Both T- and B-lymphocytes in circulating peripheral blood and in bone marrow aspiration as well as the responsiveness in vitro to PHA-P and pokeweed mitogen were studied in the patients with hypoplastic anemia.
The numbers of circulating lymphocytes and T- and B-lymphocytes decreased in proportion to the severity of hypoplastic anemia while the null cell had increased. Significantly suppressed responsiveness to PHA-P in vitro was observed in the circulating lymphocytes and in the bone marrow lymphocytes.
On the contrary soloculture cpm increased in the bone marrow lymphocytes than in the circulating lymphocytes, and the responsiveness to pokeweed mitogen remained in the normal range in the circulating lymphocytes and suppressed in the bone marrow lymphocytes.
Effectively splenectomized cases showed an increased T- and B-lymphocytes in the circulating lymphocytes.

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The incidence of meningeal leukemia and the relationship between the incidence of meningeal leukemia and different parameters (median survival, VCR-administration, type of leukemia, initial peripheral WBC count, hepatomegaly, splenomegaly, and lymph-node swelling) was studied in 93 adults with acute leukemia.
The following results were obtained:
1) During May, 1959 - May, 1968, no meningeal leukemia was recognized in 50 adults with acute leukemia; during May, 1968 - Dec., 1973, the incidence was 16.3% (7/43).
It was speculated that the increased incidence between both series was largely due to increased length of survival.
2) In this study, the leukemic population with high risk of developing meningeal leukemia was as follows; a) acute monocytic leukemia, b) acute leukemia with negative peroxidase reaction, c) VCR-administered case of acute leukemia with the positive peroxidase reaction, d) acute leukemia with an peripheral WBC count greater than 50,000/cmm, e) acute leukemia with splenomegaly, f) and with lymphnode swelling.
3) In these population, the aggressive and prophylactic treatments for meningeal leukemia are recommended.
4) The transient, recurrent symptoms of neurologic and psychic disturbance without meningism and manifestations of increased CSF pressure, were very suggestive signs of initial symptom of meningeal leukemia.

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von Willebrand's disease is autosomal dominant bleeding disorder characterized in most patients by a prolonged bleeding time, low factor VIII procoagulant activity, defective platelet retention to glass and other normal platelt functions. Patients with von Willebrand's disease have low levels of factor VIII-related antigen and defective or decreased platelet aggregation in response to the antibiotic Ristocetin.
We studied about platelet function, factor VIII activity, Ristocetin induced platelet aggregation and factor VIII-related antigen in 11 patients of 6 families, suffering from typical von Willebrand's disease and 5 patients of 4 families with von Willebrand-like disease.
Detailed platelet studies demonstrated abnormal aggregation in response to ADP (Case 3) and collagen (Case 2, 3, 4, and 13). A patient (Case 2) revealed impaired ADP release and another showed so poor clot retraction as thromboasthenia and 5 patients (Case 1, 3, 8, 9 and 11) had platelet factor 3 defect. However, all these platelet function abnormalities were transient. Ristocetin induced platelet aggregation was absent or impaired in 6 of the 8 typical cases. Two typical and 4 atypical cases revealed normal Ristocetin aggregation. Four of the 8 typical cases had low levels of factor VIII-related antigen. Four typical and four atypical cases had normal levels of this antigen. However, defective Ristocetin induced platelet aggregation was normalized by infusion of either normal, or hemophiliac plasma cryoprecipitate, containing normal factor VIII related antigen.
These findings suggested that in von Willebrand's disease impairment of Ristocetin aggregation might be due to either a low concentration of factor VIII-related antigen or quantitative defect of factor VIII-related antigen.

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A 38-year-old teacher was first seen on January 7, 1972, for the evaluation of splenomegaly. He had been admitted to the Kanto Chuo Hospital in October 1971, when a diagnosis of myelofibrosis had been made by a biopsy material of the iliac marrow.
On physical examination he was anemic and the spleen was felt 2 cm. below the navel. Blood examination revealed hemoglobin 9.9 Gm. per 100 ml., RBC 3,800,000 per cu. mm., hematocrit 31%, reticulocytes 1.2%, WBC 13,900 per cu. mm. with 13% myeloblasts, 12.5% basophils and 7 nucleated red cells per 200 white cells. Neutrophil alkaline phosphatase score was low and Ph¹ chromosome negative. Platelet count was 645,000 per cu. mm.
The first admission was on January 28, 1972, for the ferrokinetic study. PID T/2 was 30.4 minutes and highest RCIU 41%. A body surface counting study revealed a highest radioactivity over the spleen region.
A diagnosis of primary myelofibrosis with myeloid metaplasia of the spleen was made and he was placed on a daily dose of 20 mgm. of 6-mercaptopurine. On September 16, 1972, he was readmitted with sudden symptoms of ileus, which was relieved by a high pressure enema.
At the beginning of February 1973 his conditions deteriorated with high fever, anemia and tenderness of the enlarged spleen and he was admitted for the third time on March 2, 1973.
On the third admission 60% of the peripheral leukocytes were identified as atypical myeloblasts. He expired on April 11, 1973, after high fever and recurrent ileus.
Autopsy revealed hypercellular marrow with atypical myeloblasts and myelofibrosis. Spleen weighed 4,070 Gm. with myeloid metaplasia and an infiltration of immature blastoid cells. Direct cause of death was ileus attributed to adhesion and distortion of the jejunum.

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“Castleman's lymphoma” was first described as “mediastinal lymph node hyperplasia resembling thymoma” by Castleman in 1954. Up to 1974, approximately 190 cases have been reported throughout the world.
A 17-year-old high school girl was referred to our clinic because of an abnormal shadow in the right lung roentgenologically, which was discovered by mass screening on April 1969. Since the patient had otherwise no abnormal clinical and laboratory findings except the mass, we decided to follow up her clinically without any particular treatment. The shadow has been enlarged gradually from 2.3×2.3 cm to 3.9×4.5 cm on the roetogenogram during 4 years without any clinical symptoms. On September 1973 the tumor was excised for probable hamartoma. Surgically, the tumor was found around pulmonary artery of the right hilus. Grossly, this tumor measured 4.5×4×3 cm, weighed 21 g, was elastic firm in consistency and was encapsulated by pinkishyellow fibrous membrane. Histologically, the lesion consisted mainly of mature lymphocytes although lacked usual architechture of a lymph node, and onion-like structures resembling Hassall's corpuscles were studded among the markedly proliferating lymphocytes and radiating capillaries, histologically being consistent with a typical hyaline vascular lesion of giant lymph node hyperplasia by Castleman.
This is the 24th case of Castleman's lymphoma ever reported among Japanese population. All of the cases reported in this country were the hyaline vascular type. The age of the patients ranged from 9 to 60 years (the median: 18 years), and there appeared to be no particular sex preference. The 20 of 24 cases (83%) of the lesions were located in the chest. 15 of them being at the hilus, 3 cases at the neck, the remaining one case at the supraclavicular fossa, and ectopic occurrence was not reported yet. Majority of the cases were discovered by chance through routine x-ray examinations of the chest, and 6 cases complained of frequent common cold or general malaise. There was no specific hematological abnormalities. The number of the tumor extirpated was single to 10, and the largest tumor reported measured 16×9×5.5 cm and weighed 390 g. The pathogenesis of this disease remains to be elucidated.

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A 20-year-old woman, a product of a nonconsanguinous mating, was first referred for evaluation of short stature in February, 1974. The parents and two living siblings were phenotypically and hematologically normal but one brother died of unknown cause 2 days after birth. The patient was born at term, normally. But subsequent development was poor, showing L. C. C., malformation of fingers and toes and infirmity against infection. After that, she continued normal mental development, but remained shorter for her age. The menarche had occurred at the age of 18 years and her menses were irregular, occurring only 4 times a year. There was no history of ingestion of or exposure to substances known to cause bone marrow depression. Physical examination revealed a 138.2 cm tall, 26.5 kg, normally proportioned individual. There were a light brown pigmentation of the skin, DuBois' sign, brachydactylia and dental hypoplasia. No petechie, lymphadenopathy, hepatosplenomegaly and hyperreflexia were found. Hematological examinations revealed pancytopenia, espicially neutropenia, and bone marrow hypoplasia, but almost normal pattern in ferrokinetics studies. Chromosome aberrations were found in 36% of cells in lymphocyte culture. Hypogonadism was presumed by endocrinological studies. No abnormality was found in immunological examination. The patient is still being followed up in this clinic, without receiving any medication because of keeping clinical good condition.

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Patient was of 58 year-old female.
For about 40 years, she had had repeated periodic fever since 18 year-old, and the etiology could not be determined. She was diagnosed as chronic lymphocytic leukemia at the age of 58, and was observed for 6 months without therapy. During that time, her lymphocyte count altered periodically in range from 20,000 to 90,000 in about 1 month.
Lymph nodes were swollen during the period of lymphocyte proliferation.
In the febrile periods, her lymphocyte count began to decrease, and lymph nodes were decreased in size and consistency. In the afebrile periods, lymphocyte proliferation and lymphoma were demonstrated.
Therapeutic trial of prednisolone unexpectedly resulted in marked increase of peripheral lymphocyte count and diminished the febril phase. Then she was treated by Chlorambucil and got into remission of CLL, but she died of pulmonary cancer 1.5 years later. The histology of pulmonary cancer was carcinoma simplex.
Problems of tumor growth and host immunity on the basis of clinical course of this case were discussed.

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This case report is concerned with a 30-year-old woman who began to have genital bleeding during the remission of AML, and it was found to have massive leukemic cell infiltration in the female genital organs on autopsy. A diagnosis of AML was made and she was admitted to the hospital in Dec. 1973. She got well with combination therapy of DM, Ara-C, 6-MP and steroid, and was discharged. She had complaints of genital bleeding and fatigue with fever in July 1974, and was hospitalized again. In spite of the use of antileukemic therapy and antibiotics, she died on Sept. 5. On autopsy, there were massive leukemic cell infiltrations in the vagina, cervix of the uterus and the ovarium. Therefore, it may be necessary to examine the infiltration of the leukemic cells by biopsy whenever the patient has abnormal genital bleeding during the remission of AML.

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Two cases of macroglobulinemia, 65-year-old female and 59-year-old male, associated with obvious destructive bone lesions caused by neoplastic proliferation of plasma cells were reported.
Classical criteria for primary macroglobulinemia of Waldenström were scored by 1) presence of monoclonal gammopathy of IgM type, 2) proliferation of lymphoid or plasmocytoid lymphocytes, 3) lack of punched-out bone lesion, 4) high incidence of hepato-splenomegaly and of lymphadenopathy, 5) hyperviscosity syndrome associated with bleeding tendency and 6) relative benign course of the disease. Especially the lack of punched out bone lesion and proliferation of plasmocytoid lymphocytes, instead of plasma cells in multiple myeloma, are stressed repeatedly to differentiate the primary macroglobulinemia from multiple myeloma. Both cases reported here showed obvious punahed-out bone lesions, caused by proliferation of plasma cells, which were confirmed by X-ray bone survey and by autopsy.
Recently, three cases of macroglobulinemia associated with apparent bone lesion were reported among 80 reported cases of primary macroglobulinemia in Japan. characteristic findings of those cases were the lack of hepato-splenomegaly and lymphadenopathy, and marked neoplastic proliferation of plasma cells in bone marrow. The neoplastic proliferation of plasma cells associated with punched-out bone lesions are the charcteristic fiindings for multiple myeloma rather than that of primary macroglobulinemia.
The presence of IgM-secreting plasma cell clone has been confirmed by several investigators. Thus, those cases with monoclonal IgM associated with punched-out bone lesions caused by neoplastic proliferation of plasma cells should be defined as “Multiple myeloma of IgM type”.

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