RESUMEN

Relapsing polychondritis is a rare multisystem disease involving cartilaginous and proteoglycan-rich structures. The diagnosis of this disease is mainly suggested by the presence of flares of inflammation of the cartilage, particularly in the ears, nose or respiratory tract, and more rarely, in the presence of other manifestations. The spectrum of clinical presentations may vary from intermittent episodes of painful and often disfiguring auricular and nasal chondritis to an occasional organ or even life-threatening manifestations such as lower airway collapse. There is a lack of awareness about this disease is mainly due to its rarity. In 2020, VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome, a novel autoinflammatory syndrome, was described. VEXAS syndrome is attributed to somatic mutations in methionine-41 of UBA1, the major E1 enzyme that initiates ubiquitylation. This new disease entity connects seemingly unrelated conditions: systemic inflammatory syndromes (relapsing chondritis, Sweet's syndrome, and neutrophilic dermatosis) and hematologic disorders (myelodysplastic syndrome or multiple myeloma). Therefore, this article reviews the current literature on both disease entities.

Asunto(s)

Enfermedades Óseas , Policondritis Recurrente , Humanos , Policondritis Recurrente/diagnóstico , Policondritis Recurrente/tratamiento farmacológico , Policondritis Recurrente/genética , Inflamación/complicaciones , Enfermedades Óseas/complicaciones

RESUMEN

Abstract Relapsing polychondritis is a rare multisystem disease involving cartilaginous and proteoglycan-rich structures. The diagnosis of this disease is mainly suggested by the presence of flares of inflammation of the cartilage, particularly in the ears, nose or respiratory tract, and more rarely, in the presence of other manifestations. The spectrum of clinical presentations may vary from intermittent episodes of painful and often disfiguring auricular and nasal chondritis to an occasional organ or even life-threatening manifestations such as lower airway collapse. There is a lack of awareness about this disease is mainly due to its rarity. In 2020, VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome, a novel autoinflammatory syndrome, was described. VEXAS syndrome is attributed to somatic mutations in methionine-41 of UBA1, the major E1 enzyme that initiates ubiquitylation. This new disease entity connects seemingly unrelated conditions: systemic inflammatory syndromes (relapsing chondritis, Sweet's syndrome, and neutrophilic dermatosis) and hematologic disorders (myelodysplastic syndrome or multiple myeloma). Therefore, this article reviews the current literature on both disease entities.

RESUMEN

We present the case of a 53-yr-old woman with an inherited bone marrow failure coexisting with uncommon extrahematological symptoms, such as cirrhosis and skin abnormalities. Whole-exome sequencing revealed a diagnosis of Shwachman-Diamond syndrome (SDS) with an atypical presentation. Unexpected was the age of disease expression, normally around the pediatric age, with a predominantly median survival age of 36 yr. To our knowledge, she was the first adult patient with a molecular diagnosis of Shwachman-Diamond in Uruguay. The patient was referred to our service when she was 43-yr-old with a history of bone marrow failure with anemia and thrombocytopenia. All secondary causes of pancytopenia were excluded. Bone marrow aspirate and biopsy specimens were hypocellular for the patient's age. Numerous dysplastic features were observed in the three lineages. She had a normal karyotype and normal chromosomal fragility. A diagnosis of low-risk hypoplastic MDS was made. Dermatological examination revealed reticulate skin pigmentation with hypopigmented macules involving the face, neck, and extremities; nail dystrophy; premature graying; and thin hair. Extrahematological manifestations were present (e.g., learning difficulties, short stature). Last, she was diagnosed with cryptogenic liver cirrhosis CHILD C. This rules out all other possible causes of chronic liver disease. This clinical presentation initially oriented the diagnosis toward telomeropathy, so we did a telomeropathy NGS panel that came up negative. Finally, we did an exome sequencing that confirmed the diagnosis of SDS. Using whole-exome sequencing, we were able to find two compound heterozygous mutations in the SBDS gene that were responsible for the phenotype of a patient that was undiagnosed for 10 years. An earlier genetic diagnosis could have influenced our patient's outcome.

Asunto(s)

Enfermedades de la Médula Ósea , Insuficiencia Pancreática Exocrina , Femenino , Humanos , Síndrome de Shwachman-Diamond/genética , Insuficiencia Pancreática Exocrina/diagnóstico , Enfermedades de la Médula Ósea/diagnóstico , Enfermedades de la Médula Ósea/genética , Mutación , Proteínas/genética

RESUMEN

Green tea (GT) treatment was evaluated for its effect on the immune and antineoplastic response of elderly acute myeloid leukemia patients with myelodysplasia-related changes (AML-MRC) who are ineligible for aggressive chemotherapy and bone marrow transplants. The eligible patients enrolled in the study (n = 10) received oral doses of GT extract (1000 mg/day) alone or combined with low-dose cytarabine chemotherapy for at least 6 months and/or until progression. Bone marrow (BM) and peripheral blood (PB) were evaluated monthly. Median survival was increased as compared to the control cohort, though not statistically different. Interestingly, improvements in the immunological profile of patients were found. After 30 days, an activated and cytotoxic phenotype was detected: GT increased total and naïve/effector CD8+ T cells, perforin+/granzyme B+ natural killer cells, monocytes, and classical monocytes with increased reactive oxygen species (ROS) production. A reduction in the immunosuppressive profile was also observed: GT reduced TGF-ß and IL-4 expression, and decreased regulatory T cell and CXCR4+ regulatory T cell frequencies. ROS levels and CXCR4 expression were reduced in bone marrow CD34+ cells, as well as nuclear factor erythroid 2-related factor 2 (NRF2) and hypoxia-inducible factor 1α (HIF-1α) expression in biopsies. Immune modulation induced by GT appears to occur, regardless of tumor burden, as soon as 30 days after intake and is maintained for up to 180 days, even in the presence of low-dose chemotherapy. This pilot study highlights that GT extracts are safe and could improve the immune system of elderly AML-MRC patients.

Asunto(s)

Leucemia Mieloide Aguda , Té , Anciano , Linfocitos T CD8-positivos , Citarabina , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Proyectos Piloto

RESUMEN

Congenital malformations are functional and structural changes in organ systems, tissues, or organs that may develop during the embryonic or fetal phase. Spinal cord malformations, such as segmental hypoplasia of the spinal cord (SHSC) and syringomyelia, are rare in bovines. A Girolando calf from Valença, Rio de Janeiro, was admitted to the Veterinary Hospital of Universidade Federal Rural do Rio de Janeiro because of motor incoordination. Clinical evaluation revealed a 5-cm depression area in the spine at the dorsal line of the thoracic region. Neurological examination revealed reduced proprioception, pelvic limb extension with increased nociceptive activity, and reduced anal reflex. In radiographic examination, the body of the T11 vertebra had a trapezoidal wedge shape with ventral hemivertebra, probable agenesis or hypoplasia of the T11-T12 spinous processes, and fusion of the T9-T10 spinous processes. Myelography revealed extradural spinal compression caused by vertebral malformations. Necropsy showed no spinous processes (T11-T12), cranial stenosis in the medullary canal (T11-T13), and 1-3-mm pores in the white matter of the thoracic spinal cord (T8-T11). Microscopy revealed cystic dilatations in the white matter (T9-T11), cystic areas of varying sizes (T8-T9), and moderate reduction in the gray matter around the central canal of the medulla (T11-T13). Here, we reported the clinical and pathological findings of SHSC and syringomyelia in a Girolando calf. The features should be differentiated from other spinal cord syndromes. Congenital malformations are of economic importance, and their etiology and diagnosis are fundamental to disease control and progenitor-selection programs.(AU)

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Malformações congênitas são alterações funcionais e estruturais dos sistemas, tecidos ou órgãos que podem ocorrer na fase embrionária ou fetal. Malformações na medula espinhal, como hipoplasia segmentar da medula espinhal (HSME) e siringomielia, possuem raras descrições em bovinos. Uma bezerra Girolando, proveniente do Município de Valença, RJ, foi atendida no Hospital Veterinário da Universidade Federal Rural do Rio de Janeiro (UFRRJ), com quadro de incoordenação motora. À avaliação clínica, na coluna vertebral, à linha dorsal da região torácica havia uma área com depressão de 5 cm. Ao exame neurológico foi observado propriocepção reduzida, extensão de membros pélvicos com aumento da atividade nociceptiva e redução de reflexo anal. Ao exame radiográfico, o corpo vertebral T11 apresentou forma trapezoidal em cunha com hemivértebra ventral, provável agenesia ou hipoplasia dos processos espinhosos T11-T12 e fusão dos processos espinhosos T9-T10. À mielografia indicou compressão medular extradural provocada pelas malformações vertebrais. À necropsia não foram observados os processos espinhosos T11-T12, o canal medular apresentou estenose cranial (T11-T13) e, na medula espinhal torácica (T8-T11) foram observados poros de 1-3 mm na substância branca. À microscopia, os segmentos T9-T11 apresentaram dilatações císticas na substância branca e os segmentos T8-T9, formações de áreas císticas de tamanhos variados; nos segmentos T11-T13 denotou-se moderada redução da substância cinzenta ao redor do canal central da medula. O presente trabalho tem o objetivo de apresentar os achados clínicos e patológicos desta bezerra Girolando com HSME e siringomielia, que devem ser diferenciadas de outras síndromes da medula espinhal. As malformações congênitas possuem importância econômica e sua etiologia e diagnóstico são fundamentais para a condução de programas de controle de doenças e seleção de progenitores.(AU)

Asunto(s)

Animales , Bovinos , Médula Espinal/patología , Disgenesias Tiroideas/veterinaria , Siringomielia , Anomalías Congénitas , Defectos del Tubo Neural

RESUMEN

ABSTRACT: Congenital malformations are functional and structural changes in organ systems, tissues, or organs that may develop during the embryonic or fetal phase. Spinal cord malformations, such as segmental hypoplasia of the spinal cord (SHSC) and syringomyelia, are rare in bovines. A Girolando calf from Valença, Rio de Janeiro, was admitted to the Veterinary Hospital of Universidade Federal Rural do Rio de Janeiro because of motor incoordination. Clinical evaluation revealed a 5-cm depression area in the spine at the dorsal line of the thoracic region. Neurological examination revealed reduced proprioception, pelvic limb extension with increased nociceptive activity, and reduced anal reflex. In radiographic examination, the body of the T11 vertebra had a trapezoidal wedge shape with ventral hemivertebra, probable agenesis or hypoplasia of the T11-T12 spinous processes, and fusion of the T9-T10 spinous processes. Myelography revealed extradural spinal compression caused by vertebral malformations. Necropsy showed no spinous processes (T11-T12), cranial stenosis in the medullary canal (T11-T13), and 1-3-mm pores in the white matter of the thoracic spinal cord (T8-T11). Microscopy revealed cystic dilatations in the white matter (T9-T11), cystic areas of varying sizes (T8-T9), and moderate reduction in the gray matter around the central canal of the medulla (T11-T13). Here, we reported the clinical and pathological findings of SHSC and syringomyelia in a Girolando calf. The features should be differentiated from other spinal cord syndromes. Congenital malformations are of economic importance, and their etiology and diagnosis are fundamental to disease control and progenitor-selection programs.

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RESUMO: Malformações congênitas são alterações funcionais e estruturais dos sistemas, tecidos ou órgãos que podem ocorrer na fase embrionária ou fetal. Malformações na medula espinhal, como hipoplasia segmentar da medula espinhal (HSME) e siringomielia, possuem raras descrições em bovinos. Uma bezerra Girolando, proveniente do Município de Valença, RJ, foi atendida no Hospital Veterinário da Universidade Federal Rural do Rio de Janeiro (UFRRJ), com quadro de incoordenação motora. À avaliação clínica, na coluna vertebral, à linha dorsal da região torácica havia uma área com depressão de 5 cm. Ao exame neurológico foi observado propriocepção reduzida, extensão de membros pélvicos com aumento da atividade nociceptiva e redução de reflexo anal. Ao exame radiográfico, o corpo vertebral T11 apresentou forma trapezoidal em cunha com hemivértebra ventral, provável agenesia ou hipoplasia dos processos espinhosos T11-T12 e fusão dos processos espinhosos T9-T10. À mielografia indicou compressão medular extradural provocada pelas malformações vertebrais. À necropsia não foram observados os processos espinhosos T11-T12, o canal medular apresentou estenose cranial (T11-T13) e, na medula espinhal torácica (T8-T11) foram observados poros de 1-3 mm na substância branca. À microscopia, os segmentos T9-T11 apresentaram dilatações císticas na substância branca e os segmentos T8-T9, formações de áreas císticas de tamanhos variados; nos segmentos T11-T13 denotou-se moderada redução da substância cinzenta ao redor do canal central da medula. O presente trabalho tem o objetivo de apresentar os achados clínicos e patológicos desta bezerra Girolando com HSME e siringomielia, que devem ser diferenciadas de outras síndromes da medula espinhal. As malformações congênitas possuem importância econômica e sua etiologia e diagnóstico são fundamentais para a condução de programas de controle de doenças e seleção de progenitores.

RESUMEN

BACKGROUND: GATA2 is a transcription factor that is a critical regulator of gene expression in hematopoietic cells. GATA2 deficiency presents with multi-lineage cytopenia, mycobacterial, fungal and viral infections. Patients with GATA2 mutation have a high risk of developing myelodysplastic syndrome or acute myeloid leukemia. CASE PRESENTATION: We described a 43 years-old white male with 20-year follow-up of autoimmune and thrombotic phenomena, hypothyroidism, disseminated refractory Mycobacterium kansasii infection and MonoMAC syndrome. GATA2 c.1061 C > T; p.T354 M mutation was identified after he progressed from myelodysplastic pancytopenia to refractory anemia with excess blasts type II. His relatives were also investigated and he underwent unsuccessful haematopoietic stem cell transplantation. We discuss the clinical features, genetic diagnosis and treatment of this immunodeficiency disorder. CONCLUSIONS: This case illustrates the challenge how a multidisciplinary disease should be handle. Once usual causes of immunodeficiency were excluded, clinicians should considerGATA2 deficiency in patients with myelodysplasia and long-standing Mycobacterium kansasii infection.

Asunto(s)

Deficiencia GATA2/genética , Factor de Transcripción GATA2/genética , Mutación , Infecciones por Mycobacterium no Tuberculosas/genética , Infecciones por Mycobacterium no Tuberculosas/microbiología , Mycobacterium kansasii/aislamiento & purificación , Síndromes Mielodisplásicos/genética , Adulto , Antibacterianos/uso terapéutico , Humanos , Masculino , Infecciones por Mycobacterium no Tuberculosas/complicaciones , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico

RESUMEN

Cytogenetics is essential in myeloid neoplasms (MN) and pre-analytical variables are important for karyotyping. We assessed the relationship between pre-analytical variables (time from collection to sample processing, material type, sample cellularity, and diagnosis) and failures of karyotyping. Bone marrow (BM, n=352) and peripheral blood (PB, n=69) samples were analyzed from acute myeloid leukemia (n=113), myelodysplastic syndromes (n=73), myelodysplastic syndromes/myeloproliferative neoplasms (n=17), myeloproliferative neoplasms (n=137), and other with conclusive diagnosis (n=6), and reactive disorders/no conclusive diagnosis (n=75). The rate of unsuccessful karyotyping was 18.5% and was associated with the use of PB and a low number of nucleated cells (≤7×103/µL) in the sample. High and low cellularity in BM and high and low cellularity in PB samples showed no metaphases in 3.9, 39.7, 41.9, and 84.6% of cases, respectively. Collecting a good BM sample is the key for the success of karyotyping in MN and avoids the use of expensive molecular techniques.

Asunto(s)

Humanos , Masculino , Femenino , Adolescente , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Adulto Joven , Manejo de Especímenes/métodos , Síndromes Mielodisplásicos/genética , Células de la Médula Ósea/patología , Leucemia Mieloide/genética , Cariotipificación/métodos , Trastornos Mieloproliferativos/genética , Manejo de Especímenes/normas , Síndromes Mielodisplásicos/diagnóstico , Leucemia Mieloide/diagnóstico , Trastornos Mieloproliferativos/diagnóstico

RESUMEN

Apesar da prevalência da peritonite infecciosa felina (PIF) ser alta em praticamente o mundo todo, estudos anatomopatológicos recentes acerca dessa doença são escassos. Não obstante, as características microscópicas da medula óssea de gatos com PIF estão ausentes da literatura consultada. O objetivo deste artigo é descrever alterações medulares ósseas vistas em casos espontâneos de PIF. As medulas ósseas colhidas sistematicamente da região diafisária dos fêmures de 16 gatos necropsiados no Laboratório de Patologia Veterinária (LPV) da Universidade Federal de Santa Maria (UFSM), Rio Grande do Sul, entre janeiro de 2000 e junho de 2017, e que tiveram diagnóstico definitivo de PIF, foram avaliadas fenotípica (histopatologia - hematoxilina e eosina e histoquímica - reação de Perls) e imunofenotipicamente (utilizando marcadores mieloides (anti-MAC387) e de linfócitos (anti-CD79αcy e anti-CD3). Os resultados permitem afirmar que, independentemente da apresentação clinicopatológica da doença ocorrem as seguintes alterações: 1) hiperplasia mieloide; 2) hipoplasia eritroide, 3) displasia megacariocítica (dismegacariocitopoiese) e 4) plasmocitose medular. Exclusivamente nos casos de PIF seca há hemossiderose medular óssea e hepática. Essas alterações permitem estabelecer que gatos com PIF desenvolvem mielodisplasia, uma lesão mieloproliferativa muito semelhante àquela relatada em humanos infectados pelo HIV. Sugere-se que a partir dos achados aqui descritos, a mielodisplasia seja considerada a principal responsável pelas alterações hematológicas observadas na PIF, especialmente pela anemia e trombocitopenia arregenerativas frequentemente desenvolvidas pelos pacientes com essa doença.(AU)

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Although the prevalence of feline infectious peritonitis (FIP) is high worldwide, recent anatomopathological studies about this disease are scarce. Information on the microscopic characteristics of the bone marrow in FIP-affected cats are absent in the available literature. Based on this, the purpose of this article is to describe bone marrow lesions seen in spontaneous cases of FIP. The bone marrow collected systematically from the femoral diaphysis of 16 cats necropsied in the Laboratory of Veterinary Pathology (LPV) of the Federal University (UFSM) of Southern Brazil, between January 2000 and June 2017, with a definitive diagnosis of FIP, were evaluated phenotypically (histopathology - hematoxylin and eosin and histochemistry - Perls stain) and immunophenotypically (immunohistochemistry using myeloid - Anti-MAC387, and lymphocytic - Anti-CD79 αcy and Anti-CD3 markers). Regardless the following was observed the clinicopathological form of the disease ("dry" - noneffusive or "wet" - effusive): 1) myeloid hyperplasia; 2) erythroid hipoplasia; 3) megakaryocytic dysplasia (dismegakaryocytopoiesis); and 4) medullary plasmacytosis. Exclusively in cases of "dry FIP" was bone marrow and hepatic hemosiderosis. These lesions allowed establishing that cats with FIP develop myelodysplasia, a myeloproliferative lesion very similar to that reported in HIV-infected humans. It is suggested that, based on the findings described here, myelodysplasia is considered to be the main cause of hematological abnormalities observed in FIP, especially for non-regenerative anemia and thrombocytopenia, frequently developed by patients.(AU)

Asunto(s)

Animales , Gatos , Gatos/anomalías , Peritonitis Infecciosa Felina/diagnóstico , Hiperplasia/veterinaria , Defectos del Tubo Neural/diagnóstico

RESUMEN

Apesar da prevalência da peritonite infecciosa felina (PIF) ser alta em praticamente o mundo todo, estudos anatomopatológicos recentes acerca dessa doença são escassos. Não obstante, as características microscópicas da medula óssea de gatos com PIF estão ausentes da literatura consultada. O objetivo deste artigo é descrever alterações medulares ósseas vistas em casos espontâneos de PIF. As medulas ósseas colhidas sistematicamente da região diafisária dos fêmures de 16 gatos necropsiados no Laboratório de Patologia Veterinária (LPV) da Universidade Federal de Santa Maria (UFSM), Rio Grande do Sul, entre janeiro de 2000 e junho de 2017, e que tiveram diagnóstico definitivo de PIF, foram avaliadas fenotípica (histopatologia - hematoxilina e eosina e histoquímica - reação de Perls) e imunofenotipicamente (utilizando marcadores mieloides (anti-MAC387) e de linfócitos (anti-CD79αcy e anti-CD3). Os resultados permitem afirmar que, independentemente da apresentação clinicopatológica da doença ocorrem as seguintes alterações: 1) hiperplasia mieloide; 2) hipoplasia eritroide, 3) displasia megacariocítica (dismegacariocitopoiese) e 4) plasmocitose medular. Exclusivamente nos casos de PIF seca há hemossiderose medular óssea e hepática. Essas alterações permitem estabelecer que gatos com PIF desenvolvem mielodisplasia, uma lesão mieloproliferativa muito semelhante àquela relatada em humanos infectados pelo HIV. Sugere-se que a partir dos achados aqui descritos, a mielodisplasia seja considerada a principal responsável pelas alterações hematológicas observadas na PIF, especialmente pela anemia e trombocitopenia arregenerativas frequentemente desenvolvidas pelos pacientes com essa doença.(AU)

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Although the prevalence of feline infectious peritonitis (FIP) is high worldwide, recent anatomopathological studies about this disease are scarce. Information on the microscopic characteristics of the bone marrow in FIP-affected cats are absent in the available literature. Based on this, the purpose of this article is to describe bone marrow lesions seen in spontaneous cases of FIP. The bone marrow collected systematically from the femoral diaphysis of 16 cats necropsied in the Laboratory of Veterinary Pathology (LPV) of the Federal University (UFSM) of Southern Brazil, between January 2000 and June 2017, with a definitive diagnosis of FIP, were evaluated phenotypically (histopathology - hematoxylin and eosin and histochemistry - Perls stain) and immunophenotypically (immunohistochemistry using myeloid - Anti-MAC387, and lymphocytic - Anti-CD79 αcy and Anti-CD3 markers). Regardless the following was observed the clinicopathological form of the disease ("dry" - noneffusive or "wet" - effusive): 1) myeloid hyperplasia; 2) erythroid hipoplasia; 3) megakaryocytic dysplasia (dismegakaryocytopoiesis); and 4) medullary plasmacytosis. Exclusively in cases of "dry FIP" was bone marrow and hepatic hemosiderosis. These lesions allowed establishing that cats with FIP develop myelodysplasia, a myeloproliferative lesion very similar to that reported in HIV-infected humans. It is suggested that, based on the findings described here, myelodysplasia is considered to be the main cause of hematological abnormalities observed in FIP, especially for non-regenerative anemia and thrombocytopenia, frequently developed by patients.(AU)

Asunto(s)

Animales , Gatos , Gatos/anomalías , Peritonitis Infecciosa Felina/diagnóstico , Hiperplasia/veterinaria , Defectos del Tubo Neural/diagnóstico

RESUMEN

La fase leucémica como presentación de un linfoma folicular es rara y debe ser considerada factor de mal pronóstico. Por otra parte, la asociación entre linfoma folicular y síndrome mielodisplásico no se ha descrito. Se presenta el caso de una paciente en la que se detectó marcada leucocitosis y a la que se diagnosticó un linfoma folicular. Recibió quimioterapia con R-CHOP y FCR cuando recayó. Meses después, se realizó un aspirado medular en el cual se observaron cambios compatibles con mielodisplasia, únicamente recibió terapia de soporte y finalmente evolucionó a leucemia mieloide aguda. Aunque se conoce que la mielodisplasia puede ser secundaria al uso de quimioterapia, la paciente presentó además trisomía del cromosoma 11, descrita previamente en mielodisplasia y linfoma tipo Burkitt, la cual pudiera estar en relación con la evolución a leucemia mieloide aguda(AU)

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Follicular lymphoma rarely presents with a leukemic phase and this should be considered a negative prognostic factor. Also, follicular lymphoma and myelodysplastic syndrome association has not been previously reported. Herein we present a patient who debuted with marked hyperleukocytosis and was diagnosed with follicular lymphoma, receiving CHOP-R and FCR after she relapsed. Several months later, secondary myelodysplastic changes were observed in her bone marrow. She received supportive therapy and finally progressed into acute myeloid leukemia. Although secondary myelodysplasia is known to be produced by chemotherapy, this patient additionally had trisomy 11, previously described in myelodysplasia and Burkitt's lymphoma, which could be linked to progression to acute myeloid leukemia(AU)

Asunto(s)

Humanos , Femenino , Adulto , Leucemia/mortalidad , Linfoma Folicular/complicaciones , Leucocitosis/complicaciones , Linfoma Folicular

RESUMEN

La fase leucémica como presentación de un linfoma folicular es rara y debe ser considerada factor de mal pronóstico. Por otra parte, la asociación entre linfoma folicular y síndrome mielodisplásico no se ha descrito. Se presenta el caso de una paciente en la que se detectó marcada leucocitosis y a la que se diagnosticó un linfoma folicular. Recibió quimioterapia con R-CHOP y FCR cuando recayó. Meses después, se realizó un aspirado medular en el cual se observaron cambios compatibles con mielodisplasia, únicamente recibió terapia de soporte y finalmente evolucionó a leucemia mieloide aguda. Aunque se conoce que la mielodisplasia puede ser secundaria al uso de quimioterapia, la paciente presentó además trisomía del cromosoma 11, descrita previamente en mielodisplasia y linfoma tipo Burkitt, la cual pudiera estar en relación con la evolución a leucemia mieloide aguda(AU)

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Follicular lymphoma rarely presents with a leukemic phase and this should be considered a negative prognostic factor. Also, follicular lymphoma and myelodysplastic syndrome association has not been previously reported. Herein we present a patient who debuted with marked hyperleukocytosis and was diagnosed with follicular lymphoma, receiving CHOP-R and FCR after she relapsed. Several months later, secondary myelodysplastic changes were observed in her bone marrow. She received supportive therapy and finally progressed into acute myeloid leukemia. Although secondary myelodysplasia is known to be produced by chemotherapy, this patient additionally had trisomy 11, previously described in myelodysplasia and Burkitt's lymphoma, which could be linked to progression to acute myeloid leukemia(AU)

Asunto(s)

Humanos , Femenino , Adulto , Trisomía , Leucemia/mortalidad , Linfoma Folicular/complicaciones , Leucocitosis/complicaciones , Linfoma Folicular/tratamiento farmacológico

RESUMEN

OBJECTIVE: To evaluate the expression of genes related to nuclear excision (ERCC8, XPA and XPC), homologous recombination and non-homologous end-joining (ATM, BRCA1, BRCA2 and LIG4) repair mechanisms, using quantitative PCR methodologies, and it relation with bone marrow cellularity in myelodysplastic syndrome (MDS). METHODS AND RESULTS: A total of 51 adult de novo patients with MDS (3 refractory anaemia (RA), 11 refractory anaemia with ringed sideroblasts (RARS), 28 refractory cytopenia with multilineage dysplasia (RCMD), 3 refractory anaemia with excess blasts type I (RAEB-I), 5 refractory anaemia with excess blasts type II (RAEB-II), and 1 chronic myelomonocytic leukaemia (CMML) were evaluated. For karyotype, 16.2% patients were defined as very low prognosis, 59.5% low risk, 8.1% intermediate risk, 5.4% high risk and 10.8% very high risk. For bone marrow cellularity, 17.6%, 17.6% and 64.7% presented as hypocellular, normocellular and hypercellular, respectively. Patients with hypocellular MDS had significantly decreased expression of ATM (p=0.000), BRCA1 (p=0.014), BRCA2 (p=0.003), LIG4 (p=0.004) and ERCC8 (p=0.000) than those with normocellular/hypercellular bone marrow, whereas XPA (p=0.049) and XPC (p=0.000) genes were increased. In patients with hypoplastic MDS, a low expression of ATM (p=0.0268), LIG4 (p=0.0199) and ERCC8 (p=0.0493) was significantly associated with the presence of chromosomal abnormalities. We detected positive correlations between BRCA1 and BRCA2 (r=0.416; p=0.007), ATM and LIG4 (r=0.472; p=0.001), LIG4 and BRCA1 (r=0.333; p=0.026), LIG4 and BRCA2 (r=0.334; p=0.025), ATM and XPA (r=0.377; p=0.008), ATM and XPC (r=0.287; p=0.046), LIG4 and XPC (r=0.371; p=0.007) and XPA and XPC genes (r=0.895; p=0.0000). We also found among all patients evaluated that correlation with LIG4 occurred most often. CONCLUSIONS: These correlations demonstrate the important intrinsic relations between single and double DNA strand breaks genes in MDS, emphasising that these genes are related to MDS pathogenesis.

Asunto(s)

Células de la Médula Ósea/patología , Enzimas Reparadoras del ADN/genética , Reparación del ADN , Síndromes Mielodisplásicos/genética , Síndromes Mielodisplásicos/patología , Adulto , Anciano , Anciano de 80 o más Años , Proteínas de la Ataxia Telangiectasia Mutada/genética , Proteína BRCA1/genética , Proteína BRCA2/genética , Biopsia , Examen de la Médula Ósea , Roturas del ADN de Doble Cadena , Roturas del ADN de Cadena Simple , ADN Ligasa (ATP)/genética , Proteínas de Unión al ADN/genética , Femenino , Regulación Enzimológica de la Expresión Génica , Marcadores Genéticos , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/mortalidad , Valor Predictivo de las Pruebas , Reacción en Cadena en Tiempo Real de la Polimerasa , Factores de Transcripción/genética , Proteína de la Xerodermia Pigmentosa del Grupo A/genética , Adulto Joven

RESUMEN

AIMS: The myelodysplastic syndromes (MDS) are a heterogeneous group of clonal haematopoietic stem cell disorders characterised by inefficient haematopoiesis and risk of progression to acute myeloid leukaemia. Metaphase cytogenetics is an extremely valuable clinical tool in the management of haematological malignancies. However, metaphase cytogenetics requires cellular proliferation, its sensitivity and resolution depends on the proportion of clonal cells in the sample and size of the lesion, respectively. Single-nucleotide polymorphism array (SNP-A) does not depend on the presence of dividing cells, is able to detect copy number variations with a high resolution and to detect copy number neutral loss of heterozygosity or uniparental disomy (UPD). The aim of this study was to illustrate that the use of SNP-A can cover cryptic chromosomal lesions not identified by metaphase cytogenetics in patients with MDS. METHODS: Metaphase cytogenetics was performed on bone marrow aspirate using standard methods. Genomic DNA from total bone marrow cells were submitted to SNP-A using Affymetrix Genome-Wide Human SNP CytoScan HD. RESULTS: In our cohort of 15 patients with a diagnosis of MDS and related diseases, chromosomal abnormalities were found in 47% of the cases by SNP-A and in 33% by metaphase cytogenetics. SNP-A detected all lesions identified by metaphase cytogenetics, except a balanced translocation and a marker chromosome. Notably, SNP-A detected a total of 30 new lesions: 1 (3%) gain, 17 (57%) losses and 12 (40%) UPDs in 5 patients with MDS. CONCLUSIONS: SNP-A may complement metaphase cytogenetics to improve the detection of chromosomal abnormalities in myeloid neoplasms.

Asunto(s)

Aberraciones Cromosómicas , Variaciones en el Número de Copia de ADN/genética , Neoplasias Hematológicas/genética , Síndromes Mielodisplásicos/genética , Trastornos Mieloproliferativos/genética , Polimorfismo de Nucleótido Simple/genética , Anciano , Anciano de 80 o más Años , Brasil , Estudios de Cohortes , Análisis Citogenético , Femenino , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/patología , Humanos , Cariotipificación , Masculino , Metafase , Persona de Mediana Edad , Síndromes Mielodisplásicos/diagnóstico , Síndromes Mielodisplásicos/patología , Trastornos Mieloproliferativos/diagnóstico , Trastornos Mieloproliferativos/patología , Disomía Uniparental

RESUMEN

As síndromes mielodisplásicas (SMD) são um grupo de desordens adquiridas da medula óssea, caracterizadas por citopenias no sangue periférico, e hipercelularidade na medula óssea com alterações displásicas em uma ou mais linhagens celulares hematopoiéticas. O objetivo do presente relato é descrever um caso de SMD uma vez que esta enfermidade é de ocorrência rara e existem poucos relatos na medicina veterinária.

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The myelodysplastic syndromes (MDS) are a group of bone marrow acquired disorders, characterized by peripheral blood cytopenias, and hypercellular bone marrow with displastyc changes in one or more hematopoietic cell lines. This paper’s aim is to report a MDS case since this is a rare disease and there are just a few reports in veterinary medicine.

Asunto(s)

Animales , Perros , Células Sanguíneas , Células de la Médula Ósea , Síndromes Mielodisplásicos/veterinaria , Mielografía/veterinaria

RESUMEN

As síndromes mielodisplásicas (SMD) são um grupo de desordens adquiridas da medula óssea, caracterizadas por citopenias no sangue periférico, e hipercelularidade na medula óssea com alterações displásicas em uma ou mais linhagens celulares hematopoiéticas. O objetivo do presente relato é descrever um caso de SMD uma vez que esta enfermidade é de ocorrência rara e existem poucos relatos na medicina veterinária.(AU)

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The myelodysplastic syndromes (MDS) are a group of bone marrow acquired disorders, characterized by peripheral blood cytopenias, and hypercellular bone marrow with displastyc changes in one or more hematopoietic cell lines. This papers aim is to report a MDS case since this is a rare disease and there are just a few reports in veterinary medicine.(AU)

Asunto(s)

Animales , Perros , Síndromes Mielodisplásicos/veterinaria , Células de la Médula Ósea , Células Sanguíneas , Mielografía/veterinaria

RESUMEN

We review the murine and human microenvironment and hematopoietic stem cell niche in the context of intact bone marrow architecture in man and mouse, both in normal and in myelodysplastic syndrome marrow. We propose that the complexity of the hematopoietic stem cell niche can usefully be approached in the context of its topobiology, and we provide a model that incorporates in vitro and in vivo models as well as in situ findings from intact human marrow to explain the changes seen in myelodysplastic syndrome patients. We highlight the clinical application of the study of the bone marrow microenvironment and its topobiology in myelodysplastic syndromes.

Asunto(s)

Médula Ósea/patología , Células Madre Hematopoyéticas/patología , Síndromes Mielodisplásicos/patología , Nicho de Células Madre , Animales , Humanos , Macrófagos/patología , Células Madre Mesenquimatosas/patología , Ratones

RESUMEN

AIMS: To study the immunoexpression of proteins related to the mitotic checkpoint (cell division cycle 20 (CDC20), mitotic arrest deficient 2 (MAD2)) and the mitotic spindle (Aurora-B) in patients with myelodysplastic syndrome (MDS). METHODS: Protein expression was analysed in bone marrow tissue samples from 40 patients with MDS using immunohistochemistry. Prognostic markers (transfusion dependency, depth of cytopenias, chromosomal abnormalities and survival) were also studied. RESULTS: Higher MAD2 expression was observed among patients with platelets <50×10(9)/L than among patients with platelets ≥50×10(9)/L (42.6±22.8% vs 22.7±19.1%, respectively). Higher CDC20 expression was identified among patients with three dysplasias compared with patients who presented with one or two dysplasias (33.9±24.1% vs 10.5±5.7% vs 12.8±7.8%, respectively), among patients who exhibited a complex versus non-complex karyotype (50.0±30.2% vs 18.4±14%, respectively) and among patients with platelets <50×10(9)/L vs platelets ≥50×10(9)/L (38.2±26.2% vs 16.1±12.4%, respectively). Higher Aurora-B expression was found in patients with an abnormal versus normal karyotype (21.2±13.2% vs 7.5±5.0%, respectively). High expression of MAD2 and CDC20 (≥50%) was associated with severe thrombocytopenia. We also found statistically significant differences in the overall survival rate when comparing different degrees of CDC20, MAD2 and Aurora-B protein expression. CONCLUSIONS: To the best of our knowledge, this is the first report to demonstrate that these proteins are associated with chromosomal abnormalities and poor prognosis in patients with MDS.

Asunto(s)

Aurora Quinasa B/análisis , Médula Ósea/química , Proteínas Cdc20/análisis , Inestabilidad Cromosómica , Puntos de Control de la Fase M del Ciclo Celular , Proteínas Mad2/análisis , Síndromes Mielodisplásicos/metabolismo , Huso Acromático/química , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Médula Ósea/patología , Bandeo Cromosómico , Femenino , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Cariotipo , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/sangre , Síndromes Mielodisplásicos/genética , Síndromes Mielodisplásicos/mortalidad , Síndromes Mielodisplásicos/patología , Recuento de Plaquetas , Pronóstico , Estudios Retrospectivos , Trombocitopenia/sangre , Trombocitopenia/genética , Trombocitopenia/metabolismo , Adulto Joven

RESUMEN

Background: The nervous system is one of the most affected by congenital malformations. These can occur during neural tube formation or failed neurogenesis. Segmental spinal cord hypoplasia commonly involves two or three spinal segments in the thoracolumbar region. It is characterized by incomplete formation of the spinal cord and may also be followed by spine column malformations. Clinical signs usually include functional impairment of the hindlimbs. Diagnosis is based on history, clinical signs, age, radiographs and is confi rmed with necropsy and histopathological fi ndings. There is no treatment for this condition and the animals present low life quality. This paper aims to report the clinical, radiographic and histopathological aspects of multiple segmental spinal cord hypoplasia in a domestic cat. Case: A 52-days-old, female, Persian breed, domestic cat weighing 0.55 kg was treated presenting a history of pelvic limb paraplegia associated with urinary and fecal incontinence since birth. On clinical examination there were fl accid paraplegia of hind limbs associated with absence of proprioception, anal refl ex and tone and postural defi cits. Also, all spinal refl exes of pelvic limbs and deep and superfi cial pain were absent. There was no clinical history of muscular tremors, nystagmus, seizures or other central nervous system signs. The other animals of the litter showed...(AU)

Asunto(s)

Animales , Femenino , Gatos , Defectos del Tubo Neural/diagnóstico por imagen , Defectos del Tubo Neural/diagnóstico , Defectos del Tubo Neural/veterinaria , Anomalías Congénitas/veterinaria

RESUMEN

Background: The nervous system is one of the most affected by congenital malformations. These can occur during neural tube formation or failed neurogenesis. Segmental spinal cord hypoplasia commonly involves two or three spinal segments in the thoracolumbar region. It is characterized by incomplete formation of the spinal cord and may also be followed by spine column malformations. Clinical signs usually include functional impairment of the hindlimbs. Diagnosis is based on history, clinical signs, age, radiographs and is confi rmed with necropsy and histopathological fi ndings. There is no treatment for this condition and the animals present low life quality. This paper aims to report the clinical, radiographic and histopathological aspects of multiple segmental spinal cord hypoplasia in a domestic cat. Case: A 52-days-old, female, Persian breed, domestic cat weighing 0.55 kg was treated presenting a history of pelvic limb paraplegia associated with urinary and fecal incontinence since birth. On clinical examination there were fl accid paraplegia of hind limbs associated with absence of proprioception, anal refl ex and tone and postural defi cits. Also, all spinal refl exes of pelvic limbs and deep and superfi cial pain were absent. There was no clinical history of muscular tremors, nystagmus, seizures or other central nervous system signs. The other animals of the litter showed...

Asunto(s)

Femenino , Animales , Gatos , Defectos del Tubo Neural/diagnóstico , Defectos del Tubo Neural/diagnóstico por imagen , Defectos del Tubo Neural/veterinaria , Anomalías Congénitas/veterinaria