Noboru Mohri

Some problems on the histopathological diagnosis of non-Hodgkin's malignant lymphoma -- a proposal of a new type.

A new classification for non‐Hodgkins malignant lymphoma is proposed as the one suited for the Lymphomas in Japan, which is to provide a new subtype “pleomorphic” for those more or less rapid‐growing lymphomas of peripheral T‐cell nature, along with another subtype lymphoblastic, after Nathwani et al. for those of central T‐cell nature. The proposal is based on the result of the investigation by the Study Group for Histopathological Diagnosis on Malignant Lymphoma that (1) the presence of a significant number of T‐cell lymphomas with peculiar “pleomorphism” is responsible for the very low reproducibility rate of histopathological diagnosis on the diffuse, mixed L&H type of Rappaport classification, and (2) the relative incidence of lymphoms of peripheral T‐cell nature including the so‐called adult T‐cell leukemia is much higher in Japan than in the Western countries.

Cellular characteristics of neoplastic angioendotheliosis. An immunohistological marker study of 6 cases.

Neoplastic angioendotheliosis (NAE) is a rare, mostly fatal disease characterized by proliferation of large blastoid cells in small vessels of various organs. The origin of neoplastic cells remain undetermined. In this study, cell markers were studied immunohistologically on paraffin sections of six cases of NAE, by applying avidin-biotin-peroxidase (ABC) method and five antibodies which can demonstrate marker antigens on formalin fixed and paraffin embedded specimens. It was shown that the neoplastic cells were heavily stained with an anti-B lymphocyte monoclonal antibody LN-1 (6/6), moderately stained with another anti-B lymphocyte antibody LN-2 (5/6) and heavily stained with a monoclonal antibody which reacts with all levels of leukocytes (Dako-LC) (6/6). The cells did not show positive reaction with an anti-myelomonocytic antibody anti-Leu M1. The reaction against anti-Factor VIII, which can depict endothelial cells, was mostly negative, and if positive, was faint and undefinite, leading to an assumption that the reaction was against antigens in serum and not against neoplastic cells. These results suggest that the neoplastic cells of NAE are in the B lymphocyte lineage.

The distribution of cells expressing a natural killer cell marker (HNK-1) in normal human lymphoid organs and malignant lymphomas

SummaryA murine monoclonal antibody, HNK-1, is known to react with some human leukocytes including all natural killer (NK) cells in peripheral blood. The distribution of cells reacting with this antibody (HNK-1 + cell) was studied in human peripheral lymphoid organs, consisting of five lymph nodes, two specimens of gastric mucosa with lymphoid tissue, two tonsils, one appendix, and two thymuses. Fourteen cases of malignant lymphoma (ML) were also examined. For the demonstration of HNK-1 + cells, the peroxidase-antiperoxidase (PAP) bridge method was applied to cryostat sections of these specimens.It was found that in normal lymphoid organs most HNK-1 + cells were located in lymph follicles, especially in germinal centers, and some were found in ‘mixed” regions which indicate outsides of both the follicles and T-zones. Amongst the ML, large clusters of HNK-1 + cells were observed only in two cases of follicular lymphoma, although a few scattered HNK-1 + cells were noted in other ML, including five diffuse B-cell lymphomas, six T-cell lymphomas and one null cell lymphoma. The possible significance of these findings is discussed.

Primary gastric non-Hodgkin's lymphomas in Japan

A pathological study was carried out on 124 cases of primary gastric non-Hodgkins lymphoma (NHL) in Japan. Macroscopically the cases were divided into three groups; flat, polypoid, and ulcerative types. Early lymphomas were distinguished from advanced by the depth of infiltration. Histologically the commonest type was ML, immunoblastic (ML, ibl.). Most were high grade malignancy, in terms of morphology. Lymph node involvement was found in 44 cases. Correlation between macroscopical appearance, histological diagnosis, stage and accompanying reactive lymphoid hyperplasia (RLH) was studied. Three main prototypes of gastric NHL were noted: The first was macroscopically ulcerative type, histologically high grade malignancy and lacked RLH; the second was mostly flat, ML, lymphoplasmacytic/ lymphoplasmacytoid (ML, l-p.) or ML, ibl., associated with RLH, and arose from neoplastic proliferation of the interfollicular lymphoid cell in RLH (termed gastric NHL of interfollicular type); the third was mostly flat, ML, centroblastic (ML, cbl.) or lymphoblastic (ML, lbl.), associated with RLH, and originated from neoplastic proliferation of the follicular center cell in RLH (gastric NHL of follicular type).

RHABDOMYOSARCOMA WITH BONE MARROW METASTASIS SIMULATING ACUTE LEUKEMIA

Rhabdomyosarcoma manifested as a systemic disease is very rare and cases showing diffuse metastasis in the bone marrow are most unusual. Recently we encountered two cases of rhabdomyosarcoma with diffuse bone marrow metastasis which were clinically manifested as acute leukemia. The first patient was a 15‐year‐old female, who was admitted in 1982 with pancytopenia and many large primitive cells in bone marrow aspirates, hematological malignancy being diagnosed. Thereafter the bilateral breasts showed rapid swelling and a biopsy specimen revealed the histological features of typical alveolar rhabdomyosarcoma. The primary site of the neoplasm remained undetermined during the course. At autopsy, it was disclosed that the neoplasm originated from the left thigh and showed generalized metastasis. The second patient was a 38‐year‐old man, who was admitted in 1986 because of a nasal polyp obstructing the nasal cavity, and persistent nasal bleeding. Peripheral blood samples showed leucoerythroblastosis and thrombocytopenia, and large primitive cells were found In bone marrow aspirates, so that hematological malignancy was initially diagnosed. A biopsy specimen of the nasal polyp showed proliferation of large round cells and electron microscopy demonstrated the ultrastructural features of rhabdomyosarcoma.

REACTIVE LYMPHOID HYPERPLASIA OF THE STOMACH

The surgically excised stomachs were re‐examined histopathologically, and eighteen cases were placed in the category of reactive lymphoid hyperplasia (RLH). The distribution and the classes of infiltrating immunoglobulin (Ig) bearing cells were examined on lesions of RLH cases together with ten histopathologically determined malignant lymphomas (ML) of the stomach and the control stomachs. It was found that in eleven cases of RLH and one case of ML, many lymphoid cells bearing different classes of Ig were present in those lesions in an intermingled way (polyspecific group). Meanwhile, lymphoid cells in three RLH cases and two ML cases bore only a single mono‐specific Ig (monospecific group). In other cases, the number of Ig bearing cells were not sufficient to reach any clear conclusions (undetermined group). It was speculated that regardless of the histopathological diagnosis, the mono‐specific group might belong to the category of neoplasm of B cell type and the polyspecific group in the category of true reactive process. The possible histopathological criteria for differentiation of the reactive process and lymphoid neoplasm of the stomach were re‐checked, and the importance of immunohistochemical study on these cases were stressed.

A CASE REPORT OF “LIPOMATOUS HYPERTROPHY OF THE CARDIAC INTERATRIAL SEPTUM”, WITH A PROPOSAL FOR A NEW TERM “LIPOMATOUS HAMARTOMA OF THE CARDIAC ATRIAL SEPTUM”

An autopsy case of “lipomatous hypertrophy of the cardiac interatrial septum“ (LHIS) combined with marked stenosis and calcification of the aortic and mitral valves due to fibrous valvular endocarditis, malignant lymphoma, and mucin‐producing cancer of the pancreas is reported. LHIS and mucin‐producing cancer of the pancreas were incidental findings at autopsy. Microscopically, the LHIS in this case consisted of proliferation of mature fat cells, brown fat cells and cardiac muscle cells. Since these threee cell types are normal structural components of the Interatrial septum, it was considered that the LHIS was a hamartomatous rather than hypertrophic lesion, of the cardiac atrial septum. Accordingly it was concluded that the term “lipomatous hamartoma of the cardiac atrial septum” was more appropriate for this lesion in the case presented here. As far as we know, this is the first reported case of LHIS in Japan. ACTA PATHOL JPN 38: 1583‐1589, 1988.

DISTRIBUTION OF HNK‐1+ CELLS IN MALIGNANT LYMPHOMAS

HNK‐1, a murine monoclonal antibody, is known to react with most of the natural killer (NK) and killer (K) cells in peripheral blood. Cells reacting with this antibody (HNK‐1+ cells) were studied on tissue sections of ninety two cases of malignant lymphomas (MLs) by using immunoperoxidase technique, in an attempt to elucidate the role of this type of cells in MLs. Follicular lymphomas were found to be highly infiltrated with HNK‐1+ cells. The mode of infiltration in follicular lymphomas is just like in normal germinal centers. Many cases of diffuse lymphomas with cleaved nuclei, indicative of diffuse B‐cell lymphomas of follicular center cell origin, as well as diffuse ML with heavy fibrosis (sclerosis) or histiocytic reaction, were also found to be infiltrated with abundant HNK‐1+ cells. Meanwhile, other types of B‐cell ML and all types of T‐cell ML, as well as Hodgkins disease, were shown to be very poor in HNK‐1+ cell reaction. From a prognostic viewpoint, the low grade malignancy group in the NCI Working Formulation or Kiel Classification was found to be infiltrated with significantly much more HNK‐1+ cells as compared to the high grade malignancy group. The significance of these findings are discussed, with the stress on the possible suppressive function of HNK‐1+ cells on proliferation and differentiation of follicular center cell type B‐cell MLs. ACTA PATHOL. JPN. 35: 339–350, 1985.

EXPRESSION OF IgD ON B CELL MALIGNANCY|An Immunopathological Study of 50 Cases

Expression of IgD was studied immunopathologically on 50 cases of B cell lymphomas (B MLs), together with various B cell markers including IgM, ϰ and Λ chains, B1, B2, (OK)B2, (OB)B7, (OK)T10, NUB1, Leu 1, Leu 14, and PCA. IgD was demonstrated on 19 cases heavily and on 8 weakly. It associated well with expression of two antigens, B2 (C3d receptor molecule) and Leu1 (pan‐T antigen), besides IgM, while, B2 was closely related in expression on B MLs to (OK)B2, (OK)B7, and NUB1. Λ chain was dominant on IgD heavily‐stained cases. Histopathologically, IgD positive MLs were distributed in various types. All of diffuse intermediate type were shown to be IgD positive (4/4, 3 heavily). As cases of this type were shown to express most of other B cell antigens present on non‐tumorous primary follicle B cells or mantle zone B cells, this type of MLs is speculated to be a neoplastic counterpart of such non‐tumorous B cells. Eight out of 18 cases of diffuse large cell type were IgD heavily positive, suggesting some unusual mechanisms in IgD expression on these neoplastic large cells, as non‐tumorous B cells lose most of their surface IgD soon after blastoid transformation. Other types of MLs were discussed with special emphasis on expression of IgD. ACTA PATHOL. JPN. 36: 1429‐1440, 1986.

Malignant Fibrous Histiocytoma of the Nasal Septum

A case of malignant fibrous histiocytoma of the nasal septum is described in a 51 -year-old woman who has presented with nasal pain, nasal obstruction and a swelling at the base of the nose. Histologi