A case of diffuse midline glioma,H3 K27M mutant mimicking a hemispheric malignant glioma in an elderly patient

Diffuse midline glioma, H3 K27M mutant arises from midline structures of the central nervous system and predominately affects pediatric patients. However, this disease entity was only recently established, and the clinical phenotypic spectrum remains largely unclear. We herein report a rare case of diffuse midline glioma, H3 K27M mutant with an unusual distribution in an elderly woman who presented with a diffuse glioma that invaded both sides of the thalami, and left hippocampus and frontoparietal lobes, thus mimicking a hemispheric malignant glioma. A biopsy of the lobular lesion led to a molecular diagnostic confirmation of diffuse midline glioma, H3 K27M mutant. The patient received concurrent bevacizumab and temozolomide therapy with radiation therapy and survived for 30 months. This case highlights the possibility that a glioma with cerebral hemispheric spread in an elderly patient may harbor the H3 K27M mutation.     

A juvenile case of epilepsy-associated,isocitrate dehydrogenase wild-type/histone 3 wild-type diffuse glioma with a rare BRAF A598T mutation

Here, we report a juvenile (18-year-old male) case of epilepsy-associated, isocitrate dehydrogenase wild-type/histone 3 wild-type diffuse glioma with a rare BRAF mutation and a focal atypical feature resembling diffuse astrocytoma. The patient presented with refractory temporal lobe epilepsy. Subsequently, magnetic resonance imaging revealed a hyperintense lesion in the right temporal lobe on fluid attenuated inversion recovery images. The patient underwent right lateral temporal lobectomy and amygdalohippocampectomy. Histopathologically, the tumor showed isomorphic, diffuse, infiltrative proliferation of glial tumor cells and intense CD34 immunoreactivity. The tumor cells were immunonegative for isocitrate dehydrogenase 1 (IDH1) R132H and BRAF V600E. Notably, the tumor cells showed the lack of nuclear staining for α-thalassemia/mental retardation syndrome, X-linked (ATRX). In addition, the Ki-67 labeling index, using a monoclonal antibody MIB-1, was elevated focally at tumor cells with p53 immunoreactivity. Molecular analyses identified a BRAF^A598T mutation, the first case reported in a glioma. BRAF^A598T is predicted to result in loss of kinase action; however, inactive mutants can stimulate mitogen-activated protein kinase kinase (MEK)-extracellular signal-regulated kinase (ERK) signaling through CRAF activation. Thus, according to the recent update of the consortium to inform molecular and practical approaches to central nervous system tumor taxonomy (cIMPACT-NOW update 4), our case is also compatible with diffuse glioma with the mitogen-activated protein kinase (MAPK) pathway alteration. Thorough immunohistochemical and molecular studies are necessary for diagnosis of epilepsy-associated, diffuse gliomas. Partial resemblance in histopathological and molecular genetic features to diffuse astrocytoma also calls for attention.     

Possible role of apoptotic cells of the oral epithelium in the pathogenesis of aphthous ulceration

Electron microscopic examination of the normal oral mucosa of patients with recurrent aphthous ulceration or Beh?et's syndrome revealed that the degenerate dark prickle cells are apoptotic cells. Such dark prickle cells showed characteristic findings of apoptosis, such as the shrinkage of nucleus and cytoplasm and the formation of contraction vacuoles. The number of intraepithelial mononuclear cells phagocytosing apoptotic cellular debris increased remarkably at the preulcerative stage of the aphthous lesions. The apoptotic debris also attracted neutrophilic leukocytes in the prickle cell layer at the preulcerative stage but not in the normal oral epithelium. It is speculated that the onset of aphthous ulceration is closely related to phagocytosis of these apoptotic cells by intraepithelial mononuclear cells.     

Experimental model of invasion and metastasis by orthotopic transplantation of oral squamous and adenoid cystic carcinomas into the tongue of nude mice

Three squamous cell carcinoma (SCC) cell lines established from oral cancer, seven specimens of SCC and three of adenoid cystic carcinomas taken from the oral cavity during operations were transplanted into the tongues of nude mice. Metastases to the regional lymph nodes and the lungs were examined histologically. We were able to transplant every cell line or specimen of tissue into the tongue of nude mice, and found that cancer transplanted in the tongue invaded diffusely to the surrounding tissues without forming a capsule, and that the mode of invasion of the transplanted SCC was similar to that of the biopsy specimen of the patient from whom the material had been obtained. We also found that all three of the SCC cell lines, 3 of the 7 SCC specimens and 2 of the 3 adenoid cystic carcinoma tissues metastasized to the regional lymph node. SCC did not metastasize to the lung, but in two of the three adenoid cystic carcinomas we did see micrometastases to the lung. The study indicates that this method can be used as a model of metastasis in oral squamous cell carcinoma and adenoid cystic carcinoma to show the stages of metastasis in cancer.