Katsuyuki Hirai

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.

Loss of ABCB7 gene: pathogenesis of mitochondrial iron accumulation in erythroblasts in refractory anemia with ringed sideroblast with isodicentric (X)(q13)

An isodicentric (X)(q13) (idicXq13) is a rare, acquired chromosomal abnormality originated by deletion of the long arm from Xq13 (Xq13-qter), and is found in female patients with hematological disorders involving increased ringed sideroblasts (RSs), which are characterized by mitochondrial iron accumulation around the erythroblast nucleus. The cause of increased RSs in idicXq13 patients is not fully understood. Here, we report the case of a 66-year-old female presenting with refractory anemia with ringed sideroblasts (RARS), and idicXq13 on G-banded analysis. We identify the loss of the ABCB7 (ATP-binding cassette subfamily B member-7) gene, which is located on Xq13 and is involved in mitochondrial iron transport to the cytosol, by fluorescent in situ hybridization (FISH) analysis and the decreased expression level of ABCB7 mRNA in the patient’s bone marrow cells. Further FISH analyses showed that the ABCB7 gene is lost only on the active X-chromosome, not on the inactive one. We suggest that loss of ABCB7 due to deletion of Xq13-qter at idicXq13 formation may have contributed to the increased RSs in this patient. These findings suggest that loss of the ABCB7 gene may be a pathogenetic factor underlying mitochondrial iron accumulation in RARS patients with idicXq13.

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.

PLURAL IMMUNOGLOBULIN SYNTHESIS IN A SINGLE CELL : AN ULTRASTRUCTURAL STUDY OF TWO CASES WITH THREE M-PROTEINS

Electrophoresis revealed two cases of malignant lymphoma that each contained three M-proteins (IgM lambda.lgG kappa.lgG lambda and IgM lambda.IgM kappa.lgG kappa) in the sera. To determine cellular origin of each M-protein, atypical lymphoid and plasmacytoid cells of both cases were examined by electron microscopy. Atypical lymphoid and plasmacytoid cells possessed rough endoplasmic reticula (RERs) in varying degrees, as seen by conventional electron microscopy, and showed double-stainability for plural antibodies against immunoglobulins following double stainings of immunoelectron microscopy using immunogold staining. Rabbit antibodies against human IgM, lgG, free kappa-light chain and free lambda-light chain were used for the immunoelectron microscopic staining. By the double staining method, plural immunoglobulins, IgM/IgG, IgM/free kappa, IgM/free lambda, IgG/free kappa, IgG/free lambda and free kappa/free lambda, were simultaneously detected in varying degrees in the Golgi area, RERs, and dense bodies of lymphoid and plasmacytoid cells. In conclusion, this study directly exhibited, through electron microscopy, that plural immunoglobulins were synthesized at the same time in a single cell, and that the process of immunoglobulin synthesis in the lymphoid and plasmacytoid cells was different from that in a normal B-cell.

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.

Inflammatory Fibroid Polyp of the Ileum Which Could be Endoscopically Diagnosed —A Case Report and Review of the Literature—

Abstract: Inflammatory fibroid polyp (IFP) of the small intestine is a very rare disease. Our review of the literature revealed only 40 cases of small intestinal IFP were reported from July 1975 through August 1989 in Japan. It is extremely difficult to make a definite diagnosis of IFP prior to surgery; none of the cases reported were diagnosed preoperatively. We describe here the first case of small intestinal IFP in Japan whose diagnosis was strongly suspected from an endoscopic examination prior to surgery.

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.