An unusual cause of a right nasal mass in a 73-year-old male

We report a case of a 73-year-old male presenting with a right nasal mass on a background of two years of constitutional symptoms. We outline an approach to the evaluation of nasal mass biopsies, which in this case led to the unusual diagnosis of myeloid sarcoma. This is a relatively rare neoplasm, representing an extra-medullary deposit of acute myeloid leukaemia (AML). The differential diagnosis of myeloid sarcoma is discussed, along with the clinical, histological and immunohistochemical findings that permit differentiation of this entity from more common malignancies seen at this site including carcinoma, non-Hodgkin lymphoma and melanoma.     

Dysgonomonas capnocytophagoides bacteraemia in a neutropenic patient treated for acute myeloid leukaemia

Dysgonomonas capnocytophagoides, formerly known as CDC group DF-3, is an opportunistic pathogen associated with diarrhoea and very rarely bacteraemia. We report a case of D. capnocytophagoides found in blood cultures from a severely neutropenic patient treated for acute myeloid leukaemia. The isolate was found resistant to penicillin, cephalosporins, meropenem, aminoglycosides and ciprofloxacin, and susceptible to ampicillin, tetracycline, chloramphenicol, clindamycin and trimethoprim-sulphamethoxazole. It was identified using conventional phenotypic testing but remained unidentified by the automated identification system (Vitek-2) as this system did not contain DF-3 or D. capnocytophagoides in its database.     

Bone marrow biopsy changes in acute myeloid leukaemia I: observations before chemotherapy

Pretreatment bone marrow trephine biopsy sections (BMB) from 34 patients with acute myeloid leukaemia (AML) were studied in parallel with bone marrow aspiration smears and peripheral blood films. In four cases marrow aspiration was inadequate and in five cases it was unsatisfactory. In two other cases hypoplastic AML was diagnosed, the aspirate in one suggested hypercellularity and in another it was unsatisfactory. Trephine biopsy was superior to aspiration for the evaluation of fat and marrow cellularity, pattern and extent of blast cell infiltration, homogeneity of the leukaemic infiltrate, frequency of mitoses, residual haemopoietic activity and presence of inflammatory cells. Of the various features studied in the sections, the presence of an increased number of plasma cells and considerable myelodysplasia (MD) appeared to be unfavourable prognostic features. We conclude that trephine biopsies are essential for the diagnosis of hypoplastic AML and are most useful when marrow aspiration is either inadequate or unsatisfactory. They also provide additional information about the bone marrow changes in AML and suggest that some histological features may also have prognostic significance.     

Diagnostic approach to myelodysplastic syndromes and related neoplasms

Myelodysplastic syndromes (MDS) are clonal disorders of the bone marrow characterized by ineffective haematopoiesis and an intrinsic predisposition to evolve into acute myeloid leukaemia. Impaired haematopoiesis manifests clinically with worsening cytopenia(s) responsible of patients’ symptoms and morphologically with myelodysplasia and with the progressive accumulation of immature myeloid cells and blasts. Therefore, the diagnosis of MDS is always an integrated process which requires the combination of clinical and morphologic data. In recent years a larger body of knowledge has accumulated regarding the molecular events occurring in MDS, including chromosomal abnormalities and somatic gene mutations. So called “myeloid gene panels” and fluorescence in situ hybridization panels have joined conventional karyotyping in the diagnostic workup of MDS. None of these alterations is disease-specific; however, their identification supports the existence of a clonal disease, especially in cases with subtle dysplasia and/or mild cytopenia, and provides prognostic information for disease stratification and treatment.     

The value of immunohistochemistry for CD14, CD123, CD33, myeloperoxidase and CD68R in the diagnosis of acute and chronic myelomonocytic leukaemias

Rollins‐Raval M A & Roth C G
(2012) Histopathology  60, 933–942 The value of immunohistochemistry for CD14, CD123, CD33, myeloperoxidase and CD68R in the diagnosis of acute and chronic myelomonocytic leukaemias Aims: In the absence of adequate aspirate films and touch imprints, distinction of chronic myelomonocytic leukaemia (CMML) from acute myeloid leukaemia with monocytic differentiation (Mo‐AML) may be difficult solely on the basis of bone marrow biopsy morphological features. The aim of this study was to evaluate the diagnostic utility of a novel immunohistochemical panel for the diagnosis of acute and chronic myelomonocytic leukaemias in bone marrow biopsies. Methods and results: Immunohistochemical labelling for CD14, CD123, CD33, myeloperoxidase (MPO) and CD68R was assessed in 49 myeloid neoplasms with monocytic differentiation (24 CMMLs and 25 Mo‐AMLs) and compared with that of 15 non‐monocytic acute myeloid leukaemias (NM‐AMLs) and 17 non‐neoplastic controls. More than 20% CD14 immunohistochemistry (IHC)+ cells were seen only in Mo‐AMLs and CMMLs, although Mo‐AMLs showed wide variability and overlapped with other categories. More than 20% CD68R IHC+ cells had the highest sensitivity and specificity for Mo‐AML. Discrepant MPO–/CD33+ expression was specific for Mo‐AML but insensitive. A subset of blasts in Mo‐AMLs and NM‐AMLs were weakly CD123+. Conclusions: A significantly increased number of CD14+ cells raises the possibility of a myelomonocytic neoplasm but does not distinguish between CMML and Mo‐AML. Significantly increased numbers of CD68R IHC+ cells and a discrepant MPO–/CD33+ staining pattern are specific for Mo‐AML but are best utilized in a comprehensive panel.     

NPM1基因突变与急性髓细胞白血病

NPM1(nucleophosmin,又称B23, numatrin或N038)是一种主要定位于核仁，可在核仁与胞浆之间穿梭的核磷蛋白。第12外显子突变导致NPM1胞浆异位从而发生肿瘤转化。NPM1突变与正常核型的急性髓细胞白血病、成年女性、多系受累、CD34-、 FLT3-ITD、独特的临床表现及良好的预后有关。对于NPM1+/FLT3-ITD-患者，移植与否对预后无差别。NPM1突变导致白血病发生的机制尚不清楚。     

TERT rs2853669 as a predictor for overall survival in patients with acute myeloid leukaemia

Introductionthe aim of the study was to investigate the contribution of TERT rs2736100 and rs2853669 gene polymorphisms in defining the genetic predisposition to acute myeloid leukaemia (AML), their association with different prognostic markers, and their impact on survival, outcome, and the prognosis of affected patients. Also, we investigated the association of TERT SNPs in AML in the presence or absence of DNMT3A (R882), NPM1, and FLT3 mutations.Material and methodsA total of 509 participants were enrolled in our study, consisting of 146 AML patients and 363 healthy participants, with no history of malignancy. TERT rs2736100 and rs2853669 polymorphisms were genotyped by using TaqMan SNP genotyping assay FLT3 (ITD, D835), DNMT3A (R882), and NPM1 c.863_864insTCTG (type A) mutations were analised in each AML case.ResultsTERT rs2736100 and rs2853669 were not associated with AML risk in the codominant, dominant, recessive, or allelic models. Multivariate Cox regression showed that TERT rs2853669 was a significant predictor for overall survival in AML patients. After adjusting for age, gender, cytogenetic risk group, ECOG status, FLT3, DNMT3A, NPM1 mutation, AML subtype, and treatment, the estimated adjusted hazard ratio (HR adjusted = 1.54, 95% CI: 1.01–2.35) showed that the TERT rs2853669 variant genotype had a negative influence on survival time.ConclusionsTERT rs2853669 and rs2736100 polymorphisms were not risk factors for developing AML in the Romanian population, but the TERT rs2853669 variant genotype had a negative effect on AML patients’ overall survival in the presence of other known prognostic factors.     

Prediction of Two- and Three-Amino-Acid Sequences of Acute Myeloid Leukaemia 1 Protein from its Amino Acid Composition

The repeated amino acid sequences in human acute myeloid leukaemia 1 protein (AML-1) are indispensable for its function and such repetitions cannot be simply attributed to chance. In order to fully explore the functional units in human AML-1, it may be necessary to analyse all the amino acid pairs, triplets, etc. along human AML-1 from one terminal to the next, to count their frequencies and calculate their probabilities. The amino-acid sequence of human AML-1 was counted according to two-, three- and four-amino acid sequences. The counted frequency and probability were compared with the predicted frequency and probability. The amino acid sequences, which appear in human AML-1 and can be predicted from its amino acid composition according to a purely random mechanism, are not deliberately evolved or conserved. By contrast, the amino acid sequences, which appear in human AML-1 but cannot be predicted from its amino acid composition according to a purely random mechanism, are deliberately evolved and conserved. Accordingly 77 (17.035%) and 41 (9.071%) of 452 two-amino acid sequences can be predicted by the frequency and probability according to a purely random mechanism. Some kinds of amino acid sequences, which are absent from human AML-1 but can be predicted from its amino acid composition according to a purely random mechanism, should not be excluded as possibilities in human AML-1. By contrast, some kinds of amino acid sequences, which are absent from human AML-1 and cannot be predicted from its amino acid composition according to a purely random mechanism, can be appropriately excluded from human AML-1. Accordingly 115 (63.187%) and 52 (28.571%) of 182 kinds of absent two-amino-acid sequences can be predicted by the frequency and probability according to a purely random mechanism and 7567 (99.881%) of 7576 kinds of absent three-amino-acid sequences can be predicted by the frequency according to a purely random mechanism.     

Evaluation of neoplastic human mast cells by tryptase-immunoelectron microscopy

AIMS: To analyse and characterize the ultrastructural morphology of normal tissue mast cells (MC) and neoplastic bone marrow MC. METHODS: We have examined the ultrastructure and cytomorphological features of MC derived from cord blood cells, neoplastic bone marrow MC in patients with systemic mastocytosis (SM, n = 4), myelomastocytic leukaemia (MML, n = 2), mast cell leukaemia (MCL, n = 2) and tryptase-positive acute myeloid leukaemia (AML, n = 4). RESULTS: Based on their ultrastructure and morphology, four distinct cell types could be delineated: (i) mature well-granulated tissue MC exhibiting a round central nucleus; (ii) atypical MC type I with oval nuclei, hypogranulated cytoplasm, and prominent surface projections; (iii) immature atypical MC with bi- or polylobed nuclei (atypical MC type II = promastocytes); and (iv) metachromatic blasts. Type I atypical MC were detected in a patient with indolent SM, whereas type II MC and metachromatic blasts were primarily found in MML, MCL and tryptase-positive AML. In all samples examined, the identity of MC could be reconfirmed by immunoelectron microscopy, irrespective of the stage of cell maturation or the disease variant, all types of MC contained tryptase in their cytoplasmic granules. CONCLUSION: Immunoelectron microscopy may be a helpful approach in confirming the identity of neoplastic MC in myeloid neoplasms.     

Achieving pregnancy against the odds: successful implantation of frozen-thawed embryos generated by ICSI using spermatozoa banked prior to chemo/radiotherapy for Hodgkin's disease and acute leukaemia

Two cases are reported of successful pregnancies following long-term semen banking prior to chemotherapy and radiotherapy for malignancy. With the first case, the patient banked semen at the age of 20 years prior to chemotherapy for Hodgkin's disease; 11 years later the thawed semen was used for IVF with intracytoplasmic sperm injection (ICSI), resulting in twins being born following the transfer of frozen-thawed embryos. In the second case, the patient banked semen at the age of 17 years prior to chemotherapy and radiotherapy for acute myeloid leukaemia; 8 years later it was used for ICSI, resulting in triplets being born following the transfer of frozen-thawed embryos. These cases support long-term semen banking for men whose future fertility may be compromised by suppression of spermatogenesis secondary to administration of chemo/radiotherapy treatment. The advent of successful ICSI combined with embryo cryopreservation has increased the chance of thawed cryopreserved semen achieving fertilization. Banking of a single ejaculate prior to commencement of chemotherapy/radiotherapy treatment may preserve potential fertility without compromising the oncology treatment.     

Deletion of chromosome 3 and a 3;20 reciprocal translocation demonstrated by chromosome painting

The combined use of high resolution banding and chromosome painting techniques allowed us to identify a reciprocal translocation involving chromosomes 3 and 20 and simultaneous interstitial deletion of chromosome 3 in a patient with several minor anomalies of the face and hands. His karyotype is described as 46,XY,t(3;20) (p14.2;p12.2),del(3)(p11-p14.1). © 1995 Wiley-Liss, Inc.     

Differences in nuclear RNA labelling patterns of BURKITT lymphoma,leukaemic lymphosarcoma and various human leukaemias

Summary Nuclear RNA was isolated from citric acid nuclei derived from AML, CML, CLL, leukaemic lymphosarcoma and BURKITT lymphoma cells after 6 hours incubation with³²P-orthophosphate in a phosphate-free medium. In fractionations on sucrose density gradients, marked differences were found in the distribution of the³²P-radioactivity mainly in the 45S fraction containing the ribosomal precursor RNA. The lowest specific activities of nuclear 45S RNA were found in CML; very high labelling accurred in cells of AML, leukaemic lymphosarcoma and BURKITT lymphoma. In CLL cells which are known for lack in DNA synthesis, pre-ribosomal 45S and 35S RNA were labelled to a remarkable extent. Studies are in progress in order to define possible differences in nuclear RNA structures between lymphocytic and granulocytic cell lines.Mit Unterstützung durch das Landesamt für Forschung, Nordrhein-Westfalen.     

Overcoming the problem of pseudohypoxemia in myeloproliferative disorders: Another trick in the bag

Pseudohypoxaemia or spurious hypoxaemia is a recurrent problem faced on arterial blood gas analysis in patients with hyperleucocytosis leading to management dilemmas and unnecessary respiratory interventions. Various methods have been suggested to reduce the magnitude of this problem. We report a case of pseudohypoxaemia due to blast crisis in a patient of chronic myeloid leukaemia where arterial blood gas analysed from precooled syringe helped us resolve the problem and hastened our weaning from oxygen therapy.     

Clinicopathological features of acute megakaryoblastic leukaemia: Relationship between fibrosis and platelet‐derived growth factor

Acute megakaryoblastic leukaemia (AMGL) is an uncommon disease with poor prognosis. Histopathologically, AMGL cases show variable degree of fibrosis and the presence of uniform blasts or mature dysplastic megakaryocytes. Here we examined 18 cases of AMGL, including idiopathic (n = 9) and secondary (n = 9) cases. Fourteen cases were males and four were females, ranging in age from 14 to 87 years (median, 58). All cases had anaemia, but leukocyte and platelet counts varied. Blast cells were detected in the peripheral blood of 14 cases. Fourteen of 16 cases showed chromosomal abnormalities. The median survival was 6 months (range, 1–48 months). Survival rates did not correlate with the severity of fibrosis, proportion of blast cells and cause of AMGL. Nine of the 11 cases examined immunohistochemically were positive for platelet‐derived growth factor (PDGF)(‐BB), especially megakaryoblasts and a few fibroblasts. The PDGF‐positive cases showed various degrees of fibrosis, while the negative cases showed no evidence of fibrosis. Our results confirmed the poor prognosis of patients with AMGL, irrespective of the degrees of fibrosis, and demonstrated that PDGF could play an important role in the pathogenesis of marrow fibrosis.