Detection of Leptomeningeal Disease Using Cell-Free DNA From Cerebrospinal Fluid.

Importance: Leptomeningeal disease (LMD) is a devastating complication of cancer that is frequently underdiagnosed owing to the low sensitivity of cerebrospinal fluid (CSF) cytologic assessment, the current benchmark diagnostic method. Improving diagnostic sensitivity may lead to improved treatment decisions. Objective: To assess whether cell-free DNA (cfDNA) analysis of CSF may be used to diagnose LMD more accurately than cytologic analysis. Design, Setting, and Participants: This diagnostic study conducted in a neuro-oncology clinic at 2 large, tertiary medical centers assessed the use of genomic sequencing of CSF samples obtained from 30 patients with suspected or confirmed LMD from 2015 through 2018 to identify tumor-derived cfDNA. From the same CSF samples, cytologic analyses were conducted, and the results of the 2 tests were compared. This study consisted of 2 patient populations: 22 patients with cytologically confirmed LMD without parenchymal tumors abutting their CSF and 8 patients with parenchymal brain metastases with no evidence of LMD. Patients were considered positive for the presence of LMD if previous CSF cytologic analysis was positive for malignant cells. The analysis was conducted from 2015 to 2018. Main Outcomes and Measures: The primary outcome was the diagnostic accuracy of cfDNA analysis, defined as the number of tests that resulted in correct diagnoses out of the total number of tests assayed. Hypotheses were formed before data collection. Results: In total, 30 patients (23 women [77%]; median age, 51 years [range, 28-81 years]), primarily presenting with metastatic solid malignant neoplasms, participated in this study. For 48 follow-up samples from patients previously diagnosed via cytologic analysis as having LMD with no parenchymal tumor abutting CSF, cfDNA findings were accurate in the assessment of LMD in 45 samples (94%; 95% CI, 83%-99%), whereas cytologic analysis was accurate in 36 samples (75%; 95% CI, 60%-86%), a significant difference (P = .02). Of 43 LMD-positive samples, CSF cfDNA analysis was sensitive to LMD in 40 samples (93%; 95% CI, 81%-99%), and cytologic analysis was sensitive to LMD in 31 samples (72%; 95% CI, 56%-85%), a significant difference (P = .02). For 3 patients with parenchymal brain metastases abutting the CSF and no suspicion of LMD, cytologic findings were negative for LMD in all 3 patients, whereas cfDNA findings were positive in all 3 patients. Conclusions and Relevance: This diagnostic study found improved sensitivity and accuracy of cfDNA CSF testing vs cytologic assessment for diagnosing LMD with the exception of parenchymal tumors abutting CSF, suggesting improved ability to diagnosis LMD. Consideration of incorporating CSF cfDNA analysis into clinical care is warranted.

Metachronous mediastinal seminoma occurring after intracranial germinoma in an adolescent.

We report a case of a mediastinal seminoma occurring 19 months after the resolution of a pineal germinoma. A 15-year-old boy with headaches and visual changes was diagnosed with a pineal germinoma by biopsy and mildly elevated beta-human chorionic gonadatropin (beta-HCG) in serum and cerebral spinal fluid. Radiation therapy leads to the resolution of his pineal germinoma and normalization of the beta-HCG. A mediastinal seminoma (germinoma) was diagnosed nearly 2 years later because of rising serum beta-HCG. There was no evidence of recurrent central nervous system disease. The patient underwent systemic chemotherapy with the complete resolution of the mediastinal seminoma.

Granulocytic sarcoma with orbit, cauda equina, muscle and peripheral nerve extension but without bone marrow involvement.

We report a very rare case of granulocytic sarcoma (GS) with muscle and peripheral nerve extension but without bone marrow involvement. A 53-year-old woman presented with sciatic pain and diplopia. Magnetic resonance imaging revealed bilateral orbital and cauda equina region tumors. The blood cell count, and bone marrow histology and cytology were normal. The characteristic cerebrospinal fluid (CSF) cytologic picture of CD14+, CD33+, CD4+, CD56+ and positive nonspecific erastase staining suggested the diagnosis of GS. The patient underwent intrathecal and systemic chemotherapy, as if she had acute myeloid leukemia (AML). This case emphasizes the value of CSF cytological examination and the use of an immunocytochemical marker.

[Multiple cerebral glioma or tumor dissemination via CSF pathways? Case report]. / Przypadek mnogiego glejaka mózgu, czy rozsiew guza drogami plynowymi? Opis przypadku.

A case is presented of a 38-year-old female patient who developed bifocal metachronous cerebral glioma with the same histological appearance (glioblastoma multiforme). Two separate tumors were operated on within six months: the first one was localized in the left parieto-occipital area, and the other in the right temporal lobe. The tumor cells dissemination occurred probably via the CSF pathways: during the first operation the posterior horn of the left lateral ventricle was opened, and the second neoplastic lesion was situated also in the direct vicinity of CSF spaces (the Sylvian cistern). For all practical purposes, the case presented testifies to the necessity of intraoperative protection of the CSF spaces by separating any open CSF cisterns from the removed tumor mass with cotton pads. In case of diagnosing cerebral glioma, a possibility of the presence of multiple foci should be taken into account. It is especially important for the differentiation of multiple lesions occurring synchronically, where similarity of radiological features is seen in metastases, cerebral abscesses and demyelinating lesions.