Martin Sacks

Aberrant (ectopic) adrenocortical tissue along the spermatic cord.

Aberrant adrenocortical tissue along the spermatic cord is a far more common finding than has previously been reported. During a period of 12 consecutive months, 360 children, aged 13 days to 13 yr, underwent 386 operations for common inguinoscrotal pathology at the Soroka Medical Center. In 12 cases ectopic adreno-cortical tissue was found along the spermatic cord, an overall incidence of 3.8%. None was found in females. Considering the group operated upon for undescended testis, in which by nature of the procedure the spermatic cord was dissected throughout its length, the frequency of ectopic adrenal tissue found rose to 9.3%, the highest figure cited for this location. The nature of aberrant adrenocortical tissue is briefly discussed, including its embryology, histology, and clinical implications. It usually appears as an incidental finding during surgery. Its removal is indicated whenever found although no special attempt should be made to search for it.

Selectins and anti-CD15 (Lewis x/a) antibodies transmit activation signals in Hodgkin's lymphoma–derived cell lines

OBJECTIVE The CD15 (Lewis x) cell surface oligosaccharide moiety is expressed in a variety of normal and tumor cells and recognized by selectins. The detection of CD15 on malignant Hodgkin-Reed-Sternberg (HRS) cells serves as a diagnostic marker of Hodgkins lymphoma (HL). Retrospective studies suggest that the expression of nonsialylated CD15 molecules on HRS cells has a positive prognostic value while presence of sialylated CD15 may correlate with a poor outcome. However, the relevance of the CD15 antigen expression to the pathobiology of the disease is not clear. In this work, we studied the contribution of CD15 to cell adhesion and the activation of signaling cascades in two HL-derived cell lines, KMH-2 and L428. METHODS Immobilized anti-CD15 monoclonal antibodies and recombinant E- and P-selectins were used to activate KMH-2 and L428 cells. Immunoblotting, immunoprecipitation, and the electrophoretic mobility shift assay were performed to detect tyrosine phosphorylation of c-Cbl, c-Jun nuclear translocation, and AP-1 DNA binding. RESULTS Treatment of cells with antibodies against the sialylated and nonsialylated forms of CD15, or with immobilized selectins, induced changes in cell morphology. Tyrosine phosphorylation of c-Cbl, together with tyrosine phosphorylation of multiple protein substrates, was also induced. In addition, binding of the CD15 molecules induced nuclear translocation of c-Jun and an increase in AP-1 DNA binding activity. CONCLUSIONS We suggest that CD15 has a dual physiological role, both as an adhesion molecule recognized by selectins and as a regulatory molecule upstream to specific intracellular signaling cascades with implications to the pathogenesis of HL.

Apoptotic Index as a Prognostic Factor in Hodgkin's Disease

Hodgkins disease (HD) is an unusual malignant neoplasm, mainly because of the rarity of tumor cells in the diseased tissues, but also due to a relatively favorable response to treatment. In a previous study, we have shown a variable degree of apoptosis in lymph nodes from HD patients. We now looked for clinicopathological correlations of apoptosis with special emphasis on the prognosis in this disease. A retrospective study of 92 patients was carried out, using in situ end labelling of DNA fragments and an apoptosis detection kit. An apoptotic index (Al) was calculated in each case, as the percentage of apoptotic Hodgkin-Reed-Sternberg cells out of the total number of tumor cells in 10 selected high power fields. An association between a high Al and advanced stages was noted. A Kaplan-Meier analysis showed a negative correlation between Al and survival (p=0.05). In a multivariable analysis adjusting for Ann Arbor stage, a high Al carried a 3.27 fold risk of dying of HD (OR=3.27; Cl=0.89-11.94). However, in our limited cohort of HD patients, Al was not an independent prognostic factor. The results of this study confirm the important role played by apoptosis in HD and suggest that the apoptotic index is probably a negative prognostic marker in this disease. Its assessment in patients with HD may provide a new, important clinical tool.

Differential Expression of Sialyl and Non-Sialyl-CD15 Antigens on Hodgkin-Reed-Sternberg Cells: Significance in Hodgkin's Disease

CD15 expression has been used for years to confirm the diagnosis of Hodgkins disease (HD). Little is, however, known on the relevance of the CD15 antigen to the pathobiology of the disease and there is conflicting evidence as to the prognostic value of its expression. To investigate the significance of the differential expression of CD 15 in Hodgkins disease, a retrospective study of 102 patients with “classical” Hodgkins disease was performed. Immuno-histochemical studies were carried out using antibodies against two types of CD 15: non-sialylated CD15 (LeuM1 and 80H5) and sialylated CD15 (FH6 and CSLEX1). Cases that were negative for non-sialylated CD 15 or positive for the sialylated variant were stained again following neuraminidase pretreatment. The cohort included 27 patients in whom sequential biopsies were available. Both CD15 expression in its non-sialylated form and absence of sialyl-CD15 expression correlate with a favorable outcome. Subsequent biopsies show a preferential expression of sialyl-CD15, notably in bone marrow metastases. Our findings suggest that, in the progression of HD towards a widely disseminated disease, the LewisX moiety of the CD 15 antigen on the tumor cells acquires a sialyl-group. This change may confer on the tumor cells the capacity to metastasize.

Antibody Pattern to Human Cytomegalovirus in Patients with Adenocarcinoma of the Colon

The role of human cytomegalovirus (CMV) was examined according to serological patterns in 37 patients with adenocarcinoma of the colon (ACC). The sera were examined for the presence of IgG antibodies by the immunoperoxidase antibody to membrane antigens (IPAMA) method and by the complement-fixation (CF) test. Antibody determinations were also performed by the IPAMA method for three other members of the herpesvirus group: Epstein-Barr virus (EBV), herpes simplex virus (HSV) and varicella-zoster virus (VZV). Comparison groups included normal subjects, ACC patients treated with chemotherapy, and patients operated on for benign diseases. No significant difference was found in the geometric mean titers (GMTs) for CMV and the other herpesviruses in the sera of nontreated ACC patients when compared with the control groups. However, a significantly elevated antibody titer to CMV was found in chemotherapy-treated ACC patients by both the IPAMA and CF methods. In this group, elevated titers were found by the IPAMA method for EBV and HSV, but not for VZV. The significance of serological studies in elucidating the role of CMV in ACC patients is discussed.

Is Classical Hodgkin's Disease Indeed a Single Entity?

We present a retrospective clinicopathological study on the significance of the histologic type of classical Hodgkins disease (HD) in a cohort of patients from southern Israel. This was performed to critically evaluate the generally accepted view that classical HD is a single clinicopathological entity and the resultant impression that its segregation into four different histologic types remains essential only for the pathologist in his diagnostic endeavor. We confirmed the existence of a uniform response of nodular sclerosis (NS), and mixed cellularity-lymphocyte depletion (MC-LD)-HD to treatment, consideration being given to other classical prognostic factors. We also accept the fact that histological type is not a significant independent factor in terms of survival. Our findings, however, do suggest that NS-HD, on the one hand, and MC-LD-HD, on the other, are distinct biologic entities. Cases of NS differ significantly from those of MC-LD-HD with regard to sex and age distribution, and in the expression of several antigens and gene products, including sialylated-CD15, CD30, LMP1 and the p53 and mdm-2 gene products.

Lymphocyte-depleted classic Hodgkin lymphoma—a neglected entity?

Changes in the definition of lymphocyte-depleted classic Hodgkin lymphoma (LDcHL) have recently led to reclassification of many cases as other pleomorphic lymphomas. We have set out to identify LD cases in our cohort of cHL patients and determine their clinical and biological characteristics properties. We defined the morphologic picture of LDcHL according to selected criteria and determined how its features differ from those of other subtypes of cHL. Twelve of 201 cHL patients (5.9%) were diagnosed as showing LDcHL histology, a higher percentage of LDcHL than in most recent series. The LD cases were most often positive for Epstein–Barr virus and for sialyl-CD15. Defining the cases as either reticular (eight) or as diffuse fibrosis (three) variants was critical to the diagnostic approach. We conclude that LDcHL may be a neglected entity.

Hyperreactive malarial splenomegaly and AIDS: proguanil prevents recurrent pneumonia.

An Ethiopian immigrated to Israel and gave a positive test result for human immunodeficiency virus. Soon after, he was thrice admitted to hospital in 3 months for severe pneumonia. Acquired immunodeficiency syndrome was diagnosed, as was hyperreactive malarial splenomegaly (HMS). Thereafter, during maintained proguanil treatment for HMS, the patient remained well for 16 months. Then, after another pneumonic illness, pneumococcal vaccine was administered. Proguanil was maintained for another 10 months and, despite declining CD4 cell counts, good health continued for a further 18 months.