Ryuichi Onodera

DURABLE REMISSION AFTER SPLENECTOMY FOR WALDENSTROM'S MACROGLOBULINEMIA WITH MASSIVE SPLENOMEGALY IN LEUKEMIC PHASE

A patient with M-proteinemia (IgM, kappa type), lymphocytosis, anemia, and massive splenomegaly, was diagnosed as having Waldenströms macroglobulinemia (WM). Since this case was refractory to chemotherapy, splenic irradiation was performed, which effectively reduced the serum IgM level, spleen size, and lymphocyte counts; however, its effect was transient. Splenectomy was then carried out. The spleen contained abundant IgM-producing lymphocytes, and after splenectomy, the serum IgM values decreased and the peripheral blood counts returned to near normal. The transient increases of serum IgM occurred during two infectious episodes postoperatively. The patient has now been in a satisfactory remission for six years after splenectomy. The removal of an IgM-producing/secreting site and release from hypersplenism may be the major mechanisms involved in achieving the durable remission after splenectomy. In individual cases of WM with massive splenomegaly, we recommend splenectomy as part of the management of this disorder.

Satisfactory remission achieved by PUVA therapy in a case of crisis-type adult T-cell leukaemia/lymphoma with generalized cutaneous leukaemic cell infiltration

We used PUVA therapy in a patient with crisis‐type adult T‐cell leukaemia/lymphoma and generalized cutaneous leukaemic cell infiltration. PUVA proved very effective in reducing leukaemic cells and in clearing the eruption. To understand the way in which PUVA produced a reduction in the number of leukaemic cells, we examined peripheral blood cells by light and electron microscopy. Light microscopy was of little help, but electron microscopy revealed that PUVA induced apoptosis‐like changes in circulating leukaemic cells. This suggests that apoptosis‐like changes in leukaemic cells might be the reason for the success of this treatment.

Light and electron microscopic study of omental milky spots in New Zealand black mice, with special reference to the extramedullary hematopoiesis.

Omental milky spots are especially large and numerous in New Zealand Black (NZB) mice, which are known to develop spontaneous autoimmune diseases. We investigated omental milky spots in NZB mice by light and electron microscopy. The milky spots were composed of abundant lymphocytes/plasma cells with macrophages, neutrophils, eosinophils, megakaryocytes, and various stromal cells. In addition, clustered neutrophils in various maturation stages with occasional mitotic figures were frequently present in the milky spots: apparent neutrophilic myelopoiesis was present. The presence of megakaryocytes was sporadic. Considering the giant size of megakaryocytes, their direct migration into the milky spots from the bone marrow or spleen seems improbable. Thus, the presence of megakaryocytes was interpreted as probable megakaryopoiesis. Erythroblasts were not contained in the milky spots. These findings seem to indicate that the milky spots in NZB mice represent a special type of lymphoid tissue with active neutrophilic myelopoiesis and probable megakaryopoiesis. Reticulum cells in the milky spots in NZB mice had well-developed dense bodies consisting of clustered parallel tubules that showed a hexagonal array. However, the biological significance of these cells remains unknown.

Vacuolated Glycogen-laden Leukemic Cells in a Case of Crisis Type Chronic Adult T-cell Leukemia

We present a unique case of crisis type chronic adult T-cell leukemia (ATL), in which the majority of leukemic cells had abundant periodic acid-Schiff (PAS)-positive cytoplasmic inclusions. These inclusions were found to be composed of glycogen because the PAS-positivity completely disappeared after digestion with amylase or human saliva. Electron microscopy also revealed that the inclusions consisted of aggregated beta particles of glycogen. The mechanism of glycogen accumulation in leukemic cells remains unknown; however, the presence of such inclusions in leukemic cells may be helpful diagnostically in T-lymphocyte malignancies.

Ultrastructural study of periodic lamellar granules in human neutrophils

Granules consisting of periodically arranged membranous lamellae and amorphous electron-opaque material, i.e., periodic lamellar granules, are present in human neutrophils. To date, no extensive ultrastructural studies have been carried out on these granules because of their infrequent presence in neutrophils. The bone marrow of 18 cases of chronic myeloproliferative disorders, including one case of chronic neutrophilic leukemia in which periodic lamellar granules were frequently seen in neutrophils, was investigated by electron microscopy. Periodic lamellar granules were seen in neutrophils in 12 of the 18 cases at varying frequencies. They were preferentially seen in immature neutrophils. The transverse profiles of these granules revealed concentric complete/incomplete rings or periodic parallel straight lines, i.e., various patterns of lamellar arrangement were present. Periodic lamellar granules were positive for myeloperoxidase and lysozyme at the electron-microscopic level. These results suggest that these granules represent a primary neutrophil granule subtype. However, their functional and pathologic significance remains unknown.

Parallel Tubular Granules in Human Immature Neutrophils- An Electron Microscopic Study

Unique rounded granules consisting of clustered parallel tubules, 29-31 nm in diameter, with occasional, flocculent or amorphous electron-dense material (parallel tubular granules, PTGs) were found in immature neutrophils in the bone marrow in a case of chronic neutrophilic leukemia (CNL). PTGs were positive for electron microscopic myeloperoxidase. Since no structures similar to PTGs have been documented, we investigated the bone marrow of 65 adult patients with hematologic diseases, and 7 adult patients with miscellaneous non-hematologic diseases, by electron microscopy. The results showed that no PTGs were found in any cases other than the original CNL case. These findings suggest that PTGs are rare granules representing certain primary granules. In addition, the presence of PTGs might be helpful in diagnosing CNL.

An ultrastructural study of primary granule subtypes in human neutrophils from chronic myeloproliferative disorders

The bone marrow of 17 patients with chronic myeloproliferative disorders (CMPDs) was investigated by electron microscopy. Three subtypes of primary granules, i.e., parallel tubular granules (PTGs), fibrillar granules (FGs), and periodic lamellar granules (PLGs), were found in neutrophils from the CMPDs. Only one case of chronic neutrophilic leukemia (CNL) showed PTGs. Both FGs and PLGs were found in various CMPDs in varying frequencies. These granules tested positive for myeloperoxidase, and were seen primarily in immature neutrophils. In addition, the presence of hybrid FG/PTG granules and hybrid FG/PLG granules was confirmed. These results suggest that PTGs, FGs, and PLGs represent subtypes of primary granules, and that a close association exists between them.