A 45-year-old man presented with a 3-week history of fever, night sweats, weight loss, worsening abdominal pain and distention. He reported intermittent diarrhea with a maculopapular rash on his torso. On admission he had mild thrombocytopenia (platelet count 51x109/L) and a leukocytosis with a neutrophil count of 12.5 x109/L. CT imaging revealed diffuse lymphadenopathy, hepatosplenomegaly and thickening of small bowel and colon. Peripheral blood smear showed circulating mast cells including atypical forms. Bone marrow biopsy and flow cytometry confirmed the diagnosis of mast cell leukemia with 54% mast cells in the bone marrow aspirate. Sequencing of exons 8 and 17 of the KIT gene did not show any mutation and serum tryptase level was greater than 200 ug/L (reference range 3.8 to 11.4). 

On the third day of admission, he experienced severe epigastric pain with free intra-peritoneal air in the setting of large-volume ascites. He became hemodynamically unstable and underwent immediate exploration that revealed a large duodenum perforation and a mass in the mid small bowel. Small bowel pathology showed massive infiltration of mucosa by mast cells. The patient was initially treated with steroids, antihistamines and imatinib.  Given the aggressive progression of his disease and further complications, palliative treatment was instituted and the patient died soon after. 

The presence of multifocal mast cell clusters (Major criteria) alongwith atypical morphology (minor1), elevated tryptase>20 ng/mL (minor2) and CD25/CD2 expression (minor3) satisfied the criteria for Systemic mastocytosis (SM). The additional presence of >20% mast cells on the aspirate smears allows further designation as Mast cell leukemia (MCL) in this case. Although the presence of less than 10% circulating mast cells in this case allows designation as 'aleukemic' MCL, the presence of C findings (Organ damage as noted by cytopenias, and organomegaly) and clinical course suggests that this is an acute form of MCL.

 
Learning points from the case: 

1. Mast cell leukemia is a highly aggressive form of SM with ≥ 20% mast cells (of all nucleated cells) in the marrow and often with significant atypia.
2. All mast cells (benign and neoplastic) are positive for tryptase, and CD117, while only neoplastic mast cells often express CD25 and/or CD2. 
3. Aleukemic (<10% circulating mast cells), chronic (No 'C' findings) and acute (>=1 'C' finding) forms of MCL exist.

REF:

Diagnosis and management of mastocytosis: an emerging challenge in applied hematology. Valent P. ASH Education program 2015.