įeldman AL, Arber DA, Pittaluga S, Martinez A, Burke JS, Raffeld M, Camos M, Warnke R, Jaffe ES (2008) Clonally related follicular lymphomas and histiocytic/dendritic cell sarcomas: evidence for transdifferentiation of the follicular lymphoma clone. Kommalapati A, Tella SH, Durkin M, Go RS, Goyal G (2018) Histiocytic sarcoma: a population-based analysis of incidence, demographic disparities, and long-term outcomes. Péricart S, Waysse C, Siegfried A, Struski S, Delabesse E, Laurent C, Evrard S (2020) Subsequent development of histiocytic sarcoma and follicular lymphoma: cytogenetics and next-generation sequencing analyses provide evidence for transdifferentiation of early common lymphoid precursor-a case report and review of literature. Laurent C, Syrykh C, Hamon M, Adélaïde J, Guille A, Escudié F, Jalowicki G, Fina F, Bardet A, Mescam L, Molina TJ, Dartigues P, Parrens M, Sujobert P, Besson C, Birnbaum D, Xerri L (2021) Resistance of B-cell lymphomas to CAR T-cell therapy is associated with genomic tumor changes which can result in transdifferentiation. Singh N, Orlando E, Xu J, Xu J, Binder Z, Collins MA, O’Rourke DM, Melenhorst JJ (2020) Mechanisms of resistance to CAR T cell therapies. Mohty M, Dulery R, Jordan G, Malard F, Brissot E, Aljurf M, Bazarbachi A, Christian C, Kharfan-Dabaja MA, BipinSavani N, Huang H, SaadKenderian S, Miguel-Angel P, Yakoub-Agha I, Nagler A (2020) CAR T-cell therapy for the management of refractory/relapsed high-grade B-cell lymphoma: a practical overview. Wei J, Mao Z, Wang N, Huang L, Cao Y, Sun W, Long X, Tan J, Li C, Xiao Y, Gu C, Zhang S, Zhang Y, Zhang T, Zhou J, Huang L (2020) Long‐term outcomes of relapsed/refractory double‐hit lymphoma (r/r DHL) treated with CD19/22 CAR T‐cell cocktail therapy. Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, Braunschweig I, Oluwole OO, Siddiqi T, Lin Y, Timmerman JM, Stiff PJ, Friedberg JW, Flinn IW, Goy A, Hill BT, Smith MR, Deol A, Farooq U, McSweeney P, Munoz J, Avivi I, Castro JE, Westin JR, Chavez JC, Ghobadi A, Komanduri Kv, Levy R, Jacobsen ED, Witzig TE, Reagan P, Bot A, Rossi J, Navale L, Jiang Y, Aycock J, Elias M, Chang D, Wiezorek J, Go WY (2017) Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. 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. 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. However, the FISH analysis revealed the same MYC and BCL2 rearrangements in both populations. 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. 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. 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.

The ideas put forward in this paper can be seen as a contribution to a morphology of sociotechnical systems and thereby support efforts to investigate or promote specific directions of change.Histiocytic sarcoma/malignant histiocytosis is a rare, aggressive neoplasm that can occur as a primary malignancy or secondary to another hematologic neoplasm.

We also provide three illustrative empirical examples where directionality has resulted in systems with different technical, social and spatial characteristics. Our aim is therefore to unpack and conceptualize the multidimensional space in which sociotechnical systems may adopt different shapes and configurations. The specific characteristics of the potential outcomes of directionality have, however, received little attention. This implies a dual interest in the directionality of innovation some directions of change can be perceived as more desirable, while others may be more plausible due to the path dependent nature of sociotechnical change. The sustainability transitions literature departs from the idea that grand challenges such as climate change and rising inequality call for far-reaching changes in sociotechnical systems of production and consumption.

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