Inflammatory Demyelinating Lesions: True Sentinel Lesion or Immune-Mediated Response to Lymphoma?

BACKGROUND: Inflammatory demyelinating changes in the absence of malignant cells can sometimes be found on initial biopsies preceding the diagnosis of primary central nervous system lymphoma (PCNSL), resulting in the term "sentinel" lesion. Sentinel lesions have been reported sporadically in literature, resulting in many cases of misdiagnosis and delayed treatment. We aim to address the problem of misdiagnosis in PCNSL presenting as inflammatory demyelinating changes or sentinel lesions on initial biopsies, and to discuss our view of the mechanism underlying this phenomenon. CASE DESCRIPTION: Herein we report 3 cases of PCNSL that were diagnosed via brain biopsy. We retrospectively reviewed 2 cases of initially misdiagnosed PCNSL presenting with sentinel lesions at our institution. Careful revision of preoperative magnetic resonance imaging (MRI) revealed heterogeneously enhancing tumors with strong peripheral enhancement and hypoenhancing cores. Analysis of our 2 cases revealed that initial biopsy samples in both patients were taken from the hypoenhancing regions on MRI. In the third case, we targeted the peripherally enhancing region for sampling and arrived at the proper diagnosis of PCNSL on initial biopsy. CONCLUSIONS: Based on our cases and those reported in literature, we speculate that the inflammatory demyelinating changes observed on initial biopsies are immune-mediated responses that coexist with PCNSL in different tumor regions, and that they are the direct result of inadvertent sampling from hypoenhancing regions of the tumor, rather than sentinel lesions, as their name implies. We strongly recommend that biopsy target the most enhanced region on MRI when there is high clinical and radiologic suspicion for PCNSL.

Imaging characteristics of adult H3 K27M-mutant gliomas.

OBJECTIVE: H3 K27M-mutant gliomas present heterogeneously in terms of pathology, imaging, and prognosis. This study aimed to summarize the imaging characteristics of adult H3 K27M-mutant gliomas. METHODS: The authors retrospectively identified all cases of glioma diagnosed using histopathological studies (n = 3300) that tested positive for histone H3 K27M mutations (n = 75) between January 2016 and December 2018 in a single hospital. Preoperative and follow-up MR images of 66 adult patients (age ≥ 18 years) were reviewed for anatomical location, degree of contrast enhancement, enhancement patterns, hemorrhage, edema, diffusion restriction, tumor dissemination, and tumor spread. RESULTS: The study included 66 cases (40 in men, 26 in women) of H3 K27M-mutant glioma in adult patients. Tumors were found in the following sites: thalamus (n = 38), brainstem (n = 6), brainstem with cerebellar or thalamic involvement (n = 4), whole brain (n = 8), corpus callosum (n = 3), hypothalamus (n = 1), hemispheres (n = 2), and spinal cord (n = 4). All pure brainstem lesions were located posteriorly, and all corpus callosal lesions were in the genu. Most spinal tumors were long-segment lesions. Hemispheric lesions mimicked gliomatosis cerebri in presentation, with the addition of traditional midline structure involvement. Most tumors were solid with relatively uniform signals on plain MRI. Of the 61 cases with contrast-enhanced MR images, 36 (59%) showed partial to no enhancement, whereas 25 (41%) showed diffuse or irregular peripheral enhancement. Hemorrhage and edema were rare. Most lesions were solid and showed mild diffusion restriction on diffusion-weighted imaging. Tumor dissemination to the leptomeninges (n = 8) and subependymal layer (n = 3) was observed. CONCLUSIONS: The authors described the MRI features of diffuse midline glioma with H3 K27M mutation in the largest study done to date in adult patients. Tumors were found in both midline and nonmidline structures, with the thalamus being the most common site. Although adult H3 K27M-mutant gliomas demonstrated highly variable presentations in this cohort of patients, the authors were able to observe shared characteristics within each location.

Slow-Growing Thalamic Glioma with Histone H3 Lysine 27-to-Methionine Mutation: 3-Year Follow-Up Before Surgical Intervention.

BACKGROUND: The 2016 World Health Organization Classification of Tumours of the Central Nervous System was revised to include a new diagnostic entity, diffuse midline glioma, H3 K27M-mutant (DMG-K27M), a highly aggressive tumor with a mean survival time of 1 year after diagnosis. DMG-K27M is classified as a World Health Organization grade IV tumor regardless of histopathologic features, and there is currently no effective treatment for it despite ongoing research. CASE DESCRIPTION: We present a case of a 39-year-old man with a slow-growing thalamic glioma with histone H3 lysine 27-to-methionine mutation. This patient received surgical intervention 3 years after the initial discovery of the tumor. Because the patient did not receive any preoperative treatment for DMG-K27M, this case reflects 1 possible natural course of progression for this type of malignancy. CONCLUSIONS: There are currently no effective therapeutic options for treatment of DMG-K27M. The slow tumor growth and prolonged survival time (≥ 3 years) in the absence of intervention in this case serve as a reminder that much is still not known about histone H3 lysine 27-to-methionine mutation and how it impacts the pathophysiology, diagnosis, treatment, and prognosis of the disease. Careful evaluation is warranted to determine if early intervention is the best approach when treating DMG-K27M.

Exophytic Primary Intramedullary Spinal Cord Glioblastoma: Case Report and Critical Review of Literature.

BACKGROUND: Primary intramedullary spinal cord (IMSC) glioblastoma (GBM) is an extremely rare entity; we report the first case of primary IMSC GBM presenting with exophytic involvement. The prognosis of glioblastoma remains poor due to the aggressive nature of the disease and lack of effective treatment. CASE DESCRIPTION: A 27-year-old Asian female presented to our hospital with a 1-month history of dysuria, incomplete bladder emptying, progressive numbness, and weakness of both lower limbs, as well as a 1-year history of back pain. Spinal magnetic resonance imaging (MRI) revealed an intramedullary lesion and exophytic growth in the T4-T12 and T5-12 regions, respectively. The patient's MRI findings were atypical of spinal glioblastoma. The diagnosis was made on the basis of immunohistochemical and pathologic analyses of tissue samples obtained from an open biopsy. The patient received a standard course of glioblastoma radiotherapy and adjuvant temozolomide chemotherapy, which improved her symptoms in the absence of an apparent reduction in tumor size. CONCLUSIONS: Although MRI is of indisputable importance in the diagnosis of spinal cord lesions, immunohistochemical and histopathologic studies are often required to establish a definitive diagnosis. It remains unclear how the unusual involvement of exophytic growth will affect the prognosis of primary IMSC GBM.