Myeloid sarcoma: an uncommon presentation of myeloid neoplasms; a case series of 4 rare cases reported in a tertiary care institute

Myeloid sarcoma (MS) is a rare extramedullary neoplasm of myeloid cells, which can arise before, concurrently with, or following hematolymphoid malignancies. We report 04 such cases of MS, diagnosed in this institute over a period of 6 years, during various phases of their respective myeloid neoplasms/leukemias. These cases include MS occurring as a relapse of AML (Case 1), MS occurring as an initial presentation of CML (Case 2), MS occurring during ongoing chemotherapy in APML (Case 3), and MS presenting as a progression of MDS to AML (Case 4). In the absence of relevant clinical history and unemployment of appropriate immunohistochemical (IHC) studies, these cases have a high risk of being frequently misdiagnosed either as Non-Hodgkin's Lymphoma (NHL) or small round cell tumors or undifferentiated carcinomas, which may further delay their management, making an already bad prognosis worse. This case series has been designed to throw light on the varied presentation of MS and the lineage differentiation of its neoplastic cells through the application of relevant IHC markers along with their clinical correlation.

AAcute WT1-positive promyelocytic leukemia with hypogranular variant morphology, bcr-3 isoform of PML-RARα and Flt3-ITD mutation: a rare case report / Leucemia promielocítica aguda WT1-positivo com morfologia variante hypogranular, isoforma bcr-3 da PML-RARα e mutação Flt3-ITD: relato de caso raro

ABSTRACT CONTEXT: Acute promyelocytic leukemia (APL) accounts for 8% to 10% of cases of acute myeloid leukemia (AML). Remission in cases of high-risk APL is still difficult to achieve, and relapses occur readily. CASE REPORT: Here, we describe a case of APL with high white blood cell counts in blood tests and hypogranular variant morphology in bone marrow, together with fms-like tyrosine kinase-3 with internal tandem duplication mutations (FLT3-ITD), and bcr-3 isoform of PML-RARα. Most importantly, we detected high level of Wilms’ tumor gene (WT1) in marrow blasts, through the reverse transcription polymerase chain reaction (RT-PCR). To date, no clear conclusions about an association between WT1 expression levels and APL have been reached. This patient successively received a combined treatment regimen consisting of hydroxycarbamide, arsenic trioxide and idarubicin plus cytarabine, which ultimately enabled complete remission. Unfortunately, he subsequently died of sudden massive hemoptysis because of pulmonary infection. CONCLUSION: Based on our findings and a review of the literature, abnormal functioning of WT1 may be a high-risk factor in cases of APL. Further studies aimed towards evaluating the impact of WT1 expression on the prognosis for APL patients are of interest.

RESUMO CONTEXTO: Leucemia promielocítica aguda (LPA) compreende 8% a 10% dos casos de leucemia mieloide aguda (LMA). A remissão em casos de LPA de alto risco ainda é dificilmente conseguida, e recorrência é comum. RELATO DE CASO: Descrevemos aqui um caso de LPA com glóbulos brancos elevados no exame de sangue e a morfologia variante hipogranular na medula óssea, juntamente com fms-like tirosina-quinase-3 com mutações de duplicação em tandem interna (FLT3-ITD) e a isoforma bcr-3 de PML- RARα. Mais importante, detectamos alto nível de gene do tumor de Wilms (WT1) em blastos medulares por RT-PCR (reverse transcription polimerase chain reaction). Até agora, não há conclusões claras sobre a associação entre os níveis de expressão WT1 e APL. Este paciente recebeu sucessivamente regime de tratamento combinado, de hidroxicarbamida, trióxido de arsênico e idarrubicina e citarabina, alcançando finalmente a remissão completa. Infelizmente, em seguida, ele morreu de repente de hemoptise maciça devido a uma infecção pulmonar. CONCLUSÃO: Com base em nossos resultados e numa revisão da literatura, a função anormal de WT1 pode ser um fator de alto risco em casos de APL. Novos estudos, com o objetivo de avaliar o impacto da expressão de WT1 no prognóstico dos doentes com APL, são de interesse.

Evaluación de la actividad antiproliferativa y proapoptótica de compuestos kauranos sobre líneas celulares de leucemia humana / Evaluation of the antiproliferative and proapoptotic activity of kauran compounds on human leukemia cell lines

En Venezuela y el mundo, el cáncer es la segunda causa de morbi-mortalidad, y la leucemia es uno de los tipos de cáncer que afecta a nuestra población. La principal características de las celulas linfoides y mieloides presentes en la leucemia es que son pocos funcionales y además no responden a las señales proapoptóticas. Por lo tanto, en la búsqueda de compuestos de mejor perfil terapéutico, se evaluó el efecto de compuestos de tipo seco ent-kauranos aislados de plantas terrestres en las lineas celulares jurka E6.1 y HL60 sobre el crecimiento celular a través del método colorimétrico del MTT, la inducción de apoptosis a través del uso de la microscopia confocal, la citometría de flujo y los micro arreglos de proteínas; y sobre el ciclo celular, la actividad de la vía del NFkB y la diferenciación celular también a través de la citometría de flujo. Se determino que el ácido de casacasina, y la caracasina, disminuyeron la proliferación cecular, indujeron el arresto del ciclo celular, provocaron la externalización de la fosfatidilserina y la activación de las capasas 3, 7, 8 y 9, a la vez que promovieron la disminución del potencial mitocondrial, incrementaron la expresión de las proteínas proapoptóticas en ambas líneas celulares, disminuyeron la activación de la vía de señalización del NFkB en la línea celular Jurkat E6.1, y ademas indujeron la expresión de la proteína CD40 e incrementaron la producción de especies reactivas de oxigeno en la línea celular HL60, por lo que estos compuestos ent-kauranos poseen un alto potencial anticancerígeno para la leucemia linfocítica aguda de células T y para la leucemia promielocítica

Clinico-pathological profile of acute promyelocytic leukaemia at Al-Amal oncology-haematology centre, Qatar

This cases series describes the profile of adult patients with acute promyelocytic leukaemia [APL] at a referral hospital in Qatar of 34 acute myeloid leukaemia [AML] cases diagnosed, 11 [32%] were classified as APL. Disseminated intravascular coagulation was common at presentation [91%]. Severe thrombocytopenia was seen in 73%, leukocytosis in 55% and severe anaemia in 45%. Only 2 patients were of the classic hypergranular type. In the remaining 9 patients, 3 morphological subtypes were recognized: microgranular variant [6 patients], hyperbasophilic [2 patients] and regular nuclear outline M3r [1 patient]. Translocation t[15;17] was detected in 63% of cases. APL constitutes a high proportion of AML cases in Qatar, with considerable morphological heterogeneity and a predominance of APL variants with unfavourable presenting features

Trióxido de arsénico: una nueva luz en el tratamiento de la leucemia promielocítica / Arsenic trioxide: a new light in the treatment of promyelocytic leukemia

En los últimos 20 años, y gracias a la efectividad del ácido retinoico todo en trans (ATRA), medicamento introducido por investigadores chinos en el tratamiento de la leucemia promielocítica, esta variedad de leucemia pasó de ser la más agresiva y de peor pronóstico por su alta mortalidad, a ser en la que se logra una mayor sobrevida y posibilidad de curación; pero a pesar de las bondades de este medicamento, aproximadamente el 20 por ciento de los pacientes pueden tener una recaída tanto hematológica como molecular en algún momento de la evolución de la enfermedad. Nuevamente investigadores chinos demostraron los beneficios del trióxido de arsénico (TOA), medicamento que por diferentes vías logra la maduración y diferenciación del promielocito leucémico y finalmente la desaparición del gen anormal PML/RARá y de su proteína híbrida. En los primeros trabajos realizados, el trióxido de arsénico se utilizó en los pacientes que tenían algún tipo de recaída o en aquellos que no respondían al ATRA y se logró alrededor del 80 por ciento de remisiones hematológicas y moleculares en estos enfermos; posteriormente varios grupos de trabajo han reportado resultados similares. Ante estos resultados, el TOA se comenzó a utilizar como droga de primera línea con excelentes resultados.

In the last 20 years and thanks to the effectivity of all-trans retinoic acid (ATRA), a drug introduced by Chinese researchers in the treatment of promyelocytic leukemia, this variety of leukemia that was the most aggressive and had the poorest prognosis due to its high mortality, has showed the highest survival and possibility of cure. In spite of its benefits, at about 20 percent of the patients may have a relapse both hematological and molecular some time during the evolution of the disease. Once again, the Chinese researchers showed the benefits or arsenic trioxide, a drug that allows by different routes the maturation and differentiation of leukemic promyelocite and, finally, the disappearance of the abnormal PML/RAR? gene and of its hybrid protein. In the first trials, arsenic trioxide was used in patients with some type of relapse or in those who did not respond to ATRA. 80 percent of hematological and molecular remissions were observed in these patients. Similar outcomes have been reported by various groups. According to its effects, it is being used as a first-line drug with excellent results.

Does acute promyelocytic leukemia in Indian patients have biology different from the West?

Acute promyelocytic leukemia (APML) is a well-characterized malignancy with typical clinico-hematological and molecular features. However, Indian data on this malignancy are limited. This study was conducted to determine the clinico-hematological profile of APML in India. Thirty-five patients with APML presenting to Hematology Department, AIIMS, New Delhi, between July 2003 and June 2005 were evaluated for presenting clinical features, hemogram, peripheral smear, bone marrow morphology and cytochemistry. Reverse transcriptase PCR (RT-PCR) for PML-RARalpha was done in all cases. Male-to-female ratio was 0.9:1 (males--17 and females--18) with median age 25 years (range 11-57 years). Presenting features included anemia, bleeding, fever, gum hypertrophy and scrotal ulceration. All cases showed hypergranular abnormal promyelocytes. Median hemoglobin was 6.3 g/dL (range - 3.0-9.0 g/dL), total leukocyte count (TLC) was 33.88 x 10(9) /L (range - 1-170 x 10(9) /L). Platelet count was 28 x 10(9) /L (range - 4-170 x 10(9) /L). All cases were positive for myeloperoxidase and sudan black (SB), whereas 60% cases also showed non specific esterase (NSE) positivity with 40% cases being fluoride sensitive. RT-PCR showed PML-RARalpha in 33/35 cases with the bcr3 isoform being present in 24/33 positive cases (72.7%). The two cases negative for PML-RARalpha showed typical morphology and responded to ATRA. On statistical analysis, no correlation was found between bcr isoform and TLC, platelet count, age sex and early death. Unusual features included gum hypertrophy and scrotal ulceration at presentation and high median presenting TLC (33.8 x 10(9) /L). There was, however, no microgranular variant. Another interesting feature was a high incidence of NSE positivity (60%), which was fluoride sensitive in 40%. Moreover, the bcr3 isoform was significantly overexpressed (72.7%) in comparison to other studies. APML in India has certain unusual features, which may reflect a different biology.

Construction and significance of directional expression cDNA library from human NB4 cells / 华中科技大学学报（医学）（英德文版）

Human acute premyeloid leukemia cell cDNA expression library was constructed to screen acute premyeloid leukemia tumor antigen. Total RNA and purified mRNA were extracted from human premyeloid cell line NB4. First and second strands of cDNA were synthesized by reverse transcription. After blunting, the cDNA fragments were ligated with EcoR I adapters. Then the cDNAs were digested with Xho I, and less than 400 bp cDNA fragment was removed by Sephacryl-S400 spin column, the remaining were ligated with lambdaZAP vector. The recombinants were packaged in vitro, and a small portion of packaged phage was used to infect E. coli XL1-Blue-MRF' for titration. The recombinants were examined by color selection. In order to evaluate the size of cDNA inserts and the diversity of library, the pBK-CMV phagemid was excised from the ZAP express vector by using ExAssist helper phage with XLOLR strain, and then the pBK-CMV phagemid was digested by Xho I and EcoR I. The results showed that the NB4 cell line cDNA library consisting of 1.65 x 10(6) recombinant bacteriophages was constructed with the recombinant ratio of 99.6%. The average length of the recombinant exogenous inserts was about 1.7 kb. It was concluded that the constructed cDNA library are deserved to screen target clones.

Leucemia aguda promielocítica: revisión de 36 casos de autopsias en el Hospital General de México en un periodo de 12 años / Acute promylocytic leukaemia: review of 36 autopsy cases in the Hospital General de Mexico in a 12 years period

Se registraron y revisaron 36 casos de leucemia aguda promielocítica en material de autopsia del Hospital general de México. Esta cifra representó el 0.4 por ciento del total de sujetos (8,140) autopsiados en un periodo de 12 años (1980-1991); el 11 por ciento de los casos diagnosticados como leucemias de todas las variedades (325 casos) y el 12.8 por ciento de leucemias agudas (281 casos). Treinta y cuatro casos fueron clasificados como leucemia aguda promielocítica de la variedad hipergranular y dos de la variedad microgranular. La medida de la edad fue de 20 años, la relación hombre:mujer fue de 1.2:1. Se observó infiltración neoplásica en varios órganos; los más frecuentemente afectados fueron: médula ósea, hígado y ganglios linfáticos. Las hemorragias fueron un dato constante y los sitios más frecuentes fueron pulmones y sistema nervioso central. Se encontraron datos histológicos de coagulación intravascular diseminada en ocho casos. La supervivencia media de los 36 casos fue de 8.2 semanas; esta media no varió para el grupo tratado, pues solamente recibieron la primera dosis de quimioterapia, por lo que no hubo casos de remisión

Leucemia M3 variante: aspectos clínicos e diagnósticos / M3 variant leukemia: clinical and diagnosis features

A leucemia promielocítica (LMA M3) representa em média 5-10// dos casos de leucemias melóides agudas (LMA) registrados na literatura, acometendo preferencialmente adultos jovens e cursando com comportamento clínico-biológico distinto, quando comparada com as demais LMA. Caracteriza-se por morfolofia particular das células blásticas (M3 na classificaçäo FAB), translocaçäo dos cromossomos 15 e 17, e coagulaçäo intravascular disseminada ao diagnóstico ou após início da quimioterapia . Dentro deste subgrupo säo observados dois subtipos morfológicos conhecidos como LMA M3 hipergranular e LMA M3 hipogranular ou variante. Os autores analisaram 19 casos de LMA M3, diagnosticados dentre 217 casos de LMA, em seus aspectos clínicos e laboratoriais, e observaram que o reconhecimento da LMA M3 variante, apesar de se basear geralmente apenas em dados citomorfológicos, näo tem sido feito corretamente em nosso meio. Dos oito casos recebidos no serviço dos autores para estudo, apenas quatro foram encaminhados com o diagnóstico correto de seus serviços de origem, sendo os outros quatro casos diagnosticados como leucemia mielomonocítica (LMA M4). A imunofenotipagem, como técnica diagnóstica complementar à citomorfologia, permite esclarecer, definitivamente, casos duvidosos. A classificaçäo correta se faz cada vez mais necessária devido a aspectos terapêuticos e prognósticos particulares das LMA M3, que, ao contrário das outras formas de LMA, têm sido tratadas näo só com drogas citotóxicas, mas também com agentes indutores de diferenciaçäo celular, com excelentes resultados

Correlation between morphological and cytochemical heterogeneity of acute promyelocytic leukemia (APL) and its association with myelodysplasia.

Sixty one cases of acute promyelocytic leukemia (M3) were diagnosed between Jan., 1985 and Dec., 1988. Morphologically 46 cases (75.4%) were characterised as typical M3 and 15 cases (24.6%) as M3 variant. Typical M3 cases had higher number of hypergranular promyelocytes and Auer rods (P less than 0.001). The cytochemical stains of myeloperoxidase, Sudan Block and Black and chloroacetate esterase were strongly positive in M3 typical and mild to moderately positive in M3 variant cases. Alpha-naphthyl acetate esterase positivity with fluoride inhibition was seen only in M3 variant cases (80%). The clinical and haematological parameters including marrow blast count were not significantly different in the two groups. This study has shown that M3 variant cases more frequently express heteregenous cytochemical patterns and myelodysplastic changes.