Case 10 -

Myeloid Sarcoma with Mast Cell and Megakaryocytic Differentiation Elaine S. Jaffe National Cancer Institute NIH, Bethesda, MD

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Clinical History A 51 year old female had a history of systemic mastocytosis associated with a myelodysplastic syndrome. She underwent an HLA-matched peripheral blood stem cell transplant. Approximately 3 years later she developed an scalp mass. A biopsy was obtained. Case 10 - Figure 1 - A skin biopsy from 2001 shows infiltration of the dermis by atypical mast cells with a polygonal appearance. Case 10 - Figure 2 - The mast cells are strongly positive for tryptase by immunohistochemistry Case 10 - Figure 3 - In 2004, following bone marrow transplantation, the patient developed a scalp mass. Deep dermis and subcutaneous tissues are infiltrated by large blastic cells. Rare eosinophilic myelocytes are identified. Case 10 - Figure 4 - The scalp mass also contains giant cells suggestive of megakaryocytes. Case 10 - Figure 5 - Many of the blastic cells are positive for chloroacetate esterase, but negative for myeloperoxidase (not shown). Case 10 - Figure 6 - The megakaryocytes show staining for p-selectin. Discussion: In recent years, systemic mastocytosis (systemic tissue mast cell disease) has been recognized as one of the myeloproliferative disorders, in which multiple cell lineages may be involved [1] . Patients may show evidence of a myeloproliferative disorder at presentation, or a systemic myeloproliferative disorder may evolve during the patient's course. Cutaneous involvement is common in patients with systemic tissue mast cell disease [2] . Normal mast cells express chloroacetate esterase, tryptase and c-kit (CD117) [3]. They are negative for myeloperoxidase. In systemic mastocytosis the mast cells may show aberrant expression of CD2 and CD25 [4] . Myeloid sarcoma is a proliferation of immature cells of myeloid origin occurring outside the bone marrow, or as a mass lesion in a bony site. Synonyms include extramedullary myeloid tumor, granulocytic sarcoma, and the older term, chloroma, which is derived from the green color seen grossly in those lesions composed of immature neutrophils [5] . Myeloid sarcomas can be derived from immature cells of diverse lineages, including granulocytes, eosinophils, monocytic cells, and megakaryocytes. Tumors with erythroid differentiation are rare. In patients with underlying mast cell disease, immature mast cells may be present [6] . Myeloid sarcomas can be associated with many types of bone marrow disorders. They may precede or occur concurrently with acute or chronic myeloid leukemia, myeloproliferative disorders, and myelodysplastic syndromes. Extramedullary tumors are somewhat more common with acute monoblastic leukemias, and skin is a common site of involvement. Cutaneous lesions may be the initial manifestation of acute monoblastic leukemia. Myeloid sarcomas may also be the primary evidence of relapse following therapy. The development of a myeloblastic tumor in someone with chronic myelogenous leukemia is evidence of blastic transformation. In the WHO classification [7] , myeloid sarcomas are classified according to lineage and also the stage of differentiation. There are three major types: 1) blastic; 2) immature; and 3) differentiated. As the names imply, blastic tumors are composed primarily of blasts. In immature lesions, a combination of blasts and immature myeloid precursors is seen. In the differentiated form, maturation to mature neutrophils and other elements is seen. Useful immunohistochemical or enzyme cytochemical stains include myeloperoxidase (MPO), performed as an enzymatic or immunohistochemical stain; chloroacetate esterase (Leder stain); CD68, and c-Kit [3, 5, 8, 9, 10] . CD99 may be positive, but is also positive in lymphoblastic malignancies, and of course, PNET/ Ewing's sarcoma [11] . CD43 is consistently present but does not have lineage specificity. P-Selectin may be positive in cells showing megakaryocytic differentiation. Lymphoid markers such as CD3, CD20 and TDT should be negative, but CD7, CD2, and CD56 may be expressed in some very immature myeloid tumors [12, 13, 14] . A somewhat related phenomenon is the tumor of "plasmacytoid monocytes" often seen in association with chronic myelomonocytic leukemia (CMML) [15, 16] . These tumors are thought to be related to dendritic cells, and are clonally related to the underlying CMML. Lymph node is the most common site of involvement, but these lesions can also be identified in cutaneous sites. References Valent P, Akin C, Sperr WR, Horny HP, Metcalfe DD. Mast cell proliferative disorders: current view on variants recognized by the World Health Organization. Hematology-Oncology Clinics of North America 2003;17(5):1227. Brockow K, Akin C, Huber M, Metcalfe DD. 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