Skip to main content
SpringerLink
Log in

Hepatosplenic T-Cell Lymphoma

  • Chapter
  • First Online:
Novel Therapeutics for Rare Lymphomas

Abstract

Hepatosplenic T-cell lymphoma (HSTL) is a rare, mature peripheral T-cell lymphoma with predilection for affecting young men, and cases often have an aggressive, morbid, or fatal clinical course. Here we review the molecular/biologic basis as well as salient clinical features, diagnostic criteria, and current treatment pathways in this disease. Lastly, we describe potential ways forward for improving the outcome in this dreaded disease based upon ongoing basic and translational research in HSTL and extrapolation from experience with other T-cell lymphoma subtypes.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 79.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 99.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Vose J, Armitage J, Weisenburger D. International peripheral T-cell and natural killer/T-cell lymphoma study: pathology findings and clinical outcomes. J Clin Oncol. 2008;26:4124–30.

    Article  PubMed  Google Scholar 

  2. Durani U, Go RS. Incidence, clinical findings, and survival of hepatosplenic T-cell lymphoma in the United States. Am J Hematol. 2017;92:E99–e101.

    Article  PubMed  Google Scholar 

  3. Thai A, Prindiville T. Hepatosplenic T-cell lymphoma and inflammatory bowel disease. J Crohn’s Colitis. 2010;4:511–22.

    Article  Google Scholar 

  4. Mackey AC, Green L, Leptak C, Avigan M. Hepatosplenic T cell lymphoma associated with infliximab use in young patients treated for inflammatory bowel disease: update. J Pediatr Gastroenterol Nutr. 2009;48:386–8.

    Article  PubMed  Google Scholar 

  5. Mackey AC, Green L, Liang LC, Dinndorf P, Avigan M. Hepatosplenic T cell lymphoma associated with infliximab use in young patients treated for inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 2007;44:265–7.

    Article  PubMed  Google Scholar 

  6. Kotlyar DS, Osterman MT, Diamond RH, et al. A systematic review of factors that contribute to hepatosplenic T-cell lymphoma in patients with inflammatory bowel disease. Clin Gastroenterol Hepatol. 2011;9:36–41.e1.

    Article  CAS  PubMed  Google Scholar 

  7. Weidmann E. Hepatosplenic T cell lymphoma. A review on 45 cases since the first report describing the disease as a distinct lymphoma entity in 1990. Leukemia. 2000;14:991–7.

    Article  CAS  PubMed  Google Scholar 

  8. Belhadj K, Reyes F, Farcet JP, et al. Hepatosplenic gammadelta T-cell lymphoma is a rare clinicopathologic entity with poor outcome: report on a series of 21 patients. Blood. 2003;102:4261–9.

    Article  CAS  PubMed  Google Scholar 

  9. Falchook GS, Vega F, Dang NH, et al. Hepatosplenic gamma-delta T-cell lymphoma: clinicopathological features and treatment. Ann Oncol. 2009;20:1080–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Lu CL, Tang Y, Yang QP, et al. Hepatosplenic T-cell lymphoma: clinicopathologic, immunophenotypic, and molecular characterization of 17 Chinese cases. Human Pathol. 2011;42:1965–78.

    Article  CAS  Google Scholar 

  11. Yabe M, Medeiros LJ, Tang G, et al. Prognostic factors of hepatosplenic T-cell lymphoma: clinicopathologic study of 28 cases. Am J Surg Pathol. 2016;40:676–88.

    Article  PubMed  Google Scholar 

  12. McKinney M, Moffitt AB, Gaulard P, et al. The genetic basis of hepatosplenic T-cell lymphoma. Cancer Discov. 2017;7:369–79.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Yabe M, Miranda RN, Medeiros LJ. Hepatosplenic T-cell Lymphoma: a review of clinicopathologic features, pathogenesis, and prognostic factors. Hum Pathol. 2018;74:5–16.

    Article  CAS  PubMed  Google Scholar 

  14. Arnoux I, Loosveld M. Hepatosplenic T-cell lymphoma: an acute leukemia presentation. Blood. 2016;127:269.

    Article  CAS  PubMed  Google Scholar 

  15. Pizzi M, Covey S, Mathew S, et al. Hepatosplenic T-Cell lymphoma mimicking acute myeloid leukemia. Clin Lymphoma Myeloma Leuk. 2016;16:e47–50.

    Article  PubMed  Google Scholar 

  16. Hocker TL, Wada DA, McPhail ED, Porrata LF, el-Azhary RA, Gibson LE. Relapsed hepatosplenic T-cell lymphoma heralded by a solitary skin nodule. J Cutan Pathol. 2011;38:899–904.

    Article  PubMed  Google Scholar 

  17. Karpate A, Barcena C, Hohl D, Bisig B, de Leval L. Cutaneous presentation of hepatosplenic T-cell lymphoma-a potential mimicker of primary cutaneous gamma-delta T-cell lymphoma. Virchows Arch. 2016;469:591–6.

    Article  PubMed  Google Scholar 

  18. Yabe M, Medeiros LJ, Wang SA, et al. Clinicopathologic, immunophenotypic, cytogenetic, and molecular features of gammadelta T-Cell large granular lymphocytic leukemia: an analysis of 14 patients suggests biologic differences with alphabeta T-Cell large granular lymphocytic leukemia. [corrected]. Am J Clin Pathol. 2015;144:607–19.

    Article  CAS  PubMed  Google Scholar 

  19. Macon WR, Levy NB, Kurtin PJ, et al. Hepatosplenic alphabeta T-cell lymphomas: a report of 14 cases and comparison with hepatosplenic gammadelta T-cell lymphomas. Am J Surg Pathol. 2001;25:285–96.

    Article  CAS  PubMed  Google Scholar 

  20. Gaulard P, Bourquelot P, Kanavaros P, et al. Expression of the alpha/beta and gamma/delta T-cell receptors in 57 cases of peripheral T-cell lymphomas. Identification of a subset of gamma/delta T-cell lymphomas. Am J Pathol. 1990;137:617–28.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Felgar RE, Macon WR, Kinney MC, Roberts S, Pasha T, Salhany KE. TIA-1 expression in lymphoid neoplasms. Identification of subsets with cytotoxic T lymphocyte or natural killer cell differentiation. Am J Pathol. 1997;150:1893–900.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Cooke CB, Krenacs L, Stetler-Stevenson M, et al. Hepatosplenic T-cell lymphoma: a distinct clinicopathologic entity of cytotoxic gamma delta T-cell origin. Blood. 1996;88:4265–74.

    Article  CAS  PubMed  Google Scholar 

  23. Wang CC, Tien HF, Lin MT, et al. Consistent presence of isochromosome 7q in hepatosplenic T gamma/delta lymphoma: a new cytogenetic-clinicopathologic entity. Genes Chromosomes Cancer. 1995;12:161–4.

    Article  CAS  PubMed  Google Scholar 

  24. Jonveaux P, Daniel MT, Martel V, Maarek O, Berger R. Isochromosome 7q and trisomy 8 are consistent primary, non-random chromosomal abnormalities associated with hepatosplenic T gamma/delta lymphoma. Leukemia. 1996;10:1453–5.

    CAS  PubMed  Google Scholar 

  25. Alonsozana E, Stamberg J, Kumar D, et al. Isochromosome 7q: the primary cytogenetic abnormality in hepatosplenic T cell lymphoma. Leukemia. 1997;11:1367–72.

    Article  CAS  PubMed  Google Scholar 

  26. Shetty S, Mansoor A, Roland B. Ring chromosome 7 with amplification of 7q sequences in a pediatric case of hepatosplenic T-cell lymphoma. Cancer Genet Cytogenet. 2006;167:161–3.

    Article  CAS  PubMed  Google Scholar 

  27. Lavergne A, Brocheriou I, Delfau MH, Copie-Bergman C, Houdart R, Gaulard PH. Primary intestinal gamma-delta T-cell lymphoma with evidence of Epstein-Barr virus. Histopathology. 1998;32:271–6.

    Article  CAS  PubMed  Google Scholar 

  28. Belhadj K, Reyes F, Farcet J-P, et al. Hepatosplenic γδ T-cell lymphoma is a rare clinicopathologic entity with poor outcome: report on a series of 21 patients. Blood. 2003;102:4261–9.

    Article  CAS  PubMed  Google Scholar 

  29. Voss MH, Lunning MA, Maragulia JC, et al. Intensive induction chemotherapy followed by early high-dose therapy and hematopoietic stem cell transplantation results in improved outcome for patients with hepatosplenic T-cell lymphoma: a single institution experience. Clin Lymphoma Myeloma Leuk. 2013;13:8–14.

    Article  PubMed  Google Scholar 

  30. Iannitto E, Barbera V, Quintini G, Cirrincione S, Leone M. Hepatosplenic gammadelta T-cell lymphoma: complete response induced by treatment with pentostatin. Br J Haematol. 2002;117:995–6.

    Article  PubMed  Google Scholar 

  31. Corazzelli G, Capobianco G, Russo F, Frigeri F, Aldinucci D, Pinto A. Pentostatin (2’-deoxycoformycin) for the treatment of hepatosplenic gammadelta T-cell lymphomas. Haematologica. 2005;90:Ecr14.

    PubMed  Google Scholar 

  32. Mittal S, Milner BJ, Johnston PW, Culligan DJ. A case of hepatosplenic gamma-delta T-cell lymphoma with a transient response to fludarabine and alemtuzumab. Eur J Haematol. 2006;76:531–4.

    Article  CAS  PubMed  Google Scholar 

  33. Jaeger G, Bauer F, Brezinschek R, Beham-Schmid C, Mannhalter C, Neumeister P. Hepatosplenic gammadelta T-cell lymphoma successfully treated with a combination of alemtuzumab and cladribine. Ann Oncol. 2008;19:1025–6.

    Article  CAS  PubMed  Google Scholar 

  34. Rashidi A, Cashen AF. Outcomes of allogeneic stem cell transplantation in hepatosplenic T-cell lymphoma. Blood Cancer J. 2015;5:e318.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Piekarz RL, Frye R, Prince HM, et al. Phase 2 trial of romidepsin in patients with peripheral T-cell lymphoma. Blood. 2011;117:5827–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Coiffier B, Pro B, Prince HM, et al. Results from a pivotal, open-label, phase II study of romidepsin in relapsed or refractory peripheral T-cell lymphoma after prior systemic therapy. J Clin Oncol. 2012;30:631–6.

    Article  CAS  PubMed  Google Scholar 

  37. Dupuis J, Morschhauser F, Ghesquieres H, et al. Combination of romidepsin with cyclophosphamide, doxorubicin, vincristine, and prednisone in previously untreated patients with peripheral T-cell lymphoma: a non-randomised, phase 1b/2 study. Lancet Haematol. 2015;2:e160–5.

    Article  PubMed  Google Scholar 

  38. O’Connor OA, Horwitz S, Masszi T, et al. Belinostat in patients with relapsed or refractory peripheral T-Cell lymphoma: results of the pivotal phase II BELIEF (CLN-19) study. J Clin Oncol. 2015;33:2492–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Zinzani PL, Pellegrini C, Broccoli A, et al. Lenalidomide monotherapy for relapsed/refractory peripheral T-cell lymphoma not otherwise specified. Leukemia Lymphoma. 2011;52:1585–8.

    Article  CAS  PubMed  Google Scholar 

  40. Morschhauser F, Fitoussi O, Haioun C, et al. A phase 2, multicentre, single-arm, open-label study to evaluate the safety and efficacy of single-agent lenalidomide (Revlimid) in subjects with relapsed or refractory peripheral T-cell non-Hodgkin lymphoma: the EXPECT trial. Eur J Cancer. 2013;49:2869–76.

    Article  CAS  PubMed  Google Scholar 

  41. Hopfinger G, Nosslinger T, Lang A, et al. Lenalidomide in combination with vorinostat and dexamethasone for the treatment of relapsed/refractory peripheral T cell lymphoma (PTCL): report of a phase I/II trial. Ann Hematol. 2014;93:459–62.

    Article  CAS  PubMed  Google Scholar 

  42. Ogura M, Imaizumi Y, Uike N, et al. Lenalidomide in relapsed adult T-cell leukaemia-lymphoma or peripheral T-cell lymphoma (ATLL-001): a phase 1, multicentre, dose-escalation study. Lancet Haematol. 2016;3:e107–18.

    Article  PubMed  Google Scholar 

  43. Duvic M, Pinter-Brown LC, Foss FM, et al. Phase 1/2 study of mogamulizumab, a defucosylated anti-CCR4 antibody, in previously treated patients with cutaneous T-cell lymphoma. Blood. 2015;125:1883–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Travert M, Huang Y, de Leval L, et al. Molecular features of hepatosplenic T-cell lymphoma unravels potential novel therapeutic targets. Blood. 2012;119:5795–806.

    Article  CAS  PubMed  Google Scholar 

  45. Nicolae A, Xi L, Pittaluga S, et al. Frequent STAT5B mutations in gammadelta hepatosplenic T-cell lymphomas. Leukemia. 2014;28:2244–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Quintas-Cardama A, Vaddi K, Liu P, et al. Preclinical characterization of the selective JAK1/2 inhibitor INCB018424: therapeutic implications for the treatment of myeloproliferative neoplasms. Blood. 2010;115:3109–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Verstovsek S. Therapeutic potential of JAK2 inhibitors. Hematology/the Education Program of the American Society of Hematology American Society of Hematology Education Program 2009:636–42.

    Article  Google Scholar 

  48. Fruman DA, Rommel C. PI3Kdelta inhibitors in cancer: rationale and serendipity merge in the clinic. Cancer Discov. 2011;1:562–72.

    Article  CAS  PubMed  Google Scholar 

  49. Moffitt AB, Ondrejka SL, McKinney M, et al. Enteropathy-associated T cell lymphoma subtypes are characterized by loss of function of SETD2. J Exp Med. 2017;214:1371–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Roberti A, Dobay MP, Bisig B, et al. Type II enteropathy-associated T-cell lymphoma features a unique genomic profile with highly recurrent SETD2 alterations. Nat Commun. 2016;7:12602.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Fahey CC, Davis IJ. SETting the stage for cancer development: SETD2 and the consequences of lost methylation. Cold Spring Harbor Perspect Med. 2017;7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Li J, Duns G, Westers H, Sijmons R, van den Berg A, Kok K. SETD2: an epigenetic modifier with tumor suppressor functionality. Oncotarget. 2016;7:50719–34.

    PubMed  PubMed Central  Google Scholar 

  53. Kanu N, Gronroos E, Martinez P, et al. SETD2 loss-of-function promotes renal cancer branched evolution through replication stress and impaired DNA repair. Oncogene. 2015;34:5699–708.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Zhang Y, Xie S, Zhou Y, et al. H3K36 histone methyltransferase Setd2 is required for murine embryonic stem cell differentiation toward endoderm. Cell Rep. 2014;8:1989–2002.

    Article  CAS  PubMed  Google Scholar 

  55. Pfister SX, Ahrabi S, Zalmas LP, et al. SETD2-dependent histone H3K36 trimethylation is required for homologous recombination repair and genome stability. Cell Rep. 2014;7:2006–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Park IY, Powell RT, Tripathi DN, et al. Dual chromatin and cytoskeletal remodeling by SETD2. Cell. 2016;166:950–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Pfister SX, Markkanen E, Jiang Y, et al. Inhibiting WEE1 selectively Kills Histone H3K36me3-Deficient cancers by dNTP starvation. Cancer Cell. 2015;28:557–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Chalmers AW, Katz DA, Miller IJ, Gregory SA. Successful treatment of hepatosplenic T-cell lymphoma with ESHAP followed by autologous stem cell transplant. Clin Adv Hematol Oncol. 2013;11:109–13.

    PubMed  Google Scholar 

  59. Rizzieri DA, Johnson JL, Byrd JC, et al. Improved efficacy using rituximab and brief duration, high intensity chemotherapy with filgrastim support for Burkitt or aggressive lymphomas: cancer and Leukemia Group B study 10 002. British J Haematol. 2014;165:102–11.

    Article  CAS  Google Scholar 

  60. Amengual JE, Lichtenstein R, Lue J, et al. A phase 1 study of romidepsin and pralatrexate reveals marked activity in relapsed and refractory T-cell lymphoma. Blood. 2018;131:397–407.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Jiang L, Yuan CM, Hubacheck J, et al. Variable CD52 expression in mature T cell and NK cell malignancies: implications for alemtuzumab therapy. British J Haematol. 2009;145:173–9.

    Article  CAS  Google Scholar 

  62. Al-Toma A, Goerres MS, Meijer JW, et al. Cladribine therapy in refractory celiac disease with aberrant T cells. Clin Gastroenterol Hepatol. 2006;4:1322–7; quiz 00.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Medical Oncology and Cellular Therapy, Duke University Medical Center, Durham, NC, USA

    Shekeab Jauhari

  2. Division of Hematologic Malignancies, Department of Medicine, Duke University School of Medicine, Durham, NC, USA

    Matt McKinney

Authors
  1. Shekeab Jauhari
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Matt McKinney
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Matt McKinney .

Editor information

Editors and Affiliations

  1. Department of Medicine, Division of Hematology and Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Christopher Dittus

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Jauhari, S., McKinney, M. (2020). Hepatosplenic T-Cell Lymphoma. In: Dittus, C. (eds) Novel Therapeutics for Rare Lymphomas. Springer, Cham. https://doi.org/10.1007/978-3-030-25610-4_13

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-25610-4_13

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-25609-8

  • Online ISBN: 978-3-030-25610-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation