MGMT Methylated High Grade Glioma with Distant Recurrence and Stable Original Tumor Site: Case Series.

We present three cases of O6-Methylguanine-DNA Methyl-transferase (MGMT) methylated high grade gliomas with distant recurrence. All three patients had a radiographic stability of original tumor site at time of distant recurrence indicating impressive local control with Stupp protocol in patients with a MGMT methylated tumors. All patients had a poor outcome after distant recurrence. For one patient Next Generation Sequencing (NGS) was available for both original and recurrent tumor and did not reveal any difference other than high tumor mutational burden in the distant recurrent tumor. Understanding risk factors of distant recurrence in MGMT methylated tumors and investigating correlations between recurrences will help plan therapeutic strategies to prevent distant recurrence and improve survival of these patients.

Adenovirus-Associated Acute Interstitial Nephritis With Graft Survival and Novel Follow-Up Biopsy Findings Including Karyomegaly: A Case Series.

Adenoviral infections in post-transplant patients have been described in multiple organ systems, most classically the lung, liver, and alimentary tract. In the genitourinary tract, hemorrhagic cystitis is most frequently observed. Clinically apparent renal involvement with adenovirus is rare, and adenovirus-associated interstitial nephritis (AAIN) is an uncommon cause of renal allograft failure. Here, we present three cases of AAIN in patients who, after prompt diagnosis and treatment adjustment, experienced a return of allograft function. All patients were on standard triple therapy with tacrolimus levels within the target range at the time of biopsy. None of the patients had respiratory symptoms, and despite diarrhea, colon biopsies were negative. Only case one had positive adenovirus serology (IgG only) and case three had positive urine; two patients had leukopenia without neutropenia. Renal biopsies showed a characteristic granulomatous tubulocentric mixed lymphocytic and neutrophilic infiltrate. Adenovirus immunohistochemistry (IHC) showed strong staining in the tubular epithelium (nuclear and cytoplasmic) while staining for polyomavirus was negative. A follow-up biopsy two months after the diagnosis of AAIN in one patient revealed persistent cytopathic effects with negative adenoviral IHC staining while a biopsy at one year in another patient showed glomerular and tubulointerstitial scarring. AAIN is an uncommon but important etiology to consider in cases of acute renal allograft dysfunction. Although the presenting symptoms for AAIN are nonspecific, hematuria is frequently noted. Adenovirus IHC should be considered in cases with granulomatous inflammation associated with necrosis and mixed inflammatory infiltrate. As demonstrated in this single-institution case series, prompt diagnosis can result in the preservation of the renal allograft. Lasting cytopathic effects after adenoviral infection should also be considered in patients with a history, or potential history, of AAIN.

Internal Auditory Canal Glioneural Hamartoma: A Rare Mass Masquerading as a Vestibular Schwannoma.

Glioneural hamartomas are exceedingly rare lesions. When localized to the internal auditory canal (IAC), they can cause symptoms referrable to seventh and eighth cranial nerve compression. Here, the authors present a rare case of an IAC glioneural hamartoma. A 57-year-old male presented for evaluation of presumed intracanalicular vestibular schwannomas found on work-up of dizziness and progressive right-sided hearing loss. Surgical intervention pursued progressive symptoms and new onset headaches. The patient underwent uncomplicated retrosigmoid craniectomy for gross total resection. Histopathological evaluation revealed a glioneural hamartoma. A MEDLINE database search used the terms' cerebellopontine angle' OR 'internal auditory canal' AND 'hamartoma' OR 'heterotopia'. Clinicopathological characteristics and outcomes of the present case were compared to those in the literature. The literature review yielded nine articles describing 11 cases (eight females, three males; median age 40 years, range 11-71) of intracanalicular glioneural hamartomas. Patients most commonly presented with hearing loss and were presumed to have a diagnosis of vestibular schwannoma before histologic diagnosis. Glioneural hamartomas are rare lesions that may be found in the IAC. Although benign, they may be safely resected for cranial nerve function preservation goals with a low risk of recurrence.

Blastomycosis of the Central Nervous System.

The reported incidence of blastomycosis is increasing in certain regions of the United States. The diagnosis is primarily made via urine antigen testing, culture, or cytology smear. The differential diagnosis for blastomycosis includes pneumonia, tuberculosis, and non-infectious pulmonary disease. Clinical context and epidemiologic exposure play a crucial role in diagnosis. However, the differential can expand significantly if there is disseminated central nervous system involvement, especially if pulmonary manifestations are not seen. Imaging begins to play a vital role when differentiating disseminated blastomycosis from other etiologies such as malignancy. Herein we present a case of a 58-year-old male who presented with seizures and right sided gaze preference found to have disseminated central nervous system blastomycosis. In this article, we will discuss symptoms and imaging findings of disseminated blastomycosis to help guide diagnosis and management.

Case report and review of literature: Isolated intramedullary spinal neurocysticercosis.

Background: Cases of isolated intramedullary spinal neurocysticercosis are extremely rare. Only 25 cases have been reported before 2022. Due to its rarity, the diagnosis of spinal neurocysticercosis may be missed. Case presentation: We describe a 37-year-old female patient who developed back pain and lower extremity weakness and was found to have an intramedullary thoracic spine cystic lesion. She was taken to the operating room for resection of the lesion. Pathology revealed a larval cyst wall consistent with neurocysticercosis. The patient was started on albendazole and dexamethasone. Her exam improved post-operatively, and she was able to ambulate with minimal difficulty at the time of follow up. Conclusion: The case provides insights on the diagnosis and treatment of isolated intramedullary spinal neurocysticercosis. Review of the literature suggests that combined surgical and medical intervention results in significant improvement in the patient's neurological exam, and decreases morbidity associated with the disease. We propose a treatment paradigm for this rare manifestation of neurocysticercosis.

Deep learning from multiple experts improves identification of amyloid neuropathologies.

Pathologists can label pathologies differently, making it challenging to yield consistent assessments in the absence of one ground truth. To address this problem, we present a deep learning (DL) approach that draws on a cohort of experts, weighs each contribution, and is robust to noisy labels. We collected 100,495 annotations on 20,099 candidate amyloid beta neuropathologies (cerebral amyloid angiopathy (CAA), and cored and diffuse plaques) from three institutions, independently annotated by five experts. DL methods trained on a consensus-of-two strategy yielded 12.6-26% improvements by area under the precision recall curve (AUPRC) when compared to those that learned individualized annotations. This strategy surpassed individual-expert models, even when unfairly assessed on benchmarks favoring them. Moreover, ensembling over individual models was robust to hidden random annotators. In blind prospective tests of 52,555 subsequent expert-annotated images, the models labeled pathologies like their human counterparts (consensus model AUPRC = 0.74 cored; 0.69 CAA). This study demonstrates a means to combine multiple ground truths into a common-ground DL model that yields consistent diagnoses informed by multiple and potentially variable expert opinions.

High-grade glioma with pleomorphic and pseudopapillary features (HPAP): a proposed type of circumscribed glioma in adults harboring frequent TP53 mutations and recurrent monosomy 13.

Tumors of the central nervous system (CNS) often display a wide morphologic spectrum that has, until recently, been the sole basis for tumor classification. The introduction of the integrated histomolecular diagnostic approach in CNS tumors has facilitated a classification system that is increasingly data-driven and with improved alignment to clinical outcome. Here, we report a previously uncharacterized glioma type (n = 31) using unsupervised clustering analysis of DNA methylation array data from approximately 14,000 CNS tumor samples. Histologic examination revealed circumscribed growth and morphologic similarities to pleomorphic xanthoastrocytoma (PXA), astroblastoma, ependymoma, polymorphous neuroepithelial tumor of the young (PLNTY), and IDH-wildtype glioblastoma (GBM). Median age (46.5 years) was significantly older than other circumscribed gliomas and younger than GBM. Dimensionality reduction with uniform manifold approximation and projection (UMAP) and hierarchical clustering confirmed a methylation signature distinct from known tumor types and methylation classes. DNA sequencing revealed recurrent mutations in TP53 (57%), RB1 (26%), NF1 (26%), and NF2 (14%). BRAF V600E mutations were detected in 3/27 sequenced cases (12%). Copy number analysis showed increased whole chromosome aneuploidy with recurrent loss of chromosome 13 (28/31 cases, 90%). CDKN2A/B deletion (2/31, 6%) and MGMT promoter methylation (1/31, 3%) were notably rare events. Most tumors showed features of a high-grade glioma, yet survival data showed significantly better overall survival compared to GBM (p < 0.0001). In summary, we describe a previously uncharacterized glioma of adults identified by a distinct DNA methylation signature and recurrent loss of chromosome 13.

Primary Intradural Extramedullary Sporadic Spinal Hemangioblastomas: Case Report and Systematic Review.

BACKGROUND: Hemangioblastomas are benign vascular neoplasms of the central nervous system that may occur sporadically or in association with Von Hippel-Lindau disease. A minority of these lesions can occur in the spine, mostly as intramedullary masses. The authors present a rare case of primary sporadic spinal hemangioblastoma occurring as an intradural extramedullary (IDEM) lesion. Diagnostic workup and surgical management of the patient are described. METHODS: A systematic MEDLINE search was conducted using the keywords "hemangioblastoma" and "intradural extramedullary," "extramedullary," or "cauda equina." Clinicopathological characteristics and outcomes of the present case were reviewed and compared with those in the literature. RESULTS: A 72-year-old man was found to have an IDEM lesion in his cervical spine after presenting with neck and shoulder pain. Gross total resection was successfully performed with sacrifice of an involved dorsal nerve rootlet. Screening for Von Hippel-Lindau was negative. Thirty-three additional patients with sporadic IDEM hemangioblastomas are reported in the literature. There was a slight male preponderance (54%) with a median age of 52 years. Patients presented with pain (54%), radiculopathy (33%), or myelopathy (32%). The majority of lesions were located in the lumbosacral spine (56%). All patients underwent maximal safe resection with stable or improved clinical status. CONCLUSION: Primary IDEM hemangioblastomas are a rare entity. Differential diagnosis includes other IDEM lesions, such as schwannomas, meningiomas, or some vascular malformations. Resection of these sporadic tumors can be safely performed and result in improvement of neurologic deficits associated with mass effect from the tumor with low likelihood of recurrence.

Anaplastic Hemangiopericytoma of the Jugular Foramen: Case Report and Systematic Review.

BACKGROUND: Hemangiopericytomas (HPCs) and solitary fibrous tumors (SFTs) are rare tumors of mesenchymal origin. Here, the authors present a rare case of anaplastic HPC in the jugular foramen (JF). The authors also conduct a systematic review of the literature to examine the current fund of knowledge on JF HPC/SFTs. METHODS: A systematic MEDLINE search was conducted using key words "hemangiopericytoma" OR "solitary fibrous tumor" AND "jugular foramen" OR "extracranial" OR "skull base." Clinicopathologic characteristics and outcomes of the present case were reviewed and compared with those in the literature. RESULTS: A 41-year-old male, who had undergone stereotactic radiation therapy 6 years ago for a presumed glomus jugulare tumor, presented to our institution with worsening dysphagia, hoarseness, persistent tongue weakness, and radiographic evidence of tumor progression. The patient underwent uncomplicated gross total resection with sacrifice of the infiltrated hypoglossal nerve. Histopathologic evaluation revealed anaplastic HPC/SFT (World Health Organization grade III). Review of the literature yielded 9 additional cases of JF HPC/SFT in 5 males (56%) and 4 females (44%), with a mean age of 49.6 years old. Patients commonly presented with pain (37.5%) and lower cranial nerve deficits (100%). Preoperative diagnoses included glomus jugulare (n = 2) or JF schwannomas (n = 3). All patients underwent microsurgical resection of the lesion, except for 1 who refused all treatment after diagnostic biopsy. CONCLUSION: The authors present the only reported case of anaplastic HPC of the JF. The illustrative case and those found on systematic review of the literature highlight the importance of tissue diagnosis and appropriate management.

Acute Kidney Injury Associated With Semaglutide.

Case reports of acute kidney injury in patients taking the glucagon-like peptide 1 (GLP-1) receptor agonists exenatide and liraglutide have been reported. We report 2 patients with chronic kidney disease due to diabetic kidney disease who experienced rapid worsening of kidney function and increased proteinuria after being prescribed the GLP-1 receptor agonist semaglutide. In 1 patient, kidney biopsy showed advanced diffuse and nodular glomerulosclerosis accompanied by interstitial lymphoplasmacytic and eosinophilic infiltrate and evidence of acute tubular injury. At this time, the long-term outcomes of patients who experience acute kidney injury associated with GLP-1 receptor agonists is not known. We recommend that caution be used with these agents in patients with moderate to severe chronic kidney disease due to limited kidney reserve in the event of an adverse kidney event. Because most adverse kidney events have occurred in patients who experience adverse gastrointestinal symptoms, such patients should have laboratory tests and discontinuation of the medication if there is acute worsening of kidney function.

Long-Term Outcomes of Pituitary Gland Preservation in Pituitary Macroadenoma Apoplexy: Case Series and Review of the Literature.

Introduction For patients presenting with neurological changes from pituitary tumor apoplexy, urgent surgical intervention is commonly performed for diagnosis, tumor resection, and optic apparatus decompression. Although identification and preservation of the pituitary gland during the time of surgery can be challenging, it may lead to improve endocrine outcomes. Methods A retrospective case series of all patients with macroadenomas presenting with apoplexy at Loyola University Medical Center from 2016 to 2018 was studied. Demographic, radiographic, and intraoperative characteristics were collected including age, gender, comorbidities, presenting symptoms, preoperative size of pituitary adenoma, Knosp's grade, Hardy's grade, identification and/or preservation of the gland, pre- and postoperative hormonal levels, intraoperative and/or postoperative complications, and follow-up time. Results A total of 68 patients underwent endoscopic endonasal surgery for resection of a macroadenoma. Among them, seven (10.2%) presented with apoplexy; five patients were male and two were female and presenting symptoms and signs included headache (100%), endocrinopathies (57%), visual acuity deficit (71%), visual field deficit (71%), and oculomotor palsy (57%). A gross-total resection rate was achieved in 86% of patients. Among them, 71% of patients obtained complete symptomatic neurological improvement. A statistically significant difference between gender and endocrine function was found, as no females and all males required some form of postoperative hormonal supplementation ( p = 0.047) . Conclusion Endoscopic endonasal resection of macroadenomas with sparing of the pituitary gland in the setting of apoplexy is safe and effective. Preservation of the normal gland led to no posterior pituitary dysfunction, and a statistically significant difference between gender and postoperative endocrinopathy was identified. Further studies with larger samples sizes are warranted.

Hypertrophic cranial pachymeningitis and orbital apex syndrome secondary to infection of the eye: illustrative case.

BACKGROUND: Hypertrophic cranial pachymeningitis is a rare inflammatory disorder characterized by thickening of the dura mater and multiple cranial neuropathies. Although an infectious etiology may be present, often no specific cause is discovered. OBSERVATIONS: The authors described a 71-year-old man with progressive right eye vision loss, ptosis, and complete ophthalmoplegia with imaging findings suggestive of hypertrophic cranial pachymeningitis. Extensive studies, including cerebrospinal fluid studies, showed negative results. Blood serum, cell-free evaluation, and paraffin-embedded dural tissue testing had positive results for Pseudomonas aeruginosa, which allowed treatment tailored to the organism and a salutary clinical outcome. LESSONS: The constellation of neurological and radiological findings may make a diagnosis difficult in an inflammatory setting. The most precise methodology for establishing a diagnosis involves sampling the dura and testing it for infectious pathology. However, if results are inconclusive, further cell-free serum sampling with next-generation sequencing is a viable option for identifying pathogens with infectious concerns. This case highlighted the importance of multimodality studies for identifying a targetable pathogen.

The Utility of Using Preoperative MRI as a Predictor for Intraoperative Pituitary Adenoma Consistency and Surgical Resection Technique.

Objective Most pituitary adenomas are of soft consistency and can be resected during surgery with routine suction instruments. However, fibrous adenomas may require more aggressive techniques. The ability to predict consistency on magnetic resonance imaging (MRI) would improve preoperative preparation and may have implications on the extent of resection. Design A retrospective review of MRI and tumor histology of 50 consecutive patients who underwent endoscopic endonasal resection for nonfunctional adenomas was performed. Methods An intensity ratio was calculated based on quantitative MRI signal intensity of the adenoma and pons. Intraoperatively, a sequentially graded technique required for resection ranged from suction (R1) for softer tumors, curettes (R2) for tumors with intermediate consistency, and aspirators and/or other microinstruments (R3) for firmer tumors. Fibrotic content was determined from histologic collagen percentage, and rates of gross total resection (GTR) were calculated from postoperative imaging. Statistical analyses were performed to determine if resection classification could be predicted by intensity ratio or collagen percentage, calculate ratio of cut-off points for clinical use, and assess for correlation between intensity ratios and collagen percentage. Results Tumors with ratios < 1.6 on the T2-weighted coronal image and collagen content > 5.3% were likely to have required a more aggressive resection technique. Statistically significant lower rates of GTR and higher rates of perioperative complications were seen with such tumors. Conclusion Preoperative MRI analyses can be helpful but not definitive in predicting adenoma consistency. Fibrous adenomas, associated with higher collagen content, are more difficult to resect and have higher rates of subtotal resection.

Caudal Homeobox Gene-2 Staining Defines Intracranial Mature Teratoma with Differentiation to Colonic Adenocarcinoma.

BACKGROUND: Malignant transformation of a mature intracranial teratoma into an adenocarcinoma is an extremely rare event and portends a poor prognosis. The clinical progression, radiographic changes, histopathological findings, and immunohistochemistry findings from these unique cases might provide clues regarding this transformation. Caudal homeobox gene-2 (CDX-2) is a specific and robust marker for colonic adenocarcinomas and can also be used to identify differentiation of mature intracranial teratoma into colonic-type adenocarcinoma. To the best of our knowledge, this is the first case report of the use of this specific marker for an intracranial malignancy. CASE DESCRIPTION: We present the case of a 55-year-old right-handed Hispanic-American woman with progressive headaches who was found to have a left posterior parietotemporal tumor with intraventricular extension. Surgical debulking was performed, and the pathologic examination revealed a mature teratoma. Despite surgical resection and radiotherapy, the teratoma progressed to a malignant mature intracranial teratoma both radiographically and histologically. Histological analysis of the third specimen revealed a moderately differentiated adenocarcinoma. The tumor cells were positive for CDX-2 and cytokeratin 20 and negative for cytokeratin 7 and thyroid transcription factor-1, consistent with an enteric/colonic-type adenocarcinoma, demonstrating progressive atypia and malignancy. CONCLUSIONS: Malignant transformation of a mature intracranial teratoma portends a poor prognosis. The exact histopathological diagnosis can facilitate treatment of these patients. CDX-2 is a specific robust marker for identifying differentiation of a mature intracranial teratoma into a colonic adenocarcinoma. This positive staining can also be observed in primary colonic and other adenocarcinomas. To the best of our knowledge, this is the first report of the use of CDX-2 in the diagnosis of an intracranial malignancy. The triangulation of clinical progression, radiographic findings, and histopathological and immunohistochemistry findings provided clues regarding this unique transformation.

Value of K i -67 Labeling Index in Predicting Recurrence of WHO Grade I Cranial Base Meningiomas.

Objectives Assess impact of K i -67 labeling index (LI; K i -67 LI) on risk of recurrence or progression of WHO grade I meningiomas. Study Design Retrospective study of adult patients who underwent resection of cranial base meningioma between 2004 and 2016. Results 272 patients fulfilled criteria for inclusion in the study. Average age was 61.8 years; 196 (72%) were females. Simpson's grade 1 resection was noted in 77 patients (32%), grade 2 in 39 (16%), grade 3 in 36 (15%), and grade 4 in 88 (37%). The K i -67 LI was low (1-4%) in 214 (78.7%), intermediate (5-9%) in 44 (16.2%), and high (>10%) in 14 (5.2%). Median follow-up was 39 months (IQR: 16-71 months); 221 (87.1%) tumors remained stable or did not recur, 19 (7.4%) recurred, and 14 (5.5%) progressed. Compared with tumors with low K i -67 LI, those with intermediate K i -67 LI had 2.47 times (2.47 [1.09-5.59], p = 0.03), and those with high K i -67 LI had 3.38 times (3.38 [1.16-9.89], p = 0.03) higher risk of recurrence or progression. Tumors with K i -67 LI > 4% had a shorter time to recurrence or progression ( p = 0.01). Recurrence or progression-free survival rates at 3, 5, and 10 years for tumors with low K i -67 LI were 95%, 89%, and 75%, respectively; tumors with intermediate K i -67 LI, 87%, 69%, and 52%, respectively; tumors with high K i -67 LI, 78%, 49%, and 49%, respectively. Conclusions Following surgical resection of a WHO grade I cranial base meningioma, K i -67 LI > 4% may predict an increased risk of recurrence or progression of residual tumor.

Thrombectomy of Ventricular Assist Device-Originated Embolic Stroke: A Clinical Decision Model.

BACKGROUND AND PURPOSE: The use of ventricular assist devices (VADs) for the treatment of heart failure has become increasingly common. These patients have a considerable risk of cerebral embolism. We describe such a patient and his successful treatment by thrombectomy, compare his attributes with those previously published, and describe the construct of a clinical decision model, whose results bear practical implications for patient management. METHODS: The details of our patient and his treatment are presented, followed by a literature review of all previously reported similar cases. Using this information, as well as that available from published series, we constructed a probabilistic decision tree, completed all calculations (ie, "folding back"), and, in order to assess the strength of the results, subjected them to multiple independent sensitivity analyses of each of the variables. RESULTS: The therapeutic success of our case, the 14th reported to date, when combined with previous reports, shows: (1) recanalization times of 184 minutes, (2) "successful" recanalization (ie, TICI = 2b or 3) achieved in 71% of procedures, (3) ultimate functional outcome (ie, mRS = 0-2) achieved in 57% patients, and (4) ultimate successful heart transplantations in 66% of cases. The clinical decision model showed the predicted utility of thrombectomy to be superior to conservative management (3.33 QALY vs. 2.56 QALY, respectively). The sensitivity analyses support the validity of these results. CONCLUSIONS: In conclusion, thrombectomy appears to be a safe and effective method (and often the only viable one) for urgent treatment of patients with VAD-originated cerebral embolism.

Sellar Metastasis of Cervical Adenocarcinoma.

BACKGROUND: Pituitary metastasis of cervical adenocarcinoma is an exceedingly rare phenomenon. CASE DESCRIPTION: The authors present a case of a 66-year-old female with cervical adenocarcinoma who was discovered to have a rapidly growing intrasellar mass in the work-up of adrenal insufficiency and hypothyroidism. The patient underwent subsequent endoscopic endonasal subtotal resection of the mass. Histopathological analysis of the resected lesion demonstrated features consistent with metastatic mucinous adenocarcinoma of the cervix. While initially neurologically asymptomatic following surgery, the patient developed an oculomotor nerve palsy several weeks following surgical debulking, at which time neuroimaging revealed marked regrowth and suprasellar extension of the metastatic lesion. CONCLUSIONS: While metastatic cervical adenocarcinoma to the sella is rare, it should be considered in the differential based on the history of the patient.