Yoshihiro Nozawa

Characterization and comparison of two newly established Epstein-Barr virus-negative lymphoma B-cell lines: surface markers, growth characteristics, cytogenetics, and transplantability

Two Epstein‐Barr virus (EBV)‐negative lymphoma B‐cell lines, HBL‐1 and HBL‐2, were established from a pleural effusion and a lymph node biopsy of two patients with diffuse large cell lymphoma. HBL‐1 and HBL‐2 showed the characteristics of activated B‐cells in B‐cell lineage, as did original lymphoma cells. Chromosome analyses revealed that HBL‐1 exhibiting 14q+ marker‐positive lymphoid cancer showed a new subclass of 14q32 translocation resulting from a translocation between chromosomes 14 and 16, which had been masked in a complex translocation involving five chromosomes, and that HBL‐2 had a 14q+ marker chromosome, the result of an 11;14 translocation [t(11;14)(q13;32)]. Successful heterotransplantation into athymic nude mice demonstrated tumorigenicity of HBL‐1 and HBL‐2. The transplantability and tumor growth rate of HBL‐2 were higher and more rapid than those of HBL‐1. HBL‐1 and HBL‐2 appear useful for facilitating therapeutic investigations as well as immunologic and oncogenic studies in B‐cell lymphomas.

Costimulatory molecules (CD80 and CD86) on Reed-Sternberg cells are associated with the proliferation of background T cells in Hodgkin's disease.

To elucidate the relationship between Reed‐Sternberg (R‐S) cells and background T cells, the expression of CD80 and CD86 of R‐S cells in Hodgkins disease (HD), and the ligand CD28 expression and the MIB‐1 index of background T cells were immunohistochemically investigated. CD80 and CD86 were found to be expressed on R‐S cells in almost all cases of HD. CD28 was expressed with strong intensity on many background T cells around R‐S cells. The MIB‐1 index of background T cells was 30.3% (range, 15.5–38.9%) and was much higher than 10.9% (range, 9.8–11.7%) in B cell lymphomas. These results suggest that the interaction between CD80 and CD86 on R‐S cells, and CD28 on background T cells may induce T cell proliferation and be associated with tumor mass of HD.

A histogenesis of malignant lymphoma, small cleaved cell of the B cell type and intermediate lymphocytic lymphoma (mantle zone lymphoma). An immuno- and enzymehistochemical study.

We have studied the histogenesis of malignant lymphoma (ML), small cleaved cell of the B-cell type and intermediate lymphocytic lymphoma (mantle zone lymphoma) by comparing immunophenotypes and ALP-activity of neoplastic cells with those of germinal center cells (follicular center cells) anti mantle zone (MZ) cells of secondary follicles in non-neoplastic lymphoid tissues. The neoplastic cells in 3 cases of ML, follicular, small cleaved cell and 1 case of ML, small cleaved cell expressed the phenotypes similar to those of germinal center (GC) B lymphocytes (SIgM+, B1+, B2+, CALLA+, SigD−, IL-2R−, Leu-1− and ALP−). The neoplastic cells in 2 cases of ML, follicular, small cleaved cell and 12 cases of ML, diffuse, small cleaved cell displayed the characteristic phenotypes of MZ B lymphocytes (SIgM+, SIgD+, BA-1+, IL-2R+, Leu-1+ and ALP+). The phenotypes of 2 cases of mantle zone lymphoma were closely comparable with those of MZ B lymphocytes. These findings indicate that the histogenesis of ML, small cleaved cell of the B-cell type is heterogeneous and can be divided phenotypically into 2 types (GC B lymphocyte origin and MZ B lymphocyte origin). It is also apparent that intermediate lymphocytic lymphoma (mantle zone lymphoma) is derived from MZ B lymphocytes of secondary follicles.

Phaseolus vulgaris leukoagglutinating lectin-binding reactivity in human diffuse large B-cell lymphoma and its relevance to the patient's clinical outcome : Lectin histochemistry and lectin blot analysis

Many reports have suggested a strong correlation between certain lectin‐binding patterns and biological behavior in various tumors. To clarify a relationship between lectin‐binding reactivity and survival of patients with diffuse large B‐cell lymphoma (B‐DLCL), 57 cases with B‐DLCL were analyzed by lectin histochemistry and lectin blot method with or without treatment of neuraminidase or acidic hydrolytic conditions. B‐DLCL cases were grouped into three types based on the data on lectin‐binding reactivity under neuraminidase‐treated or untreated conditions: (i) Group A (non‐reactive type); (ii) Group B (sialylated type); and (iii) Group C (non‐sialylated type). Among various lectins, Phaseolus vulgaris‐L (L‐PHA) binding reactivity showed that the survival of patients with Group A + B or Group B was significantly shorter than that of patients with Group C. Lectin blot analysis revealed failure of L‐PHA‐binding to 32 kd and 29 kd glycoproteins, which may be attributable to the masking of L‐PHA‐binding sites by sialylation or the lack of L‐PHA‐binding sites, leading to the short survival of patients with B‐DLCL. L‐PHA‐binding reactivity may be a useful marker for the evaluation of survival of patients with B‐DLCL.

An immunohistochemical study of Warthin-Finkeldey cells in measles

An autopsy case of an 18 month old male infant with measles infection Is reported. An autopsy revealed generalized lym‐phadenopathy, splenomegaly and hyperplastic thymus. Histologically, there were many Warthin‐Finkeldey cells (WFC) in hyperplastic lymphoid tissues. Although viral particles and inclusions were not detected electronmicroscopicaliy, the infection of measles virus was detected in WFC by immunofluorescent technique using anti‐measles antibody. Warthin‐Finkeldey cells were morphologically and immu‐nohistochemically divided into two groups. The first type was WFC appearing in the germinal centers of lymphoid tissue, revealing many large nuclei and B cell markers. The second type was WFC appearing in the interfollicular areas and thymus, showing many small hyperchromatlc nuclei and T cell markers. The data indicate that there might be a morphologic and immunophenotypic heterogeneity in WFC.

A case of hepatic inflammatory pseudotumor with primary biliary cirrhosis.

Inflammatory pseudotumor (IPT) of the liver is an unusual non-neoplastic benign lesion. A 75-year-old man was hospitalized for esophageal varices and gastric cancer. Three years before admission, he had been diagnosed as having primary biliary cirrhosis (PBC) without Sjögrens syndrome. Computed tomography (CT) and magnetic resonance imaging (MRI) scans showed multiple masses (S3, S5, S6) less than 2 cm in diameter in the liver. Since these masses were difficult to distinguish from hepatocellular carcinoma, or metastatic liver carcinoma, one of the masses (S5) was removed during an operation for gastric cancer. Histological examination demonstrated marked infiltration of plasma cells and some histiocytes, findings consistent with the histological features of IPT. The coexistence of hepatic IPT and PBC in this case may have been an accidental event. However, the immunological and environmental factors associated with PBC are thought to be involved in the development of IPT; in addition, cholangitis associated with PBC could have contributed to the development of IPT.

NECROTIZING LYMPHADENITIS Electron Microscopical and Immunohistochemical Study

Seven cases of necrotizing lymphadenitis (NEL) including a pair of male siblings, a female suffering from non‐bacterial meningitis, and two cases with the proliferation of monocytes and/or macrophages in the bone marrow are reported. This disease is clinically documented by the occurrence in young adults usually accompanied by painful cervical lymphadenopathy with fever and leukopenia (below 4,000/mm3). Morphological features were characterized by nuclear debris from degenerated lymphocytes and the appearance of blastoid cells and/or immunoblasts and macrophages. Ultrastructurally, tubular Inclusions with a close relation to the endoplasmic reticulum were observed in various kinds of cells in the lesion. Immunohistochemical studies revealed that the ratio of helper/suppressor T‐lymphocytes became low at the active stage and returned to normal range at the recovery stage. By immunohistochemical study it was confirmed that suppressor cells mainly corresponded to large transformed lymphocytes and/or immunoblasts and helper cells were degenerated by an unknown agent. Though the pathogenesis of NEL is still uncertain, it is suggested that T‐lymphocytes are mainly involved during the course of the disease and lymphocytes show cellular debris or blastoid transformation. ACTA PATHOL. JPN. 37:1071–1084, 1987.

Adenoid cystic carcinoma of the breast: report of a case.

Adenoid cystic carcinoma of the breast is an uncommon form of cancer, and only a few articles have described the cytological findings of this disease. We report herein the case of a 48-year-old woman who presented with a breast mass beneath the nipple, the aspirate from which consisted of globules of mucous balls surrounded by epithelial cells with scant cytoplasm and hyperchromatic nuclei. Microscopically, the tumor was formed by myoepithelial cells and glandular epithelial cells in a biphasic pattern. Immunohistochemical study revealed positivity for smooth muscle actin. A left total mastectomy with axillary lymph node dissection was performed. None of the 22 axillary lymph nodes contained metastases, and the patient remains well and free from recurrence 29 months after her operation. This case report provides some information about the cytological diagnosis and the accuracy of fine-needle aspiration, which must be considered despite the rarity of this disease.

A Case of Pancreatic Oncocytic Tumor

An uncommon case of potentially malignant oncocytoma arising in the pancreatic tail of 54‐year‐old woman is reported. The tumor was encapsulated and measured 11×7×6cm. The tumor cells were uniform in appearance, plump and polyhedral, with distinct finely granular eosinophilic cytoplasm, and were arranged in solid acinar groups. Electron microscopy revealed that the tumor cells contained numerous mitochondria in the cytoplasm. In the present case, the tumor cells showed perineural and small venous invasion in the pancreas and potentially malignant characteristics. However, neither recurrence nor metastasis has been detected 3 years after resection. These findings indicate that the present tumor had apparent low‐grade malignancy.

Clinicopathological and immunophenotypic studies on 12 cases with B cell chronic lymphocytic leukemia

To clarify the histogenesis of B cell chronic lymphocytic leukemia (BCLL), clinicopathological and immunophenotypic studies were performed using a large panel of monoclonal antibodies on 12 cases with BCLL including three caes with prolymphocytic/chronic lymphocytic leukemia (CLL/PL). Immunophenotypically, CD19 and CD20 were positive for all cases of this series and CD5, CD21, CD22, CD23, CD25, CD38, Leu‐8, KB‐61, and bcl‐2 protein were expressed in variable proportion from case to case. CD10, however, did not react. No alkaline phosphatase (ALP) positive cases were found. The phenotype of BCLL was similar to that of B cells of the mantle zone (MZ) of secondary follicle in the lymph node. It is therefore postulated that the neoplastic cells of BCLL in these cases might be derived from B cells of the MZ. Moreover, the cells possibly originated from the lymphocytes located in the inner layer of the MZ, since ALP+ B cells are usually observed in the outer layer of the MZ. The pseudofollicular (PF) pattern was observed in four biopsied lymph nodes among five cases tested, but no such a pattern in an aspiration clot of bone marrow. These four cases consisted of three cases with CLL and a case with CLL/PL. The immunohistochemical study showed that there were many proliferating cells showing Ki‐67+ in the PF area of the lymph nodes. In these cases, leukemic cells might have developed from the PF area of the lymph node.