Análisis integrado clínico, molecular e histopatológico de la médula ósea en las neoplasias mieloproliferativas crónicas / Comprehensive clinical, molecular and histopathological analysis of bone marrow in chronic myeloproliferative neoplasia

OBJETIVOS: Análisis de las posibles correlaciones entre las alteraciones moleculares en los genes JAK2, MPL y CALR, el patrón morfológico de la médula ósea y el perfil clínico-hematológico de los pacientes. PACIENTES Y MÉTODOS: Se trata de un estudio retrospectivo que incluye 140 pacientes con diagnóstico de neoplasias mieloproliferativas Filadelfia negativas (NMP Fi−) de un único centro. RESULTADOS: En la TE, los pacientes con la mutación el JAK2 V617F, presentaron un mayor número de leucocitos y neutrófilos que aquellos que presentaron la mutación en CALR. Los CALR mutados obtuvieron un mayor número de plaquetas y mayor necesidad de tratamiento citorreductor. Estos hallazgos apoyan el hecho de que el estado mutacional en la TE parece definir subtipos de pacientes con un curso clínico y pronóstico substancialmente diferentes. En la MF el estado mutacional parece influir en los cambios histopatológicos encontrados en la BMO, lo que no ocurrió en PV y TE

OBJECTIVES: To analyse the possible correlation between molecular changes in the JAK2, MPL and CALR genes, the morphological pattern of bone marrow and the clinical-haematologic profile of patients. PATIENTS AND METHODS: We conducted a retrospective study that included 140 patients diagnosed with Philadelphia-negative myeloproliferative neoplasia (Ph-MPN) in a single centre. RESULTS: In essential thrombocythaemia (ET), the patients with the JAK2 V617F mutation presented more leucocytes and neutrophils than patients who presented the CALR mutation, who had more platelets and a greater need for cytoreductive therapy. These findings support the fact that the mutational state in ET appears to define subtypes of patients with substantially different clinical courses and prognoses. In myelofibrosis, the mutational state appears to influence the histopathological changes found in the bone marrow biopsy, which did not occur in polycythaemia vera or ET

Comprehensive clinical, molecular and histopathological analysis of bone marrow in chronic myeloproliferative neoplasia. / Análisis integrado clínico, molecular e histopatológico de la médula ósea en las neoplasias mieloproliferativas crónicas.

OBJECTIVES: To analyse the possible correlation between molecular changes in the JAK2, MPL and CALR genes, the morphological pattern of bone marrow and the clinical-haematologic profile of patients. PATIENTS AND METHODS: We conducted a retrospective study that included 140 patients diagnosed with Philadelphia-negative myeloproliferative neoplasia (Ph-MPN) in a single centre. RESULTS: In essential thrombocythaemia (ET), the patients with the JAK2 V617F mutation presented more leucocytes and neutrophils than patients who presented the CALR mutation, who had more platelets and a greater need for cytoreductive therapy. These findings support the fact that the mutational state in ET appears to define subtypes of patients with substantially different clinical courses and prognoses. In myelofibrosis, the mutational state appears to influence the histopathological changes found in the bone marrow biopsy, which did not occur in polycythaemia vera or ET.

Splenic marginal zone lymphoma--a clinicopathological study in a series of 16 patients.

Splenic marginal zone lymphoma (SMZL), characterized in the WHO classification of lymphoid tumors, is a rare disorder comprising less than 1% of lymphoid neoplasms; only a few series concerning this entity have been published. Although this type of lymphoma is well defined histologically, its histogenesis remains obscure. Moreover, specific biological markers are still lacking and immunophenotype profile is not specific. These and other reasons, such as the existence of cytogenetic subtypes, have led to some authors to suspect that SMZL constitutes a heterogeneous entity. We have analyzed a series of sixteen SMZL cases from four hospitals in our community, from a clinical, biological and pathological point of view. When compared with those reported in the literature, our findings show three main differences: our patients less frequently showed an intrasinusoidal bone marrow infiltration pattern; the presence of a serum monoclonal component was rarely seen; and CD5-positive SMZL cases appear to be more common than previously thought.

Tuberculosis peritoneal como complicación en un caso de síndrome mielodisplásico/mieloproliferativo inclasificable / Peritoneal tuberculosis as a complication in a case of unclassificable myelodysplastic/myeloproliferative disease

Presentamos el caso de un paciente de 68 años diagnosticado de síndrome mieloproliferativo/mielodisplásico inclasificable (clasificación OMS), con tratamiento corticoesteroideo prolongado y mala respuesta a terapia citorreductora, que presenta en su evolución un cuadro clínico de astenia progresiva, dolor torácico, disnea a mínimos esfuerzos y distensión abdominal, que hace sospechar inicialmente una rotura esplénica. La laparotomía exploradora pone de manifiesto la existencia de implantes peritoneales múltiples, y la biopsia de éstos es diagnóstica de tuberculosis peritoneal. A ello se añade la positividad del cultivo y la PCR en orina, para Mycobacterium tuberculosis, y la posibilidad de probables afectaciones tuberculosas pleural y esplénica. La respuesta al tratamiento antituberculoso fue favorable. No hemos encontrado en la literatura revisada un caso de características similares

We report the case of a 68-year-old male with a diagnosis of unclassifiable myelodysplatic/myeloproliferative disease (WHO classification),under prolonged steroid treatment and unsuccesful chemotherapy response, who developed progressive asthenia, thoracic pain, minimal efforts dyspnea, and abdominal distension, that initially was suspicious of splenic rupture. Exploratory laparotomy showed multiple peritoneal implants, and a diagnosis of peritoneal tuberculosis was obtained from local biopsy. Definitive diagnosis included a positive result to cultureand PCR urine test, together with a possible pleural and splenic tuberculous affectation. Response to tuberculostatic treatment was successful.To the best of our knowledge, this is the first reported case with such characteristics

[Peritoneal tuberculosis as a complication in a case of unclassifiable myelodysplastic/myeloproliferative disease]. / Tuberculosis peritoneal como complicación en un caso de síndrome mielodisplásico/mieloproliferativo inclasificable.

We report the case of a 68-year-old male with a diagnosis of unclassifiable myelodysplatic/myeloproliferative disease (WHO classification), under prolonged steroid treatment and unsuccesful chemotherapy response, who developed progressive asthenia, thoracic pain, minimal efforts dyspnea, and abdominal distension, that initially was suspicious of splenic rupture. Exploratory laparotomy showed multiple peritoneal implants, and a diagnosis of peritoneal tuberculosis was obtained from local biopsy. Definitive diagnosis included a positive result to culture and PCR urine test, together with a possible pleural and splenic tuberculous affectation. Response to tuberculostatic treatment was successful. To the best of our knowledge, this is the first reported case with such characteristics.

Essential thrombocythemia in young individuals: frequency and risk factors for vascular events and evolution to myelofibrosis in 126 patients.

The frequency of vascular events and evolution to myelofibrosis (MF) in young individuals with essential thrombocythemia (ET) is not well known. The incidence and predisposing factors to such complications was studied in 126 subjects diagnosed with ET at a median age of 31 years (range: 5-40). Overall survival and probability of survival free of thrombosis, bleeding and MF were analyzed by the Kaplan-Meier method and the presence of the Janus Kinase 2 (JAK2) V617F mutation correlated with the appearance of such complications. The JAK2 mutation (present in 43% of patients) was associated with higher hemoglobin (Hb) (P<0.001) and lower platelets at diagnosis. With a median follow-up of 10 years (range: 4-25), 31 thrombotic events were registered (incidence rate: 2.2 thromboses/100 patients/year). When compared with the general population, young ET patients showed a significant increase in stroke (odds ratio 50, 95% CI: 21.5-115) and venous thromboses (odds ratio 5.3, 95% CI: 3.9-10.6). Thrombosis-free survival was 84% at 10 years, with tobacco use being associated with higher risk of thrombosis. Actuarial freedom from evolution to MF was 97% at 10 years. In conclusion, young ET patients have thrombotic events, especially stroke and venous thrombosis, more frequently than generally considered, whereas they rarely transform to MF.

[Indurated erythema as the presenting form of a case of chronic myelomonocytic leukemia]. / Eritema indurado como forma de presentación de un caso de leucemia mielomonocítica crónica.

Chronic myelomonocytic leukemia (CMML) is an oncohematologic disease with a mixed nature, myeloproliferative and myelodysplastic, and presenting features are usually the consequence of peripheral blood cytopenias (anemic syndrome, infections or bleeding). Specific or non-specific cutaneous involvement in patients with myelodysplastic syndromes or chronic leukemias is exceptional, and it takes place often in advanced stages of the disease, as a preample of a transformation from chronic illness to acute leukemia. Recognition and early diagnosis of the skin lesion by cutaneous biopsy, in every patient with myelodysplastic or myeloproliferative disease, have therapeutic and prognostic significance. We describe a patient who presented with a non-especific cutaneous lesion, Bazin's erhythema induratum, as initial manifestation of chronic myelomonocytic leukemia; we also comment diagnostic, therapeutic and clinical evolution aspects.

HIV-associated primary body-cavity-based lymphoma: clinico-biologic features in three patients diagnosed at the same institution.

Primary effusion lymphoma (PEL) is a recently individualized form of non-Hodgkin lymphoma (WHO classification) that mainly develops in HIV infected males, more frequently in homosexuals and advanced stages of the disease (total CD4+ lymphocyte count below 100-200/mL). Occasionally, it appears in others immunodepressive states (such as solid organs postransplant period) and even, although very rarelly, in immunocompetents patients. From a pathogenetic point of view, PEL has been related to Kaposi's sarcoma-associated herpes virus (also named human herpesvirus 8) and to the clinical antecedent of Kaposís sarcoma. Relative unfrequency of this disease, the absence of wide casuistics allowing a better characterization, and its unfavorable outcome, support the need of a deeper knowledge. We present here the clinical-biological findings of three patients that were diagnosed of pleural PEL in our institution in the last two years.

Linfoma primario de cavidades asociado a infección por VIH: características clínico-biológicas en tres pacientes diagnosticados en un mismo centro / Hiv-associated primary body-cavity-based lymphoma: clinico-biologic features in three patients diagnosed at the same institution

El linfoma primario de cavidades (LPC) constituye un variedad de linfoma no Hodgkin individualizada por la clasificación OMS, que se desarrolla principalmente en pacientes varones con infección por HIV, más frecuentemente homosexuales y en estadios avanzados de la enfermedad (recuento total de linfocitos CD4+ inferior a 100-200/µL), aunque en ocasiones pueden aparecer en otras circunstancias asociadas a estados de inmunodepresión (como puede ser en el postrasplante de órganos sólidos) e incluso, de forma muy ocasional, en pacientes inmunocompetentes. Desde un punto de vista patogenético se ha relacionado con el virus herpes asociado a sarcoma de Kaposi (también denominado virus herpes tipo 8) y al propio antecedente clínico de sarcoma de Kaposi. La relativa rareza de esta enfermedad, la falta de casuísticas amplias que logren caracterizarla mejor y su pronóstico tan desfavorable, obligan a profundizar en un mejor conocimiento de la misma. Presentamos los hallazgos clínico-biológicos de tres pacientes diagnosticados de LPC pleural en nuestro centro en los últimos dos años (AU)

Eritema indurado como forma de presentación de un caso de leucemia mielomonocítica crónica / Erythema induratum as presenting form in a case of chronic myelomonocytic leukemia

La leucemia mielomonocítica crónica (LMMC) constituye un proceso oncohematológico de naturaleza mixta, mieloproliferativa y mielodisplásica, siendo su forma habitual de presentación consecuencia, generalmente, de las citopenias en sangre periférica (síndrome anémico, infecciones o diátesis hemorrágica). La afectación cutánea en pacientes con síndromes mielodisplásicos o leucemias crónicas, ya bien sea específica o inespecífica, es una circunstancia excepcional, teniendo lugar más frecuentemente en estadios avanzados de la enfermedad como preámbulo a una transformación del proceso crónico en leucemia aguda. El reconocimiento y el diagnóstico precoces del tipo de afectación cutánea en cualquier paciente con síndrome mielodisplásico o mieloproliferativo crónico, obtenido dicho diagnóstico mediante biopsia de la lesión, resulta de gran importancia, pues conlleva un claro significado pronóstico y terapéutico. Describimos a continuación el caso de un paciente que presentó una lesión cutánea inespecífica, un eritema indurado de Bazin, como manifestación inicial de una LMMC; se comentan aspectos diagnósticos, terapéuticos y evolutivos del mismo (AU)

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Diagnóstico simultáneo de leucemia linfocítica crónica y policitemia vera en un paciente / Simultaneous diagnosis of chronic lymphocytic leukemia and polycytyhemia vera in a patient

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Deoxycoformycin in the treatment of patients with hairy cell leukemia: results of a Spanish collaborative study of 80 patients.

BACKGROUND: Deoxycoformycin (DCF) has been reported to produce high response rates in patients with hairy cell leukemia (HCL), but to the authors' knowledge data regarding experience with such therapy in a large HCL series are scarce. METHODS: Between 1988-1997, DCF (4 mg/m(2)/day, every 2 weeks) was administered to 80 HCL patients in 32 Spanish institutions. In 35 of 78 evaluable patients DCF was the first-line therapy; the remaining 43 patients had received other therapies. Pretreatment variables influencing the achievement of complete remission (CR) and event free survival were identified by multivariate analyses. RESULTS: The median number of cycles administered was 7 (range, 1-22 cycles). A CR was obtained in 56 patients (72%) and a partial remission was obtained in 13 patients, for an overall response rate of 88%. In the multivariate analysis previous splenectomy and an Eastern Cooperative Oncology Group (ECOG) performance status > or = 2 were the parameters adversely influencing CR achievement. With a median follow-up of 31.2 months (range, 0.4-126.5 months), disease recurrence was observed in 11 of the CR patients, 5 of whom showed a further response to DCF. An ECOG performance status > or = 2 was the only pretreatment variable associated with a shorter event free survival. Seven patients died, four during the treatment period. The actuarial median event free survival was 46 months (95% confidence interval, 22.5-69.5 months), and 48.7% of the 56 patients who achieved a CR were expected to be alive and disease free at 5 years. Hematologic toxicity (marked neutropenia [22 cases], anemia [6 cases], and thrombocytopenia [1 case]) was the main side effect, followed by nausea and emesis (5 cases); 14 patients required hospitalization. CONCLUSIONS: The results of the current study confirm the effectiveness and acceptable toxicity of DCF in the treatment of patients with HCL.

[Neutrophil mobilization test with intravenous hydrocortisone in the study of chronic idiopathic neutropenias. Experience with 19 cases and usefulness of a new diagnostic index]. / Prueba de movilización de los neutrófilos con hidrocortisona intravenosa en el estudio de las neutropenias crónicas idiopáticas. Experiencia en 19 casos y utilidad de un nuevo índice diagnóstico.

BACKGROUND: Some patients with chronic benign neutropenia present granulocytes distribution disorders within their different physiologic pools, and this situation can be exposed by granulocyte mobilization tests. Stimulation with hydrocortisone is the best known test, but its performance and interpretation are not well standardized. Granulocyte mobilization test with hydrocortisone was performed in 19 patients with chronic peripheral idiopathic granulocytopenia, by applying homogeneous criteria. PATIENTS AND METHOD: The test included an injection of intravenous hydrocortisone 200 mg after a first basal blood neutrophil determination, and a second neutrophil count four hours after steroid administration. Following data were registered: basal blood neutrophil count (BNC), final blood neutrophil count (FNC), difference between both counts or increment (INCR), and the ratio = 60% of INCR/2.0 (109/1) BNC, which we name demargination index (DI). RESULTS: Three response patterns (three patient groups) were observed: pattern I, with FNC > 2.0 109/1 and DI >/= 1 (false neutropenia with hypermargination component); pattern II, with FNC > 2.0 (109/1) and DI < 1 (false neutropenia with pathogenic mechanisms others than hypermargination), and pattern III, with FNC < 2.0 (109/1) and DI < 1 (true neutropenia). There were no significant differences in BNC or INCR when groups I and II were compared, but we found differences in FNC (p = 0.026) and DI (p = 0.026). Comparison between groups I and III showed differences in all four parameters (BNC P = 0.07, FNC p < 0.001, INCR p = 0.02, and DI p < 0.001). No differences were found between groups II and III. CONCLUSIONS: Granulocyte mobilization test with intravenous hydrocortisone 200 mg and a four-hours interval between basal and final neutrophil counts, allows differentiation between false neutropenia with hypermargination component and true neutropenia.

Sensitization to Blomia kulagini in a general population of a subtropical region of Spain (Canary Islands).

The Blomia genus has been described as allergenic in man. The present study aimed to assess the prevalence of B. kulagini sensitization in a large population of allergic subjects without occupational exposure in a subtropical region (Canary Islands, Spain). Secondarily, a new standardized B. kulagini extract was evaluated. The study population comprised 207 patients. RAST for B. kulagini was positive in 76.2% of patients, and 47 of them were selected for the biologic standardization. When the prick test was performed with the nonstandardized extracts, results were positive in 76.6%, whereas when the test was repeated with the standardized extract, sensitivity rose to 95.7%. The conjunctival provocation test was positive in 78.3% of 46 evaluated patients. The bronchial provocation test was positive in 18 sensitized patients and negative in five controls. In conclusion, B. kulagini is an important cause of sensitization among the occupationally unexposed population of the studied area and should be included in allergy diagnostic tests. For reliable prick tests, the use of standardized extracts is mandatory.