Systemic mastocytosis with extensive polypoid lesions in the intestines; successful treatment with interferon-alpha.

A 35-year-old female presented in 1989 with hepatosplenomegaly, but no conclusive diagnosis was established. From 1992, she experienced transient episodes of facial flushing and palpitations. Osteosclerotic change was detected radiologically. Colonoscopy revealed massive polypoid lesions. Mast cells were demonstrated in bone marrow smear and imprinted preparations of colon biopsy specimens by toluidine blue staining. Plasma concentrations of histamine and soluble c-kit were elevated. She was successfully treated with interferon-alpha and prednisolone, resulting in the disappearance of histamine-related attacks and a gradual decrease in tumor size. However, the remission was interferon dose dependent. This case was considered as systemic mastocytosis with massive polypoid colon lesions and showed the importance of maintenance therapy with interferon-alpha.

A unique case of t(15;17) acute promyelocytic leukaemia (M3) developing into acute myeloblastic leukaemia (M1) with t(7;21) at relapse.

This report describes a case of t(15;17) acute promyelcytic leukaemia (APL, FAB subtype M3) with dysgranulopoiesis at diagnosis in a patient who developed myelodysplasia (MDS) and then a second phenotype of t(7;21) acute myeloblastic leukaemia (AML, FAB subtype M1) at the time of relapse. To our knowledge, there is no report of a second phenotype of AML occurring after complete remission (CR) of APL. Furthermore, this is the first report of chromosomal abnormality t(7;21) in a case of AML. Several hypotheses for this unusual course of APL are discussed.

Characteristics of chemotherapy-induced clinical remission in long survivors with aggressive adult T-cell leukemia/lymphoma.

The acute and lymphoma types of adult T-cell leukemia/lymphoma (ATL) usually have a very poor prognosis, although some patients achieve long survival after chemotherapy. A total of 114 patients with these aggressive types of ATL were newly diagnosed at our institution from 1975 to 1989. By multivariate analysis, poor performance status and high serum creatine levels were associated with shortened survival. With combination chemotherapy, 20 patients achieved complete remission (CR), 53 achieved partial remission (PR) and 35 showed no response. Fifteen of the CR or PR patients survived for more than two years and all other patients survived for less than two years. As compared with short survivors (< 2 years) after remission, long survivors (> or = 2 years) after remission had a higher CR/PR ratio, a longer time until remission and a higher doxorubicin dose to achieve remission. Death due to causes other than the primary disease occurred in 18% of short survivors after remission and in 11.2% of nonresponders, but in none of the long survivors. Long survivors with acute ATL included 6 patients with CR and 5 patients with PR. All four lymphoma type ATL long survivors achieved CR. Monoclonal integration of HTLV-I provirus was detected in the peripheral blood mononuclear cells of all 3 PR long survivors with acute ATL studied, but was not detected in all 4 CR cases studied at remission. The minimum CD4/CD8 ratio of peripheral mononuclear cells at remission was < 1.0 in all acute ATL long survivors with CR, and was > 1.0 in all acute ATL long survivors with PR. Three out of six acute ATL long survivors with CR developed suspected viral infection just before achieving CR. Our findings show that in aggressive ATL the characteristics of remission are heterogeneous even among long survivors.

Prognostic significance of the proportion of Ki-67-positive cells in adult T-cell leukemia.

The authors examined peripheral blood samples from patients with adult T-cell leukemia (ATL) using the monoclonal antibody Ki-67 which detects a nuclear antigen present in actively proliferating cells. In patients with chronic ATL, the percentage of Ki-67-positive cells was significantly lower than in acute ATL patients (median values, 3.3% versus 18.9%, P less than 0.001). Furthermore, there was a significant inverse correlation between the percentage of Ki-67-positive cells and the length of survival (P less than 0.001). Serum lactic dehydrogenase (LDH) levels also showed a significant inverse correlation with survival, but this was less strong than that for Ki-67 (0.01 less than P less than 0.02). Thus, Ki-67 positivity appears to indicate the aggressiveness of ATL, and can possibly be used for the clinical classification of ATL patients as well as for the prediction of prognosis.

Cytogenetic studies of human T-cell leukemia virus type I carriers. A family study.

Recently, the chromosome 14q11 anomaly has been reported to be specific to adult T-cell leukemia (ATL), and this anomaly has also been confirmed in the preleukemic state of adult T-cell leukemia (pre-ATL) patients. Because the cytogenetic abnormality at the stage of human T-cell leukemia virus type I (HTLV-I) carrier remains uncertain, we performed cytogenetic studies of lymphocytes stimulated with phytohemagglutinin in three HTLV-I carriers and three non-HTLV-I carriers in an ATL family. As a result, in three HTLV-I carriers, four of 311 cells examined (1.3%) had chromosome 14q11 anomaly. However, in three non-HTLV-I carriers, none of 260 cells examined had chromosome 14q11 anomaly. These results suggest that chromosome 14q11 anomaly is already present at the stage of HTLV-I carrier and seems to be an important cytogenetic clue to the pathogenesis of ATL.

[Trisomy of chromosome 11 in a case of common ALL antigen-positive acute myeloblastic leukemia (FAB-M1)].

In February 1986, a 68-year-old woman was diagnosed as having acute myeloblastic leukemia (FAB-M1). At the time of diagnosis, 86.0% of the bone marrow cells were myeloblastoid, and 15% of these myeloblastoid cells were positive to myeloperoxidase. Surface marker analysis by flow cytometry disclosed granulocyte-associated antigen (MY7) and also lymphocyte-associated antigen (CALLA) on the leukemic cells. Chromosomal banding studies of bone marrow cells revealed trisomy 11 in 6 of 19 metaphases examined and normal karyotype in the others. Complete remission was attained after intensive combination chemotherapy, and has remained for 38 months. Only 19 patients with trisomy 11-associated acute nonlymphocytic leukemia (ANLL) including the present case have been reported. Morphologic analyses have revealed that the frequency of FAB-M1 is high. However, except for the present case, surface marker findings were apparent in only one M5a patient, in whom monocyte-macrophage-associated antigen was detected. Accordingly, careful surface marker studies will be needed to clarify the frequency of acute mixed lineage leukemia in such patients.

[Cytogenetic studies of healthy HTLV-I carriers (Report 1): Cytogenetic studies of an ATL family].

The chromosome 14q11 anomaly has been reported to be specific to adult T-cell leukemia (ATL) and this anomaly has also been confirmed in preleukemic state of ATL (pre-ATL) patients though the frequency is low. In an attempt to clarify if the same chromosome aberrations could be found also at the stage of HTLV-I carrier and if there is any cytogenetic difference from non-HTLV-I carriers, a cytogenetic study of lymphocytes stimulated with phytohemagglutinin in three HTLV-I healthy carriers and three non-HTLV-I carriers in an ATL family was performed. The results were as follows. 1. In three HTLV-I carriers, 7 of 311 cells examined (2.3%) showed chromosome aberrations, and 4 cells (1.3%) had 14q11 anomaly. 2. In three non-HTLV-I carriers, 4 of 260 cells examined (1.5%) showed chromosome aberrations, whereas no cells had 14q11 anomaly. These findings suggest that 14q11 anomaly is already present at the stage of HTLV-I carrier and seems to be an important cytogenetic clue to the pathogenesis of ATL.

[A trial for prolongation of chronic phase of chronic myeloid leukemia--maintenance of leukocyte counts within normal range with busulfan].

To prolong the survival of patients with chronic myeloid leukemia (CML), 19 patients were treated with busulfan to keep their leukocyte counts within normal range by controlling bone marrow hyperplasia. The duration of chronic phase in these patients was significantly longer than that in historical controls who were treated conventionally with busulfan. This prolongation was not ascribable to the difference in such prognostic factors between the two therapy groups as splenomegaly, leukocyte count and percentage of peripheral blasts. There was a significant difference again in the duration of chronic phase between the two therapy group even when restricted to each 11 patients with intermediate relative risk (0.7-1.5) according to Sokal et al. Four patients showed thrombocytopenia less than 5 x 10(4)/microliters, but all these patients recovered within 4 months and there was no further critical side effect except subcutaneous bleeding. This study suggests that maintenance of leukocyte count within normal range and suppression of granuloid hyperplasia in bone marrow with busulfan may prolong chronic phase of CML. Probability of clonal evolution may be decreased by reducing the total leukemic cell mass and suppressing cellular turnover of primitive CML stem cells. Another possibility is that prolongation of chronic phase might be dependent on the appearance of normal karyotype clone after long-term bone marrow suppression just like after intensive chemotherapy or alpha-interferon therapy.

Chromosomes and surface markers in lymph node cells from 2 patients with AILD and IBL-like T-cell lymphoma.

Chromosomes and surface markers in lymph node cells from 2 patients with angioimmunoblastic lymphadenopathy associated with dysproteinemia (AILD) or immunoblastic lymphadenopathy (IBL) and with IBL-like T-cell lymphoma, respectively, were examined before treatment. In the patient with AILD, a small clone with chromosome abnormality was found in lymph node cells although a surface marker study failed to demonstrate monoclonality. In this patient, the clinical and cytogenetic findings suggested a subtype of lymphoma with a mild clinical course and a benign histological appearance. In the patient with IBL-like T-cell lymphoma, a high percentage of metaphases showed chromosome abnormalities such as ring chromosomes. The clinical, immunological and cytogenetic findings suggested an aggressive type of lymphoma, even though the histologic appearance was similar to that of IBL.

[Epidemiological studies on malignant lymphoma in Nagasaki City, especially in relation to atomic bomb exposure].

One hundred and eighty-two (182) cases of malignant lymphoma registered at the Nagasaki Tumor Registry from 1973 to the end of 1977 were studied in relation to atomic bomb exposure. No significant difference in the incidence of malignant lymphoma was found between the exposed and nonexposed groups. One hundred and thirty-one (131) cases excluding Hodgkin's disease and mycosis fungoides were histologically reviewed and classified according to Lymphoma Study Group (L.S.G.) and Working Formulation (W.F.) Classifications. Using the L.S.G. Classification, the three histological types (diffuse large cell, diffuse pleomorphic, and diffuse medium sized cell) occupied 72.7% and 69.0% of the exposed and nonexposed groups respectively. No significant difference in histological type between the exposed and nonexposed groups could be found with an exception of a slightly higher incidence of the diffuse medium sized cell type in the exposed group than in the nonexposed group. An evaluation of these results was made in comparison with the results in Hiroshima.

Prognostic significance of the morphological dysplastic changes in chronic myelogenous leukemia.

Various morphological dysplastic changes were observed in patients with chronic myelogenous leukemia, especially in the acute crisis. To clarify their significance, we divided 45 patients in the acute crisis into two groups by our scoring system, the dysplastic group and the non-dysplastic group. Five of 25 subjects in the non-dysplastic group entered complete remission. None of 20 subjects in the dysplastic group did so, and the mean survival after the onset of acute crisis is significantly shorter in the dysplastic group than in the non-dysplastic group. Some patients in the dysplastic group had obvious dysplastic changes several months before the acute crisis. These findings suggest that acute crises in some cases may occur with or be preceded by the development of dysplastic clones similar to myelodysplastic syndrome; these patients respond poorly to conventional chemotherapy.

Primary pancreatic carcinoma in childhood. Pancreatoblastoma.

A case of primary pancreatic carcinoma confirmed by postmortem examination in a 15-year-old girl is presented. The tumor was studied by light and electron microscopy and an indirect immunoperoxidase technique. Some of the tumor cells contained eosinophilic, PAS-positive, diastase-resistant granules. Electron microscopy revealed large electron-dense granules resembling zymogen granules. The granules seen in the islet cell tumors were not demonstrated by electron microscopy and immunoperoxidase technique. These findings suggest that the tumor is of duct cell origin with some differentiation toward the acinar cells. The tumor appears to belong to the so-called "pancreatoblastoma".

[Epidemiological studies on thyroid cancer in Nagasaki City].

We studied 89 cases of thyroid cancer registered at the Nagasaki Tumor Registry during the period from 1973--1977. The incidence of thyroid cancer tended to be higher in persons exposed to the atomic bomb, especially women, than in the nonexposed population. Compared with nonexposed individuals, the relative risk for thyroid cancer was increased in distally as well as proximally exposed persons, but not in early entrants to the bombed city. In 83 histologically examined patients, papillary carcinomas were highly predominant, they were more prevalent in the exposed than in the nonexposed population.