Aneal S. Masih

Clinical and immunologic studies in reticular erythematous mucinosis and Jessner's lymphocytic infiltrate of skin.

BACKGROUND Little is understood about reticular erythematous mucinosis and Jessners lymphocytic infiltrate of skin. OBJECTIVE Our purpose was to define reticular erythematous mucinosis and Jessners lymphocytic infiltrate of skin further with focus on immunologic studies. METHODS In patients with reticular erythematous mucinosis and Jessners lymphocytic infiltrate of skin, we measured circulating immune complexes before, during, and after therapy. We examined natural killer cells in a functional assay; we performed direct immunofluorescence and T- and B-cell marker studies in skin biopsy specimens. RESULTS The infiltrate in reticular erythematous mucinosis is composed of helper T cells. Circulating immune complexes are increased in both reticular erythematous mucinosis and Jessners lymphocytic infiltrate of skin and decrease with hydroxychloroquine therapy and clinical clearing. Natural killer cell function is decreased in reticular erythematous mucinosis and Jessners lymphocytic infiltrate of skin. CONCLUSION Changes in circulating immune complex titers accompanying therapy with hydroxychloroquine and clinical clearing, with recurrence of the condition and increase in circulating immune complexes on discontinuation of treatment, point to a possible relation between these events.

Histologic grade does not predict prognosis in optimally treated, advanced-stage nodular sclerosing Hodgkin's disease

Forty‐two patients with advanced‐stage nodular sclerosing Hodgkins disease (NSHD) were treated uniformly with combination chemotherapy and radiation therapy at the University of Nebraska Medical Center between 1982 and 1987. The cases were subclassified into low‐grade (13 cases) and high‐grade (29 cases) categories using the British National Lymphoma Investigation (BNLI) histologic criteria. After a median follow‐up interval of 48 months, no significant differences with regard to the complete remission rate (100% versus 90%), remission durability (85% versus 96%), or predicted 4‐year actuarial survival (92% versus 86%) were observed between the two groups, respectively. It was concluded that the BNLI grading scheme for NSHD does not predict the clinical outcome of patients with advanced‐stage NSHD who receive optimal therapy.

Immunophenotypic and genotypic characterization of lymphomatoid papulosis

BACKGROUND Lymphomatoid papulosis (LyP) is a chronic dermatosis that histologically resembles malignant lymphoma. Thus far, only a few cases of LyP have been characterized in detail with regard to immunophenotype, genotype, and karyotype. OBJECTIVE Our purpose was to study seven patients with LyP and compare the results to those reported in the literature. METHODS Skin biopsy specimens were analyzed by frozen section immunohistochemical and molecular biologic techniques. Cytogenetic analysis was also performed in three cases. RESULTS The atypical lymphoid cells consisted of activated helper T cells; four of the seven patients had lesions with a detectable clonal T-cell population. A peripheral T-cell lymphoma developed in one patient before the emergence of a genotypically different LyP T-cell clone. Cytogenetic studies were abnormal in one case of LyP and normal in another, whereas the karyotype of the lymphoma was abnormal. CONCLUSION LyP is a preneoplastic proliferation of activated helper T cells, which is often clonal and may regress and expand with the development of new LyP clones or lymphoma.

Characterization of a human herpes virus-6 (HHV-6) and epstein-barr virus (EBV) associated leukemic cell line, J6-1

This report characterizes the J6-1 cell line derived from a Chinese acute myelomonocytic leukemia patient and previoulsy reported to be associated with EBV. These studies showed that J6-1 cells were also infected with HHV-6 as demonstrate at the DNA level by PCR and Southern blot hybridization and by expression of HHV-6 early membrane antigen on the J6-1 cell surface. Further characterization showed J6-1 was co-infected with EBV type 2. Generally, cells infected with EBV type 2 do not grow wellin vitro, However, J6-1, although difficult to maintainin vitro, has been growth for 15 years. Possibly, co-infection with HHV-6 confers this property. In this regard, J6-1 cells exhibited density dependent growth which could be inhibited with an anti-HHV-6-MA monoclonal antibody (MAb). In contrast, anti-HHV-6-VCA MAb stimulate the J6-1 cell proliferation. Electron microscopic analysis showed that, morphologically, there were two types of J6-1 cell, one with lymphoblastoid features and one with a monocytoid appearance. Accordingly, the flow profile of the J6-1 cell line showed heterogeneity with two populations comprised of CD15-, CD19+cells with low light scatter (small cells) and a population with greater light scatter (larger cells) which was CD15+, CD19+, The population was negative for progenitor cell markers (CD33, 34), and T cell markers. Southern analysis showed no T cell receptor rearrangement, however there was a clonal JH and kappa light chain expressing population. Glycocytochemical analysis showed several endogenous lectin receptors on the J6-1 cell surface: BSA-Xylose, BSA-Rhamnose, BSA-Gal, BSA-Lac. This cell line shares many characteristics with other monocytic/lymphoblastoid cell lines isolated elsewhere and provides circumstantial evidence linking Herpes viruses, as least as co-factors, to leukemia cell growth.

Nerve growth factor receptor expression on dendritic reticulum cells in follicular lymphoid proliferations

Using an antibody to the nerve growth factor receptor (NGFR), we examined dendritic reticulum cells (DRCs) immunohistochemically in 62 formalin-fixed, paraffin-embedded lymph nodes from patients with reactive follicular hyperplasia or with various types of lymphoma. A dendritic staining pattern within germinal centers was present in 25 of 26 routinely processed lymph nodes with reactive follicular hyperplasia. In contrast, dendritic staining with anti-NGFR was present within neoplastic follicles in only three of 28 follicular lymphomas. Staining of benign, residual germinal centers with anti-NGFR was present in mantle zone lymphoma and Hodgkins disease. These findings suggest a possible role for the NGFR in the maturation and/or activation of normal DRCs. The loss of NGFR expression in most follicular lymphomas indicates that DRCs are altered as part of the neoplastic process. The possibility that DRCs may play a role in the pathogenesis of follicular lymphoma is suggested.

Oncogene rearrangement in non-hodgkin's lymphoma with a 14q + chromosome of unknown origin

Southern blot analysis was performed with a panel of DNA probes to detect rearrangements of c-myc, bcl-1, bcl-2 and bcl-3 in 14 cases of B-cell non-Hodgkins lymphoma (NHL) with a clonal cytogenetic rearrangement involving the chromosome 14q32 locus and no known donor chromosome [t(14;?)(q32;?)]. In our experience, 21% of all chromosomal abnormalities involving the 14q32 locus in B-cell NHL are of this type. We found oncogene rearrangements in five of the 14 cases: bcl-1 rearrangement on one mantle zone lymphoma, bcl-2 rearrangements in two follicular lymphomas, and c-myc rearrangements in two small noncleaved cell lymphomas. We conclude that a 14q32+ abnormality of unknown origin is a relatively frequent karyotypic finding in B-cell NHL. In one third of the cases, known oncogenes that have been previously described in reciprocal translocations involving the immunoglobulin heavy chain locus were shown to be involved in the 14q32+ abnormality. The translocations in the other cases are likely to have involved one of the above oncogenes with breakpoints not revealed by the probes employed, other known oncogenes, or oncogenes that have not yet been identified.