Desmoplastic myxoid tumor (DMT), SMARCB1-mutant is a recently proposed brain tumor that occurs in the pineal region of adults. This tumor is characterized by desmoplastic stroma and various degrees ...of myxoid matrix. Tumor cells with low-grade morphology show polyphenotypic immunoreactivity, and rhabdoid cells are rare. We herein present a case with some uncommon features such as no myxoid stroma and slightly elevated proliferating activity. To date, knowledge on the variety of SMARCB1/INI1-deficient tumors of the central nervous system is gradually increasing, encompassing highly aggressive to slow-growing varieties. DMT, SMARCB1-mutant seems to be relatively benign, but careful attention is necessary because SMARCB1/INI1 deficiency is generally a genetic signature of concern.
Epithelioid glioblastoma (E‐GBM) is a rare aggressive variant of IDH‐wildtype glioblastoma newly recognized in the 2016 World Health Organization classification, composed predominantly of monotonous, ...patternless sheets of round cells with laterally positioned nuclei and plump eosinophilic cytoplasm. Approximately 50% of E‐GBM harbor BRAF V600E, which is much less frequently found in other types of glioblastomas. Most E‐GBM are recognized as primary/de novo lesions; however, several E‐GBM with co‐ or pre‐existing lower‐grade lesions have been reported. To better understand associations between E‐GBM and the lower‐grade lesions, we undertook a histological and molecular analysis of 14 E‐GBM, 10 of which exhibited lower‐grade glioma‐like components (8 E‐GBM with co‐existing diffuse glioma‐like components, 1 E‐GBM with a co‐existing PXA‐like component and 1 E‐GBM with a pre‐existing PXA). Molecular results demonstrated that the prevalence of BRAF V600E, TERT promoter mutations and CDKN2A/B homozygous deletions in E‐GBM were 13/14 (93%), 10/14 (71%) and 11/14 (79%), respectively, and concurrent BRAF V600E, TERT promoter mutations and CDKN2A/B homozygous deletions were observed in 7/14 (50%) of E‐GBM. These alterations were also frequently seen in the lower‐grade lesions irrespective of the histology. Genetic analysis including array comparative genomic hybridization performed for 5 E‐GBM with co‐ and pre‐existing lower‐grade components revealed that all molecular changes found in the lower‐grade components were also observed in the E‐GBM components, and additional changes were detected in the E‐GBM components. In conclusion, E‐GBM frequently exhibit BRAF V600E, TERT promoter mutations and CDKN2A/B homozygous deletions and these alterations tend to coexist in E‐GBM. Taken together with the facts that only one PXA preceded E‐GBM among these lower‐grade lesions, and that co‐occurrence of BRAF V600E, TERT promoter mutations and CDKN2A/B homozygous deletions have been reported to be rare in conventional lower‐grade diffuse gliomas, the diffuse glioma‐like components may be distinct infiltrative components of E‐GBM, reflecting intratumoral heterogeneity.
Epithelioid glioblastoma (E‐GBM) is a rare variant of glioblastoma (GBM), characterized by epithelioid cells with eosinophilic round cytoplasm devoid of stellate cytoplasmic processes. A number of ...studies have demonstrated that more than half of E‐GBMs harbor a valine to glutamic acid substitution at position 600 of the serine/threonine‐protein kinase BRAF (BRAF V600E). However, there are no previous reports on E‐GBM with telomerase reverse transcriptase (TERT) promoter mutation in addition to BRAF V600E mutation. Here, we report an E‐GBM case in an 18‐year‐old man with BRAF V600E and TERT promoter mutations. The tumor composed of 80% E‐GBM and 20% diffuse astrocytoma‐like components, and BRAF V600E and TERT promoter mutations were detected in both. E‐GBM generally arises as a primary lesion; however, a few previous cases have been demonstrated to accompany low‐grade areas. Demonstration of concurrent BRAF V600E and TERT promoter mutations in low‐ and high‐grade lesions strongly suggested their identical origin, and acquisition of each mutation may be an early event, possibly playing a pivotal role in the genesis and subsequent progression to E‐GBM.
A multicenter randomized controlled trial was conducted to compare the effectiveness of incisional and nonincisional surgical techniques for treating lower lid epiblepharon in children. The study ...included 89 eyes from 50 children aged 3-15 years (mean, 7.5 ± 2.4 years) with moderate lower lid epiblepharon. Patients were randomly assigned to either incisional (modified Hotz procedure with lid margin splitting; 45 eyes of 25 patients) or nonincisional (44 eyes of 25 patients) surgery groups. Treatment outcomes and changes in astigmatism were evaluated 6 months after surgery. Incisional surgery provided a significantly higher percentage (77.8%) of well-corrected treatment results (P = 0.026; odds ratio, 2.88; 95% confidence interval, 1.07-8.22) than nonincisional surgery (55.4%). The mean change in astigmatism 6 months after surgery was - 0.24 ± 0.42 and - 0.01 ± 0.47 D in the incisional and nonincisional surgery groups, respectively. The improvement in astigmatism was significantly higher in the incisional surgery group than in the nonincisional surgery group (P = 0.008). The incisional surgical treatment for moderate epiblepharon in children resulted in a higher number of well-corrected patients, indicating an absence of both ciliary touch and superficial keratitis as well as statistically significant improvements in astigmatism correction.
Papillary craniopharyngiomas are characterized by the BRAF V600E mutation. Enhancement of glucose metabolism may be involved in the downstream of the BRAF V600E mutation in many types of tumors. ...Glucose metabolism was investigated in craniopharyngioma using immunohistochemical analysis. The study included 29 cases of craniopharyngioma (18 adamantinomatous type ACP, 11 papillary type PCP). Immunohistochemical analysis was performed with anti-glucose transporter-1 (GLUT-1), anti-hexokinase-II (HK-II), anti-BRAF V600E, and anti-beta-catenin antibodies. Expressions of GLUT-1 and HK-II were evaluated using a semiquantitative 4-tiered scale as 0, 1+, 2+, 3+, and divided into negative (0 or 1+) or positive (2+ or 3+) group. GLUT-1 expression level was significantly higher in PCPs than ACPs (0, 1+, 2+, 3+ = 2, 12, 4, 0 cases in ACP, respectively, 0, 1+, 2+, 3+ = 0, 2, 5, 4 in PCP, p = 0.001), and most PCPs were classified into positive group (positive rate, 22.2% 4/18 in ACP, 81.8% 9/11 in PCP; p = 0.003). HK-II expression was also conspicuous in PCPs (0, 1+, 2+, 3+ = 7, 9, 2, 0 cases in ACP, 0, 3, 3, 5 in PCP; p = 0.001), and most of them divided into positive group (positive rate, 11.1% 2/18 in ACP, 72.7% 8/11 in PCP; p = 0.001). Expression patterns of BRAF V600E and beta-catenin reflected the clinicopathological subtypes. Both GLUT-1 and HK-II expressions were prominent in PCP. Glucose metabolism might be more enhanced in PCP than ACP. PCP may use the glucose metabolic system downstream of the BRAF V600E mutant protein.
To examine the causes of congenital nasolacrimal duct obstruction (CNLDO) using dacryoendoscopy, and to evaluate the surgical outcomes of primary transcanalicular endoscopic dacryoplasty.
The ...subjects of this study were a total of 56 eyes of 46 Japanese children aged one to five years old (mean, 29.1 ± 14.0 months old) with clinically diagnosed CNLDO. The blockage was visualized and probed using a dacryoendoscope (MD10 with a 20 G probe, Fiber Tech Co., Ltd., Japan) under general anesthesia. We used a self-retaining bicanalicular lacrimal stent (Lacrifast®, Kaneka Co., Ltd., Japan) for nasolacrimal duct intubation.
In each case the obstruction was found to be caused by a single focal blockage at the distal end of the duct. A nasolacrimal dacryolith was observed in 5 eyes (9%) and successfully removed using the dacryoendoscope. The success rate of probing by subsequent nasolacrimal duct intubation was 100%. No complications were observed.
We obtained a 100% success rate with primary transcanalicular endoscopic dacryoplasty for the treatment of CNLDO. Direct visualization inside the lacrimal passage allowed for precise probing, even in infants, leading to successful treatment of CNLDO without any complications.
An 82‐year‐old man, who was healthy and had worked as a farmer, experienced worsening neurological symptoms over a seven‐month period, which eventually caused his death. Multiple fluctuating brain ...lesions were detected radiographically. Clinically, sarcoidosis was ranked high among the differential diagnoses because of the presence of skin lesions showing granulomatous inflammation, confirmed by biopsy. The patient's cerebrospinal fluid was also examined, but no definitive diagnosis was made while he was alive. An autopsy revealed multiple granulomatous amebic encephalitis lesions in the brain. Genetic and immunohistochemical analyses identified Balamuthia (B.) mandrillaris, a free‐living ameba, which resides in soil and fresh water, as the causative organism. A retrospective examination revealed B. mandrillaris in the biopsied skin as well as cerebrospinal fluid, strongly suggesting that the ameba had spread into the brain percutaneously. Few studies have detailed the cutaneous pathology of B. mandrillaris infections. In general, granulomatous amebic encephalitis is extremely difficult to diagnose without autopsy, but the present case provides a clue that could allow similar cases to be diagnosed earlier; that is, the presence of skin lesions.
Purpose
Dysembryoplastic neuroepithelial tumors (DNTs) are slow-growing glioneuronal tumors, and their genetic backgrounds are getting unveiled. Recently,
fibroblast growth factor receptor 1
internal ...tandem duplication (
FGFR1
-ITD) of the tyrosine kinase domain (TKD) has been demonstrated by whole-genome sequencing.
Methods and Results
Here, we analyzed 22 DNTs using multiplex ligation-dependent probe amplification (MLPA) with formalin-fixed paraffin-embedded specimens and found a copy number gain in TKD of
FGFR1
(13 cases, 59%), which suggested the presence of
FGFR1
-ITD. Another 5 DNTs harbored
FGFR1
hot spot mutations including a double mutant case, and
FGFR1
alterations were detected in 18 DNTs (82%). The
BRAF
V600E mutation, another important mutation in DNTs, was not observed.
Conclusions
With recent findings of less frequent or absent
FGFR1
-ITD in pilocytic astrocytomas or rosette-forming glioneuronal tumors, the analysis of
FGFR1
aberrations, especially
FGFR1
-ITD, was suggested to be helpful to discriminate DNTs from their histological mimics.
Dysembryoplastic neuroepithelial tumors (DNTs) are regarded as benign glioneuronal neoplasms because of their excellent outcomes; however, rare DNTs show malignant transformation. We herein described ...a case of DNT showing malignant transformation. The patient had intractable epilepsy caused by a tumor at 1 year of age and partial resection was performed. After surgery, the residual tumor showed regrowth and surgery was performed again at 4 years of age. The resected tumor showed the typical histological features of DNT, such as specific glioneuronal elements and alveolar structures. Tumor regrowth was detected again at 6 years of age, and the patient underwent gross total resection. Histologically, the tumor was composed of a high-grade glial component mixed with atypical neuronal cells, and the diagnosis of an anaplastic glioneuronal tumor was made. Genetically, DNT and the anaplastic glioneuronal tumor both shared a copy number gain of the tyrosine kinase domain of
fibroblast growth factor receptor 1
(
FGFR1
), as demonstrated by multiplex ligation-dependent probe amplification (MLPA), corresponding to internal tandem duplication (ITD). A frequent
FGFR1
-ITD in DNT was previously reported. To the best of our knowledge, an identical mutation between primary and transformed DNT has not yet been demonstrated by MLPA.
Adult cerebellar high-grade gliomas (HGG) are rare and their molecular basis has not been fully elucidated. Although a diffuse midline glioma H3 K27M-mutant, a recently characterized variant of HGG, ...was reported to occasionally occur in the cerebellum, adult cases were rarely tested for this mutation; only five mutant cases have been reported to date. It currently remains unknown whether H3 K27M-mutant cerebellar gliomas share common histological features or have a uniformly dismal prognosis. In the present study, we assessed the prevalence of histone H3 K27M mutations in ten adult cerebellar HGG, identifying two
H3F3A
-mutant cases. One case was a 70-year-old female with a cystic lesion. Histologically, the tumor was considered to be glioblastoma; however, a part of the tumor exhibiting low proliferative activity appeared to be consistent with long-standing H3 K27M-mutant tumors in the literature. Another case was a 69-year-old male. The tumor showed a distinct circumscribed histology with minimal astrocytic differentiation, suggesting a nosological issue in the diagnosis of diffuse midline glioma. More cerebellar tumors need to be tested for H3 K27M mutations to clarify the clinical and histopathological spectra of this tumor.
PDF
