{"doi":"10.1111/bpa.13133","title":"A 64‐year‐old woman with frontal lobe lesion and drug‐resistant epilepsy","abstract":"A 64-year-old woman with a 29-year history of drug resistant epilepsy presented to the NIH Clinical Center for surgical evaluation. Seizure onset occurred at age 35 with two generalized tonic–clonic seizures. Despite treatment with multiple seizure medications, she continued to experience focal unaware seizures 12–15 times per month. MRI performed at age 58 identified a lesion in the inferior aspect of the left frontal lobe, interpreted as encephalomalacia, with no other known seizure risk factors. Her neurological examination on admission at NIH was remarkable only for mild intentional and postural tremor bilaterally. EEG monitoring was notable for left greater than right frontal interictal and ictal activity. MRI performed at NIH presentation (Figure 1A,B) demonstrated a lesion centered in the left orbitofrontal gyrus unchanged from the MRI performed 7 years prior. The lesion was interpreted as benign, non-neoplastic, most likely representing a hamartoma such as a focal cortical dysplasia, and a likely epileptogenic focus. Intracranial EEG recordings from stereotactically placed depth electrodes in bilateral frontal regions were consistent with seizure onsets in the left frontal lesion region seen on MRI. Surgical resection of the left frontal lobe lesion revealed a firm area with the appearance of scar tissue. The specimen was sent for histologic evaluation. The patient did well postoperatively with no neurologic deficits. She was seizure free for 3 months, although later reported five brief focal seizures occurring over the next 3 months of follow up (Box 1). Access at https://isn-slidearchive.org/?col=ISN&fol=Archive&file=BPA-22-06-162.svs Hematoxylin and eosin-stained sections (Figure 2A) demonstrated a moderately cellular lesion comprised of cytologically bland, spindle-shaped cells without definite perivascular aggregation. Although imaging was negative for neoplasm, we entertained the diagnosis of schwannoma and angiocentric glioma based on H&E review. No necrosis or mitotic figures were evident. Immunohistochemistry studies (Figure 2B–E) revealed the lesional cells were diffusely positive for GFAP and S100, predominately negative for OLIG2, while negative for CD34, EMA, and BRAFV600E. In addition, the lesional cells were negative for IDH1 R132H mutation and retained expression for ATRX. Ki-67 showed low proliferation index (<1%). Collagen IV immunostain was negative. The overall morphological and immunohistochemical profile was more indicative of a low-grade glioma. DNA methylation microarrays classifier analysis (V11) of this case indicated a match to low-grade glioma, MYB/MYBL1 (calibrated score 0.99). Additionally, the Version 12 classifier further suggested this tumor was a diffuse glioma, MYB(L1)-family, subtype A (calibrated score 0.70) which corresponds to the angiocentric glioma-type. Additional evaluation including Uniform Manifold Approximation and Projection for dimensionality reduction (UMAP) clustering analysis of DNA methylation (Figure 2F) also placed the patient's tumor in the same group. Next Generation Sequencing RNA exome fusion panel analysis showed MYB-QK1 e13:e5 fusion which is known to be associated with angiocentric glioma. The copy number variation plot was essentially flat without detectable chromosomal alterations. Diffuse low-grade glioma, MYB/MYBL1 family, most consistent with angiocentric glioma by molecular analysis. Low-grade, developmental, epilepsy-associated brain tumors comprise a major component of tumors in patients undergoing surgery for epilepsy. Characteristic tumors associated with epilepsy include gangliogliomas, dysembryoplastic neuroepithelial tumors, angiocentric gliomas, isomorphic diffuse gliomas, and papillary glioneuronal tumors [1]. The H&E histology of this tumor and immunohistochemistry results were not conclusive as to differential diagnosis of diffuse astrocytoma, MYB-/MYBL1-altered and angiocentric glioma. While the lack of a classical angiocentric pattern and a","journal":"Brain Pathology","year":2022,"id":293441,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9362,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":240507,"name":"Zied Abdullaev","orcid":"0000-0001-6345-2088","position":1,"is_corresponding":false},{"id":439997,"name":"John A. Butman","orcid":"0000-0002-1547-9195","position":2,"is_corresponding":false},{"id":282982,"name":"Sara K. Inati","orcid":"0000-0002-7587-5085","position":3,"is_corresponding":false},{"id":978153,"name":"Shareena Rahman","orcid":"0009-0001-3110-2734","position":4,"is_corresponding":false},{"id":265853,"name":"Kareem A. Zaghloul","orcid":"0000-0001-8575-3578","position":5,"is_corresponding":false},{"id":311195,"name":"Antonios Papanicolau‐Sengos","orcid":"0009-0008-9276-7052","position":6,"is_corresponding":false},{"id":238039,"name":"Drew Pratt","orcid":"0000-0003-3583-8308","position":7,"is_corresponding":false},{"id":13200,"name":"Kenneth Aldape","orcid":"0000-0001-5119-7550","position":8,"is_corresponding":false},{"id":474953,"name":"Martha Quezado","orcid":"0009-0004-0941-8662","position":9,"is_corresponding":false},{"id":838920,"name":"Xueting Jin","orcid":"0000-0003-3876-5298","position":0,"is_corresponding":true}],"reference_count":4,"raw_metadata":null,"created_at":"2026-07-19T00:30:53.818562Z","pmid":"36490308","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}