Hodgkin's disease in siblings

An incidence survey of Hodgkin's disease in Greater Boston during 1959-1973 detected five sibling pairs under the age of 45. The expected number is 0.7; thus, siblings of young adults with Hodgkin's disease have about a sevenfold excess risk of the disease (P = 0.0008). Eight sibling pairs, not in the incidence series, were also identified. Among all 13 pairs, 12 were sex concordant; the number expected is 6.8 (P = 0.01). The literature includes 46 sibling pairs under 45 of which 30 are sex concordant. The expected number is 23.9 (P = 0.05). Combining the present and the literature series suggests that siblings of the same sex as an affected person have a risk of Hodgkin's disease double that of siblings of the opposite sex. The sex concordance suggests that the excess Hodgkin's disease among siblings of affected persons is due either to inter-personal transmission of an etiologic agent by prolonged or intimate contact or to common-source exposures.     

Secondary amyloidosis in Hodgkin's disease

One case with secondary amyloidosis is described, manifested by a nephrotic syndrome, 13 years after the establishment of lymphogranulomatosis in a male, ages 46. Amyloidosis diagnosis with biopsy, after a long-term remission in a patient with a relatively restricted lymphogranulomatosis is of certain interest. The diagnostic difficulties of secondary amyloidosis in Hodgkin disease are discussed as well as the mechanism origination and the role of certain medicaments in amyloidosis origination and treatment.     

Fibrin deposits in Hodgkin's disease

Fibrin deposits were observed in the involved lymph nodes and/or spleens of 15 patients with Hodgkin's disease by specific immunofluorescence and by electron microscopy. Two basic patterns of fibrin deposition were observed: 1) intercellular deposits, chiefly associated with nonneoplastic-appearing lymphoid cells and 2) deposits associated with the collagen fibers of young connective tissue. In addition, coarse fibrin deposits were observed in areas of necrosis, presumably a non-specific finding. Fibronectin was also observed in intercellular areas, but staining was less intense than for fibrin. Fibrin deposits were also observed in 3 of 6 cases of non-Hodgkin's lymphoma, indicating that the finding is not an exclusive feature of Hodgkin's disease. The pathogenesis and possible significance of fibrin deposition in Hodgkin's disease are related to earlier observations of activation of the coagulation system on neoplasia and cell-mediated immunity and to the possible role of fibrin, fibronectin, and their breakdown products in angiogenesis and fibroplasia.     

Telomerase activity in Hodgkin's disease

Telomere maintenance executed by the action of telomerase seems to be a prerequisite for immortalization. Telomerase is found in most cell lines and malignant tumors. A telomerase-independent mechanism for telomere maintenance in Hodgkin's disease has been proposed in the absence of detectable telomerase activity. In this study, telomerase activity was detected in 31 of 77 Hodgkin's disease samples and a strong correlation between eosinophilia and absence of detectable telomerase activity was found. Purified eosinophils and specifically eosinophil-derived neurotoxin and eosinophilic cationic protein, both ribonucleases, were found to degrade telomerase. Purified neutrophils also exhibited weak telomerase degradative activity. Reanalysis of previously telomerase-negative Hodgkin's disease samples with eosinophilia using ribonuclease inhibitors resulted in the detection of telomerase activity. Ribonuclease-containing cells in vivo thus have a considerable impact on the detectability of telomerase. In Hodgkin's disease samples without eosinophilia, 24 of 27 exhibited telomerase activity at decreased levels compared with non-Hodgkin's lymphomas and at increased levels compared with reactive nodes indicative of a telomerase positive tumor component in Hodgkin's disease. Telomerase positivity of the Hodgkin's and Reed-Sternberg cells in vivo was also supported by high levels of telomerase expression in Hodgkin's disease cell lines. Based on our data, Hodgkin's lymphomas are potential targets for antitelomerase therapy.     

Cytogenetics of Hodgkin's disease

Cytogenetic studies over the past 35 years have made a major contribution towards the understanding of the nature of Hodgkin's disease by demonstrating unequivocally the consistent presence of a clonal population of cells that have the cardinal features of malignancy e.g. more or less gross aneuploidy, frequently with complex chromosomal changes and showing considerable variation from case to case, thus comparable to the findings in carcinomas and other solid cancers. The mode is frequently in the triploid-tetraploid region, as we found in 17 of 27 cases studied in this laboratory by Feulgen microspectrophotometry, compared to only 10 cases with neardiploid modes. It is disappointing that no specific change, such as a translocation that could give a clue to the chromosomal location of a gene or genes involved in the etiology of Hodgkin's disease, has yet been found. Nevertheless it is clear that a number of nonrandom changes, including several that are also common in other malignancies including the non-Hodgkin's lymphomas, are frequently present, e.g., deletions of 1p, 6q, and 7q. Interestingly, deletions of 4q, with loss of 4q25 --> q27, that have also been reported may show some specificity for Hodgkin's disease.     

Granulocyte turnover in advanced Hodgkin's disease

In 30 adult patients with III and IV Hodgkin's disease the studies of granulocytic turnover were performed. Bone marrow storage pool was measured by hydrocortisone test. Total blood granulocyte pool was judged by the estimation of muramidase activity and serum unsaturated vitamin B12 binding capacity. The epinephrine test was used for the marginated granulocyte pool determination. The circulating granulocyte pool was calculated from the count of granulocytes in the samples of venous blood. The tissue mobilization of granulocytes was measured by Senn's et al. method. After hydrocortisone application the releasing of the mature granulocytes from the bone-marrow was significantly lower in patients with Hodgkin's disease than in controls. The circulating and marginated pools of granulocytes in Hodgkin's disease did not differ from the normal persons. The tissue migration of granulocytes was decreased in patients with Hodgkin's disease. It is concluded that these abnormalities of granulocytic turnover in advanced Hodgkin's disease may be considered to be an additional cause of the defence mechanism in this disease.     

Paraneoplastic cerebellar degeneration in Hodgkin's disease

HISTORY AND CLINICAL FINDINGS: A 30-year-old previously healthy man suddenly developed double vision, unsteady gait and some difficulty in speech articulation. Within 4 weeks he had become markedly ataxic, unable to walk, stand or sit down unaided. Neurological examination indicated a severe cerebellar syndrome. There were no other abnormal findings on physical examination. INVESTIGATIONS: There was no pleocytosis and no oligoclonal bands in cerebrospinal fluid (CSF). A test for anti-Purkinje cell antibodies was negative in both CSF and serum. Computed tomography and nuclear magnetic imaging (NMI) of the brain were normal. TREATMENT AND COURSE: As a para- or postinfectious or paraneoplastic process was suspected. I.v. immunoglobulin and oral corticosteroids were administered, but without improvement. 13 month later, a mediastinal mass was noted on a chest radiogram. This led to the diagnosis of a stage IA Hodgkin's disease. Retrospectively the cerebellar degeneration was most likely a paraneoplastic change related to the Hodgkin's disease. However, an independent second disease cannot be excluded. While the treatment of Hodgkin's disease was successful, the neurological symptoms remained unchanged. Severe cerebellar atrophy was demonstrated on NMI. CONCLUSION: In case of cerebellar atrophy of undetermined aetiology a paraneoplastic cause should be considered and an underlying malignant disease looked for.     

Role of autotransplantation in Hodgkin's disease

Autologous bone marrow transplantation offers the opportunity for long-term disease-free survival in patients with Hodgkin's disease who might be considered incurable with other treatments. The appearance of late relapses in some reports is worrisome, but it is hoped that the majority of long-term survivors are indeed cured. Fundamental questions remain concerning the best conditioning regimen, the best rescue source, the optimal timing of transplantation, and ultimately whether transplantation is better than conventional salvage techniques. Some of these answers may be provided if long-term follow-up studies are reported and results are analyzed with reference to known prognostic factors. Ultimately, prospective trials will be needed to more clearly define the role of transplantation in Hodgkin's disease. It is hoped that ongoing trials will lead to higher remission rates, lower relapse rates, and diminished transplant-related mortality.     

Progressive disease after ABMT for Hodgkin's disease

A major limitation of ABMT for relapsed/refractory Hodgkin's disease is disease recurrence post-transplantation. We retrospectively reviewed 68 patients undergoing ABMT from January 1987 to June 1993. All received a uniform preparatory regimen (CBV). The median patient age was 30; 75% received prior radiation therapy and all patients received prior chemotherapy. Thirty-one percent presented at the time of transplantation with tumor masses larger than 10 cm. Sixty-two percent received autologous marrow alone and 38% PBPC with or without autologous bone marrow. Overall and progression-free survival are 43 and 36% at 5 years. Median follow-up for survivors is 59 months. Multivariate analysis revealed that tumor bulk was the most powerful poor prognostic factor for both survival and progression-free survival. Those transplanted with non-bulky tumors had an overall survival and progression-free survival of 52 and 44%, respectively, compared to those transplanted with bulky tumors who had an overall survival and progression-free survival of 22 and 16% (P = 0.03 and P = 0.04, respectively). Twenty-seven patients have relapsed. Four relapsed more than 2 years after ABMT. Four of the 27 patients who have relapsed remain alive, two without evidence of disease. The time after transplant to relapse was prognostically important, with no patients who relapsed within 6 months of ABMT still being alive, compared with 25% of patients who relapsed 7 or more months after ABMT who are still alive. We conclude that salvage therapy for relapse after ABMT is appropriate, as some patients may achieve prolonged survival. The time from transplant to relapse is an important survival predictor.     

Tuberculosis in Hodgkin's disease in a child

During its evolution, Hodgkin disease is accompanied by changes in the cell immunity, mainly of delayed type. Tuberculosis can precede Hodgkin disease or complicate its evolution during a simultaneous development of both diseases, or the lymph node tuberculosis can hurry hemopathy onset. Tb lesions in such patients can have atypical features.     

Hodgkin's disease presenting as pericarditis

Two patients presented with initial symptoms of pericarditis. Palpable lymph nodes developed a few weeks later and a diagnosis of Hodgkin's disease was made. Although rare, this mode of presentation of Hodgkin's disease has been reported previously, and it should be considered in the differential diagnosis of any patient with pericarditis with severe general symptoms or a prolonged course.