Figure18F-Fluorodeoxyglucose positron emission tomography/computed tomography before (A) and after (B) 3 courses of nivolumab, showing a marked regression of the number and intensity of thoracic hypermetabolic adenopathies. Only hypermetabolic nodes persist: left supraclavicular, maximum standard uptake value (SUVmax) of 9 vs 21; anterior para-aortic mediastinal, SUVmax of 10 vs 27; left internal mammary, SUVmax of 14 vs 13; left anterior paracardiac, SUVmax of 3 vs 33. A regression of the size and intensity of paramediastinal infiltration (SUVmax, 5.6 vs 34) was also observed.
Malignant histiocytosis (or histiocytic sarcoma) is a rare disease characterized by a malignant proliferation of cells resembling mature tissue histiocytes.1Emile J.F. Abla O. Fraitag S. et al.Revised classification of histiocytoses and neoplasms of the macrophage-dendritic cell lineages. Median age at diagnosis is 63 years; the prognosis is usually poor, with a median overall survival of 6 months, because no standard treatment has yet been established and responses to conventional chemotherapy at advanced stages are generally poor.2Kommalapati A. Tella S.H. Durkin M. Go R.S. Goyal G. Histiocytic sarcoma: a population-based analysis of incidence, demographic disparities, and long-term outcomes. Mutations affecting the RAS-MAPK signaling pathway are detected in most cases,3Shanmugam V. Griffin G.K. Jacobsen E.D. Fletcher C.D. Sholl L.M. Hornick J.L. Identification of diverse activating mutations of the RAS-MAPK pathway in histiocytic sarcoma. and the off-label use of targeted therapies has been reported to yield clinical responses in several cases.4Jacobsen E. Shanmugam V. Jagannathan J. Rosai-Dorfman disease with activating KRAS mutation—response to cobimetinib. It has been suggested that PD-L1 expression is detectable in most cases, but the utility of PD-L1/PD-1 blockade in histiocytic neoplasms remains unclear.5Xu J. Sun H.H. Fletcher C.D.M. et al.Expression of programmed cell death 1 ligands (PD-L1 and PD-L2) in histiocytic and dendritic cell disorders. We report here the first case of a response to nivolumab in an adult with malignant histiocytosis. Next-generation sequencing appears to be essential for the diagnosis of this rare histiocytic condition, given the therapeutic options available. However, immune checkpoint inhibition may also be a valuable therapeutic option for patients with malignant histiocytosis expressing PD-L1.Potential Competing InterestsL.C. and J-P.S.: consultant or advisory role (fees): Bristol Myers Squibb. J.H., J-F.E., A.V. and D.K. have no conflicts of interest to disclose.
ReferencesEmile J.F. Abla O. Fraitag S. et al.Revised classification of histiocytoses and neoplasms of the macrophage-dendritic cell lineages.
Blood. 127: 2672-2681Kommalapati A. Tella S.H. Durkin M. Go R.S. Goyal G.Histiocytic sarcoma: a population-based analysis of incidence, demographic disparities, and long-term outcomes.
Blood. 131: 265-268Shanmugam V. Griffin G.K. Jacobsen E.D. Fletcher C.D. Sholl L.M. Hornick J.L.Identification of diverse activating mutations of the RAS-MAPK pathway in histiocytic sarcoma.
Mod Pathol. 32: 830-843Jacobsen E. Shanmugam V. Jagannathan J.Rosai-Dorfman disease with activating KRAS mutation—response to cobimetinib.
N Engl J Med. 377: 2398-2399Xu J. Sun H.H. Fletcher C.D.M. et al.Expression of programmed cell death 1 ligands (PD-L1 and PD-L2) in histiocytic and dendritic cell disorders.
Am J Surg Pathol. 40: 443-453Article InfoIdentificationDOI: https://doi.org/10.1016/j.mayocp.2022.05.012
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