Transdifferentiation of high-grade B-cell lymphoma with MYC and BCL2 rearrangements into histiocytic sarcoma after CAR T-cell therapy: a case report

• Published in: Journal of hematopathology Vol. 15; no. 4; pp. 229 - 237
• Main Authors: Gauto-Mariotti, Estefania, Nguyen, Amanda J., Waters, Chloe, Scurti, Gina M., Haddad, Sandra, Velankar, Milind M., Dalheim, Annika V., Dronzek, Victoria, Ketterling, Rhett P., Nishimura, Michael I., Dalland, Joanna C., Hossain, Nasheed M.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-12-2022
• Subjects: Case Report; Hematology; Medicine; Medicine & Public Health; Pathology; CAR T-cell therapy; Clonal relationship; Histiocytic sarcoma; Transdifferentiation; Malignant histiocytosis
• ISSN: 1868-9256; 1865-5785
• DOI: 10.1007/s12308-022-00519-2

Histiocytic sarcoma/malignant histiocytosis is a rare, aggressive neoplasm that can occur as a primary malignancy or secondary to another hematologic neoplasm. While it is relatively well established that hematopoietic cells can display lineage plasticity in response to anti-lymphoma therapy, transdifferentiation following CAR T-cell therapy is a rare phenomenon. We report a unique case of transdifferentiation of high-grade B-cell lymphoma with MYC and BCL2 rearrangements into histiocytic sarcoma/malignant histiocytosis shortly after receiving CAR T-cell therapy. Immunohistochemical stains on core biopsies of the patient’s right thigh mass showed two morphologically and immunophenotypically distinct cell populations with B-cell lineage and histiocytic lineage. However, the FISH analysis revealed the same MYC and BCL2 rearrangements in both populations. The presence of the same MYC and BCL2 rearrangements detected by FISH analysis and identical immunoglobulin gene rearrangement patterns in both the B-cell component and the histiocytic component supports that these two processes are clonally related. This case highlights the diagnostic and therapeutic challenges associated with histiocytic sarcoma/malignant histiocytosis and calls attention to a rare potential complication of CAR T-cell therapy.