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© 2002 American Society for Clinical Oncology
Unusual Hematologic MalignanciesCase 1. Hematologic Malignancy Presenting With Diarrhea and Bony Lesions: Systemic MastocytosisUniversity of Pennsylvania, Philadelphia, PA A 47-year-old man presented with fever, profuse watery diarrhea, lower-extremity weakness, headaches, night sweats, and weight loss for several months. Physical examination showed abdominal distention, splenomegaly, and pedal edema. Laboratory evaluation revealed a leukocyte count of 8.7 x 109/L with a normal differential, hemoglobin of 10.4 g/dL, and platelet count of 108 x 109/L. Radiographic evaluation included a chest and abdominal computed tomography scan that showed retroperitoneal lymphadenopathy and multiple lytic lesions in the thoracic spine and ilium and sacrum (Fig 1, bone windows). A bone scan revealed diffusely increased uptake throughout the skeleton. Results of serum chemistry analyses were within normal limits. Serum and urine electrophoresis did not reveal a paraprotein. Lymphoma, metastatic carcinoma, multiple myeloma, and infections were considered in the differential diagnosis. Bone marrow biopsy showed a hypercellular marrow with myelofibrosis and a mononuclear cell infiltrate (Fig 2, A and B). The abnormal cells were immunoreactive for CD45 (leukocyte common antigen) and CD43 but were negative for T-cell antigens (CD3, CD5, and CD45RO), B-cell antigens (CD20 and CD79a), and the myeloid antigen myeloperoxidase. Additional evaluation showed that the cells were positive for CD68, CD117 (c-kit), tryptase (Fig 3), and alpha-1-antitrypsin but that they were negative for classical Hodgkin’s lymphoma-associated antigens (CD15 and CD30), as well as cytoplasmic immunoglobulin and the epithelial antigen cytokeratin. On the basis of these findings, the diagnosis of systemic mastocytosis was made. Serum and urine histamine were subsequently tested and found to be elevated. The patient was initially treated with systemic corticosteroids. After a decrease in both serum and urine histamine levels with this regimen, interferon-alfa-2b was added. The patient then received two cycles of cladribine. He remains symptomatically well but with persistent disease 1 year after diagnosis.
Mast cell disease is a rare disorder characterized by an abnormal proliferation of mast cells.1,2 Although most commonly limited to the skin (cutaneous mastocytosis), 10% to 20% of patients have systemic mast cell disease (SMCD), in which the bone marrow, spleen, lymph nodes, liver, or other organs are involved, with or without skin involvement. Cutaneous mastocytosis occurs primarily in early childhood, and fewer than 20% of cases have an adult onset. A small proportion of patients with cutaneous mast cell disease do develop dissemination, and in these cases, the ensuing SMCD is usually indolent. Some patients develop SMCD without cutaneous lesions. Such patients generally tend to have a more aggressive disease course than those with skin lesions, with a median survival of 2 to 4 years.1,2 Almost 30% to 40% of cases of SMCD have an associated hematologic malignancy, such as myelodysplastic syndrome, myeloproliferative disorder, or malignant lymphoma. These cases also generally have a poor prognosis.1,2 Clinically, a diagnosis of SMCD may be elusive because of the nonspecific symptoms, most of which are related to the consequences of the release of mast cell granules, such as pruritus, urticaria, abdominal pain, diarrhea, hypertension, and anaphylaxis. Some patients with SMCD present with splenomegaly, lymphadenopathy, or bone lesions.2 The most common findings in the peripheral blood in patients with SMCD are also nonspecific, including anemia, eosinophilia, leukocytosis or leukopenia, and thrombocytopenia. On occasion, circulating mast cells may be seen (mast cell leukemia). Bone marrow involvement occurs in approximately 90% of patients with SMCD. The bone marrow biopsy usually can be diagnostic and show focal, paratrabecular, perivascular, or randomly distributed aggregates of mast cells mixed with varying numbers of lymphocytes, neutrophils, and eosinophils.3 Typically, the cytology of the mast cells is somewhat bland, with round, oval, or elongated nuclei and moderate to abundant eosinophilic cytoplasm, which may lead to confusion with various non-Hodgkin’s lymphomas, such as diffuse large cell lymphoma, marginal cell lymphoma, and hairy cell leukemia. The fibrosis and inflammatory background may sometimes cause confusion with Hodgkin’s lymphoma. The spindle shape and lobulation of the nuclei may make it difficult to distinguish SMCD from acute myeloblastic leukemia, especially when the marrow is inaspirable due to marrow fibrosis, as in our case.4 The immunohistochemical staining for tryptase or CD117 is invaluable in differentiating mast cells from cells of lymphoid or other lineage.5,6 Radiographically, bone lesions in systemic mastocytosis can be either lytic or sclerotic. The severity of bone lesions on x-ray correlate with urinary histamine levels.7 Lytic lesions, which are the predominant finding, have been associated with moderate increases in bone marrow mast cells.8 Significantly more mast cell infiltration has been correlated with sclerotic lesions. In conclusion, systemic mastocytosis is an unusual and potentially misdiagnosed entity. A high index of suspicion for mastocytosis is of paramount importance, especially in the context of a patient with a neoplastic process, diarrhea, and bony lesions.
NOTES Copyright © 2002 American Society of Clinical Oncology REFERENCES 1. Travis WD, Li CY, Bergstralh EJ, et al: Systemic mast cell disease: Analysis of 58 cases and literature review. Medicine 67: 345-368, 1998 2. Golkar L, Bernhard JD: Mastocytosis. Lancet 349: 1379-1385, 1997[CrossRef][Medline] 3. Horny HP, Parwaresch MR, Lennert K: Bone marrow findings in systemic mastocytosis. Hum Pathol 16: 808-814, 1985[Medline] 4. Lawrence JB, Friedman BS, Travis WD, et al: Hematologic manifestations of systemic mast cell disease: A prospective study of laboratory and morphologic features and their relation to prognosis. Am J Med 91: 612-624, 1991[CrossRef][Medline] 5. Welle M: Development, significance and heterogeneity of mast cells with particular regard to the mast cell-specific proteases chymase and tryptase. J Leukoc Biol 621: 233-245, 1997 6. Li WV, Kapadia SB, Sonmez-Alpan E, et al: Immunohistochemical characterization of mast cell disease in paraffin sections using tryptase, CD68, myeloperoxidase, lysozyme and CD20 antibodies. Mod Pathol 9: 982-988, 1996[Medline]
7. Johannson C, Roupe G, Lindstedt G, et al: Bone density, bone markers and bone radiological features in mastocytosis. Age Ageing 25: 1-7, 1996 8. de Gennes C, Kuntz D, de Vernejoul MC: Bone mastocytosis: A report of nine cases with a bone histomorphometric study. Clin Orthop June( 279): 281-291, 1992
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Copyright © 2002 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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