Clinical and pathological features of myeloid leukemia cutis

Abstract: Background: Myeloid leukemia cutis is the terminology used for cutaneous manifestations of myeloid leukemia. Objective: The purpose of this study was to study the clinical, histopathological and immunohistochemical features of myeloid leukemia cutis. Methods: This was a retrospective study of clinical and pathological features of 10 patients with myeloid leukemia cutis. Results: One patient developed skin lesions before the onset of leukemia, seven patients developed skin infiltration within 4-72 months after the onset of leukemia, and two patients developed skin lesions and systemic leukemia simultaneously. Of these patients, five presented with generalized papules or nodules, and five with localized masses. The biopsy of skin lesions showed a large number of tumor cells within the dermis and subcutaneous fat layer. Immunohistochemical analysis showed strong reactivity to myeloperoxidase (MPO), CD15, CD43 and CD45 (LCA) in most cases. NPM1 (nucleophosmin I) and FLT3-ITD (Fms-like tyrosine kinase 3-internal tandem duplication) mutations were identified in one case. Five patients with acute myelogenous leukemia and one patient with chronic myelomonocytic leukemia died within two months to one year after the onset of skin lesions. Study limitations: This was a retrospective and small sample study. Conclusions: In patients with myelogenous leukemia, skin infiltration usually occurs after, but occasionally before, the appearance of hemogram and myelogram abnormalities, and the presence of skin infiltration is often associated with a poor prognosis and short survival time. myeloid leukemia cutis often presents as generalized or localized nodules or masses with characteristic pathological and histochemical findings.

Tratamiento de la leucemia promielocítica aguda con acido transretinoico en dosis de 25 miligramos por metro cuadrado / Treatment of acute promyelocytic leukemia with acid trans dose of 25 milligrams per square meter

Se realizó un estudio observacional, descriptivo, de serie de casos, en el Hospital Esdcuela Dr. Roberto Calderón G. (HEDRCG) durante el periodo de 2002 al 2007, con el objetivo de determinar la respuesta a la administración de acido transretinoico en dosis de 25 mg/m cudrado de superficie corporal en los pacientes con diagnóstico de leucemia promielocitica aguda. Ingresados en el servicio de Heamto- ontología del Hospital en estudio. El universo lo constituyeron todos los pacientes diagnósticados con leucemia promielocitica aguda en el HEDRCG registrados en el servicio de estadísticas del Hospital. La muestra la conformaron 14 pacientes diagnósticados con leucemia promielocitica aguda en el HEDRCG durante el periodo de estudio que fueron seleccionados según criterios de inclusión y de exclusíon. No podemos dejar de mencionar que aunque nuestra muestra es poica, los estudios internacionales tampoco reportan en gran cantidad de pacientes, en la mayor parte los estudios no pasan de 25 pacientes estudiados. El 92 por ciento tenían manifestaciones de sangrado al ingreso al Hospital y la localización más frecuente fue la piel y mucosa...

Extra mammary tumors metastasis to the breast

In patients with known extramammary malignancies, Metastatic disease should be considered in the differential diagnosis of a palpable breast mass, particularly if there is a history of extramammary malignancy. Breast metastasis is usually indicative of diffuse metastatic disease and a poor prognosis. Biopsy and careful review of previous pathologic material assures prompt treatment and avoids an unnecessary radical operation. Breast metastases from extramammary tumors are rare with few cases reported. Four cases of metastasis to the breast are presented and the diagnostic problems of this condition are reviewed. Correlation between the histology of primary tumor and the cytology of breast metastatic tumors can avoid the surgical breast biopsy and unnecessary mastectomy. In conclusion, Metastasis to the breast has poor prognosis. We report a case of metastasis leukemia to breast presenting as a breast lump

Impaired responses of leukemic dendritic cells derived from a human myeloid cell line to LPS stimulation

Several myeloid leukemia-derived cells have been reported to possess the ability to differentiate into dendritic cells (DC). MUTZ-3, a myeloid leukemia cell line, responds to GM-CSF, IL-4 and TNF-alpha, and acquires a phenotype similar to immature monocyte-derived DC (MoDC). In the present study, MUTZ-3-derived DC (MuDC) showed high level expression of HLA class II molecules, CD80 and CD86, and were able to function as potent antigen presenting cells as previously reported. Interestingly, MuDC maturation was induced by CD40-mediated stimulation, but not by LPS stimulation. We analyzed CCR1, CCR7 and Toll-like receptor (TLR) expressions in MuDC, and measured IL-10 and IL-12 production after maturation stimuli. Although MuDC expressed the mRNA for TLR4, a major component of the LPS receptor system, they did not show an enhanced level of CCR7 or cytokine production after LPS stimulation. In contrast, they responded to CD40 stimulation, which resulted in increased levels of CD83, CD86 and CCR7. Moreover, while LPSstimulated MoDC could potently stimulate NK cells in a DC-NK cell co-culture, LPS-stimulated MuDC failed to stimulate primary NK cells. Taken together, our findings suggest that, although MuDC express TLR4, unlike TNF-alpha and IL-1beta, LPS does not stimulate MuDC to acquire mature phenotypes, and they may have impaired activity to initiate innate immune response.

Sarcoma granulocítico em órbita: relato de caso / Orbital granulocytic sarcoma: case report

O sarcoma granulocítico é tumor que freqüentemente aparece em pacientes portadores de leucemia mielóide aguda, podendo aparecer em diferentes regiões do corpo, incluindo a órbita. Nesta última localização, é mais freqüente em crianças e adultos jovens, com discreta predominância em pacientes do sexo masculino. Este é um caso de sarcoma granulocítico orbitário de evolução rápida, sem manifestação sistêmica associada em uma paciente de 33 anos de idade, o que o torna incomum. O surgimento do sarcoma granulocítico orbitário sem acometimento leucêmico pode ocorrer em cerca de 88 por cento dos pacientes com acometimento orbitário. A maioria dos pacientes apresenta evidências hematológicas de comprometimento sistêmico em 2 meses após a manifestação orbitária. Neste relato de caso, a paciente não apresenta acometimento sistêmico, apesar da manifestação orbitária estar presente há 30 meses. Os principais diagnósticos diferenciais do sarcoma granulocítico orbitário são o linfoma, o rabdomiossarcoma e o neuroblastoma. O diagnóstico pode ser dificultado, principalmente nos casos sem acometimento sistêmico, nos quais os exames de imagem e as manifestações clínicas pouco diferem de outras doenças. Para o diagnóstico deve-se realizar uma biópsia da lesão orbitária para análise anatomopatológica e imuno-histoquímica. O tratamento nos casos de sarcoma granulocítico orbitário sem acometimento sistêmico não é padronizado. A hipótese diagnóstica de sarcoma granulocítico orbitário deve ser aventada em casos de pacientes com tumoração orbitária mesmo que não apresentem sinais ou sintomas sistêmicos e independentes da faixa etária.

Freequency of FAB subtypes i acute myeloid leukemia patients at Aga Khan University Hospital Karachi

Acute myeloid leukemia [AML] is a heterogeneous disease. Therefore, various parameters are needed to classify this disease into subtypes, so that specific treatment approaches can be utilized effectively. The commonly used method for diagnosis and classification is based on FAB criteria using morphology and cytochemical stains. For sonic of the categories, imnninophenotyping is necessary. The aim of present study is to determine the frequency of various sub types in acute myeloid leukemia using FAB criteria in our population. This will aid in the correct diagnosis of acute leukemia and hence proper management of the patients. Materials and This is descriptive case control study conducted at Aga Khan University Hospital from January 1999 to December 2000. The total number of subjects was 116 that included both adults and children. The patients were diagnosed on the basis of bone marrow morphology using FAB classification. Cytochemistry was done in all cases, while immunophenotyping was considered only in those cases that were found to be problematic. Among 116 patients, 70 were males and 46 were females with male to female ratio 1.5:1. The age ranged between 6 months to 85 years with a mean age of 32 years. AML-M4 was the predominant French American-British [FAB] subtype [36.2%] followed by M2 [30.25%], M3 [10.4%], M1 [7.7%]. M5a [3.5%], M5b [2.5%] and M6 [0.8%]. Conclusions: The most common FAB subtype observed in our study was Acute myclomonocytic leukemia [M4] which is in accordance with studies reported from Saudia Arabia and a previous study reported from our institution. However, other national and international studies have reported Myeloblastic Leukemia with maturation [M2] as the predominant subtype of AML

Role of Ras/ERK-dependent pathway in the erythroid differentiation of K562 cells

The chronic myelogenous leukemic K562 cell line carrying Bcr-Abl tyrosine kinase is considered as pluripotent hematopoietic progenitor cells expressing markers for erythroid, granulocytic, monocytic, and megakaryocytic lineages. Here we investigated the signaling modulations required for induction of erythroid differentiation of K562 cells. When the K562 cells were treated with herbimycin A (an inhibitor of protein tyrosine kinase), ras antisense oligonucleotide, and PD98059 (a specific inhibitor of MEK), inhibition of ERK/MAPK activity and cell growth, and induction of erythroid differentiation were observed. The ras mutant, pZIPRas61leu-transfected cells, K562-Ras61leu, have shown a markedly decreased cell proliferation rate with approximately 2-fold doubling time, compared with the parental K562 cells, and about 60% of these cells have shown the phenotype of erythroid differentiation. In addition, herbimycin A inhibited the growth rate and increased the erythroid differentiation, but did not affect the elevated activity of ERK/MAPK in the K562-Ras61leu cells. On the other hand, effects of PD98059 on the growth and differentiation of K562-Ras61leu cells were biphasic. At low concentration of PD98059, which inhibited the elevated activity of ERK/MAPK to the level of parental cells, the growth rate increased and the erythroid differentiation decreased slightly, and at high concentration of PD98059, which inhibited the elevated activity of ERK/MAPK below that of the parental cells, the growth rate turned down and the erythroid differentiation was restored to the untreated control level. Taken together, these results suggest that an appropriate activity of ERK/MAPK is required to maintain the rapid growth and transformed phenotype of K562 cells.

CSF cytokines, nitric oxide and prostaglandins in diagnosis and pathophysiology of childhood CNS leukemia and lymphoma

To clarify the role of cytokines, nitric oxide [NO] and prostaglandin- E2 [PG-E2] in diagnosis and pathogenesis of infiltration of central nervous system [CNS] in cases with leukemia and lymphoma, the levels of these indices in the cerebrospinal fluid [CSF] of those children were determined. Their levels were correlated with other laboratory studies of CSF and clinical criteria. This study included twenty- seven children with acute leukemia [twenty with acute lymphoblastic leukemia [ALL] and seven with acute myeloid leukemia [AML]] and fifteen with non- Hodgkin's lymphoma [NHL]. Clinical evidence of CNS involvement was present in seventeen patients with acute leukemia and seven cases with NHL. The study revealed significantly elevated levels of two types of cytokines [TNF-alpha, IL-6] NO and PG-E2 in CSF of children with acute leukemias and lymphoma compared with control group [children with tension headache or meningism]

Incidência de síndrome de lise tumoral aguda em pacientes portadores de hemopatias malignas / Incidence of acute tumor lysis syndrome in patients with malignant blood diseases

O emprego de quimioterapia em tumores de alta replicaçäo celular é responsável pela liberaçäo de constituintes celulares, que podem levar a sérias alteraçöes metabólicas. Estas alteraçöes compreendem distúrbios no metabolismo do: potássio, cálcio, fosfato, uréia e ácido úrico; que caracterizam a SINDROME de LISE TUMORAL AGUDA (SLTA). No período de 29/03/93 a 23/08/93, foram estudados 20 pacientes com hemopatias malignas, com indicaçäo de tratamento poliquimioterápico. Estes pacientes receberam hiper-hidrataçäo com 2000ml/m2 de soluçäo fisiológico 0,9 por cento e alopurinol 200mg/m2 iniciando-se no dia anterior até o último dia de quimioterapia. O diagnóstico de SLTA foi considerado nos pacientes que nos 4 dias do tratamento, apresentaram duas ou mais das seguintes alteraçöes metabólicas: aumento de 25 por cento nos níveis de potássio, ácido úrico, uréia e fosfato; ou diminuiçäo de 25 por cento no nível de cálcio sérico. A SINDROME DE LISE TUMORAL AGUDA CLINICA (SLTAC), foi definida como SLTAC, associada a condiçöes clínicas que implicassem em risco de vida nenhum dos nossos pacientes apresentou SLTAC e apenas 30 por cento desenvolveram SLTAL, demonstrando que este esquema de tratamento foi efetivo.

Integrin receptors and TGF-Beta expression in chronic myeloid leukemia cells

To understand relationiship between transforming growth factor beta-1 (TGF-ß1) and the integrin profile presented by chronic myeloid leukemia cells, we have studied, using Northen analysis, the expression of TGF-ß1 messenger RNA (TGF-ß mRNA) in myeloid cell lines and in patient with acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). In addition we determined the positivity for alfa4 and alfa5 integrin moleculas in those cell using specific monoclonal antibodies and flow cytometry. CML patients (N=3) presented mean values of alfa4 higher (alfa4: 60 ñ 20 per cent); alfa5: 70 ñ 41 per cent) than AML (N=10) blast cells (alfa4: 25 ñ 23 per cent); alfa5: 18 ñ 16 per cent). Northern analysis revealed an almost four-fold higher expression of TGF-ß mRNA in K562 (derived from a patient with chronic myeloid leukemia) compared to the myeloblastic cell line HL60. The highest TGF-ß mRNA levels were seen in the U937 lineage. CML leukemic cells (N=3) showed high TGF-ß mRNA levels comparable to the levels expressed by K562 which was paralleled by high ß1 integrin mRNA. AML blast cells presented a variable degree of expression of TGF-ß mRNA when compared to HL60. One patient with acute megakaryoblastic leukemia (FAB subtype M7), usually associated with myelofibrosis, presented the highest TGF-ß mRNA levels. We conclude that studing TGF-ß1 and its mechanisms of action will help in understanding fibrosis in leukemic patients, and perhaps to design treatments for such conditions

Meningioma-like intracranial granulocytic sarcoma (chloroma): radiologic and surgical findings

Se presenta el caso de una paciente de 23 años de edad con leucemi granulocítica crónica en quien se identificaron dos lesiones tumorales con características típicas de meningiomas intracraneales. Durante la cirugía de la masa tumoral de mayor tamaño, que provocaba hipertensión intracraneana, se encontraron todas las características macroscópicas de un meningioma. El tratamiento fue exitoso y el estudio histopatológico reveló un sarcoma granulocítico. La otra masa tumoral fue radiada disminuyendo el volumen tumoral en el término de un mes y dejando a la paciente asintomática desde el punto de vista neurológico. Se propone tratamiento quirúrgico en casos futuros de grandes cloromas

Granulocytic sarcoma of the paranasal sinus.

We describe a young adult male with granulocytic sarcoma of the paranasal sinuses and nose with acute non-lymphoblastic leukaemia. Complete remission was achieved after systemic chemotherapy and localised radiation therapy. The patient died four months later due to disseminated aspergillosis.

Coagulation disorders in different types of acute leukemia

The results of the coagulation studies performed on blood from 32 leukemic patients with different types of acute leukemia showed evidence in favor of fibrinolysis. The fibrinolysis seems to occur as a primary process independent of DIC, as a result of the release of enzymes with fibriolytic activity from the leukemic leukocytes

Photosensitization of cultured cells and viruses by pyrene lipids.

Administration of pyrene-linked fatty acids and lipids to cultured cells or an enveloped (vesicular stomatitis) virus induced photosensitization which, following irradiation with a long ultra-violet light (LUV), resulted in killing of the cells and loss of the infectivity of the virus with the following specific effects. (i) LUV illumination of the pyrene-sphingomyelin administered cultured skin fibroblasts derived from normal individuals and patients with Niemann-Pick disease permitted selective killing of the latter. (ii) Similarly LUV illumination of pyrenedodecanoic acid (P12) incubates of leukemic cell lines mixed with human bone marrow cells permitted selective killing of the former. (iii) LUV illumination of P12 incubates of vesicular stomatitis virus decreased the infectivity of the virus by up to 12 logs.

Leucemia mielomonocítica crónica / Chronic myelomonocytic leukemia

Se estudiaron las biopsias medulares óseas de 10 pacientes con diagnóstico hematológico de Leucemia Mielomonocítica Crónica (LMMC). Los cilindros fueron obtenidos de la cresta ilíaca, descalcificados, incluidos en parafina y los cortes obtenidos coloreados con diversas técnicas. Se estableció estimativamente la celularidad global así como las características madurativas y topográficas de las progenias, cantidad de hemosiderina, magnitud de la trama reticular y otras observaciones complementarias. Los pacientes comprendieron 8 hombres y 2 mujeres, con un rango etario de 63 a78 años y una media de 70 años. Se registró la presencia de síntomas generales en 5 pacientes, hepatomegalia en 8, esplenomegalia en 9 y adenomegalias en 8 pacientes. Todos evidenciaban monocitosis en sangre periférica (> 1 x 10**9/l). Las médulas fueron hipercelulares, con 80 a 100% de celularidad hemopoyética. La serie mieloide mostró maduración completa con topografía conservada y precursores aislados, y presencia de elementos monocitoides más o menos conspicuos. La serie eritroide mostró disminución de grado variable en todos los casos. El sector megacariocítico evidenció alteraciones morfológicas discretas con topografía conservada. La hemosiderina estaba aumentada en 5 casos. La trama reticular se presentó incrementada en 8 pacientes. Como alteraciones asociadas se observó plasmocitosis reactiva en tres casos y cambios óseos en 6 pacientes. En base a los resultados obtenidos se concluye que la LMMC posee un cuadro histológico distintivo, que difiere de las Mielodisplasisa y guarda una relación en ocasiones estrecha, con los Síndromes Mieloproliferativos Crónicos, en especial la Leucemia Mieloide Crónica