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Clonal hematopoiesis (CH) denotes somatic mutations in genes related to myeloid neoplasms present at any variant allele frequency (VAF). Clonal hematopoiesis is associated with increasing age and with a factor 6 increase in the risk of developing therapy-related myeloid neoplasms (tMNs) following autologous stem cell transplantation (ASCT). However, the impact of specific mutations on progression from CH to tMN has yet to be unraveled, and it remains unclear whether mutations directly impact or even drive the development of tMN. We performed deep sequencing in longitudinal samples from a cohort of 12 patients with either multiple myeloma or lymphoma who developed tMN following ASCT. Nine patients had one or more mutations that could be tracked longitudinally. Seven patients had clonal expansion from time of ASCT to diagnosis of tMN. Of these, six patients had CH at VAF < 2% at baseline. The median VAF of non-DNMT3A clones increased from 1% (IQR 0.7%-10.0%) at time of ASCT to 37% (IQR 17%-47%) at tMN diagnosis (P = 0.002), while DNMT3A clones showed quiescent trajectories (P = 0.625). Our data provide evidence to support the hypothesis that the development of tMN following ASCT is likely instigated by CH present at VAFs as low as 0.5%, detectable years before tMN onset., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: The hallmark of myelodysplastic syndrome (MDS) remains dysplasia in the bone marrow (BM). However, diagnosing MDS may be challenging and subject to inter-observer variability. Thus, there is an unmet need for novel objective, standardized and reproducible methods for evaluating dysplasia. Imaging flow cytometry (IFC) offers combined analyses of phenotypic and image-based morphometric parameters, for example, cell size and nuclearity. Hence, we hypothesized IFC to be a useful tool in MDS diagnostics., Methods: Using a different-from-normal approach, we investigated dyserythropoiesis by quantifying morphometric features in a median of 5953 erythroblasts (range: 489-68,503) from 14 MDS patients, 11 healthy donors, 6 non-MDS controls with increased erythropoiesis, and 6 patients with cytopenia., Results: First, we morphometrically confirmed normal erythroid maturation, as immunophenotypically defined erythroid precursors could be sequenced by significantly decreasing cell-, nuclear- and cytoplasm area. In MDS samples, we demonstrated cell size enlargement and increased fractions of macronormoblasts in late-stage erythroblasts (both p < .0001). Interestingly, cytopenic controls with high-risk mutational patterns displayed highly aberrant cell size morphometrics. Furthermore, assisted by machine learning algorithms, we reliably identified and enumerated true binucleated erythroblasts at a significantly higher frequency in two out of three erythroblast maturation stages in MDS patients compared to normal BM (both p = .0001)., Conclusion: We demonstrate proof-of-concept results of the applicability of automated IFC-based techniques to study and quantify morphometric changes in dyserythropoietic BM cells. We propose that IFC holds great promise as a powerful and objective tool in the complex setting of MDS diagnostics with the potential for minimizing inter-observer variability., (© 2020 International Clinical Cytometry Society.)

Therapy-related myeloid neoplasms (tMN) develop after exposure to cytotoxic and radiation therapy, and due to their adverse prognosis, it is of paramount interest to identify patients at high risk. The presence of clonal hematopoiesis has been shown to increase the risk of developing tMN. The value of analyzing hematopoietic stem cells harvested at leukapheresis before autologous stem cell transplantation (ASCT) with next-generation sequencing and immunophenotyping represents potentially informative parameters that have yet to be discovered. We performed a nested case-control study to elucidate the association between clonal hematopoiesis, mobilization potential, and aberrant immunophenotype in leukapheresis products with the development of tMN after ASCT. A total of 36 patients with nonmyeloid disease who were diagnosed with tMN after treatment with ASCT were included as case subjects. Case subjects were identified from a cohort of 1130 patients treated with ASCT and matched with 36 control subjects who did not develop tMN after ASCT. Case subjects were significantly poorer mobilizers of CD34+ cells at leukapheresis (P = .016), indicating that these patients possess inferior bone marrow function. Both clonal hematopoiesis (odds ratio, 5.9; 95% confidence interval, 1.8-19.1; P = .003) and aberrant expression of CD7 (odds ratio, 6.6; 95% confidence interval, 1.6-26.2; P = .004) at the time of ASCT were associated with an increased risk of developing tMN after ASCT. In conclusion, clonal hematopoiesis, present at low variant allele frequencies, and aberrant CD7 expression on stem cells in leukapheresis products from patients with nonmyeloid hematologic cancer hold potential for the early identification of patients at high risk of developing tMN after ASCT., (© 2020 by The American Society of Hematology.)

An association between hepatitis and aplastic anemia (AA) is known as hepatitis-associated AA, and is characterized by an acute attack of hepatitis followed by the development of AA. We report 2 clinical cases of acute seronegative hepatitis in which pancytopenia with mild dysplasia developed after 3 months; however, neither of our cases fulfilled the histological criteria of AA, but rather myelodysplastic syndrome. This novel association bears considerable resemblance to hepatitis-associated AA, and raises the question of whether hepatitis-associated dysmyelopoiesis should be included in the spectrum of hypocellular myelodysplastic syndrome.

Evidence of distinct disease propagating stem cells in myelodysplastic syndrome (MDS) has emerged in recent years. However, immunophenotypic characterization of these cancer stem cells remains sparse. In acute myeloid leukaemia (AML), we have previously described aberrant expression of the C-type lectin domain family 12, member A (CLEC12A) as a stable and reliable marker of leukaemia blasts and as a tool for assessing minimal residual disease. Furthermore, CLEC12A has been proposed as a promising marker of leukaemic stem cells in AML. The role of CLEC12A in MDS, however, remains to be elucidated. In this study, we found CLEC12A aberrantly expressed on the CD34 + CD38 - cell compartment in 71% (22/31) of MDS patients, distributed across all Revised International Prognostic Scoring System risk groups. We showed that the CD34 + CD38 - CLEC12A + cells were indeed malignant and possessed functional stem cell properties in the long-term colony-initiating cell assay. As opposed to reported findings in AML, we showed that cancer stem cells from MDS samples derived from both CLEC12A positive and negative CD34 + CD38 - subpopulations. Due to the absence of CLEC12A on normal haematopoietic stem cells, CLEC12A stem cell immunophenotyping may contribute to diagnosing and monitoring MDS patients and could furthermore add knowledge about disease propagating cells in MDS., (© 2016 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.)

Refractory cytopenia of childhood is the most common subtype of myelodysplastic syndrome in children. In this study, we compared the outcome of immunosuppressive therapy using horse antithymocyte globulin (n=46) with that using rabbit antithymocyte globulin (n=49) in 95 patients with refractory cytopenia of childhood and hypocellular bone marrow. The response rate at 6 months was 74% for horse antithymocyte globulin and 53% for rabbit antithymocyte globulin (P=0.04). The inferior response in the rabbit antithymocyte globulin group resulted in lower 4-year transplantation-free (69% versus 46%; P=0.003) and failure-free (58% versus 48%; P=0.04) survival rates in this group compared with those in the horse antithymocyte globulin group. However, because of successful second-line hematopoietic stem cell transplantation, overall survival was comparable between groups (91% versus 85%; P=ns). The cumulative incidence of relapse (15% versus 9%; P=ns) and clonal evolution (12% versus 4%; P=ns) at 4 years was comparable between groups. Our results suggest that the outcome of immunosuppressive therapy with rabbit antithymocyte globulin is inferior to that of horse antithymocyte globulin. Although immunosuppressive therapy is an effective therapy in selected patients with refractory cytopenia of childhood, the long-term risk of relapse or clonal evolution remains. (ClinicalTrial.gov identifiers: NCT00662090).

During a 15-year period, 161 adult patients were diagnosed with secondary acute myeloid leukemia (s-AML) in the region of Southern Denmark. In 73 patients, the AML diagnosis was preceded by myelodysplastic syndrome (MDS-AML), in 31 patients by an antecedent hematologic disease, and in 57 patients by treatment with chemotherapy and/or irradiation (t-AML). Cytogenetic analysis was carried out in 93%, of which 61% had clonal chromosome aberrations. MDS-AML correlated to a normal karyotype (P < 0.001). t-AML correlated to abnormal clones with numerical and structural aberrations (P = 0.03), five or more unrelated aberrations (P = 0.03), marker chromosomes (P = 0.006), abnormal mitoses only (P = 0.01), female sex (P < 0.001), and -7 (P = 0.006). Centromeric breakage correlated to a complex karyotype (P = 0.01). The frequencies of aberrations in s-AML patients were compared with an age-matched group of de novo AML patients diagnosed in the same area and period. In this comparison, s-AML only correlated to -7 (P = 0.02). In 42 patients, we found that MDS patients with an abnormal karyotype were more likely to show cytogenetic evolution during progression to AML than MDS patients with a normal karyotype (P = 0.01). We conclude that population-based cytogenetic studies of adult s-AML and age- and sex-matched de novo AML show comparable distributions of chromosome abnormalities., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Background: Several laboratories have shown that cells with a memory B-cell phenotype can have the same clonotype as multiple myeloma tumor cells., Design and Methods: The aim of this study was to determine whether some memory B cells have the same genetic alterations as their corresponding multiple myeloma malignant plasma cells. The methodology included sorting multiple myeloma or memory B cells into RNA stabilizing medium for generation of subset-specific polymerase chain reaction complementary DNA libraries from one or 100 cells., Results: Cells with the phenotype of tumor plasma cells (CD38(++)CD19(-)CD45(-/+)CD56(-/+/++)) or memory B cells (CD38(-)/CD19(+)/CD27(+)) were isolated by flow activated cell sorting. In samples from all four patients with multiple myeloma and from two of the three with monoclonal gammopathy of undetermined significance, we identified memory B cells expressing multiple myeloma-specific oncogenes (FGFR3; IGH-MMSET; CCND1 high) dysregulated by an IGH translocation in the respective tumor plasma cells. By contrast, in seven patients with multiple myeloma, each of whom had tumor plasma cells with a K-RAS61 mutation, a total of 32,400 memory B cells were analyzed using a sensitive allele-specific, competitive blocker polymerase chain reaction assay, but no K-RAS mutations were identified., Conclusions: The increased expression of a specific "early" oncogene of multiple myeloma (monoclonal gammopathy of undetermined significance) in some memory B cells suggests that dysregulation of the oncogene occurs in a precursor B-cell that can generate memory B cells and transformed plasma cells. However, if memory B cells lack "late" oncogene (K-RAS) mutations but express the "early" oncogene, they cannot be involved in maintaining the multiple myeloma tumor, but presumably represent a clonotypic remnant that is only partially transformed.

Osteolytic bone disease (OBD) in multiple myeloma (MM) is caused by interactions between MM cells and the bone marrow microenvironment and is characterized by increased osteoclastic bone resorption and decreased osteoblastic bone formation. Recently, the role of osteoblast inhibition has come into focus, especially the possible role of overexpression of DKK1, an inhibitor of the Wnt signalling pathway. Further, CKS2, PSME2 and DHFR have also been reported as candidate genes for OBD. We studied the gene expression by quantitative reverse transcription polymerase chain reaction of TNFSF11 (RANKL), TNFSF11A (RANK), TNFRSF11B (OPG), CCL3 (MIP1A), CCL4 (MIP1B), PTHR1 (PTHrp), DKK1, CKS2, PSME2 and DHFR in purified, immunophenotypic FACS-sorted plasma cells from 171 newly diagnosed MM patients, 20 patients with monoclonal gammopathy of undetermined significance and 12 controls. The gene expressions of the analysed genes were correlated with radiographically assessed OBD. Only overexpression of DKK1 was correlated to the degree of OBD. Myeloma cells did not express TNFSF11A, TNFSF11, or TNFRSF11B, and very rarely expressed CCL3 and PTHR11. CCL4, CKS2, PSME2 and DHFR were variably expressed, but the expression of these genes showed no correlation with OBD. In contrast, loss of PSME2 expression in MM plasma cells was significantly correlated with OBD.

Interphase fluorescence in-situ hybridization (i-FISH) was used to investigate 192 patients with multiple myeloma (MM; n = 182) and benign monoclonal gammopathy of undetermined significance (MGUS; n = 10). Of the 182 MM cases, 132 were investigated without and 50 with positive plasma cell identification (PC-ID+); 134 were investigated at diagnosis, 32 at time of progression, 7 at time of relapse, and 9 were investigated with partial remission or no response. The FISH analysis detected 11q23 (n = 61), 13q13 approximately q14 (n = 181), 14q32 (n = 121), 17p13.1 (n = 181), t(4;14) (n = 76), and t(11;14) (n = 73). Of the 132 patients investigated without PC-ID+, 61 (46%) showed chromosomal abnormalities, compared with 45 of 49 of evaluable cases (92%) with PC-ID+. The increase in abnormal cases identified was due mainly to the detection of more cases with 13q-, 17p-, and der(14)(q32). G-banding cytogenetics was performed in 72 patients; abnormalities were revealed in 19 cases (26%). Concordance between G-banding and i-FISH for one or more aberrations was found in 14 patients. Translocation (11;14) was detected by both methods in four of five cases. In four out of seven cases with either near-tetraploidy/triploidy or hypoploidy in the G-banded karyotypes, the modal number in the G-banded karyotypes could not be elucidated with certainty with i-FISH. Three of the 10 MGUS patients showed abnormalities. In conclusion, PC-ID+ is important for the detection of structural aberrations and disclosing translocations involving 14q32. Of these, translocations t(4;14) constituted 9% and t(11;14), 20%. Finally, based on the small number of cytogenetically abnormal cases, it is recommended to include cytogenetics (and, for example, the DNA index) in the prognostic armamentarium.

Chromosomal aberrations in polycythemia vera (PV) are heterogenous and nonrandom. A prognostic predictive value of these aberrations has not been established. The V617F mutation in the JAK2 gene on chromosome 9p24.1 was identified recently in peripheral blood leukocytes in the majority of patients with PV and in approximately half of patients with essential thrombocythemia and idiopathic myelofibrosis. Within the JAK2 V617F-positive PV patients, however, clinical presentation and degree of myeloproliferation varies to a great extent. Here we report four cases of chronic myeloproliferative disorders [two with PV, one with PV in transformation to idiopathic myelofibrosis (IMF) and one IMF patient], with the distinct karyotypic abberations der(18) t(9;18) (p13;p11) and der(9;18)(p10;q10). Two patients had hyperproliferative PV and two had "transitional PV" and IMF, respectively. All four patients harbored the JAK2 V617F mutation. Our data, together with previously published data, clearly indicate an association of these chromosomal abnormalities with a highly proliferative PV phenotype with a propensity to transform into postpolycythemic myelofibrosis. Cytogenetic analysis seems to identify a subgroup of patients with a distinct prognostic profile, and should be performed in conjunction with a JAK2 mutation analysis in patients suspected of a chronic myeloproliferative disease.

The Philadelphia-negative chronic myeloproliferative disorders feature autonomous myeloid hyperproliferation and hypersensitivity to a number of growth factors, which most recently have been shown to be explained by a guanine-to-thymidine mutation in the Janus tyrosine kinase (JAK2) gene, implicating that phenylalanine is substituted with valine in position 617 (V617F mutation). JAK2 is of particular importance to haematopoiesis, since JAK2 proteins are activated mainly by the haematopoietic growth factors. The JAK2 mutation is present in most patients with polycythaemia vera and about 50% of patients with essential thrombocytosis and idiopathic myelofibrosis. The identification of the JAK2 mutation is a major molecular breakthrough in the understanding of the pathobiology of these disorders, and it is a new molecular marker to be used in the future classification of the diseases as well as a simple and rapid diagnostic test. The mutated JAK2 tyrosine kinase is an obvious potential target for a small-molecule inhibitor of tyrosine kinase activity.

PRV-1 is a new molecular marker within the Ph-negative chronic myeloproliferative disorders. PRV-1 is a useful, highly sensitive and specific marker in the differentiation between polycythaemia vera (PV) and secondary erythrocytosis (ET), and seems to identify those PV patients presenting in the early phase of the disease with dominating thrombocytosis and thus a clinical phenotype of ET. These PRV-1 positive ET patients can be regarded as having "masked" PV or, more accurately, as having early PV. Moreover, PRV-1 positivity may be associated with a particular risk of thromboembolic complications. The biological role of PRV-1 and the significance of alterations in PRV-1 gene expression levels during treatment remain to be clarified.

We investigated 150 acute myeloid leukemia (AML) patients and 48 acute lymphoblastic leukemia (ALL) patients by multiplex RT-PCR to 7evaluate the adjuvant diagnostic effect, vis-à-vis G-banding and spectral karyotyping (SKY), and the potentials of this method for providing means for monitoring residual disease by real-time quantitative RT-PCR. An abnormal G-banded karyotype was found in 57% of AML and 68% of ALL cases. Ninety-six patients were investigated by SKY in parallel which extended or confirmed the G-banding finding in 94/96 cases. In patients with an abnormal G-banded karyotype, classification of chromosomes involved in structural aberrations by SKY was possible in 98% of the cases and SKY extended the G-banded karyotype in 34% of cases. In 32 cases, an mRNA hybrid was detected by PCR. These cases constitute 16% of the cases investigated at diagnosis (AML: 11% and ALL: 31%). In 13 of these cases, we detected an mRNA hybrid the equivalent of which was not found by G-banding or SKY (AML: 4% and ALL: 13%). By including multiplex RT-PCR, we were able to detect abnormalities in 62% of the investigated patients as opposed to 59% by G-banding. Genetic techniques complement each other and selection of relevant and targeted primer kits for the multiplex RT-PCR assay is recommended.

Lipoblastomatous tumours are rare, and they occur primarily in children younger than 3 years of age. They are benign and may be divided in lipoblastomas and lipoblastomatosis. A case with cervical lipoblastoma causing respiratory difficulty is reported, and a clinical characterisation of patients with lipoblastomatous tumours in the neck is presented. A 6-year-old boy with complains of stridorous respiration and significant reduction in physical capacity was referred to the ENT Department, Odense University Hospital, Denmark. He was treated with total surgical resection of a soft and slowly growing tumour in the left side of the neck, extending from the base of the skull to the upper part of the mediastinum. The histological examination showed a lipoblastoma. After surgery all symptoms disappeared, and the patient was without any operative sequelae. Including the actual case, a review of English literature resulted in the identification of 37 patients with cervical lipoblastoma or lipoblastomatosis. However, in most cases the information was sparse, and only 13 patients were eligible for an analysis of basic clinical and demographic data. The median age was 25 months (range: 7-75 months), and the median tumour size 9 cm (range: 3-18 cm). No difference in sex distribution was found. Lipoblastomas (85%) seemed more frequent than lipoblastomatosis (15%). Stridorous respiration was present in 31%. It is concluded that a considerable part of lipoblastomatous tumours in the neck are combined with respiratory difficulties (31%), and that complete but gentle surgical treatment in most cases will restore normal physiological conditions.

During a 10-year period (1992-2001) in the region of Southern Denmark, 337 patients aged 15 years or older (range 16-93 years, median 67 years) were diagnosed with acute myeloid leukaemia (AML). Cytogenetic analysis was carried out in 90%, of whom 53% had clonal chromosome aberrations. Some 24% and 31% had only numerical or structural abnormalities respectively. The remaining patients showed both types of abnormalities. Ploidy levels in decreasing order were: pseudodiploidy, 41%; hyperdiploidy, 32%; and hypodiploidy, 27%. Pseudodiploidy characterizes type M3 (70%) and hypodiploidy M6 (56%). Recurrent cytogenetic abnormalities--t(8;21), t(15;17) and inv(16)--were found in 3.3%, 3.3% and 2.0% of all patients respectively. Prognostically intermediate and adverse aberrations were found in 39% and 44%, respectively, of those with an abnormal karyotype. Rare recurrent aberrations were found in two patients in this material. A previously described non-recurrent abnormality was found to be recurrent in one patient [der(20)t(11;20)(q13.2;p13)]. New, previously undescribed abnormalities were found in 41 patients. Statistically significant correlations were found between t(15;17) and young age (P < 0.001), inv(16) and young age (P < 0.006), -17 and M6 (P = 0.007), and M6 and complex karyotype with five or more unrelated aberrations (P = 0.004). We conclude that this truly population-based cytogenetic study of adult AML showed distributions of chromosome abnormalities that differ from those described so far.

The development of human cytogenetics has gained momentum during the past 20 years and many chromosome aberrations have been described to be specifically associated with more than 60 constitutional syndromes and more than 27,000 acquired neoplastic diseases. Chromosome analysis has in later years been further refined by the application of fluorescent in situ hybridisation technologies which enables the detection of genetic rearrangements, depending on the method employed down to single gene levels. Chromosome analysis is not only important in the diagnostic situation, but even more so in the prognostication of a wide range of diseases and especially with regard to malignant diseases in the follow-up to monitor treatment response. In addition, cytogenetics play an important role for unravelling the biology of neoplastic disease and the addition of relevant fluorescent in situ hybridisation and chip technologies will contribute with important information on pathogenetic mechanisms of both constitutional and acquired disease states.

The aim of the present study was to analyse the distribution of cytogenetic aberrations in adult ALL in a population based material and compare the results with literature data. Forty-one patients were diagnosed during a 12-year period. The age varied between 14 and 82 (mean 37, median 32). Thirty-two patients were cytogenetically investigated and in all cases analysable metaphases were obtained (range 10-29, mean 24, median 25, success rate: 100%). Nine (28%) patients had a T-phenotype and 23 (72%) had a pre-B phenotype. High hyperdiploidy was found in four patients (13%). Hypodiploidy was found in 5 patients (16%), 10 (31%) had a pseudodiploid chromosome mode and four (13%) showed low hyperdiploidy (chromosome mode 47-51). Chromosomes 10 and 18 were most frequently involved in numerical aberrations. Structural aberrations most frequently involved chromosomes 6, 9 and 22. t(9;22) was seen in six cases (19%), del(6q) in five cases (16%) and der(9p) in five cases (16%). High hyperdiploid clones, which are associated with a favorable prognosis, were found with the same frequency as in other studies. The frequency of t(9;22) was 19% in our study, others have found frequencies between 11% and 30%. Compared to previously published studies our patients with t(9;22) were younger. Furthermore, those with del(6q) were older, showing a median age equivalent to the patient group as a whole. The differences between our data and previously published studies may be explained by population-based derived data and especially by an optimal technique in obtaining metaphases.

We have, during a 12-month period, evaluated the adjuvant effect of combining G-band karyotyping and multi-color spectral karyotyping (SKY) in acute leukemia patients. Forty-four cases were evaluated; fewer cases than those routinely analyzed by G-band cytogenetics had mitoses left for SKY analysis. Of the 44 patients, 35 were acute myeloid leukemia (AML) and 9 acute lymphatic leukemia (ALL) cases. Twenty-seven of 35 AML and 7 of 9 ALL patients had an abnormal G-band karyotype. Thirteen of these 34 abnormal cases had a simple clonal chromosome aberration, and the remaining 21 cases had a complex karyotype. The SKY confirmed the simple karyotype in 11 and in 7 with a complex karyotype. In 13 of the cases with a complex karyotype, ambiguous structural aberrations were classified, in 6 of these, SKY disclosed cryptic translocations. Thus, SKY either extended or confirmed G-band karyotypes in 31 of 34 analyzed abnormal cases. Cases where SKY did not reveal the abnormal clone showed only few abnormal mitoses by G-banding (2/23, 2/25, and 4/27). Additional or confirmatory information was therefore obtained in 91% of analyzed cases, and SKY proved to be a valuable additional tool for hematologic cytogenetics.

A three-year-old boy was diagnosed with acute lymphoblastic leukemia. Two years later, while on maintenance chemotherapy, the patient was readmitted due to thrombocytopenia. The thrombocytopenia was caused by parvovirus B19 infection as evidenced by the finding of specific DNA in serum and bone marrow samples. Previous reports have highlighted the role of parvovirus B19 as a haematological pitfall and the present case shows that this virus has the potential to mimic a leukemic relapse.

Cytogenetic investigation in renal cell tumours may supplement morphological and immunohistological investigation. Cytogenetic aberrations may be an adjuvant in several situations: 1. For distinction between renal cell adenoma (RCA) and renal cell carcinoma (RCC). 2. For identification of specific genetic diseases with an increased incidence of RCC. 3. As support for a diagnosis of Wilms Tumour (WT) in children and for identification of genetic diseases with a higher incidence of WT. 4. As a possible aid in the distinction of RCA and RCC from rare kidney tumours.

During a 6-year period, 31 patients with Hodgkin disease (HD) were analyzed for chromosome aberrations on lymphoid tissue. We obtained metaphases in 87% (27/31). The number of cells analyzed per case ranged from 17 to 31 (median 25), and the number of abnormal mitoses was between 1 and 17 (median 6). Chromosome aberrations were found in 59% (16/27). Numerical aberrations involved all chromosomes. The most frequently gained chromosomes were numbers 2 and 9, and the most frequently lost were numbers 10, 16, 21, 22, and X. Chromosomes most frequently involved in structural aberrations were numbers 1 and 6. The most frequent subgroups were nodular sclerosis (NS) (n = 16) and mixed cellularity (MC) (n = 10). Six NS patients and 8 patients with MC showed an abnormal clone. For the NS patients with an abnormal karyotype, 4 of 6 had a gain of chromosome 2, and all had structural aberrations of chromosome 1. Of the 6 MC patients, where a partial analysis was possible, 4 had a gain of chromosome 9, 2 had structural aberrations involving chromosome 6 and 2 of chromosome 14. In 1 case a translocation normally associated with non-Hodgkin lymphoma (NHL) was found (t[11;14]), whereas other translocations characteristic of NHL, such as t(8;14), t(14;18), and t(2;5) were not observed. A review of the literature on cytogenetic investigations in HD performed on lymphoid tissue showed that the most frequently gained or lost chromosomes were 1, 2, 5, 9, and 12 for NS and 2, 5, and 9 for MC. The most frequently affected chromosomes in structural aberrations were 1 and 6 for NS, and 1, 7, and 14 for MC. Involvement of chromosome 1, 6, and 14 in structural aberrations is characteristic of lymphoid neoplasms, as are the most frequently involved bands (1p36, 6q21-q26, 14q11, and 14q32) further supporting a B- or T-cell origin of the neoplastic cell in HD. The high hyperploidy seen in HD is not a frequent observation in NHL. Although certain chromosome aberrations seem to be characteristic of HD as opposed to NHL, specific nonrandom aberrations have yet to be identified. The rather low number of abnormal mitoses found in most HD cases underlies the importance of analyzing a large number of metaphases.

We describe a case of acute myeloid leukemia in a 2 1/2-year-old boy presenting with a mediastinal tumor causing respiratory distress, and lymph node enlargement in the cervical and inguinal regions. Apart from myeloid markers CD13 and CD33, blast cells also expressed stem cell marker CD34 and megakaryocytic marker CD61. Cytogenetically, inv(7)(p21q31) was found in 9/25 and 15/25 analyzed metaphases from short-term cultures of lymph node and bone marrow cells, respectively. The patient is in continued complete remission 26 months post diagnosis. The case demonstrates that chromosome aberrations other than inv(16), t(8;21), and t(9;11) may be associated with extramedullary disease, and that not all chromosome 7 aberrations are prognostic adverse findings.

A 5.5-year-old girl with renal cell carcinoma and chromosomal abnormalities is described. Morphology was diagnostic of an adenopapillary renal cell carcinoma. The karyotype was 57, XX, +X, +2, +3, +4, +7, +12, +13, +16, +17, +20, +21[8]/58,idem, +17[17]. This karyotype has not previously been described in the rare cases of childhood renal cell carcinoma. It is similar to the karyotypes described in adults of the same morphologic subtype. This poses the question whether different types, from a genotype point of view, of renal cell carcinoma exist in childhood.