Vizcaíno, M. Adelita

Abstract OBJECTIVE To demonstrate that Prostate-specific membrane antigen (PSMA) PET imaging, though primarily used in prostate cancer surveillance, can reveal PSMA uptake in non-prostatic tumors due to neovascular PSMA expression. BACKGROUND PSMA PET imaging is increasingly used for staging and monitoring prostate cancer. However, PSMA uptake is not exclusive to prostate carcinoma and may be observed in non-prostatic malignancies, including glioblastoma, due to neovascular expression. CASE REPORT We present a 67-year-old gentleman with metastatic prostate carcinoma, diagnosed in 2014 and treated with neoadjuvant Lupron, prostatectomy, and salvage radiation. In 2019, he developed nodal recurrence in retroperitoneal and bilateral iliac chain nodes, treated with lymphadenopathy, six cycles of Taxotere-based chemotherapy, and consolidative proton beam radiation (56.25 Gy/25 fractions). He later developed progression to the right proximal humerus and left coracoid process, treated with stereotactic body radiation therapy (25Gy/5 fractions). Follow-up PSMA PET/CT revealed no systemic abnormalities but showed a new PSMA-avid lesion in the right medial temporal lobe. Brain MRI confirmed a 3.5 x 1.7 x 2.5 cm ring-enhancing, intra-axial lesion with edema. The patient was asymptomatic. PSA was undetectable on abiraterone/prednisone and leuprolide. He underwent right frontotemporal craniotomy and resection. Pathology confirmed Glioblastoma, IDH-wildtype, CNS WHO Grade 4 with focal epithelioid features and positive MGMT promoter methylation. He received standard-of-care treatment with radiation, temozolomide, and TTF device. Surveillance PSMA PET and MRI showed no residual brain avidity or progression. Discussion: PSMA is a type II transmembrane glycoprotein expressed by prostatic and various non-prostatic tissues. In healthy brain parenchyma, PSMA expression is typically absent but is overexpressed in neovasculature of high-grade gliomas, including glioblastoma, IDH-wildtype, allowing for radiotracer uptake, as seen in this case. CONCLUSION This case illustrates the potential role of PSMA as a diagnostic tool, as it allows for easy identification of glioblastoma neovasculature, as demonstrated in our case report.

Abstract Pleomorphic xanthoastrocytomas (PXAs) harbor CDKN2A homozygous deletion in >90% of cases, resulting in loss of p16 expression by immunohistochemistry. Considering the proximity of MTAP to CDKN2A and their frequent concurrent deletions, loss of MTAP expression may be a surrogate for CDKN2A homozygous deletion. We evaluated p16 and MTAP expression in 38 patient PXAs (CNS WHO grade 2: n = 23, 60.5%; grade 3: n = 15, 39.5%) with available chromosomal microarray data to determine whether MTAP can be utilized independently or in combination with p16 to predict CDKN2A status. CDKN2A, CDKN2B, and MTAP homozygous deletion were present in 37 (97.4%), 36 (94.7%), and 25 (65.8%) cases, respectively. Expression of p16 was lost in 35 (92.1%) cases, equivocal in one (2.6%), and failed in 2 (5.3%), while MTAP expression was lost in 27 (71.1%) cases, retained in 10 (26.3%), and equivocal in one (2.6%). This yielded a sensitivity of 94.6% for p16 and 73.0% for MTAP in detecting CDKN2A homozygous deletion through immunohistochemistry. MTAP expression was lost in the 2 cases with failed p16 staining (combined sensitivity of 100%). Our findings demonstrate that combined p16 and MTAP immunostains correctly detect CDKN2A homozygous deletion in PXA, while MTAP expression alone shows reduced sensitivity.

Abstract Ganglioglioma (GG) with anaplasia (anaplastic ganglioglioma) is a rare and controversial diagnosis. When present, anaplasia involves the glial component of the tumor, either at presentation or at recurrence. To date, most published cases lack molecular characterization. We describe the histologic and molecular features of 3 patients presenting with BRAF p. V600E-mutant GG (CNS WHO grade 1) with high-grade glial transformation at recurrence. The tumors occurred in pediatric patients (age 9–16 years) with time to recurrence from 20 months to 7 years. At presentation, each tumor was low-grade, with a BRAFV600E-positive ganglion cell component and a glial component resembling pleomorphic xanthoastrocytoma (PXA) or fibrillary astrocytoma. At recurrence, tumors resembled anaplastic PXA or high-grade astrocytomas without neuronal differentiation. CDKN2A homozygous deletion (HD) was absent in all primary tumors. At recurrence, 2 cases acquired CDKN2A HD; the third case showed loss of p16 and MTAP immunoexpression, but no CDKN2A/B HD or mutation was identified. By DNA methylation profiling, all primary and recurrent tumors either grouped or definitely matched to different methylation classes. Our findings indicate that malignant progression of the glial component can occur in GG and suggest that CDKN2A/B inactivation plays a significant role in this process.

Abstract Primary leptomeningeal lymphoma is exceedingly rare. We describe 2 rare lymphoma cases with exclusive leptomeningeal disease: 1 ALK-positive (ALK+) anaplastic large cell lymphoma (ALCL) and 1 primary effusion lymphoma (PEL). Case 1: A 19-year-old man presented with symptoms concerning for leptomeningitis. Cerebrospinal fluid (CSF) analysis revealed lymphocytic pleocytosis. Spine MRI demonstrated pial enhancement from T10 through the conus medullaris and cauda equina enhancement/thickening. A biopsy showed leptomeningeal involvement by large lymphoma cells with hallmark cells and brisk mitotic activity. By immunohistochemistry, cells were CD7/CD30-positive with cytoplasmic ALK staining. No systemic disease was identified. The diagnosis of primary leptomeningeal ALK+ ALCL was made. Despite 2 CSF relapses requiring systemic therapy and autologous bone marrow transplant, the patient was in complete clinical remission 9 years after the diagnosis. Case 2: A 60-year-old, human immunodeficiency virus-positive man presented with symptoms suggestive of leptomeningitis. Brain MRIs revealed multifocal, supratentorial, and infratentorial leptomeningeal enhancement. A right frontal biopsy demonstrated leptomeningeal involvement by large lymphoma cells negative for B-cell immunostains, but CD138, MUM-1, and HHV8-positive, with aberrant CD3 expression. EBV-encoded RNA in situ hybridization was positive. In absence of solid lesions/extracranial involvement, the diagnosis of leptomeningeal PEL was rendered. Despite initial complete remission after chemotherapy, the patient died 9 months later.

Abstract Introduction Neurenteric cysts (NECs) are rare, congenital lesions lined by endodermal cell-derived columnar or cuboidal epithelium. Based on previous studies, gross total removal of the capsule has been presumed to be the ideal surgical goal. Objective This series was undertaken to further understand the risk of recurrence based on the extent of capsule resection. Methods Records were retrospectively reviewed for all patients with radiographic or pathological evidence of intracranial NEC from 1996 to 2021. Results A total of eight patients were identified; four of eight (50%) presented with headache, and four had signs of one or more cranial nerve syndromes. One patient (13%) presented with third nerve palsy, one (13%) had sixth nerve palsy, and two (25%) with hemifacial spasm. One patient (13%) presented with signs of obstructive hydrocephalus. Magnetic resonance imaging demonstrated T2 hyper- or isointense lesions. Diffusion-weighted imaging was negative in all patients (100%) and T1 contrast-enhanced imaging demonstrated minimal rim enhancement in two patients (25%). In three of eight (38%), a gross total resection (GTR) was achieved, while in four (50%), a near-total resection, and in one (13%), a decompression was performed. Recurrences occurred in two (25%) patients, one with decompression and another with near-total resection, among these 1/2 required repeat surgery after a mean follow-up of 77 months. Conclusion In this series, none from GTR group demonstrated recurrence, while 40% of those receiving less than GTR recurred, underpinning the importance of maximally safe resection in these patients. Overall patients did well without major morbidity from surgery.