ABSTRACT Introduction Oncohematological patients require the evaluation for possible infiltration of the central nervous system (CNS) by neoplastic cells at diagnosis and/or during the monitoring of the chemotherapeutic treatment. Morphological analysis using conventional microscopy is considered the method of choice to evaluate the cerebrospinal fluid (CSF) samples, despite technical limitations. Objective This study aimed to compare the performance of the cytomorphology and flow cytometric immunophenotyping (FC) in the detection of CNS infiltration. Method We evaluated 520 CSF samples collected from 287 oncohematological patients for whom the detection of neoplastic cells was simultaneously requested by cytomorphology and FC. Results Laboratory analyses revealed 435/520 (83.7%) conclusive results by the two methods evaluated, among which 385 (88.5%) were concordant. Discordance between the methods was observed in 50/435 (11.5%) samples, 45 (90%) being positive by FC. Furthermore, the FC defined the results in 69/72 (95.8%) inconclusive samples by cytomorphology. The positivity of FC was particularly higher among hypocellular samples. Among 431 samples with a cell count of < 5/μL, the FC identified neoplastic cells in 75 (17.4%), while the cytomorphology reported positive results in 26 (6%). Among the samples that presented adequate cell recovery for evaluation by both methods (506/520), the comparative analysis between FC and cytomorphology revealed a Kappa coefficient of 0.45 (CI: 0.37-0.52), interpreted as a moderate agreement. Conclusion The data showed that the CSF analysis by FC helps in the definition of CNS infiltration by neoplastic cells, particularly in the cases with dubious morphological analysis or in the evaluation of samples with low cellularity.

ABSTRACT Objectives: To describe cytogenetic and molecular abnormalities observed in children and adolescents with acute myeloid leukemia (AML), classify AML according to the World Health Organization (WHO) classifications from 2008 and 2016, and evaluate the prognosis according to clinical characteristics and cytogenetic abnormalities. Methods: A retrospective longitudinal study was performed on a population of 98 patients with AML, aged up to 16 years, seen in a single hospital from 2004 to 2015. Results: Among the 80 patients for whom it was possible to analyze the karyotype, 78.7% had chromosomal changes, the most frequent being t(15;17)(q22;q21). Of the 86 patients for whom we had cytogenetic or molecular data, making it possible to classify their AML according to the WHO classification, 52.3% belonged to the group with recurrent genetic abnormalities, 22% to the "AML not otherwise specified" group, 18.6% to the group with myelodysplasia-related cytogenetic changes, and 7% to the group with Down syndrome-related leukemia. Five-year overall survival (OS) for the whole group was 49.7% ± 5.2%. In the univariate and multivariate analyses, patients with myelodysplasia-related cytogenetic changes (OS 28.1% ± 12.2%) and those with "AML not otherwise specified" (OS 36.1% ± 11.2%) had an unfavorable prognosis when compared to patients with AML with recurrent genetic abnormalities (OS 71% ± 5.8%) and patients with Down syndrome-related AML (OS 83% ± 15.2%, p = 0.011). Conclusions: The results corroborate the importance of cytogenetic abnormalities as a prognostic factor and indicate the need for cooperative and prospective studies to evaluate the applicability of the WHO classification in the pediatric population.

RESUMO Objetivo: Analisar as características clínicas, laboratoriais e histopatológicas e o percurso até o estabelecimento do diagnóstico e do tratamento de pacientes com carcinoma de suprarrenal (CSR). Métodos: Estudo retrospectivo com 13 pacientes tratados no serviço de oncologia pediátrica do Hospital das Clínicas da Universidade Federal de Minas Gerais (HC-UFMG) entre 2004 e 2015. Resultados: A idade ao diagnóstico variou de 1,0 a 14,8 anos (mediana: 2,0 anos). As manifestações de hipercortisolismo foram identificadas em todos os casos, e as de virilização, em todas as meninas. Todos os pacientes preencheram os critérios de Weiss para diagnóstico histopatológico de CSR. A imuno-histoquímica foi realizada em 61,5% dos casos. A maioria dos pacientes apresentou doença em estádio I (76,9%). Todos foram submetidos à ressecção tumoral total. Dois pacientes (estádios III e IV) receberam quimioterapia associada ao mitotano. O único óbito observado foi do paciente com doença em estádio IV. A probabilidade de sobrevida global para todo o grupo aos 5,0 anos foi de 92,3±7,4%. A mediana de tempo entre o início dos sintomas e o diagnóstico foi de 9,5 meses, e de 6,0 meses entre a primeira consulta e o início do tratamento. Conclusões: A baixa idade ao diagnóstico, o predomínio de casos com doença localizada e a ressecção tumoral completa - com apenas um caso de ruptura de cápsula tumoral - são possivelmente a explicação para a evolução favorável da população estudada. O longo percurso entre o início dos sintomas e o diagnóstico sugere a importância da capacitação dos pediatras para o reconhecimento precoce dos sinais e dos sintomas do CSR.

ABSTRACT Objective: To analyze clinical, laboratory and histopathological features and the path to diagnosis establishment and treatment of patients with adrenal carcinoma (AC). Methods: Retrospective study with 13 patients assisted at the pediatric oncology service of Hospital das Clínicas, Universidade Federal de Minas Gerais, Brazil, between 2004 and 2015. Results: Age at diagnosis ranged from 1.0 to 14.8 years (median: 2.0 years). Manifestations of hypercortisolism were identified in all cases and virilization in all girls. All patients met the Weiss criteria to AC histopathological diagnosis. Immunohistochemistry was performed in 61.5% of the cases. Most patients had stage I disease (76.9%). All subjects were submitted to total tumor resection. Two patients (stages III and IV disease) received chemotherapy associated to mitotane. The only death case was that of a patient with stage IV disease. The probability of overall survival for the entire group up to 5.0 years was 92.3±7.4%. The median time between the onset of symptoms and diagnosis was 9.5 months, and 6.0 months between first visit and start of treatment. Conclusions: Low age at diagnosis, predominance of cases with localized disease and complete tumor resection - with only one case of tumor capsule rupture - can possibly explain the favorable evolution of the studied population. The long period between onset of symptoms and diagnosis highlights the importance of training pediatricians for early recognition of AC signs and symptoms.

Objective:To evaluate the approach to palliative care for hematological oncology patients in the pediatric ward of a tertiary hospital.Methods:This was a retrospective, descriptive study of 29 hematological oncology patients who died between 2009 and 2011. Data regarding the approach and prevalence of pain, prevalence of other symptoms, multidisciplinary team participation, communication between staff and family and limited invasive therapy were collected from the medical records.Results:Twenty-seven (93.1%) patients displayed disease progression unresponsive to curative treatment. The median age at death was ten years old. Pain was the most prevalent symptom with all patients who reported pain receiving analgesic medications. The majority took weak (55.2%) and/or strong (65.5%) opioids. The patients were followed by pediatricians and a pediatric hematologist/oncologist. Participation of other professionals was also documented: 86.2% were followed by social services and 69% by psychologists, among others. There were explicit descriptions of limitation of invasive therapy in the medical records of 26 patients who died with disease progression. All these decisions were shared with the families.Conclusion:Although the hospital where this study was conducted does not have a specialized team in pediatric palliative care, it meets all the requirements for developing a specific program. The importance of approaching pain and other prevalent symptoms in children with cancer involving a comprehensive multidisciplinary team is evident. Discussions were had with most of the families on limiting invasive therapy, but no record of a well-defined and coordinated treatment plan for palliative care was found.

Objective:To describe the clinical and laboratory presentation of hemophagocytic lymphohistiocytosis in children treated at a referral institution.Methods:A retrospective descriptive study was carried out of seven children diagnosed with hemophagocytic lymphohistiocytosis between 2010 and 2012. The criteria for diagnosis were those proposed by the Histiocyte Society. When indicated, immunochemotherapy was prescribed according to the HLH94 and HLH2004 protocols of the Histiocyte Society.Results:The patients' ages at diagnosis ranged from one month to nine years. All patients had splenomegaly, fever, anemia, thrombocytopenia, hyperferritinemia and hypertriglyceridemia. Bone marrow hemophagocytosis was detected in six patients. In six cases, infectious diseases triggered the syndrome. In two cases, associated with visceral leishmaniasis, remission was achieved after treatment of the underlying infection. Three patients, who had Epstein–Barr-related hemophagocytic lymphohistiocytosis, required treatment with immunochemotherapy. They are alive and in remission; one patient had symptoms of juvenile rheumatoid arthritis and another, who was suspected of having primary hemophagocytic lymphohistiocytosis, entered into remission after bone marrow transplantation. Two deaths (28.6%) occurred in patients with suspected primary hemophagocytic lymphohistiocytosis; one whose clinical picture was triggered by cytomegalovirus infection did not respond to immunochemotherapy and the other died before any specific treatment was provided.Conclusion:As reported before, hemophagocytic lymphohistiocytosis has a multifaceted presentation with nonspecific signs and symptoms. In secondary forms, remission may be achieved by treating the underlying disease. In the primary forms, remission may be achieved with immunochemotherapy, but bone marrow transplantation is required for cure.

A expansão tecnológica das últimas décadas modificou o perfil dos pacientes na pediatria, tornando cada vez mais frequente a assistência a crianças com doenças crônicas e ameaçadoras à vida. Cuidados paliativos envolvem a assistência ativa e total prestada a essas crianças, nas dimensões de seu corpo, mente e espírito, bem como o suporte oferecido a sua família. O presente estudo revisa aspectos relevantes na abordagem paliativa: a prevalência e abordagem dos sintomas, a participação de equipe multiprofissional, a comunicação com a família, os cuidados ao final da vida e a limitação de terapêuticas invasivas. A despeito do reconhecimento da importância da medicina paliativa, nossas universidades ainda priorizam a medicina curativa. Instituir esse tema no processo de formação do médico é uma necessidade real e absoluta, visando proporcionar vida e morte dignas aos nossos pacientes.

The technological expansion in recent decades changed the profile of the patients in pediatrics, with assistance to children with chronic and life-threatening conditions more frequent each time. Palliative care involves an active and full assistance provided to these children, in the context of their body, mind and spirit as well as the support offered to their entire family. This study provides a review of relevant aspects in palliative approach: the prevalence and approach of symptoms, the participation of a multidisciplinary team, communication with family, care at end of life and limitation of invasive therapies. Despite recognition of the importance of palliative medicine, our universities still give priority to curative medicine. Introducing this theme in the process of medical education is a real and absolute need, aiming to provide dignified life and death to our patients.

La expansión tecnológica de las últimas décadas ha cambiado el perfil de los pacientes de pediatría, volviendo cada vez más frecuente la asistencia a los niños con enfermedades crónicas y potencialmente mortales. Cuidados paliativos involucran la asistencia activa y total prestada a estos niños y niñas, en el ámbito de su cuerpo, mente y espíritu, así como el apoyo ofrecido a toda su familia. Este estudio proporciona un análisis de los aspectos relevantes en el enfoque paliativo: la prevalencia y abordaje de los síntomas, la participación de un equipo multidisciplinario, la comunicación con la familia, la atención al final de la vida y la limitación de las terapias invasivas. A pesar del reconocimiento de la importancia de la medicina paliativa, nuestras universidades siguen dando prioridad a la medicina curativa. Establecer ese tema en el proceso de la educación médica es una necesidad real y absoluta, con el objetivo de proporcionar una vida y una muerte dignas a nuestros pacientes.

O sistema nervoso central (SNC) é o sítio extramedular mais acometido na leucemia linfoide aguda. A avaliação morfológica do líquido cefalorraquidiano (LCR), apesar de ser o exame tradicional para o diagnóstico da infiltração leucêmica no SNC, é um método pouco sensível. O presente estudo pretendeu avaliar a imunofenotipagem como método auxiliar na detecção de blastos no LCR em crianças e adolescentes com leucemia linfoide aguda.

The central nervous system is the most commonly affected extramedullary site in acute lymphoblastic leukemia. Although morphologic evaluation of the cerebrospinal fluid has been traditionally used for diagnosing central nervous system involvement, it is a method of low sensitivity. The present study aimed at evaluating the use of immunophenotyping in the detection of blasts in the cerebrospinal fluid from children and adolescents with acute lymphoblastic leukemia.

OBJECTIVE To detect markers for minimal residual disease monitoring based on conventional polymerase chain reaction for immunoglobulin, T-cell receptor rearrangements and the Sil-Tal1 deletion in patients with acute lymphocytic leukemia. METHODS Fifty-nine children with acute lymphocytic leukemia from three institutions in Minas Gerais, Brazil, were prospectively studied. Clonal rearrangements were detected by polymerase chain reaction followed by homo/heteroduplex clonality analysis in DNA samples from diagnostic bone marrow. Follow-up samples were collected on Days 14 and 28-35 of the induction phase. The Kaplan-Meier and multivariate Cox methods were used for survival analysis. RESULTS Immunoglobulin/T-cell receptor rearrangements were not detected in 5/55 children screened (9.0%). For precursor-B acute lymphocytic leukemia, the most frequent rearrangement was IgH (72.7%), then TCRG (61.4%), and TCRD and IgK (47.7%); for T-acute lymphocytic leukemia, TCRG (80.0%), and TCRD and Sil-Tal deletion (20.0%) were the most common. Minimal residual disease was detected in 35% of the cases on Day 14 and in 22.5% on Day 28-35. Minimal residual disease on Day 28-35, T-acute lymphocytic leukemia, and leukocyte count above 50 x 109/L at diagnosis were bad prognostic factors for leukemia-free survival in univariate analysis. Relapse risk for minimal residual disease positive relative to minimal residual disease negative children was 8.5 times higher (95% confidence interval: 1.02-70.7). CONCLUSION Immunoglobulin/T-cell receptor rearrangement frequencies were similar to those reported before. Minimal residual disease is an independent prognostic factor for leukemia-free survival, even when based on a non-quantitative technique, but longer follow-ups are needed.

Apesar dos altos índices de cura, cerca de 20% dos pacientes com leucemia linfóide aguda (LLA) apresentam recidiva da doença. Recidiva isolada na cavidade oral é extremamente incomum. O objetivo deste trabalho é relatar um caso de recidiva isolada em criança com LLA de linhagem T. A apresentação clínica foi quadro de edema e dor na cavidade oral, na região superior da gengiva à direita, sem outras alterações clínicas ou hematológicas. O diagnóstico foi confirmado por meio de biópsia e imuno-histoquímica. O mielograma era normal. Cinco meses após a manifestação inicial na cavidade oral, foi detectada infiltração leucêmica na medula óssea. O tratamento com quimioterapia sistêmica foi reintroduzido. Este relato de caso ressalta a importância do acompanhamento clínico e odontológico durante e após o tratamento quimioterápico, não somente com o objetivo de tratar as alterações na cavidade oral decorrentes da própria doença ou dos efeitos adversos do tratamento, mas para que sejam detectadas apresentações incomuns de recidiva na LLA.

Despite high cure rates, approximately 20% of patients with acute lymphoblastic leukemia (ALL) have disease relapse. Isolated recurrence in oral cavity is extremely unusual. The aim of this paper is to report a case of an isolated relapse occurred in a child with T-lineage ALL. Clinical picture included swelling and pain in the right upper gingiva of the oral cavity, with no other clinical or hematological alterations. Diagnosis was confirmed by biopsy and immunohistochemical staining. Bone marrow aspiration was normal. Five months later leukemic infiltration of the bone marrow was detected and systemic chemotherapy was reintroduced. This case report highlights the relevance of dental care during and after chemotherapy, not only to treat lesions in the oral cavity resulting from the disease itself or from treatment side effects, but also to detect unusual sites of ALL relapse.

BACKGROUND: Despite all the advances in the treatment of childhood acute lymphoblastic leukemia, central nervous system relapse remains an important obstacle to curing these patients. This study analyzed the incidence of central nervous system relapse and the risk factors for its occurrence in children and adolescents with acute lymphoblastic leukemia. METHODS: This study has a retrospective cohort design. The studied population comprised 199 children and adolescents with a diagnosis of acute lymphoblastic leukemia followed up at Hospital das Clinicas, Universidade Federal de Minas Gerais (HC-UFMG) between March 2001 and August 2009 and submitted to the Grupo Brasileiro de Tratamento de Leucemia da Infância - acute lymphoblastic leukemia (GBTLI-LLA-99) treatment protocol. RESULTS: The estimated probabilities of overall survival and event free survival at 5 years were 69.5% ( 3.6%) and 58.8% ( 4.0%), respectively. The cumulative incidence of central nervous system (isolated or combined) relapse was 11.0% at 8 years. The estimated rate of isolated central nervous system relapse at 8 years was 6.8%. In patients with a blood leukocyte count at diagnosis > 50 x 10(9)/L, the estimated rate of isolated or combined central nervous system relapse was higher than in the group with a count < 50 x 10(9)/L (p-value = 0.0008). There was no difference in cumulative central nervous system relapse (isolated or combined) for the other analyzed variables: immunophenotype, traumatic lumbar puncture, interval between diagnosis and first lumbar puncture and place where the procedure was performed. CONCLUSIONS: These results suggest that a leukocyte count > 50 x 10(9)/L at diagnosis seems to be a significant prognostic factor for a higher incidence of central nervous system relapse in childhood acute lymphoblastic leukemia.

OBJECTIVES: To improve the level of 'definitive' diagnosis of Langerhans cell histiocytosis by immunohistochemical investigation of the CD1a surface antigen and to compare outcomes in respect to age, gender, stage of the disease, treatment response and level of diagnostic accuracy. METHODS: A retrospective study was carried out of 37 children and adolescents with possible Langerhans cell histiocytosis between 1988 and 2008. The diagnoses were revisited using immunohistochemical investigations for CD1a, S-100 and CD68 in an attempt to reach definitive diagnoses for all cases. RESULTS: Before the study, only 13 of 37 patients (35.1%) had a 'definitive' diagnosis; by the end of the study, this number rose to 25 patients (67.6%). All reviewed cases were positive for the CD1a antigen. Overall survival was 88.5%. Multisystem disease (Stage 2; n=19) and absence of response at the 6th week of therapy (n=5) were associated to significantly lower overall survival (p-value = 0.04 and 0.0001, respectively). All deaths occurred in patients with multisystem disease and organ dysfunction at diagnosis. Other potential prognostic factors were not significant. Reactivation episodes occurred in 75% of the patients with multisystem disease. Diabetes insipidus was the most common sequel (21.6%). CONCLUSION: The level of diagnostic accuracy was increased through immunohistochemistry. The overall survival rate was similar to international multicentric studies. Multisystem disease and absence of response at six weeks of treatment were the most important unfavorable prognostic factors. The frequency of reactivation for patients with multisystem disease was higher than described in the literature, probably because maintenance chemotherapy was used only in two cases.

OBJETIVOS: conhecer a percepção dos pais para o diagnóstico de leucemia em seus filhos. MÉTODOS: pesquisa qualitativa tendo como referencial a teoria das representações sociais ancorada na tradição da sociologia compreensiva. Utilizou-se entrevista semi estruturada para a coleta de dados. Foram entrevistados 20 pais de crianças e adolescentes com diagnóstico de leucemia linfóide aguda (LLA). Para análise dos dados empregou-se a técnica de "análise do conteúdo". As diretrizes de humanização da assistência e princípios bioéticos foram os eixos norteadores da análise dos dados. RESULTADOS: os pais recordaram-se claramente da progressão dos sintomas da doença até o diagnóstico. A palavra leucemia foi associada ao câncer e à morte. Dificuldades relacionadas à escuta dos sintomas, a particularidades clínicas da leucemia e ao encaminhamento no sistema de saúde foram os principais motivos para a demora do diagnóstico definitivo. Destacam-se as peregrinações por diferentes locais, perda da resolubilidade, gastos desnecessários, desgaste emocional e atraso nas ações de saúde. CONCLUSÕES: o câncer envolve valores culturais sobre a morte, cuja carga simbólica é maior no caso da criança. A busca do diagnóstico da leucemia pelos pais é exemplo emblemático do tortuoso caminho percorrido quando o mal que acomete a criança não se enquadra no rótulo das doenças "comuns".

OBJECTIVES: to investigate how parents perceive a diagnosis of lymphoid leukemia in their children. METHODS: qualitative research based on the sociological theory of social representations was used. Data was gathered by way of semi-structured interviews. Twenty parents of children diagnosed as having acute lymphoid leukemia (ALL). The content analysis technique was used to analyze data. Data analysis was guided by the principles of bioethics and humane care. RESULTS: the parents clearly recalled the progression of symptoms up to diagnosis. The word leukemia was associated with cancer and death. Difficulties related to listening to the symptoms, the specific clinical features of leukemia and the referral system were the main reasons for delay in arriving at a final diagnosis. The parents highlighted the need to move about a lot from one place to another, the lack of resolution, unnecessary costs, emotional strain and the slowness of the health services. CONCLUSIONS: cancer brings with out cultural values concerning death and these bear greater weight when a child is involved. The search for a diagnosis of leukemia by parents is a good example of the tortuous path they have to tread when what is wrong with their children is not something that bears the label of a "common" disease.

Os linfomas cutâneos compreendem um grupo heterogêneo de desordens linfoproliferativas que envolvem a pele e são classificados como um subgrupo dos linfomas não Hodgkin. No período de 1981 a 2007, 100 casos de linfomas em crianças foram admitidos no Serviço de Hematologia, do Hospital das Clínicas da Universidade Federal de Minas Gerais, sendo que nove apresentaram manifestação cutânea inicial. Três pacientes foram classificados como linfoma cutâneo primário e seis como sistêmicos. Sete pacientes apresentaram linfoma de células T, um, linfoma linfoblástico B e um, imunofenótipo indefinido. Nenhum óbito ocorreu nos pacientes com linfoma cutâneo primário

Cutaneous lymphomas comprise a heterogeneous group of lymphoproliferative disorders with skin involvement and are classified as a subgroup of non-Hodgkin lymphomas. From 1981 to 2007, 100 children with non-Hodgkin lymphomas were admitted to the Hematology Unit of the Federal University of Minas Gerais Teaching Hospital. In nine of these children, the skin was involved at the onset of the disease. Three patients were classified as having primary cutaneous lymphoma, while in six the disease was systemic with cutaneous involvement. In seven patients, the immunophenotype was T-cell, in one it was B-cell, and in the remaining case the immunophenotype was indefinable. No deaths occurred in any of the children with primary cutaneous lymphoma

BACKGROUND: Remission rates achieved after the initial treatment of acute lymphoblastic leukemia may be similar in both developed and developing countries, but relapse rates are much higher in the latter. Thus, other reasons are needed, in addition to biological characteristics of the leukemic cells themselves, to explain the unfavorable evolution of patients living in unfavorable socioeconomic and cultural conditions. OBJECTIVE: The aim of this study was to retrospectively evaluate compliance to an acute lymphoblastic leukemia treatment protocol. METHODS: Main abstracted data were: total duration and reasons for interruption of chemotherapy, prescribed doses of 6-mercaptopurine, and median white blood cell and neutrophil counts during the maintenance phase. Interruptions of chemotherapy were considered inappropriate if they did not follow predetermined criteria established in the protocol. RESULTS: Fourteen of 73 patients (19.2%) unduly interrupted chemotherapy by determination of their physicians. The median white blood cell count was higher when compared with the protocol recommendations; the median 6-MP dose was lower than the standard recommended dose. The estimated probability of event-free survival was higher for patients with lower median leukocyte counts and close to those predetermined by the protocol. Event-free survival was also higher for children with a higher percentage of days without chemotherapy due to bone marrow or liver toxicity excluding undue interruptions. In multivariate analysis, both factors remained statistically significant. These results suggest that the intensity of maintenance chemotherapy may not have been enough in some children, to achieve adequate myelosuppression, hence the observation of higher leukocyte counts and none or rare episodes of therapy interruption. CONCLUSIONS: Compliance to the therapeutic protocol by both doctors and patients should always be considered in the evaluation of therapeutic failure in acute lymphoblastic leukemia; strict adherence to treatment protocols contributes to better treatment results in acute lymphoblastic leukemia children.