Anaplastic large cell lymphoma, ALK-negative exhibiting rare CD4 [ +] CD8 [ +] double-positive immunophenotype

Anaplastic large cell lymphoma is a relatively rare type of T cell lymphoma characterized by strong and uniform CD30 expression with a typical cohesive growth pattern and hallmark cells. Most cases are single-positive for CD4 or less often CD8-positive, with only very rare descriptions of having double positivity for both antigens. Agent Orange is a herbicide which was used during the Vietnam War and has been associated with non-Hodgkin lymphoma (including chronic lymphocytic leukemia, hairy cell leukemia, and other chronic B cell leukemias), Hodgkin lymphoma and monoclonal gammopathy of undetermined significance. Herein, we describe a unique case of anaplastic large cell lymphoma ALK-negative arising in a military veteran with documented Agent Orange exposure featuring double positivity for both CD4 and CD8 with a brief literature review that highlights the uniqueness of this rare phenotype. Our patient underwent a left neck lymph node biopsy that was worked up for a lymphoproliferative process. Based on the diagnosis rendered, a T cell lymphoma fluorescence in situ hybridization [FISH] panel was done. T cell receptor gene rearrangement studies could not be performed due to consumption of the material. A core biopsy of the left neck lymph node showed an infiltrate of frankly malignant large lymphoid cells with many featuring eccentric horseshoe/kidney shaped nuclei with an eosinophilic region near the nucleus, consistent with hallmark cells with admixed small lymphocytes, plasma cells and few neutrophils and eosinophils. The neoplastic cells were positive for CD45, CD30, CD2 [subset +], CD5, and also showed double-positive [DP] CD4 + CD8 + and were negative for CD3. FISH studies for T cell lymphoma FISH panel that included rearrangements involving ALK, TP63 and DUPS22 [IRF4] gene regions were negative. Through this case, we demonstrate a unique case of anaplastic large cell lymphoma, ALK-negative in a patient with Agent Orange exposure and featuring double positivity for CD4 and CD8.