Extramedullary Imaging Manifestations of Leukemia/Lymphoblastic Lymphoma in Pediatrics: A Case Series.

Leukemia is the most common childhood malignancy and often presents with nonspecific symptoms. Occasionally, it presents with extramedullary manifestations, which have been more frequent in cases of myeloid lineage or T cells. However, precursor B-cell leukemia/lymphoblastic lymphoma can also have extramedullary manifestations in some patients. Describing certain clinical features along with diagnostic imaging can establish a presentation pattern and suggest a diagnosis in the pediatric population. Herein, we present a series of four patients with extramedullary manifestations of B-cell lymphoblastic leukemia, describing their clinical imaging and histopathological characteristics.

Hemocromatosis: actualización clínica y diagnóstica / Hemochromatosis: clinical and diagnostic update

La hemocromatosis es un desorden en el cual la sobrecarga progresiva de hierro puede llevar a complicaciones sistémicas con gran morbimortalidad. Es una entidad clinicopatológica, con múltiples genes comprometidos y una fisiopatología común, con una expresión clínica y fenotípica variable, que depende de múltiples factores, tanto individuales como ambientales. Para su diagnóstico y seguimiento adecuado es necesario tener en cuenta elementos clínicos, bioquímicos y moleculares. En esta revisión, se presentan las generalidades de la hemocromatosis, además de sus mecanismos fisiopatológicos y moleculares, teniendo en cuenta su valor para el diagnóstico de la enfermedad. Adicionalmente, se describe la clasificación y un algoritmo diagnóstico propuestos recientemente por grupos de trabajo de expertos, así como las opciones de manejo y seguimiento de los pacientes con hemocromatosis

Hemochromatosis is a disorder in which progressive iron overload may lead to systemic complications with potential morbidity and mortality. It is a clinicopathologic entity that involves multiple genes and common pathophysiology, and has a variable clinical and phenotypic expression that depends on several individual and environmental factors. To make the diagnosis and perform a proper follow-up, clinical, biochemical, and molecular elements must be considered. This review aims to present the general characteristics of hemochromatosis, its molecular and pathophysiologic mechanisms, and their significance in the diagnosis of this disorder. In addition, a new classification and a proposed diagnostic algorithm by an expert working group are described, as well as management and follow-up options for patients with hemochromatosis

Linfoma de Hodgkin clásico: diferentes caras, una misma entidad / Classic Hodgkin lymphoma: different faces, same entity

El linfoma de Hodgkin clásico es una neoplasia linfoide maligna derivada de las células B del centro germinal, que corresponde aproximadamente al 85 % de los casos de linfoma de Hodgkin. Esta entidad afecta principalmente a pacientes jóvenes, y cuenta con un excelente pronóstico gracias a los avances en los métodos diagnósticos para su estadificación y tratamiento. Su enfoque diagnóstico correcto y completo requiere de una historia clínica exhaustiva y una biopsia de ganglio linfático adecuada para el análisis e identificación de los hallazgos histopatológicos e inmunohistoquímicos característicos, ya que a diferencia de otros linfomas donde las células neoplásicas son una población importante o dominante, las células de Hodgkin y Reed-Sternberg generalmente representan menos del 10 % de la lesión tumoral. Aunque todavía falta mucho por entender sobre la naturaleza biológica de este linfoma y sus diferentes subtipos, en los últimos años se ha avanzado considerablemente en la comprensión de su linfomagénesis, especialmente cuando está relacionada con la infección por el virus de Epstein-Barr. Su alta heterogeneidad y posible superposición morfológica, obligan a continuar su estudio para poder identificarlo, al igual que a sus posibles diagnósticos diferenciales en aquellos casos donde se presente con una variante o patrón infrecuente. Este artículo pretende ofrecer una descripción integral resumida y actualizada sobre la fisiopatología, la clínica, el diagnóstico histopatológico con énfasis en aquellos patrones raros que podrían llegar a ser factores distractores y de confusión, y el pronóstico del linfoma de Hodgkin clásico, buscando lograr una mejor comprensión de la enfermedad

Classic Hodgkin lymphoma is a malignant lymphoid neoplasm derived from B cells in the germinal center, and accounts for approximately 85% of all Hodgkin lymphoma cases. This disease mainly affects young patients and has an excellent prognosis due to advances in diagnostic methods for staging and treatment. A correct and complete diagnostic approach requires a thorough clinical history and an adequate lymph node biopsy for the analysis and identification of characteristic histopathological and immunohistochemical findings. Unlike other lymphomas where neoplastic cells are an important or dominant population, Reed-Sternberg/ Hodgkin cells generally represent less than 10% of the tumor lesion. Although much remains to be understood about the biological nature of this lymphoma and its different subtypes, considerable progress has been made in understanding its lymphomagenesis in recent years, especially when it is related to Epstein-Barr virus infection. Its high heterogeneity and possible morphological overlap require ongoing study to identify it and its possible differential diagnoses in cases where it presents with a rare variant or pattern. This article aims to provide a comprehensive updated summary on the pathophysiology, clinical presentation, histopathological diagnosis, with emphasis on rare patterns that could become distracting and confusing factors, and prognosis of classic Hodgkin lymphoma, seeking to achieve a better understanding of the disease

Myeloproliferative Syndrome With Eosinophilia Associated With Translocation t(8; 13) and T-cell Lymphoblastic Lymphoma: A Case Report and Review of the Literature.

The 8p11 myeloproliferative syndrome (EMS) is an aggressive neoplasm associated with chromosomal translocations involving the fibroblast growth factor receptor 1 tyrosine kinase gene on chromosome 8p11. We report the case of a 31-year-old man with no prior medical history who presents with two weeks of sore throat and cervical lymphadenopathy up to 5 cm. Initial peripheral blood examination showed leukocytosis with predominantly neutrophils and eosinophilia. A CT scan demonstrated mediastinal lymphadenopathies, liver enlargement and splenomegaly. An excisional biopsy of a cervical lymph node demonstrated findings consistent with a diagnosis of T-cell lymphoblastic lymphoma. Bone marrow aspirate and biopsy revealed hypercellular marrow with granulocytic predominance, left-shifted granulopoiesis, eosinophilia and the cytogenetic analysis showed the following karyotype: 46, XY, t(8;13). The final diagnosis was a myeloproliferative syndrome with eosinophilia related to t(8;13) and T-cell acute lymphoblastic lymphoma (8p11 myeloproliferative syndrome). We review the relevant literature about this unusual entity.

Hemofilia A: una enfermedad huérfana / Hemophilia A: a rare disease

La hemofilia A es una enfermedad hereditaria ligada al cromosoma X, causada por mutaciones en el gen F8 del factor VIII de la coagulación. Se considera una enfermedad huérfana, ya que su prevalencia es baja, de 26,6 por cada 100.000 nacidos vivos de sexo masculino. Los pacientes con hemofilia A tienen fases de inicio y amplificación de la coagulación relativamente normales y son capaces de formar el tapón plaquetario inicial en el lugar de la hemorragia, pero debido a la deficiencia del factor VIII, son incapaces de generar una cantidad de trombina en la superficie de las plaquetas, que sea suficiente para estabilizar el coágulo de fibrina. En un paciente masculino con hemorragias inusuales debe descartarse un trastorno de coagulación tipo hemofilia A, y se debe solicitar un recuento de plaquetas y un tiempo de protrombina (TP), los cuales usualmente son normales, y un tiempo de tromboplastina parcial activado (TPT) que se presenta prolongado. Para el diagnóstico diferencial con otras coagulopatías se realiza la medición de factores de coagulación, y pruebas de corrección cuando existe la sospecha de un inhibidor o de una hemofilia adquirida. Los pacientes afectados pueden presentar formas leves, moderadas o severas de la enfermedad, según el nivel plasmático del factor. En Colombia y en el mundo, la hemofilia fue reconocida como una enfermedad huérfana que representa un problema de salud pública, debido a su proceso de atención altamente especializado, que incrementa los costos asociados con la asistencia sanitaria, y afecta la calidad de vida de los pacientes y de aquellos que los rodean, además de que representa un reto diagnóstico que requiere constante actualización, para que pueda ser tratada de manera efectiva

Hemophilia A is an X-linked inherited disease caused by mutations in the coagulation factor VIII F8 gene. It is considered a rare disease, as its prevalence is 26.6 per 100,000 live male births. Patients with hemophilia A have a relatively normal coagulation onset and amplification phases, and are able to form the initial platelet plug at the site of hemorrhage; but due to factor VIII deficiency, they are unable to generate a sufficient amount of thrombin on the platelet surface to stabilize the fibrin clot. In a male patient with unusual bleeding, a hemophilia A-type coagulation disorder should be ruled out, and blood tests such as a platelet count and prothrombin time (PT), which are usually normal, and an activated partial thromboplastin time (APTT), which is prolonged, should be requested immediately. For differential diagnosis with other coagulopathies, measurement of coagulation factors and correction tests are performed when there is suspicion of an inhibitor or acquired hemophilia. Affected patients may present mild, moderate or severe forms of the disease, depending on the plasma level of the factor. In Colombia and worldwide, hemophilia was recognized as a rare disease that represents a public health problem due to its highly specialized care, which increases the costs associated with health care, and affects the quality of life of patients and those around them, as well as representing a diagnostic challenge that requires constant updating, so that it can be treated effectively

Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal Gammopathy, and Skin Changes (POEMS) Syndrome With IgG Kappa/IgG Lambda Biclonal Gammopathy: A Rare Presentation of a Rare Disease.

Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome is a low prevalence multisystemic paraneoplastic disease. The name is an acronym composed by its most relevant clinical manifestations, which are polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes. More than 95% of the POEMS syndrome cases are monoclonal for lambda light chains; however, few cases have been reported in the literature with a biclonal component. In this paper, we report a rare case of a patient who has POEMS syndrome with biclonal gammopathy. To the best of our knowledge, this is the first reported case in the literature of POEMS syndrome with expression of IgG kappa/IgG lambda biclonal gammopathy.

Cytotoxic Epstein-Barr virus-positive large B cell lymphoma: a regulatory B cell-derived neoplasia?

AIMS: A new subtype of granzyme B (GrB)-producing regulatory B cells (Bregs ) has been described recently; these peculiar cytotoxic B cells are increased significantly in interleukin (IL)-21-rich settings, and in particular during HIV and Epstein-Barr virus (EBV) infection. Our aim is to report a unique case of an EBV-positive diffuse large B cell lymphoma (DLBCL) with cytotoxic features arisen in an HIV+ patient, and to understand if this lesion may represent a proliferation of neoplastic cytotoxic Bregs . METHODS AND RESULTS: We describe a 66-year-old male patient who presented with cervical lymph node enlargement and B symptoms; subsequently, HIV infection was diagnosed. Histopathological, immunohistochemical and molecular studies were performed, and revealed an EBV-positive DLBCL with cytotoxic features. Considering the immunological setting and unconventional phenotype observed, we tried to evaluate further the expression of GrB and IL-21 in another 150 aggressive B cell lymphomas (17 of 150 EBV+ , two of 150 EBV+ /HIV+ ). Minimal dot-like expression of GrB was found in seven lymphomas (in fewer than 1% of tumour cells), three of which were EBV-positive. CONCLUSIONS: Breg origin has never been reported in B cell lymphomas. We describe an exceptional case of EBV-positive DLBCL with aberrant expression of cytotoxic markers in a patient with a previously unknown HIV infection. We propose cytotoxic Bregs as a possible normal counterpart for this unusual tumour.

Desorden linfoproliferativo T sistémico de la infancia asociado al virus Epstein-Barr: reporte de un caso / Systemic Epstein-Barr virus-positive T celllymphoproliferative disease of childhood: a case report

Resumen: el desorden linfoproliferativo T sistémico de la infancia asociado al virus Epstein-Barres una entidad clínica de descripción reciente, potencialmente mortal en niños y en adultos jóvenes.Se caracteriza por una proliferación clonal de linfocitos T con un fenotipo citotóxico activadoinfectados por el virus. Es más frecuente en países de Asia y México, y se desconoce su incidenciaen el medio. Se reporta un caso de esta enfermedad, con progresión indolente y desenlace fatal.

Abstract: systemic Epstein-Barr virus-positive T cell Iymphoproliferative disease of childhood is arecently described, potentially lethal clinical entity in children and young adults, characterized bya clonal proliferation of EBV-infected T-cells with an activated cytotoxic phenotype. It is typicallyprevalent in Asian countries and Mexico, and its incidence is unknown in our country. This reportdescribes a case of systemic Epstein-Barr virus positive.

Tumor de células gigantes de hueso: serie de casos durante 64 años en un único centro / Giant cell tumor of bone: a 64 years single center experience

Introducción: El tumor de células gigantes de hueso es una lesión localmente agresiva que tien-de a la recurrencia local y ocasionalmente presenta metástasis a distancia. Objetivo: describir la presentación clínica e histológica y la frecuencia relativa del tumor de células gigantes de hueso en un único centro, Medellín-Colombia. Materiales y métodos: estudio descriptivo; se revisaron todos los casos diagnosticados como tumor de células gigantes de hueso entre 1944 y 2008 en el Departamento de Patología de la Universidad de Antioquia, y para cada uno se revisaron las prin-cipales características clínicas e histológicas. Resultados: entre 1944 y 2008 se diagnosticaron 2.185 tumores óseos; de éstos, 302 tenían diagnóstico de tumor de células gigantes del hueso y se confirmó el diagnóstico en 117, correspondiente al 5,3% de todos los tumores óseos. La rela-ción mujer: hombre fue de 1,1:1. Las localizaciones más frecuentes fueron fémur distal (19,7%), tibia proximal (25,6%), manos y pies (11,1%), radio distal (9,4%) y húmero proximal (8,5%). Las características histológicas atípicas que se observaron fueron áreas fusocelulares, invasión de tejidos blandos, necrosis, hemorragia, áreas de quiste óseo aneurismático secundario, áreas de células mononucleadas con escasas células gigantes y formación de osteoide dentro del tumor...

Introduction: Giant cell tumors of bone are locally aggressive lesions that tend to recur locally and that rarely metastasize. Objective: to describe clinical and histological features, and relative frequency of giant cell tumors of bone in a single center, in the city of Medellín-Colombia. Materials and methods: a cross-sectional study was conducted. All the tumors diagnosed as giant cell tumor of bone between 1944 and 2008 in the Department of Pathology of Universidad de Antioquia were reviewed, and for each patient, important clinical and histological features were assessed. Results: between the years 1944 and 2008, 2,185 bone tumors were diagnosed; of these, 302 were diagnosed as giant cell tumor of bone, but in this study the diagnosis was confirmed only in 117 cases; 5.3% of all bone tumors. The female: male ratio was 1.1:1. The tumors were most requently found in the distal femur (19.7%), proximal tibia (25.6%), hands and feet (11.1%), distal radio (9.4%), and proximal humerus (8.5%). Atypical features observed in the tumors included spindle cell areas, soft tissue invasion, necrosis, hemorrhage, aneurysmal bone cyst-like changes, and osteoid formation...