Skip to main content

Rare T-Cell Subtypes

  • Chapter
  • First Online:
T-Cell and NK-Cell Lymphomas

Part of the book series: Cancer Treatment and Research ((CTAR,volume 176))

Abstract

There are a number of rare T-cell lymphoma subtypes that may be encountered in clinical practice. In recent years, improved immunohistochemical techniques and molecular tumor profiling have permitted refinement of some of the diagnostic categories in this group, as well as the recognition of distinct conditions not previously well elucidated. In this chapter, we cover the diagnostic and clinical features of some of the more common of these conditions, including subcutaneous panniculitis-like T-cell lymphoma, cutaneous gamma-delta T-cell lymphoma, enteropathy-associated T-cell lymphoma, monomorphic epitheliotropic intestinal T-cell lymphoma, primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma, CD4-positive small/medium T-cell lymphoproliferative disorder, and acral CD8-positive T-cell lymphoma. Given the rarity of these conditions, optimal treatments approaches are not always well established, not least as data from large-scale clinical trials are lacking. In this chapter, we aim to provide a summation of current thinking around best treatment, as well as highlighting some controversies in the management of these diagnoses.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 169.99
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. Gonzalez CL, Medeiros LJ, Braziel RM, Jaffe ES (1991) T-cell lymphoma involving subcutaneous tissue. A clinicopathologic entity commonly associated with hemophagocytic syndrome. Am J Surg Pathol 15(1):17–27

    Article  CAS  PubMed  Google Scholar 

  2. Jaffe ES, Harris NL, Stein H, Vardiman JW (2001) Pathology and genetics of tumours of haematopoietic and lymphoid tissues. IARC Press, Lyon, France

    Google Scholar 

  3. Willemze R, Kerl H, Sterry W, Berti E, Cerroni L, Chimenti S et al (1997) EORTC classification for primary cutaneous lymphomas: a proposal from the Cutaneous Lymphoma Study Group of the European Organization for Research and Treatment of Cancer. Blood 90(1):354–71

    CAS  PubMed  Google Scholar 

  4. Willemze R, Jansen PM, Cerroni L, Berti E, Santucci M, Assaf C et al (2008) Subcutaneous panniculitis-like T-cell lymphoma: definition, classification, and prognostic factors: an EORTC Cutaneous Lymphoma Group Study of 83 cases. Blood 111(2):838–45

    Article  CAS  PubMed  Google Scholar 

  5. Salhany KE, Macon WR, Choi JK, Elenitsas R, Lessin SR, Felgar RE et al (1998) Subcutaneous panniculitis-like T-cell lymphoma: clinicopathologic, immunophenotypic, and genotypic analysis of alpha/beta and gamma/delta subtypes. Am J Surg Pathol 22(7):881–93

    Article  CAS  PubMed  Google Scholar 

  6. Toro JR, Liewehr DJ, Pabby N, Sorbara L, Raffeld M, Steinberg SM et al (2003) Gamma-delta T-cell phenotype is associated with significantly decreased survival in cutaneous T-cell lymphoma. Blood 101(9):3407–12

    Article  CAS  PubMed  Google Scholar 

  7. Hoque SR, Child FJ, Whittaker SJ, Ferreira S, Orchard G, Jenner K et al (2003) Subcutaneous panniculitis-like T-cell lymphoma: a clinicopathological, immunophenotypic and molecular analysis of six patients. Br J Dermatol 148(3):516–25

    Article  CAS  PubMed  Google Scholar 

  8. Kong YY, Dai B, Kong JC, Zhou XY, Lu HF, Shen L et al (2008) Subcutaneous panniculitis-like T-cell lymphoma: a clinicopathologic, immunophenotypic, and molecular study of 22 Asian cases according to WHO-EORTC classification. Am J Surg Pathol 32(10):1495–502

    Article  PubMed  Google Scholar 

  9. Willemze R, Jaffe ES, Burg G, Cerroni L, Berti E, Swerdlow SH et al (2005) WHO-EORTC classification for cutaneous lymphomas. Blood 105(10):3768–85

    Article  CAS  PubMed  Google Scholar 

  10. Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R et al (2016) The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood 127(20):2375–90

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Michonneau D, Petrella T, Ortonne N, Ingen-Housz-Oro S, Franck N, Barete S et al (2017) Subcutaneous Panniculitis-like T-cell Lymphoma: Immunosuppressive Drugs Induce Better Response than Polychemotherapy. Acta Derm Venereol 97(3):358–64

    Article  PubMed  Google Scholar 

  12. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H (2008) WHO classification of tumours of haematopoietic and lymphoid tumours. IARC Press, Lyon, France

    Google Scholar 

  13. He A, Kwatra SG, Kazi N, Sweren RJ (2016) Atypical lymphocytic lobular panniculitis: an overlap condition with features of subcutaneous panniculitis-like T-cell lymphoma and lupus profundus. BMJ Case Rep 2016

    Google Scholar 

  14. Bosisio F, Boi S, Caputo V, Chiarelli C, Oliver F, Ricci R et al (2015) Lobular panniculitic infiltrates with overlapping histopathologic features of lupus panniculitis (lupus profundus) and subcutaneous T-cell lymphoma: a conceptual and practical dilemma. Am J Surg Pathol 39(2):206–11

    Article  PubMed  Google Scholar 

  15. Pincus LB, LeBoit PE, McCalmont TH, Ricci R, Buzio C, Fox LP et al (2009) Subcutaneous panniculitis-like T-cell lymphoma with overlapping clinicopathologic features of lupus erythematosus: coexistence of 2 entities? Am J Dermatopathol 31(6):520–6

    Article  PubMed  Google Scholar 

  16. Arps DP, Patel RM (2013) Lupus profundus (panniculitis): a potential mimic of subcutaneous panniculitis-like T-cell lymphoma. Arch Pathol Lab Med 137(9):1211–5

    Article  PubMed  Google Scholar 

  17. Magro CM, Crowson AN, Kovatich AJ, Burns F (2001) Lupus profundus, indeterminate lymphocytic lobular panniculitis and subcutaneous T-cell lymphoma: a spectrum of subcuticular T-cell lymphoid dyscrasia. J Cutan Pathol 28(5):235–47

    Article  CAS  PubMed  Google Scholar 

  18. Dornmair K, Goebels N, Weltzien HU, Wekerle H, Hohlfeld R (2003) T-cell-mediated autoimmunity: novel techniques to characterize autoreactive T-cell receptors. Am J Pathol 163(4):1215–26

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Wang X, Magro CM (2012) Human myxovirus resistance protein 1 (MxA) as a useful marker in the differential diagnosis of subcutaneous lymphoma versus lupus erythematosus profundus. Eur J Dermatol. 22(5):629–33

    PubMed  Google Scholar 

  20. Liau JY, Chuang SS, Chu CY, Ku WH, Tsai JH, Shih TF (2013) The presence of clusters of plasmacytoid dendritic cells is a helpful feature for differentiating lupus panniculitis from subcutaneous panniculitis-like T-cell lymphoma. Histopathology 62(7):1057–66

    Article  PubMed  Google Scholar 

  21. Maliniemi P, Hahtola S, Ovaska K, Jeskanen L, Vakeva L, Jantti K et al (2014) Molecular characterization of subcutaneous panniculitis-like T-cell lymphoma reveals upregulation of immunosuppression- and autoimmunity-associated genes. Orphanet J Rare Dis. 9:160

    Article  PubMed  PubMed Central  Google Scholar 

  22. Go RS, Wester SM (2004) Immunophenotypic and molecular features, clinical outcomes, treatments, and prognostic factors associated with subcutaneous panniculitis-like T-cell lymphoma: a systematic analysis of 156 patients reported in the literature. Cancer 101(6):1404–13

    Article  PubMed  Google Scholar 

  23. Ohtsuka M, Miura T, Yamamoto T (2017) Clinical characteristics, differential diagnosis, and treatment outcome of subcutaneous panniculitis-like T-cell lymphoma: a literature review of published Japanese cases. Eur J Dermatol. 27(1):34–41

    CAS  PubMed  Google Scholar 

  24. Lee WS, Hwang JH, Kim MJ, Go SI, Lee A, Song HN et al (2014) Cyclosporine A as a Primary Treatment for Panniculitis-like T-cell Lymphoma: A Case with a Long-Term Remission. Cancer Res Treat. 46(3):312–6

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Iqbal N, Raina V (2014) Successful treatment of disseminated subcutaneous panniculitis-like T-cell lymphoma with single agent oral cyclosporine as a first line therapy. Case Rep Dermatol Med. 2014:201836

    PubMed  PubMed Central  Google Scholar 

  26. Chen R, Liu L, Liang YM (2010) Treatment relapsed subcutaneous panniculitis-like T-cell lymphoma together HPS by Cyclosporin A. Hematol Rep. 2(1):e9

    Article  PubMed  PubMed Central  Google Scholar 

  27. Mizutani S, Kuroda J, Shimura Y, Kobayashi T, Tsutsumi Y, Yamashita M et al (2011) Cyclosporine A for chemotherapy-resistant subcutaneous panniculitis-like T-cell lymphoma with hemophagocytic syndrome. Acta Haematol 126(1):8–12

    Article  CAS  PubMed  Google Scholar 

  28. Rojnuckarin P, Nakorn TN, Assanasen T, Wannakrairot P, Intragumtornchai T (2007) Cyclosporin in subcutaneous panniculitis-like T-cell lymphoma. Leuk Lymphoma 48(3):560–3

    Article  CAS  PubMed  Google Scholar 

  29. Jung HR, Yun SY, Choi JH, Bae SH, Ryoo HM, Kum YS (2011) Cyclosporine in Relapsed Subcutaneous Panniculitis-like T-cell Lymphoma after Autologous Hematopoietic Stem Cell Transplantation. Cancer Res Treat. 43(4):255–9

    Article  PubMed  PubMed Central  Google Scholar 

  30. Gibson JF, Alpdogan O, Subtil A, Girardi M, Wilson LD, Roberts K et al (2015) Hematopoietic stem cell transplantation for primary cutaneous gammadelta T-cell lymphoma and refractory subcutaneous panniculitis-like T-cell lymphoma. J Am Acad Dermatol. 72(6):1010–5e5

    Google Scholar 

  31. Mukai HY, Okoshi Y, Shimizu S, Katsura Y, Takei N, Hasegawa Y et al (2003) Successful treatment of a patient with subcutaneous panniculitis-like T-cell lymphoma with high-dose chemotherapy and total body irradiation. Eur J Haematol 70(6):413–6

    Article  PubMed  Google Scholar 

  32. Reimer P, Rudiger T, Muller J, Rose C, Wilhelm M, Weissinger F (2003) Subcutaneous panniculitis-like T-cell lymphoma during pregnancy with successful autologous stem cell transplantation. Ann Hematol 82(5):305–9

    CAS  PubMed  Google Scholar 

  33. Nakahashi H, Tsukamoto N, Yamane A, Saitoh T, Uchiumi H, Handa H et al (2009) Autologous peripheral blood stem cell transplantation to treat CHOP-refractory aggressive subcutaneous panniculitis-like T-cell lymphoma. Acta Haematol 121(4):239–42

    Article  PubMed  Google Scholar 

  34. Sakurai E, Satoh T, Akiko YA, Maesawa C, Tsunoda K, Endo M et al (2013) Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) with hemophagocytosis (HPS): successful treatment using high-dose chemotherapy (BFM-NHL & ALL-90) and autologous peripheral blood stem cell transplantation. J Clin Exp Hematop. 53(2):135–40

    Article  PubMed  Google Scholar 

  35. Yuan L, Sun L, Bo J, Zhou Y, Li HH, Yu L et al (2011) Durable remission in a patient with refractory subcutaneous panniculitis-like T-cell lymphoma relapse after allogeneic hematopoietic stem cell transplantation through withdrawal of cyclosporine. Ann Transplant. 16(3):135–8

    Article  CAS  PubMed  Google Scholar 

  36. Ichii M, Hatanaka K, Imakita M, Ueda Y, Kishino B, Tamaki T (2006) Successful treatment of refractory subcutaneous panniculitis-like T-cell lymphoma with allogeneic peripheral blood stem cell transplantation from HLA-mismatched sibling donor. Leuk Lymphoma 47(10):2250–2

    Article  PubMed  Google Scholar 

  37. Guitart J, Weisenburger DD, Subtil A, Kim E, Wood G, Duvic M et al (2012) Cutaneous gammadelta T-cell lymphomas: a spectrum of presentations with overlap with other cytotoxic lymphomas. Am J Surg Pathol 36(11):1656–65

    Article  PubMed  Google Scholar 

  38. Vin H, Talpur R, Tetzlaff MT, Duvic M (2014) T-cell receptor-gamma in gamma-delta phenotype cutaneous T-cell lymphoma can be accompanied by atypical expression of CD30, CD4, or TCRbetaF1 and an indolent clinical course. Clin Lymphoma Myeloma Leuk 14(6):e195–200

    Article  PubMed  Google Scholar 

  39. Youn SH, Lee YW, Min SK, Park HR, Kim KH, Kim KJ (2011) Fatal Cutaneous gamma/delta T-cell Lymphoma with Central Nerve System Metastasis. Ann Dermatol 23(Suppl 1):S100–4

    Article  PubMed  PubMed Central  Google Scholar 

  40. Chakrapani A, Avery A, Warnke R (2013) Primary cutaneous gamma delta T-cell lymphoma with brain involvement and hemophagocytic syndrome. Am J Dermatopathol 35(2):270–2

    Article  PubMed  Google Scholar 

  41. Harrington L, Sokol L, Holdener S, Shao H, Zhang L (2014) Cutaneous gamma-delta T-cell lymphoma with central nervous system involvement: report of a rarity with review of literature. J Cutan Pathol 41(12):936–43

    Article  PubMed  Google Scholar 

  42. Toro JR, Beaty M, Sorbara L, Turner ML, White J, Kingma DW et al (2000) gamma delta T-cell lymphoma of the skin: a clinical, microscopic, and molecular study. Arch Dermatol 136(8):1024–32

    CAS  PubMed  Google Scholar 

  43. Kucuk C, Jiang B, Hu X, Zhang W, Chan JK, Xiao W et al (2015) Activating mutations of STAT5B and STAT3 in lymphomas derived from gammadelta-T or NK cells. Nat Commun. 6:6025

    Article  CAS  PubMed  Google Scholar 

  44. Trottestam H, Horne A, Arico M, Egeler RM, Filipovich AH, Gadner H et al (2011) Chemoimmunotherapy for hemophagocytic lymphohistiocytosis: long-term results of the HLH-94 treatment protocol. Blood 118(17):4577–84

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Kao GF, Resh B, McMahon C, Gojo I, Sun CC, Phillips D et al (2008) Fatal subcutaneous panniculitis-like T-cell lymphoma gamma/delta subtype (cutaneous gamma/delta T-cell lymphoma): report of a case and review of the literature. Am J Dermatopathol 30(6):593–9

    Article  PubMed  Google Scholar 

  46. Guan YK, Gan CC (2016) Primary Cutaneous T-cell Lymphoma (Gamma Delta subtype). Med J Malaysia 71(5):296–7

    CAS  PubMed  Google Scholar 

  47. Koch R, Jaffe ES, Mensing C, Zeis M, Schmitz N, Sander CA (2009) Cutaneous gamma/delta T-cell lymphoma. J Dtsch Dermatol Ges. 7(12):1065–7

    PubMed  PubMed Central  Google Scholar 

  48. Paralkar VR, Nasta SD, Morrissey K, Smith J, Vassilev P, Martin ME et al (2012) Allogeneic hematopoietic SCT for primary cutaneous T-cell lymphomas. Bone Marrow Transplant 47(7):940–5

    Article  CAS  PubMed  Google Scholar 

  49. Coiffier B, Pro B, Prince HM, Foss F, Sokol L, Greenwood M et al (2012) 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 30(6):631–6

    Article  CAS  PubMed  Google Scholar 

  50. Piekarz RL, Frye R, Prince HM, Kirschbaum MH, Zain J, Allen SL et al (2011) Phase 2 trial of romidepsin in patients with peripheral T-cell lymphoma. Blood 117(22):5827–34

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Sieniawski M, Angamuthu N, Boyd K, Chasty R, Davies J, Forsyth P et al (2010) Evaluation of enteropathy-associated T-cell lymphoma comparing standard therapies with a novel regimen including autologous stem cell transplantation. Blood 115(18):3664–70

    Article  CAS  PubMed  Google Scholar 

  52. Verbeek WH, Van De Water JM, Al-Toma A, Oudejans JJ, Mulder CJ, Coupe VM (2008) Incidence of enteropathy–associated T-cell lymphoma: a nation-wide study of a population-based registry in The Netherlands. Scand J Gastroenterol 43(11):1322–8

    Article  PubMed  Google Scholar 

  53. Delabie J, Holte H, Vose JM, Ullrich F, Jaffe ES, Savage KJ et al (2011) Enteropathy-associated T-cell lymphoma: clinical and histological findings from the international peripheral T-cell lymphoma project. Blood 118(1):148–55

    Article  CAS  PubMed  Google Scholar 

  54. Ellin F, Landstrom J, Jerkeman M, Relander T (2014) Real-world data on prognostic factors and treatment in peripheral T-cell lymphomas: a study from the Swedish Lymphoma Registry. Blood 124(10):1570–7

    Article  CAS  PubMed  Google Scholar 

  55. Gough KR, Read AE, Naish JM (1962) Intestinal reticulosis as a complication of idiopathic steatorrhoea. Gut 3:232–9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Ludvigsson JF, Leffler DA, Bai JC, Biagi F, Fasano A, Green PH et al (2013) The Oslo definitions for coeliac disease and related terms. Gut 62(1):43–52

    Article  PubMed  Google Scholar 

  57. Al-Toma A, Verbeek WH, Hadithi M, von Blomberg BM, Mulder CJ (2007) Survival in refractory coeliac disease and enteropathy-associated T-cell lymphoma: retrospective evaluation of single-centre experience. Gut 56(10):1373–8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Cellier C, Delabesse E, Helmer C, Patey N, Matuchansky C, Jabri B et al (2000) Refractory sprue, coeliac disease, and enteropathy-associated T-cell lymphoma. French Coeliac Disease Study Group. Lancet. 356(9225):203–8

    CAS  Google Scholar 

  59. Daum S, Weiss D, Hummel M, Ullrich R, Heise W, Stein H et al (2001) Frequency of clonal intraepithelial T lymphocyte proliferations in enteropathy-type intestinal T-cell lymphoma, coeliac disease, and refractory sprue. Gut 49(6):804–12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Farstad IN, Johansen FE, Vlatkovic L, Jahnsen J, Scott H, Fausa O et al (2002) Heterogeneity of intraepithelial lymphocytes in refractory sprue: potential implications of CD30 expression. Gut 51(3):372–8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Tack GJ, van Wanrooij RL, Langerak AW, Tjon JM, von Blomberg BM, Heideman DA et al (2012) Origin and immunophenotype of aberrant IEL in RCDII patients. Mol Immunol 50(4):262–70

    Article  CAS  PubMed  Google Scholar 

  62. Verbeek WH, Goerres MS, von Blomberg BM, Oudejans JJ, Scholten PE, Hadithi M et al (2008) Flow cytometric determination of aberrant intra-epithelial lymphocytes predicts T-cell lymphoma development more accurately than T-cell clonality analysis in Refractory Celiac Disease. Clin Immunol. 126(1):48–56

    Article  CAS  PubMed  Google Scholar 

  63. Kooy-Winkelaar YM, Bouwer D, Janssen GM, Thompson A, Brugman MH, Schmitz F et al (2017) CD4 T-cell cytokines synergize to induce proliferation of malignant and nonmalignant innate intraepithelial lymphocytes. Proc Natl Acad Sci U S A. 114(6):E980–E9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Gale J, Simmonds PD, Mead GM, Sweetenham JW, Wright DH (2000) Enteropathy-type intestinal T-cell lymphoma: clinical features and treatment of 31 patients in a single center. J Clin Oncol 18(4):795–803

    Article  CAS  PubMed  Google Scholar 

  65. Isaacson PG, Du MQ (2005) Gastrointestinal lymphoma: where morphology meets molecular biology. J Pathol. 205(2):255–74

    Article  CAS  PubMed  Google Scholar 

  66. Nijeboer P, de Baaij LR, Visser O, Witte BI, Cillessen SA, Mulder CJ et al (2015) Treatment response in enteropathy associated T-cell lymphoma; survival in a large multicenter cohort. Am J Hematol 90(6):493–8

    Article  PubMed  Google Scholar 

  67. Chan JK, Chan AC, Cheuk W, Wan SK, Lee WK, Lui YH et al (2011) Type II enteropathy-associated T-cell lymphoma: a distinct aggressive lymphoma with frequent gammadelta T-cell receptor expression. Am J Surg Pathol 35(10):1557–69

    Article  PubMed  Google Scholar 

  68. Mallant M, Hadithi M, Al-Toma AB, Kater M, Jacobs M, Manoliu R et al (2007) Abdominal computed tomography in refractory coeliac disease and enteropathy associated T-cell lymphoma. World J Gastroenterol 13(11):1696–700

    Article  PubMed  PubMed Central  Google Scholar 

  69. Hoffmann M, Vogelsang H, Kletter K, Zettinig G, Chott A, Raderer M (2003) 18F-fluoro-deoxy-glucose positron emission tomography (18F-FDG-PET) for assessment of enteropathy-type T-cell lymphoma. Gut 52(3):347–51

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Hadithi M, Mallant M, Oudejans J, van Waesberghe JH, Mulder CJ, Comans EF (2006) 18F-FDG PET versus CT for the detection of enteropathy-associated T-cell lymphoma in refractory celiac disease. J Nucl Med 47(10):1622–7

    PubMed  Google Scholar 

  71. Laird J, Leach M, Ballantyne S (2008) The value of small bowel magnetic resonance imaging in the management of enteropathy associated T-cell lymphoma. Br J Haematol 142(1):136–7

    Article  PubMed  Google Scholar 

  72. Tomita S, Kikuti YY, Carreras J, Kojima M, Ando K, Takasaki H et al (2015) Genomic and immunohistochemical profiles of enteropathy-associated T-cell lymphoma in Japan. Mod Pathol 28(10):1286–96

    Article  CAS  PubMed  Google Scholar 

  73. Zettl A, Ott G, Makulik A, Katzenberger T, Starostik P, Eichler T et al (2002) Chromosomal gains at 9q characterize enteropathy-type T-cell lymphoma. Am J Pathol 161(5):1635–45

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Deleeuw RJ, Zettl A, Klinker E, Haralambieva E, Trottier M, Chari R et al (2007) Whole-genome analysis and HLA genotyping of enteropathy-type T-cell lymphoma reveals 2 distinct lymphoma subtypes. Gastroenterology 132(5):1902–11

    Article  CAS  PubMed  Google Scholar 

  75. Nicolae A, Xi L, Pham TH, Pham TA, Navarro W, Meeker HG et al (2016) Mutations in the JAK/STAT and RAS signaling pathways are common in intestinal T-cell lymphomas. Leukemia 30(11):2245–7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Roberti A, Dobay MP, Bisig B, Vallois D, Boechat C, Lanitis E et al (2016) Type II enteropathy-associated T-cell lymphoma features a unique genomic profile with highly recurrent SETD2 alterations. Nat Commun. 7:12602

    Article  PubMed  PubMed Central  Google Scholar 

  77. Nairismagi ML, Tan J, Lim JQ, Nagarajan S, Ng CC, Rajasegaran V et al (2016) JAK-STAT and G-protein-coupled receptor signaling pathways are frequently altered in epitheliotropic intestinal T-cell lymphoma. Leukemia 30(6):1311–9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Irving J, Matheson E, Minto L, Blair H, Case M, Halsey C et al (2014) Ras pathway mutations are prevalent in relapsed childhood acute lymphoblastic leukemia and confer sensitivity to MEK inhibition. Blood 124(23):3420–30

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Gallamini A, Stelitano C, Calvi R, Bellei M, Mattei D, Vitolo U et al (2004) Peripheral T-cell lymphoma unspecified (PTCL-U): a new prognostic model from a retrospective multicentric clinical study. Blood 103(7):2474–9

    Article  CAS  PubMed  Google Scholar 

  80. de Baaij LR, Berkhof J, van de Water JM, Sieniawski MK, Radersma M, Verbeek WH et al (2015) A New and Validated Clinical Prognostic Model (EPI) for Enteropathy-Associated T-cell Lymphoma. Clin Cancer Res 21(13):3013–9

    Google Scholar 

  81. Daum S, Ullrich R, Heise W, Dederke B, Foss HD, Stein H et al (2003) Intestinal non-Hodgkin’s lymphoma: a multicenter prospective clinical study from the German Study Group on Intestinal non-Hodgkin’s Lymphoma. J Clin Oncol 21(14):2740–6

    Article  PubMed  Google Scholar 

  82. Wohrer S, Chott A, Drach J, Puspok A, Hejna M, Hoffmann M et al (2004) Chemotherapy with cyclophosphamide, doxorubicin, etoposide, vincristine and prednisone (CHOEP) is not effective in patients with enteropathy-type intestinal T-cell lymphoma. Ann Oncol 15(11):1680–3

    Article  CAS  PubMed  Google Scholar 

  83. Honemann D, Prince HM, Hicks RJ, Seymour JF (2005) Enteropathy-associated T-cell lymphoma without a prior diagnosis of coeliac disease: diagnostic dilemmas and management options. Ann Hematol 84(2):118–21

    Article  PubMed  Google Scholar 

  84. Novakovic BJ, Novakovic S, Frkovic-Grazio S (2006) A single-center report on clinical features and treatment response in patients with intestinal T-cell non-Hodgkin’s lymphomas. Oncol Rep 16(1):191–5

    PubMed  Google Scholar 

  85. Babel N, Paragi P, Chamberlain RS (2009) Management of Enteropathy-Associated T-cell Lymphoma: An Algorithmic Approach. Case Rep Oncol. 2(1):36–43

    Article  PubMed  PubMed Central  Google Scholar 

  86. Di Sabatino A, Biagi F, Gobbi PG, Corazza GR (2012) How I treat enteropathy-associated T-cell lymphoma. Blood 119(11):2458–68

    Article  PubMed  CAS  Google Scholar 

  87. Malamut G, Chandesris O, Verkarre V, Meresse B, Callens C, Macintyre E et al (2013) Enteropathy associated T-cell lymphoma in celiac disease: a large retrospective study. Dig Liver Dis. 45(5):377–84

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Egan LJ, Walsh SV, Stevens FM, Connolly CE, Egan EL, McCarthy CF (1995) Celiac-associated lymphoma. A single institution experience of 30 cases in the combination chemotherapy era. J Clin Gastroenterol 21(2):123–9

    Article  CAS  PubMed  Google Scholar 

  89. Tse E, Gill H, Loong F, Kim SJ, Ng SB, Tang T et al (2012) Type II enteropathy-associated T-cell lymphoma: a multicenter analysis from the Asia Lymphoma Study Group. Am J Hematol 87(7):663–8

    Article  PubMed  Google Scholar 

  90. Wierdsma NJ (2016) Nijeboer P, de van der Schueren MA, Berkenpas M, van Bodegraven AA, Mulder CJ. Refractory celiac disease and EATL patients show severe malnutrition and malabsorption at diagnosis. Clin Nutr 35(3):685–91

    Article  PubMed  Google Scholar 

  91. Di Sabatino A, Brunetti L, Carnevale Maffe G, Giuffrida P, Corazza GR (2013) Is it worth investigating splenic function in patients with celiac disease? World J Gastroenterol 19(15):2313–8

    Article  PubMed  PubMed Central  Google Scholar 

  92. Gritti G, Boschini C, Rossi A, Delaini F, Grassi A, Algarotti A et al (2015) Primary treatment response rather than front line stem cell transplantation is crucial for long term outcome of peripheral T-cell lymphomas. PLoS ONE 10(3):e0121822

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  93. Bishton MJ, Haynes AP (2007) Combination chemotherapy followed by autologous stem cell transplant for enteropathy-associated T-cell lymphoma. Br J Haematol 136(1):111–3

    Article  CAS  PubMed  Google Scholar 

  94. d’Amore F, Relander T, Lauritzsen GF, Jantunen E, Hagberg H, Anderson H et al (2012) Up-front autologous stem-cell transplantation in peripheral T-cell lymphoma: NLG-T-01. J Clin Oncol 30(25):3093–9

    Article  PubMed  CAS  Google Scholar 

  95. Jantunen E, Juvonen E, Wiklund T, Putkonen M, Nousiainen T (2003) High-dose therapy supported by autologous stem cell transplantation in patients with enteropathy-associated T-cell lymphoma. Leuk Lymphoma 44(12):2163–4

    Article  CAS  PubMed  Google Scholar 

  96. Al-Toma A, Verbeek WH, Visser OJ, Kuijpers KC, Oudejans JJ, Kluin-Nelemans HC et al (2007) Disappointing outcome of autologous stem cell transplantation for enteropathy-associated T-cell lymphoma. Dig Liver Dis. 39(7):634–41

    Article  CAS  PubMed  Google Scholar 

  97. Rongey C, Micallef I, Smyrk T, Murray J (2006) Successful treatment of enteropathy-associated T-cell lymphoma with autologous stem cell transplant. Dig Dis Sci 51(6):1082–6

    Article  PubMed  Google Scholar 

  98. Okuda M, Nomura J, Tateno H, Kameoka J, Sasaki T (2002) CD56 positive intestinal T-cell lymphoma: treatment with high dose chemotherapy and autologous peripheral blood stem cell transplantation. Intern Med 41(9):734–7

    Article  PubMed  Google Scholar 

  99. Jantunen E, Boumendil A, Finel H, Luan JJ, Johnson P, Rambaldi A et al (2013) Autologous stem cell transplantation for enteropathy-associated T-cell lymphoma: a retrospective study by the EBMT. Blood 121(13):2529–32

    Article  CAS  PubMed  Google Scholar 

  100. Chonabayashi K, Kondo T, Tanaka Y, Ichinohe T, Ishikawa T, Uchiyama T (2007) Sustained complete remission of refractory enteropathy-type T-cell lymphoma following reduced-intensity unrelated cord blood transplantation. Bone Marrow Transplant 40(9):905–6

    Article  CAS  PubMed  Google Scholar 

  101. Nava VE, Cohen P, Bishop M, Fowler D, Jaffe ES, Ozdemirli M (2007) Enteropathy-type T-cell lymphoma after intestinal diffuse large B-cell lymphoma. Am J Surg Pathol 31(3):476–80

    Article  PubMed  Google Scholar 

  102. Regelink JC, Tack GJ, Huijgens PC, Mulder CJ, Janssen JJ, Visser O (2010) Disappointing outcome of allogeneic hematopoietic SCT in two EATL patients. Bone Marrow Transplant 45(5):959–60

    Article  CAS  PubMed  Google Scholar 

  103. Toumishey E, Prasad A, Dueck G, Chua N, Finch D, Johnston J et al (2015) Final report of a phase 2 clinical trial of lenalidomide monotherapy for patients with T-cell lymphoma. Cancer 121(5):716–23

    Article  CAS  PubMed  Google Scholar 

  104. Morschhauser F, Fitoussi O, Haioun C, Thieblemont C, Quach H, Delarue R et al (2013) 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 49(13):2869–76

    Article  CAS  PubMed  Google Scholar 

  105. Gallamini A, Zaja F, Patti C, Billio A, Specchia MR, Tucci A et al (2007) Alemtuzumab (Campath-1H) and CHOP chemotherapy as first-line treatment of peripheral T-cell lymphoma: results of a GITIL (Gruppo Italiano Terapie Innovative nei Linfomi) prospective multicenter trial. Blood 110(7):2316–23

    Article  CAS  PubMed  Google Scholar 

  106. Kircher SM, Gurbuxani S, Smith SM (2007) CHOP plus alemtuzumab can induce metabolic response by FDG-PET but has minimal long-term benefits: a case report and literature review. J Gastrointest Cancer. 38(1):59–62

    Article  PubMed  Google Scholar 

  107. Soldini D, Mora O, Cavalli F, Zucca E, Mazzucchelli L (2008) Efficacy of alemtuzumab and gemcitabine in a patient with enteropathy-type T-cell lymphoma. Br J Haematol 142(3):484–6

    Article  PubMed  Google Scholar 

  108. Ferreri AJ, Zinzani PL, Govi S, Pileri SA (2011) Enteropathy-associated T-cell lymphoma. Crit Rev Oncol Hematol 79(1):84–90

    Article  PubMed  Google Scholar 

  109. Raderer M, Troch M, Kiesewetter B, Puspok A, Jaeger U, Hoffmann M et al (2012) Second line chemotherapy in patients with enteropathy-associated T-cell lymphoma: a retrospective single center analysis. Ann Hematol 91(1):57–61

    Article  CAS  PubMed  Google Scholar 

  110. Berti E, Tomasini D, Vermeer MH, Meijer CJ, Alessi E, Willemze R (1999) Primary cutaneous CD8-positive epidermotropic cytotoxic T-cell lymphomas. A distinct clinicopathological entity with an aggressive clinical behavior. Am J Pathol 155(2):483–92

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Nofal A, Abdel-Mawla MY, Assaf M, Salah E (2012) Primary cutaneous aggressive epidermotropic CD8 + T-cell lymphoma: proposed diagnostic criteria and therapeutic evaluation. J Am Acad Dermatol 67(4):748–59

    Article  PubMed  Google Scholar 

  112. Diwan H, Ivan D (2009) CD8-positive mycosis fungoides and primary cutaneous aggressive epidermotropic CD8-positive cytotoxic T-cell lymphoma. J Cutan Pathol 36(3):390–2

    Article  PubMed  Google Scholar 

  113. Wobser M, Reinartz T, Roth S, Goebeler M, Rosenwald A, Geissinger E (2016) Cutaneous CD8 + Cytotoxic T-cell Lymphoma Infiltrates: Clinicopathological Correlation and Outcome of 35 Cases. Oncol Ther. 4(2):199–210

    Article  PubMed  Google Scholar 

  114. Gormley RH, Hess SD, Anand D, Junkins-Hopkins J, Rook AH, Kim EJ (2010) Primary cutaneous aggressive epidermotropic CD8 + T-cell lymphoma. J Am Acad Dermatol 62(2):300–7

    Article  PubMed  Google Scholar 

  115. Liu V, Cutler CS, Young AZ (2007) Case records of the Massachusetts General Hospital. Case 38-2007. A 44-year-old woman with generalized, painful, ulcerated skin lesions. N Engl J Med 357(24):2496–505

    Article  CAS  PubMed  Google Scholar 

  116. Introcaso CE, Leber B, Greene K, Ubriani R, Rook AH, Kim EJ (2008) Stem cell transplantation in advanced cutaneous T-cell lymphoma. J Am Acad Dermatol 58(4):645–9

    Article  PubMed  Google Scholar 

  117. Santucci M, Pimpinelli N, Massi D, Kadin ME, Meijer CJ, Muller-Hermelink HK et al (2003) Cytotoxic/natural killer cell cutaneous lymphomas. Report of EORTC Cutaneous Lymphoma Task Force Workshop. Cancer 97(3):610–27

    Article  PubMed  Google Scholar 

  118. Petrella T, Maubec E, Cornillet-Lefebvre P, Willemze R, Pluot M, Durlach A et al (2007) Indolent CD8-positive lymphoid proliferation of the ear: a distinct primary cutaneous T-cell lymphoma? Am J Surg Pathol 31(12):1887–92

    Article  PubMed  Google Scholar 

  119. Li XQ, Zhou XY, Sheng WQ, Xu YX, Zhu XZ (2009) Indolent CD8 + lymphoid proliferation of the ear: a new entity and possible occurrence of signet ring cells. Histopathology 55(4):468–70

    Article  PubMed  Google Scholar 

  120. Swick BL, Baum CL, Venkat AP, Liu V (2011) Indolent CD8 + lymphoid proliferation of the ear: report of two cases and review of the literature. J Cutan Pathol 38(2):209–15

    Article  PubMed  Google Scholar 

  121. Geraud C, Goerdt S, Klemke CD (2011) Primary cutaneous CD8 + small/medium-sized pleomorphic T-cell lymphoma, ear-type: a unique cutaneous T-cell lymphoma with a favourable prognosis. Br J Dermatol 164(2):456–8

    Article  CAS  PubMed  Google Scholar 

  122. Zeng W, Nava VE, Cohen P, Ozdemirli M (2012) Indolent CD8-positive T-cell lymphoid proliferation of the ear: a report of two cases. J Cutan Pathol 39(7):696–700

    Article  PubMed  Google Scholar 

  123. Valois A, Bastien C, Granel-Broca F, Cuny JF, Barbaud A, Schmutz JL (2012) Indolent lymphoma of the ear. Ann Dermatol Venereol 139(12):818–23

    Article  CAS  PubMed  Google Scholar 

  124. Suchak R, O’Connor S, McNamara C, Robson A (2010) Indolent CD8-positive lymphoid proliferation on the face: part of the spectrum of primary cutaneous small-/medium-sized pleomorphic T-cell lymphoma or a distinct entity? J Cutan Pathol 37(9):977–81

    Article  PubMed  Google Scholar 

  125. Ryan AJ, Robson A, Hayes BD, Sheahan K, Collins P (2010) Primary cutaneous peripheral T-cell lymphoma, unspecified with an indolent clinical course: a distinct peripheral T-cell lymphoma? Clin Exp Dermatol 35(8):892–6

    Article  CAS  PubMed  Google Scholar 

  126. Greenblatt D, Ally M, Child F, Scarisbrick J, Whittaker S, Morris S et al (2013) Indolent CD8(+) lymphoid proliferation of acral sites: a clinicopathologic study of six patients with some atypical features. J Cutan Pathol 40(2):248–58

    Article  PubMed  Google Scholar 

  127. Butsch F, Kind P, Brauninger W (2012) Bilateral indolent epidermotropic CD8-positive lymphoid proliferations of the ear. J Dtsch Dermatol Ges. 10(3):195–6

    PubMed  Google Scholar 

  128. Beltraminelli H, Mullegger R, Cerroni L (2010) Indolent CD8 + lymphoid proliferation of the ear: a phenotypic variant of the small-medium pleomorphic cutaneous T-cell lymphoma? J Cutan Pathol 37(1):81–4

    Article  PubMed  Google Scholar 

  129. Milley S, Bories N, Balme B, Thomas L, Dalle S (2012) Indolent CD8 + lymphoid proliferation on the nose. Ann Dermatol Venereol 139(12):812–7

    Article  CAS  PubMed  Google Scholar 

  130. Wobser M, Petrella T, Kneitz H, Kerstan A, Goebeler M, Rosenwald A et al (2013) Extrafacial indolent CD8-positive cutaneous lymphoid proliferation with unusual symmetrical presentation involving both feet. J Cutan Pathol 40(11):955–61

    Article  PubMed  Google Scholar 

  131. Kempf W, Kazakov DV, Cozzio A, Kamarashev J, Kerl K, Plaza T et al (2013) Primary cutaneous CD8(+) small- to medium-sized lymphoproliferative disorder in extrafacial sites: clinicopathologic features and concept on their classification. Am J Dermatopathol 35(2):159–66

    Article  PubMed  Google Scholar 

  132. Hagen JW, Magro CM (2014) Indolent CD8 + lymphoid proliferation of the face with eyelid involvement. Am J Dermatopathol 36(2):137–41

    PubMed  Google Scholar 

  133. Wobser M, Roth S, Reinartz T, Rosenwald A, Goebeler M, Geissinger E (2015) CD68 expression is a discriminative feature of indolent cutaneous CD8-positive lymphoid proliferation and distinguishes this lymphoma subtype from other CD8-positive cutaneous lymphomas. Br J Dermatol 172(6):1573–80

    Article  CAS  PubMed  Google Scholar 

  134. Kluk J, Kai A, Koch D, Taibjee SM, O’Connor S, Persic M et al (2016) Indolent CD8-positive lymphoid proliferation of acral sites: three further cases of a rare entity and an update on a unique patient. J Cutan Pathol 43(2):125–36

    Article  PubMed  Google Scholar 

  135. Beltraminelli H, Leinweber B, Kerl H, Cerroni L (2009) Primary cutaneous CD4 + small-/medium-sized pleomorphic T-cell lymphoma: a cutaneous nodular proliferation of pleomorphic T lymphocytes of undetermined significance? A study of 136 cases. Am J Dermatopathol 31(4):317–22

    Article  PubMed  Google Scholar 

  136. Choi M, Park SY, Park HS, Byun HJ, Cho KH (2011) A Case of Primary Cutaneous CD4 Positive Small/medium T-cell Lymphoma. Ann Dermatol 23(1):76–80

    Article  PubMed  PubMed Central  Google Scholar 

  137. Beljaards RC, Meijer CJ, Van der Putte SC, Hollema H, Geerts ML, Bezemer PD et al (1994) Primary cutaneous T-cell lymphoma: clinicopathological features and prognostic parameters of 35 cases other than mycosis fungoides and CD30-positive large cell lymphoma. J Pathol. 172(1):53–60

    Article  CAS  PubMed  Google Scholar 

  138. Rodriguez Pinilla SM, Roncador G, Rodriguez-Peralto JL, Mollejo M, Garcia JF, Montes-Moreno S et al (2009) Primary cutaneous CD4 + small/medium-sized pleomorphic T-cell lymphoma expresses follicular T-cell markers. Am J Surg Pathol 33(1):81–90

    Article  PubMed  Google Scholar 

  139. Ally MS, Prasad Hunasehally RY, Rodriguez-Justo M, Martin B, Verdolini R, Attard N et al (2013) Evaluation of follicular T-helper cells in primary cutaneous CD4 + small/medium pleomorphic T-cell lymphoma and dermatitis. J Cutan Pathol 40(12):1006–13

    Article  PubMed  Google Scholar 

  140. Battistella M, Beylot-Barry M, Bachelez H, Rivet J, Vergier B, Bagot M (2012) Primary cutaneous follicular helper T-cell lymphoma: a new subtype of cutaneous T-cell lymphoma reported in a series of 5 cases. Arch Dermatol 148(7):832–9

    Article  PubMed  Google Scholar 

  141. von den Driesch P, Coors EA (2002) Localized cutaneous small to medium-sized pleomorphic T-cell lymphoma: a report of 3 cases stable for years. J Am Acad Dermatol 46(4):531–5

    Article  PubMed  Google Scholar 

  142. James E, Sokhn JG, Gibson JF, Carlson K, Subtil A, Girardi M et al (2015) CD4 + primary cutaneous small/medium-sized pleomorphic T-cell lymphoma: a retrospective case series and review of literature. Leuk Lymphoma 56(4):951–7

    Article  CAS  PubMed  Google Scholar 

  143. Grogg KL, Jung S, Erickson LA, McClure RF, Dogan A (2008) Primary cutaneous CD4-positive small/medium-sized pleomorphic T-cell lymphoma: a clonal T-cell lymphoproliferative disorder with indolent behavior. Mod Pathol 21(6):708–15

    Article  CAS  PubMed  Google Scholar 

  144. Garcia-Herrera A, Colomo L, Camos M, Carreras J, Balague O, Martinez A et al (2008) Primary cutaneous small/medium CD4 + T-cell lymphomas: a heterogeneous group of tumors with different clinicopathologic features and outcome. J Clin Oncol 26(20):3364–71

    Article  PubMed  Google Scholar 

  145. Buder K, Poppe LM, Brocker EB, Goebeler M, Rosenwald A, Geissinger E et al (2013) Primary cutaneous follicular helper T-cell lymphoma: diagnostic pitfalls of this new lymphoma subtype. J Cutan Pathol 40(10):903–8

    PubMed  Google Scholar 

  146. Ohmatsu H, Sugaya M, Fujita H, Kadono T, Sato S (2014) Primary cutaneous follicular helper T-cell lymphoma treated with allogeneic bone marrow transplantation: immunohistochemical comparison with angioimmunoblastic T-cell lymphoma. Acta Derm Venereol 94(1):54–7

    Article  PubMed  Google Scholar 

  147. Shamsuyarova A, Kamil Z, Delabie J, Al-Faraidy N, Ghazarian D (2017) Primary Cutaneous Follicular Helper T-cell Lymphoma in a Patient With Neurofibromatosis Type 1: Case Report and Review of the Literature. Am J Dermatopathol 39(2):134–9

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to C. van der Weyden .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

van der Weyden, C., McCormack, C., Lade, S., Johnstone, R.W., Prince, H.M. (2019). Rare T-Cell Subtypes. In: Querfeld, C., Zain, J., Rosen, S. (eds) T-Cell and NK-Cell Lymphomas. Cancer Treatment and Research, vol 176. Springer, Cham. https://doi.org/10.1007/978-3-319-99716-2_10

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-99716-2_10

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-99715-5

  • Online ISBN: 978-3-319-99716-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics