By Craig Litz, M.D.
A 75-year-old female with a 6-year history of systemic mastocytosis presented with fevers and pancytopenia. A bone marrow aspiration and biopsy were performed. The aspirate differential showed: myeloblasts 13%, monoblasts 77%, eosinophils 1%, erythroid progenitors 9%, and maturing granulocytes 6% (figure 1). The biopsy material showed a hypercellular marrow effaced primarily by blasts. There were also paratrabecular aggregates of spindled mast cells that were CD117 positive involving approximately 10% of the marrow cellularity (figure 2a).
By flow cytometry the blasts were: CD13+, CD14+ (partial), CD15+, CD34+, and CD36+, Myeloperoxidase +(dim partial). Cytogenetic studies showed complex, clonal karyotypic abnormalities.
Final Diagnosis: Acute Myelomonocytic Leukemia arising in a background of Systemic Mastocytosis.
Systemic mastocytosis is characterized by an abnormal proliferation of tissue mast cells with variable morphologic and clinical manifestations. Originally described in its cutaneous form by Nettleship and Unna in the 1800’s, systemic mastocytosis is diagnosed in men and women from young adulthood to old age with median ages ranging from 48 to 71 years Clinical manifestations result from effects of chemical mediators released by the mast cells, most notably histamine, and include generalized pruritis, urticaria, episodic flushing, bronchospasm, arthralgia, headache, tachycardia, hypotension, and syncope; younger patients typically show cutaneous manifestations (urticaria pigmentosa). 25 to 80% of patients show gastrointestinal manifestations including abdominal pain, diarrhea, nausea, vomiting, and bleeding. Radiographic evidence of bone lesions is present in more than half of the patients. Blood eosinophilia and neutrophilic leukocytosis are common although circulating mast cells are not typically noted.
Marrow involvement is present in 90% of cases; trephine biopsy specimens show focal involvement in 80% of specimens and diffuse involvement in 20%. Focal involvement by mastocytosis typically shows two pattern types: polycellular and monocellular. Polycellular lesions commonly show compartmentalization with a central focus of lymphocytes encircled by mast cells or a cluster of mast cells ringed by lymphocytes (figure 2b). Monocellular lesions are composed chiefly of mast cells alone and frequently are spindled cell in appearance as was the current case (figure 2a). In mast cell leukemia, the marrow is effaced by immature, atypical appearing mast cells. Immunohistochemically, mast cells are positive for mast cell tryptase and CD117. The clinical course in non-leukemic forms of mastocytosis is generally chronic with slow progression of symptoms. Patients often die of unrelated causes. Clinical factors associated with poor prognosis include constitutional symptoms, abnormal liver function tests, anemia, thrombocytopenia, and other hematologic disorders. Progression to mast cell leukemia is rare but the occurrence of other malignancies is relatively common. The second malignancy is most often a myeloid leukemia but lymphomas and carcinomas have also been reported. Typically, the prognosis usually reflects the course of the associated second malignancy as uncomplicated mastocytosis is an indolent but incurable disease.
Antihistaminic therapy is the mainstay treatment for mastocytosis with epinephrine reserved for anaphylactic episodes. Chemotherapy is generally only of benefit in those with aggressive disease or secondary malignancies.
1. Horny HP, Valent P. Diagnosis of Mastocytosis: General Histopathological Aspects, Morphological Criteria, and Immunohistochemical Findings. Leuk Res 25:543-551, 2001.
2. Valent P, Horny HP, Escribano L et al. Diagnostic Criteria and Classification of Mastocytosis: A Consensus Proposal. Leuk Res 25: 603-625, 2001.
3. Parker RI. Hematologic Aspects of Systemic Mastocytosis. Hematol Oncol Clin North Am 14:557-568, 2001.
4. Brunning RD, McKenna RW. Mast Cell Disease in Tumors of the Bone Marrow, Atlas of Tumor Pathology, Third Series, Fascicle 9, Washington, D.C., Armed Forces Institute of Pathology, 1994.