.04), high tumor grade (HR 3.46, 95% CI 1.83 - 6.55, p&amp;lt;0.001), and pathologic N1 stage (HR 2.30, 95% CI 1.06 - 4.94, p=0.03) were associated with worse OS in patients who underwent R0 resection. Conclusions: Treatment with adjuvant RT in patients with ACC who underwent R0 resection was not associated with an OS benefit. Further studies assessing optimal treatment for large and high-grade tumors with lymph node metastases are warranted. Presentation: Friday, June 16, 2023

FRI211 Recurrent Hypertensive Crises In A Patient With A Large Pheochromocytoma; A Complicated Intensive Care Unit Course

Abstract Disclosure: S. Sokoloff: None. A. Iwamaye: None. Introduction: Hypertensive crisis is a well-known complication of surgery in patients with pheochromocytomas. However, as demonstrated in this case, these crises can be triggered by even routine intensive care unit procedures if sufficient alpha blockade has not been achieved. Thus, prevention of these episodes in the critical care setting presents a therapeutic challenge. Case: A 47-year-old female with a medical history of hypertension and intraductal papilloma presented for right lumpectomy for recent increase in papilloma size. General anesthesia and a laryngeal mask airway (LMA) were used. Intraoperatively, hypertensive crisis developed with systolic blood pressure of three hundred and oxygen saturation of forty percent. Hypoxia persisted after LMA was exchanged for endotracheal intubation and ECMO initiation was necessary to restore oxygenation. The patient was admitted to the Intensive Care Unit and blood pressure normalized postoperatively. Echo showed normal ejection fraction with an incidental finding of a peri-hepatic mass. This prompted evaluation for pheochromocytoma, which was biochemically confirmed with plasma free metanephrine and normetanephrine of 13,900 (&amp;lt;= 57 pg/mL) and 2,560 (&amp;lt;= 148 pg/mL), respectively. Abdominal CT-scan showed an 8.0 x 7.0 x 8.0 cm right adrenal mass. MIBG showed increased activity in the mass without evidence of metastatic disease. Doxazosin was initiated for alpha blockade. One week postoperatively, ECMO was weaned off and the patient was extubated. Shortly after extubation, a second hypertensive crisis occurred with an increase in systolic blood pressure to over two hundred and a decrease in oxygen saturation to forty percent. Re-intubation was unsuccessful and cricothyrotomy was required. Both nitroprusside and clevidipine failed to reduce blood pressure and a labetalol infusion was necessary to end the episode. The patient underwent surgery for cricothyrotomy to tracheostomy conversion two days later. By that point, labetalol had been weaned off and doxazosin had been titrated to three mg every twelve hours. A titratable IV phentolamine infusion was used for further alpha blockade intra-operatively and normotension was maintained. Over the next two weeks, adequate alpha blockade was achieved with titration of doxazosin dosage to thirteen mg two times daily. Uncomplicated adrenalectomy was then completed. Pathology showed a pheochromocytoma with retained SDHB, focal positivity for ACTH, and without capsular or vascular invasion. Conclusion: Routine critical care procedures such as extubation can trigger hypertensive crises in patients with pheochromocytomas. These episodes may be resistant to multiple intravenous anti-hypertensive agents. Titratable intravenous phentolamine can be used as a precautionary measure during necessary procedures if adequate alpha blockade with oral agents has not yet been achieved. Presentation: Friday, June 16, 2023

SAT171 An Unusual Presentation Of Insulinoma With Postprandial Hypoglycemia

Abstract Disclosure: J.G. Melendez-Rivera: None. F.H. Morgan: None. A. Aneja: None. Background: Insulinomas are rare neuroendocrine tumors of the pancreas with an incidence of four cases per million individuals per year. The most common presentation of insulinoma is fasting hypoglycemia with associated neuroglycopenic symptoms. Postprandial hypoglycemia has been previously reported, usually in combination with fasting hypoglycemia. Exclusive postprandial hypoglycemia is estimated to occur in 6% of insulinomas. Clinical Case: A 61-year-old woman presented with episodes of postprandial blurry vision, diaphoresis, nausea, and dizziness occurring for the last 18 months that have become more frequent. The patient reported blood glucose measurements in the 35 - 40 mg/dL range at the time of symptoms. Fasting blood glucose levels remained consistently in the 70 - 90 mg/dL range. These symptoms were originally sporadic but progressively became more common to the point that they were occurring daily after meals, and she gained 20 pounds due to increased food intake. BMI was 36.28. Her physical exam was unremarkable. Fasting labs revealed a glucose of 82mg/dl and C-peptide of 2.8ng/ml with normal cortisol. After a short trial of a reactive hypoglycemia diet, the patient had no improvement in symptoms, and was admitted for a 72-hour fast. She developed hypoglycemia with a glucose of 42mg/dl within four hours of starting her inpatient fast. At the time of hypoglycemia, insulin and C-peptide were inappropriately normal (insulin 15.9 mIU/mL and C-peptide 2.57 ng/mL) with an elevated proinsulin (42.3 pmol/L). An MRI abdomen with and without IV contrast showed a 16 mm hypervascular mass in the head of the pancreas. She subsequently underwent endoscopic ultrasonography with fine needle aspiration showing findings consistent with a well-differentiated pancreatic neuroendocrine tumor. Ga-68 DOTATATE PET CT revealed increased DOTATATE avidity in the pancreatic head mass compatible with neuroendocrine tumor but no evidence of metastatic disease. She underwent surgical resection of the tumor with resolution of symptoms. Conclusion: The absence of fasting hypoglycemia does not rule out pancreatic neuroendocrine tumors. While rare, exclusive postprandial hypoglycemia can be seen in these types of tumors, especially proinsulin-secreting tumors. This case illustrates the importance of considering insulinoma during the evaluation of postprandial hypoglycemia in the absence of fasting hypoglycemia and persistent hypoglycemia despite dietary modifications. Presentation: Saturday, June 17, 2023

FRI224 A Rare Case Of Recurrent Paraganglioma Presented With Liver Metastasis

Abstract Disclosure: E. Gupta: None. M. Al Mushref: None. Malignant Paragangliomas (PGLs) and Pheochromocytomas (PCC) are extremely rare. Approximately 10% of PCCs and 25% of PGLs are metastatic. Metastatic PGLs typically occur in patients with predisposing genetic mutations. We present a case of recurrent metastatic PGL in a young female with no known genetic predisposition to metastatic disease occurring after surgical resection. Our patient is a 28-year-old female with a history of PGL status post left adrenalectomy and nephrectomy two and a half years prior who presented to the ED for abdominal pain. She was first diagnosed after being admitted for hypertensive emergency. During time of diagnosis, plasma and urinary metanephrines were significantly elevated at 1.13 nmol/L and 907 ug/gCr respectively and plasma and urinary normetanephrines were elevated at 80.2 nmol/L and 52043 ug/gCr respectively. MRI showed a 16 cm left retroperitoneal mass and MIBG scan showed increased uptake in the mass however no evidence of metastatic disease was noted then. The patient had immigrated from Haiti. Her mother had passed away at age 20 of unknown cause and her father has no known history. Genetic testing was negative for hereditary gene mutations including multiple SDHDs, VHL, NF1, MEN1 and MAX. Surgical exploration showed a giant left retroperitoneal neoplasm involving the left kidney and left adrenal and both organs were resected. Pathology revealed PGL, focally extending to peripheral specimen margin and benign retroperitoneal lymph nodes and soft tissues. Post-resection meta- and normetanephrines levels were normal. Unfortunately, the patient was lost to follow up after surgery. On this admission, she endorsed right lower quadrant abdominal pain. Plasma normetanephrine was 1.72 nmol/L, metanephrine was normal, and chromogranin A level was elevated at 545 ng/mL. CT scan revealed multiple hepatic lesions and MIBG scan further showed new increased uptake suggesting metastasis. The patient was asymptomatic and blood pressure remained normal during her hospitalization. Due to concerns of recurrent PGL with metastasis, she established care with Oncology for initiation of treatment. PGL is an extremely rare neuroendocrine tumor and is closely related to PCC. Sympathetic PGLs cause catecholamine surge symptoms but low volume disease may remain asymptomatic. Genetic predisposition is common in malignant PGL particularly succinate dehydrogenase mutation subunit B. Patients should be closely followed up to screen for recurrence and genetic testing should also be done. In our patient’s case, despite surgical resection and negative genetic testing, she developed recurrence of the PGL with new metastasis emphasizing the importance of close surveillance in the case of PGL to monitor for recurrence. Presentation: Friday, June 16, 2023

FRI365 A Patient With A Bronchial Carcinoid Presents With Cushingoid Symptoms Due To A Potentially Dangerous Supplement

Abstract Disclosure: T. Morales: None. S. Samarasinghe: None. Introduction: Well-differentiated bronchial neuroendocrine neoplasms often follow a clinically indolent course and rarely cause Ectopic ACTH syndrome. Iatrogenic corticosteroid use is the most common cause of Cushing syndrome and should be considered in all patients regardless of clinical background. Clinical Case: A 59-year-old woman with an 11-year history of a 1.5 cm well differentiated bronchial carcinoid, presented with Cushingoid features. Hormonal activation of her known bronchial carcinoid was considered. Testing resulted in a normal 24-hour urine 5-HIAA (6 mg/d, n&amp;lt;15 mg/dL), elevated chromogranin A (201 ng/mL, n&amp;lt;103 ng/mL), normal histamine (&amp;lt;1.5 ng/mL, n &amp;lt;1.7 ng/mL), low-normal 7 AM serum cortisol (5.1 ug/dL, n 3.6-19.3 ug/dL), normal 7 AM ACTH (17 pg/mL, n&amp;lt;46 pg/mL) and a surprisingly low 24-hr urinary free cortisol (1.8 mcg/hr, n 4.0-50.0 mcg/hr). A late night saliva cortisol was 0.03 mcg/dL (n 3.4-16.8 mcg/dL). Echocardiography showed no evidence of carcinoid heart disease. A Dotatate PET-CT scan to assess for neuroendocrine tumor progression showed a stable right upper lobe pulmonary nodule with no evidence of metastatic disease. Ectopic Cushing syndrome was excluded given the low cortisol levels, and exogenous steroids were suspected, however the patient denied the use of oral, inhaled, or injected steroids. A cosyntropin stimulation test yielded a pre-stimulation cortisol of 6.2 ug/dL with an adequate post-stimulation cortisol of 23.5 ug/dL (n &amp;lt;46 pg/mL). At this stage of evaluation, the patient received an FDA alert regarding a glucosamine supplement she had started 4 months prior for joint pain. The notification advised of hidden drug ingredients including dexamethasone, diclofenac, and methocarbamol contained within Artri King glucosamine supplements not listed on the product label, but verified by FDA lab analysis. The FDA had received several adverse event reports including liver toxicity and death associated with such products. The patient’s symptoms gradually improved after discontinuation of the supplement. Conclusion: Ectopic ACTH production is reported in less than 5% of patients with squamous cell lung cancer and 3% of patients with lung or pancreatic (non-MEN1) neuroendocrine tumors. Factitious corticoid exposure is rare and can be evaluated with synthetic corticosteroid serum testing. Cushing syndrome due to supplements containing unreported corticosteroid doses should be considered in patients with typical Cushingoid features and contradictory hormonal testing.

SAT547 Hereditary Paraganglioma: The Rare Co-Existence Of Two Genetic Syndromes Associated With PPGL-pheochromocytoma

Abstract Disclosure: K. Samuel: None. Hereditary Paraganglioma: the rare co-existence of two genetic syndromes associated with PPGL-Pheochromocytoma Kelara Samuel MD, Bryan McIver MD, Colleen Veloski MD, Julie Hallanger-Johnson MD, Valentina D. Tarasova, John Tourtelot MD, George Q. Yang MD, Sarimar Agosto-Salgado MD Background: Paragangliomas are neuroendocrine tumors arising from neural crest chromaffin cells of the autonomic ganglia and can be parasympathetic or sympathetic in nature. Approximately 30 percent of all paragangliomas are hereditary either associated with familial paraganglioma syndromes and other autosomal dominant syndromes, such as multiple neuroendocrine neoplasia 2A and 2B, neurofibromatosis type 1, and von Hippel Lindau disease.Case: A 73-year-old Hispanic female with a past medical history of hypothyroidism, hypertension, hyperlipidemia, and Lupus presented with a large neck mass of 11 years of evolution. An evaluation revealed a large near 12cm hypervascular, hyperenhancing left neck mass that encased the distal common carotid artery, carotid bifurcation, and internal and external carotid arteries and their branches. The multidisciplinary team recommended, given the tumor's extent, a non-surgical localized treatment consisting of radiation. Clinically, the patient had compressive symptoms, including tenderness over the tumor region, hoarseness, dysphagia, and changes in phonation. The patient also had a positive family history of paraganglioma in her grandson and nephew, but specific genetic alteration data from relatives was unavailable. Plasma normetanephrines were 0.68 (normal range 0-0.89), and plasma metanephrines were 0.23 (normal range 0-0.49). Genetic testing was positive for germline alterations in both SDHB p.Q214 and NF1 c.2970_2972delAAT. At this time, there is no evidence of metastatic disease and no clinical manifestations of NF1, suggesting a mild neurofibromatosis phenotype. Restaging imaging revealed an ongoing partial response to radiation and clinically patient has noted a significant improvement in the prior compressive symptoms. Conclusion: We present a case where we see an uncommon presentation of a non-secretory, hereditary paraganglioma with two concomitant rare genetic syndromes. This case highlights the importance of genetic testing for patient-appropriate tumor surveillance and family counseling implications. Presentation Date: Saturday, June 17, 2023