75 year old male with ECOG PS: 1 who had chronic persistent leukocytosis since 10 years, initially with negative work up for MPN, including bone marrow biopsy. Since early 2023 his leukocytosis has been progressive with development of generalized lymphadenopathy. Negative infectious work up. WBC 33k, Hb 10.7 g/dl, Plt 144k. Monocytosis. Molecular testing is positive for NRAS, TET2, SEPBP1 and ASXL1 mutations. Cytogenetics is positive for 47XY +19; bone marrow is hypercellular and consistent with CMML. PET/CT showed widespread hypermetabolic adenopathy in head and neck, mediastinal, hilar and axillary nodes. Excisional cervical LN consistent with infiltration by histiocytic large multinucleated cells. The histiocytic cells have strong positive staining for CD45, S-100, Lysozyme, CD68, and vimentin. Negative for cytokeratin AE1/AE3, CD30, CD20, CD3, CD23, CD34, CD1a, myeloperoxidase and Melan-A. There is significant plasma cell infiltrate positive for CD138 and kappa and lambda light chains indicating plasma cells are polyclonal. Ki-67 35 to 40%, overall favoring histiocytic sarcoma. He continues to have PS of ECOG 1; constitutional symptoms include weight loss and fatigue. Patient is not a candidate for SCT. My questions are is there a relation between CMML and histiocytic sarcoma? How would you approach this case? Would treatment with CHOP reasonable. Any treatment guidance. I appreciate the input.
Yes there is definitely an association between histiocytic sarcoma and other hematologic neoplasms. The classic associations are follicular lymphoma and ALL but myeloid neoplasms including AML and CMML can also occur. This is presumably due to clonal plasticity. I would suggest molecular testing of the lymph node biopsy specimen to see if there are targetable MAPkinase pathway or other targetable mutations. I favore ICE in HS but I suspect this patient will not be a candidate. CHOP is a reasonable option if there is not a targetable mutation. If CHOP is not effective, then I would usually use mid-dose cytarabine as done in AML consolidation if the patient can tolerate that regimen.
