The patient is a 64-year-old male with a history of non-alcoholic steatohepatitis with cirrhosis.  A PET-CT performed upon evaluation for a liver transplant showed multistational lymphadenopathy, splenomegaly, numerous scattered osseous sclerotic lesions, and diffuse hypermetabolism of the axial and appendicular marrow compartment.  The excisional supraclavicular lymph node biopsy as well as a bone marrow biopsy were performed for further evaluation.   

The lymph node demonstrated involvement by systemic mastocyosis, as well as concordant involvement by Rosai Dorfman disease and IgG4-related disease (discussed in a separate image set).  

The markedly hypercellular bone marrow biopsy confirmed the diagnosis of systemic mastocytosis with large aggregates (>15 cells) of atypical mast cells (>25%) exhibiting spindled morphology and were positive for CD25 and CD117 by immunohistochemistry.  Reticulin staining demonstrated moderate reticulin fibrosis (MF 2/3).  The bone marrow was negative for Rosai-Dorfman and IgG4-related diseases by morphology and immunohistochemistry. 

Flow cytometry identified an atypical population suggestive of mast cells with phenotype positive for bright CD9, CD25, CD33, bright CD117, and negative for CD2 and CD34. 

Notably, the patient’s peripheral blood had a moderate absolute monocytosis (1200 k/µL) and a few dysplastic appearing megakaryocytes were seen in the bone marrow that displayed small and hypolobated nuclei.  Due to an unsuccessful aspirate, the peripheral blood was used to perform next generation sequencing for a myeloid profile, which showed KIT D816V mutation, as well as missense mutations of SH2B and SRSF2 genes, and a frameshift and nonsense mutation in the TET2 gene.  All mutations showed between 30% to 52% variant allele frequency.    These genetic findings in the context of the peripheral blood absolute monocytosis and dysmegakaryopoiesis in the bone marrow were suspicious for possible underlying chronic myelomonocytic leukemia, thereby suggesting the possibility of systemic mastocytosis with an associated hematologic neoplasm.