Intracranial Hodgkin's disease in two patients with familial Hodgkin's disease

Intracranial Hodgkin's disease is very rare and is often a terminal event. The case of a 33-year-old man who relapsed in the anterior pituitary gland without other evidence of disease 6 months after extended field radiation therapy for Stage IIA Hodgkin's disease is presented. He remains well with no evidence of disease five years after surgery and chemotherapy for intracranial relapse. The case of a 16-year-old boy with a dural relapse of Hodgkin's disease associated with positive cerebrospinal fluid cytology is also presented. These two patients are members of different families each with multiple cases of Hodgkin's disease. Central nervous system involvement with Hodgkin's disease may be more frequent in familial Hodgkin's disease in which immune deficiency is common. Med. Pediatr. Oncol. 28:255–258. © 1997 Wiley-Liss, Inc.     

Hodgkin's disease and non-Hodgkin's lymphoma in children and young adults: A clinicopathologic study of 127 cases

One hundred twenty-seven cases of non-Hodgkin's lymphoma and Hodgkin's disease in children and young adults at the University of Wisconsin Hospital between 1969 and 1980 have been reviewed. Nodular sclerosing was the most frequent histologic type in patients with Hodgkin's disease. Malignant lymphoblastic lymphoma (MLLB) was the most common type of non-Hodgkin's lymphoma. The relationship of the histological pattern to age and sex as well as clinical behavior and survival are discussed.     

Primary Hodgkin's disease of the bone

A primary extranodal presentation occurs in less than 0.25% of patients with Hodgkin's disease (HD) and we describe the primary clinicopathologic findings in a rare case of a 21-year-old female with primary bony involvement of Hodgkin's disease. The patient presented with microcytic, hypochromic anemia and shoulder pain. The diagnosis of HD (lymphocyte depleted type) was made by biopsy taken from a lytic lesion in the lateral third of the clavicle. Staging work-up revealed an additional lesion in the ilium, but there was no evidence of lymph node involvement. MOPP/ABV (nitrogen mustard, Oncovin, procarbazine, prednisone/adriamycin, bleomycin, and vinblastine) chemotherapy resulted in complete response lasting, to date, 36 months. To the best of our knowledge, this is only the second reported case of disseminated primary Hodgkin's disease of the bone and all have had a favourable response to combination chemotherapy. A review of the literature is also presented. © 1995 Wi1ey-Liss Inc.     

Benign proliferative lesions mimicking recurrence of Hodgkin's disease

Salvage treatment in patients with recurrent Hodgkin's disease is more effective when tumor burden is minimal. That is why more intensive follow-up strategies, including frequent imaging tests, have been recently developed for the detection of early relapse. However, as screening procedures become more sensitive, there is an increasing risk of false-positive results, demonstrating nonmalignant proliferative disorders. We describe three young patients who had lymphocyte-predominant or mixed-cellularity Hodgkin's disease and were in clinical complete remission for 2.5–3 years after a combined treatment with chemotherapy and radiation. Imaging tests revealed new gallium-avid lymphadenopathy in the chest in two cases. Pathologically enlarged pelvic lymph nodes were identified in another case, after a diagnosis of recurrent disease in axilla. Those findings were interpreted as relapse, and the patients underwent thoracotomy and laparotomy, respectively, for histologic confirmation. The results showed progressively transformed germinal centers and sarcoid-like lesions, two benign proliferative disorders. When patients with Hodgkin's disease in remission show new lymphadenopathy, even with positive gallium scan, it seems mandatory to obtain tissue for histologic examination, even through invasive procedures such as laparotomy and thoracotomy, to avoid wrong diagnosis and unnecessary treatment. Med. Pediatr. Oncol. 28:187–190 © 1997 Wiley-Liss, Inc.     

Unusual secondary tumors after childhood lymphoid malignancy

Second malignant neoplasms (SMN) in individuals who survived childhood cancer have been reported with increasing frequency during the last decades. The overall probability of developing second malignancy for children treated for cancer was estimated at about 2–5% at 25 years. In children, the tumors most often associated with the development of SMN are retinoblastoma and Hodgkin's disease. We report two cases of unusual second tumors in two patients cured of lymphoid malignancy: one boy cured of acute lymphoblastic leukemia developed mediastinal ganglioneuroma nine years later and one girl had gastric carcinoma seven years after Hodgkin's disease. Both developed a tumor in nonirradiated areas. Gastric carcinoma and ganglioneuroma are not reported as recurrent SMN in survivors after childhood cancer, with one single case of gastric carcinoma and one of ganglioneuroblastoma having been reported as second tumor in survivors after childhood cancer. © 1995 Wi1ey-Liss Inc.     

Simultaneously occurring alopecia areata and Hodgkin's lymphoma: Complete remission of both diseases with MOPP/ABV chemotherapy

A 43-year-old man presented with simultaneously occurring alopecia areata and stage IIIB nodular sclerosing Hodgkin's disease. Systemic symptoms of Hodgkin's disease were present for 6 months, and rapidly developing patchy hair loss of the scalp was present for 2 weeks prior to presentation. The patient was treated with eight cycles of MOPP-ABV chemotherapy that resulted in complete remission of Hodgkin's disease. Four months after the completion of chemotherapy, the patient had normal hair regrowth with no evidence of alopecia areata. Alopecia areata may be an autoimmune disease and may respond to chemotherapy. © 1992 Wiley-Liss, Inc.     

INTRACRANIAL INVOLVEMENT IN HODGKIN'S DISEASE

The authors report 3 cases of Hodgkin's disease with intracranial involvement. The patients were 4, 12, and 15 years old (male/female = 1/2). Initially, they were treated with ABVD or COPP chemotherapies and low-dose involved field radiotherapy. Intracranial recurrences occurred 27, 40, and 42 months after initial diagnosis, respectively. Two patients experienced convulsions and the other complained of diplopia. The metastatic lesions were located supratentorially with CT or MRI. Despite initial response achieved following systemic chemotherapy and external irradiation to cranial lesions, all patients died with disseminated disease. In patients with intracranial involvement of Hodgkin's disease, prolonged disease-free survival may be achieved by combined modality treatment.     

Epstein-barr virus (EBV) latent membrane protein (LMP) in tumor cells of Hodgkin's disease in pediatric patients

Twenty-nine out of 31 consecutive pediatric patients with Hodgkin's disease treated at our hospital from 1988 to 1992 were studied. The selection criterion was the availability of sufficient formalin-fixed, paraffin-embedded tissue for analysis. Patient age ranged from 3 to 15 years with a median age of 7 years. Lymph node biopsies were examined for the presence of Epstein-Barr virus (EBV)-encoded latent membrane protein (LMP) in malignant cells by peroxidase immunolabeling. LMP positivity was present in 10/15 (67%) of mixed cellularity, 1/6 (17%) of lymphocyte predominance, 0/7 (0%) of nodular sclerosis, and 1/1 (100%) of lymphocyte depletion. Positive cases by age range were: 10/12 (83%) for 3–6 years and 2/17 (11%) for 7–15 years. The association between EBV and Hodgkin's disease in children appeared to be more frequent in patients with mixed cellularity and those in the 3–6 age range, though examples of EBV-positive tumors were found in other histologic subtypes, stages and ages. Findings indicate that Hodgkin's disease in children is at least as strongly linked to EBV as in adults. Furthermore, we suggest that the EBV is associated with a subgroup of patients which can be defined on the basis of the age at diagnosis. © 1995 Wiley-Liss, Inc.     

Late recurrence in Hodgkin's disease: A report of two cases

Two cases of Hodgkin's disease are described who relapsed 22 and 19 years after regional radiation therapy. One of the patients also developed a carcinoma of the large bowel soon after first relapse. The importance of long follow-up and documentation of cause of death in Hodgkin's disease is stressed.     

Secondary malignancies in a child with Hodgkin's disease: Peripheral T-cell lymphoma and myelodysplastic syndrome evolving into acute nonlymphoblastic leukaemia

Hodgkin's disease (HD) has been linked to an increased risk of second malignant neoplasms (SMN), especially non-Hodgkin's lymphoma (NHL) and acute nonlymphoblastic leukaemia (ANLL). The mutagenic property of cytotoxic therapy as well as defective immunity have been implicated as playing a major role in the development of SMN in patients previously treated for HD. We report a case of a 14-year-old girl with HD who developed two different second malignancies within a latent period of 28 months following HD diagnosis. The patient presented initially with bilateral cervical and supraclavicular as well as mediastinal and paraaortic lymphadenopathy. She was staged as IIIA, nodular sclerosing type HD, and was given eight alternative cycles of MOPP-ABVD followed by “mantle” field radiotherapy to a total dose of 3.3 Gy plus 0.4 Gy to the upper mediastinum. Within 8 months following the completion of therapy, a period of myelodysplasia and progressive severe immune deficiency, considered as a result of initial treatment, occurred. Eighteen months after HD diagnosis while the patient was continuously neutropenic and heavily immunocompromised, a peripheral T-cell lymphoma of the angiocentric immunoproliferative lesion type (AIL) Grade III, appeared in both lungs within and beyond the radiation field, with no evidence of HD in biopsy specimens. After institution of a new chemotherapy regimen. (L17M), a satisfactory response regarding NHL lesions was noted. However, 10 months later the myelodysplastic syndrome (MDS) accompanied by complex chromosomal abnormalities evoluted to frank ANLL with a rapid fatal course. This case supports the hypothesis that combined modality treatment accompanied by severe immunodeficiency may result in the development of multiple second malignancies even within a very short latent period, especially in a subgroup of HD patients who may be at particularly increased risk for second cancers. © 1996 Wiley-Liss, Inc.     

Hodgkin's disease associated with central pontine myelinolysis

We describe a 12-year-old black male who presented with cervical lymphadenopathy, hepatosplenomegaly of 3 months duration, and ataxia and incoordination of recent onset. Hodgkin's disease, stage IVB, was diagnosed. An MRI of the head demonstrated a nonenhancing, well-defined pontine lesion. The pontine lesion and the associated neurologic symptoms were consistent with central pontine myelinolysis. Treatment of Hodgkin's disease resulted in complete remission and complete disappearance of the pontine abnormality. © 1993 Wiley-Liss, Inc.     

Langerhans Cell Histiocytosis Arising After Hodgkin's Disease

We present the case of a 19-year-old male who suffered from Langerhans cell histiocytosis (LCH) 12 months after having been treated for recurrent Hodgkin 's disease (HD). Immunophenotypic characterization and electron microscopic analysis were useful for the exclusion of a bone relapse of Hodgkin's disease or any other differential diagnosis. The association of LCH with HD or other malignancies is rare but more frequent than previously believed. The significance of such an association and the pathophysiology of LCH are still open questions.     

Survival in Hodgkin's disease by stage and age

Patterns of care for Hodgkin's disease in the United States were surveyed through voluntary audits of hospitals with cancer programs nonapproved and approved by the Cancer Commission of the American College of Surgeons. Four hundred and seventy-three hospitals reported 6,345 patients diagnosed immediately preceding December 31, 1975. The survival rates varied with age, being better at younger ages and worse in the elderly. By pathologic stage, the younger patients faired better than the elderly in each stage grouping. Histologic type was not a factor in this poor prognosis. Hodgkin's disease in elderly patients has a different biologic behavior than in younger patients.     

Randomized study for the treatment of adult advanced Hodgkin's disease: Epirubicin,vinblastine, bleomycin,and dacarbazine (EVBD) versus mitoxantrone,vinblastine, bleomycin,and dacarbazine (MVBD)

Seventy patients with previously untreated advanced Hodgkin's disease and without bulky disease were entered in a prospective randomized clinical trial comparing epirubicin in combination with vinblastine, bleomycin, and dacarbazine (EVBD) with a regimen containing mitoxantrone, vinblastine, bleomycin, and dacarbazine (MVBD). Both groups were comparable for the variables of age, sex, stage, and presence of B symptoms and histology. Thirty-one (88%) of EVBD-treated patients achieved a pathologically documented complete remission (CR) compared to the 24 cases (68%) of the MVBD-treated group. After a median follow-up of 36 months, duration of CR is better in the EVBD-treated patients with an actuarial 5-year duration of CR of 80%, statistically different to the MVBD group: 53% (P < 0.01). Both regimens ahowed the same gastrointestinal toxicity, but the patients treated with the MVBD regimen shown most and severe hematological and cardiac toxicities. Also, biochemical alterations in hepatic test were observed in these patients. The alternative use of epirubicin in combination chemotherapy appears to be as effective in advanced Hodgkin's disease without bulky disease, with reduced clinical toxicity. Mitoxantrone containing regimen was not found to have an equivalent efficacy and clinical toxicity was most frequent and severe. We feld that mitoxantrone could be consider a second-line drug in the treatment of advanced Hodgkin's disease. © 1994 Wiley-Liss, Inc.     

Staphylococcal Pyomyositis in a Child with Fanconi Aplastic Anemia

We retrospectively analyzed all 164 cases of pediatric lymphoma diagnosed in northern Israel during the 18-year period from 1973 to 1990. Our findings generally conformed to those of other studies with regard to annual incidence (24.7/million), age at diagnosis (5 to 9 years for Jewish males, later for others), histology (Hodgkin's disease most commonly), and male predominance. The northern Israeli pediatric lymphoma pattern of incidence is similar to the Asian-African-South American pattern and unlike that of Europe or North America; in Israel, lymphoma rather than brain tumor is the second most common childhood malignancy. The nodular sclerosing variant was the most common histology seen in Hodgkin's lymphoma (especially in females), followed by mixed cellularity. Malignancies are generally more common in Jewish children but lymphomas in particular were seen more often in Arabs (28.7/million), while the Ashkenasi (20.81 million) and Sephardi (21.61 million) Jewish populations had similar incidences. The high rate of consanguineous marriages among Arabs and their lower socioeconomic level may explain the high incidence of lymphomas in this group.     

Hodgkin's Disease in Children in the West Midlands, 1957–1986: A Large Population-Based Study

One hundred forty-one children were diagnosed with Hodgkin's disease between 1957 and 1986 in the West Midlands Health Authority Region (1991 population, 1.I million children). Eighty-seven were boys and 54 were girls, representing a significant male:female ratio of 1.5:1 (P < 0.01). The average age-standardized incidence rate was 3.6 per million per year with a significant increase in the older age group (≥ 10 years) in the second half of the period (P= 0.02). The mixed cellularity subtype was more common in those younger than 10 years, with nodular sclerosing disease being seen more in those ≤ 10 years. Overall survival at 5 years was 76% (65% at 10 years) with a significant difference (P < 0.001) in survival between the first and last decades. There were six second malignancies, five of which could have been treatment related. A positive history of cancer in close relatives was found in 11 patients, and higher social class war found in more older than younger children. These findings support the hypothesis that Hodgkin's disease may have a viral etiology and may be linked with socioeco-nomic conditions.     

Second malignant tumours in childhood Hodgkin's disease

This study was undertaken to determine the treatment-specific incidence of second malignant tumours (SMT) in childhood Hodgkin's disease. The institutional databases at The Hospital for Sick Children, the Princess Margaret Hospital, and the Toronto-Bayview Regional Cancer Centre were reviewed for the years 1958–1993. Three hundred and forty-three consecutive newly diagnosed children were evaluated. The overall 30 year cumulative SMT incidence was 31%. The 20 year SMT incidence was greater for patients who relapsed (n = 129), 27%, compared with patients who remained relapse free (n = 214), 13%. For patients with stage 1–3B disease who remained relapse free, the 10 year SMT rate was 7% for patients who were surgically staged and treated with extended field radiation treatment (EF RT) (35 G), compared with 3% in clinically staged patients treated with MOPP (six cycles) and EF RT (25–30 G). To date there is no significant difference in the oncogenicity of these treatment protocols. However, EF RT alone was less effective in disease control. For stages 1–3B, 62% of patients relapsed after EF RT alone compared with 18% after bimodal treatment. Therefore treatment intensification due to relapse was more frequent in the former group. The overall 10 year SMT incidence for patients treated with these protocols was 11% and 3%, respectively. The 20 year SMT incidence following EF RT alone was 24%. We conclude that SMTs were a common late complication in childhood Hodgkin's disease and are a limiting factor in the achievement of cure. The incidence of SMTs was increased in children who required retreatment and was minimal in children who remained in a first complete remission. Therefore the initial treatment strategy in childhood Hodgkin's disease must be to minimize the risk of relapse, in order to avoid the morbidity and mortality associated with both relapse and SMT induction, and to achieve this objective with a primary treatment protocol of low oncogenicity. © 1996 Wiley-Liss, Inc.     

Treatment of childhood Hodgkin's disease with ABVD without radiotherapy

Seventeen previously untreated children with Hodgkin's disease were treated with six courses of the combination adriamycin, bleomycin, vinblastine, and DTIC (ABVD), without radiotherapy, from 1984–1987. In all patients, complete remission was attained. After a median follow-up period of 73.5 months (range 59–98 months), five patients had a relapse after 4, 5, 11, 21, and 34 months, respectively, from attainment of complete remission. In 12 patients with stages I and II, two relapses occurred. Three out of five patients with stage III and stage IV developed a relapse. Based upon these results, we conclude that ABVD might be an appropriate treatment for newly diagnosed children with Hodgkin's disease stages I and II. However, for children with stages III and IV, more intensive treatment is needed. Radio-therapy should be withheld for children with refractory disease, residual disease, or relapse. © 1996 Wiley-Liss, Inc.     

Results of a randomized study of early stage Hodgkin's disease using ABVD,EBVD, or MBVD

From January 1986 to December 1989, 157 previously untreated patients, with Hodgkin's disease stage I or II without bulky disease, were enrolled in a clinical comparative study. The objectives of the study were to compare the efficacy and safety of using epirubicine or mitoxantrone instead of adriamycin in the combination chemotherapy regimen ABVD (adriamycin, bleomycin, vinblastine, and dacarbazine). The complete response rate was better in the patients treated with the ABVD or EBVD regimens compared to the MBVD arm. Also, differences in overall survival and relapse-free survival were better in the patients who received ABVD or EBVD compared to the MBVD regimen. Hematological, gastrointestinal and cardiac toxicity were similar in the three groups. Dose intensity, delays and complications were also similar in the three groups. The mitoxantrone-containing regimen was found to have less efficacy in comparison to the other regimens tested in the present study in patients with favorable stage I or II Hodgkin's disease. © 1995 Wi1ey-Liss Inc.     

Hodgkin's disease presenting in epitrochlear nodes

Two cases of Hodgkin's Disease (HD) presenting in epitrochlear nodes are described, and compared to four similar cases gleaned from the literature. The nodular sclerosis type of HD was present in 5 of the 6 patients. Of the four patients staged with laparotomy, two had infradiaphragmatic disease. A treatment approach using radiation alone for patients with disease limited to the epitroclear region is presented, and anatomical considerations of the treatment technique are given.