Characterization of sperm chromatin quality in testicular cancer and Hodgkin's lymphoma patients prior to chemotherapy

BACKGROUND: Although the incidences of testicular cancer and Hodgkin's lymphomahave increased in young men over the past decade, combinationchemotherapy has improved survival. As fertility is of importanceto these patients, characterization of sperm chromatin structureis needed. We assessed sperm chromatin in testicular cancerand Hodgkin's lymphoma patients prior to chemotherapy, in comparisonwith control community and idiopathic infertile volunteers. METHODS: DNA damage was assessed with the sperm chromatin structure assay(SCSA), terminal deoxynucleotidyl transferase-mediated dUTPnick end labeling (TUNEL) and comet assays; reactive thiols(SH) and DNA compaction were determined with the monobromobimane(mBBr) and chromomycin A3 (CMA3) assays, respectively. RESULTS: Both testicular cancer (37%) and Hodgkin's lymphoma (81%) patientshad normospermic samples with increased DNA damage, comparedwith controls. Cancer patients also had higher reactive thiolsand CMA3 staining, indicating low DNA compaction. CONCLUSIONS: Sperm DNA integrity and compaction were affected in testicularcancer and Hodgkin's lymphoma patients prior to chemotherapy.Although SCSA, TUNEL and comet assays all detected DNA damage,the latter was optimal for use in cancer patients. A combinationof the comet assay with tests that evaluate sperm DNA compaction,such as flow cytometry-based CMA3 and mBBr assays, is a reliablestrategy to characterize sperm chromatin quality in cancer patientsat the time of sperm banking.     

A programme of semen cryopreservation for patients with malignant disease in a tertiary infertility centre: lessons from 8 years' experience

The improved survival in recent years of young males suffering from cancer, and an understanding of the gonadotoxic effects of chemotherapy treatment, have motivated patients and clinicians to preserve fertility potential before embarking on adjuvant therapy. Among 231 men (mean age 28.0; range 15-56 years) diagnosed with malignant disease and referred to our unit for semen cryopreservation, 112 patients (49.8%) had reduced sperm quality of <10 x 10(6) motile spermatozoa per ejaculate; however, most had sufficient suitable spermatozoa for freezing. In 40 patients (17.3 %) the semen samples were not frozen because of complete azoospermia (n = 32) or only immotile sperm in the ejaculate (n = 2), while six men were unable to produce a single sample. Some 79 men had testicular tumours (group I), 121 suffered from haematological malignancy (leukaemia or lymphoma; group II), and 27 had cancer of different causes (group III). Men in group I had significantly lower (P < 0.001) sperm quality compared with groups II and III. There was no difference between patients with seminoma and non-seminoma tumours. In the haematological malignancy group there was no difference in sperm parameters between leukaemia (n = 12) and lymphoma (n = 77) patients, but patients with Hodgkin's lymphoma had significantly lower sperm quality compared with non-Hodgkin's lymphoma. Following chemotherapy, six couples attended the clinic for assisted conception treatment using the frozen semen. Two had successful intrauterine insemination cycles which each resulted in delivery of a healthy girl; one couple had conceived in their first in-vitro fertilization (IVF) attempt, followed by delivery of healthy twins. Two women conceived after intracytoplasmic sperm injection treatment and the sixth woman achieved only biochemical pregnancy after numerous IVF and frozen embryo replacement cycles. We recommend that a properly designed programme for semen cryopreservation for cancer patients should be developed in leading tertiary assisted conception centres, which have adequate facilities and experience for cryopreservation and can offer the whole range of appropriate assisted reproductive treatment and counselling.      

Semen quality and cryopreservation in adolescent cancer patients

BACKGROUND: Adult cancer patients are routinely offered pre-treatment sperm cryopreservation. However, only recently has the welfare of adolescent cancer sufferers gained momentum, including their infertility, and unsurprisingly relatively little is known about their semen quality and feasibility of cryopreservation. METHODS AND RESULTS: A total of 238 adolescent cancer patients referred to our centre between 1991 and 2000, from post-pubertal age up to 19 years 11.9 months, were included. Their semen was processed after appropriate counselling. Semen cryopreservation was possible in 205 of the initial 238 patients referred (86.1%). The pathology of the cancer cases included Hodgkin's lymphoma, non-Hodgkin's lymphoma, osteosarcoma, Ewing's sarcoma, acute lymphoblastic leukaemia (ALL), acute myeloid leukaemia (AML), testicular, leukaemia, and others. The mean sperm counts were broadly uniform across the disease and age groups, except for the AML group. There was no cancer group analysed in which sperm could not be stored. Semen volume was broadly uniform across the disease groups, except the ALL and Ewing's sarcoma groups, which showed relatively lower and higher mean semen volumes respectively. Older adolescent patients appeared to have a higher mean semen volume. CONCLUSIONS: Semen cryopreservation was possible in most adolescent cancer cases regardless of age or diagnosis. In all cases the quality of the semen was potentially useful for assisted conception procedures. An offer to freeze sperm in all patients aged >12 years should be made. Adequate support and counselling of both the boys and their parents is essential.     

Testicular cancer and Hodgkin's disease: evaluation of semen quality

BACKGROUND: The aim of our study was to establish whether there is a difference in semen quality between patients with testicular cancer (TC) and Hodgkin's disease (HD). METHODS: We evaluated 342 patients affected by TC (n = 232) or HD (n = 110) who cryobanked sperm before initiating chemo- or radiotherapy. All TC patients were evaluated approximately 1 month after orchidectomy. RESULTS: A total of 14 patients were azoospermic or cryptozoospermic. In the TC group (n = 222) the mean of the semen parameters was normal according to the World Health Organization (1992). However, dividing the cases into total sperm count > or =40x10(6)/ejaculate and <40x10(6)/ejaculate, 35.5% of the patients showed an impaired semen quality. The quality of sperm parameters was higher in seminoma patients than for the other histological groups. A significant difference for all semen variables was observed between patients with serum betahCG levels classified as pathological (>5 mIU/ml) and those with normal serum betahCG. Comparison of semen parameters between TC stages I and II showed no significant differences. In the HD group (n = 106), we found that by and large they showed normal spermatogenesis, with only 24.5% having a total sperm count <40x10(6)/ejaculate. There was a significant decrease in semen quality in stages III and IV of HD. CONCLUSIONS: Better semen quality was observed in patients with HD than in those with TC. The semen quality observed in our TC and HD groups seems better than previous results reported in the literature.     

Effect of chemo- or radiotherapy on sperm parameters of testicular cancer patients

BACKGROUND: The aims of our study were to investigate the short- and long-term effects of chemo- or radiotherapy on spermatogenesis in patients with testicular cancer and to establish any correlation between pre-therapy sperm parameters, histotype and treatment type/intensity and the progress of spermatogenesis during the post-therapy period. METHODS: We evaluated 166 patients affected by testicular cancer, who cryobanked about 1 month after the removal of the cancerous testis and before beginning chemo- (CH group; n = 71) or radiotherapy (RT group; n = 95). RESULTS: For the CH group, there was a statistically significant decrease in sperm parameters, which was most significant 3 months after the end of chemotherapy. For the RT group, this decrease was most relevant 6 months after the end of radiotherapy. Two years after therapy, 3% of the CH group and 6% of the RT group remained azoospermic. To evaluate whether spermatogenesis recovery is a function of baseline semen quality, we divided each group into two subgroups by pre-therapy total sperm count (A, <40 x 10(6)/ejaculate; B, >or=40 x 10(6)/ejaculate). At t(24), subgroup A of both the CH and RT groups showed improved sperm parameters over the baseline, whereas subgroup B for both CH and RT groups showed a return of sperm parameters to those of baseline values. CONCLUSIONS: In conclusion, the recovery of spermatogenesis after chemo- or radiotherapy in our group of testicular cancer patients was not a function of pre-therapy sperm parameter quality. Cryopreservation of sperm before performing such therapy is therefore imperative.     

Sperm aneuploidy frequencies analysed before and after chemotherapy in testicular cancer and Hodgkin's lymphoma patients

BACKGROUND Multicolour fluorescent in situ hybridization was utilized to detect sperm aneuploidy for chromosomes 13, 21, X and Y in testicular cancer and Hodgkin's lymphoma chemotherapy patients. METHODS Aneuploidy was assessed before, and 6, 12 and/or 18-24 months after, the initiation of chemotherapy, and compared with age matched controls. 635 396 sperm were scored blindly with 5000 sperm/patient/chromosome/ time point, where sperm was available. (First two phrases have been reversed). RESULTS Comparing testicular cancer and Hodgkin's lymphoma patients to each other and with controls, cancer-specific differences were identified. Hodgkin's lymphoma patients, particularly, exhibited significantly increased aneuploidy frequencies for all chromosomes throughout treatment. At 6 months, all cancer patients showed significantly increased frequencies of XY disomy and nullisomy for chromosomes 13 and 21. In general, aneuploidy frequencies declined to pretreatment levels 18 months after treatment initiation, but increased aneuploidy frequencies persisted in some chromosomes for up to 24 months. CONCLUSIONS Because of elevated aneuploidy frequencies prior to and up to 24 months from the start of chemotherapy, patients should receive genetic counselling about the potentially increased risk of an aneuploid conceptus from sperm cryopreserved prior to chemotherapy, and for conceptions up to 2 years after the initiation of treatment.     

Semen quality before and after gonadotoxic treatment

BACKGROUND: The aim of this study was to analyse the semen quality of patients before and after gonadotoxic therapy. PATIENTS AND METHODS: We evaluated semen quality in 314 patients over a 26 year period. The diagnostic categories were leukaemia (n = 13); lymphoma (n = 128); testicular cancer (n = 102); benign conditions (n = 13); and other malignant neoplasms (n = 58). The degree of azoospermia or oligozoospermia for each disease category was recorded. We then analysed the recovery in semen quality over time for each disease category. RESULTS: The mean patient age was 27.9 years (range 13-65 years). A total of 1115 post-treatment semen samples were analysed from 314 patients. There was a significant reduction in the post-treatment sperm concentration, sperm motility and semen volume compared with pre-treatment levels (P < 0.05) in the entire cohort. However, the sperm movement and motility grade remained unaffected. Patients with testicular carcinoma had the lowest pre-treatment sperm concentrations but also the lowest incidence of azoospermia after cancer treatment. Patients with lymphoma and leukaemia had the highest incidence of post-treatment azoospermia and oligospermia. Patients having the largest reductions in their sperm concentration after treatment required the longest recovery period for spermatogenesis. The diagnostic category was the only significant predictor of post-treatment azoospermia. CONCLUSION: Gonadotoxic treatment results in a significant reduction in sperm quality. The type of cancer or disease, and the pre-treatment sperm concentrations were found to be the most significant factors governing post-treatment semen quality and recovery of spermatogenesis. All categories of patients displayed varying degrees of azoospermia and oligozoospermia, and recovery of gonadal function from these states was not significant. This highlights the importance of ensuring sperm banking before treatment, including for patients with benign conditions. Several factors and associations are discussed further in order to give an insight into the pre- and post-gonadotoxic treatment effects.     

Testicular cancer and spermatogenesis

We retrospectively analysed the characteristics of 54 men with testicular cancer. The group comprised 32 men with pure seminoma and 22 with non-seminoma germ cell tumours (NSGCT). This group was further compared to 190 healthy sperm donor candidates. Sperm quality was found to be higher in the seminoma versus the NSGCT patients in: sperm concentration [50 (0-230) versus 17 (0-288) x 10(6)/ml, P < 0.001], total motile sperm counts (TMC) [57 (0-508) versus 12 (0-854) x 10(6)/ejaculate, P = 0.002], post-thaw forward motile concentration [3 (0-28) versus 1.7 (0-17) x 10(6)/ml, P = 0.003] and motility percentage [20 (0-57) versus 12.5 (0-42) %, P = 0.002]. Serum hormone concentrations did not differ between these two sub-groups, although the follicle stimulating hormone concentrations were higher than normal in both (14.6 +/- 2.5 versus 10.4 +/- 1.4 mIU/ml, P > 0.05). As is well documented, cancer patients were found to have lower sperm quality compared to healthy candidates. The existence of these differences, and the fact that testicular cancer affects spermatogenesis, indicated that the mechanisms involved in the deterioration of sperm quality can, at least partially, be attributed to the type and origin of the malignant cancer. The higher sperm counts in the seminoma group may be related to the fact that the resemblance of the seminoma cells to normal germ cells is greater than that of the NSGCT cells, and therefore they retain a better capacity to function. Due to modern assisted reproductive technologies and micromanipulation achievements, the lower yield of spermatozoa in severe cases is no longer a major obstacle to offering cryopreservation to these patients.      

Occurrence of non-Hodgkin's lymphoma after therapy for Hodgkin's disease.

We studied the clinical and pathological features of six cases of non-Hodgkin's lymphoma (diffuse undifferentiated in four cases and diffuse histiocytic in two cases) occuring in patients treated for Hodgkin's disease. All six patients had received both radiation and chemotherapy. Abdominal or gastrointestinal involvement was present in five of the six cases. None of the patients had evidence of Hodgkin's disease when the diagnosis of non-Hodgkin's lymphoma was made. Five of the six patients were among a study group of 579 patients with Hodgkin's disease, prospectively followed since diagnosis. At 10 years the actuarial risk of development of non-Hodgkin's lymphoma in this study group is 4.4 per cent (1.2 to 15.0) (per cent probability with 95 per cent confidence limits) and is similar to that of developing acute leukemia: 2.0 per cent (0.3 to 12.9). Non-Hodgkin's lymphoma is a second tumor that may occur late in the course of patients treated for Hodgkin's disease--particularly in patients who have received both radiation therapy and chemotherapy. Like acute leukemia, non-Hodgkin's lymphoma may be another cancer that represents a substantial late risk of combined-modality therapy.     

Follow-up of sperm concentration and motility in patients with lymphoma

Lymphomas are a group of diseases, prevalent at reproductive age. Fertility is notoriously reduced among lymphoma patients. This study evaluates pre- and post-treatment semen concentration and motility, and factors associated with semen quality deterioration. We followed-up 33 patients with non-Hodgkin's lymphoma or with Hodgkin's disease during the years 1987-1997 who were referred for semen cryopreservation. Pretreatment semen analysis, and hormonal profile were recorded at diagnosis and at least 1 year after completion of the treatment, and compared. Medical records for disease type, disease stage and treatment protocols were related to long-term sperm outcome. Hormonal concentrations were not predictive of post-treatment sperm concentration. In patients with localized disease, initial sperm concentration and motility tended to be preserved, compared with patients with widespread disease (P: = 0. 016). In Hodgkin's disease patients, treatment with the adriamycin, bleomycin, vinblastine and dacarbazine (ABVD) protocol was superior to the mechloretamine, vincristine, procarbazine and prednisone with ABV protocol regarding germinal toxicity (P: = 0.0008). The post-treatment sperm outcome was better in patients treated with local irradiation than in those who did not undergo irradiation (P: = 0.0027). No predictive tools for post-treatment fertility were found and, therefore, every patient with a lymphoma should have his semen cryopreserved at diagnosis.     

Use of Leu M1 and antiepithelial membrane antigen monoclonal antibodies for diagnosing Hodgkin's disease

Biopsies of 82 patients diagnosed as having Hodgkin's disease were reviewed. Seventeen were reclassified histologically as non-Hodgkin's lymphoma or reactive lymphoid hyperplasia. A substantial number of cases of Hodgkin's disease were negative when stained with Leu M1. Staining for Leu M1 was not found in the cases of non-Hodgkin's lymphoma or reactive lymphoid hyperplasia. With the exception of the lymphocyte predominant nodular subtype of Hodgkin's disease, epithelial membrane antigen staining was seen in a few cases of Hodgkin's disease and non-Hodgkin's lymphomas. This was not a useful discriminating feature.     

Bilateral trephine bone marrow biopsies in Hodgkin's and non-Hodgkin's lymphoma.

This study was undertaken to investigate the usefulness of bilateral rather than unilateral iliac trephine biopsies in demonstrating Hodgkin's disease and non-Hodgkin's lymphoma in the bone marrow. One hundred and seventy adequate bilateral biopsies were obtained from 145 patients. Among 76 bilateral trephine biopsies from 65 patients with Hodgkin's disease, tumour was found bilaterally in 3 cases and on only one side in 2 cases. Among 94 bilateral biopsies from 80 patients with non-Hodgkin's lymphoma, tumour was found bilaterally in 17 cases and on only one side in 12. Considering all of the cases in the series, the performance of bilateral biopsy increased the yield of positive marrows from an estimate of 27 to 34, an increase of 26%. We conclude that bilateral trephine biopsy is superior to unilateral biopsy for the demonstration of bone marrow involvement by Hodgkin's disease or non-Hodgkin's lymphoma and recommend that bilateral trephine biopsies be performed when a knowledge of the state of the bone marrow is important for clinical decision making.     

Identification of common germinal-center B-cell precursors in two patients with both Hodgkin's disease and non-Hodgkin's lymphoma

BACKGROUND: Hodgkin's disease and non-Hodgkin's B-cell lymphoma occasionally occur in the same patient. The identification of a common precursor of the two types of lymphoma would show definitively that Reed-Sternberg cells originate from B cells. METHODS: We studied lymphomas from two patients, one with a composite lymphoma (classic Hodgkin's disease and a follicular lymphoma in the same lymph node) and the other with a T-cell-rich B-cell lymphoma that was followed by classic Hodgkin's disease. Single Reed-Sternberg cells and non-Hodgkin's lymphoma cells from frozen sections were micromanipulated. The rearranged immunoglobulin variable-region genes (V genes) of the heavy and light chains were amplified by the polymerase chain reaction from genomic DNA and sequenced. RESULTS: In both patients, the Reed-Sternberg cells were related clonally to the non-Hodgkin's lymphoma B cells. The V genes carried somatic mutations (a hallmark of germinal-center B cells and their descendants). In both patients, some somatic mutations were shared by the Reed-Sternberg and non-Hodgkin's lymphoma cells, whereas other somatic mutations were found exclusively in one or the other cell type. CONCLUSIONS: In two patients with classic Hodgkin's disease and non-Hodgkin's B-cell lymphoma, we identified a common B-cell precursor, probably a germinal-center B-cell, for both lymphomas. This finding suggests that the two types of lymphoma underwent both shared and distinct transforming events and provides proof of the B-cell derivation of Reed-Sternberg cells in classic Hodgkin's disease.     

Testicular sperm extraction (TESE) and ICSI in patients with permanent azoospermia after chemotherapy

BACKGROUND: Patients persistently azoospermic after chemotherapy have been considered traditionally as sterile unless sperm was frozen before therapy. Recent advances during the last decade combining testicular sperm extraction (TESE) and ICSI in patients with non-obstructive azoospermia allow these males to father their own genetic offspring. METHODS: A retrospective study was conducted of 12 patients with non-obstructive azoospermia after chemotherapy undergoing TESE between 1995 and 2002. Cancer type and anti-neoplastic treatments were recorded, together with maximum testicular volume, serum FSH levels and testicular histopathology. When TESE was successful, spermatozoa were cryopreserved for performing ICSI later. RESULTS: In five patients (41.6%) motile spermatozoa for cryopreservation and ICSI were retrieved. Four of them had received chemotherapy for testicular cancer, and one had been treated by chemotherapy/radiotherapy for Hodgkin's disease. Clinical and histological parameters were unable to predict with certainty TESE outcome in an individual patient. Eight ICSI cycles were performed on five couples and one pregnancy was obtained which resulted in the delivery of a healthy girl. CONCLUSION: Some patients with permanent azoospermia after chemotherapy can be successfully treated by TESE-ICSI. This procedure, however, may have potential genetic risks. Therefore, freezing semen before starting gonadotoxic therapy is the strategy of choice, and patients should be counselled accordingly.     

The distinction of Hodgkin's disease from T cell lymphoma.

With the ability to accurately detect T cell lymphoid differentiation, both by immunophenotypic and genetic probe methods available only within the past decade, pathologists have become increasingly aware of similarities between some pleomorphic T cell lymphomas and Hodgkin's disease. In Workshop Session B, nine cases were reviewed in detail. Consensus was attained on seven cases, four of which were considered Hodgkin's disease and three of which were considered non-Hodgkin's lymphomas. Two of these seven cases exhibited morphologic features that alone would have indicated Hodgkin's disease, but manifested clinical, immunophenotypic, or genetic probe findings that instead favored their classification as non-Hodgkin's T cell lymphoma. In two cases, no consensus could be reached; ie, features in aggregate overlapped Hodgkin's disease and non-Hodgkin's lymphoma with T cell differentiation, and therefore their classification remained indeterminate. It is concluded that in most cases of differential diagnostic difficulty, consideration of the pathobiology and ancillary-study findings allows assignment to either Hodgkin's disease or (T cell) non-Hodgkin's lymphoma. However, in rare cases, even with exhaustive application of such criteria, this distinction cannot be made.     

Effects of hypercholesterolaemia on Leydig and Sertoli cell secretory function and the overall sperm fertilizing capacity in the rabbit.

The effects of hypercholesterolaemia on testicular endocrine and exocrine function were evaluated. The influence of hypercholesterolaemia on sperm quality, quantity, and fertilizing potential was also determined. Ten mature rabbits (group A) were fed chow containing 3% cholesterol for 12 weeks. Ten control rabbits (group B) were fed normal chow for the same period. At the end of the experimental period testosterone profiles and sperm parameters were evaluated and the sperm reproductive potential was assessed by in vitro fertilization (IVF) techniques. Peripheral serum testosterone responses to testicular stimulation with human chorionic gonadotrophin, androgen-binding protein activity in testicular cytosols, sperm concentration, sperm motility, length of sperm midpiece, and IVF outcome were all significantly lower in group A than in group B. In contrast, serum cholesterol concentrations were significantly higher in group A. There were no significant differences in either testicular versus intra-abdominal temperature differences or cholesterol concentrations in seminal plasma or testicular tissue between groups A and B. The results suggest that hypercholesterolaemia has a detrimental effect on Leydig and Sertoli cell secretory function, spermatogenesis, epididymal sperm maturation process, and the overall sperm fertilizing capacity.     

T-cell rich B-cell non-Hodgkin's lymphoma: a progressed form of follicle centre cell lymphoma and lymphocyte predominance Hodgkin's disease

T-cell rich B-cell non-Hodgkin's lymphoma (T-cell rich B-cell lymphoma) is a morphological variant of diffuse large B-cell lymphoma. It is important to recognize this variant in the differential diagnosis of T-cell non-Hodgkin's lymphoma. The main differential diagnosis of T-cell rich B-cell lymphoma, nodular and diffuse lymphocyte predominance Hodgkin's disease (lymphocyte predominance Hodgkin's disease), is, however, even more difficult and differentiating criteria are still not satisfactorily defined. Moreover, T-cell rich B-cell lymphoma may not represent a clinicopathological entity. Twelve cases of T-cell rich B-cell lymphoma, selected on the basis of morphology and limited immunohistochemistry without previous knowledge of clinical data, were studied by immunohistochemistry and polymerase chain reaction for bcl-2 rearrangements to investigate the histogenetic background. In three of 12 cases, bcl-2 rearrangements were found, strongly suggesting a follicle centre cell origin. In three other cases, a documented history of definite nodular lymphocyte predominance Hodgkin's disease 29 months to 20 years prior to the diagnosis of the lymphoma was present. No differences in growth pattern, residual nodularity, tumour cell distribution, cellular morphology and composition, or immunophenotypical differences were noted in these six cases as compared to the remaining cases. These data underscore the histogenetic diversity in T-cell rich B-cell lymphoma and identify it as a progressed form of lymphoma derived from entities as diverse as follicle centre cell lymphoma and nodular lymphocyte predominance Hodgkin's disease. Moreover, it shows a complete morphological overlap with the diffuse form of lymphocyte predominance Hodgkin's disease and may actually encompass this disease entity.     

Hepatic parenchymal lymphoid aggregates in Hodgkin's disease

One hundred twenty-three liver biopsies performed at staging laparotomy for Hodgkin's disease were reviewed. Discrete parenchymal lymphoid infiltrates with variable cytologic atypia were identified in 12 patients. None of these patients had liver involvement by Hodgkin's disease. All 12 patients were alive with no clinical evidence of liver disease at last follow-up examination; however, two had extrahepatic relapses of Hodgkin's disease. Parenchymal lymphoid aggregates, a nonspecific finding in the livers of patients with Hodgkin's disease, may show some degree of cytologic atypia, but they do not represent lymphoma. Such aggregates may be relatively common and they may be overinterpreted as neoplastic, particularly in patients with non-Hodgkin's lymphoma.     

Nucleoli of blood monocytes in malignant lymphoma. A morphometric study

Morphometric methods were used to study the nucleolar ultrastructure of blood monocytes in 23 patients with Hodgkin's disease, 12 patients with non-Hodgkin's lymphoma, and 20 normal subjects. Nucleolar volume (Vn), surface area (Sn), volume fraction within the nucleus (VVn), surface-to-volume ratio, and number of nucleolar profiles per section were measured. The results were examined with the use of multivariate and univariate analyses of variance, and significant differences between the patient and normal groups were found. Compared with the normals, values for Vn, Sn, VVn and number of profiles per section were 16-20% smaller in the Hodgkin's monocytes and 19-32% smaller in those of the patients with non-Hodgkin's lymphoma. The changes in nucleolar ultrastructure may be related to the known mononuclear phagocyte dysfunction in patients with lymphoma.     

Non-Hodgkin's lymphoma of the central nervous system after treatment of Hodgkin's disease

A case of a 34-year-old man with stage IIIB nodular sclerosis Hodgkin's disease complicated by the development of a central nervous system non-Hodgkin's lymphoma is described. The second tumor became symptomatic eight months after the initial diagnosis of Hodgkin's disease, but a tissue diagnosis was not made until autopsy two months later. The Hodgkin's disease was, at that time, in remission, and the autopsy revealed no persistent or recurrent Hodgkin's disease. Despite radiotherapy, the brain lymphoma had progressed to involve the spinal leptomeninges extensively, but there was no lymphoma outside the central nervous system (CNS) at autopsy. The significance of this unique case is discussed in light of the known risk for non-Hodgkin's lymphoma as a second malignancy after Hodgkin's disease and in view of recent information concerning CNS lymphoma.