Refractory Hydroa Vacciniforme-like Lymphoma: Biological Insights from Morphoproteomic Analysis.

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.