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13.01.2020 | Lymphome | CME Zertifizierte Fortbildung

Kutane Lymphome

Klinik – Diagnostik – Therapie

verfasst von: PD Dr. Marion Wobser, Prof. Dr. Matthias Goebeler

Erschienen in: Die Pathologie | Ausgabe 1/2020

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Zusammenfassung

Kutane Lymphome umfassen prognostisch heterogene Subgruppen. Die Mycosis fungoides ist das häufigste Hautlymphom und weist einen stadienhaften Verlauf (Patches, Plaques, Tumoren, Erythrodermie) auf. Zu den Behandlungsoptionen zählen in frühen Stadien hautgerichtete Therapiemaßnahmen, während in fortgeschrittenen Stadien und beim Sézary-Syndrom Systemtherapien mit z. B. Bexaroten, Interferon oder Brentuximab vedotin indiziert sind. Seltenere T‑Zell-Lymphome wie die CD4-positive Lymphoproliferation oder das akrale CD8-positive Lymphom zeigen im Gegensatz zu den aggressiven peripheren T‑Zell-Lymphomen einen indolenten Verlauf. Auch innerhalb der kutanen B‑Zell-Lymphome finden sich prognostisch differente Entitäten: Während die Lebenserwartung bei kutanem Marginalzonenlymphom und kutanem follikulärem B‑Zell-Lymphom nahezu nicht beeinträchtigt ist, zeigt das kutane großzellige B‑Zell-Lymphom ein hohes Risiko einer systemischen Disseminierung mit vergleichsweise hoher Letalität.

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):2375–2390PubMedPubMedCentral

Dippel E, Assaf C, Becker JC, von Bergwelt-Baildon M, Beyer M, Cozzio A et al (2017) S2k guidelines—Cutaneous lymphomas update 2016—Part 1: Classification and diagnosis (ICD10 C82–C86). J Dtsch Dermatol Ges 15(12):1266–1273PubMed

Nicolay JP, Assaf C (2017) Treatment of mycosis fungoides and Sézary syndrome. Hautarzt 68(9):702–710PubMed

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):317–322PubMed

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):955–961PubMed

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):1573–1580PubMed

Bekkenk MW, Vermeer MH, Jansen PM, van Marion AMW, Canninga-van Dijk MR, Kluin PM et al (2003) Peripheral T‑cell lymphomas unspecified presenting in the skin: Analysis of prognostic factors in a group of 82 patients. Blood 102(6):2213–2219PubMed

Dippel E, Assaf C, Becker JC, von Bergwelt-Baildon M, Beyer M, Cozzio A et al (2018) S2k guidelines—Cutaneous lymphomas update 2016—Part 2: Treatment and follow-up (ICD10 C82–C86). J Dtsch Dermatol Ges 16(1):112–122PubMed

Stranzenbach R, Theurich S, Schlaak M (2017) Role of stem cell transplantation in treatment of primary cutaneous T‑cell lymphoma. Hautarzt 68(9):716–720PubMed

10.

Hughes CFM, Khot A, McCormack C, Lade S, Westerman DA, Twigger R et al (2015) Lack of durable disease control with chemotherapy for mycosis fungoides and Sézary syndrome: A comparative study of systemic therapy. Blood 125(1):71–81PubMed

11.

Humme D, Nast A, Erdmann R, Vandersee S, Beyer M (2014) Systematic review of combination therapies for mycosis fungoides. Cancer Treat Rev 40(8):927–933PubMed

12.

Weberschock T, Strametz R, Lorenz M, Röllig C, Bunch C, Bauer A et al (2012) Interventions for mycosis fungoides. Cochrane Database Syst Rev 9:CD8946

13.

Argnani L, Broccoli A, Zinzani PL (2017) Cutaneous T‑cell lymphomas: Focusing on novel agents in relapsed and refractory disease. Cancer Treat Rev 61:61–69PubMed

14.

Bagot M (2017) New targeted treatments for cutaneous T‑cell lymphomas. Indian J Dermatol 62(2):142–145PubMedPubMedCentral

15.

Duvic M, Tetzlaff MT, Gangar P, Clos AL, Sui D, Talpur R (2015) Results of a phase II trial of brentuximab vedotin for CD30+ cutaneous T‑cell lymphoma and lymphomatoid papulosis. J Clin Oncol 33(32):3759–3765PubMedPubMedCentral

16.

Kim YH, Tavallaee M, Sundram U, Salva KA, Wood GS, Li S et al (2015) Phase II investigator-initiated study of brentuximab vedotin in mycosis fungoides and Sézary syndrome with variable CD30 expression level: A multi-institution collaborative project. J Clin Oncol 33(32):3750–3758PubMedPubMedCentral

17.

Prince HM, Kim YH, Horwitz SM, Dummer R, Scarisbrick J, Quaglino P et al (2017) Brentuximab vedotin or physician’s choice in CD30-positive cutaneous T‑cell lymphoma (ALCANZA): An international, open-label, randomised, phase 3, multicentre trial. Lancet 390(10094):555–566PubMed

18.

Wilcox RA (2015) Mogamulizumab: 2 birds, 1 stone. Blood 125(12):1847–1848PubMed

19.

Yano H, Ishida T, Inagaki A, Ishii T, Ding J, Kusumoto S et al (2007) Defucosylated anti CC chemokine receptor 4 monoclonal antibody combined with immunomodulatory cytokines: A novel immunotherapy for aggressive/refractory Mycosis fungoides and Sezary syndrome. Clin Cancer Res 13(21):6494–6500PubMed

20.

Duvic M, Pinter-Brown LC, Foss FM, Sokol L, Jorgensen JL, Challagundla P et al (2015) Phase 1/2 study of mogamulizumab, a defucosylated anti-CCR4 antibody, in previously treated patients with cutaneous T‑cell lymphoma. Blood 125(12):1883–1889PubMedPubMedCentral

21.

Querfeld C, Rosen ST, Guitart J, Duvic M, Kim YH, Dusza SW et al (2014) Results of an open-label multicenter phase 2 trial of lenalidomide monotherapy in refractory mycosis fungoides and Sézary syndrome. Blood 123(8):1159–1166PubMed

22.

Lesokhin AM, Ansell SM, Armand P, Scott EC, Halwani A, Gutierrez M et al (2016) Nivolumab in patients with relapsed or refractory hematologic malignancy: Preliminary results of a phase Ib study. J Clin Oncol 34(23):2698–2704PubMedPubMedCentral

23.

Cetinözman F, Jansen PM, Vermeer MH, Willemze R (2012) Differential expression of programmed death‑1 (PD-1) in Sézary syndrome and mycosis fungoides. Arch Dermatol 148(12):1379–1385PubMed

24.

Veillette A, Chen J (2018) SIRPα-CD47 immune checkpoint blockade in anticancer therapy. Trends Immunol 39(3):173–184. https://doi.org/10.1016/j.it.2017.12.005 CrossRefPubMed

25.

Wilcox RA (2016) Cutaneous T‑cell lymphoma: 2016 update on diagnosis, risk-stratification, and management. Am J Hematol 91(1):151–165PubMed

26.

Iqbal J, Wilcox R, Naushad H, Rohr J, Heavican TB, Wang C et al (2016) Genomic signatures in T‑cell lymphoma: How can these improve precision in diagnosis and inform prognosis? Blood Rev 30(2):89–100. https://doi.org/10.1016/j.blre.2015.08.003 CrossRefPubMed

27.

Ungewickell A, Bhaduri A, Rios E, Reuter J, Lee CS, Mah A et al (2015) Genomic analysis of mycosis fungoides and Sézary syndrome identifies recurrent alterations in TNFR2. Nat Genet 47(9):1056–1060PubMedPubMedCentral

28.

McGirt LY, Jia P, Baerenwald DA, Duszynski RJ, Dahlman KB, Zic JA et al (2015) Whole-genome sequencing reveals oncogenic mutations in mycosis fungoides. Blood 126(4):508–519PubMedPubMedCentral

29.

Wang L, Ni X, Covington KR, Yang BY, Shiu J, Zhang X et al (2015) Genomic profiling of Sézary syndrome identifies alterations of key T cell signaling and differentiation genes. Nat Genet 47(12):1426–1434PubMedPubMedCentral

30.

Nicolay JP, Müller-Decker K, Schroeder A, Brechmann M, Möbs M, Géraud C et al (2016) Dimethyl fumarate restores apoptosis sensitivity and inhibits tumor growth and metastasis in CTCL by targeting NF-κB. Blood 128(6):805–815PubMedPubMedCentral

31.

Prince HM, Dickinson M (2012) Romidepsin for cutaneous T‑cell lymphoma. Clin Cancer Res 18(13):3509–3515PubMed

32.

Sawas A, Radeski D, O’Connor OA (2015) Belinostat in patients with refractory or relapsed peripheral T‑cell lymphoma: A perspective review. Ther Adv Hematol 6(4):202–208PubMedPubMedCentral

33.

Vaqué JP, Gómez-López G, Monsálvez V, Varela I, Martínez N, Pérez C et al (2014) PLCG1 mutations in cutaneous T‑cell lymphomas. Blood 123(13):2034–2043PubMed

34.

Rallis E, Economidi A, Verros C, Papadakis P (2006) Successful treatment of patch type mycosis fungoides with tacrolimus ointment 0.1%. J Drugs Dermatol 5(9):906–907PubMed

35.

Martínez-González MC, Verea-Hernando MM, Yebra-Pimentel MT, Del Pozo J, Mazaira M, Fonseca E (2008) Imiquimod in mycosis fungoides. Eur J Dermatol 18(2):148–152PubMed

36.

Rook AH, Gelfand JC, Wysocka M, Troxel AB, Benoit B, Surber C et al (2015) Topical resiquimod can induce disease regression and enhance T‑cell effector functions in cutaneous T‑cell lymphoma. Blood 126(12):1452–1461PubMedPubMedCentral

37.

Lessin SR, Duvic M, Guitart J, Pandya AG, Strober BE, Olsen EA et al (2013) Topical chemotherapy in cutaneous T‑cell lymphoma: Positive results of a randomized, controlled, multicenter trial testing the efficacy and safety of a novel mechlorethamine, 0.02 %, gel in mycosis fungoides. JAMA Dermatol 149(1):25–32PubMedPubMedCentral

38.

Kim YH, Jensen RA, Watanabe GL, Varghese A, Hoppe RT (1996) Clinical stage IA (limited patch and plaque) mycosis fungoides. A long-term outcome analysis. Arch Dermatol 132(11):1309–1313PubMed

39.

Maurus K, Appenzeller S, Roth S, Kuper J, Rost S, Meierjohann S et al (2018) Panel sequencing shows recurrent genetic FAS alterations in primary cutaneous marginal zone lymphoma. J Invest Dermatol 138(7):1573–1581PubMed

40.

Wobser M (2017) Treatment of indolent cutaneous B‑cell lymphoma. Hautarzt 68(9):721–726PubMed

41.

Lamos C, Dippel E (2017) Aggressive primary cutaneous B‑cell lymphomas and novel EBV+ entities. Hautarzt 68(9):727–739PubMed

42.

Nicolay JP, Wobser M (2016) B‑Zell-Lymphome der Haut – Pathogenese, Diagnostik und Therapie. J Dtsch Dermatol Ges 14(12):1207–1225PubMed

43.

Kodama K, Massone C, Chott A, Metze D, Kerl H, Cerroni L (2005) Primary cutaneous large B‑cell lymphomas: Clinicopathologic features, classification, and prognostic factors in a large series of patients. Blood 106(7):2491–2497PubMed

44.

Senff NJ, Hoefnagel JJ, Jansen PM, Vermeer MH, van Baarlen J, Blokx WA et al (2007) Reclassification of 300 primary cutaneous B‑Cell lymphomas according to the new WHO-EORTC classification for cutaneous lymphomas: Comparison with previous classifications and identification of prognostic markers. J Clin Oncol 25(12):1581–1587PubMed

45.

Grange F, Bekkenk MW, Wechsler J, Meijer CJ, Cerroni L, Bernengo M et al (2001) Prognostic factors in primary cutaneous large B‑cell lymphomas: A European multicenter study. J Clin Oncol 19(16):3602–3610PubMed

46.

Grange F, Joly P, Barbe C, Bagot M, Dalle S, Ingen-Housz-Oro S et al (2014) Improvement of survival in patients with primary cutaneous diffuse large B‑cell lymphoma, leg type, in France. JAMA Dermatol 150(5):535–541PubMed

47.

Byrd JC, Flynn JM, Kipps TJ, Boxer M, Kolibaba KS, Carlile DJ et al (2016) Randomized phase 2 study of obinutuzumab monotherapy in symptomatic, previously untreated chronic lymphocytic leukemia. Blood 127(1):79–86PubMedPubMedCentral

48.

Gupta IV, Jewell RC (2012) Ofatumumab, the first human anti-CD20 monoclonal antibody for the treatment of B cell hematologic malignancies. Ann N Y Acad Sci 1263:43–56PubMed

49.

Fang C, Zhu D, Dong H, Ji M, Wu J, Xu X et al (2015) Lenalidomide alone or in combination with chemotherapy treatment for subtypes of diffuse large B cell lymphoma: A systematic review and meta-analysis. Int J Clin Exp Med 8(7):10705–10713PubMedPubMedCentral

50.

Zinzani PL, Corradini P, Martelli M, Minotti G, Oliva S, Spina M et al (2016) Critical concepts, practice recommendations, and research perspectives of pixantrone therapy in non-Hodgkin lymphoma: A SIE, SIES, and GITMO consensus paper. Eur J Haematol 97(6):554–561PubMed

51.

Bohers E, Mareschal S, Bouzelfen A, Marchand V, Ruminy P, Maingonnat C et al (2014) Targetable activating mutations are very frequent in GCB and ABC diffuse large B‑cell lymphoma. Genes Chromosomes Cancer 53(2):144–153PubMed

52.

Pham-Ledard A, Prochazkova-Carlotti M, Andrique L, Cappellen D, Vergier B, Martinez F et al (2014) Multiple genetic alterations in primary cutaneous large B‑cell lymphoma, leg type support a common lymphomagenesis with activated B‑cell-like diffuse large B‑cell lymphoma. Mod Pathol 27(3):402–411PubMed

53.

Menguy S, Gros A, Pham-Ledard A, Battistella M, Ortonne N, Comoz F et al (2016) MYD88 somatic mutation is a diagnostic criterion in primary cutaneous large B‑cell lymphoma. J Invest Dermatol 136(8):1741–1744. https://doi.org/10.1016/j.jid.2016.04.018 CrossRefPubMed

54.

Koens L, Zoutman WH, Ngarmlertsirichai P, Przybylski GK, Grabarczyk P, Vermeer MH et al (2014) Nuclear factor-κB pathway-activating gene aberrancies in primary cutaneous large B‑cell lymphoma, leg type. J Invest Dermatol 134(1):290–292PubMed

55.

Mareschal S, Pham-Ledard A, Viailly PJ, Dubois S, Bertrand P, Maingonnat C et al (2017) Identification of somatic mutations in primary cutaneous diffuse large B‑cell lymphoma, leg type by massive parallel sequencing. J Invest Dermatol 137(9):1984–1994PubMed

56.

Jardin F (2014) Next generation sequencing and the management of diffuse large B‑cell lymphoma: From whole exome analysis to targeted therapy. Discov Med 18(97):51–65PubMed

57.

Sehn LH, Gascoyne RD (2015) Diffuse large B‑cell lymphoma: Optimizing outcome in the context of clinical and biologic heterogeneity. Blood 125(1):22–32PubMed

58.

Gupta E, Accurso J, Sluzevich J, Menke DM, Tun HW (2015) Excellent outcome of immunomodulation or Bruton’s tyrosine kinase inhibition in highly refractory primary cutaneous diffuse large B‑cell lymphoma, leg type. Rare Tumors 7(4):6067PubMedPubMedCentral

Titel: Kutane Lymphome
Klinik – Diagnostik – Therapie
verfasst von: PD Dr. Marion Wobser
Prof. Dr. Matthias Goebeler
Publikationsdatum: 13.01.2020
Verlag: Springer Medizin
Schlagwörter: Lymphome
Non-Hodgkin-Lymphome
Zielgerichtete Therapie
Mycosis fungoides
Sezary-Syndrom
Erythrodermien
Lymphomatoide Papulose
Brentuximab vedotin
Erschienen in: Die Pathologie / Ausgabe 1/2020
Print ISSN: 2731-7188
Elektronische ISSN: 2731-7196
DOI: https://doi.org/10.1007/s00292-019-00743-1

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