Background
The incidence of pediatric head and neck cancer (PHNC) is increasing worldwide, especially when compared with childhood cancer in general. However, there is still a lack of knowledge about ...the demographic profile of such patients across the globe. Therefore, the aim of this study was to describe demographic, topographic, and histopathological features of PHNC patients from a single Brazilian institution.
Methods
Medical records were retrospectively reviewed for all cancer cases diagnosed from 1986 to 2016 affecting patients aged 19 years and younger. The demographic variables (age, gender, race), topographic aspects of primary tumors, and histopathological diagnoses were collected and analyzed by descriptive statistics.
Results
Three hundred and sixty‐seven (5.11%) head and neck malignant tumors were found among 7181 pediatric cancers diagnosed in this period. Mean age at diagnosis was 9.35 years with male (65.67%) predominance. Patients between the age group of 10‐14 years presented the higher prevalence of malignant tumors. In terms of race, 73.02% of the patients were white and 9.54% were black. The main affected anatomic site was the neck and lymph nodes (41.42%), followed by nasopharynx (22.89%) and thyroid gland (6.54%). The most common cancer type was lymphoma (52.86%), followed by carcinoma (22.89%), and sarcoma (19.07%). Burkitt lymphoma, nodular sclerosis Hodgkin lymphoma, nasopharyngeal carcinoma, and rhabdomyosarcoma were the most common histopathological diagnoses (16.62%, 13.08%, 12.81%, and 12.81%, respectively).
Conclusion
This study originally demonstrated that lymphomas may be more frequent than carcinomas and sarcomas in Brazilian PHNC patients.
The high incidence of adrenocortical tumors and choroid plexus carcinoma in children from South and Southeastern regions of Brazil is associated with the germline p.R337H mutation of TP53 gene. The ...concomitant occurrence of neuroblastoma and adrenocortical tumors in pediatric patients harboring the p.R337H mutation at our institution prompted us to investigate the putative association between p.R337H and pediatric neuroblastoma. Genomic DNA samples from 83 neuroblastoma patients referred to a single institution during the period of 2000-2014 were screened for the p.R337H mutation. Available samples from carriers were investigated for both nuclear p53 accumulation and loss of heterozigosity in tumor. Clinical data were obtained from medical records in order to assess the impact of 337H allele on manifestation of the disease. Seven out 83 neuroblastoma patients (8.4%) were carriers of the TP53 p.R337H mutation in our cohort. Immunohistochemical analysis of p.R337H-positive tumors revealed nuclear p53 accumulation. Loss of heterozigosity was not found among available samples. The presence of 337H allele was associated with increased proportion of stage I tumors. Our data indicate that in addition to adrenocortical tumors, choroid plexus carcinoma, breast cancer and osteosarcoma, genetic counseling and clinical surveillance should consider neuroblastoma as a potential neoplasia affecting p.R337H carriers.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Embryonic tumors share few recurrent mutations, suggesting that other mechanisms, such as aberrant DNA methylation, play a prominent role in their development. The loss of imprinting (LOI) at the ...chromosome region 11p15 is the germline alteration behind Beckwith–Wiedemann syndrome that results in an increased risk of developing several embryonic tumors. This study analyzed the methylome, using EPIC Beadchip arrays from 99 sporadic embryonic tumors. Among these tumors, 46.5% and 14.6% presented alterations at imprinted control regions (ICRs) 1 and 2, respectively. Based on the methylation levels of ICR1 and ICR2, four clusters formed with distinct methylation patterns, mostly for medulloblastomas (ICR1 loss of methylation (LOM)), Wilms tumors, and hepatoblastomas (ICR1 gain of methylation (GOM), with or without ICR2 LOM). To validate the results, the methylation status of 29 cases was assessed with MS-MLPA, and a high level of agreement was found between both methodologies: 93% for ICR1 and 79% for ICR2. The MS-MLPA results indicate that 15 (51.7%) had ICR1 GOM and 11 (37.9%) had ICR2 LOM. To further validate our findings, the ICR1 methylation status was characterized via digital PCR (dPCR) in cell-free DNA (cfDNA) extracted from peripheral blood. At diagnosis, we detected alterations in the methylation levels of ICR1 in 62% of the cases, with an agreement of 76% between the tumor tissue (MS-MLPA) and cfDNA methods. Among the disagreements, the dPCR was able to detect ICR1 methylation level changes presented at heterogeneous levels in the tumor tissue, which were detected only in the methylome analysis. This study highlights the prevalence of 11p15 methylation status in sporadic embryonic tumors, with differences relating to methylation levels (gain or loss), location (ICR1 or ICR2), and tumor types (medulloblastomas, Wilms tumors, and hepatoblastomas).
Oxidative stress and inflammation act on skin squamous cell carcinoma (SSCC) development and progression. Curative therapy for SSCC patients is mainly based on surgical resection, which can cause ...various sequelae. Silver ions have in vitro activities over tumor cells, while nimesulide has antioxidant and anti-inflammatory activities. This study aimed to evaluate the effects of a silver(I) complex with nimesulide (AgNMS) incorporated in a sustained release device based on bacterial cellulose membrane, named AgNMS@BCM, on topic SSCC treatment. The antiproliferative effect of AgNMS complex was evaluated in the SCC4, SCC15 and FaDu SCC lines. AgNMS complex activity on exposure of phosphatidylserine (PS) residues and multicaspase activation were evaluated on FaDu cells by flow cytometry. The AgNMS@BCM effects were evaluated in a SSCC model induced by 7,12-dimethylbenzanthracene/12-
-tetradecanoyl-phorbol-13-acetate (DMBA/TPA) in mice. Toxicity and tumor size were evaluated throughout the study. AgNMS complex showed antiproliferative activity in SCC15 and FaDu lines in low to moderate concentrations (67.3 µM and 107.3 µM, respectively), and induced multicaspase activation on FaDu cells. The AgNMS@BCM did not induce toxicity and reduced tumor size up to 100%. Thus, the application of AgNMS@BCM was effective and safe in SSCC treatment in mice, and can be seen as a potential and safe agent for topic treatment of SSCC in humans.
Pediatric hematologic malignancies present an elevated survival rate, and these survivors may experience long‐term complications, including secondary malignancies. This case describes a 17‐year‐old ...female patient previously treated for acute lymphoblastic leukemia (ALL) who developed a squamous cell carcinoma (SCC, T2N0M0) of the lateral border of the tongue diagnosed during dental follow‐up 2 years and 9 months after the conclusion of ALL therapy (GBTLILLA99 protocol). The patient underwent exclusive surgical resection for the tongue SCC and is free of disease 11 years after the surgery. The current case report highlights the importance of monitoring the oral health of childhood cancer survivors. As part of a multidisciplinary team, our directives include counseling to avoid carcinogenic exposures.
ABSTRACT Objective: To describe the clinical, demographic, anatomopathological, molecular, and survival characteristics of patients with medulloblastoma. Methods: Retrospective study based on patient ...information obtained from the review of medical records. Overall and event-free survival were analyzed using the Kaplan-Meier estimator, and the curves were compared by the log-rank test. Results: Among the patients investigated, 70 were male (66%), and age at diagnosis ranged from 2 months to 22 years. The most frequent signs and symptoms were headache (80.8%) and vomiting (75.8%). Regarding treatment, most patients (63.2%) underwent complete surgical resection, with a predominance of classic histology (63.2%). The 5-year overall survival rate was 67.9%, and the 10-year rate was 64.2%. Patients with molecular profile characteristic of the wingless (WNT) subgroup had a better prognosis, with 5-year overall survival of 75%. Conclusions: The clinical, demographic, anatomopathological, and molecular characteristics of patients with medulloblastoma described in the present study were mostly similar to those reported in the literature. Patients submitted to complete tumor resection had better clinical outcomes than those who underwent incomplete resection/biopsy. Patients classified as high-risk showed worse overall and event-free survival than those in the standard-risk group, and the presence of metastasis at diagnosis was associated with recurrence.
RESUMO Objetivo: Descrever as características clínicas, demográficas, anatomopatológicas, moleculares e de sobrevida de pacientes portadores de meduloblastoma. Métodos: Estudo retrospectivo, no qual as informações dos pacientes foram obtidas pela revisão dos prontuários médicos. Análises de sobrevida global e de sobrevida livre de eventos foram realizadas por meio da construção de curvas de Kaplan-Meier e a comparação entre as curvas foi feita pelo teste log-rank. Resultados: Entre os pacientes analisados, 70 pertenciam ao sexo masculino (66%) e a idade ao diagnóstico variou de dois meses a 22 anos. Os sinais e sintomas de maior frequência foram cefaleia (80,8%) e vômitos (75,8%). Em relação ao tratamento, a maioria (63,2%) dos pacientes foi submetida à ressecção cirúrgica total e apresentava como histologia predominante a forma clássica (63,2%). A taxa de sobrevida global em cinco anos foi de 67,9% e, em 10 anos, de 64,2%. Os pacientes com perfil molecular característico do subgrupo wingless (WNT) apresentaram melhor prognóstico, com sobrevida global em cinco anos de 75%. Conclusões: As características clínicas, demográficas, anatomopatológicas e moleculares dos pacientes com meduloblastoma descritas no presente estudo foram majoritariamente semelhantes às descritas na literatura. Pacientes submetidos à ressecção completa do tumor tiveram melhor evolução clínica do que aqueles com ressecção incompleta/biópsia. Pacientes estratificados como de alto risco apresentaram pior sobrevida global e livre de eventos do que o grupo standard e a presença de metástases ao diagnóstico se mostrou associada à ocorrência de recidiva da doença.
Pediatric tumors share few recurrent mutations and are instead characterized by copy number alterations (CNAs). The cell-free DNA (cfDNA) is a prominent source for the detection of cancer-specific ...biomarkers in plasma. We profiled CNAs in the tumor tissues for further evaluation of alterations in 1q,
and 17p in the circulating tumor DNA (ctDNA) in the peripheral blood at diagnosis and follow-up using digital PCR. We report that among the different kinds of tumors (neuroblastoma, Wilms tumor, Ewing sarcoma, rhabdomyosarcoma, leiomyosarcoma, osteosarcoma and benign teratoma), neuroblastoma presented the greatest amount of cfDNA, in correlation with tumor volume. Considering all tumors, cfDNA levels correlated with tumor stage, metastasis at diagnosis and metastasis developed during therapy. In the tumor tissue, at least one CNA (at
,
, surrogate markers for 1q and 17p, respectively, and
) was observed in 89% of patients. At diagnosis, CNAs levels were concordant between tumor and ctDNA in 56% of the cases, and for the remaining 44%, 91.4% of the CNAs were present only in cfDNA and 8.6% only in the tumor. Within the cfDNA, we observed that 46% and 23% of the patients had
and 1q gain, respectively. The use of specific CNAs as targets for liquid biopsy in pediatric patients with cancer can improve diagnosis and should be considered for monitoring of the disease response.
Objective: To determine the relative frequency and clinicopathological features of pediatric oral and maxillofacial cancer (OMC) from a single Brazilian institution. Study Design: Medical records ...were retrospectively reviewed for all cancer cases diagnosed from 1986-2016 affecting patients aged 19 years old and younger. Demographic variables, anatomic location, and histopathological diagnoses were collected and analyzed by descriptive statistics. Results: Fifty-five (0.77%) OMC cases were found among 7181 pediatric malignancies diagnosed in this period. Mean age at diagnosis was 8 years old, with patients 5 to 9 years of age being more frequently (40%) affected than other childhood age groups. White (78.18%) male (65.45%) patients were more commonly affected by OMC. The most common cancer types affecting the oral and maxillofacial region were lymphomas (52.73%), sarcomas (27.27%) and carcinomas (20%). Burkitt lymphoma (32.73%), rhabdomyosarcoma (14.55%), diffuse large B-cell lymphoma (9.09%), and mucoepidermoid carcinoma (9.09%) were the most prevalent histopathological diagnoses. The main affected anatomic sites were the oropharynx (38.18%), salivary glands (30.91%), maxillofacial bone (20%), and the oral cavity (10.91%). Conclusion: Although pediatric OMC may have a low prevalence among Brazilians, this disease group often affects a wide variation of anatomic topographies under several different histopathological patterns of biological aggressiveness, such as lymphomas and sarcomas.
HEAD AND NECK CANCER DISTRIBUTION IN BRAZIL'S PEDIATRIC PATIENTS ARBOLEDA, PAOLA ARISTIZABAL; HOFFMANN, IVA LOUREIRO; CARDINALLI, IZILDA APARECIDA ...
Oral surgery, oral medicine, oral pathology and oral radiology,
January 2020, 2020-01-00, Letnik:
129, Številka:
1
Journal Article
Recenzirano
Demographic and clinicopathologic distribution of head and neck malignant tumors in Brazil's pediatric patients is still unknown.
Objective: To describe demographic, topographic, and histopathologic ...features of pediatric patients with head and neck cancer from a single Brazilian institution.
Study Design: Medical records were retrospectively reviewed for all cancer cases diagnosed from 1986 to 2016 affecting patients aged 19 years and younger. The demographic variables (age, sex, race), topographic aspects, and histopathologic diagnoses were collected.
Results: A total of 7181 malignant tumors were diagnosed, of which 367 (5.11%) were located in the head and neck region. Mean age at diagnosis was 9.35 years with male (65.67%) predominance. The age group of 10 to 14 years presented with higher prevalence. In terms of race, 73.02% of the patients were white. The main affected anatomic site was the neck and lymph nodes (41.42%), followed by nasopharynx (22.89%), and thyroid gland (6.54%). The most common cancer type was lymphoma (52.86%), followed by carcinoma (22.89%), and sarcoma (19.07%). Burkitt lymphoma, nodular sclerosis Hodgkin lymphoma, nasopharyngeal carcinoma, and rhabdomyosarcoma were the most common histopathologic diagnoses (16.62%, 13.08%, 12.81%, and 12.81%, respectively).
Conclusions: The present study originally demonstrated that lymphomas may be more frequent than carcinomas and sarcomas in Brazilian pediatric patients.
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