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Lacrimal punctal agenesis is an extremely rare condition with an unclear genetic basis. Here, we report a 3-year-old male patient harboring a hemizygous variant in glypican 4 (GPC4), which causes Keipert syndrome, who presented with complete lacrimal punctal agenesis, distinctive craniofacial features, mild developmental delay, mild intellectual disability, and autism. The craniofacial features included a prominent forehead, epicanthus, depressed and broad nasal bridge, hypoplastic columella, midface hypoplasia, tented upper lip, and low-set ears. Proband exome sequencing identified a hemizygous variant in GPC4: NM_001448.3:c.1051C > T (p.Arg351*). The GPC4 variant was inherited from his heterozygous mother; X-inactivation followed a skewed pattern in his mother. This patient demonstrated clinical features consistent with Keipert syndrome including craniofacial features, brachydactyly, broad distal phalanx, broad first toe, and mild developmental delay; however, agenesis of the lacrimal puncta has not been reported previously in Keipert syndrome. Our findings suggest that GPC4, which encodes a heparan-sulfate proteoglycan, may play an important role in lacrimal morphogenesis. Our observations also suggest that Keipert syndrome should be considered in patients with lacrimal punctal agenesis.
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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.
Assuntos
Amebíase , Amoeba , Balamuthia mandrillaris , Dermatite , Encefalite , Encefalite Infecciosa , Idoso de 80 Anos ou mais , Amebíase/diagnóstico , Autopsia , Encéfalo/patologia , Dermatite/patologia , Granuloma/patologia , Humanos , Encefalite Infecciosa/patologia , Masculino , Estudos RetrospectivosRESUMO
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.
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Variações do Número de Cópias de DNA , Reação em Cadeia da Polimerase Multiplex , Mutação , Neoplasias Neuroepiteliomatosas/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Adolescente , Adulto , Biomarcadores Tumorais/genética , Criança , Pré-Escolar , Classe I de Fosfatidilinositol 3-Quinases/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Multiplex/métodos , Neoplasias Neuroepiteliomatosas/diagnóstico , Neoplasias Neuroepiteliomatosas/patologia , Domínios Proteicos , Proteínas Proto-Oncogênicas B-raf/genética , Adulto JovemRESUMO
A 51-year-old man presented with a 2-week history of malaise. MRI revealed a large solid and cystic lesion with ring enhancement measuring 6.5 cm in diameter in the right frontal lobe. Histologically, the tumor consisted of various components: diffuse growth of atypical astrocytic cells consistent with glioblastoma, fascicular proliferation of atypical spindle cells such as fibrosarcoma, clusters of primitive neuronal cells, and foci of ependymal cells. The sarcomatous component also focally exhibited chondroid and osteoid differentiation. Immunohistochemically, tumor cells in the primitive neuronal component were immunoreactive for synaptophysin and CD56. The spindle cells were immunopositive for Slug and Twist, regulators of epithelial-mesenchymal transition. Direct DNA sequencing demonstrated C228T mutation in the TERT promoter in astrocytic, sarcomatous and primitive neuronal components, suggesting their identical origin. Although a few cases of gliosarcoma with primitive neuronal differentiation have previously been described, the finding that neuronal, glial and sarcomatous components share an identical mutation of the TERT promoter has not been reported. The tumor recurred at the original site 11 months after the first surgery. Interestingly, the recurrent tumor was composed exclusively of a glioblastomatous component, unlike past cases of recurrent gliosarcoma.
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Cerebellar high-grade gliomas are rare, and likely to affect younger patients compared with those of cerebral origin. Recent genetic analyses have revealed that isocitrate dehydrogenase (IDH) 1/2 mutations are rare in infratentorial gliomas. In this paper, we report two elderly cases of IDH-mutated cerebellar high-grade glioma with unusual histological features and uncommon patient ages. One case was an 83-year-old man, whose tumor was predominantly composed of densely packed round-to-polygonal epithelioid cells. The other was a 75-year-old woman's high-grade astrocytoma characterized by cord-like structures and the perivascular papillary arrangements with varying amounts of myxoid matrix. The former harbored IDH1 R132H mutation, whereas the latter had IDH2 R172K mutation. According to our literature review, eight cases of IDH-mutated infratentorial gliomas including the present cases have been reported, and four had mutations other than IDH1 R132H. Moreover, we herein report the first elderly case of IDH2-mutation. Although the number is limited, IDH-mutant infratentorial diffuse gliomas may have clinical, histological and genetic features different from supratentorial cases.
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A 40-year-old man was admitted to our hospital because of disorientation and mild left-sided weakness. Radiological examination revealed a solid and cystic tumor in the right temporal lobe, and total resection was performed. Histologically, the tumor was composed mainly of low-grade gangiloglioma and had some high-grade glial components with focal necrosis and microvascular proliferations. In the high-grade component, there were epithelioid cells with round cytoplasm and eccentric nuclei. The high-grade area with epithelioid cells was intermingled within the low-grade area, which suggests that epithelioid cells were an anaplastic transformation of ganglioglioma. The epithelioid cells were histologically similar to neoplastic cells of epithelioid glioblastoma (E-GBM), a rare aggressive variant of isocitric dehydrogenase wild-type glioblastoma. A BRAF V600E mutation, frequently observed in E-GBM, was detected in both the ganglioglioma and epithelioid cell components. The epithelioid cells were mitotically active, which suggests that if the surgery was delayed, the histological appearance might have eventually evolved into E-GBM. Indeed, a case of pleomorphic xanthoastrocytoma which transformed into E-GBM after a long latency was reported elsewhere. This is the first report to describe focal epithelioid cells in anaplastic ganglioglioma.
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Neoplasias Encefálicas/patologia , Células Epitelioides/patologia , Ganglioglioma/patologia , Adulto , Humanos , Masculino , Lobo Temporal/patologiaRESUMO
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.
Assuntos
Astrocitoma/genética , Neoplasias Encefálicas/genética , Glioblastoma/genética , Mutação , Neoplasias Primárias Múltiplas/genética , Regiões Promotoras Genéticas , Proteínas Proto-Oncogênicas B-raf/genética , Telomerase/genética , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/patologia , Adolescente , Antineoplásicos Alquilantes/uso terapêutico , Astrocitoma/diagnóstico por imagem , Astrocitoma/patologia , Astrocitoma/terapia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/terapia , Irradiação Craniana , Dacarbazina/análogos & derivados , Dacarbazina/uso terapêutico , Evolução Fatal , Glioblastoma/diagnóstico por imagem , Glioblastoma/patologia , Glioblastoma/terapia , Humanos , Imageamento por Ressonância Magnética , Masculino , Neoplasias Primárias Múltiplas/diagnóstico por imagem , Neoplasias Primárias Múltiplas/patologia , Neoplasias Primárias Múltiplas/terapia , Procedimentos Neurocirúrgicos , Temozolomida , Lobo Temporal/cirurgiaAssuntos
Ressecção Endoscópica de Mucosa , Neoplasias Esofágicas/cirurgia , Perfuração Esofágica/cirurgia , Carcinoma de Células Escamosas do Esôfago/cirurgia , Complicações Intraoperatórias/cirurgia , Escleroderma Sistêmico/patologia , Neoplasias Esofágicas/complicações , Neoplasias Esofágicas/patologia , Perfuração Esofágica/complicações , Perfuração Esofágica/patologia , Carcinoma de Células Escamosas do Esôfago/complicações , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Humanos , Complicações Intraoperatórias/patologia , Pessoa de Meia-Idade , Músculo Liso/patologia , Atrofia Muscular/patologia , Pneumotórax/etiologia , Escleroderma Sistêmico/complicações , Enfisema Subcutâneo/etiologiaRESUMO
Purpose: This prospective observational study aimed to explore the diversity in lacrimal pathway morphology among patients with congenital nasolacrimal duct obstruction (CNLDO) by examining dacryocystography (DCG) images. Patients and Methods: The study included 64 patients who underwent DCG before undergoing general anesthesia probing for unilateral CNLDO. Several parameters were measured from the lateral view of the DCG images: (1) the lacrimal sac (LS) and the nasolacrimal duct (NLD) angle, (2) the angle formed by the superior orbital rim (SOR), LS, and the NLD, (3) LS length, and (4) bony NLD length. Additionally, frontal views of the DCG images were utilized to measure (5) LS-NLD angle and (6) LS angle concerning the midline. Results: The average age of the patients was 34.3 months. The mean ± standard deviation of the measurements of the above parameters was (1) -1.2° ± 16.5° (range: -44.6° ± 46.6°), (2) -5.0° ± 10.3° (range: -24.0° ± 19.0°), (3) 10.2 ± 2.4 mm (range: 6.5-16.0 mm), (4) 8.0 ± 2.5 mm (range: 3.1-14.8 mm), (5) 15.6° ± 11.2° (range: -16.8° ± 41.0°), and (6) 15.1 ± 5.2° (range: 3.3°-29.8°). All parameters, except for parameter (3), conformed to a normal distribution. Conclusion: This study provides valuable anthropometric data derived from DCG images, highlighting the substantial variability in lacrimal pathway morphology among patients with CNLDO. Furthermore, anatomical constraints made probing with a straight metal bougie anatomically infeasible in 25.0% of the patients included in this study.
Understanding the morphology of the lacrimal pathway is crucial for the successful probing treatments in patients with congenital nasolacrimal duct obstruction (CNLDO). This study represents an initial effort to quantify anthropometric parameters of the lacrimal drainage system through dacryocystography images, specifically aiming to highlight the limitations of blind probing procedure. The results underscore significant variations in the morphology of the lacrimal drainage system among patients, which could impact diagnostic approaches and treatment strategies. Additionally, the findings suggest that patients with CNLDO who do not respond to blind probing may have underlying anatomical complexities. Therefore, rather than relying on repeated blind probing, employing dacryoendoscopy-guided probing under direct visualization could offer a more effective therapeutic alternative for complicated cases of CNLDO.
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AIM: Congenital nasolacrimal duct obstruction (CNLDO) is the most common cause of epiphora and mucous discharge in the newborn. We conducted a multicentre randomised controlled trial to determine whether Crigler massage promotes the resolution of CNLDO in infants under 1 year of age. METHODS: A total of 102 infants aged 3-11 months with unilateral CNLDO were enrolled in the study. Patients were randomly assigned to the massage and non-massage groups (n=51/group). As an allocation adjustment factor, the patients were divided into age groups of 3-5, 6-8 and 9-11 months. In the massage group, the guardian performed 10 strokes two times per day for each day until resolution or 1 month. The primary endpoint was a comparison of the 1-month resolution rate in the massage and non-massage groups. RESULTS: This study included 49 male and 53 female patients with a mean age of 6.4±2.4 months. Overall, in this study, the resolution rate was not significantly different between the massage and non-massage groups (31.4% and 33.3%, respectively). However, the resolution rate was higher in the massage group in the 3-5 months age group among the protocol-compliant patients after excluding those with insufficient massage frequency (the massage group, 68.8% and the non-massage group, 28.6%, p=0.022). CONCLUSIONS: There was no increase in the resolution rate after 1 month of lacrimal sac massage in patients 3-11 months old with unilateral CNLDO. However, in protocol-compliant younger age groups, Crigler massage may be effective. TRIAL REGISTRATION NUMBER: UMIN Clinical Trial Registry (UMIN000032840; www.umin.ac.jp/).
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Obstrução dos Ductos Lacrimais , Massagem , Ducto Nasolacrimal , Humanos , Masculino , Feminino , Lactente , Obstrução dos Ductos Lacrimais/congênito , Obstrução dos Ductos Lacrimais/terapia , Massagem/métodos , Resultado do Tratamento , SeguimentosRESUMO
We describe 3 infants with congenital dacryocystocele resistant to conservative treatment who were treated with a novel, simple intranasal cyst marsupialization (ICM) technique. Otoscopy-guided ICM was performed by an otolaryngologist in the manner of otoscopic myringotomy for cases with nasal cyst distension. All 3 infants were treated successfully by a single surgical procedure under topical anesthesia in an office setting.
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Cistos , Dacriocistorinostomia , Obstrução dos Ductos Lacrimais , Lactente , Humanos , Otoscopia , Endoscopia/métodos , Obstrução dos Ductos Lacrimais/congênito , Cistos/cirurgia , Cistos/congênitoRESUMO
Glioneuronal tumors (GNTs) are rare neoplasms consisting of both glial and neuronal components. Among the GNTs, dysembryoplastic neuroepithelial tumors (DNTs), papillary glioneuronal tumors (PGNTs), and rosette-forming glioneuronal tumors of the fourth ventricle (RGNTs) share the character of being mainly composed of small round Olig2-positive tumor cells. Using immunohistochemistry and fluorescence in situ hybridization, we examined a series of 35 GNT cases (11 DNTs, 15 PGNTs and 9 RGNTs) on the characteristics of Olig2-positive tumor cells. Histologically, Olig2-positive cells showed small round forms in most GNTs; however, there were a small number of Olig2-positive cells with neuronal morphology only in a PGNT case. These cells expressed both glial and neuronal markers by double immunostaining. With regard to labeling indices and intensity, only PGNT cells expressed neuronal markers, including α-internexin and neurofilament. These findings also suggest that some Olig2-positive PGNT cells may show neuronal differentiation. In GNTs, a considerable number of Olig2-positive cells showed immunopositivity for cyclin D1 and/or platelet-derived growth factor receptor alpha (PDGFRα), which are markers for oligodendrocyte progenitor cells. These immunostainings were particularly strong in DNTs. In RGNTs, Olig2-positive cells formed "neurocytic rosettes". Furthermore, they were also immunopositive for glial markers, including GFAP, PDGFRα and cyclin D1. These findings indicate the heterogeneous characteristics of Olig2-positive cells in GNTs, and some of them also exhibited neuronal features. So it is possible that a part of Olig2-positive GNT cells have characteristics similar to those of progenitor cells.
Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Neoplasias Encefálicas/genética , Glioma/genética , Proteínas do Tecido Nervoso/genética , Neuroglia/patologia , Neurônios/patologia , Células-Tronco/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/ultraestrutura , Criança , Pré-Escolar , Feminino , Glioma/patologia , Glioma/ultraestrutura , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Masculino , Microscopia Eletrônica , Pessoa de Meia-Idade , Fator de Transcrição 2 de Oligodendrócitos , Oligodendroglia/patologia , Formação de Roseta , Adulto JovemRESUMO
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.
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Astigmatismo , Pestanas , Ferida Cirúrgica , Humanos , Criança , Estudos Retrospectivos , Resultado do Tratamento , CórneaRESUMO
BACKGROUND: Thymoma is associated with autoimmune diseases. Myasthenia gravis is frequently associated with thymoma, but cases of thymoma complicated by alopecia areata are very rare. In this report, we present a case of thymoma associated with alopecia areata, but without Myasthenia gravis. CASE PRESENTATION: A 60-year-old woman had a complaint of rapid progression of alopecia areata. A hair follicular biopsy was performed, which showed the infiltration of CD8-positive lymphocytes. She was prescribed topical steroids for 2 months prior to surgery, but her hair loss was not improved. Screening computed tomography showed a mass in the anterior mediastinum, which was suspected to be a thymoma. Myasthenia gravis was ruled out because she had no relevant symptoms or physical findings, and no anti-acetylcholine receptor antibodies were detected in serum. We performed a transsternal extended thymectomy based on a diagnosis of thymoma Masaoka stage I, without myasthenia gravis. Pathological examination showed Type AB thymoma, Masaoka stage II. The chest drainage tube was removed on postoperative day 1, and the patient was discharged on postoperative day 6. The patient has continued topical steroids and showed improvement 2 months postoperatively. CONCLUSIONS: Although alopecia areata is a rare complication in thymoma cases without myasthenia gravis, thoracic surgeons need to keep this condition in mind because alopecia reduces the patient's quality of life.
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OBJECTIVE: Ghost cell odontogenic carcinoma (GCOC) is a rare tumor that can sometimes occur from dentinogenic ghost cell tumor (DGCT). STUDY DESIGN: We report a case of GCOC arising from DGCT that underwent long-term follow-up with multiple biopsies. The biopsy specimens were analyzed using a next-generation sequencing cancer panel. RESULTS: Histopathology of the resected tumor revealed that the boundary between benign and malignant components was clear. In immunohistochemistry, the nuclei of malignant tumor cells were positive for ß-catenin and LEF-1. CTNNBI mutation was detected in all 4 biopsy specimens, and all of these mutations were identical (c.98C>G (p.Ser33Cys)). No other gene mutations that could definitively cause malignant transformation were detected. CONCLUSIONS: This case suggested that GCOC and DGCT are ghost cell neoplasms caused by a common mutation of CTNNB1 and that the malignant cells of GCOC are derived from cells that specifically differentiate into ghost cells.
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Carcinoma , Neoplasias Maxilomandibulares , Tumores Odontogênicos , Transformação Celular Neoplásica/patologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Neoplasias Maxilomandibulares/patologia , Tumores Odontogênicos/genética , Tumores Odontogênicos/patologiaRESUMO
Bone marrow necrosis (BMN) occurs most frequently in hematological malignancies and sometimes in non-hematological disorders. Lymphoid diseases causing necrosis are regarded as high-grade disease. B-lymphoblastic leukemia/lymphoma is the most common malignant cause of BMN. Here, we present two patients with follicular lymphoma (FL) and MYC gene abnormalities who developed BMN. In one case of BMN, the necrosis disappeared in response to chemotherapy, and the patient survived with complete remission. In the other case, BMN remained even after chemotherapy, and effective chemotherapy could not be administered due to suppressed hematopoiesis, which led to the lymphoma worsening and the patient's death. Indolent lymphomas, such as FL, as in these cases, have the potential to develop BMN. It is important to detect the development of BMN and administer chemotherapy early to improve patient prognosis, since severe BMN prevents patients from receiving effective treatment.
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Linfoma Folicular , Linfoma não Hodgkin , Humanos , Genes myc , Medula Óssea/patologia , Linfoma Folicular/tratamento farmacológico , Linfoma Folicular/genética , Linfoma Folicular/patologia , Linfoma não Hodgkin/patologia , Necrose/patologiaRESUMO
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.
Assuntos
Tumor Desmoplásico de Pequenas Células Redondas/genética , Proteína SMARCB1/genética , Adulto , Neoplasias Encefálicas/genética , Proteínas Cromossômicas não Histona/genética , Proteínas de Ligação a DNA/genética , Tumor Desmoplásico de Pequenas Células Redondas/metabolismo , Feminino , Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Glândula Pineal/patologia , Pinealoma/genética , Pinealoma/patologia , Tumor Rabdoide/patologia , Proteína SMARCB1/metabolismo , Sarcoma/genética , Fatores de Transcrição/genética , Transcriptoma/genéticaRESUMO
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.
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Craniofaringioma/genética , Transportador de Glucose Tipo 1/genética , Hexoquinase/genética , Adulto , Craniofaringioma/enzimologia , Craniofaringioma/metabolismo , Feminino , Glucose/metabolismo , Transportador de Glucose Tipo 1/metabolismo , Hexoquinase/metabolismo , Humanos , Imunoquímica , Masculino , Pessoa de Meia-Idade , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas B-raf/metabolismoRESUMO
BACKGROUND: No standard treatment for anorectal fistula cancer, such as multidisciplinary therapy, has been established due to the rarity of the disease. Herein, we investigated patients with cancer associated with anorectal fistula who underwent surgery to clarify the clinicopathological characteristics and to propose future perspectives for treatment strategies. CASE PRESENTATION: Seven patients with cancer associated with anorectal fistula who underwent rectal amputation in our institute were analyzed with regard to clinical characteristics, pathological findings, surgical results, and prognosis. Four cases had Crohn's disease as an underlying cause. All seven cases were diagnosed as advanced stage. Preoperative [18F]-fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography/computed tomography (FDG-PET/CT) showed abnormal FDG accumulation in six cases including four mucinous adenocarcinomas. Three cases that received preoperative hyperthermo-chemoradiotherapy achieved pathological R0 resection. Postoperative recurrence was observed in four cases including three with Crohn's disease and one resulting in death. CONCLUSIONS: Anorectal fistula cancer is rare and difficult to be diagnosed at early stages. Mucinous adenocarcinoma associated with anorectal fistula tends to exhibit abnormal FDG accumulation by FDG-PET/CT unlike common colorectal mucinous adenocarcinoma. Preoperative hyperthermo-chemoradiotherapy may be effective in obtaining pathological complete resection.
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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.