RESUMEN
BACKGROUND: Mu heavy chain disease is a rare lymphoid neoplasm characterized by vacuolated bone marrow plasma cells and secretion of defective mu immunoglobulin heavy chains. The biological basis of mu heavy chain disease is poorly understood. CASE PRESENTATION: We report a case of mu heavy chain disease with MYD88 L265P mutation and deletion of 6q, genetic aberrations that are both strongly associated with lymphoplasmacytic lymphoma/Waldenström macroglobulinemia. Identification of the truncated mu immunoglobulin was facilitated by mass spectrometric analysis of the patient's serum. CONCLUSIONS: Mu heavy chain disease has been described as similar to chronic lymphocytic leukemia; however, the frequency of lymphocytosis in mu heavy chain disease has not been previously reported. We reviewed all previously published mu heavy chain disease reports and found that lymphocytosis is uncommon in the entity. This finding, along with the emerging genetic feature of recurrent MYD88 mutation in mu heavy chain disease, argues that at least a significant subset of cases are more similar to lymphoplasmacytic lymphoma than to chronic lymphocytic leukemia.
Asunto(s)
Enfermedad de las Cadenas Pesadas , Leucemia Linfocítica Crónica de Células B , Linfocitosis , Linfoma , Macroglobulinemia de Waldenström , Humanos , Leucemia Linfocítica Crónica de Células B/diagnóstico , Leucemia Linfocítica Crónica de Células B/genética , Mutación , Factor 88 de Diferenciación Mieloide/genética , Macroglobulinemia de Waldenström/diagnóstico , Macroglobulinemia de Waldenström/genética , Macroglobulinemia de Waldenström/patologíaRESUMEN
BACKGROUND: Mixed phenotype acute leukemia (MPAL) is a rare subset of acute leukemia in the pediatric population associated with genetic alterations seen in both acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). CASE: We describe a patient with MPAL with a NUP98 (nucleoporin 98)-NSD1 gene fusion (nuclear receptor binding SET domain protein1) and NRAS (neuroblastoma RAS viral oncogene homolog mutation) p.Gly61Arg mutation who was treated with upfront AML-based chemotherapy, received hematopoietic stem cell transplant (HSCT), but unfortunately died from relapsed disease. CONCLUSION: This case highlights the challenges faced in choosing treatment options in MPAL patients with complex genomics, with predominant myeloid features.
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GTP Fosfohidrolasas/genética , Leucemia Mieloide Aguda/diagnóstico , Proteínas de la Membrana/genética , Neoplasias Complejas y Mixtas/diagnóstico , Proteínas de Fusión Oncogénica/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biopsia , Médula Ósea/patología , Resultado Fatal , Femenino , Trasplante de Células Madre Hematopoyéticas , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patología , Leucemia Mieloide Aguda/terapia , Mutación , Terapia Neoadyuvante , Neoplasias Complejas y Mixtas/genética , Neoplasias Complejas y Mixtas/patología , Neoplasias Complejas y Mixtas/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapiaRESUMEN
Coagulation factor XIII subunit A (FXIIIa) intracellular expression has been described in platelets, megakaryocytes, monocytic cells, and leukemic blasts. Flow cytometric-based studies have suggested prognostic implications of FXIIIa expression, especially within the acute promyelocytic leukemia (APL) subgroup of acute myeloid leukemia (AML); however, its prognostic correlate by immunohistochemistry (IHC) is unknown. The aims of this study were to (1) define the clinicopathologic features of FXIIIa IHC-positive AML and (2) compare APL with other AML subtypes. Eighty-seven bone marrow biopsies or clot/particle preparations from our institution were evaluated with FXIIIa IHC. The study cohort consisted of bone marrow evaluations of 36 consecutive pretherapy APL, 42 selected pretherapy non-APL AML, and 9 negative staging cases. FXIIIa IHC expression was correlated with clinical and pathologic features and overall survival (OS). Leukemic blast FXIIIa cytoplasmic positivity was noted in 56% (20/36) APL and 74% (31/42) non-APL AML (P=0.10). FXIIIa IHC expression was associated with inferior OS within the APL cohort (P=0.04). No OS differences were noted in comparing FXIIIa IHC expression in all AML (P=0.17), or FXIIIa IHC expression within favorable, intermediate or adverse cytogenetic groups (P=0.14, 0.22 and 0.87, respectively). FXIIIa IHC expression is observed among a broad spectrum of AML subtypes and is not characterized by specific pathologic features. However, within the APL subgroup, FXIIIa IHC expression is associated with an inferior outcome and may be useful for additional prognostic risk stratification.
Asunto(s)
Factor XIII/metabolismo , Leucemia Promielocítica Aguda , Médula Ósea/patología , Citometría de Flujo/métodos , Humanos , Inmunohistoquímica/métodos , Leucemia Promielocítica Aguda/patología , Evaluación de Resultado en la Atención de Salud , PronósticoRESUMEN
Juvenile myelomonocytic leukemia (JMML) is a rare childhood neoplasm with poor prognosis except in the setting of Noonan syndrome, where prognosis is generally favorable. We present the case of a child with JMML in the setting of germline PTPN11 mutation and Noonan syndrome with suspected secondary development of monosomy 7 in the bone marrow. Diagnosed shortly after birth, she has been managed with active surveillance alone. Myeloblast percentages initially fluctuated; however, bone marrow biopsy at 4 years of age showed spontaneous remission despite persistence of the monosomy 7 clone, supporting a cautious approach in similar cases.
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Trastornos de los Cromosomas/complicaciones , Leucemia Mieloide Aguda/complicaciones , Leucemia Mielomonocítica Juvenil/complicaciones , Síndromes Mielodisplásicos/complicaciones , Síndrome de Noonan/complicaciones , Cariotipo Anormal , Preescolar , Deleción Cromosómica , Cromosomas Humanos Par 7 , Humanos , Hibridación Fluorescente in Situ , Recién Nacido , Síndrome de Noonan/genética , Proteína Tirosina Fosfatasa no Receptora Tipo 11/genéticaRESUMEN
OBJECTIVE: The aim of our study was to evaluate the adequacy and quality of the bone marrow (BM) obtained by OnControl powered drill (P-group) and to compare it with manual procedure (M-group). DESIGN: Retrospective analysis was done on 75 BM specimens; Jamshidi needle (n=44) and OnControl (n=31). Biopsy length after fixation, evaluable marrow length and total area, and fragmentation, aspiration and marrow dropout artefacts were compared. RESULTS: Biopsies were sufficient for diagnosis in 38/44 cases (86%) in the M-group and in 26/31 cases (83%) in the P-group. The most common reason for suboptimal/inadequate biopsies was subcortical specimens (4/6) in the M-group and aspiration artefact (5/5) in the P-group. Average length after fixation, evaluable marrow length, evaluable marrow area was comparable. Aspiration artefact was minimal (<10%) in the majority of BM samples in the M-group (31/44), while 25/31 BM in the P-group showed >10% aspiration artefact, p<0.0001. CONCLUSIONS: Our study suggests that quality of biopsy cylinder and adequacy rate of the biopsy is comparable between both devices. OnControl device showed more aspiration artefact.
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Médula Ósea/patología , Manejo de Especímenes/instrumentación , Biopsia con Aguja/instrumentación , Examen de la Médula Ósea/instrumentación , Examen de la Médula Ósea/normas , Diseño de Equipo , Humanos , Agujas , Estudios RetrospectivosAsunto(s)
Biomarcadores de Tumor/genética , Subunidad alfa del Receptor de Interleucina-3/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Linfocitos T/inmunología , Adulto , Anciano , Antígenos CD1/genética , Antígenos CD1/inmunología , Biomarcadores de Tumor/inmunología , Antígenos CD5/genética , Antígenos CD5/inmunología , Antígenos CD8/genética , Antígenos CD8/inmunología , Niño , Preescolar , Femenino , Expresión Génica , Humanos , Inmunohistoquímica , Inmunofenotipificación , Subunidad alfa del Receptor de Interleucina-3/inmunología , Masculino , Persona de Mediana Edad , Leucemia-Linfoma Linfoblástico de Células T Precursoras/inmunología , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patología , Pronóstico , Linfocitos T/patología , Adulto JovenAsunto(s)
Cromosomas Humanos Par 15 , Cromosomas Humanos Par 17 , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidad , Leucemia Promielocítica Aguda/mortalidad , Translocación Genética , Médula Ósea/patología , Puntos de Rotura del Cromosoma , Femenino , Humanos , Inmunofenotipificación , Hibridación Fluorescente in Situ , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Promielocítica Aguda/diagnóstico , Leucemia Promielocítica Aguda/tratamiento farmacológico , Leucemia Promielocítica Aguda/genética , Persona de Mediana Edad , Proteínas de Fusión Oncogénica/genética , Evaluación del Resultado de la Atención al Paciente , PronósticoRESUMEN
FLT3-ITD and NPM1 mutation testing in acute myeloid leukemia (AML) plays an important role in prognostic risk stratification, especially within the intermediate cytogenetic risk group. Molecular studies require adequate fresh material and are typically performed on a dedicated aspirate specimen, which may not be available in all cases. Prior flow cytometric studies have suggested an association between CD123 overexpression in AML and FLT3-ITD and/or NPM1 mutations; however, the immunohistochemical (IHC) correlate is unknown. We assessed CD123 IHC expression in 157 AML bone marrow biopsies and/or marrow particle preparations, and correlated with the morphologic, immunophenotypic, and cytogenetic features and with the presence of FLT3-ITD and NPM1 mutations. We found that CD123 IHC expression, seen in 40% of AML, occurred across a wide spectrum of 2008 World Health Organization subtypes and was most frequent within the intermediate risk group. As compared with CD123 IHC-AML, CD123 IHC+AML demonstrated higher marrow blast percentages (median 69%), monocytic differentiation (33/63 cases), and CD34 negativity (29/63 cases). Eighty-three percent (25/30) FLT3-ITD-mutated AML were CD123+ (P<0.0001) and 62% (18/29) NPM1-mutated cases were CD123 IHC+ (P=0.0052) with negative predictive values of 95% for FLT3-ITD and 88% for NPM1. CD123 IHC+AML presents with characteristic pathologic features, some of which may be related to underlying FLT3-ITD and/or NPM1 mutations.
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Biomarcadores de Tumor/genética , Subunidad alfa del Receptor de Interleucina-3/genética , Leucemia Mieloide Aguda/genética , Mutación , Proteínas Nucleares/genética , Tirosina Quinasa 3 Similar a fms/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biopsia , Médula Ósea/metabolismo , Médula Ósea/patología , Niño , Preescolar , Femenino , Expresión Génica , Humanos , Inmunohistoquímica , Lactante , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/patología , Masculino , Persona de Mediana Edad , Nucleofosmina , Secuencias Repetidas en TándemRESUMEN
We evaluated CD123 expression in 95 pediatric and 24 adult ALL patients and compared the results with the CD123 expression in normal B-cell precursors. Early B-cell precursors were negative while intermediate precursors and mature B cells showed weak CD123 expression. Leukemic blasts in 31% of precursor-B ALL samples exhibited strong expression of CD123, 61% had moderate CD123 expression and 8% were negative; 81.5% of ALL with hyperdiploid karyotype (>/= 52 chromosomes) showed strong CD123 overexpression. In contrast, cases with ETV6/RUNX1 rearrangement had weak CD123 expression. Our study suggests that overexpression of CD123 is an aberrant phenotype present in a subset of precursor-B ALL with hyperdiploid genotype, and represents an additional marker of good prognosis in pediatric precursor-B ALL. Moreover, aberrant CD123 expression in ALL is a good marker for monitoring of minimal residual disease.
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Diploidia , Regulación Leucémica de la Expresión Génica , Subunidad alfa del Receptor de Interleucina-3/biosíntesis , Subunidad alfa del Receptor de Interleucina-3/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Adolescente , Adulto , Factores de Edad , Anciano , Niño , Preescolar , Genotipo , Humanos , Lactante , Recién Nacido , Cariotipificación , Persona de Mediana Edad , Fenotipo , Leucemia-Linfoma Linfoblástico de Células Precursoras/genéticaRESUMEN
BACKGROUND: The size of colorectal polyps is important in the clinical management of these lesions. AIM: To audit the accuracy in calculating the size of "polyps" by various specialists. MATERIALS AND METHODS: Eighteen pathologists and four surgeons measured, with a conventional millimetre ruler, the largest diameter of 12 polyp phantoms. The results of two independent measurements (two weeks apart) were compared with the gold standard-size assessed at The Royal Institute of Technology, Sweden. RESULTS: Thirty-one percent (83/264-trial 1) and 33% (88/264-trial 2) of the measurements underestimated or overestimated the gold standard size by >1 mm. Of the 22 experienced participants, 95% (21/22-trial 1) and 91% (20/22-trial 2) misjudged by >1 mm the size of one or more polyps. Values given by 13 participants (4.9%) in trial 1 and by 15 participants (5.7%) in trial 2, differed by > or = +/-4 mm from the gold standard size. In addition, a big difference between the highest and the lowest values was recorded in some polyps (up to 11.4 mm). Those disparate values were regarded as a human error in reading the scale on the ruler. CONCLUSION: Using a conventional ruler (the tool of pathologists worldwide) unacceptably high intra-observer and inter-observer variations in assessing the size of polyp-phantoms was found. The volume and the shape of devices, as well as human error in reading the scale of the ruler were confounding factors in size assessment. In praxis, the size is crucial in the management of colorectal polyps. Considering the clinical implications of the results obtained, the possibility of developing a method that will allow assessment of the true size of removed clinical polyps is being explored.
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Enfermedades del Colon/patología , Pólipos Intestinales/patología , Enfermedades del Recto/patología , Humanos , Variaciones Dependientes del Observador , Patología/métodos , Patología/normas , Reproducibilidad de los ResultadosRESUMEN
Although cytogenetic analysis advanced the understanding of the pathogenesis of primary non-Hodgkin lymphoma and led to improved clinical management, there have been no large cytogenetic studies of post-transplant lymphoproliferative disorder (PTLD). We examined the karyotypes of 36 PTLD cases and correlated them with clinical, laboratory, and pathologic findings. The cases included 2 early lesions, 13 polymorphic PTLDs, and 21 monomorphic PTLDs (18 B-cell and 3 T-cell proliferations). Cytogenetic abnormalities were identified in 72% of monomorphic B-cell PTLDs and in all T-cell PTLDs, but in only 15% of polymorphic PTLDs and in no early lesions. The most frequent clonal abnormalities in monomorphic PTLD were trisomies 9 and/or 11 (5 cases), followed by rearrangements of 8q24.1 (4 cases), 3q27 (2 cases), and 14q32 (2 cases). MYC rearrangement (8q24.1) and T-cell-associated chromosomal abnormalities correlated with poor outcome and short survival. PTLD with trisomy 9 and/or 11 developed early after transplant, presenting as Epstein-Barr virus-positive large B-cell lymphoma with prolonged survival.