Jan-Inge Henter

Summary

Affiliation: Karolinska Institutet
Country: Sweden

Publications

  1. ncbi [Can cytostatics be effective in severe avian influenza? The disease picture has similarities with hemophagocytic lymphohistiocytosis]
    Jan Inge Henter
    Barncancerforskningsenheten, Institutionen for kvinnors och barns halsa, Astrid Lindgrens barnsjukhus, Karolinska Institutet, Stockholm
    Lakartidningen 103:1180-1. 2006
  2. ncbi Fatal agranulocytosis after deferiprone therapy in a child with Diamond-Blackfan anemia
    Jan Inge Henter
    Childhood Cancer Research Unit, Department of Woman and Child Health, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
    Blood 109:5157-9. 2007
  3. doi Pronounced hyperferritinemia: expanding the field of hemophagocytic lymphohistiocytosis
    Jan Inge Henter
    Childhood Cancer Research Unit, Department of Woman and Child Health, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
    Pediatr Blood Cancer 50:1127-9. 2008
  4. ncbi HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis
    Jan Inge Henter
    Childhood Cancer Research Unit, Department of Woman and Child Health, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
    Pediatr Blood Cancer 48:124-31. 2007
  5. ncbi Frequency and spectrum of central nervous system involvement in 193 children with haemophagocytic lymphohistiocytosis
    Annacarin Horne
    Childhood Cancer Research Unit, Department of Woman and Child Health, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
    Br J Haematol 140:327-35. 2008
  6. ncbi Kostmann syndrome or infantile genetic agranulocytosis, part two: Understanding the underlying genetic defects in severe congenital neutropenia
    Goran Carlsson
    Childhood Cancer Research Unit, Department of Woman and Child Health, Karolinska University Hospital, Stockholm, Sweden
    Acta Paediatr 96:813-9. 2007
  7. ncbi Low plasma levels of the protein pro-LL-37 as an early indication of severe disease in patients with chronic neutropenia
    Jenny Karlsson
    Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
    Br J Haematol 137:166-9. 2007
  8. ncbi Parents' intellectual and emotional awareness of their child's impending death to cancer: a population-based long-term follow-up study
    Unnur Valdimarsdottir
    Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden
    Lancet Oncol 8:706-14. 2007
  9. ncbi Sequence analysis of the SRGN, AP3B1, ARF6, and SH2D1A genes in familial hemophagocytic lymphohistiocytosis
    Daoxin Ma
    Childhood Cancer Research Unit, Department of Woman and Child Health, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
    Pediatr Blood Cancer 50:1067-9. 2008
  10. ncbi Severe bacteria-associated hemophagocytic lymphohistiocytosis in an extremely premature infant
    Josefine Edner
    Childhood Cancer Research Unit, Department of Women and Child Health, Karolinska University Hospital, Stockholm, Sweden
    Acta Paediatr 96:1703-6. 2007

Detail Information

Publications49

  1. ncbi [Can cytostatics be effective in severe avian influenza? The disease picture has similarities with hemophagocytic lymphohistiocytosis]
    Jan Inge Henter
    Barncancerforskningsenheten, Institutionen for kvinnors och barns halsa, Astrid Lindgrens barnsjukhus, Karolinska Institutet, Stockholm
    Lakartidningen 103:1180-1. 2006
  2. ncbi Fatal agranulocytosis after deferiprone therapy in a child with Diamond-Blackfan anemia
    Jan Inge Henter
    Childhood Cancer Research Unit, Department of Woman and Child Health, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
    Blood 109:5157-9. 2007
    ..We suggest that deferiprone not be prescribed to DBA patients unless the clinical indications are particularly strong, and that the risk of agranulocytosis in thalassemia patients be carefully considered...
  3. doi Pronounced hyperferritinemia: expanding the field of hemophagocytic lymphohistiocytosis
    Jan Inge Henter
    Childhood Cancer Research Unit, Department of Woman and Child Health, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
    Pediatr Blood Cancer 50:1127-9. 2008
  4. ncbi HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis
    Jan Inge Henter
    Childhood Cancer Research Unit, Department of Woman and Child Health, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
    Pediatr Blood Cancer 48:124-31. 2007
    ..In order to hopefully further improve diagnosis, therapy and biological understanding, participation in HLH studies is encouraged...
  5. ncbi Frequency and spectrum of central nervous system involvement in 193 children with haemophagocytic lymphohistiocytosis
    Annacarin Horne
    Childhood Cancer Research Unit, Department of Woman and Child Health, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
    Br J Haematol 140:327-35. 2008
    ..Prompt treatment of HLH at onset or relapse may reduce these complications...
  6. ncbi Kostmann syndrome or infantile genetic agranulocytosis, part two: Understanding the underlying genetic defects in severe congenital neutropenia
    Goran Carlsson
    Childhood Cancer Research Unit, Department of Woman and Child Health, Karolinska University Hospital, Stockholm, Sweden
    Acta Paediatr 96:813-9. 2007
    ..Conclusion: Future studies should aim to clarify the mechanisms underlying the evolution of secondary malignancies in these patients...
  7. ncbi Low plasma levels of the protein pro-LL-37 as an early indication of severe disease in patients with chronic neutropenia
    Jenny Karlsson
    Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
    Br J Haematol 137:166-9. 2007
    ..Plasma levels of pro-LL-37 may thus prove useful for differential diagnosis of chronic neutropenia...
  8. ncbi Parents' intellectual and emotional awareness of their child's impending death to cancer: a population-based long-term follow-up study
    Unnur Valdimarsdottir
    Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden
    Lancet Oncol 8:706-14. 2007
    ..We aimed to study care-related determinants of when parents gain awareness of their child's impending death to cancer, and whether the duration of this awareness affects the parents' long-term morbidity...
  9. ncbi Sequence analysis of the SRGN, AP3B1, ARF6, and SH2D1A genes in familial hemophagocytic lymphohistiocytosis
    Daoxin Ma
    Childhood Cancer Research Unit, Department of Woman and Child Health, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
    Pediatr Blood Cancer 50:1067-9. 2008
    ..Additionally, two novel polymorphisms, one in intron 17 of AP3B1 and another in intron 2 of SH2D1A were identified. We conclude that mutations in SRGN, ARF6, and AP3B1 are not likely to be common in patients fulfilling the FHL criteria...
  10. ncbi Severe bacteria-associated hemophagocytic lymphohistiocytosis in an extremely premature infant
    Josefine Edner
    Childhood Cancer Research Unit, Department of Women and Child Health, Karolinska University Hospital, Stockholm, Sweden
    Acta Paediatr 96:1703-6. 2007
    ..It is important to be aware of HLH in premature infants, since it is treatable...
  11. ncbi Haematopoietic stem cell transplantation in haemophagocytic lymphohistiocytosis
    Annacarin Horne
    Childhood Cancer Research Unit, Institution for Woman and Child Health, Karolinska Institutet, Department of Paediatric Haematology and Oncology, Karolinska Hospital, Stockholm, Sweden
    Br J Haematol 129:622-30. 2005
    ..Patients that responded well to initial pretransplant-induction therapy fared best, but some persisting HLH activity should not automatically preclude performing SCT...
  12. ncbi VEGF reduces astrogliosis and preserves neuromuscular junctions in ALS transgenic mice
    Chengyun Zheng
    Childhood Cancer Research Unit, Department of Woman and Child Health, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, Sweden
    Biochem Biophys Res Commun 363:989-93. 2007
    ..These findings warrant further evaluation of the mechanism(s) of regulatory effects of VEGF on neuronal and non-neuronal cells, and the relation of these events to motor neuron degeneration and the onset and progression of ALS...
  13. ncbi Kostmann syndrome or infantile genetic agranulocytosis, part one: celebrating 50 years of clinical and basic research on severe congenital neutropenia
    Goran Carlsson
    Childhood Cancer Research Unit, Department of Women and Child Health, Karolinska University Hospital, Stockholm, Sweden
    Acta Paediatr 95:1526-32. 2006
    ..Moreover, an increased degree of apoptosis of myeloid progenitor cells in the bone marrow has been shown...
  14. ncbi Treatment of hemophagocytic lymphohistiocytosis with HLH-94 immunochemotherapy and bone marrow transplantation
    Jan Inge Henter
    Childhood Cancer Research Unit, Karolinska Institutet, Department of Pediatric Hematology and Oncology, Karolinska Hospital, Stockholm, Sweden
    Blood 100:2367-73. 2002
    ..The 3-year probability of survival after BMT was 62% (+/- 12%). HLH-94 is very effective, allowing BMT in most patients. Survival of children with HLH has been greatly improved...
  15. ncbi Long-term follow-up of Langerhans cell histiocytosis: 39 years' experience at a single centre
    Cecilia Bernstrand
    Childhood Cancer Research Unit, Department of Woman and Child Health, Astrid Lindgren Children s Hospital, Karolinska Hospital, Stockholm, Sweden
    Acta Paediatr 94:1073-84. 2005
    ..To evaluate the long-term outcome of Langerhans cell histiocytosis (LCH) in children...
  16. ncbi Periodontal disease in patients from the original Kostmann family with severe congenital neutropenia
    Goran Carlsson
    Childhood Cancer Research Unit, Department of Women s and Children s Health, Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden
    J Periodontol 77:744-51. 2006
    ..However, although they no longer experience life-threatening bacterial infections, they frequently still have recurrent gingivitis and even severe periodontitis, often starting in early childhood...
  17. ncbi Combined spectral karyotyping, comparative genomic hybridization, and in vitro apoptyping of a panel of Burkitt's lymphoma-derived B cell lines reveals an unexpected complexity of chromosomal aberrations and a recurrence of specific abnormalities in chemo
    Maria B Karpova
    Childhood Cancer Research Unit, Department of Woman and Child Health, Karolinska University Hospital, S 171 76 Stockholm, Sweden
    Int J Oncol 28:605-17. 2006
    ....
  18. ncbi Pulmonary function testing and pulmonary Langerhans cell histiocytosis
    Cecilia Bernstrand
    Childhood Cancer Research Unit, Department of Woman and Child Health, Karolinska University Hospital, Stockholm, Sweden
    Pediatr Blood Cancer 49:323-8. 2007
    ..036). Disease monitoring is important in pulmonary LCH, and since PFT with diffusing capacity provides a measurement of the current lung function, it may be a valuable tool in monitoring pulmonary LCH, and a good complement to imaging...
  19. ncbi Subtyping of natural killer cell cytotoxicity deficiencies in haemophagocytic lymphohistocytosis provides therapeutic guidance
    Annacarin Horne
    Childhood Cancer Research Unit, Department of Paediatric Haematology and Oncology, Karolinska Hospital, Department of Woman and Child Health, Karolinska Institutet, Stockholm, Sweden
    Br J Haematol 129:658-66. 2005
    ..The data suggests that HLH patients with NK-cell deficiency type 3 will probably require SCT to survive. Thus, NK-cell deficiency classification may provide valuable guidance in judging whether an HLH-patient needs SCT...
  20. ncbi Efficacy and safety of two different rG-CSF preparations in the treatment of patients with severe congenital neutropenia
    Goran Carlsson
    Department of Woman and Child Health, Childhood Cancer Research Unit, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden
    Br J Haematol 126:127-32. 2004
    ..We conclude that filgrastim and lenograstim displayed equal clinical efficacy, but that ANC levels were higher during filgrastim treatment, when administered in equimolar doses...
  21. ncbi Talking about death with children who have severe malignant disease
    Ulrika Kreicbergs
    Division of Clinical Cancer Epidemiology, Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden
    N Engl J Med 351:1175-86. 2004
    ..One of the questions faced by the parents of a child who is terminally ill with a malignant disease is whether or not they should talk about death with their child...
  22. doi Incidence of Langerhans cell histiocytosis in children: a population-based study
    Helen Stålemark
    Childhood Cancer Research Unit, Department of Woman and Child Health, Karolinska University Hospital, Stockholm, Sweden
    Pediatr Blood Cancer 51:76-81. 2008
    ..Langerhans cell histiocytosis is a rare disease of unknown etiology. We wanted to assess the population-based incidence of LCH in a well-defined cohort of children...
  23. pmc Defective cytotoxic lymphocyte degranulation in syntaxin-11 deficient familial hemophagocytic lymphohistiocytosis 4 (FHL4) patients
    Yenan T Bryceson
    Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden
    Blood 110:1906-15. 2007
    ....
  24. doi Neuropsychological sequelae in patients with neurodegenerative Langerhans cell histiocytosis
    Ingrid van't Hooft
    Childhood Cancer Research Unit, Department of Woman and Child Health, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
    Pediatr Blood Cancer 51:669-74. 2008
    ..We here aimed to investigate the neuropsychological consequences in more detail...
  25. ncbi Symptoms affecting children with malignancies during the last month of life: a nationwide follow-up
    Li Jalmsell
    Department of Woman and Child Health, Karolinska University Hospital, Stockholm, Sweden
    Pediatrics 117:1314-20. 2006
    ..Understanding which symptoms affect children in the terminal phase of disease is crucial to improve palliative care...
  26. doi Parvovirus B19 infection in children with acute lymphoblastic leukemia is associated with cytopenia resulting in prolonged interruptions of chemotherapy
    Anna Lindblom
    Unit of Infectious Diseases, Department of Medicine, Solna, Center for Molecular Medicine, Stockholm, Sweden
    Clin Infect Dis 46:528-36. 2008
    ..We evaluated the complications of parvovirus B19 infection, including delays in the scheduled course of chemotherapy, in children with acute lymphoblastic leukemia (ALL)...
  27. ncbi [Kostmann's syndrome largely elucidated--by Swedish research. 50 years since Rolf Kostmann's pioneering work on severe congenital neutropenia]
    Goran Carlsson
    Institutionen för kvinnor och barns hälsa, Astrid Lindgrens barnsjukhus, Karolinska Universitetssjukhuset Solna
    Lakartidningen 103:4022-7. 2006
  28. pmc Does treatment of newly diagnosed idiopathic thrombocytopenic purpura reduce morbidity?
    Iris Treutiger
    Sachs Children s Hospital, Stockholm, Sweden
    Arch Dis Child 92:704-7. 2007
    ..To explore whether early treatment of children with idiopathic thrombocytopenic purpura (ITP) with immunoglobulin and/or corticosteroids reduces subsequent morbidity...
  29. ncbi Cytotoxic therapy for severe avian influenza A (H5N1) infection
    Jan Inge Henter
    Childhood Cancer Research Unit, Department of Woman and Child Health, Karolinska Institutet, Karolinska University Hospital Q6 05, SE 171 76 Stockholm, Sweden
    Lancet 367:870-3. 2006
    ..With this notable improvement in survival, specific HLH treatment, including cytotoxic therapy, could be considered in patients with severe avian influenza A infection complicated by secondary HLH...
  30. ncbi Sequence analysis of the granulysin and granzyme B genes in familial hemophagocytic lymphohistiocytosis
    Kim Göransdotter Ericson
    Childhood Cancer Research Unit, Department of Woman and Child Health, Karoliniska Institutet, Stockholm, Sweden
    Hum Genet 112:98-9. 2003
    ..However, none of these sequence variations were associated with the manifestations of FHL. These data do not support the notion that granulysin and granzyme B are candidate genes for FHL...
  31. ncbi Randomized study of IVIg and high-dose dexamethasone therapy for children with chronic idiopathic thrombocytopenic purpura
    Iris Hedlund-Treutiger
    Department of Pediatrics, Karolinska Institute at Sachs Children s Hospital, Sodersjukhuset, Stockholm, Sweden
    J Pediatr Hematol Oncol 25:139-44. 2003
    ..To investigate whether pulsed high-dose dexamethasone is more efficacious than intravenous immunoglobulin (IVIg) as treatment of symptomatic chronic idiopathic thrombocytopenic purpura (ITP) in childhood...
  32. ncbi Vascular endothelial growth factor prolongs survival in a transgenic mouse model of ALS
    Chengyun Zheng
    Childhood Cancer Research Unit, Department of Woman and Child Health, Karolinska Hospital, Stockholm, Sweden
    Ann Neurol 56:564-7. 2004
    ..These observations suggest that VEGF or related compounds, might be of value in the treatment of ALS patients...
  33. ncbi Kostmann syndrome: severe congenital neutropenia associated with defective expression of Bcl-2, constitutive mitochondrial release of cytochrome c, and excessive apoptosis of myeloid progenitor cells
    Goran Carlsson
    Childhood Cancer Research Center, Department of Woman and Child Health, Karolinska Hospital, Stockholm, Sweden
    Blood 103:3355-61. 2004
    ..In sum, these studies establish a role for mitochondria-dependent apoptosis in the pathogenesis of Kostmann syndrome and yield a tentative explanation for the beneficial effect of growth factor administration in these patients...
  34. ncbi Fetal hemolytic anemia and intrauterine death caused by anti-M immunization
    Agneta Wikman
    Division of Clinical Immunology and Transfusion Medicine, Neonatal Unit, Department of Woman and Child Health, Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden
    Transfusion 47:911-7. 2007
    ..Antibodies with anti-M specificity are detected in 10 percent of pregnant women with a positive antibody screen, but anti-M is only rarely associated with hemolytic anemia in the fetus...
  35. ncbi Tumor necrosis factor, interleukin 11, and leukemia inhibitory factor produced by Langerhans cells in Langerhans cell histiocytosis
    Ulrika Andersson By
    Childhood Cancer Research Unit, Department of Woman and Child Health, Karolinska Institutet, Astrid Lindgren Children s Hospital, Stockholm, Sweden
    J Pediatr Hematol Oncol 26:706-11. 2004
    ....
  36. ncbi Betulinic acid, a natural cytotoxic agent, fails to trigger apoptosis in human Burkitt's lymphoma-derived B-cell lines
    Maria B Karpova
    Childhood Cancer Research Unit, Department of Woman and Child Health, Karolinska University Hospital, Stockholm, Sweden
    Int J Cancer 118:246-52. 2006
    ..Together, these studies indicate that resistance to BA-induced apoptosis is a common feature of BL-derived cell lines...
  37. ncbi Elevated serum levels of the decoy receptor osteoprotegerin in children with Langerhans cell histiocytosis
    Diego A Rosso
    Division of Molecular Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
    Pediatr Res 59:281-6. 2006
    ..These findings show, for the first time, that serum OPG levels are elevated in LCH patients, and suggest that OPG may play a role in the pathogenesis of this enigmatic disease...
  38. ncbi A population-based nationwide study of parents' perceptions of a questionnaire on their child's death due to cancer
    Ulrika Kreicbergs
    Clinical Cancer Epidemiology, Department of Oncology and Pathology, Karolinska Institutet, Z6 01 Karolinska Hospital, SE 171 76 Stockholm, Sweden
    Lancet 364:787-9. 2004
    ..Although the numerical data cannot be directly translated to ethical conclusions, they can provide guidance for future ethical decisions...
  39. ncbi Immunogenetic heterogeneity in single-system and multisystem langerhans cell histiocytosis
    Cecilia Bernstrand
    Childhood Cancer Research Unit, Q6 05, Karolinska Hospital, S 171 76 Stockholm, Sweden
    Pediatr Res 54:30-6. 2003
    ..Further studies to confirm these findings are desired...
  40. ncbi Biology and treatment of familial hemophagocytic lymphohistiocytosis: importance of perforin in lymphocyte-mediated cytotoxicity and triggering of apoptosis
    Jan Inge Henter
    Childhood Cancer Research Unit, Karolinska Institute, Department of Pediatric Hematology and Oncology, Astrid Lindgren Children s Hospital, Karolinska Hospital, Stockholm, Sweden
    Med Pediatr Oncol 38:305-9. 2002
    ..The establishment of perforin deficiency as a cause of the rapidly fatal disease FHL has demonstrated the essential role of perforin in human immune homeostasis...
  41. ncbi Care-related distress: a nationwide study of parents who lost their child to cancer
    Ulrika Kreicbergs
    Division of Clinical Cancer Epidemiology, Department of Oncology and Pathology Karolinska Institutet, Karolinska Hospital, Stockholm
    J Clin Oncol 23:9162-71. 2005
    ..We conducted a population-based, nationwide study addressing this issue, focusing on potential care-related stressors in parents losing a child to cancer...
  42. ncbi Longitudinal follow-up of patients with Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis
    Shinsaku Imashuku
    Kyoto City Institute of Health and Environmental Sciences, Kyoto, Japan
    Haematologica 89:183-8. 2004
    ..The main purpose of this study was to determine the outcome of the EBV-HLH patients treated between 1992 and 2001...
  43. ncbi Langerhans-cell histiocytosis: neoplasia or unbridled inflammation?
    Bengt Fadeel
    Trends Immunol 24:409-10; author reply 410-1. 2003
  44. ncbi Clinical and genetic studies of familial hemophagocytic lymphohistiocytosis in Oman: need for early treatment
    Zakia Al-Lamki
    Department of Child Health, Hematology Oncology Unit, College of Medicine, Sultan Qaboos University, Al Khod, Oman
    Pediatr Hematol Oncol 20:603-9. 2003
    ....
  45. ncbi HAX1 deficiency causes autosomal recessive severe congenital neutropenia (Kostmann disease)
    Christoph Klein
    Department of Pediatric Hematology Oncology, Hannover Medical School, Carl Neuberg Strasse 1, 30625 Hannover, Germany
    Nat Genet 39:86-92. 2007
    ..Our findings suggest that HAX1 is a major regulator of myeloid homeostasis and underline the significance of genetic control of apoptosis in neutrophil development...
  46. ncbi Healing hemophagocytosis
    Alexandra H Filipovich
    Center for Heritable Immune Deficiencies, Cincinnati Children s Hospital Medical Center, Cincinnati, Ohio, USA
    Clin Immunol 117:121-4. 2005
  47. ncbi Simultaneous manifestation of fulminant infectious mononucleosis with haemophagocytic syndrome and B-cell lymphoma in X-linked lymphoproliferative disease
    Boris Hugle
    Department of Pediatrics, University of Leipzig, Oststrasse 21 25, Leipzig, Germany
    Eur J Pediatr 166:589-93. 2007
    ..Fatal EBV infection in male infants is highly indicative of XLP. Virus-associated haemophagocytic syndrome and B-cell lymphoma can occur concomitantly and may be difficult to distinguish due to their similar histological pictures...
  48. doi Why rare diseases are an important medical and social issue
    Arrigo Schieppati
    Clinical Research Centre for Rare Disease Aldo e Cele Daccò, Mario Negri Institute for Pharmacological Research, Bergamo, Italy
    Lancet 371:2039-41. 2008
  49. ncbi Anxiety and depression in parents 4-9 years after the loss of a child owing to a malignancy: a population-based follow-up
    Ulrika Kreicbergs
    Clinical Cancer Epidemiology, Department of Oncology and Pathology, Karolinska Institutet Z6 01, Karolinska Hospital, SE 171 76 Stockholm, Sweden
    Psychol Med 34:1431-41. 2004
    ..We investigated parental risk of anxiety and depression 4-9 years after the loss of a child owing to a malignancy...