Case Report
Disseminated Juvenile Xanthogranuloma Associated With Follicular Lymphoma in an Adult: Successful Treatment With Chemotherapy and Rituximab. A Review of the Literature
Xantogranuloma juvenil diseminado del adulto asociado a linfoma folicular, respuesta completa a quimioterapia y rituximab. Revisión de la literatura
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Revisión de la literatura" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1565 "Ancho" => 1655 "Tamanyo" => 562382 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">A, Infiltrate composed of cells with abundant cytoplasm and a histiocytic appearance, some multinucleated giant cells, lymphocytes with no atypia, and a few eosinophils (hematoxylin-eosin, original magnification<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>100). B, Immunohistochemistry showing a negative result for CD1a (original magnification<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>200). C, Immunohistochemistry showing granular positivity for CD68 in the cellular cytoplasm (original magnification<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>200). D, Histology of inguinal lymph node showing a lymphoid proliferation of centrocytes (small cleaved cells) (original magnification<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>100).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Juvenile xanthogranuloma (JXG) is a non-Langerhans cell histiocytosis that typically affects young children. It is characterized by multiple yellowish-brown papulonodular lesions that resolve spontaneously. Histologically, these lesions are characterized by histiocytes and Touton-type multinucleated giant cells. Most of the few cases of JXG that have been reported in adults consist of solitary lesions that do not regress spontaneously.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> JXG has gained interest because of its possible association with oncohematologic diseases.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Case Description</span><p id="par0010" class="elsevierStylePara elsevierViewall">The patient was a 61-year-old woman (occasional smoker) diagnosed 30 years earlier with latent tuberculosis. She had undergone curettage of the uterus to treat a uterine fibroid and had required a blood transfusion. In 2004, yellowish-brown papular lesions 3 to 5<span class="elsevierStyleHsp" style=""></span>mm in diameter began to appear on the patient's trunk. The lesions increased in number, gradually spreading across the abdomen and the proximal areas of the limbs (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>, A and B).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Histologic examination of one of the lesions revealed a diffuse infiltrate located mainly in the mid dermis that dissected collagen bundles and formed aggregates in the deep dermis. The infiltrate was composed primarily of cells with abundant cytoplasm and a histiocytic appearance, as well as multinucleated giant cells, some of which were Touton-type, mixed with occasional lymphocytes with no atypia and a few eosinophils (<a class="elsevierStyleCrossRefs" href="#fig0010">Figs. 2 and 3</a>). Immunohistochemistry was positive for cells of monocyte-macrophage lineage (CD68) and negative for Langerhans cells (s-100 protein and CD1a). A diagnosis of adult-onset JXG was established. The patient began outpatient follow-up care and continued to develop clinically similar lesions. After 4 years of follow-up, the patient was found to have an enlarged left inguinal lymph node that was growing rapidly, with no other associated symptoms. The lymph node was excised and histology revealed a nodular lymphoproliferative process consisting of centrocytes with a germinal center phenotype (immunohistochemistry was positive for CD20, CD23, and CD10 in follicular areas, with diffuse expression of Bcl-2 and selective expression of Bcl-6 in the follicles), which indicated clonal <span class="elsevierStyleItalic">IGH</span> gene rearrangement (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>). The staging study revealed enlarged retroperitoneal and perivascular lymph nodes, adequate differentiation of the 3 hematopoietic cell lines, and an absence of neoplastic infiltration in the bone-marrow biopsy specimen. These findings led to a final diagnosis of well-differentiated, low-grade, stage IIIA follicular B-cell lymphoma.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">The findings of a new histologic examination of a different skin lesion, performed after the lesions had increased in number, were similar to those of the first biopsy; <span class="elsevierStyleItalic">IGH</span> gene rearrangement was not detected, however, due to insufficient genetic material. The patient began treatment with monthly cycles of fludarabine (40<span class="elsevierStyleHsp" style=""></span>mg/d) and cyclophosphamide (250<span class="elsevierStyleHsp" style=""></span>mg/d) for 3 days each month followed by a single dose of rituximab (375<span class="elsevierStyleHsp" style=""></span>mg/m<span class="elsevierStyleSup">2</span>); she was administered 4 cycles. She was then administered 4 cycles of a single weekly dose of rituximab (375<span class="elsevierStyleHsp" style=""></span>mg/m<span class="elsevierStyleSup">2</span>). Six months after completing the treatment regimen, the patient had achieved complete remission of the malignancy and the skin lesions had regressed, leaving depressed, hyperpigmented scars (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>C). After 2 years of follow-up, no new skin lesions have appeared and there is no evidence of hematologic recurrence.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Discussion</span><p id="par0025" class="elsevierStylePara elsevierViewall">Adult-onset JXG was first described in 1963, since which time 125 cases have been reported, most consisting of solitary lesions.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a> Nevertheless, in the literature we have identified 21 cases with more than 10 disseminated lesions, with histologic findings similar to those seen in children with JXG.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1–6</span></a> Seven of the reviewed cases of adult-onset JXG were associated with hematologic malignancies<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3–7</span></a> (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>), most frequently leukemias (3 cases),<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3–5</span></a> followed by lymphomas (2 cases),<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,5</span></a> monoclonal gammopathy (1 case),<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> and essential thrombocytosis (1 case).<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> We did not find any cases of JXG associated with follicular lymphoma. The present case is therefore the first report of this association. In all cases in which JXG was associated with a blood dyscrasia, the patients presented multiple lesions with purely cutaneous involvement, with the exception of 1 case with periocular involvement.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> JXG developed before, concomitantly with, or after diagnosis of the hematologic malignancy, with intervals that ranged from 5 months to 9 years.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">The response of the JXG and the tumor to treatment targeting the hematologic neoplasm was variable. Remission of the tumor and regression of the skin lesions occurred in only 2 cases.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6,7</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Some studies have reported that children who have JXG and neurofibromatosis have an increased risk of developing leukemia, but doubts about this association have subsequently been raised.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Two cases have been reported in children of JXG with disseminated cutaneous involvement associated with myeloproliferative diseases. One report described a 3-year-old boy who was diagnosed with JXG and 6 months later developed B-cell acute lymphoblastic leukemia (B-ALL).<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> The patient failed to achieve remission with chemotherapy, although the skin lesions did flatten slightly. The other case was a newborn with JXG and hemophagocytic lymphohistiocytosis who developed chronic juvenile myelomonocytic leukemia.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> Castro et al.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> described the cases of 3 children between the ages of 8 and 13 years who presented JXG lesions in unusual locations—lymph nodes, bones, and lungs—in association with ALL. The intervals between the appearance of JXG and the onset of ALL ranged from 1 to 12 years. However, given the higher incidence of this disease in children, its self-resolving course, and reports of atypical forms of presentation, we believe that the association between JXG and blood neoplasms is weaker in children.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Regarding the etiology and pathogenesis, it has been speculated that histiocytoses develop as a result of the proliferation of a common CD34<span class="elsevierStyleSup">+</span> precursor cell in the bone marrow. The abnormal multiplication of these cells is caused by the action of various stimuli, including cytokines or gamma globulins produced by an underlying malignancy.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> Moreover, it has been suggested that some cases of Langerhans cell histiocytosis associated with myeloproliferative or lymphoproliferative diseases may have a common origin in a hematopoietic precursor cell capable of dedifferentiating both into tumor cells, which leads to the neoplasm, and into cells of monocyte-dendritic lineage, which leads to histiocytosis.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> A recent study described a case of JXG with visceral involvement (liver and spleen) in a child aged 5 years.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> Three months after the patient was diagnosed with T-ALL, clonal biallelic rearrangement of <span class="elsevierStyleItalic">TCRγ</span> in blasts and histiocytes was detected. In our patient, we were unable to establish a clonal relationship between the lymphoproliferative cells and the histiocytes that formed part of the skin lesions because the skin biopsy specimen contained insufficient genetic material. In the literature, we found no other cases of JXG with clonal rearrangement among either the hematologic tumor cell population or the histiocytosis. It would therefore be interesting, in future studies, to demonstrate this association in patients with both diseases. This research could be extended to other cases of blood dyscrasias associated with various types of non-Langerhans cell histiocytosis, such as xanthoma disseminatum and necrobiotic xanthogranuloma.</p><p id="par0045" class="elsevierStylePara elsevierViewall">No treatment regimen has been shown to cure disseminated adult-onset JXG. Patients with JXG and neoplastic disease whose skin lesions improved did so in response to antineoplastic therapy. Our patient received chemotherapy with fludarabine and cyclophosphamide in combination with rituximab (an anti-CD20 monoclonal antibody that inhibits CD20<span class="elsevierStyleSup">+</span> lymphocytes). The cytostatic treatment induced apoptosis in the neoplastic cells, thereby inhibiting the production of various cytokines and other mediators that might otherwise have participated in histiocytic proliferation. Various mechanisms by which rituximab may inhibit lymphocytes have been proposed, including modulation through the macrophage-histiocyte system,<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> which could have contributed to the resolution of JXG in our patient. Our review of the literature has revealed no previous reports of disseminated JXG being treated with rituximab, although there has been a description of complete resolution of a necrobiotic xanthogranuloma associated with lymphocytic lymphoma in a patient who followed the same treatment regimen as our patient.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conclusion</span><p id="par0050" class="elsevierStylePara elsevierViewall">This is the first report in an adult of disseminated JXG associated with follicular lymphoma with an excellent response to cytostatic treatment and rituximab. This result supports the hypothesis that JXG is associated with hematologic malignancies. Not enough cases have been reported for this entity to be considered a true paraneoplastic syndrome. Nevertheless, it is advisable to follow up these patients using general physical examination and additional tests to screen for tumors—especially hematologic ones—in those patients who have numerous lesions that have appeared progressively.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflicts of Interest</span><p id="par0055" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:2 [ "identificador" => "xres97880" "titulo" => "Abstract" ] 1 => array:2 [ "identificador" => "xpalclavsec85037" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xres97881" "titulo" => "Resumen" ] 3 => array:2 [ "identificador" => "xpalclavsec85036" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Case Description" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Discussion" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Conclusion" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Conflicts of Interest" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2011-07-17" "fechaAceptado" => "2012-02-10" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec85037" "palabras" => array:3 [ 0 => "Juvenile xanthogranuloma" 1 => "Lymphoma follicular" 2 => "Non-Langerhans-cell histiocytosis" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec85036" "palabras" => array:4 [ 0 => "Xantogranuloma juvenil" 1 => "Linfoma folicular" 2 => "Histiocitosis de células no" 3 => "Langerhans" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Juvenile xanthogranuloma is a non-Langerhans cell histiocytosis that typically affects children, but several cases have been reported in adults, some in connection with hematologic malignancies. We present the case of a 61-year-old woman with multiple xanthogranulomas who developed a follicular lymphoma after 4 years of follow-up. After 6 months of treatment with chemotherapy and rituximab, the cutaneous lesions disappeared and the patient achieved remission from lymphoma. We highlight this case because xanthogranuloma is a rare disorder that is difficult to diagnose in adults and also because this is the first report of an association between xanthogranuloma and follicular lymphoma. Excellent response was achieved with chemotherapy and rituximab. Finally, given the possible association between xanthogranulomas and hematologic diseases, these lesions may be a cutaneous manifestation of an occult malignancy.</p>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">El xantogranuloma juvenil (XGJ) es una histiocitosis de células no Langerhans que acontece en la edad infantil, sin embargo, se han descrito varios casos en el adulto, algunos de ellos en relación con hemopatías malignas. Presentamos el caso de una mujer de 61 años de edad con lesiones diseminadas de XGJ que a los 4 años de seguimiento desarrolló un linfoma de tipo folicular. Tras 6 meses de tratamiento con quimioterapia y rituximab se consiguió remisión del linfoma y la involución de las lesiones cutáneas. Destacamos este caso por tratarse de una entidad poco frecuente y de difícil diagnóstico en el adulto, así como por ser el primer caso asociado con linfoma folicular y que ha presentado una excelente respuesta con quimioterapia y rituximab. Además, dada su posible asociación con enfermedades hematológicas, el XGJ podría representar una manifestación de una neoplasia oculta.</p>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara">Please cite this article as: Narváez-Moreno B, et al. Xantogranuloma juvenil diseminado del adulto asociado a lin-foma folicular, respuesta completa a quimioterapia y rituximab. Revisión de la literatura. Actas Dermosifiliogr. 2013;104:242–6</p>" ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1273 "Ancho" => 1667 "Tamanyo" => 202220 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A, Multiple yellowish-brown papular lesions on the patient's trunk. B, Detail of the lesions. C, Hyperpigmented scars after completion of the treatment.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1255 "Ancho" => 1667 "Tamanyo" => 424525 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Diffuse infiltrate located mainly in the mid dermis that dissects collagen bundles and that forms aggregates in the deep dermis, shown at high magnification (hematoxylin-eosin, original magnification<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>40).</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1565 "Ancho" => 1655 "Tamanyo" => 562382 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">A, Infiltrate composed of cells with abundant cytoplasm and a histiocytic appearance, some multinucleated giant cells, lymphocytes with no atypia, and a few eosinophils (hematoxylin-eosin, original magnification<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>100). B, Immunohistochemistry showing a negative result for CD1a (original magnification<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>200). C, Immunohistochemistry showing granular positivity for CD68 in the cellular cytoplasm (original magnification<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>200). D, Histology of inguinal lymph node showing a lymphoid proliferation of centrocytes (small cleaved cells) (original magnification<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>100).</p>" ] ] 3 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Source: Adapted from Shoo et al.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Abbreviations: B-ALL, B-cell acute lymphoblastic leukemia; B-CLL, B-cell chronic lymphocytic leukemia; F, female; JXG, juvenile xanthogranuloma; M, male.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Bibliographic Reference \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Age, y/Sex \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Clinical Presentation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Hematologic Disease \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Temporal Relationship Between Hematologic Malignancy and JXG \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Treatment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Response to Treatment \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Case Presented \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">61/F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Multiple, disseminated \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Follicular lymphoma \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 y later \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Fludarabine, cyclophosphamide, rituximab \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Both \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Biswas et al.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">43/M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ocular \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">B-CLL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 y before \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">None \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">JXG, spontaneous resolution after 2 y \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Shoo et al.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">45/M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Multiple, disseminated \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">B-ALL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Simultaneous \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No data available \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No data available \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Shoo et al.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">74/F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Multiple, disseminated \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Large B-cell lymphoma \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 y later \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No data available \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">JXG, no response; lymphoma, remission \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Larson et al.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">69/M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Multiple, disseminated \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CLL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 mo before \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No data available \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Both \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Larson et al.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">76/M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Multiple, disseminated \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Monoclonal gammopathy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 mo before \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No data available \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No data available \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Pino et al.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">79/M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Multiple, disseminated \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Essential thrombocytosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 y later \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hydroxyurea \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Both \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Chiou et al.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">68/F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Multiple, disseminated \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Adult T-cell leukemia/lymphoma \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 y later \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Prednisone, chlorambucil \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No response \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab183317.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p 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| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Noviembre | 8 | 11 | 19 |
| 2024 Octubre | 77 | 63 | 140 |
| 2024 Septiembre | 99 | 41 | 140 |
| 2024 Agosto | 142 | 78 | 220 |
| 2024 Julio | 82 | 40 | 122 |
| 2024 Junio | 109 | 43 | 152 |
| 2024 Mayo | 77 | 37 | 114 |
| 2024 Abril | 74 | 27 | 101 |
| 2024 Marzo | 69 | 43 | 112 |
| 2024 Febrero | 81 | 38 | 119 |
| 2024 Enero | 70 | 42 | 112 |
| 2023 Diciembre | 87 | 24 | 111 |
| 2023 Noviembre | 99 | 23 | 122 |
| 2023 Octubre | 107 | 39 | 146 |
| 2023 Septiembre | 96 | 41 | 137 |
| 2023 Agosto | 64 | 27 | 91 |
| 2023 Julio | 67 | 50 | 117 |
| 2023 Junio | 93 | 36 | 129 |
| 2023 Mayo | 86 | 39 | 125 |
| 2023 Abril | 51 | 35 | 86 |
| 2023 Marzo | 56 | 33 | 89 |
| 2023 Febrero | 63 | 26 | 89 |
| 2023 Enero | 49 | 38 | 87 |
| 2022 Diciembre | 84 | 45 | 129 |
| 2022 Noviembre | 36 | 31 | 67 |
| 2022 Octubre | 42 | 31 | 73 |
| 2022 Septiembre | 46 | 37 | 83 |
| 2022 Agosto | 67 | 53 | 120 |
| 2022 Julio | 50 | 48 | 98 |
| 2022 Junio | 54 | 41 | 95 |
| 2022 Mayo | 95 | 40 | 135 |
| 2022 Abril | 78 | 46 | 124 |
| 2022 Marzo | 66 | 60 | 126 |
| 2022 Febrero | 51 | 24 | 75 |
| 2022 Enero | 117 | 45 | 162 |
| 2021 Diciembre | 84 | 51 | 135 |
| 2021 Noviembre | 71 | 43 | 114 |
| 2021 Octubre | 68 | 62 | 130 |
| 2021 Septiembre | 104 | 57 | 161 |
| 2021 Agosto | 75 | 31 | 106 |
| 2021 Julio | 60 | 49 | 109 |
| 2021 Junio | 38 | 51 | 89 |
| 2021 Mayo | 54 | 65 | 119 |
| 2021 Abril | 110 | 67 | 177 |
| 2021 Marzo | 72 | 47 | 119 |
| 2021 Febrero | 50 | 41 | 91 |
| 2021 Enero | 53 | 38 | 91 |
| 2020 Diciembre | 39 | 35 | 74 |
| 2020 Noviembre | 25 | 27 | 52 |
| 2020 Octubre | 16 | 18 | 34 |
| 2020 Septiembre | 50 | 15 | 65 |
| 2020 Agosto | 37 | 28 | 65 |
| 2020 Julio | 38 | 11 | 49 |
| 2020 Junio | 47 | 26 | 73 |
| 2020 Mayo | 26 | 16 | 42 |
| 2020 Abril | 82 | 24 | 106 |
| 2020 Marzo | 41 | 13 | 54 |
| 2020 Febrero | 4 | 3 | 7 |
| 2020 Enero | 4 | 1 | 5 |
| 2019 Diciembre | 10 | 3 | 13 |
| 2019 Noviembre | 4 | 1 | 5 |
| 2019 Octubre | 0 | 6 | 6 |
| 2019 Septiembre | 4 | 22 | 26 |
| 2019 Agosto | 6 | 18 | 24 |
| 2019 Julio | 4 | 14 | 18 |
| 2019 Junio | 4 | 11 | 15 |
| 2019 Mayo | 8 | 80 | 88 |
| 2019 Abril | 10 | 46 | 56 |
| 2019 Marzo | 5 | 25 | 30 |
| 2019 Febrero | 1 | 29 | 30 |
| 2019 Enero | 5 | 8 | 13 |
| 2018 Diciembre | 2 | 9 | 11 |
| 2018 Noviembre | 4 | 0 | 4 |
| 2018 Octubre | 3 | 0 | 3 |
| 2018 Septiembre | 4 | 6 | 10 |
| 2018 Agosto | 0 | 9 | 9 |
| 2018 Julio | 0 | 8 | 8 |
| 2018 Junio | 0 | 18 | 18 |
| 2018 Mayo | 0 | 7 | 7 |
| 2018 Abril | 0 | 3 | 3 |
| 2018 Marzo | 16 | 19 | 35 |
| 2018 Febrero | 76 | 6 | 82 |
| 2018 Enero | 97 | 20 | 117 |
| 2017 Diciembre | 72 | 16 | 88 |
| 2017 Noviembre | 66 | 17 | 83 |
| 2017 Octubre | 70 | 20 | 90 |
| 2017 Septiembre | 76 | 28 | 104 |
| 2017 Agosto | 126 | 33 | 159 |
| 2017 Julio | 110 | 32 | 142 |
| 2017 Junio | 133 | 87 | 220 |
| 2017 Mayo | 120 | 41 | 161 |
| 2017 Abril | 107 | 37 | 144 |
| 2017 Marzo | 79 | 30 | 109 |
| 2017 Febrero | 61 | 32 | 93 |
| 2017 Enero | 63 | 20 | 83 |
| 2016 Diciembre | 80 | 21 | 101 |
| 2016 Noviembre | 130 | 36 | 166 |
| 2016 Octubre | 121 | 49 | 170 |
| 2016 Septiembre | 220 | 17 | 237 |
| 2016 Agosto | 164 | 19 | 183 |
| 2016 Julio | 86 | 16 | 102 |
| 2016 Junio | 10 | 16 | 26 |
| 2016 Mayo | 5 | 20 | 25 |
| 2016 Abril | 3 | 1 | 4 |
| 2016 Marzo | 7 | 4 | 11 |
| 2016 Febrero | 6 | 3 | 9 |
| 2016 Enero | 10 | 1 | 11 |
| 2015 Diciembre | 8 | 3 | 11 |
| 2015 Noviembre | 4 | 5 | 9 |
| 2015 Octubre | 7 | 1 | 8 |
| 2015 Septiembre | 5 | 2 | 7 |
| 2015 Agosto | 11 | 2 | 13 |
| 2015 Julio | 134 | 127 | 261 |
| 2015 Junio | 93 | 18 | 111 |
| 2015 Mayo | 129 | 27 | 156 |
| 2015 Abril | 153 | 18 | 171 |
| 2015 Marzo | 92 | 9 | 101 |
| 2015 Febrero | 109 | 7 | 116 |
| 2015 Enero | 54 | 10 | 64 |
| 2014 Diciembre | 55 | 9 | 64 |
| 2014 Noviembre | 51 | 10 | 61 |
| 2014 Octubre | 60 | 15 | 75 |
| 2014 Septiembre | 59 | 14 | 73 |
| 2014 Agosto | 53 | 14 | 67 |
| 2014 Julio | 52 | 6 | 58 |
| 2014 Junio | 71 | 5 | 76 |
| 2014 Mayo | 56 | 12 | 68 |
| 2014 Abril | 50 | 7 | 57 |
| 2014 Marzo | 47 | 16 | 63 |
| 2014 Febrero | 47 | 19 | 66 |
| 2014 Enero | 52 | 16 | 68 |
| 2013 Diciembre | 51 | 17 | 68 |
| 2013 Noviembre | 44 | 11 | 55 |
| 2013 Octubre | 30 | 6 | 36 |
| 2013 Septiembre | 10 | 8 | 18 |
| 2013 Agosto | 16 | 13 | 29 |
| 2013 Julio | 2 | 9 | 11 |
| 2013 Junio | 6 | 14 | 20 |
| 2013 Mayo | 0 | 2 | 2 |
| 2013 Abril | 2 | 2 | 4 |
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