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Primary angiitis of the central nervous system (CNS) is an uncommon inflammatory disorder, with highly variable clinical presentation. It needs to be differentiated from several mimickers, such as CNS involvement in systemic vasculitides, connective tissue disorders, infectious disease, and leukodystrophy as well as neoplastic diseases. The diagnosis requires a combination of clinical and laboratory investigations, multimodal imaging, and histopathological examination, which should be available for confirmation. In the present paper, the histopathological features of primary angiitis of the CNS are described and highlighted to help pathologists avoid misdiagnosis of a treatable acquired disease.
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Vasculite do Sistema Nervoso Central , Humanos , Vasculite do Sistema Nervoso Central/diagnóstico , Vasculite do Sistema Nervoso Central/patologia , Diagnóstico Diferencial , Sistema Nervoso Central/patologia , Sistema Nervoso Central/diagnóstico por imagemRESUMO
The diagnosis of synchronous carcinomas, involving both the endometrium and ovaries, is not a rare finding in gynecologic pathology and represents a challenge with implications on tumor staging and therapeutic decision-making. A mono-institutional series of 11 metastatic and 6 paired synchronous endometrial and ovarian carcinomas were reviewed by 2 expert pathologists based on previously published histopathologic criteria. The series was investigated for DNA mismatch repair proteins, p53, and POLE status and was subject to DNA-based next-generation sequencing targeting 67 cancer-related genes. Out of 17 pairs, 16 featured the same histotype (10 endometrioid, 4 serous high-grade, and 2 clear cells). By using WHO 2020 criteria, 11 couples of tumors were confirmed as metastatic and 6 couples were confirmed as independent. Based on next-generation sequencing analysis, 16 of 17 cases (11 metastatic and 5 independent) of our series showed evidence of a clonal relationship between endometrial and ovarian carcinomas. In metastatic cases, the adverse outcome was associated with nonendometrioid/high-grade endometrioid histotype and with the p53-abnormal molecular subtype. Four cases originally fulfilling clinicopathological criteria of independent endometrial and ovarian carcinomas were clonally related, low-grade endometrioid histotype and POLE-mut, mismatch repair deficient, and no specific molecular profile molecular subtypes; no adverse event was recorded in this group. In summary, the molecular characterization of synchronous gynecologic carcinomas confirms their clonal origin in most cases. However, the results of our study point out that the clinical behavior of these tumors seems to be determined by the presence of high-risk WHO 2020 histologic criteria and molecular features (i.e. p53-abnormal), rather than the monoclonal origin.
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Wilms tumor (WT), or nephroblastoma, is an uncommon malignant neoplasm occurring in the kidney of pediatric patients. Its extrarenal location is extremely rare and has been reported in various sites, including the female genital tract, with only 9 cases arising in the uterine corpus. We present the case of an adult woman who underwent total abdominal hysterectomy due to a uterine mass causing persistent abdominal pain. The characteristic triphasic morphology (composed of epithelial, stromal, and blastemal elements) supported by a broad immunohistochemical panel, along with the imaging exclusion of a renal neoplasm, was diagnostic of WT of the uterus. For the first time, a comprehensive genomic profiling of a uterine primary WT was also performed by next-generation sequencing, disclosing alterations at the level of copy number variations in the genes ERBB2, FGFR23, FGF6, FGFR2, and RPS6KB1. All previously reported uterine cases were reviewed, with a summary of their main clinicopathologic characteristics, and the main differential diagnoses are presented. Further reports are needed to improve our knowledge about prognostic factors, clinical behavior and molecular alterations that could guide appropriate therapeutic decision making.
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Neoplasias Renais , Neoplasias Uterinas , Tumor de Wilms , Adulto , Feminino , Humanos , Variações do Número de Cópias de DNA , Genômica , Neoplasias Renais/diagnóstico , Neoplasias Renais/genética , Neoplasias Renais/cirurgia , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/genética , Neoplasias Uterinas/cirurgia , Útero , Tumor de Wilms/diagnóstico , Tumor de Wilms/genética , Tumor de Wilms/cirurgiaRESUMO
Objective: The use of standardized structured reports (SSR) and suitable terminologies like SNOMED-CT can enhance data retrieval and analysis, fostering large-scale studies and collaboration. However, the still large prevalence of narrative reports in our laboratories warrants alternative and automated labeling approaches. In this project, natural language processing (NLP) methods were used to associate SNOMED-CT codes to structured and unstructured reports from an Italian Digital Pathology Department. Methods: Two NLP-based automatic coding systems (support vector machine, SVM, and long-short term memory, LSTM) were trained and applied to a series of narrative reports. Results: The 1163 cases were tested with both algorithms, showing good performances in terms of accuracy, precision, recall, and F1 score, with SVM showing slightly better performances as compared to LSTM (0.84, 0.87, 0.83, 0.82 vs 0.83, 0.85, 0.83, 0.82, respectively). The integration of an explainability allowed identification of terms and groups of words of importance, enabling fine-tuning, balancing semantic meaning and model performance. Conclusions: AI tools allow the automatic SNOMED-CT labeling of the pathology archives, providing a retrospective fix to the large lack of organization of narrative reports.
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Processamento de Linguagem Natural , Systematized Nomenclature of Medicine , Humanos , Estudos RetrospectivosRESUMO
OBJECTIVE: Serous tubal intraepithelial carcinoma (STIC) is currently considered the precursor lesion of pelvic high-grade serous carcinoma. The management of STIC diagnosed after risk-reducing salpingo-oophorectomy (RRSO) in women with BRCA1-2 variants remains unclear. The aim of our study was to evaluate the incidence of STIC, serous tubal intraepithelial lesions (STIL) and occult invasive cancer (OC) and to determine the long-term outcomes of these patients. METHODS: We conducted a retrospective study of patients with BRCA 1-2 variants who underwent RRSO between January-2010 and Dicember-2020 at the Clinic of Gynaecology of University of Padova. INCLUSION CRITERIA: women with a negative pelvic examination at the last screening prior to RRSO, patients with fallopian tubes analysed using the SEE-FIM protocol. EXCLUSION CRITERIA: patients with a positive gynaecologic screening or with ovarian/tubal cancer prior to RRSO. RESULTS: We included 153 patients. STICs were diagnosed in 4 patients (2.6%) and STILs in 6 patients (3.9%). None of the patients with STIC underwent restaging surgery or adjuvant chemotherapy; all patients were followed closely every 6 months. None of the patients developed primary peritoneal carcinomas (PPCs) with a median FUP of 54.5 months (15-106). OC was diagnosed in 3 patients (2%). All patients with OC underwent staging surgery, and one patient developed a peritoneal carcinoma (PC) after 18 months by staging surgery. CONCLUSION(S): The incidence of STIC, STIL and OC after RRSO in BRCA1-2 variants was low. Our results demonstrated that long-term close surveillance in patients diagnosed with STIC should be considered a possible management strategy.
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Cistadenocarcinoma Seroso/epidemiologia , Neoplasias das Tubas Uterinas/epidemiologia , Procedimentos Cirúrgicos Profiláticos/estatística & dados numéricos , Salpingo-Ooforectomia/estatística & dados numéricos , Adulto , Proteína BRCA1/genética , Proteína BRCA2/genética , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/prevenção & controle , Neoplasias das Tubas Uterinas/genética , Neoplasias das Tubas Uterinas/patologia , Neoplasias das Tubas Uterinas/prevenção & controle , Tubas Uterinas/cirurgia , Feminino , Seguimentos , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Humanos , Incidência , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Conduta Expectante/estatística & dados numéricosRESUMO
Meningeal solitary fibrous tumors (SFTs) and hemangiopericytomas (HPCs) had been combined into a single classification until 2016. Recurrence and metastases rates are still understudied, especially for spinal SFT/HPCs. Here, we describe CNS SFT/HPCs and predictors for recurrence, metastases, and death, in spinal and intracranial SFT/HPCs, separately. We collected data from studies with patient-level data available on primary SFT/HPCs from multiple online databases. Clinico-demographic data, surgical outcomes, recurrence, metastases, and death rates were abstracted. We used logistic and Cox regression models to identify predictors for recurrence, metastases, and death for spinal and intracranial SFT/HPCs. Twenty-nine studies (368 patients) were included. Higher histological grade and subtotal resection were associated with recurrence (p values < 0.05), while higher histological grade and recurrence (p values < 0.005) were associated with metastases formation. Time to recurrence (p < 0.005) and metastases (p < 0.001) formation were shorter for spinal SFT/HPCs. Death rates were higher among intracranial SFT/HPC patients (p value = 0.001). Among patients with higher histological grade, rates of metastases formation were different between intracranial and spinal SFT/HPCs. Risk of metastases was higher in the first 5 years from surgery for both intracranial and spinal SFT/HPCs. Meningeal SFT/HPCs patients have high rates of recurrence and metastasis, which occur mostly within the first 5 years after diagnosis. Spinal and intracranial SFT/HPCs show similar behavior, but spinal SFT/HPCs tend to develop metastases and recurrences in a shorter interval of time. Careful follow-up for spinal SFT/HPCs should be considered because spinal cases seem to be slightly more aggressive and require more attention.
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Neoplasias Encefálicas/mortalidade , Hemangiopericitoma/mortalidade , Neoplasias Meníngeas/mortalidade , Recidiva Local de Neoplasia/mortalidade , Tumores Fibrosos Solitários/mortalidade , Neoplasias da Coluna Vertebral/mortalidade , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/cirurgia , Hemangiopericitoma/diagnóstico , Hemangiopericitoma/cirurgia , Humanos , Neoplasias Meníngeas/diagnóstico , Neoplasias Meníngeas/cirurgia , Metástase Neoplásica , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/cirurgia , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Tumores Fibrosos Solitários/diagnóstico , Tumores Fibrosos Solitários/cirurgia , Neoplasias da Coluna Vertebral/diagnóstico , Neoplasias da Coluna Vertebral/cirurgia , Taxa de Sobrevida/tendênciasRESUMO
BACKGROUND: Platinum-based drugs such as Cisplatin are commonly employed for cancer treatment. Despite an initial therapeutic response, Cisplatin treatment often results in the development of chemoresistance. To identify novel approaches to overcome Cisplatin resistance, we tested Cisplatin in combination with K+ channel modulators on colorectal cancer (CRC) cells. METHODS: The functional expression of Ca2+-activated (KCa3.1, also known as KCNN4) and voltage-dependent (Kv11.1, also known as KCNH2 or hERG1) K+ channels was determined in two CRC cell lines (HCT-116 and HCT-8) by molecular and electrophysiological techniques. Cisplatin and several K+ channel modulators were tested in vitro for their action on K+ currents, cell vitality, apoptosis, cell cycle, proliferation, intracellular signalling and Platinum uptake. These effects were also analysed in a mouse model mimicking Cisplatin resistance. RESULTS: Cisplatin-resistant CRC cells expressed higher levels of KCa3.1 and Kv11.1 channels, compared with Cisplatin-sensitive CRC cells. In resistant cells, KCa3.1 activators (SKA-31) and Kv11.1 inhibitors (E4031) had a synergistic action with Cisplatin in triggering apoptosis and inhibiting proliferation. The effect was maximal when KCa3.1 activation and Kv11.1 inhibition were combined. In fact, similar results were produced by Riluzole, which is able to both activate KCa3.1 and inhibit Kv11.1. Cisplatin uptake into resistant cells depended on KCa3.1 channel activity, as it was potentiated by KCa3.1 activators. Kv11.1 blockade led to increased KCa3.1 expression and thereby stimulated Cisplatin uptake. Finally, the combined administration of a KCa3.1 activator and a Kv11.1 inhibitor also overcame Cisplatin resistance in vivo. CONCLUSIONS: As Riluzole, an activator of KCa3.1 and inhibitor of Kv11.1 channels, is in clinical use, our results suggest that this compound may be useful in the clinic to improve Cisplatin efficacy and overcome Cisplatin resistance in CRC.
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Cisplatino/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Canal de Potássio ERG1/antagonistas & inibidores , Canais de Potássio Ativados por Cálcio de Condutância Intermediária/metabolismo , Animais , Apoptose/efeitos dos fármacos , Benzotiazóis/farmacologia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cisplatino/farmacocinética , Neoplasias Colorretais/patologia , Resistencia a Medicamentos Antineoplásicos , Sinergismo Farmacológico , Canal de Potássio ERG1/metabolismo , Células HCT116 , Células HT29 , Humanos , Concentração Inibidora 50 , Camundongos , Bloqueadores dos Canais de Potássio/farmacologia , Pirazóis/farmacologia , Riluzol/farmacologiaRESUMO
Nowadays pathology laboratories are worldwide facing a digital revolution, with an increasing number of institutions adopting digital pathology (DP) and whole slide imaging solutions. Despite indeed providing novel and helpful advantages, embracing a whole DP workflow is still challenging, especially for wide healthcare networks. The Azienda Zero of the Veneto Italian region has begun a process of a fully digital transformation of an integrated network of 12 hospitals producing nearly 3 million slides per year. In the present article, we describe the planning stages and the operative phases needed to support such a disruptive transition, along with the initial preliminary results emerging from the project. The ultimate goal of the DP program in the Veneto Italian region is to improve patients' clinical care through a safe and standardized process, encompassing a total digital management of pathology samples, easy file sharing with experienced colleagues, and automatic support by artificial intelligence tools.
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OBJECTIVE: The present study aimed to assess long-term follow-up outcomes in women with in situ/microinvasive adenocarcinoma (AC) of the uterine cervix treated conservatively. METHODS: Retrospective multi-institutional study including women with early glandular lesions and 5-year follow-up undergoing fertility-sparing treatment. Independent variables associated with recurrence were evaluated. Logistic regression analysis and Kaplan-Meier survival analysis with Logrank test were performed. RESULTS: Of 269 women diagnosed with in situ/microinvasive AC, 127 participants underwent conservative treatment. During follow-up, recurrences were found in nine women (7.1%). The only factor associated with recurrence during follow-up was positive high-risk Human Papillomavirus (hr-HPV) testing (odds ratio 6.21, confidence interval 1.47-26.08, p = 0.012). HPV positivity in follow-up showed a recurrence rate of 21.7% against 3.8% in patients who were HPV-negative (p = 0.002, Logrank test). Among women with negative high-risk HPV tests in follow-up, recurrences occurred in 20.0% of non-usual-type histology vs. 2.1% of usual-type cases (p = 0.005). CONCLUSION: HPV testing in follow-up is of pivotal importance in women with early glandular lesions undergoing conservative treatment, given its recurrence predictive value. However, women who are high-risk HPV-negative in follow-up with non-usual-type histopathology may represent a sub-population at increased risk of recurrences. Further studies should confirm these findings.
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BACKGROUND: Maximum safe resection for eloquent areas glioblastomas (GBMs) is the greatest tumor resection achievable without causing neurological deficits. This study aims to assess, through quantitative volumetric analysis, the outcomes of patients with eloquent areas GBMs and correlate the extent of resection (EOR), based on MRI T1-contrast enhanced (CE) and T2- fluid-attenuated inversion recovery (FLAIR) sequences, with patient outcomes and overall survival. METHODS: We prospectively collected and analyzed patients with a diagnosis of primary GBM located in an eloquent area operated between January 2012 and April 2018. We examined 295 consecutive patients' records with GBM and identified 82 eloquent GBMs who met inclusion criteria. We stratified our patients by type of treatment-awake surgery (AS) and general anesthesia (GA) craniotomies. The kind of treatment was correlated with EOR, focusing on exeresis over the limit of the contrast-enhanced signal intensity, including both T1-CE and T2-FLAIR MRI signal alterations. RESULTS: The overall mean EOR value was higher in AS than in GA on T1-CE (P value: 0.010) and T2-Flair MRI images (P value: 0.007). Also, patients who had at least 30% of T2-FLAIR signal resection (EOR≥30%) had a significantly lower risk of death and recurrence (P value: 0.020), independent of residual T1-CE tumor volume. CONCLUSIONS: Extensive T2-Flair resection and AS improve overall survival and reduce risk of recurrence while simultaneously minimizing surgical and medical complications among patients with GBMs in eloquent areas.
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Neoplasias Encefálicas , Glioblastoma , Humanos , Glioblastoma/cirurgia , Glioblastoma/patologia , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/patologia , Vigília , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Neoplasia Residual/patologiaRESUMO
Meningiomas are the most prevalent tumors of the central nervous system. Their standard treatment is surgery, which can be curative. Adjuvant radiotherapy treatment is reserved for newly diagnosed cases of grade II and grade III meningiomas in cases of recurrent disease or when surgery is not radical or feasible. However, around 20% of these patients cannot undergo further surgical and/or radiotherapy treatment. Systemic oncological therapy can find its place in this setting. Several tyrosine kinase inhibitors have been tested (gefitinib, erlotinib, sunitinib) with unsatisfactory or negative results. Bevacizumab has shown encouraging results in these settings of patients. Immunotherapy with immune checkpoint inhibitors has reported interesting results with modest objective response rates. Several ongoing studies are assessing different target therapies and multimodal therapies; the results are to be disclosed. Not only a better understanding of the molecular characteristics in meningiomas has allowed the gathering of more information regarding pathogenesis and prognosis, but in addition, the availability of new target therapy, immunotherapy, and biological drugs has widened the scope of potentially effective treatments in this patient population. The aim of this review was to explore the radiotherapy and systemic treatments of meningioma with an analysis of ongoing trials and future therapeutic perspectives.
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Neoplasias Meníngeas , Meningioma , Humanos , Meningioma/radioterapia , Meningioma/patologia , Neoplasias Meníngeas/radioterapia , Neoplasias Meníngeas/patologia , Resultado do Tratamento , Terapia Combinada , PrognósticoRESUMO
INTRODUCTION: A dura mater substitute in decompressive craniectomies must protect the brain while providing a dissection plane between the cortex and myocutaneous layer. The human amniotic membrane (AM) has anti-inflammatory, wound healing, and differentiation properties. We tested AM properties as a dural substitute by comparing the outcomes to biological ones. METHODS: We prospectively collected data on 25 patients who randomly underwent decompressive craniectomy with lyophilized AM patches and 25 in which biological substitutes were utilized between 2015 and 2019. The AM was laid with the epithelial side facing the brain because of the anti-adhesive proprieties, while the chorion facing the myocutaneous flap. We collected data on demographics, neurological status, comorbidities, and surgical outcomes. Additionally, we created a score - dura mimicking score- and reviewed postoperative imaging and pathological specimens. RESULTS: The majority (96%) of AM grafts were integrated into native dura. Thirteen patients scored as excellent and 11 good on our "dura mimicking score", showing tissue integration ability but no cerebral cortex adhesion. The histopathological analysis showed that AM had thick plates of dense fibrous tissue with small reactive vessels, reactive fibroblasts, and lymphocytes infiltrate. The AM group's first outcomes were not different from the biological substitute patients but higher integration rate to the dura and less adhesion to the myocutaneous flap in AM patients. CONCLUSIONS: We documented the anti-adhesive, protective, and integrative properties of AM dural substitute patches in patients who underwent decompressive craniectomies, comparing the intraoperative differences and postoperative outcomes to biological dural substitutes.
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Âmnio/cirurgia , Craniectomia Descompressiva/métodos , Dura-Máter/cirurgia , Complicações Pós-Operatórias/epidemiologia , Adulto , Encéfalo/cirurgia , Craniectomia Descompressiva/efeitos adversos , Humanos , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Aderências Teciduais/epidemiologia , Aderências Teciduais/etiologia , CicatrizaçãoRESUMO
We conducted a screening analysis to assess the presence of a characteristic extracellular circulating microRNAs (ci-miRNAs) profile in Behçet's syndrome (BS). Total RNA was extracted from platelets-free plasma (PFP) samples obtained from 16 BS patients and 18 healthy controls. Ci-miRNAs profiling was conducted by using dedicated Agilent microarray hybridization and data extraction technology. Statistical analysis of data extracted from microarray scanning revealed the deregulation of 36 ci-miRNAs, which turned out be differentially expressed between BS patients and healthy controls. Detailed experimental methods and data analysis were described here. The raw and normalized microarray data were deposited into Gene Expression Omnibus (GEO) under accession number GSE145191.
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OBJECTIVES/HYPOTHESIS: The accurate diagnostic assessment of clinically relevant human papillomavirus (HPV) infections in patients with head and neck squamous cell carcinoma represents an urgent unmet medical need. The aim of this study was to determine feasibility, accuracy, and clinical significance of HPV16/18 E6 oncoprotein detection on cytological specimens from oropharyngeal squamous cell carcinoma (OPSCC) and neck lymph node metastasis of SCC from unknown primary tumor (CUP) via a protein immunochromatographic assay. STUDY DESIGN: Cross-sectional study. METHODS: Cytological specimens from primary tumor and neck metastases were collected from 34 patients with OPSCC or CUP and applied to a lateral flow format test that detects HPV16 and HPV18 E6 oncoproteins. E6 oncoprotein positivity or negativity in these specimens was compared to the specimens' "HPV-driven" reference status, defined by presence of HPV-DNA in combination with p16INK4a overexpression and/or HPV E6 seropositivity. RESULTS: Eighteen of 29 OPSCC (62%) and three of five CUP (60%) were HPV-driven according to our reference method. The E6 oncoprotein lateral flow test had a sensitivity of 94% (95% CI: 70%-100%) and a specificity of 100% (95% CI: 66%-100%) on primary tumor, and a sensitivity of 88% (95% CI: 64%-99%) and a specificity of 100% (95% CI: 74%-100%) on neck metastases. Test agreement between the E6 lateral flow test and the clinical reference method, HPV-DNA plus p16INK4a was excellent, both for primary lesion and neck metastases. CONCLUSIONS: We found the detection of HPV16/18 E6 oncoproteins to be a feasible, highly reliable, and low-invasive method to assess "HPV-driven" status in OPSCC and CUP. LEVEL OF EVIDENCE: II Laryngoscope, 131:1042-1048, 2021.
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Neoplasias de Cabeça e Pescoço/virologia , Papillomavirus Humano 16/isolamento & purificação , Papillomavirus Humano 18/isolamento & purificação , Neoplasias Primárias Desconhecidas/virologia , Infecções por Papillomavirus/diagnóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Idoso , Estudos Transversais , Proteínas de Ligação a DNA/imunologia , Proteínas de Ligação a DNA/isolamento & purificação , Estudos de Viabilidade , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/cirurgia , Papillomavirus Humano 16/imunologia , Papillomavirus Humano 18/imunologia , Humanos , Imunoensaio/instrumentação , Imunoensaio/métodos , Metástase Linfática/patologia , Metástase Linfática/terapia , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Desconhecidas/patologia , Neoplasias Primárias Desconhecidas/cirurgia , Proteínas Oncogênicas Virais/imunologia , Proteínas Oncogênicas Virais/isolamento & purificação , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/cirurgia , Infecções por Papillomavirus/virologia , Kit de Reagentes para Diagnóstico , Proteínas Repressoras/imunologia , Proteínas Repressoras/isolamento & purificação , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/cirurgiaRESUMO
PURPOSE: The reasons why a specific subset of glioblastoma (GBM) patients survive longer than others is still unclear. This study analyzed a cohort of long-term and very-long-term GBM survivors to determine which genetic alterations or patient's characteristics influence survival time. METHODS: We retrospectively reviewed a cohort of GBM patients treated at our institution over the last 20â¯years, stratifying patients in three groups: those with a survival timeâ¯≥â¯36â¯months andâ¯<â¯120â¯months (LTS), ≥120â¯months (VLTS), andâ¯<â¯36â¯months, respectively. Clinical (age, sex, focality, resection degree, Karnofsky performance status), and immunohistochemical and molecular data (Ki-67 expression and multiple genes alterations) were collected. We then utilized principal component analysis, logistic regression, and Cox proportional hazard models to identify those variables associated with survival. RESULTS: Younger age at presentation (HRâ¯=â¯0.36, 95% CI 0.21-0.67, pâ¯=â¯.001), and MGMT promoter [(MGMTp), methylated, HRâ¯=â¯0.57, CI 0.34-0.96, pâ¯=â¯.034) were associated with higher odds of VLTS survival. The multivariate analysis showed how the combination of younger age (< 50â¯years), Ki-67â¯<â¯10%, and the coexistence of TERTp not mutated, MGMTp methylated, and IDH1/2 mutated in the same patient are also associated with higher odds of survival (HRâ¯=â¯0.10, CI 0.01-0.74, pâ¯=â¯.025). CONCLUSIONS: We confirmed younger age at presentation and MGMTp methylation as the only independent factors associated with VLTS. The exceptional survival of our VLTS patients is probably associated with different, still understudied, gene mutations, or with the coexistence of multiple factors.
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Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/mortalidade , Glioblastoma/diagnóstico por imagem , Glioblastoma/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/cirurgia , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Seguimentos , Glioblastoma/cirurgia , Humanos , Imageamento por Ressonância Magnética/tendências , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Fatores de Tempo , Adulto JovemRESUMO
Medulloblastoma is an embryonal neuroepithelial tumor that affects mainly childhood and more rarely adults. Medulloblastoma occurring as multiple nodules at diagnosis is a rare and tricky presentation. Here, we describe the case of a previously healthy 47-year-old woman with multiple posterior fossa cerebellar tumors. Histological, immunohistochemical, and molecular analyses were performed to best characterize the two excised lesions. The histopathological analysis revealed different variants of medulloblastoma in the excised nodules, one being extensive nodularity, rare in adults, and the other desmoplastic/nodular with areas of anaplasia. Immunostains and molecular analysis classified both nodules as SHH medulloblastoma. Adult medulloblastoma is extremely rare. Important differences exist between adult medulloblastoma and medulloblastoma arising in children and infants. Such differences are in location, distribution of histological variants and of molecular subgroups, survival rates, and therapeutic options. An extensive morphological and molecular characterization of such rare tumors is necessary to choice the best-tailored therapy.
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PURPOSE: To evaluate the prevalence of two recurrent somatic mutations (-124 C>T and -146 C>T) within the promoter of the gene encoding telomerase reverse transcriptase (TERT) as well as their relationship with TERT level, telomeres length, and outcome in patients with head and neck squamous cell carcinomas (HNSCCs). METHODS: We evaluate the prevalence of TERT promoter mutations, TERT levels, and telomere length in paired cancer tissue and adjacent mucosa (AM) in a series of HNSCCs. RESULTS: Cancer tissue and AM specimens from 105 patients were analyzed. Telomere length and TERT mRNA levels were estimated using real-time polymerase chain reaction. TERT promoter mutations were assessed using Sanger sequencing. Out of 105 cases, 101 were considered suitable for the analysis. TERT promoter harbored mutations in 12 tumors (11.9%), with -124 C>T and -146 C>T accounting for 83.3% and 16.7% of the alterations, respectively. No mutations were detected in AM samples. The prevalence of TERT promoter mutations was significantly higher in oral cavity SCCs (10 out of 27 tumors; 37%), and telomere length in AM was shorter in patients with tumors carrying TERT promoter mutations than in patients with unmutated TERT promoter cancers (p = 0.023). TERT levels in tumor did not significantly differ according to the mutational status of TERT promoter. No significant association was found between TERT promoter status and overall survival. CONCLUSION: TERT promoter mutations are most likely a late event in tumor development, occurring in a context of critically short telomeres, mostly in patients with oral cavity SCC. TERT levels, but not TERT promoter mutational status impact clinical outcome.