Case Report

Refractory Hydroa Vacciniforme-Like Lymphoma: Biological Insights from Morphoproteomic Analysis

Abstract

T-cell/natural killer cell lymphoproliferative disorders are rare, associated with poor overall survival, and have limited treatment options. We report a case of a patient who developed hydroa vacciniforme-like lymphoma (HVLL, an EBV-peripheral T-cell lymphoma), refractory to multiple lines of systemic therapy including methotrexate, mycophenolate mofetil, dapsone, thalidomide, prednisone, and romidepsin. We conducted morphoproteomic analysis of the patient’s tumor which provided important biological insights. Histopathology showed primarily lymphohistiocytic infiltrates strongly positive EBV expression with a Ki-67 of >50% in the pretreatment biopsy and approximately 90% in the post-treatment biopsy, strong expression of Enhancer of Zester Homolog 2 (EZH2), a constitutively active mTOR pathway, 50% cytoplasmic BCL-2 expression; largely negative PD-1 positive CD8 T-cells. Based on this morphoproteomic analysis and published literature, we postulated that novel agents including venetoclax, tazemetostat, and other agents may provide a targeted approach for treating HVLL. This case illustrates the use of morphoproteomic analysis to better understand the biology of tumors.

 

1. Carbone A, Gloghini A, Dotti G. EBV-associated lymphoproliferative disorders: classification and treatment. Oncologist. 2008;13(5):577-85.
2. Gupta G, Man I, Kemmett D. Hydroa vacciniforme: A clinical and follow-up study of 17 cases. J Am Acad Dermatol. 2000;42(2 Pt 1):208-13.
3. Magaña M, Sangüeza P, Gil-Beristain J, et al. Angiocentric cutaneous T-cell lymphoma of childhood (hydroa-like lymphoma): a distinctive type of cutaneous T-cell lymphoma. J Am Acad Dermatol. 1998;38(4):574-9.
4. Barrionuevo C, Anderson VM, Zevallos-Giampietri E, et al. Hydroa-like cutaneous T-cell lymphoma: a clinicopathologic and molecular genetic study of 16 pediatric cases from Peru. Appl Immunohistochem Mol Morphol. 2002;10(1):7-14.
5. Doeden K, Molina-Kirsch H, Perez E, et al. Hydroa-like lymphoma with CD56 expression. J Cutan Pathol. 2008;35(5):488-94.
6. Quesada AE, Nguyen ND, Rios A, et al. Morphoproteomics identifies constitutive activation of the mTORC2/Akt and NF-kappaB pathways and expressions of IGF-1R, Sirt1, COX-2, and FASN in peripheral T-cell lymphomas: pathogenetic implications and therapeutic options. Int J Clin Exp Pathol. 2014;7(12):8732-9.
7. Ciarapica R, Miele L, Giordano A, et al. Enhancer of zeste homolog 2 (EZH2) in pediatric soft tissue sarcomas: first implications. BMC Med. 2011;9:63.
8. McCabe MT, Ott HM, Ganji G, et al. EZH2 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations. Nature. 2012;492(7427):108-12.
9. Liu H, Smith AJ, Lott MC, et al. Sulforaphane can protect lens cells against oxidative stress: implications for cataract prevention. Invest Ophthalmol Vis Sci. 2013;54(8):5236-48.
10. Kimura H. EBV in T-/NK-Cell Tumorigenesis. Adv Exp Med Biol. 2018;1045:459-475.
11. Dobashi A, Tsuyama N, Asaka R, et al. Frequent BCOR aberrations in extranodal NK/T-Cell lymphoma, nasal type. Genes Chromosomes Cancer. 2016;55(5):460-71.
12. Aozasa K, Takakuwa T, Hongyo T, et al. Nasal NK/T-cell lymphoma: epidemiology and pathogenesis. Int J Hematol. 2008;87(2):110-117.
13. Kwong YL, Chan TSY, Tan D, et al. PD1 blockade with pembrolizumab is highly effective in relapsed or refractory NK/T-cell lymphoma failing l-asparaginase. Blood. 2017;129(17):2437-2442.
14. Broccoli A, Argnani L, Zinzani PL. Peripheral T-cell lymphomas: Focusing on novel agents in relapsed and refractory disease. Cancer Treat Rev. 2017;60:120-129.
15. Yoshimori M, Takada H, Imadome K, et al. P-glycoprotein is expressed and causes resistance to chemotherapy in EBV-positive T-cell lymphoproliferative diseases. Cancer Med. 2015;4(10):1494-504.
16. Agha ME, Monaghan SA, Swerdlow SH. Venetoclax in a Patient with a Blastic Plasmacytoid Dendritic-Cell Neoplasm. N Engl J Med. 2018;379(15):1479-1481.
17. Boidol B, Kornauth C, van der Kouwe E, et al. First-in-human response of BCL-2 inhibitor venetoclax in T-cell prolymphocytic leukemia. Blood. 2017;130(23):2499-2503.
18. Ratner L, Waldmann TA, Janakiram M, et al. Rapid Progression of Adult T-Cell Leukemia-Lymphoma after PD-1 Inhibitor Therapy. N Engl J Med. 2018;378(20):1947-1948.
19. Onozawa E, Shibayama H, Takada H, et al. STAT3 is constitutively activated in chronic active Epstein-Barr virus infection and can be a therapeutic target. Oncotarget. 2018;9(57):31077-31089.
20. Ando S, Kawada JI, Watanabe T, et al. Tofacitinib induces G1 cell-cycle arrest and inhibits tumor growth in Epstein-Barr virus-associated T and natural killer cell lymphoma cells. Oncotarget. 2016;7(47):76793-7805.
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IssueVol 16, No 3 (2022) QRcode
SectionCase Report(s)
DOI https://doi.org/10.18502/ijhoscr.v16i3.10141
Keywords
Hydroa vacciniforme-like lymphoma (HVLL); Epstein-Barr virus; T-cell lymphoproliferative disorders; Resistance mechanisms; Morphoproteomics
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Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
1.
Goswamy R, Ajufo H, Maiti A, Brown R, Juneja H, Apostolidou E. Refractory Hydroa Vacciniforme-Like Lymphoma: Biological Insights from Morphoproteomic Analysis. Int J Hematol Oncol Stem Cell Res. 2022;16(3):177-183.