The Many Faces of Philadelphia: A Mature T-Cell Lymphoma with Variant Philadelphia-Translocation and Duplication of the Philadelphia Chromosome.

Background: T-cell prolymphocytic leukemia (T-PLL) is a rare mature T-cell lymphoma that is usually associated with poor prognosis and short overall survival.

Methods: We present a case of a 61-year-old woman presenting with T-PLL and the leukemic cells harboring BCR::ABL1 (BCR-breakpoint cluster region; ABL1-ABL protooncogene 1) fusion transcripts as the result of a variant of t(9;22)(q34;q11) called Philadelphia translocation: t(9;22;18)(q34;q11;q21). Sequencing revealed a rare BCR transcript with an exon 6 breakpoint corresponding to e6a2 transcripts, which has thus far been reported in only 26 cases of leukemias.

Results: After 9 months of follow-up, the disease progressed and required treatment. Following alemtuzumab and chemotherapy, a short course of imatinib therapy stabilized the disease for six months, which was followed by progression and the demise of the patient.

Conclusions: To the best of our knowledge, this is the first report of a mature T-cell lymphoma with a variant Philadelphia-translocation and a very rare type of BCR::ABL1 transcript. This case highlights the importance of comprehensive genetic testing of malignancies, as abnormal molecular pathways may be uncovered that may be specifically targeted by drugs.