Nobuko Shima

Improved survival rate in primary intracranial lymphoma treated by high‐dose radiation and systemic vincristine‐doxorubicin‐cyclophosphamide‐prednisolone chemotherapy

Thirty patients with histologically proven primary intracranial non‐Hodgkins lymphoma were treated at Kyoto University. Ten of them were treated prospectively with a radiation‐chemotherapy protocol. All but four specimens were recently reexamined and classified according to the Working Formulation system. The predominant histologic types were diffuse large cell type, large cell immunoblastic type, and diffuse mixed small and large cell type, seen in 38%, 21%, and 21% of cases, respectively. Before 1980, 16 patients were treated with postoperative radiation without definite chemotherapy, and only one has survived more than 5 years. Local recurrence was the most common cause of failure. In 1981, the authors started a protocol in which four to six courses of systemic chemotherapy with vincristine, doxorubicin, cyclophosphamide, and prednisolone (VEPA) was given after whole brain radiation (30–40 Gy) with a local boost up to 50 to 60 Gy. Eight patients completed this protocol, and all of them are alive at 16 to 100 months after diagnosis, with three patients surviving more than 5 years. Only one patient developed recurrence. On the other hand, six patients who did not complete or receive chemotherapy after 1981 are dead or alive with recurrence. Correlation between the Working Formulation subtype and prognosis was not clear because of the variety of treatment. Two patients receiving chemotherapy developed brain necrosis, which was fatal in one case, and the other two patients treated with the protocol are in a poor state without signs of recurrence. Chemotherapy may enhance the radiation effect on normal brain tissue as well as tumor. Combination of radiotherapy and chemotherapy can improve the survival rate, but the optimal dosage needs to be investigated further.

Extranodal non-Hodgkin's lymphoma of the head and neck. A clinicopathologic study in the kyoto-nara area of japan

The clinicopathologic features of 114 Japanese patients with extranodal non‐Hodgkins lymphoma of the head and neck region were analyzed. The median age was 60.5 years and the male:female ratio was 1.5:1. The most common site of involvement was Waldeyers ring, followed by the oral cavity, thyroid gland, paranasal sinuses, nasal cavity, and larynx. Seventy‐five percent of the patients were in Stage I or Stage II at admission. Histologically, diffuse lymphoma accounted for 94% and follicular lymphoma for 6% of cases. The histologic grade according to the Working Formulation System of the National Cancer Institute was low in 11%, intermediate in 75%, and high in 14% of cases. Immunohistochemical study showed that the majority of the cases were of B‐cell type and only 13 cases (11%) were of the T‐cell type. Peripheral T‐cell lymphomas (eight cases) mainly occurred in the nasopharynx and nasal cavity, whereas four of five thymic T‐cell lymphomas were found in the palatine tonsil. The over‐all 5‐year survival rate was 54%, and the factors affecting survival were sex, histologic grade, T/B phenotype, clinical stage, and the site of initial presentation. Five‐year survival with nasal cavity and Waldeyers ring lymphoma was 24% and 46%, respectively. The poor prognosis of lymphomas at these sites might result from the predominance of T‐cell lymphoma, the paucity of low grade lymphoma, and the relatively high incidence of cases that were in an advanced stage at presentation. In Stage II, patients treated with combined therapy tended to have a better 5year survival rate than those treated with radiotherapy alone.

Malignant lymphoma of the testis: histological and immunohistological study of 28 cases.

Histological and immunohistological studies were made in 28 patients with testicular lymphoma who presented with a right (15), left (11) or bilateral (2) scrotal swelling. Patient age at hospitalization ranged from 39 to 87 years, with a median age of 64 years. The disease was stage 1 in 12 patients, stage 2 in 11 and stage 3 in 5. Histologically, most of the neoplasms were of the diffuse large cell type, with an immunoblastic type being the most common. Immunohistochemistry revealed that all but 2 cases were of the B cell type. None of the tumors reacted with monoclonal antibody for T cell. These findings suggested that testicular lymphoma exclusively consisted of the B cell type, identical to previous reports of extranodal lymphomas other than those in the skin. The pertinent literature is reviewed and the histogenesis of testicular lymphoma is discussed.

A radiotherapeutic experience for localized extranodal non-Hodgkin's lymphoma: prognostic factors and re-evaluation of treatment modality

Between 1966 and 1988, 149 patients were treated with radiotherapy for localized extranodal lymphoma. The average total dose given was 39.8 Gy for low grade disease and 48.7 Gy for all other disease. Of the 149 patients, 60 also received adjuvant chemotherapy. Twenty-four had low grade lymphoma, 109 had intermediate grade disease, and 16 had high grade disease, histologically. The distribution of histological grade and T/B phenotype varied with the primary site. Low grade lymphomas were found mainly in the orbit, and T-cell lymphomas were found in the nasal cavity and nasopharynx. The 5-year survival rates according to tumor location were 89% for oral cavity, 86% for paranasal sinus, 83% for thyroid, 69% for orbit, 47% for Waldeyers ring (WAR), 44% for testis, 23% for CNS, 21% for nasal cavity and 60% for other sites. Histological grade and T/B phenotype both had prognostic importance. Combined chemotherapy significantly improved the survival rate only for disease with intermediate or high grade histology. Other prognostic factors according to the primary site were the bulk of lymph node for WAR disease, the radiation dose for CNS disease, bone erosion for orbital disease, stridor for disease of the thyroid, and the tumor stage for disease of both the testis and the thyroid.

Intracerebral malignant lymphoma with fluctuating regression and spatial evolution

Seven patients with histologically proven primary intracerebral malignant lymphoma, characterized by a fluctuating nature with both transient regression and spatial evolution of the tumors without contiguity to the initial lesion, are presented. Although the overall outcome was unfavorable, two cases had a long-term survival of 3 years or more and one of them showed a good quality of life. Correlation among characteristic clinical presentations, computed tomography scans, and prognostic factors after management with surgery, radiation, and chemotherapy, including steroids, is discussed.

Distribution of Vitamin B12 R-binder in Lung Tumors: Implications for Cell Differentiation

Expression of vitamin B12 R-binder, a specific binding protein for vitamin B12, was studied immunohistochemically in normal lung tissues and 107 lung tumors of various types. In normal tissues, vitamin B12 R-binder (R-binder) expression was restricted to the mucous cells of bronchial or bronchiolar epithelium and submucosal glands as well as to nonciliated bronchiolar (Clara) cells. Among lung carcinomas, 38% of squamous cell carcinomas, 42% of adenocarcinomas and 23% of large cell carcinomas showed positive staining for R-binder whereas small cell carcinomas did not. These findings offer the possibility that a majority of the histologic types of lung carcinoma have common histogenetical characteristics with mucous or Clara cells. Of the bronchial gland tumors, R-binder could be detected in a mucoepidermoid carcinoma but not in adenoid cystic carcinomas. Epithelial components in both pulmonary blastomas and hamartomas showed a reactivity for R-binder, suggesting that these tumors contained components composed of cells with bronchiolar cell differentiation. The immunohistochemical examination of lung tumors, using anti-R-binder antibody, may have some implications in the cell differentiation of lung tumors.

Chemotherapeutic effects of intra-arterial administration of ACNU in primary intracerebral non-Hodgkin's lymphoma.

The authors report five patients with primary intracerebral non-Hodgkins lymphoma who were treated with several cycles of intra-arterial injection of 1-(4-amino-2-methyl-5-pyrimidinyl)-methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) at doses of 80 to 100 mg/m2/injection at several monthly intervals. There was no simultaneous use of steroids, and no patients had concomitant immunosuppression; no patient was human immunodeficiency virus positive. This therapy was initially used in four patients with advanced recurrent lymphoma. These patients experienced tumor progression despite our institutional standard therapy comprising cranial irradiation followed by repeated courses of systemic multi-agent chemotherapy (cyclophosphamide, vincristine, adriamycin, and prednisolone) more than 3 months previously. Based upon brain computed tomography scans and clinical neurologic examinations, three of the four cases showed partial responses ranging from 10 to 12 months in duration, whereas the other patient remained stable without worsening for 8 months. A fifth case was particularly noteworthy; this patient had no prior therapy and intra-arterial chemotherapy alone induced an 18-month, disease-free remission. No significant therapy-related complications nor neurotoxicity were seen. These results suggest that intra-arterial administration of ACNU may be a potential candidate for intracerebral lymphoma therapy.

Extended survival with high quality of life in patients with primary intracerebral non-Hodgkin's lymphoma: report of four cases.

Abstract Between 1977 and 1993, we treated 47 patients with histologically verified primary intracerebral non-Hodgkins lymphoma of B-cell origin. The cases of four of these patients (8.5% of the total) with long-term survival with high quality of life for more than 5 years are presented. Three have remained relapse-free for between 8.5 and 12 years after completion of original treatment; the fourth obtained complete remission for more than 5 years before death from tumor recurrence. All four patients were treated with our institutional therapeutic regimen, which includes radiotherapy consisting of 50–60 Gy to the tumor and 30–40 Gy to the whole brain, followed by four to six cycles of chemotherapy with cyclophosphamide, vincristine, adriamycin, and prednisolone at 4- and 8-week intervals. No further treatment was performed after remission had been obtained. No factors—including patient sex, age, tumor location, multiplicity of lesions, histology, or treatment modality—proved to be specific predictors of therapeutic success. The administration of chemotherapy beginning at the conclusion of radiotherapy in order to enhance the radiation antitumor effect may, however, have contributed to therapeutic success. The finding that all four patients had an immediate response to radiation may be related to their relatively high rate of survival. Histologic examination disclosed small non-cleaved cell lymphoma (high-grade malignancy) in one patient; diffuse large cell lymphoma (intermediate malignancy) in two patients; and small lymphocytic lymphoma (low-grade malignancy) in one patient. Posttherapeutic management during follow-up observation is discussed.

Follicular Center Cell Lymphoma of Childhood in Japan

Following a histologic review of 108 patients with childhood lymphoma from 20 hospitals in the Osaka, Hyogo, Nara, and Kyoto prefectures of Japan during the period 1964-1989, 16 cases (15%) were classified as follicular center cell (FCC) lymphomas. None had a follicular pattern of proliferation. The age range was from 2 to 15 years (median 10) with no peak incidence. The male/female ratio was 1.3:1. Presentation was nodal in 10 patients and extranodal in 6. Chronic infection and other predisposing factors for the development of FCC lymphomas in childhood are discussed, with a review of the literature.