Diagnosis Of Acute Monocytic Leukemia Research Articles

Leukemia Cutis – A Case Report

Abstract Leukemia cutis is a specific skin lesion which is characterized by diffuse infiltration of neoplastic cells and can occur in all types of leukemia. Leukemia cutis can have varied cutaneous presentations such as papules, macules, nodules, plaques and ulcers. We report a case of 52-year-old woman who presented with erythematous macules and papules over her trunk, thighs and upper arms. A skin punch biopsy showed monomorphic, perivascular and periadnexal infiltration by the cells positive for CD45, CD15, CD68 and lysozyme. According to the subsequent bone marrow biopsy and immunophenotypic analysis of peripheral blood cells, the diagnosis of acute monocytic leukemia (FAB AML-M5b) was made. In our case, the first clinical sign suggestive of the diagnosis of leukemia was the presence of erythematous macules and papules. Therefore, we believe that leukemia cutis should be taken into consideration in the differential diagnosis of maculopapular rush on the trunk, upper arms and leg

Acute monocytic leukemia diagnosed by flow cytometry includes acute myeloid leukemias with weakly or faintly positive non-specific esterase staining.

A diagnosis of acute monocytic leukemia (AML-M5) based on α-naphthyl butyrate esterase (α-NB) staining has some problems, because AML-M5 leukemic cells often show weak or faint positivity on α-NB staining. In these situations, some cases of AML-M5 tend to be misdiagnosed as AML-M0. Therefore, we evaluated the significance of weak or faint α-NB staining in AML-M5 diagnosed by flow cytometry (FCM). Nineteen AML cases in which leukemic cells were negative for naphthol AS-D chloroacetate esterase staining were studied. For FCM, we defined leukemic cells as having a monocytic nature when more than 10% of the leukemic cells were positive for at least one of the following antigens: CD4, CD11c, CD14, and CD64. The monocytic nature determined by FCM was consistent with positive or weak positivity on α-NB staining. Five of 6 cases in which leukemic cells exhibited faint positivity for α-NB staining could be diagnosed as AML-M5 by FCM, while negative α-NB staining was consistent with a diagnosis of AML-M0. These results suggest that AML-M5 should be taken into consideration even when leukemic cells are faintly positive for α-NB staining.

Acute Monoblastic Leukemia and Myeloproliferative Neoplasm Observed in an Elderly Man Had the Same Clonal Origin

It is reported that fonder mutations affects the development these disorders closely. However, it is unclear whether hematopoiesis carrying these mutations could contribute to the development of the different diseases, directly. We here report a case of acute monoblastic leukemia (AMoL) followed by myeloproliferative neoplasm, unclassifiable (MPN-U), 2 years later, both derived from the same clonal hematopoiesis. [Case report and Methods] A 75-year-old male was admitted to our hospital duo to fever and fatigue. WBC count was 114.7 x 109/L with 9% blasts and 82% monocytes. Bone marrow aspiration revealed 93% of blasts and promonocytes, which resulted in the diagnosis of AMoL with normal karyotype. He received three courses of chemotherapy, which brought CR, but minor monocytosis (>1 x 109/L) persisted without proliferation of immature blasts. After 2 years from the diagnosis of AMoL, platelet count started to increase. WBC count was between 10 and 20 x 109/L without blast, and platelet count reached 500 x 109/L. Bone marrow examination (2 years from the diagnosis of AMoL) revealed normal cellularity, and less than 5% of blast with normal karyotype. Considering the leukocytosis and thrombocytosis, we evaluated his status as similar to MPN, since dysplasia was not apparent on his hematopoietic cells. Although he had previously received chemotherapy for AMoL, it was diagnosed as MPN-U. Two years after the diagnosis of MPN-U, the disease transformed into AML, not AMoL. He died of AML, four years after AMoL developed. To study clonal status of AMoL and MPN-U in this case, bone marrow mononuclear cells of AMoL (at diagnosis) and MPN-U phases, and buccal swab collected during MPN-U phase were subjected to whole exome sequencing (WES). Validation of mutations was performed by amplicon-base deep sequencing. DNA obtained from bone marrow smear during CR was tested whether mutations existed or not by deep sequencing. Mean depth of WES was 89.15, 140.18, and 98.02 for AMoL, MPN-U, and buccal mucosa samples, respectively. Clonal evolution analysis was performed using clonality inference in tumors using phylogeny. [Results] We found total 22 mutations in samples of AMoL and MPN-U phase with different variant allele frequency (VAF) by WES. When AMoL was diagnosed, 16 genes were mutated with more than 10% of VAF, including genes such as ASXL1, CBL, GATA2, NPM1 (4 bp insertion), SRSF2, and TET2. On the other hand, when MPN-U was diagnosed, there were 16 genes mutated with more than 10% of VAF, and 10 mutations out of 16 were the same mutation as found in the sample of AMoL phase including mutations in SRSF2, GATA2, and TET2. Six mutated genes found only in the sample of MPN-U phase included GNAS and JAK2 (V617F mutation). Since 10 out of 22 genes were commonly mutated in both the AMoL and MPN-U samples, we next analyzed the mutational status of these 22 genes in the CR sample using deep sequencing. It was found that the commonly mutated 10 genes in both AMoL and MPN-U were also mutated in the CR sample with high VAF (> 25%). Some gene mutations found only in AMoL, and some only in MPN-U were also present during CR phase but with low VAF (< 10%). Clonal evolution pathway generated by using deep sequence data suggested that before AMoL, there was a founder clone with mutations of TET2, SRSF2, and GATA2, although we could not analyze the sample before AMoL. Mutations in NPM1, ASXL1, CBL, and ASH1L seemed to contribute to the development of AMoL from the founder clone, and those of JAK2 and GNAS for MPN-U. It is also suggested that small amount of hematopoietic stem / progenitor cells containing the JAK2 mutation already existed in CR sample, and these developed into MPN-U probably with gaining other gene mutations. Our data prospectively showed that clonal hematological disorder would arise from a pre-malignant, clonal hematopoiesis that produced normal levels of mature hematopoietic cells. Our analysis clearly demonstrated that two different clonal hematological disorders developed from the same clonal hematopoiesis that had TET2, SRSF2, and GATA2 mutation, which were previously reported as driver mutations. To our knowledge, this is the first report to analyze the progression of AML and MPN from the identical hematopoietic stem cells by WES and deep sequencing validation to model clonal evolution and a case to give a new suggestion about the development of the myeloid malignancies. DisclosuresMiyazaki:Celgene Japan: Honoraria; Chugai: Honoraria, Research Funding; Sumitomo Dainippon: Honoraria; Shin-bio: Honoraria; Kyowa-Kirin: Honoraria, Research Funding. Moriuchi:Celgene: Other: Research Funding to my institution; travel, accommodations, expenses, Speakers Bureau.

Development of Somatic NRAS Mutation Associated with Rapid Transition from Germline GATA2 Mutation Associated Myelodysplastic Syndrome to Acute Myeloid Leukemia

There is increasing recognition of the role of inherited germline predisposition for myeloid disorders such as myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). The additional somatic genetic events required for development of a malignant phenotype are however poorly understood.A 25 year old woman was referred to the NHLBI hematology branch in March 2014 for a seven year history of pancytopenia. Her medical history included recurrent pneumonias, oral ulcers, severe varicella infection and arthralgias. Prior bone marrow examinations at ages 21 and 23 at outside institutions reported normocellular marrow, tri-lineage hematopoiesis and mild dyspoiesis. Cytogenetics were remarkable for trisomy 8 in 80% (aged 21) or 90% (aged 23) of metaphases.Previously unrecognized lymphedema was noted on examination. Peripheral blood counts showed WBC 2.28 K/ul [normal range: 3.98-10.04], HGB 9.9 g/dL [11.2-15.7], PLT: 67 K/ul [173-369], ALC: 0.36 K/ul [1.18-3.74] and AMC: 0.06 [0.24-0.86]. Peripheral blood flow cytometry demonstrated decreased CD3+ CD4+ (T) cells, CD19+ (B) cells and NK cells. HLA-DR15 negative. Bone marrow examination showed trilineage hematopoiesis, 50-60% cellularity, mild erythroid predominance and mildly increased, mildly atypical megakaryocytes. Blasts less than 5%. Bone marrow flow cytometry revealed severely decreased B-cells and monocytes, absent B-cell precursors, absent dendritic cells, inverted CD4:CD8 ratio, and atypical myeloid maturation pattern. Cytogenetics demonstrated stable trisomy 8 in 90% of metaphases.On the basis of this assessment the diagnosis of MDS was confirmed. Sanger sequencing revealed a GATA2 L375S mutation in the second zinc finger of known pathogenic significance.Four months later she developed increased fatigue and easy bruising with worsening thrombocytopenia (PLT: 10K/ul). Bone marrow was dramatically changed; now markedly hypercellular (90-100%) with diffuse sheets of immature cells consistent with blasts having fine chromatin, distinct or prominent nucleoli, and visible cytoplasm. Blasts were positive for CD33, CD56, CD64, CD123, and CD163; and were negative for CD34, CD14, and myeloperoxidase. Cytogenetics showed a new trisomy 20 in 65% of metaphases, in addition to previously seen trisomy 8 in 100%. A diagnosis of acute monoblastic leukemia (M5a subtype) was made.At both clinic visits bone marrow aspirate was collected on an IRB approved research sample acquisition protocol. Whole exome sequencing of 1ug DNA was performed using Agilent SureSelect v5 Exome enrichment Kits on an Illumina HiSeq 2000 with 100-bp paired-end reads (Macrogen, Rockville, MD). Data was mapped to hg19 (BWA) and processed using an in-house pipeline (Samtools/Picard/GATK/VarScan/Annovar). Mean read depth of target regions was 157 and 149. There was high correlation between both samples with the exception of a NRAS:NM_002524:exon3:c.C181A:p.Q61K mutation (57 of 180 reads) seen only in the later sample.Confirmatory ultra-deep sequencing for NRAS was performed using Illumina TruSight Myeloid Sequencing Panel on an Illumina MiSeq. No evidence of the NRAS Q61K mutation was found in the earlier March MDS bone marrow sample even when sequenced to a depth greater than 1750 reads (see figure). The mutation was confirmed in the August AML sample at a variant allele frequency of 35%. If heterozygous this would reflect a clone size of 70%, consistent with data from both cytogenetics (new trisomy 20 in 65% of metaphases) and the 76% blasts documented by bone marrow aspirate smear differential.We report here the rapid progression to AML in a patient with germline GATA2 MDS associated with development of a new trisomy 20 karyotype and a NRAS Q61K mutation. The NRAS mutation was not detectable after the patient achieved a complete remission following induction chemotherapy further supporting this association. This NRAS mutation has been implicated in the pathogenesis of multiple cancers by constitutive activation of proliferative signaling. GATA2 associated MDS is a high-risk pre-leukemic condition with the potential for rapid evolution to AML. This is the first report of acquired somatic mutations in the RAS/RTK signaling pathway in the context of germline GATA2 insufficiency associated with acute leukemic transformation. [Display omitted] DisclosuresTownsley:Novartis: Research Funding; GSK: Research Funding.

A case of extramedullary involvement of acute monocytic leukemia that presented as obstructive jaundice

A 66-year-old woman with liver dysfunction and jaundice was referred to our hospital for further examination. She had received a diagnosis of acute monocytic leukemia (AMoL) 14 months previously, for which she received chemotherapy and achieved complete remission. Laboratory tests revealed anemia and elevation of total bilirubin, direct bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and γ-glutamyltransferase levels. However, any tumor markers were unremarkable. Contrast-enhanced CT revealed encircling wall thickening of the duodenum and dilatation of the intrahepatic and common bile ducts (A). A duodenoscopy revealed diffuse edematous changes to the mucosa and an irregular ulcer on the side of the major duodenal papilla (B). Histologic examination with hematoxylin and eosin staining showed a diffuse proliferation of round atypical cells in the mucosa (C). On staining with PG-M1, these atypical cells were found to be diffusely positive for CD68 (D). These histopathologic findings were consistent with those of the bone marrow biopsy at the time of the woman’s initial diagnosis of AMoL. Thus, her diagnosis was extramedullary relapse of AMoL.

The co-presence of deletion 7q, 20q and inversion 16 in therapy-related acute myeloid leukemia developed secondary to treatment of breast cancer with cyclophosphamide, doxorubicin, and radiotherapy: a case report

IntroductionTherapy-related acute myeloid leukemia occurs as a complication of treatment with chemotherapy, radiotherapy, immunosuppressive agents or exposure to environmental carcinogens.Case presentationWe report a case of therapy-related acute myeloid leukemia in a 37-year-old Turkish woman in complete remission from breast cancer. Our patient presented to our facility with fatigue, fever, sore throat, peripheral lymphadenopathy, and moderate hepatosplenomegaly. On peripheral blood and bone marrow aspirate smears, monoblasts were present. Immunophenotypic analysis of the bone marrow showed expression of CD11b, CD13, CD14, CD15, CD33, CD34, CD45 and human leukocyte antigen-DR, findings compatible with the diagnosis of acute monoblastic leukemia (French-American-British classification M5a). Therapy-related acute myeloid leukemia developed three years after adjuvant chemotherapy consisting of an alkylating agent, cyclophosphamide and DNA topoisomerase II inhibitor, doxorubicin and adjuvant radiotherapy. Cytogenetic analysis revealed a 46, XX, deletion 7 (q22q34), deletion 20 (q11.2q13.1) karyotype in five out of 20 metaphases and inversion 16 was detected by fluorescence in situhybridization. There was no response to chemotherapy (cytarabine and idarubicin, FLAG-IDA protocol, azacitidine) and our patient died in the 11th month after diagnosis.ConclusionsThe median survival in therapy-related acute myeloid leukemia is shorter compared to de novoacute myeloid leukemia. Also, the response to therapy is poor. In therapy-related acute myeloid leukemia, complex karyotypes have been associated with abnormalities of chromosome 5, rather than 7. To the best of our knowledge, this is the first case of therapy-related acute myeloid leukemia showing the co-presence of deletion 7q, 20q and the inversion 16 signal.

Unusual Response of Acute Monocytic Leukemia to Dandelion Root Extract

Abstract 4288 Seventy year old man presented to Windsor Regional Cancer Centre with fever and pancytopenia on June 24, 2009. Presenting CBC was as follows: WBC 47.8:Ne 0.3, Ly 0.06, Mo 0.62, Meta 0.01, bands 0.01; Hgb 123; Platelets 55,000. A bone marrow biopsy revealed the following: 70% cellularity with sheets of immature blast-like cells; the lesional cells were CD68 and MPO positive and negative for CD34, CD117, CD138, CD20 and CD3. Flow cytometry revealed 46% of the cells positive for CD33, Cd36, CD64, MY4, CD16, HLA-DR, CD13, CD 56, CD10, CD11b, dim CD4, MPO positive, consistent with acute monocytic leukemia. Cytogenetics were 46, XY [24]. He was given the diagnosis of acute monoblastic leukemia and was started on standard induction chemotherapy: 3 + 7 daunorubicin and ara-C. (doses). Repeat bone marrow biopsy on July 17, 2009 revealed lack of remission. This bone marrow revealed sheets of blast-like cells with 30% residual monoblast population and 4% myeloblast population. He was then treated with high dose cytarabine (3 gm / m2 q day 1, 3, 5) for one cycle. Repeat bone marrow biopsy on Aug 20, 2009 revealed non-remission with 20% residual monoblasts. At this time, it was explained to him that he would be treated in a palliative fashion only. He started low dose AraC at this time and received one 21 day course. He showed hematological recovery by September 2009. Repeat bone marrow biopsy on October 5th, 2009 showed 6% residual myeloblast and 40% monocytic population. Because of previous signals of response at our centre to dandelion root tea/ water extract, and because of his current palliative diagnosis, we mentioned dandelion root tea to him. He started this tea on his own and was followed expectantly. Another bone marrow biopsy at the end of November 2009 showed only residual monocytic population of 10 – 12 % with 79% myeloid cells showing dysplastic features consistent with chronic myelomonocytic leukemia type 2. In March 2010, his platelet count started a gradual decline. By December 29, 2010, the platelet count had dropped to 35,000 × 10 9, and a bone marrow biopsy was done to determine etiology. Bone marrow biopsy from January 25, 2011 shows features suggestive chronic myelomonocytic leukemia. This biopsy revealed monocytic cells, as well as occasional promonocytes. There was adequate megakaryoctyes, no Auer rods, no blasts. The monocytes expressed 9% of the total nucleated cells, and did not express CD56. Flow cytometry reported all normal. A diagnosis of idiopathic thrombocytopenic purpura was made and patient was started on prednisone with subsequent improvement in his platelet count. CBC on July 4, 2011, almost two years from his diagnosis of refractory M5 AML, patient’s CBC is almost normal with a white blood count of 7.5 ×10*9/L, hemoglobin of 122 g/L, platelets of 134 ×10*9/L, neutrophils of 3.6 × 10*9/L, monocytes of 1.65 × 10*9/L. His quality of life remains excellent. He continues using dandelion root tea. In view of this very exciting response and the more temporary response seen in chronic myelomonocytic leukemia, as well as the exciting findings we have seen in monocytic cells lines and tolerance in animal models, we moving into a phase I/II clinical trial examining the effect of dandelion root extract in patients with monocytic leukemias. Disclosures: No relevant conflicts of interest to declare.

Blueberry muffin baby with acute myeloid leukemia and spontaneous remission

Blueberry muffin baby is a rare neonatal skin disorder. Causes for the generalized hemorrhagic purpuric eruptions include congenital infections, hemolysis, and tumors. We report a 2.5-month-old female baby with a blueberry muffin appearance, respiratory distress, and decreased activity and appetite. Skin biopsy showed diffuse infiltrates of myeloperoxidase- and lysozyme-positive blast-like cells in dermis and superficial subcutis. Bone marrow study confirmed the diagnosis of acute monocytic leukemia with leukemia cutis. The skin nodules regressed spontaneously without chemotherapy over several days, and the peripheral blood cell counts normalized. This spontaneous remission lasted for 2 months. Spontaneous remission of infantile leukemia is rare, and its mechanism remains unknown. Although overt leukemia relapsed in some of these patients, a delay in chemotherapy spared these infants of the toxic effects of treatment.

1111 Measurement of Hepatic Tissular Rso2 Using Near Infrared Spectroscopy as a Witness of Hepatic Tumor Regression

Background and aims: Near InfraRed Spectroscopy (NIRS) is a tool for evaluation of local blood flow and oxygen consumption (VO2) using measurement of regional oxygen saturation (rSO2). Purpose: To describe the feasibility and accuracy of the measurement of hepatic rSO2 (lirSO2) in an infant with tumoral syndrome in acute leukemia. Methods: A 7 weeks old girl was admitted with asthenia, bleeding, respiratory distress and hepatomegaly. Hemogram showed 117000 leucoblasts/mm3, Hb=7.1g/100 ml, 24000 platelets/ mm3. Blood gaz analysis showed : pH=7.37, HCO3- =18 mmol/l, PaCO2=31 mmHg and lactatemia=888 mg/l. Sonography showed a heterogeneous hepatomegaly. Diagnosis of acute monocytic leukemia (AML-M5) was made. Chemotherapy was started (ELAM 02 protocol). Infant was monitored using cardiac monitoring, continuous measurement of oxygen saturation (SpO2) and invasive blood pressure. CerSO2 and lirSO2 were measured using NIRS. rSO2 values were recorded every 6 seconds, hemoglobin and central venous SO2 (SvO2) in vena cava superior every 6 hours. Results: rSO2 measurement began 10 hours after the first chemotherapy (H0). SpO2 value was 96.4±2.0%, cerSO2 was 75.8±3.9% SvO2 values were stable around 70%, suggesting that there was no variation in systemic oxygen transport (TO2) lirSO2 value at H0 was 24.7±7.6% and raised up to 74.0±2.5% at H12. Conclusions: NIRS provides a non-invasive assessment of lirSO2 in acute hemopathies. The decrease in lirSO2 could be the witness of tissular hypoxia induced by myeloproliferation. Our data show an increase in lirSO2 under chemotherapy. NIRS could be helpful to evaluate the decrease in VO2 and the improvement of TO2 during chemotherapy.

Neonatal acute myeloid leukemia in an infant whose mother was exposed to diethylstilboestrol in utero

We report on an acute myeloid leukemia in a neonate whose mother was exposed to diethylstilboestrol in utero. The newborn presented with leukemia cutis, hemorrhagic skin lesions, hyperleucocytosis and disseminated intravascular coagulation. A bone marrow examination confirmed the diagnosis of acute monocytic leukemia with a t(11;19) MLL-ELL fusion transcript. Chemotherapy was initiated but the child developed a bilateral pulmonary infection that led to fatal respiratory distress. This case shows acute myeloid leukemia and the third pediatric leukemia reported after maternal diethylstilboestrol exposure.

A complex 1;19;11 translocation involving the MLL gene in a patient with congenital acute monoblastic leukemia identified by molecular and cytogenetic techniques

Dear Editor, Translocations involving chromosomal band 11q23 are found in most of the infant acute lymphoblastic leukemia and in acute myeloblastic leukemia. The majority of these translocations lead to the rearrangement of the MLL gene and the formation of new chimeric genes [1]. We report here a case of congenital acute monoblastic leukemia and myeloid sarcoma associated with an apparent t(1;11)(p36; q23) which proved to be in fact a complex 1;19;11 translocation. This female child was born after a pregnancy of 33 weeks and 6 days complicated by gravidic toxemia and hydramnios. At birth, the baby was cyanosed and showed no reaction to stimuli. She had disseminated intravascular coagulation with petechiae and hematoma on the neck and the limbs. Cutaneous tumors were observed on the abdomen, the right arm and the left thigh. Her hematological data were as follows: hemoglobin 14 g/dl, white blood cells (WBC) 162×10/L with 0.5% neutrophils, 0.5% eosinophils, 9.5% lymphocytes, 8% monocytes and 80% monoblasts and promonocytes, and platelets 50×10/L. A diagnosis of acute monoblastic leukemia (FAB type M5) was made. The biopsy of one cutaneous tumor showed a massive derma infiltration by monoblasts; therefore, these skin tumors were considered to be myeloid sarcomas. Palliative care solely was applied. The child developed acute renal insufficiency and massive cerebral hemorrhage, of which she died 24 h after birth [2]. Cytogenetic analysis was performed on bone marrow cells with standard techniques. We observed a translocation which appeared to be balanced in R-banding between chromosomes 1 and 11; thus, the karyotype was written as 46,XX,t(1;11)(p36.2;q23). FISH analysis using the LSI MLL dual color probe (Abbott, Rungis, France) confirmed the disruption of the MLL gene. It showed the translocation of the 3′ region of MLL (red signal) to the derivative chromosome 1 while the 5′ region (green signal) remained on the der(11). We then used long-distance inverse PCR (LDI-PCR) to identify the MLL fusion partner involved in the chromosomal translocation of that particular patient [3]. Genomic DNA was isolated from methanol/acetic acid-fixed cells of leukemia patient that were stored at −20°C. DNA was extracted using the QIAamp DNA mini kit (Qiagen GmbH, Hilden, Germany) according to the manufacturer recommendations. After DNA digestion, resulting DNA fragments were re-ligated to form DNA circles prior to LDIPCR studies. LDI-PCR reactions were performed as Ann Hematol (2009) 88:795–797 DOI 10.1007/s00277-008-0656-8

Leukemia cutis resembling a flare-up of psoriasis

Leukemia cutis represents a skin infiltration by leukemic cells. Clinically it can mimic a wide variety of dermatoses. We describe the case of a 64-year-old man with psoriasis who presented with a 4-day history of erythematous, slightly scaly, asymptomatic plaques distributed on the trunk and upper-extremities, and associated asthenia, myalgias, and anorexia. A skin biopsy revealed a leukemic infiltrate. Studies of peripheral blood and bone marrow provided a diagnosis of acute monocytic leukemia. This case report shows the importance of the clinical suspicion for the diagnosis of leukemia.

Prenatal Presentation Supports the In Utero Development of Congenital Leukemia: A Case Report

Congenital leukemia is a rare disease developing within the first 4 to 6 weeks of life. We report a female infant born with facial mass and multiple subcutaneous nodules. The facial mass was discovered by ultrasound during a routine prenatal examination at the 36th week of gestation. Biopsies were consistent with the diagnosis of acute monoblastic leukemia (AML, FAB M5b). Cytogenetic studies showed 46 XX, t(11;19)(q23;p13.1), which is only found in acute monoblastic leukemia and involves the gene. The infant died at 12 days of age and autopsy revealed a large leukemic tumor burden in several body organs. The discovery of the facial mass prenatally and massive extramedullary leukemic burden support the notion of the in utero development of congenital leukemia.

Detection of a t(8;21)(q22;q22) in a Case of M5 Acute Monoblastic Leukemia

Although the translocation (8;21) is the single most common structural rearrangement reported in acute myeloblastic leukemia (AML), it is rarely seen in AML FAB type M5. We describe a case of a 51-year-old male with a diagnosis of acute monoblastic leukemia (AML M5b with hemophagocytic component) whose karyotype showed at (8;21)(q22;22). To our knowledge, this is the first report of this translocation in an AML M5b. The t(8;21) has been associated with a good prognosis, but our patient suffered a fast and fatal evolution.

Acute monoblastic leukemia with skin nodules in an adult

An 18-year-old man had a 3-week history of malaise, a 1-week history of a papular eruption, and increasingly severe multisystem neurologic symptoms. A diagnosis of acute monoblastic leukemia was made. Immunophenotypic characterization of peripheral blood, bone marrow, and cutaneous infiltrates revealed a predominant myelomonocytic phenotype with the coexpression of intercellular adhesion molecule type 1, IgE receptor, terminal deoxynucleotidyl transferase, and some T-cell markers. These findings may have important clinical and pathogenetic implications regarding the biologic and pathologic behavior of the myelomonocytic leukemic cells. They also explain in part the impressive presentation of the disease in the skin.

Acute monocytic leukemia with chloroacetate esterase positivity. FAB M4 or M5?

French-American-British criteria for the diagnosis of acute monocytic leukemia (M5) require that 80% of nonerythroid bone marrow cells consist of monoblasts, promonocytes, and/or monocytes. Monocytic differentiation is demonstrated by fluoride-sensitive nonspecific esterase positivity. Chloroacetate esterase positivity is accepted as a marker of granulocytic differentiation. Three cases fulfilling French-American-British criteria for M5 showed fluoride-sensitive nonspecific esterase positivity in up to 100% of nonerythroid marrow cells but also exhibited strong chloroacetate esterase positivity in 20% to 90% of the same population. Less than 5% of blasts stained for Sudan black B and peroxidase. These cases may be viewed as chloroacetic esterase-positive acute monocytic leukemia or as acute myelomonocytic leukemia. The authors favor the former because the cases were myeloperoxidase negative; however, these cases indicate that chloroacetate esterase may not be a specific marker for granulocytic differentiation.

Cutaneous Involvement as a Presenting Feature of Monocytic Leukemia: Morphological and Immunohistochemical Studies

The clinical and pathological findings in a patient with monocytic aleukemic leukemia presenting initially as multiple monoblastic tumors of the skin is described. The patient was a 35-year-old Japanese woman, who had first noticed multiple, asymptomatic, reddish-brown papules on her trunk. Asymptomatic enlargements of several lymph nodes were present in the bilateral cervical and axillary areas. There was no hepatosplenomegaly, sternal tenderness, bruising, or bleeding. The skin and lymph node biopsies were originally interpreted as malignant lymphoma. The diagnosis of acute monocytic leukemia was established when bone marrow involvement was detected. Immunohistochemical observation of the skin eruptions revealed the following: Positive staining with lysozyme was noted in almost half of the infiltrating atypical cells. Most of the infiltrating cells reacted positively with antisera to Leu-M5 and some of them reacted to Leu-M1. The helper T cell antibody, Leu-3a+3b, showed weak positive staining of most infiltrating cells. However, there were no reactions with antisera to Leu-6, Leu-7, Leu-14, CALLA, OKT 6, OKT 8, OKT 16, OKB 19, OKM 14, beta F1, or delta TCS1. OKM 5-positive keratinocytes were observed in some parts of the upper epidermis, although no OKM 5 expression could be detected on any tumor cells. Cytochemistry, immunohistochemistry, and electron microscopy can aid in the diagnosis of monocytic leukemia. This case illustrates the importance of using an expanded panel of monoclonal antisera in certain hematopoietic tumors.

Childhood Acute Megakaryoblastic Leukemia with Internalization of Hemic Cells

Two atypical cases of acute megakaryoblastic leukemia (AMKL) in infants diagnosed by immunophenotying are described. In both cases, the leukemic cells at diagnosis resembled monoblasts with reniform nuclei, fine reticular chromatin, and abundant grey-blue cytoplasm with pseudopods. In addition, these blasts frequently showed internalization of hemic cells. Therefore, the diagnosis of acute monocytic leukemia (AMOL) or malignant histiocytosis (MH) was initially suggested. However, alpha-naphthyl butyrate esterase stain was negative and immunologic studies determined megakaryocytic lineage of the blasts. Our observation in two consecutive cases of AMKL implies that there is a potential risk of misdiagnosing AMKL as AMOL or MH in infants. The incidence and significance of internalization of hemic cells by blast cells of AMKL in infancy are unknown and we cannot be certain whether these cases constitute a subgroup of AMKL in infancy.

A Case of Acute Monocytic Leukemia with Lysozyme-Positive Leukemic Monocytes and Normal Serum Lysozyme Levels

We report a case of acute monocytic leukemia with normal serum lysozyme but with immunoperoxidase positivity for lysozyme in the leukemic blasts. The diagnosis of acute monocytic leukemia was made on the basis of cellular morphology, immunocytochemistry and cytochemistry. Discrepancy between serum lysozyme and intracytoplasmic lysozyme has not previously been reported in the literature. Levels of serum lysozyme may be misleading in cases of acute monocytic leukemia (FAB classification M5).

Dermal monocytic sarcoma/monoblastic tumour: report of two cases of acute monocytic leukemia with initial dermal manifestations only

The clinical and pathological findings in 2 patients with acute monocytic leukemia (AMOL) presenting initially as multiple monoblastic tumours of the skin (monocytic sarcoma) were reviewed. The skin biopsies were originally interpreted as malignant lymphoma and the diagnosis of AMOL was established when overt bone marrow and/or peripheral blood involvement was detected. The time interval from initial skin biopsy to either blood or bone marrow involvement by AMOL was 2 and 18 mth. After diagnosis of extracutaneous dissemination, survival was less than 1 mth. Cytochemistry, immunohistochemistry and electron microscopy can aid in the diagnosis of a monocytic sarcoma. Generally, the most practical way to confirm the diagnosis, in everyday practice, on fixed paraffin-embedded tissues is the demonstration of alpha-1-antitrypsin (A1AT) and/or lysozyme by the immunoperoxidase technique.