Mast Cell Leukemia



Mast Cell Leukemia


Kaaren K. Reichard, MD





Key Facts


Terminology



  • Definition: ≥ 10% circulating mast cells and ≥ 20% mast cells in BM aspirate


  • “Aleukemic” if < 10% circulating mast cells


Etiology/Pathogenesis



  • Unknown; rare disease


Microscopic Pathology



  • Mast cells comprise ≥ 20% of nucleated cells in BM aspirate smears


  • Round cell cytologic variant is most common


  • BM infiltrates are diffuse


Ancillary Tests



  • Immunophenotyping



    • Mast cells identified by bright CD117(+), tryptase(+)


    • Expression of CD2 &/or CD25 typically aberrant


    • CD30 expression common; may initially lead to diagnostic confusion with lymphoma


  • Molecular



    • KIT D816V mutation often present


    • KIT mutation confers imatinib resistance


Top Differential Diagnoses



  • Aggressive systemic mastocytosis



    • Similar BM histologic picture


    • Key difference: < 20% mast cells of BM nucleated cells on aspirate smears


  • Myelomastocytic leukemia



    • Features of mast cell differentiation


    • Criteria for systemic mastocytosis are not met






This photomicrograph shows the typical appearance of mast cell leukemia in the bone marrow. The cells are round and small with variable degrees of degranulated abundant cytoplasm.






This tryptase immunohistochemical stain positively identifies the sheets of mast cells in the bone marrow of a patient with mast cell leukemia.


TERMINOLOGY


Abbreviations



  • Mast cell leukemia (MCL)


Definitions



  • Clonal hematopoietic myeloid neoplasm


  • Exclusive or dominant component of bone marrow (BM)-derived mast cells


  • Mast cells comprise ≥ 20% of BM aspirate nucleated cells


  • Leukemic MCL: ≥ 10% circulating mast cells


  • Aleukemic MCL: < 10% circulating mast cells


ETIOLOGY/PATHOGENESIS


Acquired Activating Mutations



  • Most common is KIT D816V


  • Other rarer mutations also described


CLINICAL ISSUES


Epidemiology



  • Incidence



    • Rare


  • Age



    • Predominantly adults


  • Gender



    • No obvious sex predilection


Presentation



  • Hepatomegaly


  • Ascites


  • Splenomegaly


  • Abnormal complete blood cell count (CBC)



    • Cytopenias, leukoerythroblastosis


  • Lytic bone lesions


  • Prominent extramedullary leukemia infiltrates



    • Liver


    • Spleen


    • Occasional involvement of other organs (e.g., stomach, kidneys, etc.)


  • Circulating mast cells


  • Pathologic bone fractures


  • Gastrointestinal disturbance



    • Malabsorption


    • Weight loss


  • Skin lesions



    • Very rare


  • Elevated serum tryptase level


Treatment



  • Cytoreductive agents


  • Chemotherapy


  • KIT D816V mutation confers imatinib resistance


  • Novel tyrosine kinase inhibitors



    • Dasatinib and midostaurin (PKC412)


    • Exhibit partial remitting activity


  • Hematopoietic stem cell transplantation



    • Only chance to achieve durable remission


Prognosis



  • Unfavorable


  • Aggressive disease course


  • Median survival is 6-7 months


  • Poor response to cytoreductive agents and chemotherapy


  • Short-term remission



    • Interferon


    • 2-CDA


    • Steroids


IMAGE FINDINGS


Radiographic Findings



  • Osteolytic lesions


  • Pathologic fractures



MICROSCOPIC PATHOLOGY


Peripheral Blood (PB) Findings



  • Circulating mast cells



    • Usually ≥ 10% of nucleated cells


    • If < 10% of nucleated cells, designated as “aleukemic”


  • Cytopenias


  • Leukoerythroblastic picture


  • If there is associated clonal hematological non-mast cell lineage disease (AHNMD)



    • May see features of non-mast cell neoplasm



      • e.g., blasts, dysplasia


Bone Marrow Aspirate Findings



  • Mast cells comprise ≥ 20% of nucleated cells on aspirate smears


  • Background hematopoiesis usually markedly decreased


  • 2 cytologic subtypes



    • Round cell variant



      • Most common


    • Spindle cell variant



      • Rare


  • Mast cell atypia: May not see all features in each case



    • Hypogranular cytoplasm


    • Abnormal or bilobed nuclei


    • Immature-appearing chromatin


    • Prominent nucleoli


  • If AHNMD, see features of non-mast cell neoplasm



    • e.g., increased blasts in acute leukemia


    • e.g., dysplasia in myelodysplastic syndrome


Bone Marrow Biopsy Findings



  • Diffuse infiltration pattern on core biopsy


  • Compact dense aggregate formation


  • Variable sparing of residual hematopoietic elements


  • Bone may be osteolytic


  • If AHNMD, see features of non-mast cell neoplasm



    • e.g., increased blasts in acute myeloid leukemia (AML)


    • e.g., dysplasia in myelodysplastic syndrome


    • Leukemic infiltrate of MCL may obscure underlying AHNMD



      • May require meticulous assessment of background hematopoietic elements


      • Would warrant classification as MCL-AML, etc.


ANCILLARY TESTS


Immunohistochemistry



  • Immunohistochemistry



    • Mast cells identified by CD117 and tryptase


  • Mast cells may demonstrate CD33 positivity


  • Aberrant expression of CD2 &/or CD25



    • Useful clue to mast cell neoplasia


    • Fulfills minor criterion for SM


  • Majority of MCL cases show CD30 expression



    • May initially contribute to diagnostic confusion with lymphoma


  • Mast cells are nonreactive for



    • CD34


    • Myeloperoxidase


    • CD14


    • CD15


    • Lymphoid-associated markers


  • Mast cells lack expression of 2D7 and BB1; markers useful to distinguish basophils

Tags:
Jun 13, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Mast Cell Leukemia

Full access? Get Clinical Tree
Get Clinical Tree app for offline access