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1/195. High-dose chemotherapy with peripheral blood stem cell rescue in blastoid natural killer cell lymphoma.

    A 25-year-old man was referred because of skin rash, lymphadenopathy and anemia. Laboratory examinations revealed severe anemia (Hb, 4.8 g/dl) and elevated levels of GOT, GPT, LDH and soluble interleukin-2 receptor. work-up studies disclosed the involvement of lymphoma cells in lymph nodes, skin, bilateral kidneys and bone marrow. Lymph node biopsy revealed diffuse proliferation of medium- to large-sized lymphoblastic cells. bone marrow aspiration showed massive infiltration of large blastic cells with no cytoplasmic granules. The lymphoma cells in bone marrow and lymph node showed surface CD3-, cytoplasmic CD3epsilon , CD4 , CD8-, CD56 , CD57-, CD16- and CD43 (MT-1) phenotype. Analyses of T cell receptor beta and gamma genes showed germ line configurations. EBER-1 was not detectable in the lymphoma cells. He was diagnosed as having blastoid natural killer (NK) cell lymphoma. In spite of several courses of combination chemotherapy, the lymphoma was progressive. He was then treated with high-dose chemotherapy and peripheral blood stem cell rescue, achieving remission which has now lasted for more than 12 months. We consider that blastoid NK cell lymphoma is an extremely aggressive subtype of CD56-positive lymphomas, and high-dose chemotherapy with peripheral blood stem cell rescue should be included for the choice of the treatment.
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2/195. Cutaneous waldenstrom macroglobulinemia in transformation.

    waldenstrom macroglobulinemia is a low-grade B-cell lymphoproliferative disorder of the elderly with characteristic monoclonal IgM-producing neoplastic infiltrates of the bone marrow, lymph node, and spleen. Cutaneous manifestations are usually nonspecific such as purpura, ulcers, and urticarial lesions. These lesions are caused by hyperviscosity of the blood, immune complex-mediated vascular damage, paraprotein deposition, and amyloid deposition. Specific skin lesions occur rarely and generally consist of translucent, flesh-colored papules composed of monoclonal IgM deposits. Rarely, there may be violaceous lesions composed of low-grade lymphoplasmacytic infiltrates characteristic of waldenstrom macroglobulinemia. Both cutaneous manifestations of the disease, as well as disease transformation to high-grade, large cell lymphoma are rare. We report two very unusual cases of waldenstrom macroglobulinemia with documented skin disease that demonstrated transformation to high-grade lymphoma. Both patients were elderly men with long-standing waldenstrom macroglobulinemia involving the bone marrow, who subsequently developed skin involvement by the disease. waldenstrom macroglobulinemia can rarely manifest as cutaneous disease, sometimes as a high-grade transformation of low-grade waldenstrom macroglobulinemia elsewhere. Distinction of cases of transformed waldenstrom macroglobulinemia from de novo cutaneous large cell lymphoma may be important, because the two entities are likely biologically different.
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3/195. The inv(11)(p15q22) chromosome translocation of therapy-related myelodysplasia with NUP98-DDX10 and DDX10-NUP98 fusion transcripts.

    Chromosomal abnormalities involving the 11p15 or 11q22-23 bands have been reported in several types of human neoplasms including hematopoietic malignancies. The abnormalities are observed in therapy-related malignancies and less frequently in de novo myeloid malignancies. Abnormality of the MLL gene located on chromosome 11q23 has been well known in therapy-related myeloid malignancies, but it has been reported only recently that the inv(11)(p15q22) in de novo or therapy-related myeloid malignancies results in the fusion of NUP98 on chromosome 11p15 and DDX10 on chromosome 11q22. NUP98 is a nucleoporin that composes the nuclear pore complex and is the target gene in leukemia with the t(7;11)(p15;p15). The DDX10 gene encodes a putative adenosine triphosphate-dependent DEAD box rna helicase. Here we present another patient with acute myelocytic leukemia (M4) transformed from chronic myelomonocytic leukemia with the inv(11) chromosome who had been treated with etoposide for a germ cell tumor. By reverse transcription polymerase chain reaction (RT-PCR) of the rna from the leukemic cells of the patient, DDX10-NUP98 and NUP98-DDX10 fusion transcripts were detected. Our case confirms that the inv(11) is a rare chromosomal translocation that is associated with therapy-related or de novo myeloid malignancy and involves NUP98 and DDX10 but not MLL. RT-PCR of the fusion transcripts might be applied to the detection of a small number of leukemic cells in the bone marrow or blood of patients in remission or in the cells harvested for autologous transplantation.
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4/195. Secondary myeloid/natural killer cell precursor acute leukemia following essential thrombocythemia.

    The de novo leukemic transformation of essential thrombocythemia is a rare event, and usually associated with previous treatments. We describe a patient who received treatments with nitrosourea for long-standing essential thrombocythemia and subsequently developed extramedullary tumors, tentatively diagnosed as lymphoblastic lymphoma. Combination chemotherapy was initially successful, but relapsed with marked bone marrow involvement. Surface marker analysis revealed that the tumor cells had CD5, CD7, CD33, CD34, and CD56 antigens but lacked other T-cell, and B-cell markers. Immunogenotypical studies revealed germline configurations for both T-cell receptors and immunoglobulin genes. These clinical and phenotypical features are consistent with a myeloid/natural killer cell precursor leukemia, a recently proposed distinct clinical entity. To our knowledge, this is the first report of secondary leukemia of myeloid/ natural killer cell precursor origin, and suggest that myeloid/natural killer cell precursor might be a potent target of therapy-related leukemia.
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5/195. Squamous cell carcinoma arising in an intradiploic epidermoid cyst.

    A 71-year-old woman presented with the symptoms of a posterior cranial fossa mass. CT and MRI revealed a lytic lesion in the occipital bone and a tumour infiltrating the dura mater, venous sinuses and cerebellum. Histopathology demonstrated a moderately differentiated squamous cell carcinoma arising from a primarily intradiploic epidermoid cyst. Despite surgery and radiotherapy, the tumour progressed and the patient died 1 year later.
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6/195. Eosinophilic myelodysplasia transforming to acute lymphoblastic leukaemia.

    A 43 year old male presented with a marked eosinophilia and associated systemic symptoms. A diagnosis of myelodysplasia was made on the basis of bone marrow morphology and karyotype. Over a 12 month period the disease transformed into acute lymphoblastic leukaemia, confirmed by flow cytometry, cytochemistry, and immunohistochemistry. karyotyping was abnormal with 5q- and -7 which persisted from diagnosis through to blastic transformation. He died following initial induction chemotherapy. Eosinophilic myelodysplasia is an uncommon condition in haematological practice and no previous report of lymphoblastic transformation has been found.
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7/195. Two cases of secondary angiosarcoma arising from fibrous dysplasia.

    Angiosarcoma associated with fibrous dysplasia is very rare. We have recently experienced two cases of angiosarcoma that secondarily arose from fibrous dysplasia. The first patient, a 55 year-old man, had noticed a deformity in the right upper arm since he was five years old. At the age of 25 years, polyostotic fibrous dysplasia was diagnosed by X-ray examination. The patient complained of swelling and pain around the left shoulder. The diaphysis of the humerus was mostly non-observable due to severe bone destruction by tumor invasion and there was a large soft tissue tumor. biopsy examination revealed grade II or III hemangioendothelioma with typical histologic findings of fibrous dysplasia. After interscapulothoracic amputation for wide tumor resection, he died of DIC. autopsy revealed multiple liver metastatic lesions of angiosarcoma. The second patient was a 66-year-old woman. She presented with a pathological fracture in the right tibia, due to an osteolytic lesion with cortical bone swelling and thinning. The histologic diagnosis was fibrous dysplasia without any sarcomatous changes. However, after a 3-time recurrence, angiosarcoma arose from the same lesion. She is now still alive with disease-free period of 6.5 years after amputation.
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8/195. Blastic crisis in previously clinically silent chronic myelogenous leukemia.

    A patient is described in whom CML first presented as blastic crisis. The diagnosis of CML was based upon the findings of Ph(1) chromosome in the bone marrow, basophilia in the peripheral blood, absence of NAP activity in the leukocytes, elevated serum vitamin B(12) and an enlarged firm spleen. CML with blastic crisis as its first expression is relatively rare, as compared to CML in which blastic crisis appears as a phase of prolonged clinically manifest disease.
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9/195. Well-differentiated intraosseous osteosarcoma of the jaws: experience of two cases from the Instituto Nacional de Cancerologia, mexico.

    Osteosarcomas of the jaws represent less than 10% of all osteosarcomas, and most of them are high-grade neoplasms. Prognostic factors in overall survival include tumor size, location and histologic grade. Examples of well-differentiated (low-grade) intraosseous osteosarcomas of the jaws (WDIOJ) have been rarely reported. This article presents two cases of this unusual lesion, one of which was located in the maxilla of a 17-year-old man and the other developed in the mandible of a 37-year-old woman. CT scan was necessary to detect the small foci of penetration into the thinned cortical bone and the reactive periosteal bone formation, which are important findings to establish the correct diagnosis of WDIOJ and help to exclude other benign intraosseous lesions that may be very similar histologically, such as fibrous dysplasia, ossifying and desmoplastic fibromas. In spite of tumor size (mean 5.2 cm), their well-demarcated borders allowed complete removal of both tumors. There is no evidence of tumoral activity in any of our patients after follow-up periods of 15 months and 5 years. Wide excision seems to be the treatment of choice for this subgroup of osteosarcomas.
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10/195. Aplasia cutis congenita with precancerous transformation - the first case. Why do these scars never develop invasive tumors?

    The term aplasia cutis congenita characterizes a heterogeneous group of diseases which have in common a focal absence of the skin. The defect may be limited to the epidermis but often involves the full thickness of the skin including the underlying bone. At birth the lesions present as erosive patches and they heal rather rapidly with a residual scar. Although more than 200 publications on aplasia cutis congenita have appeared in the medical literature between 1966 and 1999, surprisingly no case of malignant degeneration has been described. We observed a 58-year-old male patient with aplasia cutis congenita who developed crusted changes within the scar over the past 10 years. Repeated biopsies over the years have always documented a precancerous lesion without solar elastosis. Invasion has never been observed in this patient. We hypothesize that for invasive malignancies dermal-epidermal interactions are necessary. Such a cell to cell communication seems to be impossible in patients with aplasia cutis congenita, as the dermal-epidermal unit is not developed. Aplasia cutis congenita might serve as an interesting model for further investigations on the importance of epidermal-dermal interactions.
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